Influence of antiosteoporotic therapy on bone fracture consolidation processes: a systematic analysis of modern data

Background. Osteoporosis is a serious medical and social problem characterized by progressive bone loss and an increased risk of fractures. For a long time, there have been concerns in clinical practice about the negative impact of antiosteoporotic drugs on fracture healing processes, which has led to an unjustified delay in specific therapy in patients with recent injuries. Consolidation of fractures in osteoporosis occurs under conditions of an imbalance between bone resorption and bone formation, which creates the prerequisites for the formation of inadequate bone callus. The aim of the study is a systematic analysis of modern data on the effect of various groups of antiosteoporotic drugs on the processes of bone fracture consolidation in order to form an evidence base for optimizing therapeutic approaches.

Research methods. A systematic search of scientific literature was conducted in the PubMed, Scopus, Web of Science, EMBASE and Cochrane Library databases for the period 2017–2025. Search queries included combinations of terms related to osteoporosis, fractures, and antiosteoporotic therapy. The analysis included randomized controlled trials, prospective and retrospective cohort studies, meta-analyses, and systematic reviews assessing the efficacy of bisphosphonates, denosumab, teriparatide, and calcium and vitamin D supplements in fracture healing.

Study results. The analysis showed that antiosteoporotic drugs do not have a negative effect on fracture healing when the treatment regimen is selected correctly. Bisphosphonates, especially zoledronic acid, demonstrate a positive effect on bone microarchitecture and reduce the risk of recurrent fractures by 35 % while reducing mortality by 28 % after proximal femur fractures. Denosumab shows comparable efficacy and has advantages in patients with severe cortical bone loss. Teriparatide exhibits differential efficacy depending on the fracture location, accelerating the consolidation of intertrochanteric fractures, but not demonstrating significant advantages in medial femoral neck fractures. Calcium and vitamin D preparations are a necessary component of therapy, but require supplementation with specific antiosteoporotic agents. The effectiveness of therapy varies significantly depending on the type of fracture, patient age and concomitant diseases, which necessitates a personalized approach to treatment.

1. Salari N., Darvishi N., Bartina Y., Larti M., Kiaei A., Hemmati M., Shohaimi S., Mohammadi M. Global prevalence of osteoporosis among the world older adults: a comprehensive systematic review and metaanalysis. Journal of Orthopaedic Surgery and Research. 2021;16:669. https://doi.org/10.1186/s13018-021-02821-8.

2. Liang B., Burley G., Lin S. et al. Osteoporosis pathogenesis and treatment: existing and emerging avenues. Cellular and Molecular Biology Letters. 2022;27:72. https://doi.org/10.1186/s11658-022-00371-3.

3. Tkacheva O.N., Brailova N.V., Dudinskaya E.N., Kuznetsova V.A. Drug treatment of osteoporosis after fracture. Osteoporosis and Osteopathy. 2020;23(4):30-36. https://doi.org/10.14341/osteo12694.

4. Hao Y., Yang N., Sun M., Yang S., Chen X. The role of calcium channels in osteoporosis and their therapeutic potential. Frontiers in Endocrinology. 2024;15:1450328. https://doi.org/10.3389/fendo.2024.145032

5. Li J., Sun Y., Chen Z., Xie X., Gu F., Bi S., Yu T. Effects of Bisphosphonates Treatments in Osteopenic Older Women: A Systematic Review and Meta-Analysis. Frontiers in Endocrinology. 2023;14:1-10. https://doi.org/10.3389/fphar.2022.892091

6. Mironov S.P., Rodionova S.S., Torgashin A.N. Draft recommendations. Pharmacotherapy for the prevention of recurrent fractures in patients with osteoporosis after surgical treatment of pathological fracture of the proximal femur. Bulletin of Traumatology and Orthopedics named after N.N. Priorov. 2017;1:47-57.

7. Sadykov R.I., Akhtyamov I.F., Fayzrakhmanova G.M. Evaluation of the effectiveness of the combined use of ossein-hydroxyapatite complex and bisphosphonates on fracture healing time and bone mineral density. Practical Medicine. 2022;20(6):119-123 .

8. Wang B., Zhan Y., Yan L., Hao D. How zoledronic acid improves osteoporosis by acting on osteoclasts. Journal of Orthopaedic Translation. 2022;32:48-56. https://doi.org/10.3389/fphar.2022.961941

9. Lesnyak O.M., Kochish A.Yu., Belenkiy I.G. et al. Interdisciplinary consensus on care for elderly patients with proximal femoral fractures based on an orthogeriatric approach. Osteoporosis and Osteopathy. 2021;24(2):5-15. DOI: 10.14341/osteo12745 .

10. Kanis J.A. et al. Консенсус пяти европейских стран по применению золедроната (Великобритания, Франция, Германия, Италия и Испания, 2017). Osteoporosis International. 2017;28(5):1745-1757. DOI: 10.1007/s00198-017-3952-0

11. Toroptsova N.V., Baranova I.A. Modern concepts of bisphosphonates mechanism of action. Effects of long-term bisphosphonate treatment on bone tissue (preclinical studies). Scientific and Practical Rheumatology. 2023;26(3):36-42. https://doi.org/10.14341/osteo13147 .

12. Martínez-Reina J., Calvo-Gallego J.L., Martin M., Pivonka P. Assessment of Strategies for Safe Drug Discontinuation and Transition of Denosumab Treatment in PMO—Insights From a Mechanistic PK/PD Model of Bone Turnover. Frontiers in Bioengineering and Biotechnology. 2021;9:721215. https://doi.org/10.3389/fbioe.2022.886579

13. Rodionova S.S., Kolondaev A.F., Torgashin A.N., Solomyannik I.A. Zoledronic acid in osteoporosis and low-energy fractures complicating its course. Medical Council. 2022;16(21):163-173. https://doi.org/10.21518/2079-701X-2022-16-21-163-173 .

14. Velts N.Yu., Velts O.V., Alyaut din R.N. Denosumab and rebound syndrome: current aspects of osteoporosis therapy (review). Safety and Risk of Pharmacotherapy. 2024;12(2):190-200. https://doi.org/10.30895/2312-7821-2024-12-2-190-200 .

15. Jiang L., Cui X., Ma H., Tang X. Comparison of denosumab and zoledronic acid for the treatment of solid tumors and multiple myeloma with bone metastasis: a systematic review and meta-analysis based on randomized controlled trials. Journal of Orthopaedic Surgery and Research. 2021;16:400. doi: 10.1186/s13018-021-02554-8.

16. Bessueille L., Briolay A., Guillot N., Mebarek S., Viallon S., Laroche N., Lafage-Proust M.-H., Magne D. Teriparatide administration is osteoanabolic but does not impact atherosclerotic plaque calcification and progression in a mouse model of menopause. Bone. 2025;190:117316. doi: 10.1016/j.bone.2024.117316

17. Sheng O.C., Wu W.-T., Peng C.-H., Yao T.-K., Chen I.-H., Wang J.-H., Yeh K.-T. Therapeutic advantage of teriparatide in very elderly patients with proximal femoral fractures: a functional and BMD analysis. BMC Musculoskeletal Disorders. 2024;25:288

18. Gao J., Liu X., Wu X., Li X., Liu J., Li M. A brief review and clinical evidences of teriparatide therapy for atypical femoral fractures associated with long-term bisphosphonate treatment. Frontiers in Endocrinology. 2022;13:821734. doi: 10.3389/fsurg.2022.1063170.

19. Eremkina A.K., Gorbacheva A.M., Enenko V.A., Litvinova E.E., Mokrysheva N.G. Experience of using teriparatide for the treatment of postoperative hypoparathyroidism in patients receiving renal replacement therapy with programmed hemodialysis. Problems of Endocrinology. 2022;68(4):76-82. https://doi.org/10.14341/probl13075 .

20. Samoday V.G., Borisov A.K., Kolyabin D.S. The use of short-acting bisphosphonates in the treatment of long bone fractures as a factor of bone healing success. Technological innovations in traumatology, orthopedics and neurosurgery: integration of science and practice: collection of materials of the All-Russian scientific and practical conference with international participation, Saratov, April 25-26, 2019. Saratov, 2019:259-260 .

21. Belenkiy I.G. Modern approaches to surgical treatment of patients with osteoporotic fracture of the proximal femur. Osteoporosis and Osteopathy. 2022;3:36-45. https://doi.org/10.14341/osteo12986 .

22. Maltsev S.V. Current data on vitamin D — metabolism, role in the body, features of use in medical practice. Practical Medicine. 2020;18(4):12-19. DOI: 10.32364/2618-8430-2022-5-3-244-252 .

23. Povoroznyuk V.V., Dedukh N.V., Bystritskaya M.A. Vitamin d in bone regeneration: from experimental research to clinical practice. Surgery News. 2020;4:428-438. doi: 10.18484/2305-0047.2020.4.428 .

24. Chen X., Hu Y., Geng Z., Su J. The "Three in One" Bone Repair Strategy for Osteoporotic Fractures. Frontiers in Bioengineering and Biotechnology. 2021;9:654917. doi: 10.3389/fendo.2022.910602.

25. Golounina O.O., Belaya Zh.E. Bone remodeling markers and their significance in oncological diseases. Medical Council. 2021;7:150-159. https://doi.org/10.21518/2079-701X-2021-7-120-132 .

26. Liu Y., Liu X., Wu Y., Luo T. Efficacy and safety of sequential therapy for primary osteoporosis with bone formation promoters followed by bone resorption inhibitors: a meta-analysis. Journal of Orthopaedic Surgery and Research. 2025;20:147 . doi: 10.1186/s13018-025-05545-1.

27. Yakushevskaya O.V. Protective effect of zoledronic acid in transition from long-term osteoporosis therapy with denosumab. Osteoporosis and Osteopathy. 2022;25(2):24-32 . doi: 10.21518/2079-701X-2020-21-185-191 .

28. Bandeira L., Lewiecki E.M. Anabolic therapy for osteoporosis: update on efficacy and safety. Archives of Endocrinology and Metabolism. 2021;65(5):594-607. doi: 10.20945/2359-3997000000566

29. Klyuchnikova Ya.N., Tingaeva I.I. Effect of bisphosphonates on bone tissue condition. International Student Scientific Bulletin. 2023;5:34-39. https://doi.org/10.17513/msnv.21334 .

30. Khovasova N.O., Dudinskaya E.N., Naumov A.V., Tkacheva O.N., Machekhina L.V., Onuchina Yu.S. Effect of bone anabolic therapy on bone remodeling parameters and bone density in geriatric patients with osteoporosis and falling syndrome. Problems of Endocrinology. 2022;68(3):67-75. doi: 10.14341/probl13079 .

31. Gorter E.A., Reinders C.R., Krijnen P. et al. The effect of osteoporosis and its treatment on fracture healing a systematic review of animal and clinical studies. Bone Reports. 2021;15:101117. doi: 10.1016/j.bonr.2021.101117

32. Khovasova N.O., Dudinskaya E.N., Naumov A.V., Tkacheva O.N., Machekhina L.V., Onuchina J.S. Effect of bone anabolic therapy on bone remodeling and bone density in geriatric patients with osteoporosis and falling syndrome. Problems of Endocrinology. 2022;68(3):67-75. Received: 21.03.2022. Accepted: 04.04.2022. doi: https://doi.org/10.14341/probl13079

33. Rodionova S.S., Kolondaev A.F., Torgashin A.N., Solomyannik I.A. Zoledronic acid in osteoporosis and low-energy fractures complicating its course. Medical Council. 2022;16(21):163-173. https://doi.org/10.21518/2079-701X-2022-16-21-163-173 .

34. Korolik O.D., Polyakova Yu.V., Sivordova L.E., Akhverdyan Yu.R., Papichev E.V., Zavodovsky B.V. The role of the fracture prevention center in improving therapy adherence in patients with severe osteoporosis. Modern Problems of Science and Education. 2020;6:194-201. https://doi.org/10.17513/spno.30316 .