Bisphosphonates in the treatment of osteoporosis

Bisphosphonates are the mainstay in therapeutic option for the prevention and treatment of osteoporosis (1).

• they inhibit osteoclastic activity hence bone resorption (1)
• nitrogen-containing bisphosphonates include alendronate, risedronate, ibandronate, pamidronate, and zoledronic acid.
• non-nitrogen-containing bisphosphonates include etidronate, clodronate, and tiludronate
• indications for bisphosphonates include treatment of osteoporosis in postmenopausal women, osteoporosis in men, glucocorticoid-induced osteoporosis, hypercalcemia of malignancy, Paget disease of the bone, and malignancies with metastasis to the bone.

The optimal duration of bisphosphonate therapy has not been established. The continued use of a bisphosphonate should be re-evaluated in individual patients at regular intervals based on the benefits and potential risks, particularly after 5 or more years of use (2)

Time to Benefit of Bisphosphonate Therapy for the Prevention of Fractures Among Postmenopausal Women With Osteoporosis

• analysis (10 RCTs; n=23,384) found that 12.4 months (95% CI 6.3-18.4 months) were needed to avoid 1 non-vertebral fracture per 100 postmenopausal women receiving bisphosphonate therapy, suggesting treatment is likely to benefit those with a life expectancy >12.4 months (3)

Notes:

• there is evidence relating to the efficacy of using the once-yearly zoledronic acid infusion. Zoledronic acid is given as 4 mg to 5 mg intravenously over at least 15 to 30 minutes every 12 months to treat osteoporosis (4)
• frequent infusion of intravenous bisphosphonates in patients with cancer is thought to be associated with osteonecrosis of the jaw (5).

Reference:

1. Farrell KB, Karpeisky A, Thamm DH, Zinnen S. Bisphosphonate conjugation for bone specific drug targeting. Bone Rep. 2018 Dec;9:47-60.
2. Medicines and Healthcare products Regulatory Agency (MHRA). Bisphosphonates: atypical femoral fractures. Drug Safety Update 2011;4(11)
3. Deardorff WJ et al. Time to Benefit of Bisphosphonate Therapy for the Prevention of Fractures Among Postmenopausal Women With Osteoporosis: A Meta-analysis of Randomized Clinical Trials. JAMA Intern Med. Published online November 22, 2021.
4. Black DM et al. Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. N Engl J Med. 2007 May 3;356(18):1809-22.
5. Khan AA et al. International Task Force on Osteonecrosis of the Jaw. Diagnosis and management of osteonecrosis of the jaw: a systematic review and international consensus. J Bone Miner Res. 2015 Jan;30(1):3-23.