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Intra-articular calcium crystal deposition is commonly seen in knee osteoarthritis, but its significance has been debated.

Now, a new study that relied on knee radiographs and bilateral knee CT imaging to evaluate 2,093 participants, including some with and without knee mineralization, has provided some new insights.

Dr. Jean Liew, assistant professor of medicine at Boston University
Dr. Jean Liew

The study has addressed the longstanding question: Is the calcium deposition a cause or a consequence of the OA? “If it’s a cause, targeting it might be helpful,” Jean Liew, MD, MS, the study’s lead author and assistant professor of medicine at Boston University, said in an interview. “If a consequence of the OA, targeting is not going to help.”

In this new study, because of the use of advanced imaging, the researchers demonstrated a strong relationship of the presence of this calcification with different pain characteristics, said Tuhina Neogi, MD, PhD, professor of medicine and epidemiology at Boston University, the corresponding author of the study who has focused on this research for many years. “This indicates this mineralization is not inconsequential.”

The bottom line? “Calcification in the knee may not be simply inert and an innocent bystander of longstanding OA,” Dr. Neogi said in an interview.
 

Study details

Dr. Neogi and colleagues evaluated 2,093 participants (mean age, 61 years; 57% female) with a mean body mass index of 28.8 kg/m2. In all, 10.2% of knees had intra-articular mineralization. The data came from the National Institutes of Health–funded longitudinal Multicenter Osteoarthritis Study. At baseline, participants had knee radiographs and bilateral knee CT scans, and pain assessments every 8 months for 2 years. The Boston University Calcium Knee Score was used to score the CT imaging. The researchers longitudinally examined the relationship of the CT-detected intra-articular mineralization to the risk of frequent knee pain, intermittent or constant knee pain worsening, and pain severity worsening. All analyses were adjusted for age, sex, body mass index, race, site, and Kellgren-Lawrence grade.

Dr. Tuhina Neogi

Having any mineralization in the cartilage was associated with a doubling of odds for having frequent knee pain (95% confidence interval, 1.38-2.78), and 1.86 times greater likelihood of more frequent intermittent or constant knee pain (95% CI, 1.20-2.78) over the 2 years of follow-up. Similar results were seen for the presence of any intra-articular mineralization in the meniscus or joint capsule. The higher the burden of mineralization anywhere within the knee was linked with higher odds for all pain outcomes, with odds ratios ranging from 2.14 to 2.21.
 

Perspective

“Because we used more sensitive imaging to pick up the calcification, we are able to more confidently evaluate this association,” Dr. Neogi said in an interview. The problem with prior studies was their reliance on plain radiographs, which are not sensitive enough to pick up this calcification.

Among the other strengths of the new research, she said, is that it was longitudinal, included more than 2,000 people and used multiple ways to look at the pain experience, getting consistent results.

“Here we are saying there seems to be clinical relevance [to the mineralization]. That’s not so surprising. We know there are other medical conditions in which calcium calcification can cause severe pain and inflammation.” The old term, pseudogout, is now called calcium pyrophosphate deposition disease.

The next steps of research, Dr. Neogi said, are to investigate the link of the mineralization to inflammation and its association to cartilage damage.
 

 

 

Could colchicine help?

In another recent study, researchers conducted a post hoc analysis of a randomized clinical trial of the anti-inflammatory drug colchicine, finding that the use of colchicine at 0.5 mg daily was associated with a lower incidence of total knee and hip replacements (TKR, THR). In that study, 2,762 participants received colchicine, while 2,760 received placebo during the median follow-up of 28.6 months. During the trial, TKR or THR was done in 68 patients (2.5%) of those in the treated group and 97 patients (3.5%) in the placebo groups. That resulted in an incidence rate difference of –0.40 [95% CI, –0.74 to –0.06 ] per 100 person-years.

The authors wrote that the results suggest that “colchicine may slow the progression of OA, but this needs to be confirmed in an appropriately designed prospective placebo-controlled trial.”
 

Independent perspective

The new Boston University study supports the idea that there may be a larger subset of patients that may have a calcium mineralization component, said C. Kent Kwoh, MD, professor of medicine and medical imaging at the University of Arizona, Tucson. He reviewed both studies and provided perspective. He is an editorial advisory board member for MDedge Rheumatology.

Dr. C. Kent Kwoh, professor of medicine and medical imaging at the University of Arizona, Tucson, and director of the University of Arizona Arthritis Center
courtesy Banner University Medical Group–Tucson
Dr. C. Kent Kwoh

The study by Dr. Liew and colleagues shows that “there is an association of crystal deposition not just in the cartilage, but various parts of the joint.” He emphasized the study found only an association and that more study is needed.

As for the colchicine study, he said, it “really shows there is potential at least within some individuals where it may decrease symptoms to the point where people are less likely to need joint replacement.” That analysis follows some previous research, some of it shorter term, finding that colchicine was not beneficial.
 

Takeaways

Would colchicine be worth a try in patients who have knee pain and calcium mineral deposits?

Dr. Neogi noted that a formulation of colchicine (Lodoco) was recently approved by the Food and Drug Administration to reduce the risk of myocardial infarction and other cardiovascular disease. While she does not advocate adopting a practice without evidence, she suggested if someone has both mineralization and cardiovascular disease, along with difficulty managing symptoms with established treatments, it might be worth a try, if no contraindications exist.

Dr. Kwoh agreed it may be worth a try, given that it is “relatively safe and relatively inexpensive.”

On one point all agreed: More research is needed.

Dr. Kwoh, Dr. Neogi and Dr. Liew have no relevant disclosures.

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Intra-articular calcium crystal deposition is commonly seen in knee osteoarthritis, but its significance has been debated.

Now, a new study that relied on knee radiographs and bilateral knee CT imaging to evaluate 2,093 participants, including some with and without knee mineralization, has provided some new insights.

Dr. Jean Liew, assistant professor of medicine at Boston University
Dr. Jean Liew

The study has addressed the longstanding question: Is the calcium deposition a cause or a consequence of the OA? “If it’s a cause, targeting it might be helpful,” Jean Liew, MD, MS, the study’s lead author and assistant professor of medicine at Boston University, said in an interview. “If a consequence of the OA, targeting is not going to help.”

In this new study, because of the use of advanced imaging, the researchers demonstrated a strong relationship of the presence of this calcification with different pain characteristics, said Tuhina Neogi, MD, PhD, professor of medicine and epidemiology at Boston University, the corresponding author of the study who has focused on this research for many years. “This indicates this mineralization is not inconsequential.”

The bottom line? “Calcification in the knee may not be simply inert and an innocent bystander of longstanding OA,” Dr. Neogi said in an interview.
 

Study details

Dr. Neogi and colleagues evaluated 2,093 participants (mean age, 61 years; 57% female) with a mean body mass index of 28.8 kg/m2. In all, 10.2% of knees had intra-articular mineralization. The data came from the National Institutes of Health–funded longitudinal Multicenter Osteoarthritis Study. At baseline, participants had knee radiographs and bilateral knee CT scans, and pain assessments every 8 months for 2 years. The Boston University Calcium Knee Score was used to score the CT imaging. The researchers longitudinally examined the relationship of the CT-detected intra-articular mineralization to the risk of frequent knee pain, intermittent or constant knee pain worsening, and pain severity worsening. All analyses were adjusted for age, sex, body mass index, race, site, and Kellgren-Lawrence grade.

Dr. Tuhina Neogi

Having any mineralization in the cartilage was associated with a doubling of odds for having frequent knee pain (95% confidence interval, 1.38-2.78), and 1.86 times greater likelihood of more frequent intermittent or constant knee pain (95% CI, 1.20-2.78) over the 2 years of follow-up. Similar results were seen for the presence of any intra-articular mineralization in the meniscus or joint capsule. The higher the burden of mineralization anywhere within the knee was linked with higher odds for all pain outcomes, with odds ratios ranging from 2.14 to 2.21.
 

Perspective

“Because we used more sensitive imaging to pick up the calcification, we are able to more confidently evaluate this association,” Dr. Neogi said in an interview. The problem with prior studies was their reliance on plain radiographs, which are not sensitive enough to pick up this calcification.

Among the other strengths of the new research, she said, is that it was longitudinal, included more than 2,000 people and used multiple ways to look at the pain experience, getting consistent results.

“Here we are saying there seems to be clinical relevance [to the mineralization]. That’s not so surprising. We know there are other medical conditions in which calcium calcification can cause severe pain and inflammation.” The old term, pseudogout, is now called calcium pyrophosphate deposition disease.

The next steps of research, Dr. Neogi said, are to investigate the link of the mineralization to inflammation and its association to cartilage damage.
 

 

 

Could colchicine help?

In another recent study, researchers conducted a post hoc analysis of a randomized clinical trial of the anti-inflammatory drug colchicine, finding that the use of colchicine at 0.5 mg daily was associated with a lower incidence of total knee and hip replacements (TKR, THR). In that study, 2,762 participants received colchicine, while 2,760 received placebo during the median follow-up of 28.6 months. During the trial, TKR or THR was done in 68 patients (2.5%) of those in the treated group and 97 patients (3.5%) in the placebo groups. That resulted in an incidence rate difference of –0.40 [95% CI, –0.74 to –0.06 ] per 100 person-years.

The authors wrote that the results suggest that “colchicine may slow the progression of OA, but this needs to be confirmed in an appropriately designed prospective placebo-controlled trial.”
 

Independent perspective

The new Boston University study supports the idea that there may be a larger subset of patients that may have a calcium mineralization component, said C. Kent Kwoh, MD, professor of medicine and medical imaging at the University of Arizona, Tucson. He reviewed both studies and provided perspective. He is an editorial advisory board member for MDedge Rheumatology.

Dr. C. Kent Kwoh, professor of medicine and medical imaging at the University of Arizona, Tucson, and director of the University of Arizona Arthritis Center
courtesy Banner University Medical Group–Tucson
Dr. C. Kent Kwoh

The study by Dr. Liew and colleagues shows that “there is an association of crystal deposition not just in the cartilage, but various parts of the joint.” He emphasized the study found only an association and that more study is needed.

As for the colchicine study, he said, it “really shows there is potential at least within some individuals where it may decrease symptoms to the point where people are less likely to need joint replacement.” That analysis follows some previous research, some of it shorter term, finding that colchicine was not beneficial.
 

Takeaways

Would colchicine be worth a try in patients who have knee pain and calcium mineral deposits?

Dr. Neogi noted that a formulation of colchicine (Lodoco) was recently approved by the Food and Drug Administration to reduce the risk of myocardial infarction and other cardiovascular disease. While she does not advocate adopting a practice without evidence, she suggested if someone has both mineralization and cardiovascular disease, along with difficulty managing symptoms with established treatments, it might be worth a try, if no contraindications exist.

Dr. Kwoh agreed it may be worth a try, given that it is “relatively safe and relatively inexpensive.”

On one point all agreed: More research is needed.

Dr. Kwoh, Dr. Neogi and Dr. Liew have no relevant disclosures.

Intra-articular calcium crystal deposition is commonly seen in knee osteoarthritis, but its significance has been debated.

Now, a new study that relied on knee radiographs and bilateral knee CT imaging to evaluate 2,093 participants, including some with and without knee mineralization, has provided some new insights.

Dr. Jean Liew, assistant professor of medicine at Boston University
Dr. Jean Liew

The study has addressed the longstanding question: Is the calcium deposition a cause or a consequence of the OA? “If it’s a cause, targeting it might be helpful,” Jean Liew, MD, MS, the study’s lead author and assistant professor of medicine at Boston University, said in an interview. “If a consequence of the OA, targeting is not going to help.”

In this new study, because of the use of advanced imaging, the researchers demonstrated a strong relationship of the presence of this calcification with different pain characteristics, said Tuhina Neogi, MD, PhD, professor of medicine and epidemiology at Boston University, the corresponding author of the study who has focused on this research for many years. “This indicates this mineralization is not inconsequential.”

The bottom line? “Calcification in the knee may not be simply inert and an innocent bystander of longstanding OA,” Dr. Neogi said in an interview.
 

Study details

Dr. Neogi and colleagues evaluated 2,093 participants (mean age, 61 years; 57% female) with a mean body mass index of 28.8 kg/m2. In all, 10.2% of knees had intra-articular mineralization. The data came from the National Institutes of Health–funded longitudinal Multicenter Osteoarthritis Study. At baseline, participants had knee radiographs and bilateral knee CT scans, and pain assessments every 8 months for 2 years. The Boston University Calcium Knee Score was used to score the CT imaging. The researchers longitudinally examined the relationship of the CT-detected intra-articular mineralization to the risk of frequent knee pain, intermittent or constant knee pain worsening, and pain severity worsening. All analyses were adjusted for age, sex, body mass index, race, site, and Kellgren-Lawrence grade.

Dr. Tuhina Neogi

Having any mineralization in the cartilage was associated with a doubling of odds for having frequent knee pain (95% confidence interval, 1.38-2.78), and 1.86 times greater likelihood of more frequent intermittent or constant knee pain (95% CI, 1.20-2.78) over the 2 years of follow-up. Similar results were seen for the presence of any intra-articular mineralization in the meniscus or joint capsule. The higher the burden of mineralization anywhere within the knee was linked with higher odds for all pain outcomes, with odds ratios ranging from 2.14 to 2.21.
 

Perspective

“Because we used more sensitive imaging to pick up the calcification, we are able to more confidently evaluate this association,” Dr. Neogi said in an interview. The problem with prior studies was their reliance on plain radiographs, which are not sensitive enough to pick up this calcification.

Among the other strengths of the new research, she said, is that it was longitudinal, included more than 2,000 people and used multiple ways to look at the pain experience, getting consistent results.

“Here we are saying there seems to be clinical relevance [to the mineralization]. That’s not so surprising. We know there are other medical conditions in which calcium calcification can cause severe pain and inflammation.” The old term, pseudogout, is now called calcium pyrophosphate deposition disease.

The next steps of research, Dr. Neogi said, are to investigate the link of the mineralization to inflammation and its association to cartilage damage.
 

 

 

Could colchicine help?

In another recent study, researchers conducted a post hoc analysis of a randomized clinical trial of the anti-inflammatory drug colchicine, finding that the use of colchicine at 0.5 mg daily was associated with a lower incidence of total knee and hip replacements (TKR, THR). In that study, 2,762 participants received colchicine, while 2,760 received placebo during the median follow-up of 28.6 months. During the trial, TKR or THR was done in 68 patients (2.5%) of those in the treated group and 97 patients (3.5%) in the placebo groups. That resulted in an incidence rate difference of –0.40 [95% CI, –0.74 to –0.06 ] per 100 person-years.

The authors wrote that the results suggest that “colchicine may slow the progression of OA, but this needs to be confirmed in an appropriately designed prospective placebo-controlled trial.”
 

Independent perspective

The new Boston University study supports the idea that there may be a larger subset of patients that may have a calcium mineralization component, said C. Kent Kwoh, MD, professor of medicine and medical imaging at the University of Arizona, Tucson. He reviewed both studies and provided perspective. He is an editorial advisory board member for MDedge Rheumatology.

Dr. C. Kent Kwoh, professor of medicine and medical imaging at the University of Arizona, Tucson, and director of the University of Arizona Arthritis Center
courtesy Banner University Medical Group–Tucson
Dr. C. Kent Kwoh

The study by Dr. Liew and colleagues shows that “there is an association of crystal deposition not just in the cartilage, but various parts of the joint.” He emphasized the study found only an association and that more study is needed.

As for the colchicine study, he said, it “really shows there is potential at least within some individuals where it may decrease symptoms to the point where people are less likely to need joint replacement.” That analysis follows some previous research, some of it shorter term, finding that colchicine was not beneficial.
 

Takeaways

Would colchicine be worth a try in patients who have knee pain and calcium mineral deposits?

Dr. Neogi noted that a formulation of colchicine (Lodoco) was recently approved by the Food and Drug Administration to reduce the risk of myocardial infarction and other cardiovascular disease. While she does not advocate adopting a practice without evidence, she suggested if someone has both mineralization and cardiovascular disease, along with difficulty managing symptoms with established treatments, it might be worth a try, if no contraindications exist.

Dr. Kwoh agreed it may be worth a try, given that it is “relatively safe and relatively inexpensive.”

On one point all agreed: More research is needed.

Dr. Kwoh, Dr. Neogi and Dr. Liew have no relevant disclosures.

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