Bone Abstracts

We have reported femoral osteopenia in short term-vitamin D restricted rats without deterioration in tibial cortical bone volume (CBV), geometry or strength¹. This study aimed to establish the effect of extended vitamin D deficiency in aged rat tibial volume and strength. Female Sprague-Dawley rats (9 m, n=6/group) were fed a diet containing varying vitamin D₃ (D) levels (0, 2, 12, and 20 IU/day) with either low (0.1%, LCa) or high (1%, HCa) dietary calcium for 6 m. At 15 m blood was taken for 25 hydroxyvitamin D (25D) 1.25 dihydroxyvitamin D (1.25D), PTH and Ca analyses and tibiae and femora retrieved for bone analyses. 3D micro-CT scans (Skyscan 1174) were used to determine CBV, mid-shaft sagittal cortical thickness (Cth.sag) and metaphyseal BV/TV. Tibial peak load was determined by three-point bending (Test Resources 800LE4). 25D and 1.25D were determined by RIA (IDS) and PTH by IRMA (Immutopics). Group serum 25D levels ranged from 22 (±2.9) to 161 (±38.8) nmol/l and serum calcium levels from 2.5 (±0.05) to 3.2 (±0.2) mmol/l. Circulating 25D was a determinant of BV/TV (r²=0.23, P<0.001) and CBV (r²=0.22, P<0.01). In multiple linear regression neither serum Ca, PTH nor 1.25D were determinants of bone volume when 25D was accounted for. Dynamic histomorphometry indicated that high dietary Ca reduced bone turnover only in animals with circulating 25D levels above 85 nmol/l with the greatest reduction achieved in the 20 IU/day group (20D) (BFR (μm³/μm² per day): LCa20D 33.9 (3.4) vs HCa20D 21.8 (2.3), P<0.05; Oc/BPm (n×10⁻³/mm): LCa20D 2.0 (0.2) vs HCa20D 1.1 (0.1), P<0.05). Tibial peak load was related to Cth.sag (r²=0.39, P<0.01). Thus, optimisation of bone volume and strength requires the combination of high dietary Ca intake and circulating 25D above 85 nmol/l. However, our previous demonstration that high dietary Ca is required to maximise circulating 25D levels^2,3 in combination with the present findings suggest that the mechanism for vitamin D-optimisation of bone is not mediated via a calcaemic effect.

1. Lee AMC et al. JSBMB 121 284–287, 2010.

2. Anderson PH et al. JBMR 23 1789–97, 2008.

3. Anderson PH et al. JSBMB 121 288–921, 2010.