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Vitamin D Depletion Induces RANKL‐Mediated Osteoclastogenesis and Bone Loss in a Rodent Model
Author(s) -
Anderson Paul H,
Sawyer Rebecca K,
Moore Alison J,
May Brian K,
O'Loughlin Peter D,
Morris Howard A
Publication year - 2008
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1359/jbmr.080616
Subject(s) - medicine , osteopenia , endocrinology , vitamin d and neurology , rankl , bone mineral , osteoporosis , osteoclast , calcium , calcitriol receptor , calcitriol , chemistry , activator (genetics) , receptor
The association between increased risk of hip fracture and low vitamin D status has long been recognized. However, the level of vitamin D required to maintain bone strength is controversial. We used a rodent model of vitamin D depletion to quantify the 25‐hydroxyvitamin D (25D) levels required for normal mineralization. Six groups of 10‐wk‐old male Sprague‐Dawley rats ( n = 42) were fed a diet containing 0.4% calcium and various levels of dietary vitamin D 3 for 4 mo to achieve stable mean serum 25D levels ranging between 10 and 115 nM. At 7 mo of age, animals were killed, and the histomorphometry of distal and proximal femora and L 2 vertebra was analyzed. Total RNA was extracted from whole femora for real‐time RT‐PCR analyses. In the distal femoral metaphysis, trabecular bone mineral volume (BV/TV) showed a significant positive association with circulating 25D levels ( r 2 = 0.42, p < 0.01) in the animals with serum 25D levels between 20 and 115 nM. Osteoclast surface (Oc.S) levels were positively associated with RANKL:OPG mRNA ratio, higher in groups with lower serum 25D levels, and were independent of serum 1,25D levels. Serum 25D levels <80 nM gave rise to osteopenia as a result of increased osteoclastogenesis, suggesting that levels of 25D >80 nM are needed for optimal bone volume. These data indicate that serum 25D levels are a major determinant of osteoclastogenesis and bone mineral volume and are consistent with the levels of 25D recommended to reduce the risk of fracture in humans.