Bisphosphonate Drug Holiday and Fracture Risk
osteoporosis, fracture risk
Background/Aims: Among women with ≥ 3 years exposure to bisphosphonates (BPs), we compared the incidence of fragility fractures in those who discontinued BPs for ≥ 12 months (drug holiday) to those who continued to use BPs (persistent use).
Methods: This retrospective cohort study included women aged ≥ 45 years who initiated BP use from four Kaiser Permanente regions between January 1, 1998, and December 31, 2009. Drug holiday was defined as ≥ 12 months with BP use at 0% adherence. Persistent use status required ongoing use at ≥ 50% adherence. The primary outcome of interest was the first occurrence of an incident clinical osteoporosis-related fragility fracture, identified from the electronic medical record (EMR) via ICD-9-CM codes. All subjects were followed until fracture, disenrollment from the health plan, death, or December 31, 2012. From the EMR, we collected information on the following potential confounders and effect modifiers: race/ethnicity, age, body mass index, comorbidities, history of previous fragility fracture, lowest T-score prior to cohort entry, fall risk, 10-year fracture risk, and prior/concomitant use of bone-active medications. Persistent users and drug holiday subjects were compared with regard to several demographic and clinical characteristics. Time-varying Cox proportional hazards models were used to compare osteoporosis-related fracture incidence between the two groups.
Results: The cohort of 28,620 women, observed for 111,997 person-years, included 17,123 (59.8%) persistent BP users and 11,497 (40.2%) drug holiday subjects. The drug holiday group had fewer comorbidities, higher baseline T-scores, and lower fracture and fall risk scores. A total of 3,571 osteoporosis-related fractures were observed. The unadjusted rate ratio (RR) for any osteoporosis-related fractures for drug holiday compared to persistent use was 0.87 (95% confidence interval [CI]: 0.81–0.94), but was 1.0 (95% CI: 0.9–1.2) for hip fractures only. The time-varying models suggested no differences in fracture risk (hazard ratio [HR]: 0.90, 95% CI: 0.80–1.00) after adjustment for baseline fall and fracture risk, comorbidities and other bone-active medication use. Similarly, no difference in hip fracture risk was observed (HR: 0.84, 95% CI: 0.68–1.03).
Discussion: Women who undertake a holiday from BP use are not at greater risk of osteoporosis-related fragility fractures, nor hip fractures specifically, than are women who continue to use BPs persistently.
Adams AL, Adams JL, Raebel MA, Tang BT, Kuntz JL, Vijayadeva V, McGlynn EA, Gozansky WS. Bisphosphonate Drug Holiday and Fracture Risk. J Patient Cent Res Rev 2015;2:101. http://dx.doi.org/10.17294/2330-0698.1106