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Eur. J. Clin. Invest. · Jan 2003
Randomized Controlled Trial Clinical TrialDose-effect relations of loop- and thiazide-diuretics on calcium homeostasis: a randomized, double-blinded Latin-square multiple cross-over study in postmenopausal osteopenic women.
- L Rejnmark, P Vestergaard, A R Pedersen, L Heickendorff, F Andreasen, and L Mosekilde.
- Department of Endocrinology anf Metabolism C, Aarhus Amtssygehus, University Hospital, Aarhus University, Tage-Hansens Gade 2, DK-80000 Aarhus C, Denmark. rejnmark@post6.tele.dk
- Eur. J. Clin. Invest. 2003 Jan 1; 33 (1): 415041-50.
BackgroundThiazide diuretics (TDs) reduce whereas loop diuretics (LDs) increase urinary calcium. We studied the effects of different doses of a TD and LD on electrolytes, calcitropic hormones and biochemical bone markers.Subjects And MethodsIn a five-period crossover study, comparing four active doses with placebo, 40 postmenopausal women with osteopenia were treated with different doses of LD bumetanide (n = 20, 0.5-2.0 mg per day) or TD bendroflumethiazide (n = 20, 2.5-10 mg per day). Each treatment period lasted 1 week.ResultsUrinary calcium decreased dose-dependently in response to the bendroflumethiazide. The best hypocalciuric effect was achieved by 5 mg day-1 of bendroflumethiazide. Total plasma calcium levels increased, whereas ionised calcium at ambient pH-values decreased because of increased pH-values in response to the bendroflumethiazide. Plasma PTH levels did not change, whereas a slight dose-dependent increase occurred in plasma 1,25(OH)2D levels. As a marker of bone formation, plasma osteocalcin levels increased. Conversely, bumetanide dose-dependently increased renal calcium losses with a concomitant increase in plasma PTH and 1,25(OH)2D levels. Plasma osteocalcin levels increased and bone-specific alkaline phosphatase levels decreased dose-dependently.ConclusionWhether a LD or TD is chosen as diuretic therapy affects calcium homeostasis. The effects of LDs are potentially harmful to bone. Further studies are needed to evaluate whether long-term treatment with LDs causes osteoporosis. Until then, we suggest using, if possible, a TD rather than a LD as diuretic therapy in order not to risk deleterious effects on bone metabolism.
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