LONG-TERM FOLLOW-UP OF PATIENTS ON DRUG HOLIDAY FROM BISPHOSPHONATES: REAL-WORLD SETTING

Objective: Atypical femoral fractures and osteoporosis of the jaw have been associated with prolonged bisphosphonate therapy for postmenopausal osteoporosis. American Association of Clinical Endocrinologists guidelines suggest a drug holiday after 4 to 5 years of bisphosphonate treatment for moderate-risk patients and 10 years for high-risk patients, but there are minimal data on safe holiday durations. A recent U.S. Food and Drug Administration perspective suggests a treatment duration of 3 to 5 years. Our aim was to describe a group of patients on drug holiday and identify fracture risk. Methods: A retrospective chart review was conducted of 209 patients who started a bisphosphonate drug holiday between 2005 and 2010. Collected data included bone mineral density (BMD), markers of bone turnover, vitamin D status, and clinical and radiographic reports of fractures. Results: Eleven of 209 patients (5.2%) developed a fracture. Their mean age was 69.36 years (+/- 15.58), and the mean lumbar spine and femoral neck T-scores were -2.225 (+/- 1.779) and -2.137 (+/- 0.950), respectively. All patients had a significant increase in bone-specific alkaline phosphatase at 6 months, which was more pronounced in the fracture group (3.0 +/- 0.6083 mu g/L vs. 1.16 +/- 1.9267 mu g/L). Over 4 years, there was no significant change in mean lumbar spine BMD for the entire cohort, but there was a statistically significant decline in the femoral neck BMD at year 2 (-0.0084 +/- 0.03 gm/cm(2)). Conclusion: The current practice of initiating BP holidays needs further evaluation, particularly in the real-world setting. Elderly patients and those with very low BMD warrant close follow-up during a drug holiday. A fracture, early significant rise in bone turnover markers, and/or a decline in BMD should warrant resumption of osteoporosis therapy.