Metabolic Disruption in Osteoporotic Sheep: Evaluating Vitamin D Deficiency and Cortisone Effects via Biochemical Markers

TL;DR

This study examines how vitamin D deficiency and cortisone affect bone metabolism in sheep with osteoporosis using biochemical markers.

Contribution

The research identifies a unique biomarker signature from combined ovariectomy, diet, and glucocorticoids in an ovine osteoporosis model.

Findings

OVXDS sheep showed severe bone density loss and metabolic changes not seen in other groups.

OVXDS had suppressed bone turnover markers and low vitamin D levels at 3 months.

By 8 months, OVXDS showed altered bone coupling patterns under chronic stress.

Abstract

Background/Objectives: We evaluated serum and urinary biomarkers of bone and energy metabolism in an ovine osteoporosis model (Control, OVX, OVXD, OVXDS) at 0/3/8 months (M). Methods: Morning sampling; DXA (ROI ‘abdominal width’) and linear mixed models for repeated measures. Results: Only OVXDS showed severe DXA loss (Z-scores −3.29 at 3 M; −4.86 at 8 M), with ≈20% and ≈30% BMD reductions at 3 M and 8 M versus controls. OVX and OVXD remained within age-expected Z-score ranges at 8 M. At 3 M, OVXDS had hypocalcemia, markedly elevated UFEP, near-zero 25-OH-vitamin-D, and suppressed osteocalcin/NTX (depressed turnover). By 8 M, osteocalcin rose in OVXDS while NTX stayed low, consistent with altered coupling under chronic glucocorticoids and vitamin D deficiency. OVXD showed milder, later changes. Fructosamine and insulin were transiently higher in OVXDS at 3 M; IGF-1 was stable across groups/time. Conclusions: Combined ovariectomy, calcium/vitamin-D-deficient diet, and glucocorticoids produce the clearest biomarker signature and DXA loss. Assay cross-reactivity limited PTH/DKK-1/cathepsin-K measurement in sheep; we summarize DXA outcomes and expand assay limitations and future validation plans.

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