Effects of thiazide- and loop-diuretics, alone or in combination, on calcitropic hormones and biochemical bone markers: a randomized controlled study.
OBJECTIVE
Diuretics are commonly used drugs that in addition to their effect on the cardiovascular system also affect calcium homeostasis and bone metabolism. We evaluated the effects of loop diuretics (LD) and thiazide diuretics (TD) on calcitropic hormones and biochemical bone markers.


METHODS
A total of 50 postmenopausal women were randomized to 7 days of treatment with either the TD bendroflumethiazide, the LD bumetanide, bendroflumethiazide plus bumetanide, or placebo. Blood and urine (24 h) were sampled on each day. Statistical inferences were made versus the concomitant changes in the placebo group.


RESULTS
Bendroflumethiazide increased the tubular reabsorption of calcium (TRCa) (+0.46 +/- 0.11%, P=0.009), plasma levels of parathyroid hormones (PTH) (+24 +/- 10%, P=0.06), and 1,25(OH)2D (+12 +/- 6%, P=0.03). Bumetanide decreased the TRCa (-0.5 +/- 0.1%, P=0.01) and increased plasma PTH and 1,25(OH)2D levels (+27 +/- 9%, P=0.02 and +36 +/- 12%, P=0.006, respectively). Treatment with either of the drugs did not alter plasma calcium, osteocalcin, bone alkaline phosphatase (bone-ALP) or urinary NTx/creatinine ratio. However, treatment with both drugs caused an increased plasma calcium level (+2.7 +/- 1.0%, P=0.007) and decreased plasma levels of bone-ALP (-21 +/- 3%, P=0.001), osteocalcin (-6 +/- 3%, P=0.03), and urinary NTx/creatinine ratio (-39 +/- 6%, P=0.001).


CONCLUSIONS
Calcium homeostasis and bone metabolism are to a major degree influenced by diuretic treatment. Surprisingly, LD and TD exerted a similar effect on calcitropic hormones despite their opposite effects on the renal calcium excretion. In clinical practice, treatment with diuretics has to be considered as a cause of parathyroid stimulation.
Rejnmark
L
L
Department of Endocrinology and Metabolism C, Aarhus Amtssygehus, Aarhus, Denmark. rejnmark@post6.tele.dk
Vestergaard
P
P
Heickendorff
L
L
Andreasen
F
F
Mosekilde
L
L
D000368:Aged; D001539:Bendroflumethiazide / Q000009:adverse effects; D015415:Biomarkers / Q000097:blood / Q000652:urine; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism; D002034:Bumetanide / Q000009:adverse effects; D002117:Calcitriol / Q000097:blood / Q000378:metabolism* / Q000652:urine; D004232:Diuretics / Q000009:adverse effects*; D005260:Female; D006801:Humans; D008593:Menopause; D008875:Middle Aged; D010281:Parathyroid Hormone / Q000097:blood / Q000378:metabolism* / Q000652:urine; D012107:Research Design; D049993:Sodium Chloride Symporter Inhibitors / Q000009:adverse effects*
D015415:Biomarkers; D004232:Diuretics; D010281:Parathyroid Hormone; D049993:Sodium Chloride Symporter Inhibitors; D002034:Bumetanide; D001539:Bendroflumethiazide; D002117:Calcitriol