Endocrinology, Vol 118, 948-954, Copyright © 1986 by Endocrine Society

ARTICLES

The role of 1,25-dihydroxyvitamin D in the inhibition of bone formation induced by skeletal unloading

BP Halloran, DD Bikle, TJ Wronski, RK Globus, MJ Levens and E Morey-Holton

Skeletal unloading results in osteopenia. To examine the involvement of vitamin D in this process, the rear limbs of growing rats were unloaded, and alterations in bone calcium and bone histology were related to changes in serum calcium (Ca), inorganic phosphorus, 25- hydroxyvitamin D, 24,25-dihydroxyvitamin D [24,25-(OH)2D], and 1,25- dihydroxyvitamin D [1,25-(OH)2D]. Acute skeletal unloading induced a transitory inhibition of Ca accumulation in unloaded bones. This was accompanied by a transitory rise in serum Ca, a 21% decrease in longitudinal bone growth (P less than 0.01), a 32% decrease in bone surface lined with osteoblasts (P less than 0.05), no change in bone surface lined with osteoclasts, and a decrease in circulating 1,25- (OH)2D from 130 +/- 10 to 53 +/- 11 pg/ml. No significant changes in the serum concentrations of inorganic phosphorus, 25-hydroxyvitamin D, or 24,25-(OH)2D were observed. After 2 weeks of unloading, bone Ca stabilized at approximately 70% of control values, and serum Ca and 1,25-(OH)2D returned to control values. Maintenance of a constant serum 1,25-(OH)2D concentration by chronic infusion of 1,25-(OH)2D (Alza osmotic minipump) throughout the study period did not prevent the bone changes induced by acute unloading. These results suggest that acute skeletal unloading in the growing rat produces a transitory inhibition of bone formation, which, in turn, produces a transitory hypercalcemia, leading to a temporary decrease in serum 1,25-(OH)2D. No evidence could be found for a direct involvement of 1,25-(OH)2D in the bone changes induced by skeletal unloading.

This article has been cited by other articles:

				B. M. Boudignon, D. D. Bikle, P. Kurimoto, H. Elalieh, S. Nishida, Y. Wang, A. Burghardt, S. Majumdar, B. E. Orwoll, C. Rosen, et al. Insulin-like growth factor I stimulates recovery of bone lost after a period of skeletal unloading J Appl Physiol, July 1, 2007; 103(1): 125 - 131. [Abstract] [Full Text] [PDF]

				D. S. Perrien, N. S. Akel, E. E. Dupont-Versteegden, R. A. Skinner, E. R. Siegel, L. J. Suva, and D. Gaddy Aging alters the skeletal response to disuse in the rat Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2007; 292(2): R988 - R996. [Abstract] [Full Text] [PDF]

				M. R. Allen and S. A. Bloomfield Hindlimb unloading has a greater effect on cortical compared with cancellous bone in mature female rats J Appl Physiol, February 1, 2003; 94(2): 642 - 650. [Abstract] [Full Text] [PDF]

				O. Barou, M.-H. Lafage-Proust, C. Martel, T. Thomas, F. Tirode, N. Laroche, A. Barbier, C. Alexandre, and L. Vico Bisphosphonate Effects in Rat Unloaded Hindlimb Bone Loss Model: Three-Dimensional Microcomputed Tomographic, Histomorphometric, and Densitometric Analyses J. Pharmacol. Exp. Ther., October 1, 1999; 291(1): 321 - 328. [Abstract] [Full Text]

				W. Dehority, B. P. Halloran, D. D. Bikle, T. Curren, P. J. Kostenuik, T. J. Wronski, Y. Shen, B. Rabkin, A. Bouraoui, and E. Morey-Holton Bone and hormonal changes induced by skeletal unloading in the mature male rat Am J Physiol Endocrinol Metab, January 1, 1999; 276(1): E62 - E69. [Abstract] [Full Text] [PDF]

				P. J. Kostenuik, B. P. Halloran, E. R. Morey-Holton, and D. D. Bikle Skeletal unloading inhibits the in vitro proliferation and differentiation of rat osteoprogenitor cells Am J Physiol Endocrinol Metab, December 1, 1997; 273(6): E1133 - E1139. [Abstract] [Full Text] [PDF]