Abstract
Osteocytic osteolysis/perilacunar remodeling is thought to contribute to the maintenance of mineral homeostasis. Here, we utilized a reversible, adult-onset model of secondary hyperparathyroidism to study femoral bone mineralization density distribution (BMDD) and osteocyte lacunae sections (OLS) based on quantitative backscattered electron imaging. Male mice with a non-functioning vitamin D receptor (VDRΔ/Δ) or wild-type mice were exposed to a rescue diet (RD) (baseline) and subsequently to a low calcium challenge diet (CD). Thereafter, VDRΔ/Δ mice received either the CD, a normal diet (ND), or the RD. At baseline, BMDD and OLS characteristics were similar in VDRΔ/Δ and wild-type mice. The CD induced large cortical pores, osteomalacia, and a reduced epiphyseal average degree of mineralization in the VDRΔ/Δ mice relative to the baseline (−9.5%, p < 0.05 after two months and −10.3%, p < 0.01 after five months of the CD). Switching VDRΔ/Δ mice on the CD back to the RD fully restored BMDD to baseline values. However, OLS remained unchanged in all groups of mice, independent of diet. We conclude that adult VDRΔ/Δ animals on an RD lack any skeletal abnormalities, suggesting that VDR signaling is dispensable for normal bone mineralization as long as mineral homeostasis is normal. Our findings also indicate that VDRΔ/Δ mice attempt to correct a calcium challenge by enhanced osteoclastic resorption rather than by osteocytic osteolysis.
Highlights
The action of the active form of vitamin D, 1,25(OH)2D, is mediated by the vitamin D receptor (VDR) and plays an important role for calcium homeostasis [1,2,3,4,5]
We reported previously that VDR∆/∆ mice maintained on the rescue diet until adulthood showed an indistinguishable bone phenotype relative to wildtype (WT) mice but developed severe secondary hyperparathyroidism (sHPT) when they were subsequently fed a low calcium challenge diet, and that this adult-onset sHPT could be completely corrected by the administration of the rescue diet [9]
Using this model of reversible adult-onset sHPT, we sought to answer the questions of whether bone mineralization density distribution (BMDD) assessed by quantitative backscattered electron imaging is normal in VDR deficient mice and whether osteocytic osteolysis in non-growing mice occurs in the absence of a functioning VDR
Summary
The action of the active form of vitamin D, 1,25(OH)2D, is mediated by the vitamin D receptor (VDR) and plays an important role for calcium homeostasis [1,2,3,4,5]. We reported previously that VDR∆/∆ mice maintained on the rescue diet until adulthood showed an indistinguishable bone phenotype relative to wildtype (WT) mice but developed severe sHPT when they were subsequently fed a low calcium challenge diet, and that this adult-onset sHPT could be completely corrected by the administration of the rescue diet [9] Using this model of reversible adult-onset sHPT, we sought to answer the questions of whether bone mineralization density distribution (BMDD) assessed by quantitative backscattered electron imaging (qBEI) is normal in VDR deficient mice and whether osteocytic osteolysis in non-growing mice occurs in the absence of a functioning VDR
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