Loop diuretics increase bone turnover and decrease BMD in osteopenic postmenopausal women: Results from a randomized controlled study with bumetanide

Introduction: Loop diuretics may affect bone because they increase the renal calcium excretion and alters the diurnal rhythm of plasma PTH levels. We studied the effects of 1 year of treatment with the loop diuretic bumetanide on bone metabolism. Materials and Methods: In a double-blinded design, 87 healthy postmenopausal women with osteopenia were randomized to 1-year bumetanide treatment 2 mg/day or placebo. BMD, plasma levels of calcitropic hormones, and biochemical bone markers were measured at baseline, after I year of treatment (week 52), and 6 months after withdrawal of treatment (week 78). Calcium (800 mg/day) and vitamin D (10 mu g/day) were administered to all participants during the entire 1.5-year study period. Results: Compared with placebo, urinary calcium (+17%) and plasma PTH levels (+9%) increased significantly in response to bumetanide. After 1 year of treatment, BMD in the bumetanide compared with the placebo group was significantly decreased by 2% at the total hip and ultradistal forearm and by 1.4% at the whole body. In addition, levels of biochemical markers of bone turnover differed significantly (similar to 20%) between groups, with lower levels in the placebo than in the bumetanide group. Six months after the end of treatment, the effects of bumetanide were weakening. Conclusions: Treatment with loop diuretics affects bone turnover and decreases BMD. Further studies may reveal whether loop diuretics should be considered as a risk factor for fracture.