AJP - Endocrinology and Metabolism, Vol 254, Issue 3 E260-E264, Copyright © 1988 by American Physiological Society
Parathyroid hormone-independent regulation of 1,25(OH)2D in response to inhibition of bone resorption
J. P. Bonjour, U. Trechsel, C. M. Taylor and H. Fleisch
Department of Pathophysiology, University of Bern, Switzerland.
Both plasma level of 1,25-dihydroxyvitamin D [1,25(OH)2D] and intestinal Ca
absorption increase after biphosphonate-induced inhibition of bone
resorption. Parathyroid hormone (PTH) has been considered a key mediating
element of this homeostatic response. In the present work, the role of PTH
was assessed by studying the influence of
1-hydroxypentane-1,1-bisphosphonate (HPeBP) on vitamin D and Ca metabolism
in both intact and thyroparathyroidectomized (TPTX) rats. In intact rats,
HPeBP given at 0.1 mg P/kg body wt sc for 10 days strongly inhibited bone
resorption without affecting bone formation. This effect was associated
with a marked stimulation of intestinal Ca absorption and Ca balance. In
this condition, HPeBP caused a marked rise in plasma 1.25(OH)2D without
affecting the level of 25-hydroxyvitamin D. In TPTX rats, HPeBP given at
same dose also inhibited bone resorption and enhanced plasma 1,25(OH)2D,
intestinal Ca absorption and Ca balance. In summary, this study shows that
bisphosphonates such as HPeBP with prevailing inhibitory activity on bone
resorption induce a marked stimulation of both 1,25(OH)2D production and
intestinal Ca absorption. This homeostatic response is not attenuated after
PTH removal. Thus, as previously shown for the response to low Ca diet, PTH
does not appear to be an essential mediating factor for stimulating
1,25(OH)2D production in response to an increase in bone mineral retention.
