Effects of a 'drug holiday' on bone mineral density and bone turnover marker during bisphosphonate therapy

Background: Recently long-term safety of bisphosphonate raises issues about the duration of therapy. We examined the effects of a drug holiday (DH) on bone mineral density (BMD) and bone turnover markers.

Methods: In Korean, 125 women of 50 years of age or older with T-score≤-3.0 of their lumbar or left femoral BMD initiated bisphosphonate from 1999 based on retrospective chart review. 125 patients who had used bisphosphonate≥5 years started DH in 2006. Lumbar (L1-4), left femoral neck, total BMD, serum parameter (β-crossLaps [CTx], phosphorus, total calcium, total alkaline phosphatase), and urinary parameter (calcium/creatinine ratio) were measured before, the time of starting, and after DH.

Results: After DH, lumbar, femoral neck and total BMD did not change significantly (0.757±0.093→0.747±0.102, P=0.135, 0.567±0.079→0.560±0.082, P=0.351, 0.698±0.008→0.691±0.090 g/cm(2), P=0.115, respectively). Serum CTx and total alkaline phosphatase were increased significantly (0.205±0.120→0.791±0.44 ng/mL, P<0.001, 54.52±13.40→60.42±15.543 IU/L, P=0.001, respectively). Urinary calcium/creatinine ratio increased significantly (0.132±0.076→0.156±0.093, P=0.012).

Conclusions: A DH could be cautiously considered in patients with long-term use of bisphosphonate if there is a concern about severe suppression of bone turnover with respect to long-term use because insignificant changes of BMD and significant increase of bone turnover markers are shown during the period.