BACKGROUND Obesity exacerbates the age-related decline in physical function and causes frailty in older adults; however, the appropriate treatment for obese older adults is controversial. METHODS In this 1-year, randomized, controlled trial, we evaluated the independent and combined effects of weight loss and exercise in 107 adults who were 65 years of age or older and obese. Participants were randomly assigned to a control group, a weightmanagement (diet) group, an exercise group, or a weight-management-plus-exercise (diet–exercise) group. The primary outcome was the change in score on the modified Physical Performance Test. Secondary outcomes included other measures of frailty, body composition, bone mineral density, specific physical functions, and quality of life. RESULTS A total of 93 participants (87%) completed the study. In the intention-to-treat analysis, the score on the Physical Performance Test, in which higher scores indicate better physical status, increased more in the diet–exercise group than in the diet group or the exercise group (increases from baseline of 21% vs. 12% and 15%, respectively); the scores in all three of those groups increased more than the scores in the control group (in which the score increased by 1%) (P<0.001 for the between-group differences). Moreover, the peak oxygen consumption improved more in the diet–exercise group than in the diet group or the exercise group (increases of 17% vs. 10% and 8%, respectively; P<0.001); the score on the Functional Status Questionnaire, in which higher scores indicate better physical function, increased more in the diet–exercise group than in the diet group (increase of 10% vs. 4%, P<0.001). Body weight decreased by 10% in the diet group and by 9% in the diet–exercise group, but did not decrease in the exercise group or the control group (P<0.001). Lean body mass and bone mineral density at the hip decreased less in the diet–exercise group than in the diet group (reductions of 3% and 1%, respectively, in the diet–exercise group vs. reductions of 5% and 3%, respectively, in the diet group; P<0.05 for both comparisons). Strength, balance, and gait improved consistently in the diet–exercise group (P<0.05 for all comparisons). Adverse events included a small number of exercise-associated musculoskeletal injuries. CONCLUSIONS These findings suggest that a combination of weight loss and exercise provides greater improvement in physical function than either intervention alone.

BACKGROUND Obesity causes frailty in older adults; however, weight loss might accelerate age-related loss of muscle and bone mass and resultant sarcopenia and osteopenia. METHODS In this clinical trial involving 160 obese older adults, we evaluated the effectiveness of several exercise modes in reversing frailty and preventing reduction in muscle and bone mass induced by weight loss. Participants were randomly assigned to a weight-management program plus one of three exercise programs — aerobic training, resistance training, or combined aerobic and resistance training — or to a control group (no weight-management or exercise program). The primary outcome was the change in Physical Performance Test score from baseline to 6 months (scores range from 0 to 36 points; higher scores indicate better performance). Secondary outcomes included changes in other frailty measures, body composition, bone mineral density, and physical functions. RESULTS A total of 141 participants completed the study. The Physical Performance Test score increased more in the combination group than in the aerobic and resistance groups (27.9 to 33.4 points [21% increase] vs. 29.3 to 33.2 points [14% increase] and 28.8 to 32.7 points [14% increase], respectively; P=0.01 and P=0.02 after Bonferroni correction); the scores increased more in all exercise groups than in the control group (P<0.001 for between-group comparisons). Peak oxygen consumption (milliliters per kilogram of body weight per minute) increased more in the combination and aerobic groups (17.2 to 20.3 [17% increase] and 17.6 to 20.9 [18% increase], respectively) than in the resistance group (17.0 to 18.3 [8% increase]) (P<0.001 for both comparisons). Strength increased more in the combination and resistance groups (272 to 320 kg [18% increase] and 288 to 337 kg [19% increase], respectively) than in the aerobic group (265 to 270 kg [4% increase]) (P<0.001 for both comparisons). Body weight decreased by 9% in all exercise groups but did not change significantly in the control group. Lean mass decreased less in the combination and resistance groups than in the aerobic group (56.5 to 54.8 kg [3% decrease] and 58.1 to 57.1 kg [2% decrease], respectively, vs. 55.0 to 52.3 kg [5% decrease]), as did bone mineral density at the total hip (grams per square centimeter; 1.010 to 0.996 [1% decrease] and 1.047 to 1.041 [0.5% decrease], respectively, vs. 1.018 to 0.991 [3% decrease]) (P<0.05 for all comparisons). Exercise-related adverse events included musculoskeletal injuries. CONCLUSIONS Of the methods tested, weight loss plus combined aerobic and resistance exercise was the most effective in improving functional status of obese older adults. (Funded by the National Institutes of Health; LITOE ClinicalTrials.gov number, NCT01065636.)

Weight-loss therapy to improve health in obese older adults is controversial because it causes further bone loss. Therefore, it is recommended that weight-loss therapy should include an intervention to minimize bone loss such as exercise training (ET). The purpose of this study was to determine the independent and combined effects of weight loss and ET on bone metabolism in relation to bone mineral density (BMD) in obese older adults. One-hundred-seven older (age >65 yrs) obese (BMI ≥30 kg/m2) adults were randomly assigned to a control group, diet group, exercise group, and diet-exercise group for 1 year. Body weight decreased in the diet (−9.6%) and diet-exercise (−9.4%) groups, not in the exercise (−1%) and control (−0.2%) groups (between-group P<.001). However, despite comparable weight loss, bone loss at the total hip was relatively less in the diet-exercise group (−1.1%) than in the diet group (−2.6%), whereas BMD increased in the exercise group (1.5%) (between-group P<.001) Serum C-terminal telopeptide (CTX) and osteocalcin concentrations increased in the diet group (31% and 24%) while they decreased in the exercise group (−13% and −15%) (between-group P<.001). In contrast, similar to the control group, serum CTX and osteocalcin concentrations did not change in the diet-exercise group. Serum procollagen propeptide concentrations decreased in the exercise group (−15%) compared with the diet group (9%) (P=.04). Serum leptin and estradiol concentrations decreased in the diet (−25% and −15%) and diet-exercise (−38% and −13%) groups, not in the exercise and control groups (between-group P=.001). Multivariate analyses revealed that changes in lean body mass (β=.33), serum osteocalcin (β= −.24), and 1-RM strength (β=.23) were independent predictors of changes in hip BMD (all P<.05). In conclusion, the addition of ET to weight-loss therapy among obese older adults prevents weight-loss-induced increase in bone turnover and attenuates weight-loss-induced reduction in hip BMD despite weight-loss-induced decrease in bone-active hormones.

While bone mineral density (BMD) by dual-energy X-ray absorptiometry is the primary method of determining fracture risk, assessing bone turnover may add valuable information for the management of patients with low bone mass. Bone turnover markers (BTMs) are used in clinical trials where they can provide essential information on the biological efficacy of osteoporosis treatments. In such population-based studies, BTMs can predict fracture risk independent of BMD. When combined with BMD, they improve the fracture risk estimate above and beyond BMD alone in postmenopausal osteoporotic women. Since changes in bone turnover after the initiation of therapy with bone resorption inhibitors occur much more rapidly than changes in BMD, treatment efficacy could, in theory, be determined within weeks of using BTMs. However, such predictive value is limited by the large biological variability of these biochemical markers, even though newer automated methods have reduced their analytical variability. Consequently, widespread adoption as a means of predicting treatment efficacy in fracture prevention for individual patients cannot yet be recommended. BTMs may be useful for monitoring adherence to antiresorptive therapy and may aid in identifying patients for whom antiresorptive therapy is most appropriate. Thus, although BTMs are currently confined to clinical research applications, further improvement in assay precision may extend their diagnostic value in clinical settings.

Background Obesity exacerbates the age-related decline in insulin sensitivity and is associated with risk for cardiometabolic syndrome in older adults; however, the appropriate treatment for obese older adults is controversial. Objective To determine the independent and combined effects of weight loss and exercise on cardiometabolic risk factors in obese older adults. Design One-hundred-seven obese (BMI≥30 kg/m2) older (≥65 yrs) adults with physical frailty were randomized to control group, diet group, exercise group, and diet-exercise group for 1 year. Outcomes for this study included change in insulin sensitivity index (ISI), glucose tolerance, central obesity, adipocytokines, and cardiometabolic syndrome. Results Although similar increases in ISI occurred in the diet-exercise and diet groups at 6 months, the ISI improved more in the diet-exercise than in the diet group at 12 months (2.4 vs. 1.2; between-group difference, 1.2; 95% CI, 0.2-2.1); no changes in ISI occurred in both exercise and control groups. The diet-exercise and diet groups had similar improvements in insulin area under the curve (AUC) (−2.9 and −2.9 ×103mg.min/dl), glucose AUC (−1.4 and −2.2×103mg.min/dl), visceral fat (−787 and −561 cm3), tumor-necrosis factor (−17.0 and −12.8 pg/mL), adiponectin (5.0 and 4.0 ng/mL), waist circumference (−8.2 and −8.4 cm), triglyceride (−30.7 and −24.3 g/dL), and systolic/diastolic BP (−15.9 and −13.1/−4.9 and −6.7 mmHg), while no changes in these parameters occurred in both exercise and control groups. The cardiometabolic syndrome prevalence decreased by 40% in the diet-exercise and by 15% in the diet group. Body weight decreased similarly in the diet-exercise and diet groups (−8.6 and −9.7kg) but not in the exercise and control groups. Conclusions In frail, obese older adults, lifestyle interventions associated with weight loss improve insulin sensitivity and other cardiometabolic risk factors, but continued improvement in insulin sensitivity is only achieved when exercise training is added to weight loss.

We reported that weight loss induces bone loss which is prevented by exercise training; however, the mechanism for this observation remains unclear. Sclerostin, an inhibitor of bone formation, has been found to increase in states of unloading and may mediate the changes in bone metabolism associated with weight loss and exercise. The objective of the study was to determine the effect of lifestyle intervention in obese older adults on sclerostin levels, and on hip geometry parameters. One-hundred-seven obese (BMI ≥30 kg/m2) older (≥65 yrs) adults were randomly assigned to control, diet, exercise and combined diet-exercise for 1 year. Sclerostin levels were measured by ELISA at baseline, 6, and 12 months, while hip geometry parameters were obtained from bone mineral density (BMD) images done by dual-energy x-ray absorptiometry using hip structure analysis at baseline and 12 months. Both the diet and diet-exercise groups had significant decreases in body weight (−9.6% and −9.4%, respectively), while weight was stable in the exercise and control groups. Sclerostin levels increased significantly and progressively in the diet group (6.6±1.7% and 10.5±1.9% at 6 and 12 months, respectively, all P<0.05), while they were unchanged in the other groups; in particular, they were stable in the diet-exercise group (0.7±1.6% and 0.4±1.7% at 6 and 12 months, respectively, all P=NS). Hip geometry parameters showed significant decreases in cross-sectional area, cortical thickness, and BMD; and increases in buckling ratio at the narrow neck, intertrochanter and femoral shaft. These negative changes on bone geometry were not observed in the diet-exercise group. Significant correlations between changes in sclerostin and changes in certain hip geometry parameters were also observed (P<0.05). In conclusion, the increase in sclerostin levels with weight loss which was prevented by exercise may partly mediate the negative effects of weight loss on bone metabolism and the osteoprotective effect of exercise training.

Highlights d Diet-induced weight loss leads to muscle mass reduction in obese older adults d Diet-induced muscle loss is attenuated by addition of resistance exercise d Muscle protein synthesis following a meal improves with resistance exercise d Myocellular quality improves with aerobic plus resistance exercise

In this study, we evaluated the effect of polymorphisms of the CYP1A1 gene, linked to hormonerelated cancers, on estrogen metabolism and BMD. We found that variants carrying the A allele (CA and AA) for the C4887A polymorphism have a significantly higher degree of estrogen catabolism and lower femoral BMD.Introduction: Polymorphisms of the CYP1A1 gene, one of the key enzymes that metabolize estrogen, have been linked with hormone-related cancers. We investigated the impact of these polymorphisms on estrogen metabolism and BMD, which is another hormone-dependent health issue. Materials and Methods: One hundred seventy postmenopausal women (mean age, 63.5 ± 0.6 years) participated in the study, but analysis was limited to 156 white women. Genotyping was performed by restriction fragment length polymorphism analysis, urinary estrogen metabolites by enzyme immunoassay, serum estradiol by ultrasensitive radioimmunoassay, serum sex hormone-binding globulin by immunoradiometric assay, and BMD by DXA. Differences in the levels of urinary metabolites and BMD among the different variants were analyzed by analysis of covariance, whereas differences in free estradiol index, urinary N-telopeptide of type 1 collagen (NTx), and bone size were compared by one-way ANOVA. Results: We found that subjects carrying the A allele (CA or AA) for the C4887A polymorphism of the CYP1A1 gene have significantly lower free estradiol index (0.323 ± 0.08 versus 0.506 ± 0.04; p ‫ס‬ 0.04; pmol/nmol) and higher levels of total urinary estrogen metabolites (ng/mg Cr) than CC subjects (27.92 ± 2.03 versus 21.15 ± 1.04; p ‫ס‬ 0.03), suggestive of an accelerated estrogen catabolism in these (CA + AA) individuals. They also had significantly lower BMD (g/cm