In vivo bone metabolism and ex vivo bone marrow osteoprogenitors in vitamin D-deprived pigs

Vitamin D insufficiency is still a concern in countries where there is no r outine food supplementation, such as France. A low vitamin D status is clea rly associated with an increased risk of fracture in the elderly, but the l ong-term consequences of latent vitamin D insufficiency in young people and adults are not known. We fed 26 growing pigs a high calcium diet (1.1%) wi th a 1000 IU cholecalciferol/kg diet (controls), or without vitamin D (0D) for 4 months. We then analyzed the overall impact of low vitamin D status o n osteotropic hormones (calcitriol and immunoreactive parathyroid hormone), plasma markers of hone remodeling (alkaline phosphatase [ALP] activity, ca rboxyterminal propeptide of type I procollagen [PICP], osteocalcin, hydroxy proline), whole bone parameters (ash content, bending moment), histomorphom etry, and the populations of marrow osteoblastic and osteoclastic precursor s by ex vivo cultures. The fall in plasma 25-dihydroxyvitamin [25(OH)D] in the 0D pigs indicated severe depletion of their vitamin D stores. However, they remained normocalcemic, were mildly hyperparathyroid after 2 months of vitamin D deprivation, and showed only a slight decrease In plasma calcitr iol, The bone mineral content and bending moment of metatarsals decreased a nd they had increased osteoblastic (+59%, p < 0.05 OD vs. controls) and ost eoclastic (+31%, p < 0.1 OD vs. controls) surfaces. This was not paralleled by increased hone turnover, because plasma hydroxyproline and ALP were unc hanged and PICP and osteocalcin were decreased. The adherent fraction of bo ne marrow cells showed a great increase in the number of total stromal colo ny-forming units (CFU-F; +93%,p < 0.05 OD vs. controls) acid in the percent of ALP(+) CFU-F (+58 %, p < 0.01 0D vs, controls) in cultures from 0D pigs , More tartrate-resistant acid phosphatase-positive (TRAP(+)) multinucleate d cells were generated in cultures of nonadherent marrow cells from OD pigs , and the area of resorption was 345% greater than in controls. Thus, vitam in D deprivation caused only moderate hormonal changes in growing pigs fed a high-calcium diet, but affected their bone characteristics and greatly en hanced the pool of osteoblasts and osteoclasts by stimulating the commitmen t of their precursors in bone marrow, (C) 2000 by Elsevier Science Inc. All rights reserved.