The osteoporosis model in rats is achieved by ovariectomy procedure. Ovariectomy in adult animals induces estrogen deficiency and subsequent bone loss with corresponding clinical manifestations of postmenopausal osteoporosis.
In a standard design, female rats (Sprague-Dawley or Wistar) are ovariectomized at age 6 months (or later – on-demand). The earliest signs of bone loss after ovariectomy are observed in 2 weeks after surgery. Therefore pathology-dependent treatment begins in 1-2 weeks after ovariectomy (OVX). Animals are divided at least into three groups: sham-operated control (SHAM), ovariectomized vehicle-treated control (OVX-V), and compound treated group (OVX-Cpd) (n=8 per group).
After X days of treatment, bone architecture and indices of bone fragility (trabecular thickness, number, separation, etc) are evaluated in proximal tibia by histomorphometry. Animals are observed for mortality and signs of toxicity daily for treatment and post-treatment period. Specific tests, such as urinary and blood clinical chemistry analysis, and bone turnover markers are available on request. These include bone formation markers: alkaline phosphatase, osteocalcin, and aminoterminal propeptides of procollagen type I (P1NP) in the serum. Bone resorption markers including carboxy-terminal cross-linking telopeptide of type I collagen (CTX), pyridinoline, and deoxypyridinoline (in both serum and urine). Inclusion of specialized endpoints based on the pharmacology of the test article is also available.