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Sheep model that mimics senile osteoporosis reveals new therapeutic avenues



DOI:10.1038/bonekey.2013.195

Bindl et al. used a sheep model of osteoporosis, in which hypothalamic–pituitary disconnection (HPD) had reduced bone turnover, to find out whether central regulation of bone metabolism impacts on metaphyseal fracture healing.

When assessed by peripheral quantitative CT (pQCT), HPD animals showed significantly disturbed healing of a metaphyseal bone fracture. The bone mineral density (BMD) of newly formed bone in the distal region of the gap was 30% lower than in healthy control animals, while in the proximal gap it was 8% lower.

HPD sheep treated with 17β-estradiol substitution or thyroxine T4 showed restoration of bone healing capacity back to normal levels, and hormone-treated HPD sheep showed significantly improved fracture healing compared with non-treated HPD sheep. In the proximal and distal gaps, pQCT and histomorphometry detected increased BMD (71% and 56%, respectively), a higher ratio of bone volume to total volume (39% and 77%, respectively) and greater trabecular thickness (31% and 35%, respectively).

Editor’s comment: This novel sheep model of osteoporosis, in which the condition is induced by corrupting central control of bone remodeling, is similar to that seen in senile patients with very low bone turnover. Encouragingly, therapy to address estrogen deficiency and/or hypothyroidism appears to reduce the impact on bone healing. This model could be used to explore other potential therapies for senile osteoporosis.


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