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Short-term and long-term effects of osteoporosis therapies

Key Points

  • Bisphosphonates—the most widely used treatment for osteoporosis—are safe and effective, but are usually only given for 5 years followed by a drug holiday to reduce the risk of atypical femoral fractures

  • Denosumab is a potent antiresorptive, with an antifracture efficacy comparable to that of potent bisphosphonates; BMD changes with long-term use of denosumab seem to be more positive than those with bisphosphonates

  • Teriparatide—the most widely used anabolic agent—is well-tolerated and early concerns related to osteosarcoma have not been substantiated; effects of teriparatide on BMD are additive to those of antiresorptives

  • Strontium has marginal antifracture efficacy and its use is declining owing to concern about its cardiovascular safety profile

  • Cathepsin K inhibitors and sclerostin antibodies are anti-osteoporotic agents in development, which show great promise

Abstract

Progress continues to be made in the development of therapeutics for fracture prevention. Bisphosphonates are now available orally and intravenously, often as inexpensive generics, and remain the most widely used interventions for osteoporosis. The major safety concern associated with the use of bisphosphonates is the development of femoral shaft stress fractures and, although rare, this adverse event affords the principal rationale for restricting bisphosphonate therapy to those individuals with femoral T-scores <−2.5, and for providing drug holidays in those individuals requiring therapy for >5 years. Newer antiresorptive therapies, in the form of denosumab and cathepsin K inhibitors, might increase efficacy and possibly circumvent some of the safety concerns associated with bisphosphonate use (for example, gastrointestinal and renal complications). The combination of teriparatide with antiresorptives markedly increases effects on BMD; new anabolic agents are also very promising in this regard. However, whether or not these changes in BMD translate into improved efficacy of fracture prevention remains to be determined. Vitamin D is important for the prevention of osteomalacia, but does not influence BMD or fracture risk in patients not deficient in vitamin D. The balance of risks and benefits of calcium supplementation is contentious, but patients should be encouraged to adhere to a balanced diet aimed at maintaining a healthy body weight. Consideration of a patient's risk of falling, and its mitigation, are also important. In this Review, I summarize the short-term and long-term effects of osteoporosis therapies.

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Figure 1: Efficacy of treatments for the prevention of hip fractures.
Figure 2: Efficacy of treatments for the prevention of nonvertebral fractures.
Figure 3: Long-term effects of osteoporosis treatments on total hip BMD.

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Acknowledgements

I.R.R. acknowledges support from the Health Research Council of New Zealand.

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Correspondence to Ian R. Reid.

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I.R.R. has received research grants or speaking and/or consulting fees from Amgen, Lilly, Merck, Novartis and Sanofi.

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Reid, I. Short-term and long-term effects of osteoporosis therapies. Nat Rev Endocrinol 11, 418–428 (2015). https://doi.org/10.1038/nrendo.2015.71

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