Bone Matrix, Cellularity, and Structural Changes in a Rat Model with High-Turnover Osteoporosis Induced by Combined Ovariectomy and a Multiple-Deficient Diet.

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Bone Matrix, Cellularity, and Structural Changes in a Rat Model with High-Turnover Osteoporosis Induced by Combined Ovariectomy and a Multiple-Deficient Diet.

Am J Pathol. 2013 Dec 30;

Authors: Govindarajan P, Böcker W, El Khassawna T, Kampschulte M, Schlewitz G, Huerter B, Sommer U, Dürselen L, Ignatius A, Bauer NB, Szalay G, Wenisch S, Lips KS, Schnettler R, Langheinrich A, Heiss C

Abstract
In estrogen-deficient, postmenopausal women, vitamin D and calcium deficiency increase osteoporotic fracture risk. Therefore, a new rat model of combined ovariectomy and multiple-deficient diet was established to mimic human postmenopausal osteoporotic conditions under nutrient deficiency. Sprague-Dawley rats were untreated (control), laparatomized (sham), or ovariectomized and received a deficient diet (OVX-Diet). Multiple analyses involving structure (micro-computed tomography and biomechanics), cellularity (osteoblasts and osteoclasts), bone matrix (mRNA expression and IHC), and mineralization were investigated for a detailed characterization of osteoporosis. The study involved long-term observation up to 14 months (M14) after laparotomy or after OVX-Diet, with intermediate time points at M3 and M12. OVX-Diet rats showed enhanced osteoblastogenesis and osteoclastogenesis. Bone matrix markers (biglycan, COL1A1, tenascin C, and fibronectin) and low-density lipoprotein-5 (bone mass marker) were down-regulated at M12 in OVX-Diet rats. However, up-regulation of matrix markers and existence of unmineralized osteoid were seen at M3 and M14. Osteoclast markers (matrix metallopeptidase 9 and cathepsin K) were up-regulated at M14. Micro-computed tomography and biomechanics confirmed bone fragility of OVX-Diet rats, and quantitative RT-PCR revealed a higher turnover rate in the humerus than in lumbar vertebrae, suggesting enhanced bone formation and resorption in OVX-Diet rats. Such bone remodeling caused disturbed bone mineralization and severe bone loss, as reported in patients with high-turnover, postmenopausal osteoporosis. Therefore, this rat model may serve as a suitable tool to evaluate osteoporotic drugs and new biomaterials or fracture implants.

PMID: 24384131 [PubMed – as supplied by publisher]