Loss Of Lean Tissue Mass Research Articles

#2832 Lean tissue mass is associated with mortality across different stages of chronic kidney disease: a systematic review and meta-analysis

Abstract Background and Aims Loss of lean tissue mass (LLTM) commonly occurs in multiple long-term conditions (LTC), including chronic kidney disease (CKD), and is thought to be associated with adverse outcomes including mortality, frailty surrogates and poor quality of life. It remains unclear whether LLTM is directly associated with mortality in CKD after adjusting for the severity of CKD or the degree of multimorbidity, and whether such associations remain in other LTC with similar levels of multimorbidity, such as heart failure (HF). Method A systematic review was conducted in adult CKD [kidney transplant (KT), CKDG3-5 or dialysis treated kidney failure (D-KF)] and HF patients who had whole body bioimpedance defined lean tissue mass (BI-LTM). The primary outcome was mortality, with secondary outcomes including hospitalisation and health related quality of life (HRQoL). The review was registered with PROSPERO (CRD42021240688) and was conducted according to PRISMA guidelines. Electronic database searches of MEDLINE, EMBASE, AMED, CINAHL, PsychInfo, Web of Science, CENTRAL, ICTRP and ISRCTN were searched from inception until June 2023. Data extraction and risk of bias assessments, using the Quality in Prognosis Studies (QUIPS) tool, was performed by two independent reviewers. Random effects meta-analysis was conducted using STATA SE16.2 using restricted maximum likelihood (REML) estimation. Results From 10,024 citations, 126 studies were identified (100 D-KF, 12 CKDG3-5, 2 KT, 3 mixed CKD and 9 HF) reporting outcomes on 143,053 D-KF, 15,164 CKDG3-5, 346 KTR and 3716 HF patients respectively. There were 1,227 deaths (over 2-5 years) in the HF studies and 16,471 deaths (over 1-20 years) in the CKD studies. The weighted mean eGFRCreat was 54 and 42 ml/min/1.73 m2 in the KT and CKDG3-5 studies, with only 3 HF studies reporting any measure of renal function (all using categorical cut offs). In 87 studies survival analyses of all-cause mortality (ACM) showed that BI-LTM was associated with mortality in 67%, 100%, 85% and 74% of the HF, KT, CKDG3-5 and D-KF studies respectively after adjusting for age, sex, diabetic status, comorbidity score, CRP / IL-6, albumin and bioimpedance defined fluid measures in 93%, 77%, 64%, 17%, 32%, 59% and 24% of analyses. Meta-analysis within D-KF studies reporting MVA revealed a 1-degree decrease in phase angle (pooled HR 1.82, 95% CI 1.50-2.20: Fig. 1A) and lean tissue index <10th percentile (pooled HR 1.48, 95% CI 1.31-1.66: Fig. 1B) was associated with ACM. Leave one out meta-analysis and sensitivity analyses removing studies at high-risk of statistical analysis and study confounding bias confirmed these pooled estimates were robust. Of the studies reporting secondary outcomes including hospitalisation and HRQoL (including the Short Form-36 and Kidney Disease Quality of Life Instrument), 67% showed associations with BI-LTM. Conclusion LLTM is associated with mortality across all stages of CKD and in heart failure. Furthermore, LLTM is associated with adverse outcomes such as hospitalisation and poor quality of life. This study confirms that LLTM potentially has an important role in the explanatory pathway for adverse outcomes in patients with LTCs, including CKD. Using BI-LTM may provide a way to identify early LLTM and target interventions to reduce the risk of adverse outcomes in these multimorbid cohorts.

Changes in Lean Tissue Mass, Fat Mass, Biological Parameters and Resting Energy Expenditure over 24 Months Following Sleeve Gastrectomy

Sleeve gastrectomy (SG) induces weight loss but its effects on body composition (BC) are less well known. The aims of this longitudinal study were to analyse the BC changes from the acute phase up to weight stabilization following SG. Variations in the biological parameters related to glucose, lipids, inflammation, and resting energy expenditure (REE) were concomitantly analysed. Fat mass (FM), lean tissue mass (LTM), and visceral adipose tissue (VAT) were determined by dual-energy X-ray absorptiometry in 83 obese patients (75.9% women) before SG and 1, 12 and 24 months later. After 1 month, LTM and FM losses were comparable, whereas at 12 months the loss of FM exceeded that of LTM. Over this period, VAT also decreased significantly, biological parameters became normalized, and REE was reduced. For most of the BC, biological and metabolic parameters, no substantial variation was demonstrated beyond 12 months. In summary, SG induced a modification in BC changes during the first 12 months following SG. Although the significant LTM loss was not associated with an increase in sarcopenia prevalence, the preservation of LTM might have limited the reduction in REE, which is a longer-term weight-regain criterion.

Muscle wasting after coronary artery bypass graft surgery: impact on post-operative clinical status and effect of exercise-based rehabilitation

Background: Coronary artery bypass graft (CABG) surgery is known to induce significant muscle wasting. It remains to be investigated whether muscle wasting after CABG surgery relates to a worse clinical status at entry of rehabilitation and exercise-based rehabilitation remediates such muscle wasting.Design: Prospective observational study.Methods: In 21 males, changes in lean tissue mass (LTM) after CABG surgery were assessed and during a 12-week endurance exercise-based rehabilitation intervention. Changes in blood parameters and cardiopulmonary exercise capacity were assessed, and relations with changes in LTM were analysed.Results: LTM decreased by −1.9 ± 2.5 kg (p < .05) within 3 weeks after CABG surgery: greater LTM loss related to a lower ventilatory threshold at entry of rehabilitation (r = 0.58–0.61, p < .05). LTM was fully restored (+2.1 ± 2.4 kg, p < .05) during rehabilitation.Conclusion: In males, CABG-induced LTM reduction was associated with a worse aerobic exercise tolerance at entry of rehabilitation, but this LTM reduction was fully remediated by endurance exercise-based rehabilitation.

The role of bile acids in nutritional support

Nutritional support continues to receive much attention as a possible intervention to prevent loss of lean tissue mass, promote recovery and re-establish proper immune function in critical care patients. Yet there remains much controversy regarding the clinical efficacy of such interventions. In addition to the direct effect of nutrition in terms of micro- and macronutrient content, nutritional formulations may exert an effect via the physiological response to feeding. Here, we highlight the key role of postprandial reabsorbed bile acids in attenuating both the inflammatory response and autophagy. These observations suggest that not all patients would benefit from aggressive nutritional support.

The Influence of Glucose Exposure Load and Peritoneal Membrane Transport on Body Composition and Nutritional Status Changes after 1 Year on Peritoneal Dialysis.

The characteristics of peritoneal membrane transport differ among patients, affecting the prescription of peritoneal dialysis (PD) modality and glucose exposure in order to achieve an effective dialysis. This study aims to verify the influence of glucose exposure load and peritoneal membrane transport on body composition and nutritional status changes after the first year of PD. We examined a cohort of 85 incident PD patients during the first year of treatment. We established a cut-off of 5% to define changes in dry weight (DW), lean tissue mass (LTM), and fat mass (FM). In total, 50.6% of the patients presented DW gain, 41.2% showed LTM loss, and 65.9% presented FM gain. Over the time (T0 - T12), we found significant differences in DW, body mass index (BMI), adipose tissue mass (ATM), FM and fat tissue index (FTI). Patients with lower dialysate-to-plasma creatinine ratio showed DW and FM gain. We observed a higher percentage of nonfast transporters in DW gain when comparing with DW no gain. As for glucose exposure load, no body composition changes were seen. Most patients presented DW gain, FM gain, and LTM loss. The characteristics of peritoneal membrane transport affected DW during the first year, changes being greater in nonfast than in fast transporters.

High-Protein Intake during Weight Loss Therapy Eliminates the Weight-Loss-Induced Improvement in Insulin Action in Obese Postmenopausal Women

High-protein (HP) intake during weight loss (WL) therapy is often recommended because it reduces the loss of lean tissue mass. However, HP intake couldhave adverse effects on metabolic function, becauseprotein ingestion reduces postprandial insulin sensitivity. In this study, we compared the effects of ∼10% WL with a hypocaloric diet containing 0.8g protein/kg/day and a hypocaloric diet containing 1.2g protein/kg/day on muscle insulin action inpostmenopausal women with obesity. We found that HP intake reduced the WL-induced decline in lean tissue mass by ∼45%. However, HP intake also prevented the WL-induced improvements in muscle insulin signaling and insulin-stimulated glucose uptake, as well as the WL-induced adaptations in oxidative stress and cell structural biology pathways. Our data demonstrate that the protein content of a WL diet can have profound effects on metabolic function and underscore the importance of considering dietary macronutrient composition during WL therapy for people with obesity.

Imaging Techniques of Bone, Mass and Fat in Disabilities

Disability leads to immobilisation associated with profound changes in body composition. The potential risks involved with these changes i.e. loss of lean tissue mass (LM) and bone mineral density (BMD) vs. gain in fat mass (FM) in body composition have implications for the health of the disabled individuals. Body fat has been identified as a significant predictor of mortality in humans making body composition measurement to quantify nutritional and health status an important issue for human health. Moreover, some disorders such as carbohydrate intolerance, insulin resistance, lipid abnormalities, and heart disease occur prematurely and at a higher prevalence in paraplegic populations may be related to adverse changes in body composition that result from immobilization and skeletal muscle denervation. Therefore, the purpose of this paper is to present imaging techniques for bone-mineral density, bone-mineral content, and bone-mineral-free lean and fat tissue mass alterations of ambulatory and non-ambulatory subjects with disabilities of the central nervous system.

One Week of Bed‐rest Substantially Reduces Muscle Mass and Induces Insulin Resistance in Healthy, Young Males

Background The recovery from illness or injury is generally accompanied by short periods (<1 week) of bed-rest, which can contribute substantially to the development of sarcopenia. Whereas the functional and metabolic consequences of prolonged (> 1 month) bed-rest have been well-established, the impact of short-term bed-rest remains largely unexplored. The present study assessed the effects of one week of bed-rest on skeletal muscle mass, leg strength, and whole-body insulin sensitivity. Methods: Ten healthy males (23±1 y) were subjected to 7 days of strict bed-rest. Prior to and following bed-rest, a DEXA scan, CT scan of the upper leg, and a one-step hyperinsulinemic-euglycemic clamp were performed to assess lean body mass, quadriceps cross sectional area (CSA) and peripheral insulin sensitivity, respectively. Additionally, prior to and after bed-rest, an incremental cycle ergometer test and a 1-Repetition Maximum (1RM) test were performed to determine VO2peak and maximal leg strength. Results: One week of bed-rest resulted in 1.4±0.2 kg loss of lean tissue mass (P<0.01) and a 3.2±1.0% loss of quadriceps CSA (P<0.01). Glucose infusion rates decreased from 62±6 to 42±3 μmol·kg FFM-1·min-1, representing a 29±5% decline in peripheral insulin sensitivity (P<0.01). Following bed-rest, VO2peak and 1RM had declined by 6.4±2.3% (P<0.05) and 6.9±1.4% (P<0.01), respectively. Conclusion One week of bed-rest substantially reduces muscle mass, muscle strength, oxidative capacity, and peripheral insulin sensitivity. Effective strategies need to be designed to prevent the loss of muscle mass and decline in metabolic health during short periods of muscle disuse.

Six‐year longitudinal changes in body composition of middle‐aged and elderly Japanese: Age and sex differences in appendicular skeletal muscle mass

Little is known about longitudinal changes of body composition measured by dual-energy X-ray absorptiometry (DXA) in middle-aged and elderly individuals. We evaluated longitudinal changes of body composition, and age and sex differences in appendicular skeletal muscle mass. Participants were 1454 community-dwelling Japanese men and women aged 40-79 years. Body composition at baseline and 6-year follow up was measured by DXA. Fat increased significantly in men of all ages, and in women aged in their 40s and 50s. Among men, arm lean tissue mass (LTM) changed by 0.9%, -0.5%, -1.4% and -3.7%, respectively, for the 40s to the 70s, and decreased significantly in the 60s and 70s. Leg LTM in men changed by -0.4%, -1.3%, -1.7% and -3.9%, respectively, and decreased significantly from the 50s to the 70s. Compared with the preceding age groups, significant differences were observed between the 60s and 70s in arm and leg LTM change in men. Among women, arm LTM changed by 0.7%, 0.2%, 1.6% and -1.5%, respectively, which was significant in the 60s and 70s. Leg LTM decreased significantly in all age groups of women by -2.0%, -2.8%, -2.4% and -3.9%, respectively. With respect to sex differences, leg LTM loss rates were significantly higher in women than men at the 40s and 50s. Longitudinal data suggest that arm and leg LTM decreased markedly in men in their 70s, and leg LTM had already decreased in women in their 40s.

Towards a Sustainable Dairy Sector: The underappreciated role of dairy protein in the preservation of lean tissue mass in the elderly

Sarcopenia has been attributed to a diminished postprandial muscle protein synthetic response. Differences in digestion and absorption kinetics of dietary protein and/or its amino acid composition have been suggested to modulate postprandial muscle protein accretion. The amino acid composition of dairy protein, especially whey, has the potential to confer advantages above other nondairy protein sources in prevention of lean tissue mass loss. This may be attributable to its relative high concentration of the essential amino acid leucine.

Protein intake and lean tissue mass retention following bariatric surgery

Since current protein intake (PI) recommendations for the bariatric surgery (BS) patient are not supported by conclusive evidence, we aimed to evaluate the relationship between PI and lean tissue mass (LTM) loss following BS. Observational study including patients undergoing gastric bypass (GBP; n = 25) or sleeve gastrectomy (SG; n = 25). Dietary advice and daily PI were assessed prior to, and at 2- and 6-weeks, 4-, 8-, and 12-months after surgery. Body composition was assessed by dual energy X-ray absorptiometry (DXA). LTM loss as percent of weight loss (%LTM loss) at 4- and 12-months after surgery were the main outcome variables. A PI ≥ 60 g/d was associated with lower %LTM loss at 4- (p = 0.030) and 12-months (p = 0.013). Similar results were obtained when a PI ≥ 1.1 g/kg of ideal body weight (IBW)/d was considered. Multilinear regression showed the only independent predictor of %LTM loss at 4-months was PI (expressed as g/kg IBW/d) (OR: -0.376, p = 0.017), whereas PI (OR: -0.468, p = 0.001) and surgical technique (OR: 0.399, p = 0.006) predicted 12-months %LTM loss. Our data provide supportive evidence for the PI goals of >60 g/d or 1.1 g/kg IBW/d as a being associated with better LTM preservation in the BS patient.

Use of higher-protein diets during intense military training to decrease lean tissue loss and improve performance

Background Current dietary intakes of active military personnel during intense training sessions may result in loss of lean tissue mass due to lower intake of energy and protein. It was hypothesized that a higher-protein diet (HPD) with frequent meals would result in greater lean tissue maintenance and improved performance during intense military training. Design 36 Air Force cadets completed a 12-day training session. A HPD (40% carbohydrate, 30% protein, 30% fat) with frequent meals was prescribed to each participant. Cadets completed 4 hours of supervised exercise daily. Pre- and post-test assessments included: body weight, body composition, vertical jump height, leg power index (LPI) and anaerobic testing. Results A negative correlation was found between the change in average vertical jump height and protein intake. Total body mass increased by 0.6 ± 1.1 kg (p<.001), and percent body fat decreased by 1.1 ± 0.9 (p<.001). Fat-free mass increased by 1.3 ± 1.1 kg (p<.001), fat-mass decreased by 0.7 ± 0.7 (p<.001). Averaged 600 meter times decreased by 1.2 ± 1.8 seconds (p<.001). Peak LPI (LPI) and average LPI increased by 0.12 ± 0.22 (p<.001) and 0.13 ± 0.22 (p<.001), respectively. Total energy intake was 14,110 ± 4,389 kJ. Macronutrient breakdown of diets was 52 ± 11% carbohydrates (437 ± 155 g), 19 ± 4% protein (157 ± 65 g) and 32 ± 9% fat (119 ± 53 g). There was no correlation between meal frequency and anthropometric changes or performance changes. Meal frequency consisted of 64% of the subjects consuming 3 meals and 1 to 3 snacks daily, 22% of the subjects only consumed 2 meals and 1 to 3 snacks daily, and 13% of participants reported consuming 2 large meals and no snacks daily. Conclusion Frequent meals and snacking appears to have resulted in maintenance and an increase in fat-free mass. The increase in LPI may be partially due to the increase in FFM. However, due to lack of dietary adherence, the hypothesis of this study could not be tested accurately.

Additive actions of the cannabinoid and neuropeptide Y systems on adiposity and lipid oxidation

Energy homeostasis is regulated by a complex interaction of molecules and pathways, and new antiobesity treatments are likely to require multiple pharmacological targeting of anorexigenic or orexigenic pathways to achieve effective loss of excess body weight and adiposity. Cannabinoids, acting via the cannabinoid-1 (CB1) receptor, and neuropeptide Y (NPY) are important modulators of feeding behaviour, energy metabolism and body composition. We investigated the interaction of CB1 and NPY in the regulation of energy homeostasis, hypothesizing that dual blockade of CB1 and NPY signalling will induce greater weight and/or fat loss than that induced by single blockade of either system alone. We studied the effects of the CB1 antagonist Rimonabant on food intake, body weight, body composition, energy metabolism and bone physiology in wild-type (WT) and NPY knockout (NPY(-/-)) mice. Rimonabant was administered orally at 10 mg/kg body weight twice per day for 3 weeks. Oral Rimonabant was delivered voluntarily to mice via a novel method enabling studies to be carried out in the absence of gavage-induced stress. Mice with dual blockade of CB1 and NPY signalling (Rimonabant-treated NPY(-/-) mice) exhibited greater reductions in body weight and adiposity than mice with single blockade of either system alone (Rimonabant-treated WT or vehicle-treated NPY(-/-) mice). These changes occurred without loss of lean tissue mass or bone mass. Furthermore, Rimonabant-treated NPY(-/-) mice showed a lower respiratory exchange ratio than that seen in Rimonabant-treated WT or vehicle-treated NPY(-/-) mice, suggesting that this additive effect of dual blockade of CB1 and NPY involves promotion of lipid oxidation. On the other hand, energy expenditure and physical activity were comparable amongst all treatment groups. Interestingly, Rimonabant similarly and transiently reduced spontaneous and fasting-induced food intake in WT and NPY(-/-) mice in the first hour after administration only, suggesting independent regulation of feeding by CB1 and NPY signalling. In contrast, Rimonabant increased serum corticosterone levels in WT mice, but this effect was not seen in NPY(-/-) mice, indicating that NPY signalling may be required for effects of CB1 on the hypothalamo-pituitary-adrenal axis. Dual blockade of CB1 and NPY signalling leads to additive reductions in body weight and adiposity without concomitant loss of lean body mass or bone mass. An additive increase in lipid oxidation in dual CB1 and NPY blockade may contribute to the effect on adiposity. These findings open new avenues for more effective treatment of obesity via dual pharmacological manipulations of the CB1 and NPY systems.

Changes in body composition during weight loss in obese client-owned cats: Loss of lean tissue mass correlates with overall percentage of weight lost

Obesity is one of the most common medical diseases in cats, but there remains little information on success of weight loss regimes in obese client-owned cats. No information currently exists on body composition changes during weight loss in clinical cases. Twelve obese client-owned cats undertook a weight loss programme incorporating a high-protein low fat diet. Body composition was quantified by dual-energy X-ray absorptiometry, before and after weight loss. Mean (+/-standard deviation) weight loss was 27+/-6.8% of starting weight, and mean rate of weight loss was 0.8+/-0.32% per week. Mean energy allocation during weight loss was 32+/-7.0 kcal/kg target weight. Mean composition of tissue lost was 86:13:1 (fat:lean:bone mineral). The proportion of lean tissue loss was positively associated with overall percentage of weight loss (simple linear regression, r(2)=44.2%, P=0.026). Conventional weight loss programmes produce safe weight loss, but lean tissue loss is an inevitable consequence in cats that lose significant proportions of their starting body weight.

Loss of lean tissue mass in adults with CF: an independent predictor of loss of bone mineral density (BMD)

Loss of lean tissue mass in adults with CF: an independent predictor of loss of bone mineral density (BMD)

Longitudinal follow-up of bone mineral density in adults with cystic fibrosis: Loss of BMD correlates with loss of lean tissue mass

Longitudinal follow-up of bone mineral density in adults with cystic fibrosis: Loss of BMD correlates with loss of lean tissue mass

Body composition after stroke

The aim of this study was to compare the body composition, including lean tissue mass, fat tissue mass, and bone mineral content, of the paretic leg with that of the nonaffected leg in patients with stroke and to evaluate the effects of time since stroke, spasticity, and motor recovery on the body composition specifically within the first year after stroke. Thirty-five stroke patients with mean age and standard deviation of 62.69+/-9.54 years were included in the study. A full physical examination including Brunnstrom motor recovery and modified Ashworth spasticity scale was performed. Fat tissue mass (grams), lean tissue mass (grams), and bone mineral content (grams) of both the paretic and nonaffected lower extremities were obtained from the total body scans determined by using dual-energy X-ray absorptiometry (Lunar DPX-PRO). Lean tissue mass and bone mineral content of the paretic side were found to be significantly lower than those of the nonaffected side (P<0.05). A significant correlation was found between the lean tissue mass and bone mineral content of both the paretic and nonaffected legs after adjusting for age and weight (P=0.000, r=0.679; P=0.000, r=0.634, respectively). Bone mineral content and lean tissue mass of both the paretic and nonaffected sides showed a significant negative correlation with time since stroke in patients with stroke for < or =1 year (P<0.05). A higher lean tissue mass and bone mineral content were found in patients with moderate to high spasticity in comparison with patients with low or no spasticity (P<0.05). Stroke causes loss of lean tissue mass and bone mineral content prominently in the paretic side. The loss increases with increasing time since stroke. Spasticity seems to help in preventing the loss of bone mineral content and lean tissue mass.

Counteracting muscle wasting in HIV‐infected individuals

HIV-infected persons often experience a loss of lean tissue mass, which includes decreases in skeletal muscle mass. This HIV-associated wasting is significant because it has been associated with accelerated disease progression and increased morbidity. Signalling related to several circulating molecules, including tumour necrosis factor (TNF)-alpha, growth hormone, insulin-like growth factor (IGF)-1 and testosterone, has been associated with the aetiology of muscle wasting. Additionally, nutritional status related to malnutrition and specific dietary deficiencies may be involved. In an attempt to counter muscle wasting in HIV-infected persons, treatments have been suggested that target these mechanisms. Nutritional supplementation, cytokine reduction, hormone therapy and resistance exercise training are potential treatments for this condition. Resistance exercise training, which is more easily accessible to this population than other treatments, holds promise in counteracting the process of HIV wasting, as it has been successfully used to increase lean tissue mass in healthy and clinical populations. This review will explore the HIV/AIDS muscle-wasting syndrome, its aetiology, and the treatments used to counteract wasting.

Growth hormone improves protein catabolism and growth in prepubertal children with HIV infection

Poor linear growth and weight loss are well documented in children with human immunodeficiency virus (HIV) infection and past studies in adults and children have reported that loss of lean tissue mass (LTM) associated with accelerated rates of protein catabolism. We undertook this study to test the hypothesis that human recombinant GH would improve linear height in HIV-infected children. Our second goal was to determine if GH could reverse protein catabolism in HIV-infected children. We studied six HIV-infected children (mean age 9.2 years, Tanner stage I, CD4 counts 110 000--292 000, two girls, four boys). Measures of protein turnover were conducted using the stable isotope 1-[(13)C] leucine. Body composition was measured by dual X-ray absorptiometry (DXA) scan for determination of LTM. Viral burden and IGF-1 levels were measured. Studies were conducted at baseline and 6 months. The baseline growth velocity of these children was only 3.9 cm/year. After 6 months of GH, growth velocity increased to 7.9 cm/year. Protein catabolism, represented as leucine rate of appearance (Ra) in the fasted state, was high at baseline, but decreased significantly after 6 months of GH therapy. Lean tissue mass significantly improved in all subjects. Viral burden did not increase significantly in any subject during GH therapy. These results suggest that GH improves height and weight and reduces protein catabolism in HIV-infected children without negative effect on viral burden.

Bone mineral and soft-tissue changes in AIDS-associated lipoatrophy

It is well established that body weight influences bone mass, but there is considerable controversy in the literature as to whether the principal determinant is lean mass, fat mass, or combinations of both, with variable degrees of relative influence as a function of age and sex. Total body and regional tissue composition studies were performed with DXA in a cohort of 102 HIV+ males who were on highly active antiretroviral therapy. These medications may be associated with a unique peripheral lipoatrophy without commensurate loss of lean tissue mass, and thereby provide an opportunity to assess the relative influence of fat mass on BMC levels in the absence of lean mass change. A comparison of the first quartile of peripheral fat (the lowest fat mass) with the remainder of the cohort showed no significant difference in lean mass in the total body, trunk, lower limbs, and upper limbs. In contrast, a significantly lower BMC was registered in the first peripheral fat quartile for all regions, implying an association of fat mass with BMC. By quartile stratification of the regional BMC, a comparison of the first and fourth quartiles demonstrated that the percentage fat mass decrease exceeded the lean mass decrease by a factor of 1.8 to 4.5. Regional BMCs were also stratified into two groups, < or =50 percentile and >50 percentile, and analyzed by Spearman correlation and robust multiple regression. It was found that lean mass was a determinant of BMC in both groups, whereas fat mass was an independent predictor in the >50 percentile BMC group only. The BMD t-score for the total hip was significantly lower in the first quartile of lower limb fat mass than the t-score of the remaining cohort, but this difference was not significant for the BMD lumbar spine t-score. This is a reflection of the influence of preferential local peripheral lipoatrophy on the adjacent mineral content and provides further evidence of fat mass as a determinant of BMC in addition to lean mass.