Can bone turnover markers help to define the suitability and duration of bisphosphonate drug holidays?

Background: On stopping bisphosphonate treatment, bone resorption may increase before evidence of a decrease in bone density. Offset of bisphosphonate effect may therefore be monitored by measuring C-terminal telopeptide (CTX) following long-term bisphosphonate treatment to inform clinical decisions on drug holiday. Methods: Retrospective analysis of 158 patients (83% female, mean age 71 years) starting a drug holiday had plasma CTX measured at discontinuation (baseline), n=138 and 4 months and n=136, and 12 months (n=100). Premenopausal mean CTX levels and the least significant change (LSC) detectable were used to define target thresholds for bone turnover. Results: Following long-term bisphosphonate treatment (69% alendronic acid, 33% risedronate, mean duration 8 years SD 2.7), 32% patients had CTX above target (0.19 μg/L). In those with baseline CTX below threshold, 28% increased CTX to >0.19 μg/L and > LSC (0.06 μg/L) by 4 months (mean CTX increase 0.05 μg/L [95% confidence interval (CI): 0.04–0.06; p