The Effects of Synthetic Conjugated Estrogens, A (Cenestin) on Trabecular Bone Structure and Strength in the Ovariectomized Rat Model

Abstract

This study evaluated the effect of Cenestin, a synthetic conjugated estrogens product, on the maintenance of trabecular bone microarchitecture, bone strength, and of bone turnover in the ovariectomized (ovx) rat model. Two doses of Cenestin were chosen in an attempt to approximate the equivalent human oral doses of 0.3 mg and 0.625 mg. Forty-nine 6-month-old retired female breeder Sprague-Dawley rats were randomly assigned to one of four groups: (1) sham-operated + vehicle; (2) ovx + vehicle; (3) ovx + day 1 post-ovariectomy Cenestin (8.12 mg/kg); (4) ovx + day 1 post-ovariectomy Cenestin (16.24 mg/kg) for 8 weeks. Trabecular structure of the right proximal tibia of each rat was imaged noninvasively by microCT. A compression test to induce a tibial plateau fracture was performed to determine the mechanical properties of the proximal tibia. Urine was collected on days 0, 14, 28, 42 and 56 and serum on days 0, 28 and 56 to assess biochemical markers of bone turnover including deoxypyridinoline crosslinks and osteocalcin. Both biochemical markers of bone turnover were analyzed by ELISA. Trabecular bone mass, structure, and connectivity density in the Cenestin-treated groups did not differ statistically ( p>0.05) from those of the sham-operated + vehicle-treated rats, but all were significantly higher ( p<0.05) than in the ovx + vehicle-treated rats. Structure Model Index, a measure of trabecular plate morphometry, in Cenestin-treated rats maintained a more equal mix of plate- and rod-like structures similar to the sham group, whereas the ovx group had predominantly rod-like trabeculae. Fracture load in the Cenestin (16.24 mg/kg) treated group was 31% ( p<0.01) higher than in the sham + vehicle-treated group and 61% ( p<0.05) higher than in the ovx + vehicle-treated group. Both the sham-operated + vehicle-treated and Cenestin-treated groups showed significantly lower urinary deoxypyridinoline crosslink excretion at all timepoints and serum osteocalcin at day 56 compared with the ovx + vehicle-treated group. In summary, Cenestin maintained trabecular bone microarchitecture and strength in an ovariectomized rat model of estrogen deficiency.

The selective estrogen receptor modulator SCH 57068 prevents bone loss, reduces serum cholesterol and blocks estrogen-induced uterine hypertrophy in ovariectomized rats

“…OVX also causes a reduction in BMD, bending strength of the femur and compressive strength of the vertebral bodies. Our results concerning biochemical markers of bone turnover, bone strength and histomorphometry in the OVX rats are therefore consistent with published studies of this model [23][24][25][26][27][28][29][30]. Administration of SCH 57068 to the OVX-treated animals in our experiment appeared to markedly reduce the increase in overall bone turnover induced by OVX.…”

“…The OVX rat model mimics changes in bone metabolism observed in human postmenopausal osteoporosis. Biochemical markers of bone resorption and formation reflecting bone turnover are elevated after OVX and return to low levels after estrogen repletion or after treatment with antiresorptive agents [23][24][25][26]. OVX also causes a reduction in BMD, bending strength of the femur and compressive strength of the vertebral bodies.…”

No effects of in vivo micro‐CT radiation on structural parameters and bone marrow cells in proximal tibia of wistar rats detected after eight weekly scans

“…BV/TV and Tb.Th were lower and Tb.Sp was higher than normally seen in 30-week-old Wistar rats, 17 but these results are consistent with previous data on retired breeders. 18,19 Although structural parameters may differ between normal rats and retired breeders, the rats used were considered suitable for determining any possible radiation damage in general for female Wistar rats.…”

Therapeutic Effect of Organic Gallium on Ovariectomized Osteopenic Rats by Decreased Serum Minerals and Increased Bone Mineral Content

“…The methods used for calculating trabecular thickness (Tb.Th), trabecular separation (Tb. Sp), trabecular number (Tb.N), and structural model index have been described by Lane [13]. Cortical thickness (Ct.Th) was expressed as the average cortical thickness of three sections.…”