Hydrochlorothiazide inhibits bone resorption in men despite experimentally elevated serum 1,25-dihydroxyvitamin D concentrations

Abstract

We evaluated the effects of hydrochlorothiazide administration in relation to Ca balance, the PTH and vitamin D endocrine systems, acid-base balance, and bone. We studied six healthy men fed constant diets providing only 5.1 ± 0.7 SD mmoles Ca/day. Three of the men were also given calcitriol, 0.5 μg 6-hrly throughout their studies. All subjects were observed during 18 control days and then during 18 days of hydrochlorothiazide (HTZ) administration, 25 mg 12-hrly. Observations during control days 11 through 16 were compared to those during days 7 through 18 of HTZ administration, inclusively. Directional changes during HTZ did not differ among subjects not given or given calcitriol. For all six subjects, control net intestinal Ca absorption, serum 1,25-(OH)2-D concentrations, serum iPTH concentrations, and daily urine cAMP excretion averaged 0.5 ± 2.2 mmoles/day, 162 ± 51 pM, 4.3 ± 2.2 μl Eq/ml and 4.2 ± 0.9 μmoles/day, respectively; none changed during HTZ. As expected, HTZ administration was accompanied by a fall in urinary Ca excretion, averaging -1.4 ± 0.8 mmoles/day; P < 0.01. HTZ administration was also accompanied by less negative Ca balances, averaging +1.6 ± 1.0 mmoles/day; P < 0.025, and by a fall in daily urinary hydroxyproline excretion averaging -0.13 ± 0.09 mmoles/day; P < 0.025. We interpret these data to indicate that HTZ administration is accompanied by an inhibition of bone resorption. HTZ administration also raised serum HCO3 concentrations by +2.7 ± 0.5 mEq/liter; P < 0.001 and blood pH by +0.05 ± 0.02 units; P < 0.005. Since HTZ administration did not change either serum iPTH or 1,25-(OH)2-D concentrations nor urinary cAMP excretion, inhibition of bone resorption may be mediated by either relative alkalosis, a reduced skeletal sensitivity to PTH or 1,25-(OH)2-D, or, possibly, by a direct effect of HTZ on bone.