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  • Review Article
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Long-term and sequential treatment for osteoporosis

Nature Reviews Endocrinology volume 19, pages 520–533 (2023)Cite this article

Subjects

Abstract

Osteoporosis is a skeletal disorder that causes impairment of bone structure and strength, leading to a progressively increased risk of fragility fractures. The global prevalence of osteoporosis is increasing in the ageing population. Owing to the chronic character of osteoporosis, years or even decades of preventive measures or therapy are required. The long-term use of bone-specific pharmacological treatment options, including antiresorptive and/or osteoanabolic approaches, has raised concerns around adverse effects or potential rebound phenomena after treatment discontinuation. Imaging options, risk scores and the assessment of bone turnover during initiation and monitoring of such therapies could help to inform individualized treatment strategies. Combination therapies are currently used less often than ‘sequential’ treatments. However, all patients with osteoporosis, including those with secondary and rare causes of osteoporosis, as well as specific patient populations (for example, young adults, men and pregnant women) require new approaches for long-term therapy and disease monitoring. New pathophysiological aspects of bone metabolism might therefore help to inform and revolutionize the diagnosis and treatment of osteoporosis.

Key points

  • Osteoporosis and related fragility fractures are becoming increasingly common among women and men, with fewer clinical treatment studies available that include men.

  • The burden of fragility fractures is characterized not only by individual harm but also by high costs for health-care systems worldwide.

  • Osteoporosis requires long-term prevention or therapy based on specific bone medication and/or general measures; specific therapy principles encompass antiresorptive or osteoanabolic approaches or a dual approach.

  • Risks and benefits of antiresorptive and osteoanabolic therapies have been investigated and include rare but sometimes disabling adverse effects such as atypical femoral fractures and medication-related osteonecrosis of the jaw.

  • Sequential therapy options are increasingly being addressed in clinical trials more often than combination therapies, with the first results showing benefits for the maintenance of stable BMD increases and fracture risk reduction.

  • Future therapy directions include the application of an ‘osteoanabolics first’ approach and dosage variation in antiresorptive agents, as well as new therapy options including follicle-stimulating hormone, mesenchymal stem cells and extracellular vesicles.

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Fig. 1: Schematic overview of osteoporosis therapy transition in postmenopausal women in various fracture risk categories.
Fig. 2: BTMs during physiological equilibrium of bone metabolism, antiresorptive therapy and osteoanabolic therapy.

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  1. Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University Graz, Graz, Austria

    Ines Foessl, Hans P. Dimai & Barbara Obermayer-Pietsch

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  1. Ines Foessl
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B.O.-P. declares lecture fees from Immundiagnostic Systems, Eli Lilly, Gedeon Richter, Institut Allergosan, anwerina, Merck Sharp & Dome, Roche, UCB and unrestricted research grants from CBmed, Immundiagnostic Systems, Infineon, Institut Allergosan, Kinderwunschinstitut, SelenoMed, ViennaLab and Winclove. H.P.D. declares lecture and consultancy fees from Amgen, Braincon, Daiichi-Sankyo, Eli Lilly, Gedeon Richter, Genericon, Medtronic, Merck Sharp & Dohme, Novartis, Nycomed, Sanabo, Servier, Sinapharm, Stada and UCB. I.F. was a part-time employee (Medical Oncology, Amgen Austria) during the writing of the first draft, but not thereafter, all outside of the present work.

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Foessl, I., Dimai, H.P. & Obermayer-Pietsch, B. Long-term and sequential treatment for osteoporosis. Nat Rev Endocrinol 19, 520–533 (2023). https://doi.org/10.1038/s41574-023-00866-9

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