Ovariectomy-Induced Hyperphagia Does Not Modulate Bone Mineral Density or Bone Strength in Rats

Abstract

The ovariectomized (OVX) rat is a widely used animal model for the development of prevention and treatment strategies for postmenopausal osteoporosis. However, ovariectomy-induced hyperphagia results in weight gain and adiposity. To prevent potential protective effects of increased body weight on bone from confounding outcomes of preclinical studies, pair-feeding is used in some but not all studies to control food intake, but its importance is not well elucidated. We investigated if the type of feeding, pair-feeding vs. consumption of diet ad libitum, modulates bone mineral and bone strength in OVX rats. Three-month-old female Sprague-Dawley rats (n = 12/group) were randomized to 1) sham-operated control (SHAM); 2) OVX pair-fed (OVX-PF); and 3) OVX ad libitum (OVX-AL). For 14 wk, OVX-PF rats were pair-fed with the SHAM group and daily food intakes and weekly body weights were obtained. At necropsy, regional body composition was measured by dual energy X-ray absorptiometry. Bone mineral density (BMD) and biomechanical bone strength of femurs and lumbar vertebrae (LV) were also measured. OVX-AL rats had higher overall food intake (P < 0.01), final body weight (P < 0.01), weight gain (P < 0.01), and fat mass (P < 0.05) than either SHAM and OVX-PF rats. Conversely, SHAM rats had higher femur (P < 0.001) and LV1–3 BMD (P < 0.001) as well as LV4 peak load (P < 0.01) than both the OVX groups, whereas bone outcomes did not differ between the OVX-PF and OVX-AL groups. In summary, ovariectomy-induced hyperphagia and weight gain do not modulate BMD or biomechanical strength at 14 wk postovariectomy, suggesting that pair-feeding is not essential.