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Non-biological Antiresorptive: Bisphosphonates

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Indian Journal of Orthopaedics Aims and scope Submit manuscript

Abstract

Background

Bisphosphonates, synthetic analogs of endogenous pyrophosphates, are pivotal in managing various bone disorders, primarily osteoporosis, which affects millions globally. While osteoporosis, especially postmenopausal osteoporosis, significantly benefits from bisphosphonate therapy, considerations arise regarding their administration and potential side effects.

Clinical application of Bisphosphonates

Bisphosphonates, divided into nitrogen-containing and non-nitrogenous groups, exert their influence through distinct mechanisms, with the former being notably more potent. The role of bisphosphonates in other diseases, such as Paget’s bone and skeletal metastasis disease is also discussed. Detailed information on the administration routes, dosage regimens, and considerations for drug holidays is provided. The article navigates through the chemical structure, generations, and mechanism of action of bisphosphonates. The article covers administration routes, dosage regimens, and drug holidays, in addition to discussing potential adverse effects and contraindications.

Conclusions

Bisphosphonates hold an unrivaled legacy in the management of osteoporosis. The ubiquitous availability and the cost-effectiveness of these time-tested medications make them an invaluable asset in the osteoporosis treatment landscape, especially in developing nations like India.

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References

  1. Drake, M. T., Clarke, B. L., & Khosla, S. (2008). Bisphosphonates: Mechanism of action and role in clinical practice. Mayo Clinic Proceedings, 83(9), 1032–1045.

    Article  CAS  PubMed  Google Scholar 

  2. De Rosa, G., Misso, G., Salzano, G., & Caraglia, M. (2013). Bisphosphonates and cancer: What opportunities from nanotechnology? Journal of Drug Delivery, 2013, 637976. https://doi.org/10.1155/2013/637976(Epub 2013 Mar 4).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Heymann, D. (2010). Bisphosphonates and bone diseases: Past, present and future. Current Pharmaceutical Design, 16(27), 2948–2949.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Grey, A., & Reid, I. R. (2006). Differences between the bisphosphonates for the prevention and treatment of osteoporosis. Therapeutics and Clinical Risk Management, 2(1), 77–86.

    CAS  PubMed  PubMed Central  Google Scholar 

  5. McGreevy, C., & Williams, D. (2011). Safety of drugs used in the treatment of osteoporosis. Therapeutic Advances in Drug Safety, 2(4), 159–172.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Cremers, S., & Papapoulos, S. (2011). Pharmacology of bisphosphonates. Bone, 49(1), 42.

    Article  CAS  PubMed  Google Scholar 

  7. Bhadada, S. K., Chadha, M., Sriram, U., Pal, R., Paul, T. V., Khadgawat, R., et al. (2021). The Indian Society for Bone and Mineral Research (ISBMR) position statement for the diagnosis and treatment of osteoporosis in adults. Archives of Osteoporosis, 16(1), 102.

    Article  PubMed  Google Scholar 

  8. Boivin, G. Y., Chavassieux, P. M., Santora, A. C., Yates, J., & Meunier, P. J. (2000). Alendronate increases bone strength by increasing the mean degree of mineralization of bone tissue in osteoporotic women. Bone, 27(5), 687–694.

    Article  CAS  PubMed  Google Scholar 

  9. McClung, M. R., Geusens, P., Miller, P. D., Zippel, H., Bensen, W. G., Roux, C., et al. (2001). Hip Intervention Program Study Group. Effect of risedronate on the risk of hip fracture in elderly women. Hip Intervention Program Study Group. New England Journal of Medicine, 344(5), 333–340.

    Article  CAS  PubMed  Google Scholar 

  10. Cummings, S. R., Black, D. M., Thompson, D. E., et al. (1998). Effect of alendronate on risk of fracture in women with low bone density but without vertebral fractures: Results from the Fracture Intervention Trial. JAMA, 280(24), 2077–2082.

    Article  CAS  PubMed  Google Scholar 

  11. Harris, S. T., Watts, N. B., Genant, H. K., et al. (1999). Effects of risedronate treatment on vertebral and nonvertebral fractures in women with postmenopausal osteoporosis: A randomized controlled trial. JAMA, 282(14), 1344–1352.

    Article  CAS  PubMed  Google Scholar 

  12. Black, D. M., Cummings, S. R., Karpf, D. B., Cauley, J. A., Thompson, D. E., Nevitt, M. C., et al. (1996). Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures. Fracture Intervention Trial Research Group. Lancet, 348(9041), 1535–1541.

    Article  CAS  PubMed  Google Scholar 

  13. Chesnut, C. H., Skag, A., Christiansen, C., Recker, R., Stakkestad, J. A., Hoiseth, A., et al. (2004). Effects of oral ibandronate administered daily or intermittently on fracture risk in postmenopausal osteoporosis. Journal of Bone and Mineral Research., 19(8), 1241–1249.

    Article  CAS  PubMed  Google Scholar 

  14. Delmas, P. D., Recker, R. R., Chesnut, C. H., Skag, A., Stakkestad, J. A., Emkey, R., et al. (2004). Daily and intermittent oral ibandronate normalize bone turnover and provide significant reduction in vertebral fracture risk: Results from the BONE study. Osteoporosis International, 15(10), 792–798.

    Article  CAS  PubMed  Google Scholar 

  15. Black, D. M., Delmas, P. D., Eastell, R., Reid, I. R., Boonen, S., Cauley, J. A., et al. (2007). HORIZON Pivotal Fracture. Trial once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. New England Journal of Medicine, 356(18), 1809–1822.

    Article  CAS  PubMed  Google Scholar 

  16. Greenspan, S. L., Emkey, R. D., Bone, H. G., Weiss, S. R., Bell, N. H., Downs, R. W., et al. (2002). Significant differential effects of alendronate, estrogen, or combination therapy on the rate of bone loss after discontinuation of treatment of postmenopausal osteoporosis. A randomized, double-blind, placebo-controlled trial. Annals of Internal Medicine, 137(11), 875–883.

    Article  CAS  PubMed  Google Scholar 

  17. Compston, J. E., & Watts, N. B. (2002). Combination therapy for postmenopausal osteoporosis. Clinical Endocrinology - Oxford, 56(5), 565–569.

    Article  CAS  PubMed  Google Scholar 

  18. Black, D. M., Greenspan, S. L., Ensrud, K. E., Palermo, L., McGowan, J. A., Lang, T. F., et al. (2003). PaTH Study Investigators. The effects of parathyroid hormone and alendronate alone or in combination in postmenopausal osteoporosis. New England Journal of Medicine, 349(13), 1207–1215.

    Article  CAS  PubMed  Google Scholar 

  19. Finkelstein, J. S., Hayes, A., Hunzelman, J. L., Wyland, J. J., Lee, H., & Neer, R. M. (2003). The effects of parathyroid hormone, alendronate, or both in men with osteoporosis. New England Journal of Medicine, 349(13), 1216–1226.

    Article  CAS  PubMed  Google Scholar 

  20. Buckley, L., Guyatt, G., Fink, H. A., Cannon, M., Grossman, J., Hansen, K. E., et al. (2017). 2017 American College of Rheumatology guideline for the prevention and treatment of glucocorticoid-induced osteoporosis. Arthritis and Rheumatology., 69(8), 1521–1537.

    Article  PubMed  Google Scholar 

  21. Whyte, M. P. (2006). Clinical practice. Paget’s disease of bone. The New England Journal of Medicine, 355(6), 593–600.

    Article  CAS  PubMed  Google Scholar 

  22. Bhadada, S., Bhansali, A., Unnikrishnan, A. G., Khadgawat, R., Singh, S. K., Mithal, A., & Saikia, U. N. (2006). Does Paget’s disease exist in India? A series of 21 patients. Journal of the Association of Physicians of India, 54, 530–534.

    CAS  PubMed  Google Scholar 

  23. Siris, E. S. (1994). Perspectives: A practical guide to the use of pamidronate in the treatment of Paget’s disease. Journal of Bone and Mineral Research, 9(3), 303–304.

    Article  CAS  PubMed  Google Scholar 

  24. Bhadada, S. K., Pal, R., Sood, A., Dhiman, V., & Saini, U. C. (2019). Co-administration of systemic and intralesional zoledronic acid in a case of fibrous dysplasia: A potentially novel therapy. Frontiers in Endocrinology (Lausanne), 19(10), 803. https://doi.org/10.3389/fendo.2019.00803(PMID: 31803145; PMCID: PMC6877477)

    Article  Google Scholar 

  25. Lewiecki, E. M. (2010). Intravenous zoledronic acid for the treatment of osteoporosis: The evidence of its therapeutic effect. Core Evidence, 15(4), 13–23.

    Google Scholar 

  26. de Groen, P. C., Lubbe, D. F., Hirsch, L. J., Daifotis, A., Stephenson, W., Freedholm, D., Pryor-Tillotson, S., Seleznick, M. J., Pinkas, H., & Wang, K. K. (1996). Esophagitis associated with the use of alendronate. New England Journal of Medicine, 335(14), 1016–1021.

    Article  PubMed  Google Scholar 

  27. Kennel, K. A., & Drake, M. T. (2009). Adverse effects of bisphosphonates: Implications for osteoporosis management. Mayo Clinic Proceedings, 84(7), 632–637.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Do, W. S., Park, J. K., Park, M. I., Kim, H. S., Kim, S. H., & Lee, D. H. (2012). Bisphosphonate-induced severe hypocalcemia—a case report. Journal of Bone and Metabolism, 19(2), 139–145.

    Article  Google Scholar 

  29. Noriega Aldave, A. P., & Jaiswal, S. (2014). Severe resistant hypocalcemia in multiple myeloma after zoledronic acid administration: A case report. Journal of Medical Case Reports, 23(8), 353.

    Article  Google Scholar 

  30. Majumdar, S. R. (2008). Oral bisphosphonates and atrial fibrillation. BMJ, 336(7648), 784–785.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Rastogi, A., Rattan, V., & Bhadada, S. K. (2012). Osteonecrosis of jaw associated with bisphosphonate use. Indian Journal of Endocrinology and Metabolism, 16(3), 450–452. https://doi.org/10.4103/2230-8210.95711(PMID: 22629519; PMCID: PMC3354860).

    Article  PubMed  PubMed Central  Google Scholar 

  32. Xiao, Y., Chen, Y., Huang, Y., & Xiao, Y. (2023). Atypical femur fracture associated with common anti-osteoporosis drugs in FDA adverse event reporting system. Science and Reports, 13(1), 10892.

    Article  CAS  Google Scholar 

  33. Bhadada, S. K., Sridhar, S., Muthukrishnan, J., Mithal, A., Sharma, D. C., Bhansali, A., & Dhiman, V. (2014). Predictors of atypical femoral fractures during long term bisphosphonate therapy: a case series & review of literature. Indian Journal of Medical Research, 140(1), 46–54 (PMID: 25222777; PMCID: PMC4181159.A1).

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Zhang, C., & Song, C. (2021). Combination therapy of PTH and antiresorptive drugs on osteoporosis: a review of treatment alternatives. Frontiers in Pharmacology, 27(11), 607017.

    Article  Google Scholar 

  35. Diab, D. L., & Watts, N. B. (2013). Bisphosphonate drug holiday: Who, when and how long. Therapeutic Advances in Musculoskeletal Disease, 5(3), 107–111.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Author information

Authors and Affiliations

  1. Department of Endocrinology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India

    Durairaj Arjunan & Sanjay Kumar Bhadada

  2. Department of Pharmacology, Government Medical College, Patiala, India

    Tushar Bhadada

  3. Department of Pharmacology, Bangalore Medical College and Research Institute, Bangalore, India

    Subasri B Mohankumar

  4. Department of Endocrinology, Postgraduate Institute of Medical Education and Research (PGIMER), Room No: 001, Nehru Hospital Extension, Chandigarh, India

    Sanjay Kumar Bhadada

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  1. Durairaj Arjunan
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  4. Sanjay Kumar Bhadada
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Correspondence to Sanjay Kumar Bhadada.

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Arjunan, D., Bhadada, T., Mohankumar, S.B. et al. Non-biological Antiresorptive: Bisphosphonates. JOIO 57 (Suppl 1), 120–126 (2023). https://doi.org/10.1007/s43465-023-01054-7

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  • DOI: https://doi.org/10.1007/s43465-023-01054-7

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