ASBMR Annual Meeting 2019

ORLANDO – Cumulative evidence over the years has shown that bisphosphonates reduce distant metastases in postmenopausal women with early-stage breast cancer but that effect does not seem to extend to younger, premenopausal women who may experience adverse effects with bisphosphonates, nor has it been replicated in other types of cancer, such as lung or prostate, Robert Coleman MBBS, MD, said in a presentation marking the 50th anniversary of the publication of the first papers describing the then-new class of drugs.

“We have some science – at least in postmenopausal breast cancer – [showing] that we’re really making a difference, but we don’t understand why it’s not working in the other patients or in the other diseases,” said Dr. Coleman of the University of Sheffield (England) at the annual meeting of the American Society for Bone and Mineral Research.
 

Mixed findings in early studies

Early studies showing the metastases-prevention effects of bisphosphonates were with clodronate. In one study, Dr. Coleman said, researchers found that oral clodronate at a dose of 1,600 mg/day as a supplementary treatment to standard treatment for primary, operable breast cancer reduced the risk of bone metastases in a cohort of 1,069 patients with stage 1-3 breast cancer (hazard ratio, 0.692; P = .043) over 5 years (Breast Cancer Res. 2006 Mar 15. doi: 10.1186/bcr1384). Another trial, of 302 patients with breast cancer who received oral clodronate at 1,600 mg/day for 2 years, found that 20.4% of patients who received oral clodronate had died by 8.5 years of follow-up, compared with 40.7% of those who did not receive the intervention (Ann Oncol. 2008;19[12]:2007-11).

However, those results were in conflict with findings from an earlier study in which researchers followed patients with breast cancer who received 1,600 mg/day of oral clodronate or placebo for 3 years. They found a similar number of bone metastases in the clodronate and placebo groups (32% and 29%, respectively), as well as a lower overall disease-free survival rate at 10 years for the clodronate group, compared with the placebo group (45% vs. 58%; Acta Oncol. 2004;43[7]:650-6).“For various other reasons, clodronate did not gain traction as a therapeutic strategy in early-stage breast cancer,” said Dr. Coleman, although emerging evidence showed that other bisphosphonate agents were effective in some patients with breast cancer.

In a 2009 article, Gnant et al. reported that premenopausal patients, who underwent primary surgery for stage 1 or stage 2 breast cancer and received standard goserelin therapy for induced menopause and endocrine therapy (either tamoxifen or anastrozole) in addition to treatment with zoledronic acid, had a disease-free survival rate of 94.0% at a median 47.8 months of follow-up (N Eng J Med. 2009;360:679-91). After a median 94.4 months of follow-up, the investigators reported a lower risk of disease progression (HR, 0.77; 95% confidence interval, 0.60-0.99; P = .042) and death (HR, 0.66; 95% CI, 0.43-1.02; P = .064; Ann Oncol. 2015;26[2]:313-20).

In his own group, Dr. Coleman and colleagues recruited patients with early-stage breast cancer in the AZURE trial, a phase 3 study of 3,360 patients who received standard therapy with or without zoledronic acid 4 mg every 3-4 weeks for 6 doses, followed by 8 doses every 3 months then 5 doses every 6 months (N Eng J Med. 2011;365:1396-405). “We saw no effect,” said Dr. Coleman. “[That was] very different from what was shown by [Dr.] Gnant.”

For a subgroup of postmenopausal patients, Dr. Coleman and colleagues found that the adjusted HR for disease-free survival was 0.82 for women who were more than 5 years postmenopausal (95% CI, 0.67-1.00) at the time of breast cancer and bisphosphonate treatment, but women younger than 40 years had worse survival outcomes at 10 years (HR, 1.56; 95% CI, 1.09-2.22) and had a significantly higher risk of death from breast cancer (HR, 1.67; 95% CI, 1.16-2.40; J Bone Oncol. 2018 Sep 27. doi: 10.1016/j.jbo.2018.09.008).
 

Trying to reconcile disparate findings

Those findings left his group with a dilemma, said Dr. Coleman. “Do we start again and run trials, and wait another 10 years, or is there a shortcut to [understanding] what’s going on?” he asked.

In a meta-analysis of all trials from the Early Breast Cancer Trialists’ Collaborative Group in 2015 examining adjuvant bisphosphonate treatment and placebo in patients with early-stage breast cancer, intent-to-treat analyses did not show significant benefit after therapy, but postmenopausal women (11,767 women in 36 trials) saw a clear benefit in all recurrence (rate ratio, 0.86; 95% CI, 0.78-0.94), bone recurrence (RR, 0.72; 95% CI, 0.60-0.86), and breast cancer–related mortality (RR, 0.82; 95% CI, 0.73-0.93; Lancet. 2015 Jul 23. doi: 10.1016/S0140-6736[15]60908-4). The effect seemed to be similar, regardless of bisphosphonate type, with other results seen across trials that used clodronate, zoledronic acid, pamidronate, or ibandronate.

“Although those outcome differences might look quite small for a common disease, that’s a really big effect. Reducing one-sixth of breast cancer deaths at 10 years is the equivalent of saving 10,000 lives across the [European Union], and about half that in the United States,” said Dr. Coleman, noting that guidelines in North America from the American Society of Clinical Oncology and the European Society for Medical Oncology now support adjuvant bisphosphonates in postmenopausal patients with breast cancer.

However, bisphosphonates’ effect on breast cancer does not extend to other cancers, such as non–small cell lung cancer or prostate cancer. In other absorption inhibitors such as denosumab, there also seems to be no benefit for patients with breast cancer, including in postmenopausal patient subgroups, said Dr. Coleman. “In my view, osteoclast inhibition is only part of the story,” he noted.

In the AZURE trial, secondary outcomes examined how the transcription factor MAF interacted with menopausal status and treatment with zoledronic acid. The 79% of patients with tumors that were negative for MAF fluorescence in situ hybridization had improved overall survival (0.69; 95% CI, 0.50-0.94), regardless of menopause status (J Bone Oncol. 2018. doi: 10.1016/j.jbo.2018.09.008). “There’s probably a need to merge the treatment: in this case, the bisphosphonate, the biology of the cancer, and the environment the cancer finds itself in,” noted Dr. Coleman.

“From the cancer perspective, bisphosphonates have transformed the experience for many of our patients with advanced disease, and now we’re working to see great improvements, at least in common diseases such as postmenopausal breast cancer,” he concluded.

Dr. Coleman reports being a paid employee of prIME Oncology (until March 2019); is a consultant for Amgen, Astellas, Boehringer Ingelheim, Scandell, and Biocon; is on the speakers bureau for Amgen and Eisai; holds intellectual property rights for a biomarker being developed by Inbiomotion; and is on the scientific advisory board for Inbiomotion.

ORLANDO – Cumulative evidence over the years has shown that bisphosphonates reduce distant metastases in postmenopausal women with early-stage breast cancer but that effect does not seem to extend to younger, premenopausal women who may experience adverse effects with bisphosphonates, nor has it been replicated in other types of cancer, such as lung or prostate, Robert Coleman MBBS, MD, said in a presentation marking the 50th anniversary of the publication of the first papers describing the then-new class of drugs.

“We have some science – at least in postmenopausal breast cancer – [showing] that we’re really making a difference, but we don’t understand why it’s not working in the other patients or in the other diseases,” said Dr. Coleman of the University of Sheffield (England) at the annual meeting of the American Society for Bone and Mineral Research.
 

Mixed findings in early studies

Early studies showing the metastases-prevention effects of bisphosphonates were with clodronate. In one study, Dr. Coleman said, researchers found that oral clodronate at a dose of 1,600 mg/day as a supplementary treatment to standard treatment for primary, operable breast cancer reduced the risk of bone metastases in a cohort of 1,069 patients with stage 1-3 breast cancer (hazard ratio, 0.692; P = .043) over 5 years (Breast Cancer Res. 2006 Mar 15. doi: 10.1186/bcr1384). Another trial, of 302 patients with breast cancer who received oral clodronate at 1,600 mg/day for 2 years, found that 20.4% of patients who received oral clodronate had died by 8.5 years of follow-up, compared with 40.7% of those who did not receive the intervention (Ann Oncol. 2008;19[12]:2007-11).

However, those results were in conflict with findings from an earlier study in which researchers followed patients with breast cancer who received 1,600 mg/day of oral clodronate or placebo for 3 years. They found a similar number of bone metastases in the clodronate and placebo groups (32% and 29%, respectively), as well as a lower overall disease-free survival rate at 10 years for the clodronate group, compared with the placebo group (45% vs. 58%; Acta Oncol. 2004;43[7]:650-6).“For various other reasons, clodronate did not gain traction as a therapeutic strategy in early-stage breast cancer,” said Dr. Coleman, although emerging evidence showed that other bisphosphonate agents were effective in some patients with breast cancer.

In a 2009 article, Gnant et al. reported that premenopausal patients, who underwent primary surgery for stage 1 or stage 2 breast cancer and received standard goserelin therapy for induced menopause and endocrine therapy (either tamoxifen or anastrozole) in addition to treatment with zoledronic acid, had a disease-free survival rate of 94.0% at a median 47.8 months of follow-up (N Eng J Med. 2009;360:679-91). After a median 94.4 months of follow-up, the investigators reported a lower risk of disease progression (HR, 0.77; 95% confidence interval, 0.60-0.99; P = .042) and death (HR, 0.66; 95% CI, 0.43-1.02; P = .064; Ann Oncol. 2015;26[2]:313-20).

In his own group, Dr. Coleman and colleagues recruited patients with early-stage breast cancer in the AZURE trial, a phase 3 study of 3,360 patients who received standard therapy with or without zoledronic acid 4 mg every 3-4 weeks for 6 doses, followed by 8 doses every 3 months then 5 doses every 6 months (N Eng J Med. 2011;365:1396-405). “We saw no effect,” said Dr. Coleman. “[That was] very different from what was shown by [Dr.] Gnant.”

For a subgroup of postmenopausal patients, Dr. Coleman and colleagues found that the adjusted HR for disease-free survival was 0.82 for women who were more than 5 years postmenopausal (95% CI, 0.67-1.00) at the time of breast cancer and bisphosphonate treatment, but women younger than 40 years had worse survival outcomes at 10 years (HR, 1.56; 95% CI, 1.09-2.22) and had a significantly higher risk of death from breast cancer (HR, 1.67; 95% CI, 1.16-2.40; J Bone Oncol. 2018 Sep 27. doi: 10.1016/j.jbo.2018.09.008).
 

Trying to reconcile disparate findings

Those findings left his group with a dilemma, said Dr. Coleman. “Do we start again and run trials, and wait another 10 years, or is there a shortcut to [understanding] what’s going on?” he asked.

In a meta-analysis of all trials from the Early Breast Cancer Trialists’ Collaborative Group in 2015 examining adjuvant bisphosphonate treatment and placebo in patients with early-stage breast cancer, intent-to-treat analyses did not show significant benefit after therapy, but postmenopausal women (11,767 women in 36 trials) saw a clear benefit in all recurrence (rate ratio, 0.86; 95% CI, 0.78-0.94), bone recurrence (RR, 0.72; 95% CI, 0.60-0.86), and breast cancer–related mortality (RR, 0.82; 95% CI, 0.73-0.93; Lancet. 2015 Jul 23. doi: 10.1016/S0140-6736[15]60908-4). The effect seemed to be similar, regardless of bisphosphonate type, with other results seen across trials that used clodronate, zoledronic acid, pamidronate, or ibandronate.

“Although those outcome differences might look quite small for a common disease, that’s a really big effect. Reducing one-sixth of breast cancer deaths at 10 years is the equivalent of saving 10,000 lives across the [European Union], and about half that in the United States,” said Dr. Coleman, noting that guidelines in North America from the American Society of Clinical Oncology and the European Society for Medical Oncology now support adjuvant bisphosphonates in postmenopausal patients with breast cancer.

However, bisphosphonates’ effect on breast cancer does not extend to other cancers, such as non–small cell lung cancer or prostate cancer. In other absorption inhibitors such as denosumab, there also seems to be no benefit for patients with breast cancer, including in postmenopausal patient subgroups, said Dr. Coleman. “In my view, osteoclast inhibition is only part of the story,” he noted.

In the AZURE trial, secondary outcomes examined how the transcription factor MAF interacted with menopausal status and treatment with zoledronic acid. The 79% of patients with tumors that were negative for MAF fluorescence in situ hybridization had improved overall survival (0.69; 95% CI, 0.50-0.94), regardless of menopause status (J Bone Oncol. 2018. doi: 10.1016/j.jbo.2018.09.008). “There’s probably a need to merge the treatment: in this case, the bisphosphonate, the biology of the cancer, and the environment the cancer finds itself in,” noted Dr. Coleman.

“From the cancer perspective, bisphosphonates have transformed the experience for many of our patients with advanced disease, and now we’re working to see great improvements, at least in common diseases such as postmenopausal breast cancer,” he concluded.

Dr. Coleman reports being a paid employee of prIME Oncology (until March 2019); is a consultant for Amgen, Astellas, Boehringer Ingelheim, Scandell, and Biocon; is on the speakers bureau for Amgen and Eisai; holds intellectual property rights for a biomarker being developed by Inbiomotion; and is on the scientific advisory board for Inbiomotion.

ORLANDO – Cumulative evidence over the years has shown that bisphosphonates reduce distant metastases in postmenopausal women with early-stage breast cancer but that effect does not seem to extend to younger, premenopausal women who may experience adverse effects with bisphosphonates, nor has it been replicated in other types of cancer, such as lung or prostate, Robert Coleman MBBS, MD, said in a presentation marking the 50th anniversary of the publication of the first papers describing the then-new class of drugs.

“We have some science – at least in postmenopausal breast cancer – [showing] that we’re really making a difference, but we don’t understand why it’s not working in the other patients or in the other diseases,” said Dr. Coleman of the University of Sheffield (England) at the annual meeting of the American Society for Bone and Mineral Research.
 

Mixed findings in early studies

Early studies showing the metastases-prevention effects of bisphosphonates were with clodronate. In one study, Dr. Coleman said, researchers found that oral clodronate at a dose of 1,600 mg/day as a supplementary treatment to standard treatment for primary, operable breast cancer reduced the risk of bone metastases in a cohort of 1,069 patients with stage 1-3 breast cancer (hazard ratio, 0.692; P = .043) over 5 years (Breast Cancer Res. 2006 Mar 15. doi: 10.1186/bcr1384). Another trial, of 302 patients with breast cancer who received oral clodronate at 1,600 mg/day for 2 years, found that 20.4% of patients who received oral clodronate had died by 8.5 years of follow-up, compared with 40.7% of those who did not receive the intervention (Ann Oncol. 2008;19[12]:2007-11).

However, those results were in conflict with findings from an earlier study in which researchers followed patients with breast cancer who received 1,600 mg/day of oral clodronate or placebo for 3 years. They found a similar number of bone metastases in the clodronate and placebo groups (32% and 29%, respectively), as well as a lower overall disease-free survival rate at 10 years for the clodronate group, compared with the placebo group (45% vs. 58%; Acta Oncol. 2004;43[7]:650-6).“For various other reasons, clodronate did not gain traction as a therapeutic strategy in early-stage breast cancer,” said Dr. Coleman, although emerging evidence showed that other bisphosphonate agents were effective in some patients with breast cancer.

In a 2009 article, Gnant et al. reported that premenopausal patients, who underwent primary surgery for stage 1 or stage 2 breast cancer and received standard goserelin therapy for induced menopause and endocrine therapy (either tamoxifen or anastrozole) in addition to treatment with zoledronic acid, had a disease-free survival rate of 94.0% at a median 47.8 months of follow-up (N Eng J Med. 2009;360:679-91). After a median 94.4 months of follow-up, the investigators reported a lower risk of disease progression (HR, 0.77; 95% confidence interval, 0.60-0.99; P = .042) and death (HR, 0.66; 95% CI, 0.43-1.02; P = .064; Ann Oncol. 2015;26[2]:313-20).

In his own group, Dr. Coleman and colleagues recruited patients with early-stage breast cancer in the AZURE trial, a phase 3 study of 3,360 patients who received standard therapy with or without zoledronic acid 4 mg every 3-4 weeks for 6 doses, followed by 8 doses every 3 months then 5 doses every 6 months (N Eng J Med. 2011;365:1396-405). “We saw no effect,” said Dr. Coleman. “[That was] very different from what was shown by [Dr.] Gnant.”

For a subgroup of postmenopausal patients, Dr. Coleman and colleagues found that the adjusted HR for disease-free survival was 0.82 for women who were more than 5 years postmenopausal (95% CI, 0.67-1.00) at the time of breast cancer and bisphosphonate treatment, but women younger than 40 years had worse survival outcomes at 10 years (HR, 1.56; 95% CI, 1.09-2.22) and had a significantly higher risk of death from breast cancer (HR, 1.67; 95% CI, 1.16-2.40; J Bone Oncol. 2018 Sep 27. doi: 10.1016/j.jbo.2018.09.008).
 

Trying to reconcile disparate findings

Those findings left his group with a dilemma, said Dr. Coleman. “Do we start again and run trials, and wait another 10 years, or is there a shortcut to [understanding] what’s going on?” he asked.

In a meta-analysis of all trials from the Early Breast Cancer Trialists’ Collaborative Group in 2015 examining adjuvant bisphosphonate treatment and placebo in patients with early-stage breast cancer, intent-to-treat analyses did not show significant benefit after therapy, but postmenopausal women (11,767 women in 36 trials) saw a clear benefit in all recurrence (rate ratio, 0.86; 95% CI, 0.78-0.94), bone recurrence (RR, 0.72; 95% CI, 0.60-0.86), and breast cancer–related mortality (RR, 0.82; 95% CI, 0.73-0.93; Lancet. 2015 Jul 23. doi: 10.1016/S0140-6736[15]60908-4). The effect seemed to be similar, regardless of bisphosphonate type, with other results seen across trials that used clodronate, zoledronic acid, pamidronate, or ibandronate.

“Although those outcome differences might look quite small for a common disease, that’s a really big effect. Reducing one-sixth of breast cancer deaths at 10 years is the equivalent of saving 10,000 lives across the [European Union], and about half that in the United States,” said Dr. Coleman, noting that guidelines in North America from the American Society of Clinical Oncology and the European Society for Medical Oncology now support adjuvant bisphosphonates in postmenopausal patients with breast cancer.

However, bisphosphonates’ effect on breast cancer does not extend to other cancers, such as non–small cell lung cancer or prostate cancer. In other absorption inhibitors such as denosumab, there also seems to be no benefit for patients with breast cancer, including in postmenopausal patient subgroups, said Dr. Coleman. “In my view, osteoclast inhibition is only part of the story,” he noted.

In the AZURE trial, secondary outcomes examined how the transcription factor MAF interacted with menopausal status and treatment with zoledronic acid. The 79% of patients with tumors that were negative for MAF fluorescence in situ hybridization had improved overall survival (0.69; 95% CI, 0.50-0.94), regardless of menopause status (J Bone Oncol. 2018. doi: 10.1016/j.jbo.2018.09.008). “There’s probably a need to merge the treatment: in this case, the bisphosphonate, the biology of the cancer, and the environment the cancer finds itself in,” noted Dr. Coleman.

“From the cancer perspective, bisphosphonates have transformed the experience for many of our patients with advanced disease, and now we’re working to see great improvements, at least in common diseases such as postmenopausal breast cancer,” he concluded.

Dr. Coleman reports being a paid employee of prIME Oncology (until March 2019); is a consultant for Amgen, Astellas, Boehringer Ingelheim, Scandell, and Biocon; is on the speakers bureau for Amgen and Eisai; holds intellectual property rights for a biomarker being developed by Inbiomotion; and is on the scientific advisory board for Inbiomotion.

ORLANDO – Transwomen are more likely to have a lower bone mineral density (BMD) before beginning hormone therapy, compared with male reference populations, but there are no short- or long-term risks to bone health over the life of a transperson who receives hormone therapy, according to a presentation at the annual meeting of the American Society for Bone and Mineral Research.

“Hormonal treatment of transgender people is safe with respect to bone,” said Martin den Heijer, MD, PhD, of the VU University Medical Center in Amsterdam.

At baseline, transwomen have lower bone mass than do male reference populations, said Dr. den Heijer, citing a study that found 25 transwomen had less muscle mass (P less than or equal to .001), strength (P less than or equal to .05), and lower BMD at the hip, femoral neck, and spine (P less than .001), compared with 25 cisgender men in a control group and 941 men in a male reference population (Bone. 2013;54[1]:92-7). In a 2019 study from his own group, Dr. den Heijer said the z score in the lumbar spine for 711 transwomen was -0.9 and the incidence of osteoporosis was 14.2%, compared with a z score of 0.0 and 2.4% incidence of osteoporosis in 543 transmen (J Bone Min Res. 2019;34[3]:447-54).

In the prospective European Network for the Investigation of Gender Incongruence (ENIGI) study, researchers examined short-term effects of hormone therapy on BMD in 144 transwomen and 162 transmen who had a normal body mass index and were mostly white. The percentage of patients who reported they were current smokers was between 25% and 30%, and fewer than 10% said they consumed more than seven units of alcohol per week. Transwomen received estradiol (an oral estradiol valerate at a dose of 4 mg/day or an estradiol patch) together with 100 mg/day of cyproterone acetate, and transmen received testosterone in the form of a gel (50 mg/day), intramuscular esters (250 mg every 2-3 weeks), or intramuscular undecanoate at a dose of 1,000 mg every 12 weeks (J Sex Med. 2016;13[6]:994-9).

After 1 year of treatment, there were significant increases in BMD in transwomen in the lumbar spine (3.67%; 95% confidence interval, 3.20%-4.13%), femoral neck (1.86%; 95% CI, 1.41%-2.31%), and total hip (0.97%; 95% CI, 0.62%-1.31%). Transmen also had increased BMD in the lumbar spine (0.86%; 95% CI, 0.38%-1.35%) and total hip (1.04%; 95% CI, 0.64%-1.44%), with a slight decrease in femoral neck BMD (–0.46%; 95% CI, –1.07% to 0.16%).

Dr. den Heijer also discussed the long-term effects of hormone therapy on BMD in the Amsterdam Cohort of Dysphoria (ACOG) study, which consisted of 711 transwomen and 543 transmen and followed some patients out to 2 years, 5 years, and 10 years after beginning hormone therapy (J Sex Med. 2018;15[4]:582-90). Among transwomen, the median age was 33 years, 68.9% had begun hormone therapy, and 75.3% received a gonadectomy; among transmen, the median age was 25 years, 72.9% had begun hormone therapy, and 83.8% received a gonadectomy. Of these patients, dual-energy x-ray absorptiometry data were available for the lumbar spine BMD for 234 transwomen and 236 transmen at 2 years, 174 transwomen and 95 transmen at 5 years, and 102 transwomen and 70 transmen at 10 years.

Although there was no significant mean change in absolute BMD over the 10-year period, the concentration of estradiol in transwomen and transmen affected change in BMD the longer the transperson was receiving hormone therapy: Transwomen who received an estradiol concentration of 118 pmol/L had a decrease of –0.026% at 2 years, –0.044% at 5 years, and –0.009% at 10 years, compared with a dose of 443 pmol/L (+0.044% at 2 years, +0.025% at 5 years, +0.063% at 10 years), whereas transmen also had decreased BMD at the lowest estradiol concentrations of 95 pmol/L (–0.007% at 2 years, –0.024% at 5 years, +0.010% at 10 years), compared with transmen receiving the highest doses of 323 pmol/L (+0.028% at 2 years, +0.002% at 5 years, +0.053% at 10 years). There was no significant change in BMD in either group at any time point with regard to testosterone concentration.

When the investigators linked these patients to a national statistics database in the Netherlands to evaluate fracture incidence (J Bone Miner Res. 2019 Sep 5. doi: 10.1002/jbmr.3862), pairing five cisgender female controls and five cisgender male controls to every transgender patient, the researchers found transwomen had a higher incidence of osteoporotic fracture of the hip, spine, forearm, and humerus (41.8%), compared with cisgender men (26.6%; P = .014) and cisgender women (36.0%; P = .381). There was not enough information in the study to examine fracture information for transmen, Dr. den Heijer said. Transwomen and transmen who experienced a fracture were more likely to be a current smoker and have lower estradiol concentrations than were transwomen and transmen, respectively, who did not have a fracture.

“Attention for lifestyle factors remains important, especially smoking cessation, vitamin D intake, and regular exercise,” Dr. den Heijer said. “It remains important for everybody, but especially for transgender women.”

Dr. den Heijer reported no relevant conflicts of interest.
 

ORLANDO – Transwomen are more likely to have a lower bone mineral density (BMD) before beginning hormone therapy, compared with male reference populations, but there are no short- or long-term risks to bone health over the life of a transperson who receives hormone therapy, according to a presentation at the annual meeting of the American Society for Bone and Mineral Research.

“Hormonal treatment of transgender people is safe with respect to bone,” said Martin den Heijer, MD, PhD, of the VU University Medical Center in Amsterdam.

At baseline, transwomen have lower bone mass than do male reference populations, said Dr. den Heijer, citing a study that found 25 transwomen had less muscle mass (P less than or equal to .001), strength (P less than or equal to .05), and lower BMD at the hip, femoral neck, and spine (P less than .001), compared with 25 cisgender men in a control group and 941 men in a male reference population (Bone. 2013;54[1]:92-7). In a 2019 study from his own group, Dr. den Heijer said the z score in the lumbar spine for 711 transwomen was -0.9 and the incidence of osteoporosis was 14.2%, compared with a z score of 0.0 and 2.4% incidence of osteoporosis in 543 transmen (J Bone Min Res. 2019;34[3]:447-54).

In the prospective European Network for the Investigation of Gender Incongruence (ENIGI) study, researchers examined short-term effects of hormone therapy on BMD in 144 transwomen and 162 transmen who had a normal body mass index and were mostly white. The percentage of patients who reported they were current smokers was between 25% and 30%, and fewer than 10% said they consumed more than seven units of alcohol per week. Transwomen received estradiol (an oral estradiol valerate at a dose of 4 mg/day or an estradiol patch) together with 100 mg/day of cyproterone acetate, and transmen received testosterone in the form of a gel (50 mg/day), intramuscular esters (250 mg every 2-3 weeks), or intramuscular undecanoate at a dose of 1,000 mg every 12 weeks (J Sex Med. 2016;13[6]:994-9).

After 1 year of treatment, there were significant increases in BMD in transwomen in the lumbar spine (3.67%; 95% confidence interval, 3.20%-4.13%), femoral neck (1.86%; 95% CI, 1.41%-2.31%), and total hip (0.97%; 95% CI, 0.62%-1.31%). Transmen also had increased BMD in the lumbar spine (0.86%; 95% CI, 0.38%-1.35%) and total hip (1.04%; 95% CI, 0.64%-1.44%), with a slight decrease in femoral neck BMD (–0.46%; 95% CI, –1.07% to 0.16%).

Dr. den Heijer also discussed the long-term effects of hormone therapy on BMD in the Amsterdam Cohort of Dysphoria (ACOG) study, which consisted of 711 transwomen and 543 transmen and followed some patients out to 2 years, 5 years, and 10 years after beginning hormone therapy (J Sex Med. 2018;15[4]:582-90). Among transwomen, the median age was 33 years, 68.9% had begun hormone therapy, and 75.3% received a gonadectomy; among transmen, the median age was 25 years, 72.9% had begun hormone therapy, and 83.8% received a gonadectomy. Of these patients, dual-energy x-ray absorptiometry data were available for the lumbar spine BMD for 234 transwomen and 236 transmen at 2 years, 174 transwomen and 95 transmen at 5 years, and 102 transwomen and 70 transmen at 10 years.

Although there was no significant mean change in absolute BMD over the 10-year period, the concentration of estradiol in transwomen and transmen affected change in BMD the longer the transperson was receiving hormone therapy: Transwomen who received an estradiol concentration of 118 pmol/L had a decrease of –0.026% at 2 years, –0.044% at 5 years, and –0.009% at 10 years, compared with a dose of 443 pmol/L (+0.044% at 2 years, +0.025% at 5 years, +0.063% at 10 years), whereas transmen also had decreased BMD at the lowest estradiol concentrations of 95 pmol/L (–0.007% at 2 years, –0.024% at 5 years, +0.010% at 10 years), compared with transmen receiving the highest doses of 323 pmol/L (+0.028% at 2 years, +0.002% at 5 years, +0.053% at 10 years). There was no significant change in BMD in either group at any time point with regard to testosterone concentration.

When the investigators linked these patients to a national statistics database in the Netherlands to evaluate fracture incidence (J Bone Miner Res. 2019 Sep 5. doi: 10.1002/jbmr.3862), pairing five cisgender female controls and five cisgender male controls to every transgender patient, the researchers found transwomen had a higher incidence of osteoporotic fracture of the hip, spine, forearm, and humerus (41.8%), compared with cisgender men (26.6%; P = .014) and cisgender women (36.0%; P = .381). There was not enough information in the study to examine fracture information for transmen, Dr. den Heijer said. Transwomen and transmen who experienced a fracture were more likely to be a current smoker and have lower estradiol concentrations than were transwomen and transmen, respectively, who did not have a fracture.

“Attention for lifestyle factors remains important, especially smoking cessation, vitamin D intake, and regular exercise,” Dr. den Heijer said. “It remains important for everybody, but especially for transgender women.”

Dr. den Heijer reported no relevant conflicts of interest.
 

ORLANDO – Transwomen are more likely to have a lower bone mineral density (BMD) before beginning hormone therapy, compared with male reference populations, but there are no short- or long-term risks to bone health over the life of a transperson who receives hormone therapy, according to a presentation at the annual meeting of the American Society for Bone and Mineral Research.

“Hormonal treatment of transgender people is safe with respect to bone,” said Martin den Heijer, MD, PhD, of the VU University Medical Center in Amsterdam.

At baseline, transwomen have lower bone mass than do male reference populations, said Dr. den Heijer, citing a study that found 25 transwomen had less muscle mass (P less than or equal to .001), strength (P less than or equal to .05), and lower BMD at the hip, femoral neck, and spine (P less than .001), compared with 25 cisgender men in a control group and 941 men in a male reference population (Bone. 2013;54[1]:92-7). In a 2019 study from his own group, Dr. den Heijer said the z score in the lumbar spine for 711 transwomen was -0.9 and the incidence of osteoporosis was 14.2%, compared with a z score of 0.0 and 2.4% incidence of osteoporosis in 543 transmen (J Bone Min Res. 2019;34[3]:447-54).

In the prospective European Network for the Investigation of Gender Incongruence (ENIGI) study, researchers examined short-term effects of hormone therapy on BMD in 144 transwomen and 162 transmen who had a normal body mass index and were mostly white. The percentage of patients who reported they were current smokers was between 25% and 30%, and fewer than 10% said they consumed more than seven units of alcohol per week. Transwomen received estradiol (an oral estradiol valerate at a dose of 4 mg/day or an estradiol patch) together with 100 mg/day of cyproterone acetate, and transmen received testosterone in the form of a gel (50 mg/day), intramuscular esters (250 mg every 2-3 weeks), or intramuscular undecanoate at a dose of 1,000 mg every 12 weeks (J Sex Med. 2016;13[6]:994-9).

After 1 year of treatment, there were significant increases in BMD in transwomen in the lumbar spine (3.67%; 95% confidence interval, 3.20%-4.13%), femoral neck (1.86%; 95% CI, 1.41%-2.31%), and total hip (0.97%; 95% CI, 0.62%-1.31%). Transmen also had increased BMD in the lumbar spine (0.86%; 95% CI, 0.38%-1.35%) and total hip (1.04%; 95% CI, 0.64%-1.44%), with a slight decrease in femoral neck BMD (–0.46%; 95% CI, –1.07% to 0.16%).

Dr. den Heijer also discussed the long-term effects of hormone therapy on BMD in the Amsterdam Cohort of Dysphoria (ACOG) study, which consisted of 711 transwomen and 543 transmen and followed some patients out to 2 years, 5 years, and 10 years after beginning hormone therapy (J Sex Med. 2018;15[4]:582-90). Among transwomen, the median age was 33 years, 68.9% had begun hormone therapy, and 75.3% received a gonadectomy; among transmen, the median age was 25 years, 72.9% had begun hormone therapy, and 83.8% received a gonadectomy. Of these patients, dual-energy x-ray absorptiometry data were available for the lumbar spine BMD for 234 transwomen and 236 transmen at 2 years, 174 transwomen and 95 transmen at 5 years, and 102 transwomen and 70 transmen at 10 years.

Although there was no significant mean change in absolute BMD over the 10-year period, the concentration of estradiol in transwomen and transmen affected change in BMD the longer the transperson was receiving hormone therapy: Transwomen who received an estradiol concentration of 118 pmol/L had a decrease of –0.026% at 2 years, –0.044% at 5 years, and –0.009% at 10 years, compared with a dose of 443 pmol/L (+0.044% at 2 years, +0.025% at 5 years, +0.063% at 10 years), whereas transmen also had decreased BMD at the lowest estradiol concentrations of 95 pmol/L (–0.007% at 2 years, –0.024% at 5 years, +0.010% at 10 years), compared with transmen receiving the highest doses of 323 pmol/L (+0.028% at 2 years, +0.002% at 5 years, +0.053% at 10 years). There was no significant change in BMD in either group at any time point with regard to testosterone concentration.

When the investigators linked these patients to a national statistics database in the Netherlands to evaluate fracture incidence (J Bone Miner Res. 2019 Sep 5. doi: 10.1002/jbmr.3862), pairing five cisgender female controls and five cisgender male controls to every transgender patient, the researchers found transwomen had a higher incidence of osteoporotic fracture of the hip, spine, forearm, and humerus (41.8%), compared with cisgender men (26.6%; P = .014) and cisgender women (36.0%; P = .381). There was not enough information in the study to examine fracture information for transmen, Dr. den Heijer said. Transwomen and transmen who experienced a fracture were more likely to be a current smoker and have lower estradiol concentrations than were transwomen and transmen, respectively, who did not have a fracture.

“Attention for lifestyle factors remains important, especially smoking cessation, vitamin D intake, and regular exercise,” Dr. den Heijer said. “It remains important for everybody, but especially for transgender women.”

Dr. den Heijer reported no relevant conflicts of interest.
 

ORLANDO – Clinicians shouldn't let the lack of research on osteoporosis treatment compliance and barriers to care keep them from acting on what's already known about drug therapies' effectiveness in preventing fractures.

That's the advice from leaders at the American Society for Bone and Mineral Research, who discussed recent recommendations issued from a National Institutes of Health Pathways to Prevention Workshop on the “Appropriate Use of Drug Therapies for Osteoporotic Fracture Prevention.”

Speakers at a special session of the annual meeting were in agreement on the need for more research into current barriers of osteoporosis care and new methods for increasing patient and physician compliance with recommendations.

But the focus should also be on what researchers in bone health have already learned about treating osteoporosis, “which is quite a bit,” said Benjamin Z. Leder, MD, of Massachusetts General Hospital and Harvard Medical School, both in Boston, who gave the ASBMR’s perspective at the session. Dr. Leder was also first author on a perspective paper that outlined the society’s concerns about the recommendations coming from the workshop (J Bone Miner Res. 2019;34[9]:1549-51).
 

Gaps in knowledge and treatment

“We thought that [not focusing on what is already known about osteoporosis treatment] perhaps would have the potential to exacerbate the treatment gap that exists in osteoporosis therapy,” Dr. Leder said in his presentation. “We also felt that any knowledge deficits must be understood in the context of what has been unequivocally demonstrated in terms of our knowledge of osteoporosis therapies.”

That includes knowing how to identify patients at the highest risk of fracture, which medications reduce the risk of osteoporotic and osteopenic fractures, and that using these medications saves lives, Dr. Leder noted.

With limited resources in osteoporosis and the absence of any large, randomized, controlled trials or new therapies because of lack of interest from industry, stakeholders should be examining what can be done outside of trials. In osteoporosis, as is the case with any other therapeutic area or disease state, the results of randomized, placebo-controlled trials will not address every patient subgroup of interest, he said.

“Some extrapolation is always required,” Dr. Leder said. “We have to – as we treat, as we practice medicine – use the evidence we have and then try to use that to guide us when the randomized, controlled trial doesn’t answer that specific question.”

Dr. Leder also emphasized that fear of side effects such as osteonecrosis of the jaw and atypical femoral fracture are not the only barriers in osteoporosis care. Adherence is generally poor with osteoporosis treatment, and physicians usually have competing priorities when seeing their patients. “Even in the absence of the idea that these side effects are potentially paralyzing patients and physicians, we have to remember that we started from a fairly low baseline,” Dr. Leder said.

Other issues that complicate the issue of osteoporosis care are misinformation available online that may cause patients to not use medications, overestimations of the benefits of not using osteoporosis medication in favor of nondrug interventions, and conflicting, faulty, or unhelpful guidelines from medical societies, he said.

“There are a lot of issues that need to be addressed. The [Pathways to Prevention] has really done us a great service, and the ASBMR hopes to continue supporting their efforts moving forward,” he said.
 

Recommendations for secondary fracture prevention

Although there are gaps in osteoporosis treatment, there is still room to act, which the ASBMR aimed to accomplish in its Secondary Fracture Prevention Initiative, Douglas P. Kiel, MD, MPH, said in his presentation.

In 2016, the ASBMR put out a Call to Action to intensify screening for high-risk patients to prevent fractures, and 39 organizations signed on to the effort. The target population for the initiative is men and women aged 65 years or older who have experienced a vertebral or hip fracture who would ideally be appropriately evaluated, managed, and treated in a multidisciplinary clinical system with case management through systems like a fracture liaison service.

“The bottom line is, if you have a patient in this age group who has already experienced one of these fractures, they should be treated,” said Dr. Kiel, director of the Musculoskeletal Research Center at the Institute for Aging Research at Hebrew SeniorLife in Boston and a professor of medicine at Harvard Medical School. “It doesn’t mean we should ignore other populations, but we need to start somewhere, and this was a well-defined, at-risk population.”

Consensus clinical recommendations for the initiative were recently published in the Journal of Bone and Mineral Research (J Bone Miner Res. 2019 Sep 20. doi: 10.1002/jbmr.3877), and the ASBMR plans to spread the recommendations in a wide number of areas, including through stakeholder organizations, social media, webinars, educational sessions, and in other guidelines.

The next step for the initiative is to execute the ASBMR’s Action Plan, which prioritizes challenges such as reimbursement for fracture liaison services and care coordination, establishment of a national fracture registry, and sharing the society’s messaging on osteoporosis fracture–prevention in guidelines and education services. The ASBMR is also examining whether it could take advantage of a new National Institutes of Health grant for dissemination and implementation research in health to help fund the Secondary Fracture Prevention Initiative, Dr. Kiel said.

Dr. Leder and Dr. Kiel reported no relevant financial disclosures.

ORLANDO – Clinicians shouldn't let the lack of research on osteoporosis treatment compliance and barriers to care keep them from acting on what's already known about drug therapies' effectiveness in preventing fractures.

That's the advice from leaders at the American Society for Bone and Mineral Research, who discussed recent recommendations issued from a National Institutes of Health Pathways to Prevention Workshop on the “Appropriate Use of Drug Therapies for Osteoporotic Fracture Prevention.”

Speakers at a special session of the annual meeting were in agreement on the need for more research into current barriers of osteoporosis care and new methods for increasing patient and physician compliance with recommendations.

But the focus should also be on what researchers in bone health have already learned about treating osteoporosis, “which is quite a bit,” said Benjamin Z. Leder, MD, of Massachusetts General Hospital and Harvard Medical School, both in Boston, who gave the ASBMR’s perspective at the session. Dr. Leder was also first author on a perspective paper that outlined the society’s concerns about the recommendations coming from the workshop (J Bone Miner Res. 2019;34[9]:1549-51).
 

Gaps in knowledge and treatment

“We thought that [not focusing on what is already known about osteoporosis treatment] perhaps would have the potential to exacerbate the treatment gap that exists in osteoporosis therapy,” Dr. Leder said in his presentation. “We also felt that any knowledge deficits must be understood in the context of what has been unequivocally demonstrated in terms of our knowledge of osteoporosis therapies.”

That includes knowing how to identify patients at the highest risk of fracture, which medications reduce the risk of osteoporotic and osteopenic fractures, and that using these medications saves lives, Dr. Leder noted.

With limited resources in osteoporosis and the absence of any large, randomized, controlled trials or new therapies because of lack of interest from industry, stakeholders should be examining what can be done outside of trials. In osteoporosis, as is the case with any other therapeutic area or disease state, the results of randomized, placebo-controlled trials will not address every patient subgroup of interest, he said.

“Some extrapolation is always required,” Dr. Leder said. “We have to – as we treat, as we practice medicine – use the evidence we have and then try to use that to guide us when the randomized, controlled trial doesn’t answer that specific question.”

Dr. Leder also emphasized that fear of side effects such as osteonecrosis of the jaw and atypical femoral fracture are not the only barriers in osteoporosis care. Adherence is generally poor with osteoporosis treatment, and physicians usually have competing priorities when seeing their patients. “Even in the absence of the idea that these side effects are potentially paralyzing patients and physicians, we have to remember that we started from a fairly low baseline,” Dr. Leder said.

Other issues that complicate the issue of osteoporosis care are misinformation available online that may cause patients to not use medications, overestimations of the benefits of not using osteoporosis medication in favor of nondrug interventions, and conflicting, faulty, or unhelpful guidelines from medical societies, he said.

“There are a lot of issues that need to be addressed. The [Pathways to Prevention] has really done us a great service, and the ASBMR hopes to continue supporting their efforts moving forward,” he said.
 

Recommendations for secondary fracture prevention

Although there are gaps in osteoporosis treatment, there is still room to act, which the ASBMR aimed to accomplish in its Secondary Fracture Prevention Initiative, Douglas P. Kiel, MD, MPH, said in his presentation.

In 2016, the ASBMR put out a Call to Action to intensify screening for high-risk patients to prevent fractures, and 39 organizations signed on to the effort. The target population for the initiative is men and women aged 65 years or older who have experienced a vertebral or hip fracture who would ideally be appropriately evaluated, managed, and treated in a multidisciplinary clinical system with case management through systems like a fracture liaison service.

“The bottom line is, if you have a patient in this age group who has already experienced one of these fractures, they should be treated,” said Dr. Kiel, director of the Musculoskeletal Research Center at the Institute for Aging Research at Hebrew SeniorLife in Boston and a professor of medicine at Harvard Medical School. “It doesn’t mean we should ignore other populations, but we need to start somewhere, and this was a well-defined, at-risk population.”

Consensus clinical recommendations for the initiative were recently published in the Journal of Bone and Mineral Research (J Bone Miner Res. 2019 Sep 20. doi: 10.1002/jbmr.3877), and the ASBMR plans to spread the recommendations in a wide number of areas, including through stakeholder organizations, social media, webinars, educational sessions, and in other guidelines.

The next step for the initiative is to execute the ASBMR’s Action Plan, which prioritizes challenges such as reimbursement for fracture liaison services and care coordination, establishment of a national fracture registry, and sharing the society’s messaging on osteoporosis fracture–prevention in guidelines and education services. The ASBMR is also examining whether it could take advantage of a new National Institutes of Health grant for dissemination and implementation research in health to help fund the Secondary Fracture Prevention Initiative, Dr. Kiel said.

Dr. Leder and Dr. Kiel reported no relevant financial disclosures.

ORLANDO – Clinicians shouldn't let the lack of research on osteoporosis treatment compliance and barriers to care keep them from acting on what's already known about drug therapies' effectiveness in preventing fractures.

That's the advice from leaders at the American Society for Bone and Mineral Research, who discussed recent recommendations issued from a National Institutes of Health Pathways to Prevention Workshop on the “Appropriate Use of Drug Therapies for Osteoporotic Fracture Prevention.”

Speakers at a special session of the annual meeting were in agreement on the need for more research into current barriers of osteoporosis care and new methods for increasing patient and physician compliance with recommendations.

But the focus should also be on what researchers in bone health have already learned about treating osteoporosis, “which is quite a bit,” said Benjamin Z. Leder, MD, of Massachusetts General Hospital and Harvard Medical School, both in Boston, who gave the ASBMR’s perspective at the session. Dr. Leder was also first author on a perspective paper that outlined the society’s concerns about the recommendations coming from the workshop (J Bone Miner Res. 2019;34[9]:1549-51).
 

Gaps in knowledge and treatment

“We thought that [not focusing on what is already known about osteoporosis treatment] perhaps would have the potential to exacerbate the treatment gap that exists in osteoporosis therapy,” Dr. Leder said in his presentation. “We also felt that any knowledge deficits must be understood in the context of what has been unequivocally demonstrated in terms of our knowledge of osteoporosis therapies.”

That includes knowing how to identify patients at the highest risk of fracture, which medications reduce the risk of osteoporotic and osteopenic fractures, and that using these medications saves lives, Dr. Leder noted.

With limited resources in osteoporosis and the absence of any large, randomized, controlled trials or new therapies because of lack of interest from industry, stakeholders should be examining what can be done outside of trials. In osteoporosis, as is the case with any other therapeutic area or disease state, the results of randomized, placebo-controlled trials will not address every patient subgroup of interest, he said.

“Some extrapolation is always required,” Dr. Leder said. “We have to – as we treat, as we practice medicine – use the evidence we have and then try to use that to guide us when the randomized, controlled trial doesn’t answer that specific question.”

Dr. Leder also emphasized that fear of side effects such as osteonecrosis of the jaw and atypical femoral fracture are not the only barriers in osteoporosis care. Adherence is generally poor with osteoporosis treatment, and physicians usually have competing priorities when seeing their patients. “Even in the absence of the idea that these side effects are potentially paralyzing patients and physicians, we have to remember that we started from a fairly low baseline,” Dr. Leder said.

Other issues that complicate the issue of osteoporosis care are misinformation available online that may cause patients to not use medications, overestimations of the benefits of not using osteoporosis medication in favor of nondrug interventions, and conflicting, faulty, or unhelpful guidelines from medical societies, he said.

“There are a lot of issues that need to be addressed. The [Pathways to Prevention] has really done us a great service, and the ASBMR hopes to continue supporting their efforts moving forward,” he said.
 

Recommendations for secondary fracture prevention

Although there are gaps in osteoporosis treatment, there is still room to act, which the ASBMR aimed to accomplish in its Secondary Fracture Prevention Initiative, Douglas P. Kiel, MD, MPH, said in his presentation.

In 2016, the ASBMR put out a Call to Action to intensify screening for high-risk patients to prevent fractures, and 39 organizations signed on to the effort. The target population for the initiative is men and women aged 65 years or older who have experienced a vertebral or hip fracture who would ideally be appropriately evaluated, managed, and treated in a multidisciplinary clinical system with case management through systems like a fracture liaison service.

“The bottom line is, if you have a patient in this age group who has already experienced one of these fractures, they should be treated,” said Dr. Kiel, director of the Musculoskeletal Research Center at the Institute for Aging Research at Hebrew SeniorLife in Boston and a professor of medicine at Harvard Medical School. “It doesn’t mean we should ignore other populations, but we need to start somewhere, and this was a well-defined, at-risk population.”

Consensus clinical recommendations for the initiative were recently published in the Journal of Bone and Mineral Research (J Bone Miner Res. 2019 Sep 20. doi: 10.1002/jbmr.3877), and the ASBMR plans to spread the recommendations in a wide number of areas, including through stakeholder organizations, social media, webinars, educational sessions, and in other guidelines.

The next step for the initiative is to execute the ASBMR’s Action Plan, which prioritizes challenges such as reimbursement for fracture liaison services and care coordination, establishment of a national fracture registry, and sharing the society’s messaging on osteoporosis fracture–prevention in guidelines and education services. The ASBMR is also examining whether it could take advantage of a new National Institutes of Health grant for dissemination and implementation research in health to help fund the Secondary Fracture Prevention Initiative, Dr. Kiel said.

Dr. Leder and Dr. Kiel reported no relevant financial disclosures.

ORLANDO – A single infusion of zoledronic acid does not completely prevent bone mineral density (BMD) loss regardless of the timing of the infusion in patients with osteopenia who discontinued denosumab (Prolia), according to a speaker at the annual meeting of the American Society for Bone and Mineral Research.

“If you consider a treatment break in patients treated with [denosumab] for a long time, I suggest to aim for a higher BMD, allowing a smaller bone loss when transitioning via [zoledronic acid] to a treatment break, or maybe you need to give more than one infusion of [zoledronic acid],” said Bente Langdahl, MD, PhD, of Aarhus (Denmark) University Hospital during her presentation.

Dr. Langdahl and her colleagues enrolled 60 patients with osteopenia in a 2-year, randomized, open-label interventional study of patients who discontinued denosumab after more than 2 years of use (average treatment, 4.6 years). One group of 20 patients received 5 mg of zoledronic acid at 6 months after their last denosumab injection. Another group of 20 patients underwent monthly monitoring starting at 6 months after their last denosumab injection and received zoledronic acid if their s-carboxy-terminal collagen crosslinks (s-CTX) increased more than 1.26 mcg/L or if they reached 9 months after their last denosumab injection. A third group underwent observation with monthly monitoring starting at 6 months after their last denosumab injection, and they received zoledronic acid if s-CTX increased more than 1.26 mcg/L, BMD loss was 5% or more at any site, they experienced a fragility vertebral or hip fracture, or they reached 12 months after their last denosumab injection. All patients received a readministration of zoledronic acid if their BMD decreased by greater than 5% or if their s-CTX increased more than 1.26 mcg/L after 6 months, 12 months, or 24 months.

The researchers included postmenopausal women and men older than 50 years (mean, 67.7 years), but the majority of patients were women (n = 53) distributed evenly between the 6-month, 9-month, and observation groups. Patients were excluded if they had a low-energy vertebral fracture, had any hip fracture within 12 months, had a T score of less than –2.5 at any site, had received alendronate more than 3 years prior to taking denosumab, used glucocorticoids, had metabolic bone disease, had received hormone replacement therapy, or had cancer.

The observational group patients who met criteria to receive zoledronic acid because of increased s-CTX included one at 1 month after stopping denosumab, two at 2 months, six at 3 months, and one at 4 months. Of six patients who met BMD criteria for treatment at 3 months, one received retreatment 6 months after their first administration of zoledronic acid, and four patients received retreatment at 12 months.

At 2 months, two patients in the 9-month group met s-CTX criteria for treatment, four patients underwent retreatment under BMD criteria 6 months after the first administration of zoledronic acid, and one patient underwent retreatment at 12 months under BMD criteria. In the 6-month group, one patient met s-CTX criteria for retreatment at 6 months, and one patient at 12 months, with five patients meeting BMD criteria for retreatment at 6 months and at 12 months.

Overall, the average bone loss was 4.6% at the lumbar spine and 3.2% for total hip with no clinically significant between-group differences for either site. At 12 months, lumbar spine bone loss was 4.8% in the 6-month group, 4.2% in the 9-month group, and 4.9% in the observational group (P less than or equal to .006), and total hip bone loss was 2.6% in the 6-month group, 3.3% in the 9-month group, and 3.8% in the observational group (P less than or equal to .001).

Although the study followed patients for 2 years after the first zoledronic acid injection, data were available for the first year only, and the study is ongoing, Dr. Langdahl said.

This study was funded in part by Amgen, the Foundation of Vilhelm Pedersen and wife, Aarhus University, the Danish Osteoporosis Society Research Foundation, the P. Carl Petersens Foundation, and the Torkil Steenbeck Foundation. Dr. Langdahl reported receiving research funding from Amgen and Novo Nordisk and is on the advisory board for Amgen, Eli Lilly, and UCB.

SOURCE: Sølling A. ASBMR 2019. Abstract LB-1169

ORLANDO – A single infusion of zoledronic acid does not completely prevent bone mineral density (BMD) loss regardless of the timing of the infusion in patients with osteopenia who discontinued denosumab (Prolia), according to a speaker at the annual meeting of the American Society for Bone and Mineral Research.

“If you consider a treatment break in patients treated with [denosumab] for a long time, I suggest to aim for a higher BMD, allowing a smaller bone loss when transitioning via [zoledronic acid] to a treatment break, or maybe you need to give more than one infusion of [zoledronic acid],” said Bente Langdahl, MD, PhD, of Aarhus (Denmark) University Hospital during her presentation.

Dr. Langdahl and her colleagues enrolled 60 patients with osteopenia in a 2-year, randomized, open-label interventional study of patients who discontinued denosumab after more than 2 years of use (average treatment, 4.6 years). One group of 20 patients received 5 mg of zoledronic acid at 6 months after their last denosumab injection. Another group of 20 patients underwent monthly monitoring starting at 6 months after their last denosumab injection and received zoledronic acid if their s-carboxy-terminal collagen crosslinks (s-CTX) increased more than 1.26 mcg/L or if they reached 9 months after their last denosumab injection. A third group underwent observation with monthly monitoring starting at 6 months after their last denosumab injection, and they received zoledronic acid if s-CTX increased more than 1.26 mcg/L, BMD loss was 5% or more at any site, they experienced a fragility vertebral or hip fracture, or they reached 12 months after their last denosumab injection. All patients received a readministration of zoledronic acid if their BMD decreased by greater than 5% or if their s-CTX increased more than 1.26 mcg/L after 6 months, 12 months, or 24 months.

The researchers included postmenopausal women and men older than 50 years (mean, 67.7 years), but the majority of patients were women (n = 53) distributed evenly between the 6-month, 9-month, and observation groups. Patients were excluded if they had a low-energy vertebral fracture, had any hip fracture within 12 months, had a T score of less than –2.5 at any site, had received alendronate more than 3 years prior to taking denosumab, used glucocorticoids, had metabolic bone disease, had received hormone replacement therapy, or had cancer.

The observational group patients who met criteria to receive zoledronic acid because of increased s-CTX included one at 1 month after stopping denosumab, two at 2 months, six at 3 months, and one at 4 months. Of six patients who met BMD criteria for treatment at 3 months, one received retreatment 6 months after their first administration of zoledronic acid, and four patients received retreatment at 12 months.

At 2 months, two patients in the 9-month group met s-CTX criteria for treatment, four patients underwent retreatment under BMD criteria 6 months after the first administration of zoledronic acid, and one patient underwent retreatment at 12 months under BMD criteria. In the 6-month group, one patient met s-CTX criteria for retreatment at 6 months, and one patient at 12 months, with five patients meeting BMD criteria for retreatment at 6 months and at 12 months.

Overall, the average bone loss was 4.6% at the lumbar spine and 3.2% for total hip with no clinically significant between-group differences for either site. At 12 months, lumbar spine bone loss was 4.8% in the 6-month group, 4.2% in the 9-month group, and 4.9% in the observational group (P less than or equal to .006), and total hip bone loss was 2.6% in the 6-month group, 3.3% in the 9-month group, and 3.8% in the observational group (P less than or equal to .001).

Although the study followed patients for 2 years after the first zoledronic acid injection, data were available for the first year only, and the study is ongoing, Dr. Langdahl said.

This study was funded in part by Amgen, the Foundation of Vilhelm Pedersen and wife, Aarhus University, the Danish Osteoporosis Society Research Foundation, the P. Carl Petersens Foundation, and the Torkil Steenbeck Foundation. Dr. Langdahl reported receiving research funding from Amgen and Novo Nordisk and is on the advisory board for Amgen, Eli Lilly, and UCB.

SOURCE: Sølling A. ASBMR 2019. Abstract LB-1169

ORLANDO – A single infusion of zoledronic acid does not completely prevent bone mineral density (BMD) loss regardless of the timing of the infusion in patients with osteopenia who discontinued denosumab (Prolia), according to a speaker at the annual meeting of the American Society for Bone and Mineral Research.

“If you consider a treatment break in patients treated with [denosumab] for a long time, I suggest to aim for a higher BMD, allowing a smaller bone loss when transitioning via [zoledronic acid] to a treatment break, or maybe you need to give more than one infusion of [zoledronic acid],” said Bente Langdahl, MD, PhD, of Aarhus (Denmark) University Hospital during her presentation.

Dr. Langdahl and her colleagues enrolled 60 patients with osteopenia in a 2-year, randomized, open-label interventional study of patients who discontinued denosumab after more than 2 years of use (average treatment, 4.6 years). One group of 20 patients received 5 mg of zoledronic acid at 6 months after their last denosumab injection. Another group of 20 patients underwent monthly monitoring starting at 6 months after their last denosumab injection and received zoledronic acid if their s-carboxy-terminal collagen crosslinks (s-CTX) increased more than 1.26 mcg/L or if they reached 9 months after their last denosumab injection. A third group underwent observation with monthly monitoring starting at 6 months after their last denosumab injection, and they received zoledronic acid if s-CTX increased more than 1.26 mcg/L, BMD loss was 5% or more at any site, they experienced a fragility vertebral or hip fracture, or they reached 12 months after their last denosumab injection. All patients received a readministration of zoledronic acid if their BMD decreased by greater than 5% or if their s-CTX increased more than 1.26 mcg/L after 6 months, 12 months, or 24 months.

The researchers included postmenopausal women and men older than 50 years (mean, 67.7 years), but the majority of patients were women (n = 53) distributed evenly between the 6-month, 9-month, and observation groups. Patients were excluded if they had a low-energy vertebral fracture, had any hip fracture within 12 months, had a T score of less than –2.5 at any site, had received alendronate more than 3 years prior to taking denosumab, used glucocorticoids, had metabolic bone disease, had received hormone replacement therapy, or had cancer.

The observational group patients who met criteria to receive zoledronic acid because of increased s-CTX included one at 1 month after stopping denosumab, two at 2 months, six at 3 months, and one at 4 months. Of six patients who met BMD criteria for treatment at 3 months, one received retreatment 6 months after their first administration of zoledronic acid, and four patients received retreatment at 12 months.

At 2 months, two patients in the 9-month group met s-CTX criteria for treatment, four patients underwent retreatment under BMD criteria 6 months after the first administration of zoledronic acid, and one patient underwent retreatment at 12 months under BMD criteria. In the 6-month group, one patient met s-CTX criteria for retreatment at 6 months, and one patient at 12 months, with five patients meeting BMD criteria for retreatment at 6 months and at 12 months.

Overall, the average bone loss was 4.6% at the lumbar spine and 3.2% for total hip with no clinically significant between-group differences for either site. At 12 months, lumbar spine bone loss was 4.8% in the 6-month group, 4.2% in the 9-month group, and 4.9% in the observational group (P less than or equal to .006), and total hip bone loss was 2.6% in the 6-month group, 3.3% in the 9-month group, and 3.8% in the observational group (P less than or equal to .001).

Although the study followed patients for 2 years after the first zoledronic acid injection, data were available for the first year only, and the study is ongoing, Dr. Langdahl said.

This study was funded in part by Amgen, the Foundation of Vilhelm Pedersen and wife, Aarhus University, the Danish Osteoporosis Society Research Foundation, the P. Carl Petersens Foundation, and the Torkil Steenbeck Foundation. Dr. Langdahl reported receiving research funding from Amgen and Novo Nordisk and is on the advisory board for Amgen, Eli Lilly, and UCB.

SOURCE: Sølling A. ASBMR 2019. Abstract LB-1169

ORLANDO – There still are many questions left to be answered about how gender-affirming medical therapies affect gender diverse youth, Janet Y. Lee, MD, MPH, said at the annual meeting of the American Society for Bone and Mineral Research.

Fertnig/E+/Getty Images

According to a report from The Williams Institute in 2017, there were approximately 150,000 youth in the United States who identified as transgender, and among studies that measured transgender identity among youth, the percentage who identified as transgender ranged between 1.3% and 3.2% (Herman J et al. “Age of Individuals who Identify as Transgender in the United States.” Los Angeles: The Williams Institute, January 2017).

“If you’ve not seen one of these patients yet, you probably will in your career,” said Dr. Lee of the University of California, San Francisco.

At UCSF, Dr. Lee said the focus of care for transgender youth in early childhood to late childhood is on school resources and social transition, with puberty blockers such as gonadotropin-releasing hormone agents (GnRHa) beginning in late childhood and early puberty at Tanner stage 2. When patients reach early puberty and move to late puberty and adulthood, they usually begin gender-affirming sex hormones such as testosterone for masculinizing hormone therapy or estrogen and spironolactone or bicalutamide for feminizing hormone therapy in transgender women, and consideration of fertility preservation is undertaken. In adulthood, patients can begin gender-affirming surgery.

Dr. Lee said the specific timing of gender-affirming sex hormones is controversial and “seems to be a moving target in our field.” The average age to begin gender-affirming sex hormones at UCSF is 14 years old, but sometimes younger, said Dr. Lee. There also is a question of when to start gender-affirming sex hormones in gender diverse youth. “[They] may not want full adult doses of testosterone or full adult doses of estradiol,” said Dr. Lee. “It’s been very challenging to figure out [appropriate] treatment for these youth.”

In Europe, some studies have shown transwomen have lower bone mineral density (BMD) scores at baseline even after 2.5 years to 5 years of treatment with estradiol, compared with male reference standards. A study by Vlot et al. found transwomen had lower bone turnover markers and bone mineral apparent density in cohorts younger than 15 years old, compared with cohorts 15 years or older (Bone. 2017 Feb. doi: 10.1016/j.bone.2016.11.008).

As in the case of when to start gender-affirming sex hormones, how to approach treatment for gender diverse youth who have a low baseline BMD but are eligible for puberty blockers is debated. “We could go into a whole other talk about this because we have many [patients] who present with low baseline BMD,” said Dr. Lee. “We have to figure out a way to apply treatment without impairing their bone.”

Other questions that have yet to be answered are what dual x-ray absorptiometry standards to be used for transgender individuals and how body composition and height growth are affected by gender-affirming medical therapy, which is currently “really modeled after hypergonadic children,” said Dr. Lee.

Results from a National Institutes of Health–funded longitudinal observational study of transgender youth at UCSF, Children’s Hospital Los Angeles, Boston Children’s Hospital, and Ann & Robert H. Lurie Children’s Hospital of Chicago is currently examining the effect of using gender-affirming medical treatment for patients in early and late puberty and assessing factors such as mental health, psychological well-being, and bone health measures such as dual x-ray absorptiometry and quantitative computed tomography, as well as investigating dietary intake, physical activity and exercise, and vitamin D status. Preliminary findings from the study have shown low BMD z-scores in designated males at birth when compared with designated females at birth, with suboptimal dietary calcium intake in both designated males and designated females.

Dr. Lee reported no relevant conflicts of interest.

ORLANDO – There still are many questions left to be answered about how gender-affirming medical therapies affect gender diverse youth, Janet Y. Lee, MD, MPH, said at the annual meeting of the American Society for Bone and Mineral Research.

Fertnig/E+/Getty Images

According to a report from The Williams Institute in 2017, there were approximately 150,000 youth in the United States who identified as transgender, and among studies that measured transgender identity among youth, the percentage who identified as transgender ranged between 1.3% and 3.2% (Herman J et al. “Age of Individuals who Identify as Transgender in the United States.” Los Angeles: The Williams Institute, January 2017).

“If you’ve not seen one of these patients yet, you probably will in your career,” said Dr. Lee of the University of California, San Francisco.

At UCSF, Dr. Lee said the focus of care for transgender youth in early childhood to late childhood is on school resources and social transition, with puberty blockers such as gonadotropin-releasing hormone agents (GnRHa) beginning in late childhood and early puberty at Tanner stage 2. When patients reach early puberty and move to late puberty and adulthood, they usually begin gender-affirming sex hormones such as testosterone for masculinizing hormone therapy or estrogen and spironolactone or bicalutamide for feminizing hormone therapy in transgender women, and consideration of fertility preservation is undertaken. In adulthood, patients can begin gender-affirming surgery.

Dr. Lee said the specific timing of gender-affirming sex hormones is controversial and “seems to be a moving target in our field.” The average age to begin gender-affirming sex hormones at UCSF is 14 years old, but sometimes younger, said Dr. Lee. There also is a question of when to start gender-affirming sex hormones in gender diverse youth. “[They] may not want full adult doses of testosterone or full adult doses of estradiol,” said Dr. Lee. “It’s been very challenging to figure out [appropriate] treatment for these youth.”

In Europe, some studies have shown transwomen have lower bone mineral density (BMD) scores at baseline even after 2.5 years to 5 years of treatment with estradiol, compared with male reference standards. A study by Vlot et al. found transwomen had lower bone turnover markers and bone mineral apparent density in cohorts younger than 15 years old, compared with cohorts 15 years or older (Bone. 2017 Feb. doi: 10.1016/j.bone.2016.11.008).

As in the case of when to start gender-affirming sex hormones, how to approach treatment for gender diverse youth who have a low baseline BMD but are eligible for puberty blockers is debated. “We could go into a whole other talk about this because we have many [patients] who present with low baseline BMD,” said Dr. Lee. “We have to figure out a way to apply treatment without impairing their bone.”

Other questions that have yet to be answered are what dual x-ray absorptiometry standards to be used for transgender individuals and how body composition and height growth are affected by gender-affirming medical therapy, which is currently “really modeled after hypergonadic children,” said Dr. Lee.

Results from a National Institutes of Health–funded longitudinal observational study of transgender youth at UCSF, Children’s Hospital Los Angeles, Boston Children’s Hospital, and Ann & Robert H. Lurie Children’s Hospital of Chicago is currently examining the effect of using gender-affirming medical treatment for patients in early and late puberty and assessing factors such as mental health, psychological well-being, and bone health measures such as dual x-ray absorptiometry and quantitative computed tomography, as well as investigating dietary intake, physical activity and exercise, and vitamin D status. Preliminary findings from the study have shown low BMD z-scores in designated males at birth when compared with designated females at birth, with suboptimal dietary calcium intake in both designated males and designated females.

Dr. Lee reported no relevant conflicts of interest.

ORLANDO – There still are many questions left to be answered about how gender-affirming medical therapies affect gender diverse youth, Janet Y. Lee, MD, MPH, said at the annual meeting of the American Society for Bone and Mineral Research.

Fertnig/E+/Getty Images

According to a report from The Williams Institute in 2017, there were approximately 150,000 youth in the United States who identified as transgender, and among studies that measured transgender identity among youth, the percentage who identified as transgender ranged between 1.3% and 3.2% (Herman J et al. “Age of Individuals who Identify as Transgender in the United States.” Los Angeles: The Williams Institute, January 2017).

“If you’ve not seen one of these patients yet, you probably will in your career,” said Dr. Lee of the University of California, San Francisco.

At UCSF, Dr. Lee said the focus of care for transgender youth in early childhood to late childhood is on school resources and social transition, with puberty blockers such as gonadotropin-releasing hormone agents (GnRHa) beginning in late childhood and early puberty at Tanner stage 2. When patients reach early puberty and move to late puberty and adulthood, they usually begin gender-affirming sex hormones such as testosterone for masculinizing hormone therapy or estrogen and spironolactone or bicalutamide for feminizing hormone therapy in transgender women, and consideration of fertility preservation is undertaken. In adulthood, patients can begin gender-affirming surgery.

Dr. Lee said the specific timing of gender-affirming sex hormones is controversial and “seems to be a moving target in our field.” The average age to begin gender-affirming sex hormones at UCSF is 14 years old, but sometimes younger, said Dr. Lee. There also is a question of when to start gender-affirming sex hormones in gender diverse youth. “[They] may not want full adult doses of testosterone or full adult doses of estradiol,” said Dr. Lee. “It’s been very challenging to figure out [appropriate] treatment for these youth.”

In Europe, some studies have shown transwomen have lower bone mineral density (BMD) scores at baseline even after 2.5 years to 5 years of treatment with estradiol, compared with male reference standards. A study by Vlot et al. found transwomen had lower bone turnover markers and bone mineral apparent density in cohorts younger than 15 years old, compared with cohorts 15 years or older (Bone. 2017 Feb. doi: 10.1016/j.bone.2016.11.008).

As in the case of when to start gender-affirming sex hormones, how to approach treatment for gender diverse youth who have a low baseline BMD but are eligible for puberty blockers is debated. “We could go into a whole other talk about this because we have many [patients] who present with low baseline BMD,” said Dr. Lee. “We have to figure out a way to apply treatment without impairing their bone.”

Other questions that have yet to be answered are what dual x-ray absorptiometry standards to be used for transgender individuals and how body composition and height growth are affected by gender-affirming medical therapy, which is currently “really modeled after hypergonadic children,” said Dr. Lee.

Results from a National Institutes of Health–funded longitudinal observational study of transgender youth at UCSF, Children’s Hospital Los Angeles, Boston Children’s Hospital, and Ann & Robert H. Lurie Children’s Hospital of Chicago is currently examining the effect of using gender-affirming medical treatment for patients in early and late puberty and assessing factors such as mental health, psychological well-being, and bone health measures such as dual x-ray absorptiometry and quantitative computed tomography, as well as investigating dietary intake, physical activity and exercise, and vitamin D status. Preliminary findings from the study have shown low BMD z-scores in designated males at birth when compared with designated females at birth, with suboptimal dietary calcium intake in both designated males and designated females.

Dr. Lee reported no relevant conflicts of interest.

ORLANDO – Use of romosozumab (Evenity) by patients with osteoporosis in various stages of renal insufficiency did not appear to affect increases in bone mineral density, the rate of new vertebral fractures, or the number of adverse events when compared with placebo, Paul D. Miller, MD, said at the annual meeting of the American Society for Bone and Mineral Research.

“Romosozumab could be considered a treatment option for osteoporotic patients with mild to moderate reductions in renal function,” said Dr. Miller, distinguished clinical professor of medicine at the University of Colorado at Denver, Aurora.

Since bisphosphonates are not recommended for use in patients with an estimated glomerular filtration rate (eGFR) of less than 30 or 35 mL/min/1.73 m², other osteoporosis treatments such as romosozumab should also be examined. “It is important to evaluate other osteoporosis treatments in this setting, particularly in the context of monoclonal antibodies, which are not cleared in the kidneys and are metabolized in the reticular endothelial system, and have no FDA ... cut-off for their use,” Dr. Miller said.

Dr. Miller and colleagues performed a post hoc analysis of patients in the FRAME study, which enrolled 3,589 patients who received a monthly dose of subcutaneous romosozumab (215 mg) and 3,591 patients who received placebo in a double-blinded study for 12 months before moving to a 12-month, open-label portion of the study where all patients received 60 mg of subcutaneous denosumab every 6 months. After 12 months, the researchers analyzed the least squares mean (LSM) percentage change in bone mineral density (BMD) at the total hip, lumbar spine, and femoral neck as well as whether patients had any new vertebral fractures or experienced adverse events from treatment.

Patients were postmenopausal women between ages 55 and 90 years with a BMD T-score between –2.5 and –3.5 at the total hip or femoral neck. Researchers divided patients into four eGFR groups based chronic kidney disease (CKD) stage: normal (90 mL/min/1.73 m² or higher; 848 patients), mild CKD (60-89 mL/min/1.73 m²; 4,939 patients), moderate CKD (30-59 mL/min/1.73 m²; 1,360 patients), and severe (15-29 mL/min/1.73 m²; 18 patients).

The LSM percentage change was 13.1% in the lumbar spine (95% confidence interval, 12.8%-13.3%) for the romosozumab group, compared with 0.4% in the placebo group (95% CI, 0.2%-0.5%). The LSM percentage change for total hip was 6.0% in the romosozumab group (95% CI, 5.9%-6.2%), compared with 0.3% in the placebo group (95% CI, 0.1%-0.4%), while the LSM percentage change for the femoral neck was 5.5% in the romosozumab group (95% CI, 5.2%-5.7%) and 0.3% in the placebo group (0.1%-0.5%).

“[The] risk of new vertebral fractures was decreased in all eGFR subgroups and did not appear to be affected by eGFR level,” he said.

Specifically, vertebral fracture incidence was 0.5% in the romosozumab group, compared with 3.0% in the placebo group, for patients with normal renal function, 0.4% in the romosozumab group, compared with 1.5% in the placebo group, for patients with mild chronic kidney disease, and 0.6% in the romosozumab group vs. 2.1% in the placebo group for patients with moderate chronic kidney disease. The incidence of adverse events, serious adverse events, and positively adjudicated cardiovascular events were similar between patients in the romosozumab group regardless of renal function status. The researchers reported 1 patient in the romosozumab group who experienced grade 2 hypocalcemia, and 14 patients in the romosozumab group who experienced mild to moderate decreases in calcium, compared with 4 patients in the placebo group.

Dr. Miller noted the study was limited by having few patients with an eGFR of less than 30 mL/min/1.73 m² and no patients with an eGFR of less than 15 mL/min/1.73 m², but said the study strengths were its large randomized nature and well-balanced baseline characteristics between each group.

This study was sponsored in part by Amgen, Astellas, and UCB Pharma. Dr. Miller reported receiving grants from Alexion, Amgen, Radius, Regeneron, UCB, and Ultragenyx. Amgen and UCB assisted in and provided financial assistance for the preparation of Dr. Miller’s presentation.

SOURCE: Miller P et al. ASBMR 2019. Abstract 1085.

ORLANDO – Use of romosozumab (Evenity) by patients with osteoporosis in various stages of renal insufficiency did not appear to affect increases in bone mineral density, the rate of new vertebral fractures, or the number of adverse events when compared with placebo, Paul D. Miller, MD, said at the annual meeting of the American Society for Bone and Mineral Research.

“Romosozumab could be considered a treatment option for osteoporotic patients with mild to moderate reductions in renal function,” said Dr. Miller, distinguished clinical professor of medicine at the University of Colorado at Denver, Aurora.

Since bisphosphonates are not recommended for use in patients with an estimated glomerular filtration rate (eGFR) of less than 30 or 35 mL/min/1.73 m², other osteoporosis treatments such as romosozumab should also be examined. “It is important to evaluate other osteoporosis treatments in this setting, particularly in the context of monoclonal antibodies, which are not cleared in the kidneys and are metabolized in the reticular endothelial system, and have no FDA ... cut-off for their use,” Dr. Miller said.

Dr. Miller and colleagues performed a post hoc analysis of patients in the FRAME study, which enrolled 3,589 patients who received a monthly dose of subcutaneous romosozumab (215 mg) and 3,591 patients who received placebo in a double-blinded study for 12 months before moving to a 12-month, open-label portion of the study where all patients received 60 mg of subcutaneous denosumab every 6 months. After 12 months, the researchers analyzed the least squares mean (LSM) percentage change in bone mineral density (BMD) at the total hip, lumbar spine, and femoral neck as well as whether patients had any new vertebral fractures or experienced adverse events from treatment.

Patients were postmenopausal women between ages 55 and 90 years with a BMD T-score between –2.5 and –3.5 at the total hip or femoral neck. Researchers divided patients into four eGFR groups based chronic kidney disease (CKD) stage: normal (90 mL/min/1.73 m² or higher; 848 patients), mild CKD (60-89 mL/min/1.73 m²; 4,939 patients), moderate CKD (30-59 mL/min/1.73 m²; 1,360 patients), and severe (15-29 mL/min/1.73 m²; 18 patients).

The LSM percentage change was 13.1% in the lumbar spine (95% confidence interval, 12.8%-13.3%) for the romosozumab group, compared with 0.4% in the placebo group (95% CI, 0.2%-0.5%). The LSM percentage change for total hip was 6.0% in the romosozumab group (95% CI, 5.9%-6.2%), compared with 0.3% in the placebo group (95% CI, 0.1%-0.4%), while the LSM percentage change for the femoral neck was 5.5% in the romosozumab group (95% CI, 5.2%-5.7%) and 0.3% in the placebo group (0.1%-0.5%).

“[The] risk of new vertebral fractures was decreased in all eGFR subgroups and did not appear to be affected by eGFR level,” he said.

Specifically, vertebral fracture incidence was 0.5% in the romosozumab group, compared with 3.0% in the placebo group, for patients with normal renal function, 0.4% in the romosozumab group, compared with 1.5% in the placebo group, for patients with mild chronic kidney disease, and 0.6% in the romosozumab group vs. 2.1% in the placebo group for patients with moderate chronic kidney disease. The incidence of adverse events, serious adverse events, and positively adjudicated cardiovascular events were similar between patients in the romosozumab group regardless of renal function status. The researchers reported 1 patient in the romosozumab group who experienced grade 2 hypocalcemia, and 14 patients in the romosozumab group who experienced mild to moderate decreases in calcium, compared with 4 patients in the placebo group.

Dr. Miller noted the study was limited by having few patients with an eGFR of less than 30 mL/min/1.73 m² and no patients with an eGFR of less than 15 mL/min/1.73 m², but said the study strengths were its large randomized nature and well-balanced baseline characteristics between each group.

This study was sponsored in part by Amgen, Astellas, and UCB Pharma. Dr. Miller reported receiving grants from Alexion, Amgen, Radius, Regeneron, UCB, and Ultragenyx. Amgen and UCB assisted in and provided financial assistance for the preparation of Dr. Miller’s presentation.

SOURCE: Miller P et al. ASBMR 2019. Abstract 1085.

ORLANDO – Use of romosozumab (Evenity) by patients with osteoporosis in various stages of renal insufficiency did not appear to affect increases in bone mineral density, the rate of new vertebral fractures, or the number of adverse events when compared with placebo, Paul D. Miller, MD, said at the annual meeting of the American Society for Bone and Mineral Research.

“Romosozumab could be considered a treatment option for osteoporotic patients with mild to moderate reductions in renal function,” said Dr. Miller, distinguished clinical professor of medicine at the University of Colorado at Denver, Aurora.

Since bisphosphonates are not recommended for use in patients with an estimated glomerular filtration rate (eGFR) of less than 30 or 35 mL/min/1.73 m², other osteoporosis treatments such as romosozumab should also be examined. “It is important to evaluate other osteoporosis treatments in this setting, particularly in the context of monoclonal antibodies, which are not cleared in the kidneys and are metabolized in the reticular endothelial system, and have no FDA ... cut-off for their use,” Dr. Miller said.

Dr. Miller and colleagues performed a post hoc analysis of patients in the FRAME study, which enrolled 3,589 patients who received a monthly dose of subcutaneous romosozumab (215 mg) and 3,591 patients who received placebo in a double-blinded study for 12 months before moving to a 12-month, open-label portion of the study where all patients received 60 mg of subcutaneous denosumab every 6 months. After 12 months, the researchers analyzed the least squares mean (LSM) percentage change in bone mineral density (BMD) at the total hip, lumbar spine, and femoral neck as well as whether patients had any new vertebral fractures or experienced adverse events from treatment.

Patients were postmenopausal women between ages 55 and 90 years with a BMD T-score between –2.5 and –3.5 at the total hip or femoral neck. Researchers divided patients into four eGFR groups based chronic kidney disease (CKD) stage: normal (90 mL/min/1.73 m² or higher; 848 patients), mild CKD (60-89 mL/min/1.73 m²; 4,939 patients), moderate CKD (30-59 mL/min/1.73 m²; 1,360 patients), and severe (15-29 mL/min/1.73 m²; 18 patients).

The LSM percentage change was 13.1% in the lumbar spine (95% confidence interval, 12.8%-13.3%) for the romosozumab group, compared with 0.4% in the placebo group (95% CI, 0.2%-0.5%). The LSM percentage change for total hip was 6.0% in the romosozumab group (95% CI, 5.9%-6.2%), compared with 0.3% in the placebo group (95% CI, 0.1%-0.4%), while the LSM percentage change for the femoral neck was 5.5% in the romosozumab group (95% CI, 5.2%-5.7%) and 0.3% in the placebo group (0.1%-0.5%).

“[The] risk of new vertebral fractures was decreased in all eGFR subgroups and did not appear to be affected by eGFR level,” he said.

Specifically, vertebral fracture incidence was 0.5% in the romosozumab group, compared with 3.0% in the placebo group, for patients with normal renal function, 0.4% in the romosozumab group, compared with 1.5% in the placebo group, for patients with mild chronic kidney disease, and 0.6% in the romosozumab group vs. 2.1% in the placebo group for patients with moderate chronic kidney disease. The incidence of adverse events, serious adverse events, and positively adjudicated cardiovascular events were similar between patients in the romosozumab group regardless of renal function status. The researchers reported 1 patient in the romosozumab group who experienced grade 2 hypocalcemia, and 14 patients in the romosozumab group who experienced mild to moderate decreases in calcium, compared with 4 patients in the placebo group.

Dr. Miller noted the study was limited by having few patients with an eGFR of less than 30 mL/min/1.73 m² and no patients with an eGFR of less than 15 mL/min/1.73 m², but said the study strengths were its large randomized nature and well-balanced baseline characteristics between each group.

This study was sponsored in part by Amgen, Astellas, and UCB Pharma. Dr. Miller reported receiving grants from Alexion, Amgen, Radius, Regeneron, UCB, and Ultragenyx. Amgen and UCB assisted in and provided financial assistance for the preparation of Dr. Miller’s presentation.

SOURCE: Miller P et al. ASBMR 2019. Abstract 1085.

ORLANDO – Reframing the decision-making process for selecting osteoporosis treatment options may help increase adherence to medication, according to a speaker at the annual meeting of the American Society for Bone and Mineral Research.

“The language of this disease needs to be changed,” Deborah Gold, PhD, of Duke University, Durham, N.C., said in her presentation.

As medications for osteoporosis have changed over the decades – from estrogen in the 1940s and calcitonin in the 1970s to bisphosphonates in the 1990s – the delivery mechanisms of the drugs and the dosing intervals also have changed. However, long-term adherence to osteoporosis medication through various delivery mechanisms and doses have remained elusive, Dr. Gold said.

She cited the negative public and media response to osteonecrosis of the jaw (ONJ) and atypical femoral fractures (AFF) – two rare side effects of bisphosphonate treatment – as one reason why adherence to osteoporosis medications has changed.

While the more common side effects of osteoporosis medications are manageable, the emphasis in lay press has been on “rare and frightening side effects,” she said. A 2018 study found that reports in the media “strongly influence the level of awareness of osteoporosis and fracture risk” and that a gap exists between clinical recommendations and patient perceptions (J Endocrinol Invest. 2018;41[12]:1359-64. doi: 10.1007/s40618-018-0898-9). Over the same time period, another study found that 40.2% of high-risk patients hospitalized for a hip fracture were treated with osteoporosis medications in 2002, but that number declined to 20.5% in 2011 (J Bone Miner Res. 2014;29[9]:1929-37. doi: 10.1002/jbmr.2202).

Dr. Gold advised clinicians to counter negative patient perceptions about osteoporosis treatment by explaining the risks of treatment with medications as well as the risks of not undergoing treatment for osteoporosis. “A hip fracture is a lot more likely for nontreatment than ONJ or AFF are for treatment,” she said.

Dr. Gold also described the importance of listening to patients’ preferences for treatment as well as attempting to find an appropriate treatment they are likely to continue using. “This has been shown in the literature over and over again in other diseases,” she said. If “somebody says, ‘I can’t do needles,’ you can’t prescribe a medication that goes in through a needle.”

Assuring patients that they can visit again to address issues with treatment, change medications if needed, and discuss concerns about adverse outcomes such as ONJ and AFF is also relevant. “We need to promote osteoporosis understanding – not just osteoporosis – and we need to promote treatment to multiple sources,” she said.

When osteoporosis is characterized in terms of bone mineral density, T-scores, fragility fractures, appropriate exercises, and diet, there is plenty of opportunity for confusion or misunderstanding. Accurate, plain-language information, given both verbally and in handouts, works well , according to Dr. Gold.

“Health communication services – whether we’re talking about newspapers, magazines, radio shows, television shows, or even things that come out from organizations like the NOF [National Osteoporosis Foundation] and ASBMR – need to promote accurate information and not exaggerated negatives that we hear all the time,” she said.

“Cognitive reframing is not an easy thing; there’s no question,” Dr. Gold said. “I’m not standing up here telling you we can do it tomorrow. It will be difficult. But for those of us who know this disease and know how serious it is and know what the consequences are, we need to make a positive difference.”

Dr. Gold reported being a consultant for Amgen, Eli Lilly, and Radius Pharmaceuticals.

SOURCE: Gold D. ASBMR 2019. Adherence to Osteoporosis: A Conundrum of Significant Proportions.

ORLANDO – Reframing the decision-making process for selecting osteoporosis treatment options may help increase adherence to medication, according to a speaker at the annual meeting of the American Society for Bone and Mineral Research.

“The language of this disease needs to be changed,” Deborah Gold, PhD, of Duke University, Durham, N.C., said in her presentation.

As medications for osteoporosis have changed over the decades – from estrogen in the 1940s and calcitonin in the 1970s to bisphosphonates in the 1990s – the delivery mechanisms of the drugs and the dosing intervals also have changed. However, long-term adherence to osteoporosis medication through various delivery mechanisms and doses have remained elusive, Dr. Gold said.

She cited the negative public and media response to osteonecrosis of the jaw (ONJ) and atypical femoral fractures (AFF) – two rare side effects of bisphosphonate treatment – as one reason why adherence to osteoporosis medications has changed.

While the more common side effects of osteoporosis medications are manageable, the emphasis in lay press has been on “rare and frightening side effects,” she said. A 2018 study found that reports in the media “strongly influence the level of awareness of osteoporosis and fracture risk” and that a gap exists between clinical recommendations and patient perceptions (J Endocrinol Invest. 2018;41[12]:1359-64. doi: 10.1007/s40618-018-0898-9). Over the same time period, another study found that 40.2% of high-risk patients hospitalized for a hip fracture were treated with osteoporosis medications in 2002, but that number declined to 20.5% in 2011 (J Bone Miner Res. 2014;29[9]:1929-37. doi: 10.1002/jbmr.2202).

Dr. Gold advised clinicians to counter negative patient perceptions about osteoporosis treatment by explaining the risks of treatment with medications as well as the risks of not undergoing treatment for osteoporosis. “A hip fracture is a lot more likely for nontreatment than ONJ or AFF are for treatment,” she said.

Dr. Gold also described the importance of listening to patients’ preferences for treatment as well as attempting to find an appropriate treatment they are likely to continue using. “This has been shown in the literature over and over again in other diseases,” she said. If “somebody says, ‘I can’t do needles,’ you can’t prescribe a medication that goes in through a needle.”

Assuring patients that they can visit again to address issues with treatment, change medications if needed, and discuss concerns about adverse outcomes such as ONJ and AFF is also relevant. “We need to promote osteoporosis understanding – not just osteoporosis – and we need to promote treatment to multiple sources,” she said.

When osteoporosis is characterized in terms of bone mineral density, T-scores, fragility fractures, appropriate exercises, and diet, there is plenty of opportunity for confusion or misunderstanding. Accurate, plain-language information, given both verbally and in handouts, works well , according to Dr. Gold.

“Health communication services – whether we’re talking about newspapers, magazines, radio shows, television shows, or even things that come out from organizations like the NOF [National Osteoporosis Foundation] and ASBMR – need to promote accurate information and not exaggerated negatives that we hear all the time,” she said.

“Cognitive reframing is not an easy thing; there’s no question,” Dr. Gold said. “I’m not standing up here telling you we can do it tomorrow. It will be difficult. But for those of us who know this disease and know how serious it is and know what the consequences are, we need to make a positive difference.”

Dr. Gold reported being a consultant for Amgen, Eli Lilly, and Radius Pharmaceuticals.

SOURCE: Gold D. ASBMR 2019. Adherence to Osteoporosis: A Conundrum of Significant Proportions.

ORLANDO – Reframing the decision-making process for selecting osteoporosis treatment options may help increase adherence to medication, according to a speaker at the annual meeting of the American Society for Bone and Mineral Research.

“The language of this disease needs to be changed,” Deborah Gold, PhD, of Duke University, Durham, N.C., said in her presentation.

As medications for osteoporosis have changed over the decades – from estrogen in the 1940s and calcitonin in the 1970s to bisphosphonates in the 1990s – the delivery mechanisms of the drugs and the dosing intervals also have changed. However, long-term adherence to osteoporosis medication through various delivery mechanisms and doses have remained elusive, Dr. Gold said.

She cited the negative public and media response to osteonecrosis of the jaw (ONJ) and atypical femoral fractures (AFF) – two rare side effects of bisphosphonate treatment – as one reason why adherence to osteoporosis medications has changed.

While the more common side effects of osteoporosis medications are manageable, the emphasis in lay press has been on “rare and frightening side effects,” she said. A 2018 study found that reports in the media “strongly influence the level of awareness of osteoporosis and fracture risk” and that a gap exists between clinical recommendations and patient perceptions (J Endocrinol Invest. 2018;41[12]:1359-64. doi: 10.1007/s40618-018-0898-9). Over the same time period, another study found that 40.2% of high-risk patients hospitalized for a hip fracture were treated with osteoporosis medications in 2002, but that number declined to 20.5% in 2011 (J Bone Miner Res. 2014;29[9]:1929-37. doi: 10.1002/jbmr.2202).

Dr. Gold advised clinicians to counter negative patient perceptions about osteoporosis treatment by explaining the risks of treatment with medications as well as the risks of not undergoing treatment for osteoporosis. “A hip fracture is a lot more likely for nontreatment than ONJ or AFF are for treatment,” she said.

Dr. Gold also described the importance of listening to patients’ preferences for treatment as well as attempting to find an appropriate treatment they are likely to continue using. “This has been shown in the literature over and over again in other diseases,” she said. If “somebody says, ‘I can’t do needles,’ you can’t prescribe a medication that goes in through a needle.”

Assuring patients that they can visit again to address issues with treatment, change medications if needed, and discuss concerns about adverse outcomes such as ONJ and AFF is also relevant. “We need to promote osteoporosis understanding – not just osteoporosis – and we need to promote treatment to multiple sources,” she said.

When osteoporosis is characterized in terms of bone mineral density, T-scores, fragility fractures, appropriate exercises, and diet, there is plenty of opportunity for confusion or misunderstanding. Accurate, plain-language information, given both verbally and in handouts, works well , according to Dr. Gold.

“Health communication services – whether we’re talking about newspapers, magazines, radio shows, television shows, or even things that come out from organizations like the NOF [National Osteoporosis Foundation] and ASBMR – need to promote accurate information and not exaggerated negatives that we hear all the time,” she said.

“Cognitive reframing is not an easy thing; there’s no question,” Dr. Gold said. “I’m not standing up here telling you we can do it tomorrow. It will be difficult. But for those of us who know this disease and know how serious it is and know what the consequences are, we need to make a positive difference.”

Dr. Gold reported being a consultant for Amgen, Eli Lilly, and Radius Pharmaceuticals.

SOURCE: Gold D. ASBMR 2019. Adherence to Osteoporosis: A Conundrum of Significant Proportions.

ORLANDO – The burden of osteoporosis and fragility fractures in the United States remains high, particularly in older women and minorities, according to a speaker at the annual meeting of the American Society for Bone and Mineral Research.

For non-Hispanic Asian, non-Hispanic white, and Hispanic patients of various ethnic groups, as well as in women and older patients, osteoporosis and fragility fractures continue to be a problem, said Nicole C. Wright, PhD, MPH, of the department of epidemiology at the University of Alabama at Birmingham.

“It remains costly; it remains associated with more health care utilization,” Dr. Wright said. “We may be seeing some declines in some fragility fractures, but [we] are seeing increases in hip fractures.”

As part of the fourth edition of the U.S. Bone and Joint Initiative publication, “The Burden of Musculoskeletal Diseases in the United States,” Dr. Wright and colleagues examined the changes in osteoporosis burden between the third and fourth editions of the publication. They used data from the National Inpatient Sample (NIS) in 2013 and 2014 as well as the National Emergency Department Sample (NEDS) of national ED visits regardless of hospital admission status. In both databases, researchers analyzed data from adults aged 50 years or older where the primary discharge ICD-9 or ICD-10 code was a diagnosis of fracture.

Using National Health and Nutrition Examination Survey data, the researchers estimated an 11.0% osteoporosis prevalence for adults aged 50 years or older overall, a 16.5% prevalence in women, and a 5.1% prevalence in men as assessed by femoral neck and lumbar spine bone mineral density. Osteoporosis was most prevalent in Asian women (40.0%) and Asian men (7.5%), while there was a difference in prevalence in patients of Hispanic race depending on their origin; for example, Puerto Rican men had a higher prevalence of osteoporosis at 8.6%, compared with Hispanic men (2.3%) and non-Hispanic white men of other races (3.9%).

Of 19.5 million hospitalizations in the NIS database between 2013 and 2014, there were approximately 540,000 fragility fractures (2.8%), of which about 300,000 were hip fractures and about 100,000 discharges were for spine fractures, Dr. Wright said. In the NEDS database, the estimate of fragility fracture prevalence was 0.9% of 46.7 million ED visits between 2013 and 2014. Fracture prevalence was increased in women and in older age, with patients aged 80 years or older and those of non-Hispanic white race having the highest prevalence of hip fracture. However, she noted that NEDS data also showed higher prevalences of wrist and humerus fractures, which are not normally fractures that a patient visits the hospital as an inpatient for. “We need both data sets to ascertain fractures in the United States,” she said.

When examining fracture site trends over time, Dr. Wright and colleagues found hip fracture prevalence increased by 3.5% between 2010 and 2014, while there was a decrease of 11.9% in the prevalence of spine fractures over the same time period.

According to data from the Medical Expenditures Panel Survey, the direct cost of osteoporosis in aggregate was $73.6 billion between 2012 and 2014, which was 118% higher than between 1998 and 2000 when the costs were $28.1 billion. The costs were spread across ambulatory care, inpatient, and prescription costs equally, the researchers said.

Although the study was limited by examining fracture prevalence rather than incidence, the potential for missing some fractures based on methodology, and limited patient characteristics and follow-up information, the goal of the presentation was to highlight the new osteoporosis prevalence data and the continued burden of the disease.

“We hope that these new prevalence estimates continue to increase the awareness of osteoporosis and prevention,” she said.

Dr. Wright reported receiving grants from Amgen and serving as an expert witness for the law firm Norton Rose Fulbright and Pfizer.

SOURCE: Wright NC et al. ASBMR 2019, Abstract 1079.

ORLANDO – The burden of osteoporosis and fragility fractures in the United States remains high, particularly in older women and minorities, according to a speaker at the annual meeting of the American Society for Bone and Mineral Research.

For non-Hispanic Asian, non-Hispanic white, and Hispanic patients of various ethnic groups, as well as in women and older patients, osteoporosis and fragility fractures continue to be a problem, said Nicole C. Wright, PhD, MPH, of the department of epidemiology at the University of Alabama at Birmingham.

“It remains costly; it remains associated with more health care utilization,” Dr. Wright said. “We may be seeing some declines in some fragility fractures, but [we] are seeing increases in hip fractures.”

As part of the fourth edition of the U.S. Bone and Joint Initiative publication, “The Burden of Musculoskeletal Diseases in the United States,” Dr. Wright and colleagues examined the changes in osteoporosis burden between the third and fourth editions of the publication. They used data from the National Inpatient Sample (NIS) in 2013 and 2014 as well as the National Emergency Department Sample (NEDS) of national ED visits regardless of hospital admission status. In both databases, researchers analyzed data from adults aged 50 years or older where the primary discharge ICD-9 or ICD-10 code was a diagnosis of fracture.

Using National Health and Nutrition Examination Survey data, the researchers estimated an 11.0% osteoporosis prevalence for adults aged 50 years or older overall, a 16.5% prevalence in women, and a 5.1% prevalence in men as assessed by femoral neck and lumbar spine bone mineral density. Osteoporosis was most prevalent in Asian women (40.0%) and Asian men (7.5%), while there was a difference in prevalence in patients of Hispanic race depending on their origin; for example, Puerto Rican men had a higher prevalence of osteoporosis at 8.6%, compared with Hispanic men (2.3%) and non-Hispanic white men of other races (3.9%).

Of 19.5 million hospitalizations in the NIS database between 2013 and 2014, there were approximately 540,000 fragility fractures (2.8%), of which about 300,000 were hip fractures and about 100,000 discharges were for spine fractures, Dr. Wright said. In the NEDS database, the estimate of fragility fracture prevalence was 0.9% of 46.7 million ED visits between 2013 and 2014. Fracture prevalence was increased in women and in older age, with patients aged 80 years or older and those of non-Hispanic white race having the highest prevalence of hip fracture. However, she noted that NEDS data also showed higher prevalences of wrist and humerus fractures, which are not normally fractures that a patient visits the hospital as an inpatient for. “We need both data sets to ascertain fractures in the United States,” she said.

When examining fracture site trends over time, Dr. Wright and colleagues found hip fracture prevalence increased by 3.5% between 2010 and 2014, while there was a decrease of 11.9% in the prevalence of spine fractures over the same time period.

According to data from the Medical Expenditures Panel Survey, the direct cost of osteoporosis in aggregate was $73.6 billion between 2012 and 2014, which was 118% higher than between 1998 and 2000 when the costs were $28.1 billion. The costs were spread across ambulatory care, inpatient, and prescription costs equally, the researchers said.

Although the study was limited by examining fracture prevalence rather than incidence, the potential for missing some fractures based on methodology, and limited patient characteristics and follow-up information, the goal of the presentation was to highlight the new osteoporosis prevalence data and the continued burden of the disease.

“We hope that these new prevalence estimates continue to increase the awareness of osteoporosis and prevention,” she said.

Dr. Wright reported receiving grants from Amgen and serving as an expert witness for the law firm Norton Rose Fulbright and Pfizer.

SOURCE: Wright NC et al. ASBMR 2019, Abstract 1079.

ORLANDO – The burden of osteoporosis and fragility fractures in the United States remains high, particularly in older women and minorities, according to a speaker at the annual meeting of the American Society for Bone and Mineral Research.

For non-Hispanic Asian, non-Hispanic white, and Hispanic patients of various ethnic groups, as well as in women and older patients, osteoporosis and fragility fractures continue to be a problem, said Nicole C. Wright, PhD, MPH, of the department of epidemiology at the University of Alabama at Birmingham.

“It remains costly; it remains associated with more health care utilization,” Dr. Wright said. “We may be seeing some declines in some fragility fractures, but [we] are seeing increases in hip fractures.”

As part of the fourth edition of the U.S. Bone and Joint Initiative publication, “The Burden of Musculoskeletal Diseases in the United States,” Dr. Wright and colleagues examined the changes in osteoporosis burden between the third and fourth editions of the publication. They used data from the National Inpatient Sample (NIS) in 2013 and 2014 as well as the National Emergency Department Sample (NEDS) of national ED visits regardless of hospital admission status. In both databases, researchers analyzed data from adults aged 50 years or older where the primary discharge ICD-9 or ICD-10 code was a diagnosis of fracture.

Using National Health and Nutrition Examination Survey data, the researchers estimated an 11.0% osteoporosis prevalence for adults aged 50 years or older overall, a 16.5% prevalence in women, and a 5.1% prevalence in men as assessed by femoral neck and lumbar spine bone mineral density. Osteoporosis was most prevalent in Asian women (40.0%) and Asian men (7.5%), while there was a difference in prevalence in patients of Hispanic race depending on their origin; for example, Puerto Rican men had a higher prevalence of osteoporosis at 8.6%, compared with Hispanic men (2.3%) and non-Hispanic white men of other races (3.9%).

Of 19.5 million hospitalizations in the NIS database between 2013 and 2014, there were approximately 540,000 fragility fractures (2.8%), of which about 300,000 were hip fractures and about 100,000 discharges were for spine fractures, Dr. Wright said. In the NEDS database, the estimate of fragility fracture prevalence was 0.9% of 46.7 million ED visits between 2013 and 2014. Fracture prevalence was increased in women and in older age, with patients aged 80 years or older and those of non-Hispanic white race having the highest prevalence of hip fracture. However, she noted that NEDS data also showed higher prevalences of wrist and humerus fractures, which are not normally fractures that a patient visits the hospital as an inpatient for. “We need both data sets to ascertain fractures in the United States,” she said.

When examining fracture site trends over time, Dr. Wright and colleagues found hip fracture prevalence increased by 3.5% between 2010 and 2014, while there was a decrease of 11.9% in the prevalence of spine fractures over the same time period.

According to data from the Medical Expenditures Panel Survey, the direct cost of osteoporosis in aggregate was $73.6 billion between 2012 and 2014, which was 118% higher than between 1998 and 2000 when the costs were $28.1 billion. The costs were spread across ambulatory care, inpatient, and prescription costs equally, the researchers said.

Although the study was limited by examining fracture prevalence rather than incidence, the potential for missing some fractures based on methodology, and limited patient characteristics and follow-up information, the goal of the presentation was to highlight the new osteoporosis prevalence data and the continued burden of the disease.

“We hope that these new prevalence estimates continue to increase the awareness of osteoporosis and prevention,” she said.

Dr. Wright reported receiving grants from Amgen and serving as an expert witness for the law firm Norton Rose Fulbright and Pfizer.

SOURCE: Wright NC et al. ASBMR 2019, Abstract 1079.

ORLANDO – Older black women with postmenopausal osteoporosis had significantly higher mortality rates, were more likely to be placed in a long-term nursing facility, and were more likely to become newly eligible for Medicaid after a major fragility fracture event, compared with their white counterparts, according to a findings presented at the annual meeting of the American Society for Bone and Mineral Research.

Previous studies have examined racial differences in mortality and outcomes after fracture, but the data from those studies are older or limited to a certain region or health system, Nicole C. Wright, PhD, MPH, of the department of epidemiology at the University of Alabama at Birmingham, said in her presentation.

“To our knowledge, this is the first comprehensive evaluation of fractures and outcomes post fracture by race, particularly in black women,” she said.

Using Medicare data from between 2010 and 2016, Dr. Wright and colleagues performed a cohort-based, descriptive study of 400,479 white women and 11,563 black women with postmenopausal osteoporosis, who were covered by Medicare Parts A, B, C and D and had a hip, pelvis, femur, radius/ulna, humerus, or clinical vertebral fractures. Fractures were identified by way of a validated algorithm that used inpatient and outpatient claims, outpatient physical evaluations, and management claims, together with fracture repair codes (positive predictive value range, 90.9%-98.6%; from Wright N et al. J Bone Min Res. 2019 Jun 6. doi: 10.1002/jbmr.3807).

The groups had similar proportions of patients in each age group (65-75 years, 75-84 years, 85 years and older), with a slightly higher percentage of younger black patients than younger white patients (25.0% vs. 22.4%, respectively). Black patients were more likely than white patients to be from the South (58.6% vs. 39.7%) and have a Charlson Comorbidity Index score of 2 or higher (62.9% vs. 45.4%). White patients were more likely than black patients to have a Charlson score of 0 (42.0% vs. 24.1%).

The three identifying outcomes were: death/mortality, which was determined using the date in the Medicare vital status; debility, a term used for patients newly placed in a long-term nursing facility; and destitution, used to describe patients who became newly eligible for Medicaid after a major fragility fracture.

The results showed that the most common fracture types were hip and clinical vertebral fractures, with black women having a significantly lower rate of clinical vertebral fractures (29.0% vs. 34.1%, respectively) but a significantly higher rate of femur fractures (9.1% vs. 3.8%). Black women also had a significantly higher mortality rate after a fracture (19.6% vs. 15.4%), and a significantly higher composite outcome of all three identifying outcome measurements (24.6% vs. 20.2%). However, rates of debility and destitution were similar between the groups.

When measured by fracture type, black women had significantly different 1-year postfracture outcomes, compared with white women, with a 38.0% higher incidence of mortality, 40.2% higher rate of debility, 185.0% higher rate of destitution, and 35.4% higher composite outcome for hip fracture. For radius/ulna fractures, black women also had a 59.7% higher rate of death, 8.5% higher rate of debility, 164.7% higher rate of destitution, and 43.0% higher composite outcomes; and for clinical vertebral fractures, they had 11.4% higher rate of death, 10.8% higher rate of debility, 130.6% higher rate of destitution, and 13.6% higher composite outcome, compared with white women.

Overall, black women had higher incidence risk ratios for death (IRR, 1.24; 95% confidence interval, 1.15-1.33), debility (IRR, 1.19; 95% CI, 1.06-1.33), and destitution (IRR, 2.45; 95% CI, 2.20-2.73) for fractures of the hip; higher IRRs for death (IRR, 1.48; 95% CI, 1.33-1.66), debility (IRR, 1.02; 95% CI, 0.87-1.20), and destitution (IRR, 2.70; 95% CI, 2.33-3.13) for fractures of the radius or ulna; and higher IRRs for death (IRR, 1.07; 95% CI, 0.98-1.17) and destitution (IRR, 2.40; 95% CI, 2.15-2.67) for clinical vertebral fractures.

“These data show that we need to develop interventions and/or programs to mitigate and reduce disparities in fracture outcomes,” said Dr. Wright.

She noted that the study results were limited because of its observational nature, and results cannot be generalized beyond older women with postmenopausal osteoporosis with Medicare coverage. In addition, the algorithm used to determine fracture status also had a potentially low sensitivity, which may have affected the study results, she said.

The study was funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Wright reported receiving grants from Amgen and serving as an expert witness for the law firm Norton Rose Fulbright and Pfizer. Dr. Chen reported receiving grants from Amgen. Dr. Curtis reported receiving grants from, and is a consultant for, Amgen, Eli Lilly, and Radius. Dr. Saag reported receiving grants from Amgen and is a consultant for Gilead and Radius.

SOURCE: Wright NC et al. ASBMR 2019, Abstract 1125.

ORLANDO – Older black women with postmenopausal osteoporosis had significantly higher mortality rates, were more likely to be placed in a long-term nursing facility, and were more likely to become newly eligible for Medicaid after a major fragility fracture event, compared with their white counterparts, according to a findings presented at the annual meeting of the American Society for Bone and Mineral Research.

Previous studies have examined racial differences in mortality and outcomes after fracture, but the data from those studies are older or limited to a certain region or health system, Nicole C. Wright, PhD, MPH, of the department of epidemiology at the University of Alabama at Birmingham, said in her presentation.

“To our knowledge, this is the first comprehensive evaluation of fractures and outcomes post fracture by race, particularly in black women,” she said.

Using Medicare data from between 2010 and 2016, Dr. Wright and colleagues performed a cohort-based, descriptive study of 400,479 white women and 11,563 black women with postmenopausal osteoporosis, who were covered by Medicare Parts A, B, C and D and had a hip, pelvis, femur, radius/ulna, humerus, or clinical vertebral fractures. Fractures were identified by way of a validated algorithm that used inpatient and outpatient claims, outpatient physical evaluations, and management claims, together with fracture repair codes (positive predictive value range, 90.9%-98.6%; from Wright N et al. J Bone Min Res. 2019 Jun 6. doi: 10.1002/jbmr.3807).

The groups had similar proportions of patients in each age group (65-75 years, 75-84 years, 85 years and older), with a slightly higher percentage of younger black patients than younger white patients (25.0% vs. 22.4%, respectively). Black patients were more likely than white patients to be from the South (58.6% vs. 39.7%) and have a Charlson Comorbidity Index score of 2 or higher (62.9% vs. 45.4%). White patients were more likely than black patients to have a Charlson score of 0 (42.0% vs. 24.1%).

The three identifying outcomes were: death/mortality, which was determined using the date in the Medicare vital status; debility, a term used for patients newly placed in a long-term nursing facility; and destitution, used to describe patients who became newly eligible for Medicaid after a major fragility fracture.

The results showed that the most common fracture types were hip and clinical vertebral fractures, with black women having a significantly lower rate of clinical vertebral fractures (29.0% vs. 34.1%, respectively) but a significantly higher rate of femur fractures (9.1% vs. 3.8%). Black women also had a significantly higher mortality rate after a fracture (19.6% vs. 15.4%), and a significantly higher composite outcome of all three identifying outcome measurements (24.6% vs. 20.2%). However, rates of debility and destitution were similar between the groups.

When measured by fracture type, black women had significantly different 1-year postfracture outcomes, compared with white women, with a 38.0% higher incidence of mortality, 40.2% higher rate of debility, 185.0% higher rate of destitution, and 35.4% higher composite outcome for hip fracture. For radius/ulna fractures, black women also had a 59.7% higher rate of death, 8.5% higher rate of debility, 164.7% higher rate of destitution, and 43.0% higher composite outcomes; and for clinical vertebral fractures, they had 11.4% higher rate of death, 10.8% higher rate of debility, 130.6% higher rate of destitution, and 13.6% higher composite outcome, compared with white women.

Overall, black women had higher incidence risk ratios for death (IRR, 1.24; 95% confidence interval, 1.15-1.33), debility (IRR, 1.19; 95% CI, 1.06-1.33), and destitution (IRR, 2.45; 95% CI, 2.20-2.73) for fractures of the hip; higher IRRs for death (IRR, 1.48; 95% CI, 1.33-1.66), debility (IRR, 1.02; 95% CI, 0.87-1.20), and destitution (IRR, 2.70; 95% CI, 2.33-3.13) for fractures of the radius or ulna; and higher IRRs for death (IRR, 1.07; 95% CI, 0.98-1.17) and destitution (IRR, 2.40; 95% CI, 2.15-2.67) for clinical vertebral fractures.

“These data show that we need to develop interventions and/or programs to mitigate and reduce disparities in fracture outcomes,” said Dr. Wright.

She noted that the study results were limited because of its observational nature, and results cannot be generalized beyond older women with postmenopausal osteoporosis with Medicare coverage. In addition, the algorithm used to determine fracture status also had a potentially low sensitivity, which may have affected the study results, she said.

The study was funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Wright reported receiving grants from Amgen and serving as an expert witness for the law firm Norton Rose Fulbright and Pfizer. Dr. Chen reported receiving grants from Amgen. Dr. Curtis reported receiving grants from, and is a consultant for, Amgen, Eli Lilly, and Radius. Dr. Saag reported receiving grants from Amgen and is a consultant for Gilead and Radius.

SOURCE: Wright NC et al. ASBMR 2019, Abstract 1125.

ORLANDO – Older black women with postmenopausal osteoporosis had significantly higher mortality rates, were more likely to be placed in a long-term nursing facility, and were more likely to become newly eligible for Medicaid after a major fragility fracture event, compared with their white counterparts, according to a findings presented at the annual meeting of the American Society for Bone and Mineral Research.

Previous studies have examined racial differences in mortality and outcomes after fracture, but the data from those studies are older or limited to a certain region or health system, Nicole C. Wright, PhD, MPH, of the department of epidemiology at the University of Alabama at Birmingham, said in her presentation.

“To our knowledge, this is the first comprehensive evaluation of fractures and outcomes post fracture by race, particularly in black women,” she said.

Using Medicare data from between 2010 and 2016, Dr. Wright and colleagues performed a cohort-based, descriptive study of 400,479 white women and 11,563 black women with postmenopausal osteoporosis, who were covered by Medicare Parts A, B, C and D and had a hip, pelvis, femur, radius/ulna, humerus, or clinical vertebral fractures. Fractures were identified by way of a validated algorithm that used inpatient and outpatient claims, outpatient physical evaluations, and management claims, together with fracture repair codes (positive predictive value range, 90.9%-98.6%; from Wright N et al. J Bone Min Res. 2019 Jun 6. doi: 10.1002/jbmr.3807).

The groups had similar proportions of patients in each age group (65-75 years, 75-84 years, 85 years and older), with a slightly higher percentage of younger black patients than younger white patients (25.0% vs. 22.4%, respectively). Black patients were more likely than white patients to be from the South (58.6% vs. 39.7%) and have a Charlson Comorbidity Index score of 2 or higher (62.9% vs. 45.4%). White patients were more likely than black patients to have a Charlson score of 0 (42.0% vs. 24.1%).

The three identifying outcomes were: death/mortality, which was determined using the date in the Medicare vital status; debility, a term used for patients newly placed in a long-term nursing facility; and destitution, used to describe patients who became newly eligible for Medicaid after a major fragility fracture.

The results showed that the most common fracture types were hip and clinical vertebral fractures, with black women having a significantly lower rate of clinical vertebral fractures (29.0% vs. 34.1%, respectively) but a significantly higher rate of femur fractures (9.1% vs. 3.8%). Black women also had a significantly higher mortality rate after a fracture (19.6% vs. 15.4%), and a significantly higher composite outcome of all three identifying outcome measurements (24.6% vs. 20.2%). However, rates of debility and destitution were similar between the groups.

When measured by fracture type, black women had significantly different 1-year postfracture outcomes, compared with white women, with a 38.0% higher incidence of mortality, 40.2% higher rate of debility, 185.0% higher rate of destitution, and 35.4% higher composite outcome for hip fracture. For radius/ulna fractures, black women also had a 59.7% higher rate of death, 8.5% higher rate of debility, 164.7% higher rate of destitution, and 43.0% higher composite outcomes; and for clinical vertebral fractures, they had 11.4% higher rate of death, 10.8% higher rate of debility, 130.6% higher rate of destitution, and 13.6% higher composite outcome, compared with white women.

Overall, black women had higher incidence risk ratios for death (IRR, 1.24; 95% confidence interval, 1.15-1.33), debility (IRR, 1.19; 95% CI, 1.06-1.33), and destitution (IRR, 2.45; 95% CI, 2.20-2.73) for fractures of the hip; higher IRRs for death (IRR, 1.48; 95% CI, 1.33-1.66), debility (IRR, 1.02; 95% CI, 0.87-1.20), and destitution (IRR, 2.70; 95% CI, 2.33-3.13) for fractures of the radius or ulna; and higher IRRs for death (IRR, 1.07; 95% CI, 0.98-1.17) and destitution (IRR, 2.40; 95% CI, 2.15-2.67) for clinical vertebral fractures.

“These data show that we need to develop interventions and/or programs to mitigate and reduce disparities in fracture outcomes,” said Dr. Wright.

She noted that the study results were limited because of its observational nature, and results cannot be generalized beyond older women with postmenopausal osteoporosis with Medicare coverage. In addition, the algorithm used to determine fracture status also had a potentially low sensitivity, which may have affected the study results, she said.

The study was funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Wright reported receiving grants from Amgen and serving as an expert witness for the law firm Norton Rose Fulbright and Pfizer. Dr. Chen reported receiving grants from Amgen. Dr. Curtis reported receiving grants from, and is a consultant for, Amgen, Eli Lilly, and Radius. Dr. Saag reported receiving grants from Amgen and is a consultant for Gilead and Radius.

SOURCE: Wright NC et al. ASBMR 2019, Abstract 1125.

ORLANDO – Patients who took romosozumab for 12 months and then switched to alendronate continued to see benefits in bone mineral density (BMD) of the lumbar spine after 12 months of therapy with alendronate, compared with patients who began taking, and continued to take, alendronate over the same time period, according to findings from a subgroup of the ARCH study presented at the annual meeting of the American Society for Bone and Mineral Research.

“These effects occurred rapidly, as early as month 6, were sustained beyond 12 months after transitioning to alendronate, and are consistent with greater fracture-risk reduction observed in ARCH with romosozumab to alendronate versus alendronate to alendronate,” Jacques P. Brown, MD, FRCPC, of Laval University, Quebec City, said in his presentation.

In the double-blinded ARCH study, 4,093 postmenopausal women with osteoporosis and a previous fracture history were randomized to receive subcutaneous monthly romosozumab 210 mg or oral weekly alendronate 70 mg for 12 months, followed by an open-label period during which romosozumab patients received oral weekly alendronate 70 mg and alendronate patients continued to receive the same dose on the same schedule for an additional 24 months (Saag KG et al. N Eng J Med. 2017 Oct 12. doi: 10.1056/NEJMoa1708322).

Dr. Brown and colleagues performed an imaging substudy of ARCH, which included examining how the romosozumab-to-alendronate and alendronate-only groups improved lumbar spine BMD and lumbar spine bone strength. Lumbar spine BMD was assessed through quantitative CT, and lumbar spine bone strength was measured with finite element analysis. The researchers received quantitative CT images from baseline and at 6 months, 12 months, and 24 months, and determined the percentage change at each of those periods to calculate integral, trabecular, and cortical lumbar spine volumetric BMD (vBMD), and to bone mineral content (BMC). They also measured areal BMD (aBMD) at baseline, 6 months, 12 months, 18 months, and 24 months with dual-energy x-ray absorptiometry.

Overall, 49 romosozumab patients and 41 alendronate patients from the ARCH study were enrolled in the imaging substudy. Of those patients, 76 had vBMD and BMC information available at baseline and one or more time periods post baseline, and 86 patients had finite element analysis data at baseline and one or more postbaseline time periods. Patients in the romosozumab and alendronate groups had similar baseline characteristics with regard to age (73.1 years vs. 72.8 years, respectively), mean lumbar spine BMD T score (–2.82 vs. –3.38), mean total hip BMD T score (–2.65 vs. –2.75), mean femoral neck T score (–2.84 vs. –2.83), mean lumbar spine integral vBMD (130.3 mg/cm³ vs. 120.5 mg/cm³), trabecular vBMD (60.1 mg/cm³ vs. 53.7 mg/cm³) and cortical vBMD (284.6 mg/cm³ vs. 270.9 mg/cm³). Patients in both groups also had similar rates of previous osteoporotic fracture at or after aged 45 years, previous vertebral fracture, and history of hip fracture.

Beginning at 6 months, there were significant least squares mean BMD improvements in both groups, but the romosozumab group had significant improvements in aBMD percentage changes, compared with the alendronate group, which persisted until 24 months (P less than .001 at all time points). Integral, trabecular, and cortical vBMD in the romosozumab group also saw significantly greater increases from baseline, compared with the alendronate group, and those results persisted in the open-label portion of the study for patients in the romosozumab group who transitioned to alendronate and patients in the alendronate to alendronate group (P less than .001 at all time points).

“The rapid and large increases in BMD with romosozumab followed by BMD consolidation where [patients were] transitioning to alendronate, support the important role of romosozumab as a first-line therapy in treating patients who are at very high risk for fracture,” Dr. Brown said.

In regard to BMC, there were larger increases in least squares mean BMC changes from baseline in the cortical compartment than the trabecular compartment, and actual change in bone strength as measured by finite element analysis was highly correlated with integral BMC in the romosozumab group.

Dr. Brown said the study was limited to the small sample size from the imaging substudy of ARCH, and quantitative CT dictated the imaging sites for the substudy, which may have affected patient selection. However, he noted that the characteristics of the ARCH imaging substudy were similar to patients in the overall ARCH study.

Amgen, UCB Pharma, and Astellas Pharma funded the study in part. Amgen and UCB Pharma assisted in the preparation of Dr. Brown’s presentation at ASBMR 2019, including funding costs associated with its development. Dr. Brown and the other coauthors reported relationships with Amgen, UCB Pharma, and other companies in the form of consultancies, grants and research support, speaker’s bureau appointments, paid employment, and stock options.

SOURCE: Brown JP et al. ASBMR 2019, Abstract 1050.

ORLANDO – Patients who took romosozumab for 12 months and then switched to alendronate continued to see benefits in bone mineral density (BMD) of the lumbar spine after 12 months of therapy with alendronate, compared with patients who began taking, and continued to take, alendronate over the same time period, according to findings from a subgroup of the ARCH study presented at the annual meeting of the American Society for Bone and Mineral Research.

“These effects occurred rapidly, as early as month 6, were sustained beyond 12 months after transitioning to alendronate, and are consistent with greater fracture-risk reduction observed in ARCH with romosozumab to alendronate versus alendronate to alendronate,” Jacques P. Brown, MD, FRCPC, of Laval University, Quebec City, said in his presentation.

In the double-blinded ARCH study, 4,093 postmenopausal women with osteoporosis and a previous fracture history were randomized to receive subcutaneous monthly romosozumab 210 mg or oral weekly alendronate 70 mg for 12 months, followed by an open-label period during which romosozumab patients received oral weekly alendronate 70 mg and alendronate patients continued to receive the same dose on the same schedule for an additional 24 months (Saag KG et al. N Eng J Med. 2017 Oct 12. doi: 10.1056/NEJMoa1708322).

Dr. Brown and colleagues performed an imaging substudy of ARCH, which included examining how the romosozumab-to-alendronate and alendronate-only groups improved lumbar spine BMD and lumbar spine bone strength. Lumbar spine BMD was assessed through quantitative CT, and lumbar spine bone strength was measured with finite element analysis. The researchers received quantitative CT images from baseline and at 6 months, 12 months, and 24 months, and determined the percentage change at each of those periods to calculate integral, trabecular, and cortical lumbar spine volumetric BMD (vBMD), and to bone mineral content (BMC). They also measured areal BMD (aBMD) at baseline, 6 months, 12 months, 18 months, and 24 months with dual-energy x-ray absorptiometry.

Overall, 49 romosozumab patients and 41 alendronate patients from the ARCH study were enrolled in the imaging substudy. Of those patients, 76 had vBMD and BMC information available at baseline and one or more time periods post baseline, and 86 patients had finite element analysis data at baseline and one or more postbaseline time periods. Patients in the romosozumab and alendronate groups had similar baseline characteristics with regard to age (73.1 years vs. 72.8 years, respectively), mean lumbar spine BMD T score (–2.82 vs. –3.38), mean total hip BMD T score (–2.65 vs. –2.75), mean femoral neck T score (–2.84 vs. –2.83), mean lumbar spine integral vBMD (130.3 mg/cm³ vs. 120.5 mg/cm³), trabecular vBMD (60.1 mg/cm³ vs. 53.7 mg/cm³) and cortical vBMD (284.6 mg/cm³ vs. 270.9 mg/cm³). Patients in both groups also had similar rates of previous osteoporotic fracture at or after aged 45 years, previous vertebral fracture, and history of hip fracture.

Beginning at 6 months, there were significant least squares mean BMD improvements in both groups, but the romosozumab group had significant improvements in aBMD percentage changes, compared with the alendronate group, which persisted until 24 months (P less than .001 at all time points). Integral, trabecular, and cortical vBMD in the romosozumab group also saw significantly greater increases from baseline, compared with the alendronate group, and those results persisted in the open-label portion of the study for patients in the romosozumab group who transitioned to alendronate and patients in the alendronate to alendronate group (P less than .001 at all time points).

“The rapid and large increases in BMD with romosozumab followed by BMD consolidation where [patients were] transitioning to alendronate, support the important role of romosozumab as a first-line therapy in treating patients who are at very high risk for fracture,” Dr. Brown said.

In regard to BMC, there were larger increases in least squares mean BMC changes from baseline in the cortical compartment than the trabecular compartment, and actual change in bone strength as measured by finite element analysis was highly correlated with integral BMC in the romosozumab group.

Dr. Brown said the study was limited to the small sample size from the imaging substudy of ARCH, and quantitative CT dictated the imaging sites for the substudy, which may have affected patient selection. However, he noted that the characteristics of the ARCH imaging substudy were similar to patients in the overall ARCH study.

Amgen, UCB Pharma, and Astellas Pharma funded the study in part. Amgen and UCB Pharma assisted in the preparation of Dr. Brown’s presentation at ASBMR 2019, including funding costs associated with its development. Dr. Brown and the other coauthors reported relationships with Amgen, UCB Pharma, and other companies in the form of consultancies, grants and research support, speaker’s bureau appointments, paid employment, and stock options.

SOURCE: Brown JP et al. ASBMR 2019, Abstract 1050.

ORLANDO – Patients who took romosozumab for 12 months and then switched to alendronate continued to see benefits in bone mineral density (BMD) of the lumbar spine after 12 months of therapy with alendronate, compared with patients who began taking, and continued to take, alendronate over the same time period, according to findings from a subgroup of the ARCH study presented at the annual meeting of the American Society for Bone and Mineral Research.

“These effects occurred rapidly, as early as month 6, were sustained beyond 12 months after transitioning to alendronate, and are consistent with greater fracture-risk reduction observed in ARCH with romosozumab to alendronate versus alendronate to alendronate,” Jacques P. Brown, MD, FRCPC, of Laval University, Quebec City, said in his presentation.

In the double-blinded ARCH study, 4,093 postmenopausal women with osteoporosis and a previous fracture history were randomized to receive subcutaneous monthly romosozumab 210 mg or oral weekly alendronate 70 mg for 12 months, followed by an open-label period during which romosozumab patients received oral weekly alendronate 70 mg and alendronate patients continued to receive the same dose on the same schedule for an additional 24 months (Saag KG et al. N Eng J Med. 2017 Oct 12. doi: 10.1056/NEJMoa1708322).

Dr. Brown and colleagues performed an imaging substudy of ARCH, which included examining how the romosozumab-to-alendronate and alendronate-only groups improved lumbar spine BMD and lumbar spine bone strength. Lumbar spine BMD was assessed through quantitative CT, and lumbar spine bone strength was measured with finite element analysis. The researchers received quantitative CT images from baseline and at 6 months, 12 months, and 24 months, and determined the percentage change at each of those periods to calculate integral, trabecular, and cortical lumbar spine volumetric BMD (vBMD), and to bone mineral content (BMC). They also measured areal BMD (aBMD) at baseline, 6 months, 12 months, 18 months, and 24 months with dual-energy x-ray absorptiometry.

Overall, 49 romosozumab patients and 41 alendronate patients from the ARCH study were enrolled in the imaging substudy. Of those patients, 76 had vBMD and BMC information available at baseline and one or more time periods post baseline, and 86 patients had finite element analysis data at baseline and one or more postbaseline time periods. Patients in the romosozumab and alendronate groups had similar baseline characteristics with regard to age (73.1 years vs. 72.8 years, respectively), mean lumbar spine BMD T score (–2.82 vs. –3.38), mean total hip BMD T score (–2.65 vs. –2.75), mean femoral neck T score (–2.84 vs. –2.83), mean lumbar spine integral vBMD (130.3 mg/cm³ vs. 120.5 mg/cm³), trabecular vBMD (60.1 mg/cm³ vs. 53.7 mg/cm³) and cortical vBMD (284.6 mg/cm³ vs. 270.9 mg/cm³). Patients in both groups also had similar rates of previous osteoporotic fracture at or after aged 45 years, previous vertebral fracture, and history of hip fracture.

Beginning at 6 months, there were significant least squares mean BMD improvements in both groups, but the romosozumab group had significant improvements in aBMD percentage changes, compared with the alendronate group, which persisted until 24 months (P less than .001 at all time points). Integral, trabecular, and cortical vBMD in the romosozumab group also saw significantly greater increases from baseline, compared with the alendronate group, and those results persisted in the open-label portion of the study for patients in the romosozumab group who transitioned to alendronate and patients in the alendronate to alendronate group (P less than .001 at all time points).

“The rapid and large increases in BMD with romosozumab followed by BMD consolidation where [patients were] transitioning to alendronate, support the important role of romosozumab as a first-line therapy in treating patients who are at very high risk for fracture,” Dr. Brown said.

In regard to BMC, there were larger increases in least squares mean BMC changes from baseline in the cortical compartment than the trabecular compartment, and actual change in bone strength as measured by finite element analysis was highly correlated with integral BMC in the romosozumab group.

Dr. Brown said the study was limited to the small sample size from the imaging substudy of ARCH, and quantitative CT dictated the imaging sites for the substudy, which may have affected patient selection. However, he noted that the characteristics of the ARCH imaging substudy were similar to patients in the overall ARCH study.

Amgen, UCB Pharma, and Astellas Pharma funded the study in part. Amgen and UCB Pharma assisted in the preparation of Dr. Brown’s presentation at ASBMR 2019, including funding costs associated with its development. Dr. Brown and the other coauthors reported relationships with Amgen, UCB Pharma, and other companies in the form of consultancies, grants and research support, speaker’s bureau appointments, paid employment, and stock options.

SOURCE: Brown JP et al. ASBMR 2019, Abstract 1050.