Duration of Bisphosphonate Drug Holidays and Associated Fracture Risk

• Published in: Medical care Vol. 58; no. 5; p. 419
• Main Authors: Curtis, Jeffrey R, Saag, Kenneth G, Arora, Tarun, Wright, Nicole C, Yun, Huifeng, Daigle, Shanette, Matthews, Robert, Delzell, Elizabeth
• Format: Journal Article
• Language: English
• Published: United States 01.05.2020
• Subjects: Aged; Bisphosphonate-Associated Osteonecrosis of the Jaw - etiology; Bisphosphonate-Associated Osteonecrosis of the Jaw - prevention & control; Bone Density Conservation Agents - administration & dosage; Bone Density Conservation Agents - adverse effects; Cohort Studies; Diphosphonates - administration & dosage; Diphosphonates - adverse effects; Drug Administration Schedule; Female; Femoral Fractures - chemically induced; Femoral Fractures - prevention & control; Hip Fractures - epidemiology; Humans; Humeral Fractures - epidemiology; Medicare; Osteoporosis, Postmenopausal - drug therapy; Osteoporotic Fractures - epidemiology; Osteoporotic Fractures - prevention & control; Spinal Fractures - epidemiology; Time Factors; United States - epidemiology; Withholding Treatment; United States
• ISSN: 1537-1948
• DOI: 10.1097/MLR.0000000000001294

Discontinuation of bisphosphonates (BP) or a "drug holiday" after several years of treatment is increasingly common. However, the association of drug holiday duration with future fracture risk is unclear. We evaluated the rate of fracture in relation to various lengths of drug holidays among women receiving long-term BP therapy. Observational cohort study using US Medicare data 2006-2016. Incidence rates (IRs) and Cox proportional hazards models were used to evaluate the rate and adjusted hazard ratios (aHRs) controlling for potential confounders. Women aged 65 years and above enrolled in fee-for-service Medicare who had been adherent (≥80%) to alendronate, risedronate, or zoledronate for ≥3 years. Hip, humerus, distal forearm, and clinical vertebral fracture. Among 81,427 eligible women observed for a median (interquartile range) of 4.0 (2.5, 5.3) years, 28% of women underwent a drug holiday. In the alendronate cohort (73% overall), the IR of hip fracture among women who discontinued BP for >2 years was 13.2 per 1000 person-years. Risk was increased (aHR=1.3, 1.1-1.4) versus continuing therapy (IR=8.8, referent). Rates were elevated for humerus fracture with discontinuation >2 years (aHR=1.3, 1.1-1.66) and for clinical vertebral fracture with discontinuation >2 years (aHR=1.2, 1.1-1.4). Results were similar for risedronate, zoledronate, and ibandronate for hip and clinical vertebral fracture. Discontinuing alendronate beyond 2 years was associated with increased risk of hip, humerus, and clinical vertebral fractures.