•  Bone;
  • calcitrol;
  • diuretics;
  • humans;
  • osteopenia;
  • 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.