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Low-carbohydrate, high-protein (LCHP) diets have been shown to induce weight loss and beneficial changes in blood lipids that suggest cardiovascular disease risk reduction; however, LCHP diets have not been adequately investigated for health effects on the skeleton. A randomized trial to determine the effects of a LCHP diet on bone mineral status, biomarkers of bone turnover, indicators of acid-base balance, calcium homeostasis and fasting lipids in healthy pre-menopausal women was conducted. Women, aged 32 - 45 y, with a body mass index between 25-41 kg/m2 were randomized into one of two diet groups: LCHP (n = 13) or high-carbohydrate, low-fat (HCLF) (n = 12). Anthropometric (body weight, lean mass, fat mass) and bone mineral density (BMD) and content (BMC) measures and markers of lipid metabolism were taken at weeks 0, 6, and 12. Measures of acid-base balance, protein metabolism, and calcium homeostasis were conducted at weeks 0, 1-4, 6, and 12. Serum osteocalcin was analyzed at weeks 0, 1, 2, 6, and 12, while urinary NTx was analyzed at weeks 0, 1 and 2. Weight loss was significant at the end of 12 weeks in both diet groups (P < 0.05) but there was no Diet x Time interaction. Total proximal femur BMD was lower in the LCHP group (P < 0.05) compared to the HCLF group by week 12. Femoral neck BMC decreased in the LCHP diet group (P < 0.05), whereas total forearm BMC increased (P < 0.05) in the HCLF diet group by week 12 of the study. Serum osteocalcin showed significant main effects of diet (P < 0.05) and time (P < 0.0001), but a Diet x Time interaction was not observed. Urinary NTx exhibited no main diet effect, time effect or Diet x Time interaction at weeks 1 or 2. Urinary pH was lower in the LCHP group compared to the HCLF group throughout the study (P < 0.0001). Urinary calcium excretion was higher in the LCHP group and lower in the HCLF group (P < 0.0001) compared to baseline values at all intervals of the study. Urinary phosphorus excretion exhibited a significant diet effect (P < 0.001) and time effect (P < 0.002), while no Diet x Time interaction was observed. Total cholesterol, high-density and low-density lipoprotein cholesterol, and triacylglycerol concentrations did not differ between diets during the study. In conclusion, a LCHP diet appears to stimulate bone loss, while a HCLF diet appears to attenuate bone loss in healthy pre-menopausal women undergoing 12 weeks of weight loss. / Ph. D.

The early adult years are critical as they provide the final window of opportunity to maximize peak bone mass and help prevent osteoporosis later in life. Dietary habits of young women are often molded by social pressures to be thin. Negative implications for cognitive eating restraint (CER) on bone health have been shown, but direct evidence to support such contentions is limited. Therefore, this study was conducted to further investigate the relationships between CER and bone health in young women. Women aged 18 to 25 years with normal body mass index and limited physical activity participated in this study. Body composition and anthropometric variables, dietary intake, endocrine factors, biomarkers of bone turnover, and measurements of bone mineral content (BMC) and bone mineral density (BMD) were examined cross-sectionally in women with high (n = 31) and low (n = 34) CER scores. High CER participants possessed more fat mass (FM) (p < 0.05) and percent body fat (BF%) (p = 0.01) and consumed a greater number of servings of fruits and vegetables (p < 0.05) per day than the CER participants. No differences in biochemical measurements, BMC or BMD were found between groups. Using similar methods, a study was conducted to compare high (n = 27) and low (n = 26) CER groups at baseline and after 6-months. At baseline, the high CER group possessed significantly higher FM (p < 0.05) and BF% (p = 0.01) and lower biochemical markers of bone formation (p < 0.05) than the low CER group; no other group differences were apparent at baseline. Using repeated measures ANOVA, a significant Group x Time interaction was identified for salivary cortisol concentrations (p < 0.05). Mean salivary cortisol concentrations were significantly lower at 6-months versus baseline in the high CER group (p < 0.05) but did not differ between time points in the low CER group. No other significant Group x Time interactions were found. Overall, despite finding a lower serum osteocalcin concentration in the high CER group at baseline, evidence of compromised BMC or BMD between women with high versus low CER scores over 6 months was not found. / Ph. D.

STUDY 1 Aim: To compare the effects of Roux-en-Y gastric bypass (RYGB) and laparoscopic adjustable gastric banding (LAGB) on changes in bone mineral density (BMD), weight loss and blood biomarkers related to bone turnover, hormonal, and nutrient status. Subjects: Nine bariatric surgery patients. Methods: Patients had a DXA bone scan and fasting blood draw at baseline, three, and six months following surgery. Results: RYGB patients had greater weight loss vs. LAGB at both three (mean loss: 19 vs. 9%) and six months (26 vs. 11%), p<0.01. RYGB patients lost an average of 7% hip BMD at six months. Hip BMD loss at six months was correlated to decreased leptin (r=0.88) and increased adiponectin (r=-0.82), p<0.05. Bone turnover was indicated by elevated serum bone biomarkers after surgery. Conclusions: Research with larger sample sizes is warranted to better evaluate potential implications for late-life osteoporosis risk following bariatric surgery. STUDY 2 Aim: To determine repeatability for IMAT and muscle density, to evaluate the distribution of foreleg muscle and fat indices measured by pQCT and to determine predictors of muscle density and type-2 diabetes risk. Subjects: 82 women with varying BMI and physical activity levels. Methods: Subjects had DXA and pQCT bone scans, a fasting blood draw, and completed a 4-day physical activity record. Results: Fat and muscle distribution in the foreleg was highly correlated to total and central body adiposity. The pQCT device reliably measured muscle density (CV=0.8%), thus justifying use as surrogates for IMAT. Muscle density was positively related to physical activity (r=0.29; p<0.05) and negatively associated with markers of fat distribution and risk for type-2 diabetes [HOMA-IR (r=-0.44, p<0.01)]. Conclusions: Further research is necessary to determine whether specific fat or muscle depots can be targeted through exercise training to help with the prevention and treatment of obesity or type-2 diabetes. / Ph. D.

Bone mineral content (BMC) and bone mineral density (BMD), measured by dual x-ray absorptiometry are used clinically to diagnose osteoporosis and estimate risk for fragility fractures. Bone mineral explains up to 70% of bone strength; however, it does not take into account bone geometry. Mechanical Response Tissue Analysis is a method of non-invasively measuring the bending stiffness (EI) of bone which is determined by the product of Young's modulus of elasticity (E) and the areal cross sectional moment of inertia (I). The aim of the current study was to determine if high intensity strength training will increase ulnar bending stiffness in young women. Forty-nine women aged 19.9 ± 1.7 yrs, trained their nondominant arm either concentrically or eccentrically in the Isokinetic modality on the Biodex® system III 3d/wk for 32 wks. The dominant arm served as the control limb (untrained). Analysis of all subjects regardless of training mode demonstrated a significant increase in ulnar EI (22% ↑, P=0.01) with no significant difference in the untrained arm. When EI results were assessed by training mode, subjects who trained eccentrically showed a significant increase for ulnar EI in the trained limb (40% ↑, P=0.01) with no significant effect on the untrained limb while concentric training demonstrated no significant gain in either the trained or untrained arm. There was no effect of time x mode of training interaction for either the trained or untrained limb. Bone mineral density and bone mineral content of the ulna increased significantly in the trained arm in both concentric and eccentric training modes (P<0.05). These findings suggest support for the hypothesis that a critical threshold of mechanical bending loads may be necessary to effect an adaptation in bone strength and thus, eccentric training may be a novel approach to increase ulnar EI in young women. / Master of Science

High body weight seems protective of bone mass, specifically bone mineral content (BMC) and bone mineral density (BMD), thereby reducing the risk of osteoporosis. Cognitive eating restraint (CER), diet composition, and the satiety hormone, leptin, produced by adipocytes, are associated with body mass and may also influence bone mass. Few studies have examined these relationships. To investigate the relationship between leptin and CER score, 36 premenopausal, healthy weight women, as defined by body mass index (BMI) of 18-25 kg/m², aged 18-25 years were studied. Women were categorized by baseline Eating Inventory questionnaire scores into either the high CER group (score > 9, n = 20) or low CER group (score < 9, n = 16). Serum leptin concentration was significantly lower in the low CER group versus high CER group at baseline. A positive relationship between serum leptin concentration and body fat mass and body fat % in normal weight women despite differences in CER scores was observed. In a separate study, overweight and obese women, (BMI > 25 to < 43 kg/m²), aged 32-45 years, were randomly assigned to either a low-carbohydrate, high-protein (LCHP) or low-fat, high-carbohydrate (LFHC) diet for 12 weeks. Serum leptin concentration was significantly greater in the LCHP versus the LFHC diet group at 12 weeks (p < 0.05). Over time, significant decreases in serum leptin concentration, BMI, body weight, total lean mass, total fat mass, and body fat % were observed in both diet groups. Serum leptin concentration was positively associated with body weight, fat mass, and body fat % regardless of diet consumed. Both studies are novel in their respective populations and show no direct link between leptin and bone mass when considered in the context of CER or diet composition. / Master of Science