Influence of zoledronic acid therapy on long-term results of medical rehabilitation of patients with osteoporotic vertebral fracrures

Introduction. Rehabilitation programs for patients with vertebral fractures (VF) with underlying osteoporosis (OP) include various methods. Pharmacological therapy should be prescribed to all patients who have undergone pathological VF with underlying OP to reduce the risk for future fractures.  

Objective. To study the effect of intravenous infusions of zoledronic acid at a dose of 5 mg once a year compared with oral bisphosphonates on long-term outcomes of rehabilitation in patients with vertebral fractures (VF) against the background of osteoporosis (OP) during a 2-year prospective follow-up.  

Materials and methods. 120 patients aged 40–80 years with systemic OP and PP were included, who were randomized into 2 groups. In group 1 (n = 60) a rehabilitation complex was prescribed with the inclusion of mechanotherapy and zoledronic acid 5 mg/100 ml – once a year, in group 2 (n = 60) – therapeutic exercises in the hall and pool and alendronic acid 70 mg orally 1 time per week. Dynamic follow-up of patients was 24 months.  

Results. Zoledronic acid was associated with higher adherence than alendronic acid, 83.0% versus 48.8% at 12 months (p = 0.0006) and 85.7% versus 56.3% at 24 months (p = 0.046). This contributed to the increase in BMD in the spine by 1.82% after 12 months (p = 0.045) and by 3.24% after 24 months (p = 0.038), in the femoral neck – by 2.45% (p = 0.029) after 24 months. In group 1, the intensity of the pain syndrome after 12 months (p = 0.003) was lower than in group 2, and the best indicators of quality of life (p < 0.05) were noted on the scales Pain, Mobility and State of mind, General health and in terms of total.  

Conclusion. Due to good adherence to treatment when prescribed once a year and a positive effect on long-term outcomes of medical rehabilitation, zoledronic acid can be recommended as a basic therapy for OP in patients with VF undergoing rehabilitation. 

1. Белая Ж.Е., Рожинская Л.Я., Гребенникова Т.А., Kanis J.А., Пигарова Е.А., Родионова С.С. и др. Краткое изложение проекта федеральных клинических рекомендаций по остеопорозу. Остеопороз и остеопатии. 2020;23(2):4–21. https://doi.org/10.14341/osteo12710.

2. Belaya Z.E., Rozhinskaya L.Y., Grebennikova T.A., Kanis J.A., Pigarova E.A., Rodionova S.S. et al. Summary of the draft federal clinical guidelines for osteoporosis. Osteoporosis and Bone Diseases. 2020;23(2):4–21. (In Russ.) https://doi.org/10.14341/osteo12710.

3. Kanis J.A., Cooper C., Rizzoli R., Reginster J.Y. Scientific Advisory Board of the European Society for Clinical and Economic Aspects of Osteoporosis (ESCEO) and the Committees of Scientific Advisors and National Societies of the International Osteoporosis Foundation (IOF). European guidance for the diagnosis and management of osteoporosis in postmenopausal women. Osteoporos Int. 2019;30(1):3–44. https://doi.org/10.1007/s00198-018-4704-5.

4. Hernlund E., Svedbom A., Ivergård M., Compston J., Cooper C., Stenmark J. et al. Osteoporosis in the European Union: medical management, epidemiology and economic burden. A report prepared in collaboration with the International Osteoporosis Foundation (IOF) and the European Federation of Pharmaceutical Industry Associations (EFPIA). Arch Osteoporos. 2013;8(1):136. https://doi.org/10.1007/s11657-013-0136-1.

5. Михайлов Е.Е., Беневоленская Л.И., Мылов Н.М. Распространенность переломов позвоночника в популяционной выборке лиц 50 лет и старше. Вестник травматологии и ортопедии. 1997;(3):20–27. https://doi.org/10.17816/vto108314.

6. Mikhailov E.E., Benevolenskaya L.I., Mylov N.M. Spine fractures in population selection of persons of 50 years and older. N.N. Priorov Journal of Traumatology and Orthopedics. 1997;(3):20–27. (In Russ.) https://doi.org/10.17816/vto108314.

7. Longo U.G., Loppini M., Denaro L., Maffulli N., Denaro V. Osteoporotic vertebral fractures: current concepts of conservative care. Br Med Bull. 2012;102:171–189. https://doi.org/10.1093/bmb/ldr048.

8. Prather H., Hunt D., Watson J.O., Gilula L.A. Conservative care for patients with osteoporotic vertebral compression fractures. Phys Med Rehabil Clin N Am. 2007;18(3):577–591. https://doi.org/10.1016/j.pmr.2007.05.008.

9. Bautmans I., Van Arken J., Van Mackelenberg M., Mets T. Rehabilitation using manual mobilization for thoracic kyphosis in elderly postmenopausal patients with osteoporosis. J Rehabil Med. 2010;42(2):129–135. https://doi.org/10.2340/16501977-0486.

10. Giangregorio L.M., Macintyre N.J., Thabane L., Skidmore C.J., Papaioannou A. Exercise for improving outcomes after osteoporotic vertebral fracture. Cochrane Database Syst Rev. 2013;1:CD008618. https://doi.org/10.1002/14651858.CD008618.pub2.

11. Conley R.B., Adib G., Adler R.A., Åkesson K.E., Alexander I.M., Amenta K.C. et al. Secondary Fracture Prevention: Consensus Clinical Recommendations from a Multistakeholder Coalition. J Bone Miner Res. 2020;35(1):36–52. https://doi.org/10.1002/jbmr.3877.

12. Shibasaki K., Asahi T., Kuribayashi M., Tajima Y., Marubayashi M., Iwama R. et al. Potential prescribing omissions of anti-osteoporosis drugs is associated with rehabilitation outcomes after fragility fracture: Retrospective cohort study. Geriatr Gerontol Int. 2021;21(5):386–391. https://doi.org/10.1111/ggi.14145.

13. Марченкова Л.А., Макарова Е.В., Васильева В.А., Еремушкин М.А. Роль длительного приема добавок кальция и витаминов D3 и B6 в поддержании эффекта медицинской реабилитации у пациентов с остеопорозом и высоким риском переломов. Остеопороз и остеопатии. 2020;23(1):110–111. Режим доступа: https://www.osteo-endojournals.ru/jour/article/view/12779.

14. Marchenkova L.A., Makarova E.V., Vasilyeva V.A., Eremushkin M.A. The role of long-term intake of calcium supplements, vitamins D3 and B6 in maintaining the effect of medical rehabilitation in patients with osteoporosis and high risk of fractures. Osteoporosis and Bone Diseases. 2020;23(1):110–111. (In Russ.) Available at: https://www.osteo-endojournals.ru/jour/article/view/12779.

15. Марченкова Л.А., Макарова Е.В., Васильева В.А. Влияние HDBA органик комплекса с витамином D и кальцием на качество жизни у лиц с высоким риском переломов, проходящих медицинскую реабилитацию. Вестник восстановительной медицины. 2020;97(3):153–159. https://doi.org/10.38025/2078-1962-2020-97-3-153-159.

16. Marchenkova L.A., Makarova E.V., Vasileva V.A. The influence of HDBA organic complex with vitamin D and calcium on quality of life in individuals at high risk of fractures undergoing medical rehabilitation. Vestnik Vosstanovitelʹnoj Mediciny. 2020;97(3):153–159. (In Russ.) https://doi.org/10.38025/2078-1962-2020-97-3-153-159.

17. Макарова Е.В., Марченкова Л.А., Еремушкин М.А., Стяжкина Е.М., Разваляева Д.В. Эффективность нового комплексного метода реабилитации с использованием механо- и кинезиотерапии в коррекции нарушении баланса у пациентов с компрессионными переломами позвонков на фоне остеопороза. Вестник восстановительной медицины. 2020;97(3):160–166. https://doi.org/10.38025/2078-1962-2020-97-3-160-166.

18. Makarova E.V., Marchenkova L.A., Eremushkin M.A., Styazhkina E.M., Razvalyaeva D.V. Efficiency of a new complex rehabilitation method using mechano- and kinesiotherapy for balance disorders correction in patients with osteoporotic compression vertebral fractures. Vestnik Vosstanovitelʹnoj Mediciny. 2020;97(3):160–166. (In Russ.) https://doi.org/10.38025/2078-1962-2020-97-3-160-166.

19. Lips P., Cooper C., Agnusdei D., Caulin F., Egger P., Johnell O. et al. Quality of life in patients with vertebral fractures: validation of the Quality of Life Questionnaire of the European Foundation for Osteoporosis (QUALEFFO). Working Party for Quality of Life of the European Foundation for Osteoporosis. Osteoporos Int. 1999;10(2):150–160. https://doi.org/10.1007/s001980050210.

20. Буйлова Т.В. Современные подходы к реабилитации пациентов с остеопорозом. международная классификация функционирования и реабилитационный диагноз. Остеопороз и остеопатии. 2020;23(1):58–59. Режим доступа: https://www.osteo-endojournals.Ru/jour/article/view/12745.

21. Builova T.V. Modern approaches to rehabilitation of patients with osteoporosis. international classification of functioning and rehabilitation diagnosis. Osteoporosis and Bone Diseases. 2020;23(1):58–59. (In Russ.) Available at: https://www.osteo-endojournals.ru/jour/article/view/12745.

22. Егудина Е.Д., Калашникова О.С. Физическая реабилитация пациентов с остеопорозом. Вопросы курортологии, физиотерапии и лечебной физической культуры. 2020;97(2):78–85. https://doi.org/10.17116/kurort20209702178.

23. Egudina E.D., Kalashnikova O.S. Physical rehabilitation of patients with osteoporosis. Voprosy Kurortologii, Fizioterapii, i Lechebnoi Fizicheskoi Kultury. 2020;97(2):78–85. (In Russ.) https://doi.org/10.17116/kurort20209702178.

24. Erhan B., Ataker Y. Rehabilitation of Patients With Osteoporotic Fractures. J Clin Densitom. 2020;23(4):534–538. https://doi.org/10.1016/j.jocd.2020.06.006.

25. Oral A., Küçükdeveci A.A., Varela E., Ilieva E.M., Valero R., Berteanu M., Christodoulou N. Osteoporosis. The role of physical and rehabilitation medicine physicians. The European perspective based on the best evidence. A paper by the UEMS-PRM Section Professional Practice Committee. Eur J Phys Rehabil Med. 2013;49(4):565–577. Available at: https://pubmed.ncbi.nlm.nih.gov/24084415/.

26. Anderson P.A., Dimar J.R., Lane J.M., Lehman RA Jr. Rationale for Bone Health Optimization in Patients Undergoing Orthopaedic Surgery. Instr Course Lect. 2021;70:355–366. Available at: https://pubmed.ncbi.nlm.nih.gov/33438921/.

27. Di Monaco M., Castiglioni C., Bardesono F., Milano E., Massazza G. Sarcopenia, osteoporosis and the burden of prevalent vertebral fractures: a cross-sectional study of 350 women with hip fracture. Eur J Phys Rehabil Med. 2020;56(2):184–190. https://doi.org/10.23736/S1973-9087.20.05991-2.

28. St Jeor J.D., Jackson T.J., Xiong A.E., Kadri A., Freedman B.A., Sebastian A.S. et al. Osteoporosis in spine surgery patients: what is the best way to diagnose osteoporosis in this population? Neurosurg Focus. 2020;49(2):E4. https://doi.org/10.3171/2020.5.FOCUS20277.

29. Марченкова Л.А., Макарова Е.В., Герасименко М.Ю. Распространенность остеопороза, ассоциирующихся с ним переломов и уровня информированности по проблеме среди пациентов, проходящих медицинскую реабили. Лечащий врач. 2020;(2):54–57. https://doi.org/10.26295/OS.2020.16.46.010.

30. Marchenkova L.A., Makarova E.V., Gerasimenko M.Yu. Prevalence of osteoporosis, associated fractures, and level of knowledge about this problem among the patients undergoing medical rehabilitation. Lechaschi Vrach. 2020;(2):54–57. (In Russ.) https://doi.org/10.26295/OS.2020.16.46.010.

31. Black D.M., Delmas P.D., Eastell R., Reid I.R., Boonen S., Cauley J.A. et al. Onceyearly zoledronic acid for treatment of postmenopausal osteoporosis. N Engl J Med. 2007;356(18):1809–1822. https://doi.org/10.1056/NEJMoa067312.

32. Black D.M., Reid I.R., Boonen S., Bucci-Rechtweg C., Cauley J.A., Cosman F. et al. The effect of 3 versus 6 years of zoledronic acid treatment of osteoporosis: a randomized extension to the HORIZON-Pivotal Fracture Trial (PFT). J Bone Miner Res. 2012;27(2):243–254. https://doi.org/10.1002/jbmr.1494.

33. Black D.M., Reid I.R., Cauley J.A., Cosman F., Leung P.C., Lakatos P. et al. The effect of 6 versus 9 years of zoledronic acid treatment in osteoporosis: a randomized second extension to the HORIZON-Pivotal Fracture Trial (PFT). J Bone Miner Res. 2015;30(5):934–944. https://doi.org/10.1002/jbmr.2442.

34. Lyles K.W., Colón-Emeric C.S., Magaziner J.S., Adachi J.D., Pieper C.F., Mautalen C. et al. Zoledronic acid and clinical fractures and mortality after hip fracture. N Engl J Med. 2007;357(18):1799–1809. https://doi.org/10.1056/NEJMoa074941.

35. Марченкова Л.А., Древаль А.В., Прохорова Е.А., Лосева В.А. Приверженность больных постменопаузальным остеопорозом комбинированной терапии алендронатом натрия и колекальциферолом и ее влияние на эффективность лечения. Проблемы эндокринологии. 2014;60(4):22–29. https://doi.org/10.14341/probl201460422-29.

36. Marchenkova L.A., Dreval A.V., Prokhorova E.A., Loseva V.A. The adherence of postmenopausal osteoporosis patients to therapy with combination medication contains alendronic acid and colecalciferol and its impact on the effectiveness of treatment. Problems of Endocrinology. 2014;60(4):22–29. (In Russ.) https://doi.org/10.14341/probl201460422-29.

37. Landfeldt E., Ström O., Robbins S., Borgström F. Adherence to treatment of primary osteoporosis and its association to fractures--the Swedish Adherence Register Analysis (SARA). Osteoporos Int. 2012;23(2):433–443. https://doi.org/10.1007/s00198-011-1549-6.

38. Reid D.M., Devogelaer J.P., Saag K., Roux C., Lau C.S., Reginster J.Y. et al. Zoledronic acid and risedronate in the prevention and treatment of glucocorticoid-induced osteoporosis (HORIZON): a multicentre, double-blind, double-dummy, randomised controlled trial. Lancet. 2009;373(9671):1253–1263. https://doi.org/10.1016/S0140-6736(09)60250-6.

39. Dusdal K., Grundmanis J., Luttin K., Ritchie P., Rompre C., Sidhu R., Harris S.R. Effects of therapeutic exercise for persons with osteoporotic vertebral fractures: a systematic review. Osteoporos Int. 2011;22(3):755–769. https://doi.org/10.1007/s00198-010-1497-6.

40. Garg B., Dixit V., Batra S., Malhotra R., Sharan A. Non-surgical management of acute osteoporotic vertebral compression fracture: A review. J Clin Orthop Trauma. 2017;8(2):131–138. https://doi.org/10.1016/j.jcot.2017.02.001.

41. Giangregorio L., Papaioannou A., Cranney A., Zytaruk N., Adachi J.D. Fragility fractures and the osteoporosis care gap: an international phenomenon. Semin Arthritis Rheum. 2006;35(5):293–305. https://doi.org/10.1016/j.semarthrit.2005.11.001.

42. Hadji P., Ziller V., Gamerdinger D., Spieler W., Articus K., Baier M., Moericke R., Kann P.H. Quality of life and health status with zoledronic acid and generic alendronate: a secondary analysis of the Rapid Onset and Sustained Efficacy (ROSE) study in postmenopausal women with low bone mass. Osteoporos Int. 2012;23(7):2043–2051. https://doi.org/10.1007/s00198-011-1834-4.

43. Lambrinoudaki I., Vlachou S., Galapi F., Papadimitriou D., Papadias K. Onceyearly zoledronic acid in the prevention of osteoporotic bone fractures in postmenopausal women. Clin Interv Aging. 2008;3(3):445–451. https://doi.org/10.2147/cia.s2046.

44. Hamdy R.C. Zoledronic acid: clinical utility and patient considerations in osteoporosis and low bone mass. Drug Des Devel Ther. 2010;(4):321–335. https://doi.org/10.2147/DDDT.S6287.