Loop diuretics increase bone turnover and decrease BMD in osteopenic postmenopausal women: results from a randomized controlled study with bumetanide.
To study effects of loop diuretics on bone, 87 women were randomized to 1 year of treatment with bumetanide or placebo. Compared with placebo, bumetanide decreased BMD by 2% at the total hip and by 1.4% at the whole body. Levels of biochemical bone markers were lower in the placebo than in the bumetanide group. Thus, treatment with loop diuretics affects bone metabolism.


BACKGROUND
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.


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 1 year of treatment (week 52), and 6 months after withdrawal of treatment (week 78). Calcium (800 mg/day) and vitamin D (10 microg/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 (approximately 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.
Rejnmark
Lars
L
Department of Endocrinology and Metabolism C, Aarhus Sygehus, Aarhus University Hospital, Aarhus, Denmark. rejnmark@post6.tele.dk
Vestergaard
Peter
P
Heickendorff
Lene
L
Andreasen
Frederik
F
Mosekilde
Leif
L
D000368:Aged; D015519:Bone Density; D016723:Bone Remodeling / Q000187:drug effects*; D002034:Bumetanide / Q000008:administration & dosage / Q000009:adverse effects*; D002118:Calcium / Q000652:urine*; D004232:Diuretics / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D050723:Fractures, Bone / Q000473:pathology; D006801:Humans; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000473:pathology / Q000652:urine*; D012307:Risk Factors; D013997:Time Factors
D004232:Diuretics; D002034:Bumetanide; D002118:Calcium