Bisphosphonate drug holidays in postmenopausal osteoporosis: effect on clinical fracture risk

A cohort of 183 postmenopausal women, who had either discontinued or continued bisphosphonates (BPs) after first-line therapy, was used to investigate the relationships between "drug holiday" and clinical fracture. The risk of new clinical fractures was found to be 40% higher in women who had taken a BP "drug holiday." BPs are the most widely used treatment for postmenopausal osteoporosis. The optimal treatment duration, however, remains unclear. The purpose of this study was to evaluate the fracture risk in postmenopausal women with osteoporosis after discontinuing BP treatment (BP "drug holiday"). A retrospective analysis was performed at Lille University Hospital (LUH) on postmenopausal women with osteoporosis who had taken a "drug holiday" or continued treatment after first-line BP therapy (3 to 5 years). The occurrence of new clinical fractures during follow-up was also explored. Cox proportional hazards models were used to investigate the relationships between BP "drug holiday" and the occurrence of clinical fractures, while controlling for confounding factors. Survival without new clinical fractures was analyzed using Kaplan-Meier curves and log-rank tests. One hundred eighty-three women (mean age: 61.8 years; SD: 8.7) who had previously undergone BP treatment for 3 to 5 years were enrolled in our study. The patients had received alendronate (n = 81), risedronate (n = 73), zoledronic acid (n = 20), and ibandronate (n = 9). In 166 patients ("drug holiday" group: n = 31; continuous-treatment group: n = 135), follow-up ranged from 6 to 36 months (mean duration: 31.8 months; SD: 8.2). The incidences of new clinical fractures during follow-up were 16.1% (5/31) and 11.9% (16/135). After full adjustment, the hazard ratio of new clinical fractures among "drug holiday" patients was 1.40 (95% CI: 1.12-1.60; p = 0.0095). After first-line BP therapy in postmenopausal women with osteoporosis, the risk of new clinical fractures was 40% higher in subjects who took a bisphosphonate drug holiday.