Department of Endocrinology and Metabolism C (L. Rejnmark, P. Vestergaard, L. Mosekilde) and Department of Clinical Biochemistry (L. Heickendorff), Aarhus Amtssygehus, Aarhus, University Hospital, Aarhus, Denmark; Department of Clinical Pharmacology (L. Rejnmark, F. Andreasen), Faculty of Health Science (P. Vestergaard, L. Mosekilde) and Department of Biostatistics (A. R. Pedersen), Aarhus University, Aarhus, Denmark.
Dose-effect relations of loop- and thiazide-diuretics on calcium homeostasis: a randomized, double-blinded Latin-square multiple cross-over study in postmenopausal osteopenic women
Article first published online: 13 FEB 2003
European Journal of Clinical Investigation
Volume 33, Issue 1, pages 41–50, January 2003
How to Cite
Rejnmark, L., Vestergaard, P., Pedersen, A. R., Heickendorff, L., Andreasen, F. and Mosekilde, L. (2003), Dose-effect relations of loop- and thiazide-diuretics on calcium homeostasis: a randomized, double-blinded Latin-square multiple cross-over study in postmenopausal osteopenic women. European Journal of Clinical Investigation, 33: 41–50. doi: 10.1046/j.1365-2362.2003.01103.x
- Issue published online: 13 FEB 2003
- Article first published online: 13 FEB 2003
- Received 10 June 2002; accepted 29 August 2002
- parathyroid hormones
Background Thiazide 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 methods In 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.
Results Urinary 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.
Conclusion Whether 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.