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

**Authors:** Gero Knapp, Judith Langenstein, Natali Bauer, Sabine Stötzel, Christian Heiss, Vahid Jahed, Muhammad Alzweiri, Christoph Biehl, Thaqif El Khassawna

PMC · DOI: 10.3390/nu17213353 · 2025-10-24

## 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.

## Key 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.

## Linked entities

- **Proteins:** bglap2 (bone gamma-carboxyglutamate (gla) protein (osteocalcin) 2), PTH (parathyroid hormone), DKK1 (dickkopf Wnt signaling pathway inhibitor 1), IGF1 (insulin like growth factor 1)
- **Chemicals:** calcium (PubChem CID 5460341), cortisone (PubChem CID 222786), fructosamine (PubChem CID 20484), insulin (PubChem CID 70678557)
- **Diseases:** osteoporosis (MONDO:0005298)

## Full-text entities

- **Genes:** insulin [NCBI Gene 105613195], cathepsin-K [NCBI Gene 101108972], osteocalcin [NCBI Gene 677670], DKK-1 [NCBI Gene 101116876], PTH [NCBI Gene 101120013], IGF-1 [NCBI Gene 443318]
- **Diseases:** hypocalcemia (MESH:D006996), Vitamin D Deficiency (MESH:D014808), osteoporosis (MESH:D010024), Osteoporotic (MESH:D058866), depressed (MESH:D003866)
- **Chemicals:** Fructosamine (MESH:D019270), Cortisone (MESH:D003348), calcium (MESH:D002118), 25-OH-vitamin-D (-), vitamin-D (MESH:D014807)
- **Species:** Ovis aries (domestic sheep, species) [taxon 9940]

## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12610466/full.md

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Source: https://tomesphere.com/paper/PMC12610466