Introduction: Postmenopausal osteoporosis is a chronic disease requiring treatment that balances long-term fracture efficacy against risk.
Methods: We reviewed the efficacy and safety of calcium and vitamin D, the selective estrogen receptor modulators (SERMs), the bisphosphonates, denosumab, and strontium ranelate in studies of 3 years or longer.
Results: Six trials lasted for 5 years, and seven went beyond that. The evidence beyond 5 years is generally weak, mainly due to methodological issues (open-label design, small samples, or absence of placebo control). Although calcium and vitamin D appear to be beneficial, the data are insufficient to evaluate benefits and risk beyond 3 years. The fracture efficacy of SERMs beyond 5 years is not known, though increases in bone mineral density (BMD) appear to be maintained. The SERMs have good long-term safety, including protective effects against breast cancer. The bisphosphonates have established fracture efficacy to 3 years, and 4 or 5 years with alendronate and risedronate. The evidence beyond 5 years indicates sustained increases in BMD. The safety of the bisphosphonates does not appear to be modified with time, with the possible exceptions of atypical subtrochanteric fracture and other events of unknown frequency. Denosumab has been tested up to 5 years, with continued increased in BMD and no reported safety issues. There is evidence for fracture efficacy of strontium ranelate, and sustained increases in BMD over 10 years. Strontium ranelate has good long-term safety.
Conclusion: Robust long-term studies are relatively rare for the osteoporosis treatments, and generally show maintenance of BMD and, for some agents, an additional reduction in fracture incidence.