Bilateral ovariectomies or sham surgeries were performed in female Sprague Dawley rats that were 78 days of age and weighed an average of 210 g. Food was available ad libitum to the control rats and to a group of ovariectomized rats (obese OVX). The food consumption of a second group of ovariectomized rats (weight-matched OVX) was restricted to match their body weights to those of the control rats. All rats were sacrificed at 14 weeks postovariectomy. Radioimmunoassay of terminal serum estradiol confirmed the success of ovariectomy. The estradiol concentration in control rats was 24.9 +/- 20.2 pg/ml, whereas the hormone was undetectable (less than 10 pg/ml) in both groups of OVX rats. The final body weights of control and weight-matched OVX rats were nearly identical (approximately 260 g). In contrast, obese OVX rats weighed significantly more than both of the above groups (approximately 320 g, P less than 0.001). The proximal tibia and lumbar vertebra were processed undecalcified for quantitative bone histomorphometry. Tibial trabecular bone volume (TBV) was determined to be 17.6 +/- 4.5%, 7.9 +/- 5.3%, and 3.6 +/- 3.1% for the control, obese OVX, and weight-matched OVX groups, respectively. Tibial TBV for both OVX groups was significantly less than the control value (P less than 0.001). The difference in tibial TBV between obese OVX and weight-matched OVX rats was also statistically significant (P less than 0.02). Histologic indices of bone resorption and formation were indicative of increased bone turnover in the proximal tibia of both OVX groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-resorptive agents--including estrogen (E), calcitonin (CT), and bisphosphonates--are established in the treatment of osteoporosis. Intermittent administration of parathyroid hormone (PTH) stimulates bone formation and is a possible therapeutic agent for the restoration of bone mass. The purpose was to determine the effects of the anti-resorptive agents alone and in combination with intermittent PTH on bone formation in the mandible and a long bone in the aged ovariectomized (Ovx) rat. Female rats were ovariectomized or sham-operated. One year later, groups of Ovx rats were treated with E, CT, or the bisphosphonate, Risedronate (NE). Additional groups of Ovx rats were treated with each of these agents in combination with human PTH for 10 weeks. Estrogen treatment suppressed most indices of bone formation in the humerus and mandible, while NE decreased some indices of formation at the endocortical and endosteal surfaces of the mandible and humerus. Increased double-labeled surface and mineral apposition rates were observed only on the mandibular endosteal surfaces following CT treatment. When the anti-resorptive agents were combined with intermittent PTH, most indices of bone formation at all skeletal sites were substantially greater than those of the untreated Ovx controls as well as the E-, CT-, and NE-treated groups, respectively. These results provide additional evidence that established and emerging therapies for osteoporosis affect osseous tissues in the oral cavity, and this may influence the progression of diseases and/or aging changes at this site.

Dietary-induced obesity (DIO) resulting from high-fat (HF) or high-sugar diets produces a host of deleterious metabolic consequences including adverse bone development. We compared the effects of feeding standard rodent chow (Control), a 30% moderately HF (starch-based/sugar-free) diet, or a combined 30%/40% HF/high-fructose (HF/F) diet for 12 weeks on cancellous/cortical bone development in male Sprague-Dawley rats aged 8 weeks. Both HF feeding regimens reduced the lean/fat mass ratio, elevated circulating leptin, and reduced serum total antioxidant capacity (tAOC) when compared with Controls. Distal femur cancellous bone mineral density (BMD) was 23-34% lower in both HF groups (p<0.001) and was characterized by lower cancellous bone volume (BV/TV, p<0.01), lower trabecular number (Tb.N, p<0.001), and increased trabecular separation versus Controls (p<0.001). Cancellous BMD, BV/TV, and Tb.N were negatively associated with leptin and positively associated with tAOC at the distal femur. Similar cancellous bone deficits were observed at the proximal tibia, along with increased bone marrow adipocyte density (p<0.05), which was negatively associated with BV/TV and Tb.N. HF/F animals also exhibited lower osteoblast surface and reduced circulating osteocalcin (p<0.05). Cortical thickness (p<0.01) and tissue mineral density (p<0.05) were higher in both HF-fed groups versus Controls, CORRESPONDING AUTHOR: Joshua F. Yarrow, MS, PhD, NF/SG Veterans Health System, 1601 SW Archer Road, Research 151, Gainesville, FL 32608, Phone: (352) 376-1611 x6477, jfyarrow@ufl.edu. CONFLICT OF INTEREST: NonePublisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. HHS Public Access Author Manuscript Author ManuscriptAuthor ManuscriptAuthor Manuscript while whole bone biomechanical characteristics were not different among groups. These results demonstrate that "westernized" HF diets worsen cancellous, but not cortical, bone parameters in skeletally-immature male rats and that fructose incorporation into HF diets does not exacerbate bone loss. In addition, they suggest that leptin and/or oxidative stress may influence DIO-induced alterations in adolescent bone development. Keywordsosteoporosis; diet; adipose; adiposity; fat; sugar INTRODUCTIONHistorically, obesity and body mass index (BMI) have been positively associated with bone mineral density (BMD) in adults, likely a result of higher body mass increasing mechanical strain on the weight bearing portions of the skeleton and/or an altered hormonal milieu resulting from increased adiposity that may positively influence bone acquisition in adulthoo...