Medical Research: What are the main findings of the study?
1. We found high-strength evidence that several medications decrease fracture risk when used by persons with bone density in the osteoporotic range and/or with pre-existing hip or vertebral fracture. While many of the medications (alendronate, risedronate, zoledronic acid, ibandronate, denosumab, teriparatide, and raloxifene) reduce vertebral fractures, a reduction in the risk of hip fracture is not demonstrated for all of the medications. In particular, hip fracture reduction is only demonstrated for alendronate, risedronate, zoledronic acid, and denosumab. Unfortunately, due to a lack of head-to-head trials, the comparative effectiveness of the medications is unclear.
2. The adverse effects of the medications vary. For example, raloxifene is associated with an increased risk of thromboembolic events, whereas denosumab and the bisphosphonate medications have been associated with increased risk of osteonecrosis of the jaw and atypical subtrochanteric femoral fractures.
Medical Research: Were any of the findings unexpected?
Dr. Crandall: Many physicians and patients are likely to be surprised to know that there is such a tremendous lack of direct head-to-head comparisons of these medications, both for fracture reduction and for adverse effects.
Medical Research: What should clinicians and patients take away from your report?
Dr. Crandall: Clinicians and patients should realize that many agents are efficacious for decreasing fracture risk, but they differ as to their adverse effect profiles, and not all of them are demonstrated to decrease hip fractures. Also, the absolute risk for atypical subtrochanteric femoral fractures during bisphosphonate use is low, ranging from about 2 per 100,000 for women receiving bisphosphonates for less than 2 years to 100 per 100,000 for women receiving bisphosphonates for 8 years or more.
Medical Research: What recommendations do you have for future research as a result of this study?
Dr. Crandall: We need more head-to-head (direct) comparisons of these medications to clarify how their anti-fracture and adverse effects differ. Also, there is only sparse information regarding anti-fracture efficacy of the medications in men, so we desperately need randomized controlled trials to be performed in men with osteoporosis. Finally, we don’t know the optimal treatment duration for these medications.
Crandall CJ, Newberry SJ, Diamant A, Lim Y, Gellad WF, Booth MJ, et al. Comparative Effectiveness of Pharmacologic Treatments to Prevent Fractures: An Updated Systematic Review. Ann Intern Med. [Epub ahead of print 9 September 2014] doi:10.7326/M14-0317