Bisphosphonate holidays linked to modest alendronate-associated bone loss in retrospective cohort

A single-center retrospective study published in Osteoporosis International assessed skeletal outcomes during bisphosphonate drug holidays in 197 patients previously treated with at least 4.5 years of alendronate or three doses of zoledronate. Researchers compared holiday versus continued-treatment groups for alendronate (71 versus 59 patients) and zoledronate (20 versus 47), evaluating bone mineral density (BMD), bone turnover markers and three-year clinical fracture incidence.

Compared with continued alendronate, a holiday was associated with one-year BMD declines at the lumbar spine (−2.23%; 95% CI, −3.70% to −0.76%), total hip (−1.62%; −2.68% to −0.56%) and femoral neck (−1.89%; −3.49% to −0.28%). Bone turnover markers increased significantly during the first year but remained below pretreatment levels for at least three years. Zoledronate groups showed no significant differences in BMD or marker changes at one and two years.

Clinical fragility fracture rates did not differ significantly between holiday and continued-treatment groups: 9.9% versus 6.8% for alendronate (hazard ratio, 1.45) and 5% versus 6.4% for zoledronate. The findings suggest holidays may be feasible in selected patients with adequate BMD, with annual BMD and marker monitoring particularly relevant after alendronate discontinuation. However, the retrospective design and small groups, especially the zoledronate holiday group, limit causal interpretation and reassurance about fracture safety.