Catherine MacLean, MD, PhD; Sydne Newberry, PhD; Margaret Maglione, MPP; Maureen McMahon, MD; Veena Ranganath, MD; Marika Suttorp, MS; Walter Mojica, MD; Martha Timmer, MS; Alicia Alexander, MD; Melissa McNamara, MD; Sheetal B. Desai, MD, MS; Annie Zhou, MS; Susan Chen, BA; Jason Carter, BA; Carlo Tringale, BA; Di Valentine, JD; Breanne Johnsen, BA; Jennifer Grossman, MD
Although several agents are available to treat osteoporosis, the relative efficacy and toxicity of these agents when used to prevent fractures has not been well described.
To compare the benefits in fracture reduction and the harms from adverse events of various therapies for osteoporosis.
MEDLINE (1966 to November 2007) and other selected databases were searched for English-language studies.
For the efficacy analysis, investigators selected studies that reported the rate of or risk for fractures. For the adverse event analysis, they selected studies that reported the relationship between an agent and cardiovascular, thromboembolic, or upper gastrointestinal events; malignant conditions; and osteonecrosis.
Using a standardized protocol, investigators abstracted data on fractures and adverse events, agents and comparators, study design, and variables of methodological quality.
Good evidence suggests that alendronate, etidronate, ibandronate, risedronate, zoledronic acid, estrogen, parathyroid hormone (1-34), and raloxifene prevent vertebral fractures more than placebo; the evidence for calcitonin was fair. Good evidence suggests that alendronate, risedronate, and estrogen prevent hip fractures more than placebo; the evidence for zoledronic acid was fair. The effects of vitamin D varied with dose, analogue, and study population for both vertebral and hip fractures. Raloxifene, estrogen, and estrogenâ€“progestin increased the risk for thromboembolic events, and etidronate increased the risk for esophageal ulcerations and gastrointestinal perforations, ulcerations, and bleeding.
Few studies have directly compared different agents or classes of agents used to treat osteoporosis.
Although good evidence suggests that many agents are effective in preventing osteoporotic fractures, the data are insufficient to determine the relative efficacy or safety of these agents.
Sorting through the proven benefits and harms of the agents available for treating osteoporosis is difficult.
This systematic review of 76 randomized trials and 24 meta-analyses found good evidence that multiple agents, including alendronate, zoledronic acid, and estrogen, prevented vertebral and hip fractures more than placebo. Harms included increased risk for thromboembolic events with raloxifene, estrogen, and estrogen–progestin and increased gastrointestinal symptoms with bisphosphonates. No large trials directly compared 2 or more agents and established superiority of any agent.
Available data insufficiently characterize the benefits and harms of various therapies for osteoporosis relative to one another.
PTH = parathyroid hormone; SERM = selective estrogen receptor modulator. *Articles are not mutually exclusive.
PTH = parathyroid hormone; SERM = selective estrogen receptor modulator. *Pooled risk estimate from cited meta-analysis or systematic review. †Pooled risk estimate calculated by authors; restricted to studies with >12 months of follow-up. ‡Risk estimate calculated from cited individual studies. §Insufficient data to calculate risk.
NR = not reported; PTH = parathyroid hormone; SERM = selective estrogen receptor modulator. *Pooled risk estimate from cited meta-analysis or systematic review. †Pooled risk estimate calculated by authors; restricted to studies with >12 months of follow-up. ‡Risk estimate calculated from cited individual studies. §Insufficient data to calculate risk.
NR = not reported; PTH = parathyroid hormone; SERM = selective estrogen receptor modulator. *Pooled risk estimate from cited meta-analysis or systematic review. †Insufficient data to calculate risk. ‡Risk estimate calculated from cited individual studies.
NR = not reported; PTH = parathyroid hormone; SERM = selective estrogen receptor modulator; WHI = Women's Health Initiative. *Pooled risk estimate from cited meta-analysis or systematic review. †Insufficient data to calculate risk. ‡Risk estimate calculated from cited individual studies.
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MacLean C, Newberry S, Maglione M, McMahon M, Ranganath V, Suttorp M, et al. Systematic Review: Comparative Effectiveness of Treatments to Prevent Fractures in Men and Women with Low Bone Density or Osteoporosis. Ann Intern Med. 2008;148:197-213. doi: 10.7326/0003-4819-148-3-200802050-00198
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Published: Ann Intern Med. 2008;148(3):197-213.
Emergency Medicine, Endocrine and Metabolism, High Value Care, Metabolic Bone Disorders.
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Print ISSN: 0003-4819 | Online ISSN: 1539-3704
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