***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: BACKGROUND Caloric restriction ( CR ) , energy intake reduced below ad libitum ( AL ) intake , increases life span in many species . The implication s for humans can be clarified by r and omized controlled trials of CR . METHODS To determine CR 's feasibility , safety , and effects on predictors of longevity , disease risk factors , and quality of life in nonobese humans aged 21 - 51 years , 218 persons were r and omized to a 2-year intervention design ed to achieve 25 % CR or to AL diet . Outcomes were change from baseline resting metabolic rate adjusted for weight change ( " RMR residual " ) and core temperature ( primary ) ; plasma triiodothyronine ( T3 ) and tumor necrosis factor-α ( secondary ) ; and exploratory physiological and psychological measures . RESULTS Body mass index averaged 25.1 ( range : 21.9 - 28.0 kg/m(2 ) ) . Eighty-two percent of CR and 95 % of AL participants completed the protocol . The CR group achieved 11.7±0.7 % CR ( mean ± st and ard error ) and maintained 10.4±0.4 % weight loss . Weight change in AL was negligible . RMR residual decreased significantly more in CR than AL at 12 months ( p = .04 ) but not 24 months ( M24 ) . Core temperature change differed little between groups . T3 decreased more in CR at M12 and M24 ( p < .001 ) , while tumor necrosis factor-α decreased significantly more only at M24 ( p = .02 ) . CR had larger decreases in cardiometabolic risk factors and in daily energy expenditure adjusted for weight change , without adverse effects on quality of life . CONCLUSIONS Sustained CR is feasible in nonobese humans . The effects of the achieved CR on correlates of human survival and disease risk factors suggest potential benefits for aging-related outcomes that could be eluci date d by further human studies Bone turnover is increased during weight loss in postmenopausal women and can be suppressed with calcium supplementation . In this study , we assessed the influence of energy restriction with and without calcium supplementation ( 1 g/day ) in premenopausal women . Thirty-eight obese premenopausal women ( body mass index [ BMI ] of 35.0 + /- 3.9 kg/m2 ) completed a 6-month study of either moderate weight loss or weight maintenance . During weight loss , women were r and omly assigned to either a calcium supplementation ( n = 14 ) or placebo group ( n = 14 ) and lost 7.5 + /- 2.5 % of their body weight . The control group of women ( n = 10 ) maintained their body weight . Total body and lumbar bone mineral density ( LBMD ) and content were measured by dual-energy X-ray absorptiometry ( DXA ) at baseline and after weight loss . Throughout the study , blood and urine sample s were collected to measure bone turnover markers and hormones . During moderate energy restriction , dietary calcium intake decreased ( p < 0.05 ) and the bone resorption marker deoxypyridinoline ( DPD ) increased slightly ( p < or = 0.05 ) without evidence of bone loss .  Calcium supplementation during weight loss tended to increase lumbar BMD by 1.7 % ( p = 0.05 ) compared with the placebo or weight maintenance groups . In contrast to our previous findings in postmenopausal women , premenopausal obese women who consume a low calcium diet do not lose bone over a 6-month period , whether their weight is stable or decreasing moderately BACKGROUND / OBJECTIVES : Moderate , long-term weight loss results in the loss of bone mass in overweight or obese premenopausal women . However , whether these changes persist during weight maintenance or regain remains to be determined . SUBJECTS/ METHODS : Overweight or obese ( body mass index : 25.8–42.5 kg/m2 ) women ( n=40 ) with at least two risk factors for the metabolic syndrome participated in this 12-month study that examined the effects of prescribed weight loss and regain , with or without exercise , on bone turnover and on bone mineral density ( BMD ) in a subset of participants ( n=24 ) . During the first 6 month , participants lost ∼10 % of their initial body weight via energy restriction and supervised aerobic exercise . Following weight loss , participants were r and omly assigned to either an exercise or a no exercise treatment for the regain ( + 50 % of weight lost ) phase . A one-way ( time ) repeated measures one-factor analysis of variance ( RMANOVA ) tested the effects of weight loss on BMD and bone turnover , and a two-way RMANOVA ( time , exercise ) was used to examine the effects of  exercise  during weight regain . RESULTS : Hip ( P=0.007 ) and lumbar spine ( P=0.05 ) BMD decreased with weight loss , and remained reduced after weight regain with or without exercise . Likewise , the weight-loss-associated increases in osteocalcin ( P<0.001 ) and C-terminal peptide of type I collagen ( P<0.001 ) persisted following weight regain , independent of exercise . CONCLUSIONS : The results of the present study , which is the first to examine changes in bone mass and turnover during carefully controlled weight regain , suggest that weight-loss-induced perturbations in bone mass and turnover persist after partial weight regain , regardless of whether regular weight-bearing aerobic exercise was continued Orlistat is a gastrointestinal lipase inhibitor that is used to reduce dietary fat absorption and to enhance weight loss in subjects consuming a hypocaloric diet . To assess whether orlistat has an effect on the metabolism of six minerals , a 21-d , double-blind , r and omized , parallel-group , placebo-controlled mineral balance study was conducted in obese ( body mass index > 30 kg/m(2 ) ) men . Subjects consumed a hypocaloric diet with a constant daily mineral content and received daily oral treatment with orlistat ( 120 mg three times daily ) ( n = 14 ) or placebo ( three times daily ) ( n = 14 ) for 21 d. After a 14-d equilibration period , calcium , phosphorus , magnesium , iron , copper and zinc balances were assessed for d 15 - 21 . In addition , the effect of diet and orlistat treatment on bone metabolism was estimated from measurement of biomarkers of bone formation and bone resorption . Serum and urine electrolytes were also measured at baseline and at the end of treatment . Orlistat inhibited fat absorption by approximately 33 % ( P < 0.05 ) . There were no significant differences in mineral apparent absorption , urinary mineral loss or mineral balance between the orlistat and placebo groups . Markers of bone turnover and serum and urine electrolytes did not differ between the orlistat and placebo groups . Orlistat was well tolerated ; adverse events were of mild or moderate intensity , and the majority of these events were unrelated or remotely related to study treatment . In obese men consuming a hypocaloric diet , the administration of orlistat had no significant effect on the balance of six selected minerals . In addition , biomarkers of bone turnover , as well as serum and urine electrolytes , were not affected by orlistat treatment BACKGROUND Weight loss is associated with bone loss , but this has not been examined in overweight premenopausal women . OBJECTIVE The aim of this study was to assess whether overweight premenopausal women lose bone with moderate weight loss at recommended or higher than recommended calcium intakes . DESIGN Overweight premenopausal women [ n = 44 ; x ( + /-SD ) age : 38 + /- 6.4 y ; body mass index ( BMI ): 27.7 + /- 2.1 kg/m(2 ) ] were r and omly assigned to either a normal ( 1 g/d ) or high ( 1.8 g/d ) calcium intake during 6 mo of energy restriction [ weight loss ( WL ) groups ] or were recruited for weight maintenance at 1 g Ca/d intake .  Regional bone mineral density and content were measured by dual-energy X-ray absorptiometry , and markers of bone turnover were measured before and after weight loss . True fractional calcium absorption ( TFCA ) was measured at baseline and during caloric restriction by using a dual-stable calcium isotope method . RESULTS The WL groups lost 7.2 + /- 3.3 % of initial body weight . No significant decrease in BMD or rise in bone turnover was observed with weight loss at normal or high calcium intake . The group that consumed high calcium showed a strong relation ( r = 0.71 ) between increased femoral neck bone mineral density and increased serum 25-hydroxyvitamin D. No significant effect of weight loss on TFCA was observed , and the total calcium absorbed was adequate at 238 + /- 81 and 310 + /- 91 mg/d for the normal- and high-calcium WL groups , respectively . CONCLUSION Overweight premenopausal women do not lose bone during weight loss at the recommended calcium intake , which may be explained by sufficient amounts of absorbed calcium BACKGROUND Recent findings suggest that higher levels of intermuscular adipose tissue ( IMAT ) are associated with glucose dysregulation , lower levels of muscle strength , and a heightened risk of disability . Although several studies have described adaptations in muscle after reduced physical activity , the change in IMAT in healthy young adults is unknown . OBJECTIVE The objective was to determine whether reduced lower limb activity alters IMAT in healthy young adults and to assess whether this change affects muscle strength loss . DESIGN The subjects ( 6 men and 12 women aged 19 - 28 y ) underwent a 4-wk control period , which was followed by 4 wk of unilateral lower limb suspension . Volumes of whole muscle , subcutaneous adipose tissue , and IMAT were assessed by using magnetic resonance imaging in the thigh and calf . Muscle strength was assessed during maximal voluntary isometric contractions . RESULTS No changes were observed in the control period . Reduced physical activity decreased thigh and calf muscle volumes by 7.4 % and 7.9 % ( P < 0.001 ) , respectively ; no significant change in subcutaneous adipose tissue was observed . Additionally , IMAT increased in both regions ; the increase was larger in the calf ( 20 % ) than in the thigh ( 14.5 % ) ( P < or= 0.005 ) and was partially explained by the loss in muscle ( R(2 ) = 26 % ) . The loss in strength was greater in the thigh ( 20.4 % ) than in the calf ( 15 % ) . Strength loss was associated with increases in IMAT ( P = 0.039 ) after adjustment for the loss in muscle , initial strength , initial IMAT , and initial muscle volume . CONCLUSIONS IMAT accumulates markedly after reduced activity in healthy young adults . Increases in IMAT may contribute to losses in muscle strength associated with reduced physical activity , but the mechanism responsible is yet to be determined BACKGROUND Calorie restriction ( CR ) is promoted to increase longevity , yet this regimen could lead to bone loss and fracture and therefore affect quality of life . METHODS Forty-six individuals were r and omized to 4 groups for 6 months : ( 1 ) healthy diet ( control group ) ; ( 2 ) 25 % CR from baseline energy requirements ( CR group ) ; ( 3 ) 25 % energy deficit by a combination of CR and increased aerobic exercise ( CR + EX group ) ; and ( 4 ) low-calorie diet ( 890 kcal/d ; goal , 15 % weight loss ) followed by weight maintenance ( LCD group ) . Bone mineral density ( total body and hip by dual-energy x-ray absorptiometry ) and serum bone markers ( bone-specific alkaline phosphatase , osteocalcin , cross-linked C-telopeptide of type I collagen , and cross-linked N-telopeptide of type I collagen ) were measured at baseline and after 6 months . RESULTS Mean + /- SE body weight was reduced by -1.0 % + /- 1.1 % ( control ) , -10.4 % + /- 0.9 % ( CR ) , -10.0 % + /- 0.8 % ( CR + EX ) , and -13.9 % + /- 0.7 % ( LCD ) . Compared with the control group , none of the groups showed any change in bone mineral density for total body or hip . Bone resorption by serum cross-linked C-telopeptide of type I collagen was increased in all 3 intervention groups , with the largest change observed in the LCD group ( CR , 23 % + /- 10 % ; CR + EX , 22 % + /- 9 % ; and LCD , 74 % + /- 16 % vs control , 4 % + /- 10 % ) . Serum levels of cross-linked N-telopeptide of type I collagen were also increased in the LCD group . With regard to bone formation , bone alkaline phosphatase levels were decreased in the CR group ( -23 % + /- 10 % ) but were unchanged in the CR + EX , LCD , and control groups . CONCLUSIONS Moderate CR , with or without exercise , that preserves calcium intake for 6 months leads to large changes in body composition without significant bone loss in young adults . Longer studies with assessment s of bone architecture are needed to confirm that CR nutrient-dense diets have no deleterious effect on bone health . TRIAL REGISTRATION clinical trials.gov Identifier : NCT 
    Output:
    
Results and conclusions : All three obesity treatments result in statistically significant reductions in hip bone mineral density ( BMD ) and increases in bone turnover relative to pre-treatment values , with the reductions in hip BMD being strongest for bariatric surgery , notably Roux-en Y gastric bypass ( RYGB , 8%–11 % of pre-surgical values ) and weakest for dietary restriction ( 1%–1.5 % of pre-treatment values ) .
Weight loss pharmaceuticals ( orlistat or the glucagon-like peptide-1 receptor agonist , liraglutide ) induced no greater changes from pre-treatment values than control , despite greater weight loss .
There is suggestive evidence that liraglutide may increase bone mineral content ( BMC ) – but not BMD – and reduce fracture risk , but more research is required to clarify this .
However , a pressing outst and ing question is whether this BMD reduction contributes to increased fracture risk , as has been observed after RYGB , and whether any such increase in fracture risk outweighs the risks of staying obese ( unlikely )