Loop diuretics alter the diurnal rhythm of endogenous parathyroid hormone secretion. A randomized-controlled study on the effects of loop- and thiazide-diuretics on the diurnal rhythms of calcitropic hormones and biochemical bone markers in postmenopausal women.
BACKGROUND
Thiazide diuretics (TD) reduce urinary calcium, bone loss and fracture risk. Loop diuretics (LD) may have opposite effects. These effects could depend on induced rhythmic changes in bone and calcium homeostasis.


METHODS
After a run-in period of 7 days, we studied (in a factorial design) the diurnal rhythms of plasma levels of calcium, phosphate, parathyroid hormone (PTH), 1,25-dihydroxyvitamin D and osteocalcin, as well as renal excretions rates of calcium, phosphate, and cross-linked N-terminal telopeptide of type 1 collagen (NTx) in 50 postmenopausal women randomized to treatment with either a thiazide diuretic (TD; bendroflumethiazide, n = 14), a loop diuretic (LD; bumetanide, n = 13), LD plus TD (bendroflumethiazide plus bumetanide, n = 11), or placebo (n = 12).


RESULTS
In all four groups, all measured quantities showed a diurnal variation. LD caused a steep increase, with a subsequent decrease, in urinary calcium and plasma PTH. The mean 24 h plasma PTH concentration was increased (8.5 +/- 0.9 mmol L-1) compared with placebo (4.4 +/- 0.4 mmol L-1), whereas net 24 h renal calcium excretion did not differ from that of the placebo group due to a rebound hypocalciuria. Compared with placebo, diurnal rhythms of plasma phosphate and osteocalcin were changed with an increase during daytime and a decrease during the night. TD did not alter the diurnal rhythm of any of the measured quantities. However, the 24-h renal calcium excretion decreased, whereas the mean 24-h plasma calcium concentration increased without PTH suppression. LD plus TD caused changes similar to those observed with LD alone.


CONCLUSIONS
One daily dose of LD increases parathyroid activity with alterations in the diurnal pattern of osteocalcin. This could indicate a potential anabolic effect of LD.
Rejnmark
L
L
Department of Endocrinology and Metabolism C, Aarhus Amtssygehus, Aarhus, University Hospital, Aarhus, Denmark. rejnmark@post6.tele.dk
Vestergaard
P
P
Heickendorff
L
L
Andreasen
F
F
Mosekilde
L
L
D000368:Aged; D001539:Bendroflumethiazide / Q000008:administration & dosage*; D015415:Biomarkers; D001842:Bone and Bones / Q000378:metabolism; D002034:Bumetanide / Q000008:administration & dosage*; D002118:Calcium / Q000097:blood / Q000652:urine; D002940:Circadian Rhythm / Q000187:drug effects; D003094:Collagen / Q000652:urine; D024042:Collagen Type I; D004232:Diuretics / Q000008:administration & dosage*; D005260:Female; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D008875:Middle Aged; D015675:Osteocalcin / Q000097:blood; D010281:Parathyroid Hormone / Q000097:blood / Q000378:metabolism*; D010455:Peptides / Q000652:urine; D010710:Phosphates / Q000097:blood / Q000652:urine; D010919:Placebos; D017698:Postmenopause; D049993:Sodium Chloride Symporter Inhibitors / Q000008:administration & dosage*; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood
D015415:Biomarkers; D024042:Collagen Type I; D004232:Diuretics; D010281:Parathyroid Hormone; D010455:Peptides; D010710:Phosphates; D010919:Placebos; D049993:Sodium Chloride Symporter Inhibitors; C052929:collagen type I trimeric cross-linked peptide; D002034:Bumetanide; D015675:Osteocalcin; D014807:Vitamin D; D001539:Bendroflumethiazide; C097949:1,25-dihydroxyvitamin D; D003094:Collagen; D002118:Calcium