The Comparative Efficacy of Drug Therapies Used for the Management of Corticosteroid‐Induced Osteoporosis: A Meta‐Regression

Clinical Epidemiology Research and Training Unit, Department of Medicine, Boston Medical Center and Boston University School of Medicine, Boston, Massachusetts, USA
Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research (Impact Factor: 6.83). 07/2002; 17(8):1512 - 1526. DOI: 10.1359/jbmr.2002.17.8.1512


We determined the comparative efficacy of vitamin D, calcitonin, fluoride, and bisphosphonates for the management of corticosteroid-induced osteoporosis using meta-regression models. A systematic search for trials was conducted using MEDLINE, bibliographic references, abstracts from national meetings, and contact with pharmaceutical companies and content experts. We included all randomized controlled trials, lasting at least 6 months, of adult patients on oral corticosteroids that evaluated treatment comparisons between vitamin D, calcitonin, bisphosphonates, or fluoride either with no therapy/calcium or with each other and that reported extractable results. The outcome measure of interest was change in lumbar spine bone mineral density (BMD). We identified 45 eligible trials, which provided 49 eligible treatment comparisons (some trials had three arms or more). Our results indicated that bisphosphonates were the most effective class (effect size 1.03; 95% CI: 0.85, 1.17); results were similar even when newer generations of nitrogen-containing bisphosphonates were excluded from analysis. We found the efficacy of bisphosphonates was enhanced further when used in combination with vitamin D (effect size, 1.31; 95% CI: 1.07, 1.50). Vitamin D and calcitonin were more effective than no therapy/calcium (effect size, 0.46; 95% CI: 0.27, 0.62; and effect size, 0.51; 95% CI: 0.33, 0.67, respectively) and were of similar efficacy, but both were significantly less effective than bisphosphonates. Fluoride appeared effective, but there were too few studies (n = 5) to draw robust conclusions regarding its efficacy compared with the other three therapies. In summary, bisphosphonates are the most effective of evaluated agents for managing corticosteroid-induced osteoporosis. The efficacy of bisphosphonates is enhanced further with concomitant use of vitamin D.

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Available from: Michael P Lavalley, Sep 23, 2014
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    • "The other study included patients on long-term GC treatment and showed that risedronate increased the BMD. The average difference in percentage of BMD change among patients using bisphosphonates was plus 4.6% compared with patients using placebo/calcium [37]. Adding vitamin D supplementation to bisphosphonate treatment further enhanced the beneficial effect to an estimated difference of plus 6%. "
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    ABSTRACT: Glucocorticoid-induced osteoporosis (GIOP) is one of the most important side effects of glucocorticoid use, as it leads to an increased risk of fractures. Recently, many published studies have focused on the cellular and molecular mechanisms of bone metabolism, the pathophysiology of GIOP, and the intervention options to prevent GIOP. In this review, recent advances in GIOP are summarized, particularly recent progress in our understanding of the mechanisms of GIOP resulting in improved insight that might result in the development of new treatment options in the near future.
    Current Rheumatology Reports 03/2011; 13(3):233-40. DOI:10.1007/s11926-011-0173-y · 2.87 Impact Factor
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    • "These results were similar even when newer generations of nitrogen-containing bisphosphonates were excluded from analysis, and even when the trial characteristics were divided into two categories, i.e., prevention and treatment (treatment initiated within six months of corticosteroid therapy; Table 2). The efficacy of fluoride might be intermediate between that of bisphosphonates and that of vitamin D or calcitonin.15 The combined use of bisphosphonate and vitamin D has been emphasized, because the efficacy of bisphosphonates was enhanced when used in combination with vitamin D. When the outcome measure of interest was limited to the change in lumbar spine BMD, bisphosphonates were the most effective of the agents evaluated for managing corticosteroid-induced osteoporosis. "
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    ABSTRACT: Osteoporosis is one of the most serious complications of corticosteroid treatment. Loss of bone mineral density (BMD) and fractures occur early in the course of corticosteroid treatment, and thus early recognition of fracture risk and effective intervention based on evidence-based-medicine (EBM) are needed. A study of meta-analysis representing the highest level in a hierarchy of evidence showed that when the outcome measure of interest was limited to changes in lumbar spine BMD, bisphosphonates were the most effective of the agents studied in comparison with no therapy or treatment with calcium, and were also more efficacious than either vitamin D or calcitonin; the efficacy of bisphosphonates was enhanced when used in combination with vitamin D. Randomized controlled trials (RCTs) representing the second level in a hierarchy of evidence showed that bisphosphonates stabilized BMD not only in the lumbar spine, but also in the hip, and that parathyroid hormone (PTH) markedly increased lumbar spine BMD. According to the EBM, bisphosphonates and possibly PTH are suggested to be the most efficacious for preserving BMD. The efficacy of these agents in reducing the incidence of vertebral fractures in patients exposed to corticosteroids remains to be established in meta-analysis studies, although some RCTs have demonstrated the anti-fracture effects of etidronate, alendronate, and risedronate in the spine. Further RCTs of fracture prevention conducted on a large number of patients and their meta-analysis are needed to confirm the efficacy of bisphosphonates, PTH, or other agents in preventing vertebral and nonvertebral fractures.
    Yonsei Medical Journal 09/2005; 46(4):456-63. DOI:10.3349/ymj.2005.46.4.456 · 1.29 Impact Factor
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    • "With regard to glucocorticoid-induced osteoporosis (GIO), a randomized controlled trial in foreign countries3 showed that etidronate treatment reduced vertebral fractures (RR: 0.57), but this effect was not statistically significant. Recently, however, a meta-regression analysis of the effect of bisphosphonates for GIO4 showed no significant difference in the efficacy of etidronate and nitrogen-containing bisphosphonates with respect to the lumbar BMD. Thus, unlike the case for osteoporosis in postmenopausal women, the efficacy of etidronate for GIO with respect to the BMD has been confirmed to be similar to that of nitrogen-containing bisphosphonates. "
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    ABSTRACT: Etidronate is an oral bisphosphonate compound that is known to reduce bone resorption through the inhibition of osteoclastic activity. The efficacy of etidronate for involutional (postmenopausal and senile) and glucocorticoid-induced osteoporosis, as well as that for other skeletal diseases, was reviewed in Japanese patients. Cyclical etidronate treatment (200 mg or 400mg/day for 2 weeks about every 3 months) increases the lumbar bone mineral density (BMD) in patients with involutional osteoporosis and prevents incident vertebral fractures in patients with glucocorticoid-induced osteoporosis. The losses of the lumbar BMD in patients with liver cirrhosis and the metacarpal BMD in hemiplegic patients after stroke are prevented, and the lumbar BMD is possibly increased, preventing fragile fractures in adult patients with osteogenesis imperfecta type I. Furthermore, proximal bone resorption around the femoral stem is reduced and some complications may be prevented in patients who undergo cementless total hip arthroplasty. Oral etidronate treatment may also help to transiently relieve metastatic cancer bone pain followed by a decrease in abnormally raised bone resorption in patients with painful bone metastases from primary cancer sites, such as the lung, breast and prostate. Thus, oral etidronate treatment is suggested to be efficacious for osteoporosis, as well as other skeletal diseases associated with increased bone resorption, in Japanese patients. Randomized controlled trials needed to be conducted on a large number of patients to confirm these effects.
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