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What treatments work best for constipation in children?
Osmotic laxatives produce the best results. Fiber and behavior modification may have a role. Increased fiber and behavior modification are the most often recommended first steps in managing chronic functional constipation (CFC) in children, but only limited evidence supports this approach (strength of recommendation [SOR]: B for fiber, 1 randomized controlled trial [RCT]; C for behavior modification, 1 small trial).
For pharmacologic management, the best evidence supports osmotic laxatives (SOR: A, 6 fair- to good-quality RCTs).
Evidence summary
CFC with or without encopresis is a common pediatric problem that’s distressing to both the child and family. High-quality RCTs on managing CFC are lacking. Our search located 7 relevant RCTs1-7 and 2 relevant systematic reviews.8,9 The TABLE summarizes the RCTs.
TABLE
How laxatives for childhood constipation compare
| INTERVENTION VS COMPARISON | NNT | EFFECTIVE DOSE | AVERAGE COST/MONTH |
|---|---|---|---|
| Glucomannan vs placebo1 | 3 | 100 mg/kg/d | $10-$30* |
| PEG + E vs placebo2 | 2 | 7-42 g/d | $14-$60* |
| PEG + E vs lactulose3 | 4 | 3-6 g/d vs 6-12 g/d | $20 vs $20 |
| PEG + E vs mineral oil for disimpaction over 2 days 5 | 5 | 20 mL/kg/h×4 h/d 30-120 mL BID | $20 vs $20 |
| Mineral oil vs senna6 | 3 | 3 mL/kg/d vs 1-4 tab/d | $8 vs $5 |
| Lactulose vs senna7 | 4 | 15 mL/d vs 20 mL/d | $20 vs $10 |
| *Retail price varies by manufacturer. | |||
| NNT, number needed to treat; PEG + E, polyethylene glycol 3350 plus electrolytes. | |||
Fiber may help—and doesn’t hurt
A fair-quality crossover RCT (31 children, mean age 7 years, with CFC) compared fiber (glucomannan) with placebo for 4 weeks.1 More children were successfully treated with fiber than placebo (45% vs 13%; number needed to treat [NNT]=3.125; P<.05). Parents rated children as doing better on fiber (68% vs 13%), and abdominal pain occurred less often (10% vs 42%; P<.05). No adverse effects were associated with fiber.
Osmotic laxatives, especially PEG, get results
A recent high-quality RCT compared the osmotic laxative polyethylene glycol 3350 plus electrolytes (PEG + E) with placebo in 51 children with CFC, 2 to 11 years of age.2 The mean number of defecations per week was higher for children on PEG + E (3.12 vs 1.45; P<.001); straining or pain and stool consistency improved.
One good-quality RCT (100 children, 6 months to 15 years old with CFC) compared PEG + E with lactulose.3 Both significantly increased stool frequency and decreased encopresis. However, PEG + E had a markedly higher success rate (56% vs 29%; NNT=3.7; P=.02). The 8-week trial found significantly more complaints about bad taste in the PEG + E group; the lactulose group reported higher rates of abdominal pain, straining, and pain at defecation. The only dropout because of adverse events (bad taste) occurred in the PEG + E group.
Another good-quality RCT showed that PEG + E effectively relieved fecal impaction (92% of 63 children) and was superior to lactulose for maintenance treatment. The rate of adverse effects (abdominal pain) was 64% with PEG + E and 83% with lactulose.4
One fair-quality RCT of 48 children with fecal impaction compared PEG with mineral oil. PEG was more effective, but high-volume PEG caused more vomiting and less compliance.5
A small RCT found that mineral oil treated constipation more successfully than senna at 3 and 10 months of follow-up.6 One poor-quality RCT found that senna was less effective than lactulose and had more side effects (colicky pain, diarrhea).7
A Cochrane systematic review found no RCTs of stimulant laxatives for CFC and concluded that evidence concerning the efficacy of these agents is insufficient.8
Few studies focus on nonpharmacologic management
A Cochrane systematic review of 9 small, poor-quality RCTs in children with functional fecal incontinence found no significant improvement when biofeedback was added to conventional treatment for as long as 12 months (odds ratio=1.11; 95% confidence interval, 0.78-1.58).9 In 1 small trial, however, adding behavior modification to laxative therapy significantly reduced soiling episodes.
Notably, few studies have focused on nonpharmacologic management of CFC, and most laxative trials are of short duration.
Recommendations
The Constipation Guideline Committee of the North American Society for Pediatric Gastroenterology states that using medication in combination with behavior management can decrease time to remission in children with CFC. Lubricants (mineral oil) and osmotic laxatives (magnesium hydroxide, lactulose, and sorbitol) are safe and effective. Stimulants (senna and bisacodyl) can help some patients whose conditions are difficult to treat. Low doses of PEG may be an effective long-term therapy for hard-to-manage constipation.10
The University of Michigan Guidelines on CFC and soiling are similar. After clean-out, they recommend a maintenance phase that includes behavioral, dietary, and medication components. Osmotic laxatives and lubricants are recommended for long-term treatment; stimulant laxatives should be reserved for short-term use.11
1. Loening-Baucke V, Miele E, Staiano A. Fiber (glucomannan) is beneficial in the treatment of childhood constipation. Pediatrics. 2004;113:e259-e264.
2. Thomson MA, Jenkins HR, Bisset WM, et al. Polyethylene glycol 3350 plus electrolytes for chronic constipation in children: a double-blind, placebo-controlled, crossover study. Arch Dis Child. 2007;92:996-1000.
3. Voskuijl W, De Lorijn F, Verwijs W, et al. PEG 3350 (Transipeg) versus lactulose in the treatment of childhood functional constipation: a double-blind randomised, controlled, multicentre trial. Gut. 2004;53:1590-1594.
4. Candy DC, Edwards D, Geraint M. Treatment of faecal impaction with polyethylene glycol plus electrolytes (PEG + E) followed by a double-blind comparison of PEG+E versus lactulose as maintenance therapy. J Pediatr Gastroenterol Nutr. 2006;43:65-70.
5. Tolia V, Lin CH, Elitsur Y. A prospective randomized study with mineral oil and oral lavage solution for treatment of faecal impaction in children. Aliment Pharmacol Ther. 1993;7:523-529.
6. Sondheimer JM, Gervaise EP. Lubricant versus laxative in the treatment of chronic functional constipation of children: a comparative study. J Pediatr Gastroenterol Nutr. 1982;1:223-226.
7. Perkin JM. Constipation in childhood: a controlled comparison between lactulose and standardized senna. Curr Med Res Opin. 1977;4:540-543.
8. Price KJ, Elliott TM. What is the role of stimulant laxatives for constipation and soiling in children? Cochrane Database Syst Rev. 2001;(3):CD002040.-
9. Brazzelli M, Griffiths P. Behavioural and cognitive interventions with or without other treatments for the management of faecal incontinence in children. Cochrane Database Syst Rev. 2006;(2):CD002240.-
10. Constipation Guideline Committee of the North American Society for Pediatric Gastroenterology. Evaluation and treatment of constipation in infants and children: recommendations of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition. J Pediatr Gastroenterol Nutr. 2006;43:e1-e13.
11. University of Michigan Health System. Functional constipation and soiling in children. Ann Arbor, MI: University of Michigan Health System; February 2003. Available at: http://cme.med.umich.edu/ pdf/guideline/peds08.pdf. Accessed January 27, 2008.
Osmotic laxatives produce the best results. Fiber and behavior modification may have a role. Increased fiber and behavior modification are the most often recommended first steps in managing chronic functional constipation (CFC) in children, but only limited evidence supports this approach (strength of recommendation [SOR]: B for fiber, 1 randomized controlled trial [RCT]; C for behavior modification, 1 small trial).
For pharmacologic management, the best evidence supports osmotic laxatives (SOR: A, 6 fair- to good-quality RCTs).
Evidence summary
CFC with or without encopresis is a common pediatric problem that’s distressing to both the child and family. High-quality RCTs on managing CFC are lacking. Our search located 7 relevant RCTs1-7 and 2 relevant systematic reviews.8,9 The TABLE summarizes the RCTs.
TABLE
How laxatives for childhood constipation compare
| INTERVENTION VS COMPARISON | NNT | EFFECTIVE DOSE | AVERAGE COST/MONTH |
|---|---|---|---|
| Glucomannan vs placebo1 | 3 | 100 mg/kg/d | $10-$30* |
| PEG + E vs placebo2 | 2 | 7-42 g/d | $14-$60* |
| PEG + E vs lactulose3 | 4 | 3-6 g/d vs 6-12 g/d | $20 vs $20 |
| PEG + E vs mineral oil for disimpaction over 2 days 5 | 5 | 20 mL/kg/h×4 h/d 30-120 mL BID | $20 vs $20 |
| Mineral oil vs senna6 | 3 | 3 mL/kg/d vs 1-4 tab/d | $8 vs $5 |
| Lactulose vs senna7 | 4 | 15 mL/d vs 20 mL/d | $20 vs $10 |
| *Retail price varies by manufacturer. | |||
| NNT, number needed to treat; PEG + E, polyethylene glycol 3350 plus electrolytes. | |||
Fiber may help—and doesn’t hurt
A fair-quality crossover RCT (31 children, mean age 7 years, with CFC) compared fiber (glucomannan) with placebo for 4 weeks.1 More children were successfully treated with fiber than placebo (45% vs 13%; number needed to treat [NNT]=3.125; P<.05). Parents rated children as doing better on fiber (68% vs 13%), and abdominal pain occurred less often (10% vs 42%; P<.05). No adverse effects were associated with fiber.
Osmotic laxatives, especially PEG, get results
A recent high-quality RCT compared the osmotic laxative polyethylene glycol 3350 plus electrolytes (PEG + E) with placebo in 51 children with CFC, 2 to 11 years of age.2 The mean number of defecations per week was higher for children on PEG + E (3.12 vs 1.45; P<.001); straining or pain and stool consistency improved.
One good-quality RCT (100 children, 6 months to 15 years old with CFC) compared PEG + E with lactulose.3 Both significantly increased stool frequency and decreased encopresis. However, PEG + E had a markedly higher success rate (56% vs 29%; NNT=3.7; P=.02). The 8-week trial found significantly more complaints about bad taste in the PEG + E group; the lactulose group reported higher rates of abdominal pain, straining, and pain at defecation. The only dropout because of adverse events (bad taste) occurred in the PEG + E group.
Another good-quality RCT showed that PEG + E effectively relieved fecal impaction (92% of 63 children) and was superior to lactulose for maintenance treatment. The rate of adverse effects (abdominal pain) was 64% with PEG + E and 83% with lactulose.4
One fair-quality RCT of 48 children with fecal impaction compared PEG with mineral oil. PEG was more effective, but high-volume PEG caused more vomiting and less compliance.5
A small RCT found that mineral oil treated constipation more successfully than senna at 3 and 10 months of follow-up.6 One poor-quality RCT found that senna was less effective than lactulose and had more side effects (colicky pain, diarrhea).7
A Cochrane systematic review found no RCTs of stimulant laxatives for CFC and concluded that evidence concerning the efficacy of these agents is insufficient.8
Few studies focus on nonpharmacologic management
A Cochrane systematic review of 9 small, poor-quality RCTs in children with functional fecal incontinence found no significant improvement when biofeedback was added to conventional treatment for as long as 12 months (odds ratio=1.11; 95% confidence interval, 0.78-1.58).9 In 1 small trial, however, adding behavior modification to laxative therapy significantly reduced soiling episodes.
Notably, few studies have focused on nonpharmacologic management of CFC, and most laxative trials are of short duration.
Recommendations
The Constipation Guideline Committee of the North American Society for Pediatric Gastroenterology states that using medication in combination with behavior management can decrease time to remission in children with CFC. Lubricants (mineral oil) and osmotic laxatives (magnesium hydroxide, lactulose, and sorbitol) are safe and effective. Stimulants (senna and bisacodyl) can help some patients whose conditions are difficult to treat. Low doses of PEG may be an effective long-term therapy for hard-to-manage constipation.10
The University of Michigan Guidelines on CFC and soiling are similar. After clean-out, they recommend a maintenance phase that includes behavioral, dietary, and medication components. Osmotic laxatives and lubricants are recommended for long-term treatment; stimulant laxatives should be reserved for short-term use.11
Osmotic laxatives produce the best results. Fiber and behavior modification may have a role. Increased fiber and behavior modification are the most often recommended first steps in managing chronic functional constipation (CFC) in children, but only limited evidence supports this approach (strength of recommendation [SOR]: B for fiber, 1 randomized controlled trial [RCT]; C for behavior modification, 1 small trial).
For pharmacologic management, the best evidence supports osmotic laxatives (SOR: A, 6 fair- to good-quality RCTs).
Evidence summary
CFC with or without encopresis is a common pediatric problem that’s distressing to both the child and family. High-quality RCTs on managing CFC are lacking. Our search located 7 relevant RCTs1-7 and 2 relevant systematic reviews.8,9 The TABLE summarizes the RCTs.
TABLE
How laxatives for childhood constipation compare
| INTERVENTION VS COMPARISON | NNT | EFFECTIVE DOSE | AVERAGE COST/MONTH |
|---|---|---|---|
| Glucomannan vs placebo1 | 3 | 100 mg/kg/d | $10-$30* |
| PEG + E vs placebo2 | 2 | 7-42 g/d | $14-$60* |
| PEG + E vs lactulose3 | 4 | 3-6 g/d vs 6-12 g/d | $20 vs $20 |
| PEG + E vs mineral oil for disimpaction over 2 days 5 | 5 | 20 mL/kg/h×4 h/d 30-120 mL BID | $20 vs $20 |
| Mineral oil vs senna6 | 3 | 3 mL/kg/d vs 1-4 tab/d | $8 vs $5 |
| Lactulose vs senna7 | 4 | 15 mL/d vs 20 mL/d | $20 vs $10 |
| *Retail price varies by manufacturer. | |||
| NNT, number needed to treat; PEG + E, polyethylene glycol 3350 plus electrolytes. | |||
Fiber may help—and doesn’t hurt
A fair-quality crossover RCT (31 children, mean age 7 years, with CFC) compared fiber (glucomannan) with placebo for 4 weeks.1 More children were successfully treated with fiber than placebo (45% vs 13%; number needed to treat [NNT]=3.125; P<.05). Parents rated children as doing better on fiber (68% vs 13%), and abdominal pain occurred less often (10% vs 42%; P<.05). No adverse effects were associated with fiber.
Osmotic laxatives, especially PEG, get results
A recent high-quality RCT compared the osmotic laxative polyethylene glycol 3350 plus electrolytes (PEG + E) with placebo in 51 children with CFC, 2 to 11 years of age.2 The mean number of defecations per week was higher for children on PEG + E (3.12 vs 1.45; P<.001); straining or pain and stool consistency improved.
One good-quality RCT (100 children, 6 months to 15 years old with CFC) compared PEG + E with lactulose.3 Both significantly increased stool frequency and decreased encopresis. However, PEG + E had a markedly higher success rate (56% vs 29%; NNT=3.7; P=.02). The 8-week trial found significantly more complaints about bad taste in the PEG + E group; the lactulose group reported higher rates of abdominal pain, straining, and pain at defecation. The only dropout because of adverse events (bad taste) occurred in the PEG + E group.
Another good-quality RCT showed that PEG + E effectively relieved fecal impaction (92% of 63 children) and was superior to lactulose for maintenance treatment. The rate of adverse effects (abdominal pain) was 64% with PEG + E and 83% with lactulose.4
One fair-quality RCT of 48 children with fecal impaction compared PEG with mineral oil. PEG was more effective, but high-volume PEG caused more vomiting and less compliance.5
A small RCT found that mineral oil treated constipation more successfully than senna at 3 and 10 months of follow-up.6 One poor-quality RCT found that senna was less effective than lactulose and had more side effects (colicky pain, diarrhea).7
A Cochrane systematic review found no RCTs of stimulant laxatives for CFC and concluded that evidence concerning the efficacy of these agents is insufficient.8
Few studies focus on nonpharmacologic management
A Cochrane systematic review of 9 small, poor-quality RCTs in children with functional fecal incontinence found no significant improvement when biofeedback was added to conventional treatment for as long as 12 months (odds ratio=1.11; 95% confidence interval, 0.78-1.58).9 In 1 small trial, however, adding behavior modification to laxative therapy significantly reduced soiling episodes.
Notably, few studies have focused on nonpharmacologic management of CFC, and most laxative trials are of short duration.
Recommendations
The Constipation Guideline Committee of the North American Society for Pediatric Gastroenterology states that using medication in combination with behavior management can decrease time to remission in children with CFC. Lubricants (mineral oil) and osmotic laxatives (magnesium hydroxide, lactulose, and sorbitol) are safe and effective. Stimulants (senna and bisacodyl) can help some patients whose conditions are difficult to treat. Low doses of PEG may be an effective long-term therapy for hard-to-manage constipation.10
The University of Michigan Guidelines on CFC and soiling are similar. After clean-out, they recommend a maintenance phase that includes behavioral, dietary, and medication components. Osmotic laxatives and lubricants are recommended for long-term treatment; stimulant laxatives should be reserved for short-term use.11
1. Loening-Baucke V, Miele E, Staiano A. Fiber (glucomannan) is beneficial in the treatment of childhood constipation. Pediatrics. 2004;113:e259-e264.
2. Thomson MA, Jenkins HR, Bisset WM, et al. Polyethylene glycol 3350 plus electrolytes for chronic constipation in children: a double-blind, placebo-controlled, crossover study. Arch Dis Child. 2007;92:996-1000.
3. Voskuijl W, De Lorijn F, Verwijs W, et al. PEG 3350 (Transipeg) versus lactulose in the treatment of childhood functional constipation: a double-blind randomised, controlled, multicentre trial. Gut. 2004;53:1590-1594.
4. Candy DC, Edwards D, Geraint M. Treatment of faecal impaction with polyethylene glycol plus electrolytes (PEG + E) followed by a double-blind comparison of PEG+E versus lactulose as maintenance therapy. J Pediatr Gastroenterol Nutr. 2006;43:65-70.
5. Tolia V, Lin CH, Elitsur Y. A prospective randomized study with mineral oil and oral lavage solution for treatment of faecal impaction in children. Aliment Pharmacol Ther. 1993;7:523-529.
6. Sondheimer JM, Gervaise EP. Lubricant versus laxative in the treatment of chronic functional constipation of children: a comparative study. J Pediatr Gastroenterol Nutr. 1982;1:223-226.
7. Perkin JM. Constipation in childhood: a controlled comparison between lactulose and standardized senna. Curr Med Res Opin. 1977;4:540-543.
8. Price KJ, Elliott TM. What is the role of stimulant laxatives for constipation and soiling in children? Cochrane Database Syst Rev. 2001;(3):CD002040.-
9. Brazzelli M, Griffiths P. Behavioural and cognitive interventions with or without other treatments for the management of faecal incontinence in children. Cochrane Database Syst Rev. 2006;(2):CD002240.-
10. Constipation Guideline Committee of the North American Society for Pediatric Gastroenterology. Evaluation and treatment of constipation in infants and children: recommendations of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition. J Pediatr Gastroenterol Nutr. 2006;43:e1-e13.
11. University of Michigan Health System. Functional constipation and soiling in children. Ann Arbor, MI: University of Michigan Health System; February 2003. Available at: http://cme.med.umich.edu/ pdf/guideline/peds08.pdf. Accessed January 27, 2008.
1. Loening-Baucke V, Miele E, Staiano A. Fiber (glucomannan) is beneficial in the treatment of childhood constipation. Pediatrics. 2004;113:e259-e264.
2. Thomson MA, Jenkins HR, Bisset WM, et al. Polyethylene glycol 3350 plus electrolytes for chronic constipation in children: a double-blind, placebo-controlled, crossover study. Arch Dis Child. 2007;92:996-1000.
3. Voskuijl W, De Lorijn F, Verwijs W, et al. PEG 3350 (Transipeg) versus lactulose in the treatment of childhood functional constipation: a double-blind randomised, controlled, multicentre trial. Gut. 2004;53:1590-1594.
4. Candy DC, Edwards D, Geraint M. Treatment of faecal impaction with polyethylene glycol plus electrolytes (PEG + E) followed by a double-blind comparison of PEG+E versus lactulose as maintenance therapy. J Pediatr Gastroenterol Nutr. 2006;43:65-70.
5. Tolia V, Lin CH, Elitsur Y. A prospective randomized study with mineral oil and oral lavage solution for treatment of faecal impaction in children. Aliment Pharmacol Ther. 1993;7:523-529.
6. Sondheimer JM, Gervaise EP. Lubricant versus laxative in the treatment of chronic functional constipation of children: a comparative study. J Pediatr Gastroenterol Nutr. 1982;1:223-226.
7. Perkin JM. Constipation in childhood: a controlled comparison between lactulose and standardized senna. Curr Med Res Opin. 1977;4:540-543.
8. Price KJ, Elliott TM. What is the role of stimulant laxatives for constipation and soiling in children? Cochrane Database Syst Rev. 2001;(3):CD002040.-
9. Brazzelli M, Griffiths P. Behavioural and cognitive interventions with or without other treatments for the management of faecal incontinence in children. Cochrane Database Syst Rev. 2006;(2):CD002240.-
10. Constipation Guideline Committee of the North American Society for Pediatric Gastroenterology. Evaluation and treatment of constipation in infants and children: recommendations of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition. J Pediatr Gastroenterol Nutr. 2006;43:e1-e13.
11. University of Michigan Health System. Functional constipation and soiling in children. Ann Arbor, MI: University of Michigan Health System; February 2003. Available at: http://cme.med.umich.edu/ pdf/guideline/peds08.pdf. Accessed January 27, 2008.
Evidence-based answers from the Family Physicians Inquiries Network
Do inhaled steroids increase the risk of osteoporosis?
The use of inhaled corticosteroids at conventional doses for asthma and chronic obstructive pulmonary disease (COPD) does not appear to be associated with significant bone loss at 2 to 3 years of follow-up (strength of recommendation [SOR]: A, systematic reviews and randomized controlled trials [RCTs]). However, higher doses of inhaled corticosteroids may be associated with negative bone density changes at up to 4 years of follow-up (SOR: C, RCTs without change in fracture rates). No evidence exists to evaluate whether nasal steroids increase the risks of bone loss. Longer-term effects of prolonged use of inhaled steroids on BMD or fracture risk are undetermined with current evidence.
Encourage weight-bearing and aerobic exercise to all asthma or COPD patients
José E. Rodríguez, MD
Florida State University College of Medicine, Tallahassee
Asthma and COPD are prevalent among the underserved patients I see. Inhaled steroids are difficult for these patients to obtain. Once they feel better, many stop using the steroid until symptoms return.
Although we do not usually prescribe at the higher doses described in the review, our goal has always been long-term treatment. If these medications can cause osteoporosis with longer use, it may become an additional deterrent to adherence. However, consistent use may reduce the use of oral steroids for acute exacerbations, potentially even reducing bone loss.
Encourage weight-bearing and aerobic exercise for osteoporosis prevention and balance exercises to prevent falls for all asthma or COPD patients. These exercises may be prudent prevention for both lung disease and osteoporotic fractures.
Evidence summary
Inhaled corticosteroids are the primary therapy for asthma and are commonly prescribed for chronic obstructive pulmonary disease. The use of oral steroids is a well-known risk factor for osteoporosis, but the effects of inhaled corticosteroids on bone mineral density (BMD) are not well defined.
No significant changes seen in BMD at moderate doses
Our search found evidence pertaining to the use of inhaled pulmonary steroids, but no evidence meeting our inclusion criteria about the effect of inhaled nasal steroids. We located a Cochrane review, 1 other meta-analysis, and 2 individual RCTs that were not included in the systematic reviews. Three of the 7 RCTs included in the 2002 Cochrane review met our inclusion criteria for evaluating the impact of inhaled corticosteroids on BMD or fracture rate for adults with asthma or COPD.
All 3 RCTs (792 subjects total) examined the effect of conventional doses of inhaled corticosteroids on BMD and 2 of the RCTs (892 participants total) collected fracture data. No demonstrable effect was seen on vertebral fracture (odds ratio [OR]=1.87; 95% confidence interval [CI], 0.5–7.03) or BMD at 2 years follow-up.1 The subjects were otherwise healthy people with asthma or COPD with an average age of 40 years; men outnumbered women 2 to 1.
A fair-quality 2004 meta-analysis of 14 randomized trials (2300 participants) included 2 studies (448 subjects) that overlapped with the Cochrane review. There were no significant changes in BMD with moderately high doses of inhaled corticosteroids at 1 to 3 years follow-up.2
Annual changes in lumbar and femoral neck BMD (–0.23% and –0.17%, respectively) were not statistically significant. Mean changes in lumbar BMD were not significantly different from controls (–0.02). A fair-quality 2004 RCT did not demonstrate any clinically relevant effect on BMD at 2 years follow-up. This study used 800 mcg/day of fluticasone for patients with mild asthma.3
BMD changes found at higher doses
There is, however, some evidence that higher doses of inhaled corticosteroids can result in adverse BMD changes. In a high-quality RCT of 412 participants, aged 40 to 69 years, with mild to moderate COPD, use of higher-dose triamcinolone (1200 mcg/day) was associated with decreased lumbar and femoral neck BMD over 3 to 4 years.4 The differences in BMD between the inhaled corticosteroids and placebo groups at the femoral neck and lumbar spine were 1.78% (P<.001) and 1.33% (P=.007), respectively. However, the risk of fracture or height loss did not increase at follow-up.
A large fair-quality RCT from 2001 included in both meta-analyses demonstrated a dose-related fall in BMD within the subjects over 2 years at the lumbar spine (standard deviation, 3.4%; P<.010). This finding remained statistically significant after adjusting for asthma severity, but BMD changes were not different between the inhaled corticosteroids and placebo groups. However, this finding may be the result of higher oral corticosteroids use in the reference group.5
Limitations of these studies
These studies, though, have limitations. The follow-up periods for all of these studies are less than 5 years, and thus the longer-term effects of prolonged use of inhaled corticosteroids on BMD or fracture risk cannot be determined with this evidence. Furthermore, the study populations were relatively young, with few other risk factors (they were, for example, predominantly male) than populations at highest risk for osteoporosis and fracture. These factors limit interpretation of the data for long-term inhaled corticosteroids use, particularly in populations with higher baseline osteoporosis risk—older persons with chronic lung disease who take inhaled corticosteroids for more than 2 to 3 years. We need better and longer-term studies to help advise our patients about the risks and benefits of inhaled corticosteroids therapy.
Recommendations from others
The New Zealand Guideline Group says the risk of reduced BMD increased with long-term, high-dose inhaled corticosteroids.6 The Institute for Clinical Systems Improvement guidelines recommends considering osteoporosis prevention measures for those who have been (or will be) taking a daily high-dose inhaled glucocorticoid for several years as glucocorticoid use compounds fracture risk beyond that determined solely by BMD.7
1. Jones A, Fay JK, Burr M, et al. Inhaled corticosteroid effects on bone metabolism in asthma and chronic obstructive pulmonary disease. Cochrane Database Syst Rev 1, 2006.
2. Halpern MT, Schmier JK, Van Kerkhove MD, et al. Impact of long term inhaled corticosteroid therapy on bone mineral density results of a meta-analysis. Ann Allergy Asthma Immunol 2004;92:201-207.
3. Kemp JP, Osur S, Shrewsburry SB, et al. Potential effects of fluticasone propionate on bone mineral density in patients with asthma: A 2-year randomized, double-blind, placebo-controlled trial. Mayo Clin Proc 2004;79:458-466.
4. Scanlon PD, Connett JE, Wise RA, et al. Loss of bone density with inhaled triamcinolone in Lung Health Study II. Am J Respir Crit Care Med 2004;170:1302-1309.
5. Tattersfield AE, Town GI, Johnell O, et al. Bone mineral density in subjects with mild asthma randomized to treatment with inhaled corticosteroids or non-corticosteroid treatment for two years. Thorax 2001;56:272-278.
6. New Zealand Guidelines Group. The diagnosis and treatment of adult asthma. Wellington, NZ: New Zealand Guidelines Group; 2002 Sep. 101 p. Available at: www.guideline.gov/summary/summary.aspx?doc_id=3462 (NCG: 2688). Accessed on January 18, 2007.
7. Institute for Clinical Systems Improvement. Diagnosis and treatment of osteoporosis. Bloomington, Minn: Institute for Clinical Systems Improvement; 2005 Sep. 61 p. Available at: www.guideline.gov/summary/summary.aspx?doc_id=9626 (NCG: 5146). Accessed on January 18, 2007.
The use of inhaled corticosteroids at conventional doses for asthma and chronic obstructive pulmonary disease (COPD) does not appear to be associated with significant bone loss at 2 to 3 years of follow-up (strength of recommendation [SOR]: A, systematic reviews and randomized controlled trials [RCTs]). However, higher doses of inhaled corticosteroids may be associated with negative bone density changes at up to 4 years of follow-up (SOR: C, RCTs without change in fracture rates). No evidence exists to evaluate whether nasal steroids increase the risks of bone loss. Longer-term effects of prolonged use of inhaled steroids on BMD or fracture risk are undetermined with current evidence.
Encourage weight-bearing and aerobic exercise to all asthma or COPD patients
José E. Rodríguez, MD
Florida State University College of Medicine, Tallahassee
Asthma and COPD are prevalent among the underserved patients I see. Inhaled steroids are difficult for these patients to obtain. Once they feel better, many stop using the steroid until symptoms return.
Although we do not usually prescribe at the higher doses described in the review, our goal has always been long-term treatment. If these medications can cause osteoporosis with longer use, it may become an additional deterrent to adherence. However, consistent use may reduce the use of oral steroids for acute exacerbations, potentially even reducing bone loss.
Encourage weight-bearing and aerobic exercise for osteoporosis prevention and balance exercises to prevent falls for all asthma or COPD patients. These exercises may be prudent prevention for both lung disease and osteoporotic fractures.
Evidence summary
Inhaled corticosteroids are the primary therapy for asthma and are commonly prescribed for chronic obstructive pulmonary disease. The use of oral steroids is a well-known risk factor for osteoporosis, but the effects of inhaled corticosteroids on bone mineral density (BMD) are not well defined.
No significant changes seen in BMD at moderate doses
Our search found evidence pertaining to the use of inhaled pulmonary steroids, but no evidence meeting our inclusion criteria about the effect of inhaled nasal steroids. We located a Cochrane review, 1 other meta-analysis, and 2 individual RCTs that were not included in the systematic reviews. Three of the 7 RCTs included in the 2002 Cochrane review met our inclusion criteria for evaluating the impact of inhaled corticosteroids on BMD or fracture rate for adults with asthma or COPD.
All 3 RCTs (792 subjects total) examined the effect of conventional doses of inhaled corticosteroids on BMD and 2 of the RCTs (892 participants total) collected fracture data. No demonstrable effect was seen on vertebral fracture (odds ratio [OR]=1.87; 95% confidence interval [CI], 0.5–7.03) or BMD at 2 years follow-up.1 The subjects were otherwise healthy people with asthma or COPD with an average age of 40 years; men outnumbered women 2 to 1.
A fair-quality 2004 meta-analysis of 14 randomized trials (2300 participants) included 2 studies (448 subjects) that overlapped with the Cochrane review. There were no significant changes in BMD with moderately high doses of inhaled corticosteroids at 1 to 3 years follow-up.2
Annual changes in lumbar and femoral neck BMD (–0.23% and –0.17%, respectively) were not statistically significant. Mean changes in lumbar BMD were not significantly different from controls (–0.02). A fair-quality 2004 RCT did not demonstrate any clinically relevant effect on BMD at 2 years follow-up. This study used 800 mcg/day of fluticasone for patients with mild asthma.3
BMD changes found at higher doses
There is, however, some evidence that higher doses of inhaled corticosteroids can result in adverse BMD changes. In a high-quality RCT of 412 participants, aged 40 to 69 years, with mild to moderate COPD, use of higher-dose triamcinolone (1200 mcg/day) was associated with decreased lumbar and femoral neck BMD over 3 to 4 years.4 The differences in BMD between the inhaled corticosteroids and placebo groups at the femoral neck and lumbar spine were 1.78% (P<.001) and 1.33% (P=.007), respectively. However, the risk of fracture or height loss did not increase at follow-up.
A large fair-quality RCT from 2001 included in both meta-analyses demonstrated a dose-related fall in BMD within the subjects over 2 years at the lumbar spine (standard deviation, 3.4%; P<.010). This finding remained statistically significant after adjusting for asthma severity, but BMD changes were not different between the inhaled corticosteroids and placebo groups. However, this finding may be the result of higher oral corticosteroids use in the reference group.5
Limitations of these studies
These studies, though, have limitations. The follow-up periods for all of these studies are less than 5 years, and thus the longer-term effects of prolonged use of inhaled corticosteroids on BMD or fracture risk cannot be determined with this evidence. Furthermore, the study populations were relatively young, with few other risk factors (they were, for example, predominantly male) than populations at highest risk for osteoporosis and fracture. These factors limit interpretation of the data for long-term inhaled corticosteroids use, particularly in populations with higher baseline osteoporosis risk—older persons with chronic lung disease who take inhaled corticosteroids for more than 2 to 3 years. We need better and longer-term studies to help advise our patients about the risks and benefits of inhaled corticosteroids therapy.
Recommendations from others
The New Zealand Guideline Group says the risk of reduced BMD increased with long-term, high-dose inhaled corticosteroids.6 The Institute for Clinical Systems Improvement guidelines recommends considering osteoporosis prevention measures for those who have been (or will be) taking a daily high-dose inhaled glucocorticoid for several years as glucocorticoid use compounds fracture risk beyond that determined solely by BMD.7
The use of inhaled corticosteroids at conventional doses for asthma and chronic obstructive pulmonary disease (COPD) does not appear to be associated with significant bone loss at 2 to 3 years of follow-up (strength of recommendation [SOR]: A, systematic reviews and randomized controlled trials [RCTs]). However, higher doses of inhaled corticosteroids may be associated with negative bone density changes at up to 4 years of follow-up (SOR: C, RCTs without change in fracture rates). No evidence exists to evaluate whether nasal steroids increase the risks of bone loss. Longer-term effects of prolonged use of inhaled steroids on BMD or fracture risk are undetermined with current evidence.
Encourage weight-bearing and aerobic exercise to all asthma or COPD patients
José E. Rodríguez, MD
Florida State University College of Medicine, Tallahassee
Asthma and COPD are prevalent among the underserved patients I see. Inhaled steroids are difficult for these patients to obtain. Once they feel better, many stop using the steroid until symptoms return.
Although we do not usually prescribe at the higher doses described in the review, our goal has always been long-term treatment. If these medications can cause osteoporosis with longer use, it may become an additional deterrent to adherence. However, consistent use may reduce the use of oral steroids for acute exacerbations, potentially even reducing bone loss.
Encourage weight-bearing and aerobic exercise for osteoporosis prevention and balance exercises to prevent falls for all asthma or COPD patients. These exercises may be prudent prevention for both lung disease and osteoporotic fractures.
Evidence summary
Inhaled corticosteroids are the primary therapy for asthma and are commonly prescribed for chronic obstructive pulmonary disease. The use of oral steroids is a well-known risk factor for osteoporosis, but the effects of inhaled corticosteroids on bone mineral density (BMD) are not well defined.
No significant changes seen in BMD at moderate doses
Our search found evidence pertaining to the use of inhaled pulmonary steroids, but no evidence meeting our inclusion criteria about the effect of inhaled nasal steroids. We located a Cochrane review, 1 other meta-analysis, and 2 individual RCTs that were not included in the systematic reviews. Three of the 7 RCTs included in the 2002 Cochrane review met our inclusion criteria for evaluating the impact of inhaled corticosteroids on BMD or fracture rate for adults with asthma or COPD.
All 3 RCTs (792 subjects total) examined the effect of conventional doses of inhaled corticosteroids on BMD and 2 of the RCTs (892 participants total) collected fracture data. No demonstrable effect was seen on vertebral fracture (odds ratio [OR]=1.87; 95% confidence interval [CI], 0.5–7.03) or BMD at 2 years follow-up.1 The subjects were otherwise healthy people with asthma or COPD with an average age of 40 years; men outnumbered women 2 to 1.
A fair-quality 2004 meta-analysis of 14 randomized trials (2300 participants) included 2 studies (448 subjects) that overlapped with the Cochrane review. There were no significant changes in BMD with moderately high doses of inhaled corticosteroids at 1 to 3 years follow-up.2
Annual changes in lumbar and femoral neck BMD (–0.23% and –0.17%, respectively) were not statistically significant. Mean changes in lumbar BMD were not significantly different from controls (–0.02). A fair-quality 2004 RCT did not demonstrate any clinically relevant effect on BMD at 2 years follow-up. This study used 800 mcg/day of fluticasone for patients with mild asthma.3
BMD changes found at higher doses
There is, however, some evidence that higher doses of inhaled corticosteroids can result in adverse BMD changes. In a high-quality RCT of 412 participants, aged 40 to 69 years, with mild to moderate COPD, use of higher-dose triamcinolone (1200 mcg/day) was associated with decreased lumbar and femoral neck BMD over 3 to 4 years.4 The differences in BMD between the inhaled corticosteroids and placebo groups at the femoral neck and lumbar spine were 1.78% (P<.001) and 1.33% (P=.007), respectively. However, the risk of fracture or height loss did not increase at follow-up.
A large fair-quality RCT from 2001 included in both meta-analyses demonstrated a dose-related fall in BMD within the subjects over 2 years at the lumbar spine (standard deviation, 3.4%; P<.010). This finding remained statistically significant after adjusting for asthma severity, but BMD changes were not different between the inhaled corticosteroids and placebo groups. However, this finding may be the result of higher oral corticosteroids use in the reference group.5
Limitations of these studies
These studies, though, have limitations. The follow-up periods for all of these studies are less than 5 years, and thus the longer-term effects of prolonged use of inhaled corticosteroids on BMD or fracture risk cannot be determined with this evidence. Furthermore, the study populations were relatively young, with few other risk factors (they were, for example, predominantly male) than populations at highest risk for osteoporosis and fracture. These factors limit interpretation of the data for long-term inhaled corticosteroids use, particularly in populations with higher baseline osteoporosis risk—older persons with chronic lung disease who take inhaled corticosteroids for more than 2 to 3 years. We need better and longer-term studies to help advise our patients about the risks and benefits of inhaled corticosteroids therapy.
Recommendations from others
The New Zealand Guideline Group says the risk of reduced BMD increased with long-term, high-dose inhaled corticosteroids.6 The Institute for Clinical Systems Improvement guidelines recommends considering osteoporosis prevention measures for those who have been (or will be) taking a daily high-dose inhaled glucocorticoid for several years as glucocorticoid use compounds fracture risk beyond that determined solely by BMD.7
1. Jones A, Fay JK, Burr M, et al. Inhaled corticosteroid effects on bone metabolism in asthma and chronic obstructive pulmonary disease. Cochrane Database Syst Rev 1, 2006.
2. Halpern MT, Schmier JK, Van Kerkhove MD, et al. Impact of long term inhaled corticosteroid therapy on bone mineral density results of a meta-analysis. Ann Allergy Asthma Immunol 2004;92:201-207.
3. Kemp JP, Osur S, Shrewsburry SB, et al. Potential effects of fluticasone propionate on bone mineral density in patients with asthma: A 2-year randomized, double-blind, placebo-controlled trial. Mayo Clin Proc 2004;79:458-466.
4. Scanlon PD, Connett JE, Wise RA, et al. Loss of bone density with inhaled triamcinolone in Lung Health Study II. Am J Respir Crit Care Med 2004;170:1302-1309.
5. Tattersfield AE, Town GI, Johnell O, et al. Bone mineral density in subjects with mild asthma randomized to treatment with inhaled corticosteroids or non-corticosteroid treatment for two years. Thorax 2001;56:272-278.
6. New Zealand Guidelines Group. The diagnosis and treatment of adult asthma. Wellington, NZ: New Zealand Guidelines Group; 2002 Sep. 101 p. Available at: www.guideline.gov/summary/summary.aspx?doc_id=3462 (NCG: 2688). Accessed on January 18, 2007.
7. Institute for Clinical Systems Improvement. Diagnosis and treatment of osteoporosis. Bloomington, Minn: Institute for Clinical Systems Improvement; 2005 Sep. 61 p. Available at: www.guideline.gov/summary/summary.aspx?doc_id=9626 (NCG: 5146). Accessed on January 18, 2007.
1. Jones A, Fay JK, Burr M, et al. Inhaled corticosteroid effects on bone metabolism in asthma and chronic obstructive pulmonary disease. Cochrane Database Syst Rev 1, 2006.
2. Halpern MT, Schmier JK, Van Kerkhove MD, et al. Impact of long term inhaled corticosteroid therapy on bone mineral density results of a meta-analysis. Ann Allergy Asthma Immunol 2004;92:201-207.
3. Kemp JP, Osur S, Shrewsburry SB, et al. Potential effects of fluticasone propionate on bone mineral density in patients with asthma: A 2-year randomized, double-blind, placebo-controlled trial. Mayo Clin Proc 2004;79:458-466.
4. Scanlon PD, Connett JE, Wise RA, et al. Loss of bone density with inhaled triamcinolone in Lung Health Study II. Am J Respir Crit Care Med 2004;170:1302-1309.
5. Tattersfield AE, Town GI, Johnell O, et al. Bone mineral density in subjects with mild asthma randomized to treatment with inhaled corticosteroids or non-corticosteroid treatment for two years. Thorax 2001;56:272-278.
6. New Zealand Guidelines Group. The diagnosis and treatment of adult asthma. Wellington, NZ: New Zealand Guidelines Group; 2002 Sep. 101 p. Available at: www.guideline.gov/summary/summary.aspx?doc_id=3462 (NCG: 2688). Accessed on January 18, 2007.
7. Institute for Clinical Systems Improvement. Diagnosis and treatment of osteoporosis. Bloomington, Minn: Institute for Clinical Systems Improvement; 2005 Sep. 61 p. Available at: www.guideline.gov/summary/summary.aspx?doc_id=9626 (NCG: 5146). Accessed on January 18, 2007.
Evidence-based answers from the Family Physicians Inquiries Network