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Prognostic Association of Handgrip-Defined Probable or Possible Sarcopenia Status and Polygenic Risk with 10-Year Fracture Incidence among Black, Hispanic, and White Women: A Women's Health Initiative Study.

PURPOSE: The Fracture Risk Assessment Tool (FRAX) excludes objective skeletal muscle health and genetic variables. We evaluated the prognostic associations of handgrip-defined probable/possible sarcopenia and genome-wide polygenic scores (GPS) with 10-year fracture risk, and their incremental predictive value beyond FRAX across racial/ethnic groups and GPS strata. METHODS: We analyzed 2,051 postmenopausal women from the Women's Health Initiative. Race-specific analyses focused on Black, Hispanic, and White participants (n=2,009), excluding American Indian/Alaska Native and Asian/Pacific Islander individuals due to sparse fracture events. Sarcopenia status was operationalized by low handgrip strength alone via EWGSOP2 (<16.0 kg) and AWGS 2025 (<18.0-20.0 kg) criteria. Fine-Gray models estimated subdistribution hazard ratios (sHR), treating death as a competing risk. Predictive performance at 10 years was assessed using time-dependent AUC, Brier scores, and decision curve analysis (DCA). RESULTS: Handgrip-defined probable or possible sarcopenia prevalence was 4.4% (EWGSOP2) and 6.4% (AWGS 2025). Black women demonstrated lower risk for major osteoporotic fractures (MOF) (adjusted sHR=0.19, 95% CI: 0.08-0.48) and hip fractures (adjusted sHR=0.07, 95% CI: 0.01-0.52) compared to White women. Neither sarcopenia status nor high GPS showed statistically significant independent associations with fractures after FRAX adjustment. Adding sarcopenia status to baseline FRAX (AUC: 0.71 for MOF; 0.69 for hip) yielded near-identical AUCs, Brier scores, and within-sample net benefit. CONCLUSION: Handgrip-defined probable/possible sarcopenia and current GPS do not provide independent or incremental predictive value beyond the clinical FRAX framework within this genomic sub-sample of older women.

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Sarcopenia and its implications for the elderly.

Sarcopenia is the loss of muscle mass and strength with age. Sarcopenia is a part of normal aging, and occurs even in master athletes, although it is clearly accelerated by physical inactivity. Sarcopenia contributes to disability, reduced ability to cope with the stress of a major illness, and to mortality in the elderly. The etiology of sarcopenia is unclear, but several important factors have been identified. These include loss of alpha motor neurons, decline in muscle cell contractility, and several potential humoral factors, such as androgen and estrogen withdrawal and increase in production of catabolic cytokines. Treatment of sarcopenia with progressive resistance training is safe and effective, but dissemination of this technique to the general population has yet to occur. As the number of elderly persons increases exponentially in the new century, a public health approach to prevention and treatment of sarcopenia, based on increasing physical activity at all ages, will be crucial to avoiding an epidemic of disability in the future.

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Sarcopenia, calf circumference, and physical function of elderly women: a cross-sectional study.

OBJECTIVES: To determine whether calf circumference (CC), related to appendicular skeletal muscle mass, can be used as a measure of sarcopenia and is related to physical function. DESIGN: Retrospective analysis of data from 1992 to 1994 of the European Patient Information and Documentation Systems Study. SETTING: Community setting in France. PARTICIPANTS: One thousand four hundred fifty-eight French women aged 70 and older without previous history of hip fracture were recruited from the electoral lists. MEASUREMENTS: Muscular mass was assessed using dual-energy x-ray absorptiometry (DEXA). CC was measured using a tape measure. Anthropometric measurements (height; weight; and waist, hip, and calf circumference), strength markers (grip strength), and self-reported physical function were also determined. Sarcopenia was defined (using DEXA) as appendicular skeletal muscle mass (weight (kg)/height (m2)) less than two standard deviations below the mean of a young female reference group. RESULTS: The prevalence of sarcopenia was 9.5%. CC was correlated with appendicular skeletal muscle mass (r = 0.63). CC under 31 cm was the best clinical indicator of sarcopenia (sensitivity = 44.3%, specificity = 91.4%). CC under 31 cm was associated with disability and self-reported physical function but not sarcopenia (defined using DEXA), independent of age, comorbidity, obesity, income, health behavior, and visual impairment. CONCLUSION: CC cannot be used to predict sarcopenia defined using DEXA but provides valuable information on muscle-related disability and physical function.

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Appendicular lean tissue mass and the prevalence of sarcopenia among healthy women.

Studies indicate that deficient skeletal muscle mass or sarcopenia is a major cause of disability and morbidity among the elderly. In part, due to the lack of generally applicable normal values, there is still insufficient epidemiologic data available on the frequency and severity of sarcopenia in health and under various disease-related conditions. The objectives of the present study were to (1) characterize the age- and menopause-related variations in appendicular lean tissue mass (LTM(A)), (2) provide young-normal means and estimate the age-specific prevalence of sarcopenia among healthy women. A total of 754 healthy women were included in the study of cross-sectional design. LTM(A) was estimated by dual-energy x-ray absorptiometry (DEXA). Physical characteristics and menopausal status were also registered. LTM(A) as well as height showed significant negative correlation with age with Pearson's r values of -0.43 and -0.06, respectively (P <.05). Trend of finding lower mean values with advancing age remained even when LTM(A) was adjusted for height(2) (ht(2)). Menopause did not seem to have any influence on LTM(A). Young-normal means were obtained from 216 premenopausal women aged 18 to 39 years. Prevalence rates of sarcopenia in healthy women were determined with reference to a cut-off line corresponding to LTM(A) or LTM(A)/ht(2) less than young-normal mean 2 SD and were found to be 40.2% and 12.3%, respectively, among the healthy elderly (>70 years of age). Results of the present study provide further evidence that sarcopenia exists even among otherwise healthy women with increasing age-specific prevalence. Further studies are needed (1) to estimate the prevalence of sarcopenia under various health and disease-related conditions with reference to the hereby given cut-off values and (2) to find therapeutic strategies with beneficial effects in conserving skeletal muscle mass.

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Sarcopenia.

Sarcopenia is a term utilized to define the loss of muscle mass and strength that occurs with aging. Sarcopenia is believed to play a major role in the pathogenesis of frailty and functional impairment that occurs with old age. Progressive muscle wasting occurs with aging. The prevalence of clinically significant sarcopenia is estimated to range from 8.8% in young old women to 17.5% in old old men. Persons who are obese and sarcopenic (the "fat frail") have worse outcomes than those who are sarcopenic and non-obese. There is a disproportionate atrophy of type IIa muscle fibers with aging. There is also evidence of an age-related decrease in the synthesis rate of myosin heavy chain proteins, the major anabolic protein. Motor units innervating muscle decline with aging, and there is increased irregularity of muscle unit firing. There are indications that cytokines-especially interleukin-1beta, tumor necrosis factor-alpha, and interleukin-6-play a role in the pathogenesis of sarcopenia. Similarly, the decline in anabolic hormones-namely, testosterone, dehydroepiandrosterone growth hormone, and insulin-like growth factor-I-is also implicated in the sarcopenic process. The role of the physiologic anorexia of aging remains to be determined. Decreased physical activity with aging appears to be the key factor involved in producing sarcopenia. An increased research emphasis on the factors involved in the pathogenesis of sarcopenia is needed.

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Sarcopenia, obesity, and inflammation--results from the Trial of Angiotensin Converting Enzyme Inhibition and Novel Cardiovascular Risk Factors study.

BACKGROUND: Age-related body-composition changes are associated with health-related outcomes in elders. This relation may be explained by inflammation and hemostatic abnormalities. OBJECTIVES: Our objectives were to evaluate the relation between body-composition measures [body mass index (BMI), total fat mass, and appendicular lean mass (aLM)] and C-reactive protein (CRP), interleukin 6 (IL-6), and plasminogen activator inhibitor 1 (PAI-1) and to explore the effect of obesity and sarcopenia on CRP, IL-6, and PAI-1 concentrations. DESIGN: The data are from the Trial of Angiotensin Converting Enzyme Inhibition and Novel Cardiovascular Risk Factors (TRAIN) study baseline visit (n = 286; mean age = 66.0 y). Total fat mass and aLM were assessed with a dual-energy X-ray absorptiometry scan. Linear regressions were performed between body-composition measures and CRP, IL-6, or PAI-1 concentrations. The effect of sarcopenia and obesity (defined as the percentage of fat mass) on CRP, IL-6, and PAI-1 concentrations was evaluated with the use of analyses of covariance. RESULTS: CRP and IL-6 were positively associated with both BMI [beta = 0.027 (P = 0.03) and beta = 0.048 (P < 0.001), respectively] and total fat mass [beta = 0.049 (P < 0.001) and beta = 0.055 (P < 0.001), respectively] and were inversely associated with fat-adjusted aLM [beta = -0.629 (P = 0.002) and beta = -0.467 (P = 0.02), respectively]. PAI-1 was positively associated with both BMI (beta = 0.038, P = 0.005) and total fat mass (beta = 0.032, P = 0.007). No significant interaction was found between either obesity or sarcopenia and CRP, IL-6, and PAI-1 concentrations. Obesity remained significantly associated with high CRP and IL-6 concentrations after adjustments for sarcopenia. CONCLUSIONS: CRP and IL-6 are positively associated with total fat mass and negatively associated with aLM. Obesity-associated inflammation may play an important role in the age-related process that leads to sarcopenia. The relation of inflammation with sarcopenia was not independent of any of the considered obesity indexes.

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Prevalence of sarcopenia and predictors of skeletal muscle mass in nonobese women who are long-term users of estrogen-replacement therapy.

BACKGROUND: Sarcopenia refers to the loss of skeletal muscle mass with age. We have found a prevalence of sarcopenia of 22.6% in older postmenopausal women not receiving estrogen. The objective of this study was to determine the prevalence of sarcopenia in a population of older, nonobese, community-dwelling women who had been long-term users of estrogen replacement therapy (ERT). METHODS: We measured appendicular skeletal muscle mass by dual x-ray absorptiometry (DXA) in 189 women aged 59 to 78 years old who had been using ERT for at least 2 years (mean +/- SD duration, 12.7 +/- 8.2 years). We defined sarcopenia as an adjusted appendicular skeletal muscle mass (ASM) (mass divided by height squared) more than 2 SDs below the mean for a young healthy reference population. Health and menopause history were obtained. Body mass index (BMI) was calculated, and physical activity and performance were measured using the Physical Activity Scale in the Elderly, the chair rise time, the 6-minute walk, and measures of lower extremity strength and power. Serum estrone, estradiol, testosterone, and sex hormone binding globulin were measured. RESULTS: The prevalence of sarcopenia in nonobese, community-dwelling women who were long-term ERT users was 23.8%. Skeletal muscle mass correlated significantly with BMI, age at the time of starting ERT, hand grip strength, lower extremity strength and power, and testosterone level, but not with estradiol level. In linear regression analysis, BMI, leg press strength, and testosterone level contributed to adjusted ASM, accounting for 48.7% of the variance (p <.001). CONCLUSIONS: Sarcopenia is as common in nonobese women who are long-term ERT users as in community-dwelling women not using ERT, suggesting that ERT does not protect against the muscle loss of aging. BMI, strength, and testosterone level contributed to appendicular skeletal mass in women. These data suggest that interventions to target nutrition, strength training, and testosterone replacement should be further investigated for their role in preventing muscle loss with age.

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Significance of sarcopenia in the elderly.

At the present time, there is only limited understanding of the public health significance of sarcopenia. The well-recognized functional consequences of sarcopenia include gait and balance problems and increased risk for fall. Ultimately, these impairments can lead to the loss of physical functional independence. However, sarcopenia may also contribute to an increased risk for chronic diseases such as diabetes and osteoporosis. Future studies of the pathophysiologic significance of sarcopenia need to consider the contribution(s) of muscle properties (e.g., muscle fiber composition, muscle blood flow, fatigue characteristics, innervation) to alterations in physical performance, metabolism and physiology, and skeletal health. More comprehensive studies on the sequelae of sarcopenia are critical to an accurate assessment of the public health burden that sarcopenia poses to the elderly population.

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Low vitamin D and high parathyroid hormone levels as determinants of loss of muscle strength and muscle mass (sarcopenia): the Longitudinal Aging Study Amsterdam.

The age-related change in hormone concentrations has been hypothesized to play a role in the loss of muscle mass and muscle strength with aging, also called sarcopenia. The aim of this prospective study was to investigate whether low serum 25-hydroxyvitamin D (25-OHD) and high serum PTH concentration were associated with sarcopenia. In men and women aged 65 yr and older, participants of the Longitudinal Aging Study Amsterdam, grip strength (n = 1008) and appendicular skeletal muscle mass (n = 331, using dual-energy x-ray absorptiometry) were measured in 1995-1996 and after a 3-yr follow-up. Sarcopenia was defined as the lowest sex-specific 15th percentile of the cohort, translating into a loss of grip strength greater than 40% or a loss of muscle mass greater than 3%. After adjustment for physical activity level, season of data collection, serum creatinine concentration, chronic disease, smoking, and body mass index, persons with low (<25 nmol/liter) baseline 25-OHD levels were 2.57 (95% confidence interval 1.40-4.70, based on grip strength) and 2.14 (0.73-6.33, based on muscle mass) times more likely to experience sarcopenia, compared with those with high (>50 nmol/liter) levels. High PTH levels (>or=4.0 pmol/liter) were associated with an increased risk of sarcopenia, compared with low PTH (<3.0 pmol/liter): odds ratio = 1.71 (1.07-2.73) based on grip strength, odds ratio = 2.35 (1.05-5.28) based on muscle mass. The associations were similar in men and women. The results of this prospective, population-based study show that lower 25-OHD and higher PTH levels increase the risk of sarcopenia in older men and women.

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Sarcopenia: a major modifiable cause of frailty in the elderly.

Sarcopenia is the loss of muscle mass and strength that occurs with aging. It is a consequence of normal aging, and does not require a disease to occur, although muscle loss can be accelerated by chronic illness. Sarcopenia is a major cause of disability and frailty in the elderly. There are many candidate mechanisms leading to sarcopenia, including age-related declines in alpha-motor neurons, growth hormone production, sex steroid levels, and physical activity. In addition, fat gain, increased production of catabolic cytokines, and inadequate intake of dietary energy and protein are also potentially important causes of sarcopenia. The relative contribution of each of these factors is not yet clear. Sarcopenia can be reversed with high-intensity progressive resistance exercise, which can probably also slow its development. A major challenge in preventing an epidemic of sarcopenia-induced frailty in the future is developing public health interventions that deliver an anabolic stimulus to the muscle of elderly adults on a mass scale.

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Strength training for the prevention and treatment of sarcopenia.

There is a progressive loss of muscle strength, muscle mass and muscle quality with advanced age, which results in a condition known as sarcopenia. In this review, the authors outline the magnitude of these losses, their functional consequences, and the efficacy of strength training (ST) as an intervention strategy for delaying, preventing or reversing the effects of sarcopenia. The question of whether sex differences and genetics influence the effects of sarcopenia and responses to ST are also discussed. Although many potential mechanisms for sarcopenia exist, their specific contributions are still unknown. Nevertheless, proposed mechanisms of sarcopenia are outlined and, where information is available, we examine the effects of ST on these potential mechanisms, which include neurogenic factors, anabolic hormones, protein synthesis, gene expression, muscle morphology, and muscle regeneration. Finally, the potential impact of genetics in the muscle response to both sarcopenia and ST is discussed. The evidence presented suggests that ST is an effective intervention for improving strength, muscle mass and muscle quality and delaying the onset of physical disability in the elderly. However, sex differences and genetic factors may play an important role in determining the muscular response to aging and ST.

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Mechanism of Qigu capsule as a treatment for sarcopenia based on network pharmacology and experimental validation.

OBJECTIVE: To explore the potential molecular mechanism of Qigu capsule (&#xff0c;QGC) in the treatment of sarcopenia through network pharmacology and to verify it experimentally. METHODS: The active compounds of QGC and common targets between QGC and sarcopenia were screened from databases. Then the herbs-compounds-targets network, and protein-protein interaction (PPI) network was constructed. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed by R software. Next, we used a dexamethasone-induced sarcopenia mouse model to evaluate the anti-sarcopenic mechanism of QGC. RESULTS: A total of 57 common targets of QGC and sarcopenia were obtained. Based on the enrichment analysis of GO and KEGG, we took the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway as a key target to explore the mechanism of QGC on sarcopenia. Animal experiments showed that QGC could increase muscle strength and inhibit muscle fiber atrophy. In the model group, the expression of muscle ring finger-1 and Atrogin-1 were increased, while myosin heavy chain was decreased, QGC treatment reversed these changes. Moreover, compared with the model group, the expressions of p-PI3K, p-Akt, p-mammalian target of rapamycin and p-Forkhead box O3 in the QGC group were all upregulated. CONCLUSION: QGC exerts an anti-sarcopenic effect by activating PI3K/Akt signaling pathway to regulate skeletal muscle protein metabolism.

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Effects of digital health-based exercise interventions on older adults with sarcopenia: Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Sarcopenia, the progressive loss of muscle mass and function, impairs independence in older adults. Digital health exercise interventions are scalable solutions for older adults with sarcopenia. This systematic review and meta-analysis aimed to synthesize the evidence on their efficacy in populations with clinically diagnosed sarcopenia and identify influential intervention characteristics associated with treatment outcomes. METHODS: We systematically searched PubMed, EMBASE, Web of Science, Cochrane Library, CINAHL, CNKI, and Wanfang on May 20, 2026, with no date restrictions. We included randomized controlled trials involving adults aged &#x2265;60 with sarcopenia receiving digital exercise interventions. Two reviewers independently screened studies, extracted data, and assessed risk of bias; analyses were performed using R and Review Manager. RESULTS: Fourteen trials (n&#xa0;=&#xa0;927) were included. Digital interventions showed potential improvements in muscle mass (MD&#xa0;=&#xa0;0.25, 95%CI:0.03-0.46, 95% PI:-0.36 to 0.85), muscle strength (MD&#xa0;=&#xa0;2.14, 95% CI:1.18-3.11, P&#xa0;<&#xa0;0.001), balance ability (SMD&#xa0;=&#xa0;0.31, 95% CI:0.12-0.51, P&#xa0;=&#xa0;0.001), walking performance (SMD&#xa0;=&#xa0;0.55, 95% CI:0.21-0.89, 95% PI:-0.70 to 1.79), and physical function (SMD&#xa0;=&#xa0;0.89, 95% CI:0.08-1.71, 95% PI:-2.33 to 4.12), but not quality of life (SMD&#xa0;=&#xa0;0.08, 95% CI:-0.19 to 0.35, P&#xa0;=&#xa0;0.53). Exploratory subgroup analyses suggested that factors such as supervision, program duration, and measurement tools may influence outcomes; however, formal tests for subgroup differences were generally non-significant, and consistent patterns across all metrics were not observed. CONCLUSION: Digital exercise interventions show potential for managing sarcopenia in older adults, though the very low to moderate certainty of evidence indicates that true effects may differ substantially from observed estimates. This review explores potential roles of intervention design, supervision, and multimodal delivery. Future research should adopt rigorous designs and longer follow-up to validate results and enhance clinical application. TRIAL REGISTRATION: PROSPERO CRD420251135174.

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Genome-wide association study of sarcopenia index reveals sex-stratified genetic architecture.

BACKGROUND: The sarcopenia index (SI), defined as the ratio of serum creatinine to cystatin C, is a proposed biomarker of muscle mass and sarcopenia, yet its genomic basis and genetic architecture remain largely unexplored. METHODS: We performed combined-sex and sex-stratified genome-wide association studies of SI in the UK Biobank. We examined the overlap between SI-associated loci and loci previously reported for sarcopenia-related traits. We assessed sexually dimorphic effects and gene-sex interactions, performed fine-mapping, and conducted credible gene prioritization, motif and transcription factor binding enrichment, gene-set enrichment, linkage disequilibrium score regression, and cross-phenotype colocalization. RESULTS: We identified 774 unique independent SI-associated loci across all analyses, with 747 detected in the combined-sex GWAS, 283 in the male-stratified GWAS, and 311 in the female-stratified GWAS; 367 of these loci had not been previously reported for conventional sarcopenia-related traits. Sex-stratified analyses highlighted the rs1145093-chr15q21.1-GATM region, where CARMA identified sex-differentiated causal variants. We prioritized 17 male-biased and 11 female-biased credible genes. Enrichment analyses implicated androgen receptor and GATA4 in males, and ESR1 and MYOD1 in females. Enrichment revealed shared pathways involving inflammation, cellular stress, and aging-related processes. LDSC showed inverse genetic correlations between SI and heart failure (rg&#x2009;=&#x2009;-0.19, p&#x2009;=&#x2009;2.30&#x2009;&#xd7;&#x2009;10- 9) and metabolic syndrome (rg&#x2009;=&#x2009;-0.12, p&#x2009;=&#x2009;8.49&#x2009;&#xd7;&#x2009;10- 8), and a positive correlation with chronic kidney disease. Compared with female SI, male SI exhibited two additional loci showing colocalization with four metabolic traits. CONCLUSIONS: These findings clarify the genetic architecture of SI and reveal sex-dependent mechanisms underlying sarcopenia, supporting precision risk assessment and targeted interventions.

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An insight into the causal relationship between sarcopenia-related traits and venous thromboembolism: A mendelian randomization study.

BACKGROUND: As a geriatric syndrome, sarcopenia has a high prevalence in the old population and represents an impaired state of health with adverse health outcomes. A strong clinical interest in its relationship with venous thromboembolism (VTE), which is a complex trait disease with a heterogeneous annual incidence rate in different countries, has emerged. The relationship between sarcopenia and venous thromboembolism has been reported in observational studies but the causality from sarcopenia to VTE remained unclarified. We aimed to assess the causal effect of sarcopenia on the risk of VTE with the two-sample Mendelian randomization (MR) method. METHODS: Two sets of single-nucleotide polymorphisms (SNPs), derived from two published genome-wide association study (GWAS) meta-analyses and genetically indexing muscle weakness and lean muscle mass separately, were pooled into inverse variance weighted (IVW), weighted median and MR-Egger analyses. RESULTS: No evidence was found for the causal effect of genetically predicted muscle weakness (IVW: OR = 0.90, 95% CI = 0.76-1.06, p = 0.217), whole body lean mass (IVW: OR = 1.01, 95% CI = 0.87-1.17, p = 0.881) and appendicular lean mass (IVW: OR = 1.13, 95% CI = 0.82-1.57, p = 0.445) on the risk of VTE. However, both genetically predicted whole-body lean mass and appendicular lean mass can causally influence diabetes mellitus (IVW of whole-body lean mass: OR = 0.87, 95% CI = 0.78-0.96, p = 0.008; IVW of appendicular lean mass: OR = 0.71, 95% CI = 0.54-0.94, p = 0.014) and hypertension (IVW of whole-body lean mass: OR = 0.92, 95% CI = 0.87-0.98, p = 0.007; IVW of appendicular lean mass: OR = 0.84, 95% CI = 0.73-0.96, p = 0.013). CONCLUSIONS: Genetically predicted sarcopenia does not causally influence VTE directly, but it might still have an indirect effect on VTE incidence via diabetes mellitus and hypertension.

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Sarcopenia in the Caenorhabditis elegans pharynx correlates with muscle contraction rate over lifespan.

In muscles, sarcopenia, the loss of muscle mass, is the major cause of aging-related functional decline and frailty. Several factors are correlated with sarcopenia during aging, including contraction-related cellular injury, oxidative stress, endocrine changes and reduced regenerative potential. However the involvement of these factors has not been experimentally investigated. Here, we report that contraction-related injury may significantly promote the progression of sarcopenia in the pharynx of the nematode, Caenorhabditis elegans, a model of aging in non-regenerative tissues. Both functional and structural declines in the pharynx during aging were significantly delayed in mutants with reduced muscle contraction rates. We also examined the role of bacteria in pharynx muscle decline during aging, as previous studies reported that antimicrobial treatments could extend C. elegans lifespan. Although microbial infection may have enhanced functional decline in the pharynx during aging, it was not the sole cause of decreased pumping rates in old animals. This study identifies contraction-related injury as a factor affecting the initiation and progression of sarcopenia during aging. Further, characterization of the specific types of damage induced by muscle contraction will be helpful for understanding the underlying causes of sarcopenia.

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Role of endocrine-immune dysregulation in osteoporosis, sarcopenia, frailty and fracture risk.

Osteoporosis, a key predictor of hip fractures can be treated using a variety of safe and effective interventions. Nevertheless, optimally effective strategies for the prevention of hip fractures must also incorporate efforts to address a broad range of other potentially reversible factors. Hyperthyroidism, anticonvulsants, caffeine and smoking may decrease bone mass and increase fracture risk at any age. In older individuals it is important to also consider additional risk factors, including long-acting benzodiazepines, poor vision and sarcopenia. The presence of sarcopenia, an age-related decline in muscle bulk and quality enhances the risk of frailty and possibly also hip fracture, particularly if associated with diminished functional mobility, lower quadriceps strength and poor balance or body sway. In this review we examine evidence which indicates the presence of endocrine-immune dysregulation in both osteoporosis and sarcopenia. Post-menopausal declines in serum estrogen and androgen levels contribute to increases in local bone levels of cytoclastic cytokines, followed by increased osteoclastogenesis and bone loss. Similarly, the presence of decreased gonadal hormones and IGF-1, combined with unusually high peripheral levels of cytokines, inflammatory mediators and coagulation markers all enhance the risk of sarcopenia and frailty. We propose that a translational research approach which emphasizes common pathophysiologic mechanisms in osteoporosis and sarcopenia could accelerate the speed of discovery of effective strategies for both frailty and hip fracture prevention.

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Prevalence of sarcopenia and predictors of skeletal muscle mass in healthy, older men and women.

BACKGROUND: Sarcopenia refers to the loss of skeletal muscle mass with age. The objective of this study was to determine the prevalence of sarcopenia in a population of older, community-dwelling research volunteers. METHODS: Appendicular skeletal muscle mass was measured by dual x-ray absorptiometry in 195 women aged 64 to 93 years and 142 men aged 64 to 92 years. We defined sarcopenia as appendicular skeletal muscle mass/height(2) (square meters) less than 2 standard deviations below the mean for young, healthy reference populations. We used two different reference populations and compared prevalence in our population to that reported in previous studies. Body mass index (BMI) was calculated and physical activity and performance were measured with the Physical Activity Scale for the Elderly, the Short Physical Performance Battery, and the Physical Performance Test. We measured health-related quality of life by using the SF-36 general health survey. Serum estrone, estradiol, sex hormone-binding globulin, parathyroid hormone, and 25-hydroxy vitamin D were measured in all participants and bioavailable testosterone was measured only in men. Leg press strength and leg press power were determined in men. RESULTS: The prevalence of sarcopenia in our cohort was 22.6% in women and 26.8% in men. A subgroup analysis of women and men 80 years or older revealed prevalence rates of 31.0% and 52.9%, respectively. In women, skeletal muscle mass correlated significantly with BMI and levels of serum estrone, estradiol, and 25-hydroxy vitamin D; in men, it correlated significantly with BMI, single leg stance time, leg press strength, leg press power, SF-36 general health score, Physical Performance Test total score, and bioavailable testosterone levels. With the use of linear regression analysis, BMI was the only predictor of appendicular skeletal muscle mass in women, accounting for 47.9% of the variance (p <.05). In men, BMI accounted for 50.1%, mean strength accounted for 10.3%, mean power accounted for 4.1%, and bioavailable testosterone accounted for 2.6% of the variance in appendicular skeletal muscle mass (p <.05). CONCLUSIONS: Sarcopenia is common in adults over the age of 65 years and increases with age. BMI is a strong predictor of skeletal muscle mass in women and men. Strength, power, and bioavailable testosterone are further contributors in men. These data suggest that interventions to target nutrition, strength training, and testosterone replacement therapy should be further investigated for their role in preventing muscle loss with age.

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