Association between interleukin-6 and lower extremity function after hip fracture--the role of muscle mass and strength

OBJECTIVES: To examine whether an effect on muscle mass or strength explains the association between interleukin-6 (IL-6) and lower extremity function in the year after hip fracture.
DESIGN: Analysis of data from a longitudinal cohort study.
SETTING: Two Baltimore-area hospitals.
PARTICIPANTS: Community-dwelling women aged 65 and older admitted to one of two hospitals in Baltimore with a new, nonpathological fracture of the proximal femur between 1992 and 1995.
MEASUREMENTS: At 2, 6, and 12 months postfracture, serum IL-6, appendicular lean muscle mass (aLM), and grip strength were measured, and the Lower Extremity Gain Scale (LEGS), a summary measure of performance of nine lower extremity tasks was calculated. Generalized estimating equations were used to model the longitudinal relationship between IL-6 tertile and LEGS. Whether muscle mass or strength explained the relationship between IL-6 and LEGS was examined by adding measures of aLM, grip strength, or both into the model.
RESULTS: Subjects in the lowest IL-6 group performed better on the LEGS than those in the highest tertile by 4.51 (95% confidence interval (CI)=1.50–7.52) points at 12 months postfracture. Adjusting for aLM and grip strength, this difference was 4.28 points (95% CI=1.14–7.43) and 3.81 points (95% CI=0.63–7.00), respectively. Adjusting for both aLM and grip strength, the mean difference in LEGS score was 3.88 points (95% CI=0.63–7.13).
CONCLUSION: In older women, after hip fracture, reduced muscle strength, rather than reduced muscle mass, better explains the poorer recovery of lower extremity function observed with higher levels of the inflammatory marker IL-6.     

Relationship between grip strength and global muscle strength in community-dwelling older people

There are still conflicting results regarding the association between grip and global muscle strength in older people. Therefore, the objective of the present study was to determine the association between grip strength and global muscle strength, as well as between grip strength and individual trunk, hip, knee and ankle muscle strengths.MethodsGrip strength was assessed using a manual dynamometer, and trunk, hip, knee and ankle muscle strength with an isokinetic dynamometer, in order to obtain the global muscle strength variable, in 150 older men and women from the community. The association between grip and global muscle strength and between grip strength and the strength of each muscle group was determined through the Pearson correlation test, followed by multivariate linear regression adjusted for sex, age, body mass index, level of physical activity and number of comorbidities.ResultsA positive significant association was found between grip strength and global muscle strength in older people (r = 0.690; β = 10.07; p < 0.001; R² = 0.604), even after adjustment. There was also a low to moderate association between all the muscle groups and grip strength. However, when the model was adjusted, the relationship between grip strength and ankle dorsiflexor peak torque lost significance (p = 0.924).ConclusionGrip strength can represent global muscle strength in younger older people in the community, even when confounding variables are considered in the statistical model. However, grip strength does not eliminate the need for specific assessment of different muscle groups, when indicated.     

Skeletal muscle mass and muscle strength in relation to lower-extremity performance in older men and women

OBJECTIVE: Low muscle strength is associated with poorer physical function, but limited empirical evidence is available to prove the relationship between muscle mass and physical function. We tested the hypothesis that persons with lower muscle mass or muscle strength have poorer lower-extremity performance (LEP). DESIGN: A cross-sectional, population-based study. PARTICIPANTS: A cohort of 449 men and women aged 65 years and older living in Amsterdam and its surroundings participating in the second examination (1995-1996) of the Longitudinal Aging Study Amsterdam. MEASUREMENTS: Leg skeletal muscle mass was measured using dual-energy X-ray absorptiometry (DXA). Grip strength was used as an indicator of muscle strength. Timed functional performance tests, including walking and repeated chair stands, were used to assess LEP. RESULTS: After adjustment for body height and age, leg muscle mass was positively associated with LEP in men (regression coefficient 0.178 [95% confidence interval 0.013-0.343], P = .035). In women an inverse association was observed, which became positive after additional adjustment for body mass index (BMI) (0.202 [-0.001-0.405], P = .052). Grip strength was positively associated with LEP in men and women. After additional adjustment for behavioral, physiological, and psychological variables, the associations between leg muscle mass and LEP disappeared, whereas grip strength remained to be independently associated with LEP in men (0.079 [0.042-0.116], P = .0001), with a tendency in women (0.046 [-0.009-0.101], P = .11). Results were similar when quartiles of leg muscle mass or grip strength were used. CONCLUSIONS: These results suggest that low muscle strength, but not low muscle mass, is associated with poor physical function in older men and women. However, prospective studies are needed to investigate the association between loss of muscle mass and physical function.     

Does functional recovery in elderly hip fracture patients differ between patients admitted from long-term care and the community?

BACKGROUND: It is largely unknown whether functional recovery following hip fracture differs between long-term care (LTC) and community-dwelling residents. Our primary purpose was to compare recovery between these patients 6 months following hip fracture, controlling for known prognostic factors. Secondarily, we examined the contribution of residential status, in addition to patient characteristics, to functional recovery. METHODS: We studied a population-based inception cohort of 451 hip fracture patients >/= 65 years old admitted to one Canadian health region hospital between July 1999 and September 2000. Participants completed the Modified Barthel Functional Index (MBI) in hospital and again via telephone interviews 6 months postoperatively. Data were also collected on surgery and rehabilitation timing, length of hospital stay (LOS). and discharge destination. Relative change from prefracture function adjusting for known prognostic factors, and the proportion of participants returning to prefracture function were compared between the LTC and community-dwelling residents. RESULTS: LTC residents (n = 115) were older, with lower function prefracture, more comorbidities, and increased dementia than community-dwelling residents (n = 336). Six months postfracture, 17 (22%) LTC and 180 (71%) community-dwelling residents had regained prefracture function (p <.001). LTC residents had 33% lower (-40.6, -27.2) and community-dwelling residents 11.6% lower (-14.8, -8.4) 6-month MBI scores relative to prefracture scores after risk adjustment. Residential status was significantly associated with risk-adjusted functional recovery (p <.001). Median LOS was 4 days less for LTC than for community-dwelling residents (p <.001). Twelve (10%) LTC and 266 (79%) community-dwelling residents were discharged to inpatient rehabilitation (p <.001). CONCLUSION: Following hip fracture, most LTC residents do not regain prefracture function irrespective of known prognostic factors. Further investigation is needed as to the extent to which personal and environmental characteristics contribute to outcome after hip fracture.     

Bone mineral density, soft tissue body composition, strength, and functioning after hip fracture

BACKGROUND: Although substantial decrements in bone, muscle, and functional ability have been reported to follow the occurrence of hip fracture in elderly women, little is known about the interrelation of these consequences. The authors evaluated the associations among physiologic and functional factors during recovery from hip fracture to determine whether any consistent sequence of events followed and whether markers of functional outcomes could be identified. METHODS: Two hundred five community-dwelling women aged 65 years and older who sustained hip fracture between 1992 and 1995 and were admitted to one of two acute care hospitals in metropolitan Baltimore, Maryland, participated in a 1-year prospective cohort study. Bone mineral density, lean mass, and fat mass were measured by dual-energy X-ray absorptiometry during the hospitalization and 2, 6, and 12 months later. Functional limitations were self-reported and grip strength was measured during interviews at the same time points. Correlation coefficients were calculated for all possible pairs of measures and time points. RESULTS: Losses of femoral neck bone mineral density and lean body mass and gains in fat mass were observed. Grip strength showed early improvement but declined by 1 year to levels close to those seen during hospitalization. Functional outcomes showed minimal correlation with bone or body composition and only moderate correlation with strength. CONCLUSIONS: Physiologic and functional declines follow hip fracture in elderly women. These are largely independent of one another and suggest that interventions to maximize recovery must simultaneously target multiple areas, including bone, muscle, strength, and function.     

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.     

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.     

Low grip strength is associated with bone mineral density and vertebral fracture in women

OBJECTIVES: Grip strength has been reported to be associated with bone mass locally at the forearm and also at distant skeletal sites, including the spine and hip. Less is known about the association between low grip strength and risk of vertebral fracture. The aim of this study was to examine the association between low grip strength, bone mineral density at the hip and spine, and vertebral fracture in middle-aged and elderly European men and women. METHODS: Men and women aged 50 yr and over were recruited for participation in a screening survey of vertebral osteoporosis across Europe. Subjects who agreed to take part had an interviewer-administered questionnaire and lateral spinal radiographs performed. Subjects were assessed also for grip strength using a handgrip dynamometer (range 0-300 mmHg). A subsample of those recruited had bone mineral density measurements performed at the spine and femoral neck. Subjects had repeat lateral spine radiographs performed a mean of 3.8 yr following the baseline survey. Linear regression analysis was used to determine the association between low grip strength and bone mineral density at the hip and spine. Logistic regression was used to determine the association between grip strength and both prevalent and incident vertebral fracture. RESULTS: One thousand two hundred and sixty-five men and 1380 women with data concerning grip strength and bone mineral density were included in the analysis. In women, after age adjustment, compared with those with 'normal' grip, those with 'impaired' (231-299 mmHg) and low grip (<231 mmHg) had significantly lower bone mass at the spine and femoral neck. In men, those with low grip strength had a lower BMD at the spine and hip than those in the normal group. However, because of the small numbers with submaximal grip strength, the confidence intervals around all estimates included zero. Adjustment for body size and levels of physical activity had little effect on the results. In addition, among women, after adjustment for age, body mass index and physical activity levels, compared with those with normal grip, those with low grip strength had an increased risk of developing incident vertebral fracture (odds ratio = 2.67; 95% confidence interval 1.13, 6.30). Further adjustment for spine bone density had little influence on the association (odds ratio = 2.60). CONCLUSIONS: In women, low grip strength is associated with low bone mineral density at both the spine and hip and an increased risk of incident vertebral fracture. These associations cannot be explained by differences in body size or lifestyle.     

Muscle mass, muscle strength, and muscle fat infiltration as predictors of incident mobility limitations in well-functioning older persons

BACKGROUND: Lower muscle mass has been correlated with poor physical function; however, no studies have examined this relationship prospectively. This study aims to investigate whether low muscle mass, low muscle strength, and greater fat infiltration into the muscle predict incident mobility limitation. METHODS: Our study cohort included 3075 well-functioning black and white men and women aged 70-79 years participating in the Health, Aging, and Body Composition study. Participants were followed for 2.5 years. Muscle cross-sectional area and muscle tissue attenuation (a measure of fat infiltration) were measured by computed tomography at the mid-thigh, and knee extensor strength by using a KinCom dynamometer. Incident mobility limitation was defined as two consecutive self-reports of any difficulty walking one-quarter mile or climbing 10 steps. RESULTS: Mobility limitations were developed by 22.3% of the men and by 31.8% of the women. Cox's proportional hazards models, adjusting for demographic, lifestyle, and health factors, showed a hazard ratio of 1.90 [95% confidence interval (CI), 1.27-2.84] in men and 1.68 (95% CI, 1.23-2.31) in women for the lowest compared to the highest quartile of muscle area (p <.01 for trend). Results for muscle strength were 2.02 (95% CI, 1.39-2.94) and 1.91 (95% CI, 1.41-2.58), p <.001 trend, and for muscle attenuation were 1.91 (95% CI, 1.31-2.83) and 1.68 (95% CI, 1.20-2.35), p <.01 for trend. When included in one model, only muscle attenuation and muscle strength independently predicted mobility limitation (p < .05). Among men and women, associations were similar for blacks and whites. CONCLUSION: Lower muscle mass (smaller cross-sectional thigh muscle area), greater fat infiltration into the muscle, and lower knee extensor muscle strength are associated with increased risk of mobility loss in older men and women. The association between low muscle mass and functional decline seems to be a function of underlying muscle strength.     

Insulin resistance and muscle strength in older persons

BACKGROUND: The functional consequences of an age-related insulin resistance (IR) state on muscle functioning are unknown. Because insulin is needed for adequate muscle function, an age-related insulin-resistant state may also be a determining factor. We evaluated the relationship between IR and handgrip muscle strength in men and women from a large population-based study (n = 968). METHODS: The degree of IR was evaluated by the homeostasis model assessment (HOMA) and muscle strength was assessed using handgrip. RESULTS: Simple sex-stratified correlations demonstrated that, in men, body mass index-adjusted handgrip strength correlated positively with physical activity (r = 0.321; p < .001), muscle area (r = 0.420; p < .001), muscle density (r = 0.263; p = .001), plasma albumin (r = 0.156; p = .001), insulin-like growth factor-1 (r = 0.258; p < .001), calcium (r = 0.140; p = .006), and testosterone (r = 0.325; p < .001) concentrations, whereas a negative association was found for age (r = -0.659; p < .001) and myoglobin plasma levels (r = -0.164; p =.001). In women, body mass index-adjusted handgrip strength correlated positively with physical activity (r = 0.280; p < .001), muscle area (r = 0.306; p < .001), muscle density (r = 0.341; p = .001), plasma albumin (r = 0.140; p =.001), and insulin-like growth factor-1 (r = 0.300; p < .001), whereas a negative association was found for age (r = -0.563; p < .001), myoglobin levels (r = -0.164; p = .001), and IR (r = -0.130; p = .04). CONCLUSIONS: Sex-stratified analyses adjusted for multiple confounders showed that the relationship between IR and handgrip strength was found significant in women, whereas it was negligible and not significant in men.     

The association of race, gender, and comorbidity with mortality and function after hip fracture

BACKGROUND: Few studies of hip fracture have large enough samples of men, minorities, and persons with specific comorbidities to examine differences in their mortality and functional outcomes. To address this problem, we combined three cohorts of hip fracture patients to produce a sample of 2692 patients followed for 6 months. Method. Data on mortality, mobility, and other activities of daily living (ADLs) were available from all three cohorts. We used multiple regression to examine the association of race, gender, and comorbidity with 6-month survival and function, controlling for prefracture mobility and ADLs, age, fracture type, cohort, and admission year. RESULTS: The mortality rate at 6 months was 12%: 9% for women and 19% for men. Whites and women were more likely than were nonwhites and men to survive to 6 months, after adjusting for age, comorbidities, and prefracture mobility and function. Whites were more likely than were nonwhites to walk independently or with help at 6 months compared to not walking, after adjusting for age, comorbidities, and prefracture mobility and function. Dementia had a negative impact on survival, mobility, and ADLs at 6 months. The odds of survival to 6 months were significantly lower for people with chronic obstructive pulmonary disease (COPD), congestive heart failure (CHF), and/or cancer. Parkinson's disease and stroke had negative impacts on mobility and ADLs, respectively, among survivors at 6 months. CONCLUSIONS: The finding of higher mortality and worse mobility for nonwhite patients with hip fractures highlights the need for more research on race/ethnicity disparities in hip fracture care.     

More than half of hip fracture patients do not regain mobility in the first postoperative year

Aim: To measure functional recovery and determine risk factors for failure to return to the prefracture level of mobility of hip fracture patients 1 year postoperatively. Methods: A prospective cohort follow‐up study of 390 hip fracture patients aged 65 years and older was carried out. Patients were stratified in categories based on prefracture mobility: mobile without aid, with aid in‐ and outdoors, or only mobile indoors. Immobile patients were excluded. Risk factors for not regaining prefracture mobility were identified. Results: Nearly half of all patients regained their prefracture level of mobility after 1 year. Mobile patients without an aid were less likely to return to their prefracture mobility level compared with patients who were mobile with aid or mobile indoors. After 1 year, 18.7% of all patients had become immobile. Most important independent risk factors for failure to return to the prefracture level of mobility were a limited prefracture level of activities of daily living and a delirium during admission. Conclusions: The risk not to regain prefracture mobility is highest in mobile patients without an aid. The risk of becoming immobile is higher in those having a lower prefracture mobility. Activities of daily living dependence and delirium were the main risk factors for not regaining mobility. Geriatr Gerontol Int 2013; 13: 334–341 .     

Low plasma carotenoids and skeletal muscle strength decline over 6 years

BACKGROUND: Higher intake of fruits and vegetables appears to protect against inflammation, poor physical performance, and disability, but its relationship with muscle strength is unclear. We examined the association between total plasma carotenoids, an indicator of fruit and vegetable intake, and changes in muscle strength over a 6-year follow-up in the participants aged 65 years and older in the InCHIANTI study, a population-based study in Tuscany, Italy. METHODS: Plasma carotenoids were measured at enrollment (1998-2000). Hip, knee, and grip strength were measured at enrollment and 6 years later (2004-2006) in 628 of the 948 participants evaluated at baseline. Poor muscle strength was defined as the lowest sex-specific quartile of hip, knee, and grip strength at enrollment. The main outcome was poor muscle strength at the 6-year follow-up visit among those participants originally in the upper three quartiles of strength at enrollment. RESULTS: Overall, 24.9% (110/441), 25.0% (111/444), and 24.9% (118/474) participants developed poor hip, knee, and grip strength, respectively. After adjusting for potential confounders, participants in the lowest versus the highest quartile of total plasma carotenoids at enrollment were at higher risk of developing poor hip (odds ratio [OR] = 3.01, 95% CI, 1.43-6.31, p =.004), knee (OR = 2.89, 95% CI, 1.38-6.02, p =.005), and grip (OR = 1.88, 95% CI, 0.93-3.56, p =.07) muscle strength at the 6-year follow-up visit. CONCLUSION: These findings suggest that older community-dwelling adults with lower plasma carotenoids levels, a marker of poor fruit and vegetable intake, are at a higher risk of decline in skeletal muscle strength over time.     

Relationship between swallowing muscles and trunk muscle mass in healthy elderly individuals: A cross-sectional study

Background and objectiveA decrease of swallowing muscle strength causes dysphagia, and a relationship between swallowing muscle strength and appendicular muscle mass has been reported. Moreover, the effect of trunk retention function on swallowing function has been clinically recognized. However, the relationship between trunk muscle mass and swallowing muscle strength is unclear. We aimed to clarify the association between these variables in elderly individuals.MethodsSubjects were 118 healthy community-dwelling individuals aged ≥65 years (men: 37, women: 81). We measured total muscle mass, grip strength, jaw-opening force, tongue pressure, cross-sectional area (CSA) of the geniohyoid muscle, and tongue muscle thickness. The appendicular skeletal muscle mass index (ASMI) and trunk muscle mass index (TMI) were calculated based on the appendicular skeletal muscle mass and trunk muscle mass, and corrected by height squared. Multiple regression analysis was performed with jaw-opening force and tongue pressure as dependent variables and with age, sex, grip strength, ASMI, TMI, CSA of the geniohyoid muscle, and tongue muscle thickness as independent variables.ResultsSignificant explanatory factors for jaw-opening force were sex (p = 0.002) and TMI (p = 0.003). Significant explanatory factors for tongue pressure were aging (p = 0.001), tongue muscle thickness (p = 0.027), and TMI (p = 0.033).ConclusionsUntil now, the relationship between swallowing muscles and whole body muscle mass has been reported using ASMI as the indicator of whole body muscle mass. This study suggests that TMI may be used as a highly relevant indicator of swallowing muscles rather than ASMI.     

The role of muscle loss in the age-related decline of grip strength: cross-sectional and longitudinal perspectives

The decline of strength with age has often been attributed to declining muscle mass in older subjects. To investigate factors which might influence changes in strength across the life span, grip strength and muscle mass (as estimated by creatinine excretion and forearm circumference) were measured in 847 healthy volunteers, aged 20-100 years, from the Baltimore Longitudinal Study of Aging. Cross-sectional and longitudinal results concur that grip strength increases into the thirties and declines at an accelerating rate after age 40. However, the grip strength of 48% of subjects less than 40 years old, 29% of individuals 40-59 years old, and 15% of subjects older than 60 did not decline during the average 9-year follow-up. Grip strength is strongly correlated with muscle mass (r = .60, p less than .0001). However, using multiple regression analysis, grip strength is more strongly correlated with age (partial r2 = .38) than muscle mass (partial r2 = .16). Additionally, a residuals analysis demonstrates that younger subjects are stronger and older subjects are weaker than one would predict based on their muscular size. Thus, while strength losses are partially explained by declining muscle mass, there remain other yet undetermined factors beyond declining muscle mass to explain some of the loss of strength seen with aging.     

The impact of body composition,pain and resilience on physical activity,physical function and physical performance at 2 months post hip fracture

The purpose of this study was to test a model of the factors influencing physical activity, physical function and physical performance at 2 months post hip fracture and compare model fit between men and women. Age, cognitive status, comorbidities, pain, resilience, bone mineral density, total body lean mass, total body fat and grip strength were hypothesized to be directly and/or indirectly related to physical activity, physical function and physical performance. This analysis used data from the seventh Baltimore Hip Studies (BHS-7), a prospective cohort study that included 258 community-dwelling participants, 125 (48%) men and 133 (52%) women, hospitalized for treatment of a hip fracture; survey and objective data were obtained at 2 months post hip fracture. In addition to age, sex and comorbidities (modified Charlson scale), data collection included body composition from dual-energy x-ray absorptiometry (DXA) scans, grip strength, and physical activity, function and performance based on the Yale Physical Activity Survey, the Short Physical Performance Battery and the Lower Extremity Gain Scale. Age, cognition, and comorbidities were not significantly associated with resilience; and, resilience was not associated with pain. In addition, bone mineral density was not associated with physical activity, physical performance or physical function. Total lean body mass, resilience and pain were associated with physical activity, physical function and physical performance in women, but were not consistently associated with physical and functional outcomes in men. Future research should consider evaluation of muscle quality and additional psychosocial factors (e.g., depression, social supports) in model testing.     

Relationship of interleukin-6 and tumor necrosis factor-alpha with muscle mass and muscle strength in elderly men and women: the Health ABC Study

BACKGROUND: A decline in muscle mass and muscle strength characterizes normal aging. As clinical and animal studies show a relationship between higher cytokine levels and low muscle mass, the aim of this study was to investigate whether markers of inflammation are associated with muscle mass and strength in well-functioning elderly persons. METHODS: We used baseline data (1997-1998) of the Health, Aging, and Body Composition (Health ABC) Study on 3075 black and white men and women aged 70-79 years. Midthigh muscle cross-sectional area (computed tomography), appendicular muscle mass (dual-energy x-ray absorptiometry), isokinetic knee extensor strength (KinCom), and isometric grip strength were measured. Plasma levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) were assessed by enzyme-linked immunosorbent assay (ELISA). RESULTS: Higher cytokine levels were generally associated with lower muscle mass and lower muscle strength. The most consistent relationship across the gender and race groups was observed for IL-6 and grip strength: per SD increase in IL-6, grip strength was 1.1 to 2.4 kg lower (p <.05) after adjustment for age, clinic site, health status, medications, physical activity, smoking, height, and body fat. An overall measure of elevated cytokine level was created by combining the levels of IL-6 and TNF-alpha. With the exception of white men, elderly persons having high levels of IL-6 (>1.80 pg/ml) as well as high levels of TNF-alpha (>3.20 pg/ml) had a smaller muscle area, less appendicular muscle mass, a lower knee extensor strength, and a lower grip strength compared to those with low levels of both cytokines. CONCLUSIONS: Higher plasma concentrations of IL-6 and TNF-alpha are associated with lower muscle mass and lower muscle strength in well-functioning older men and women. Higher cytokine levels, as often observed in healthy older persons, may contribute to the loss of muscle mass and strength that accompanies aging.     

Musculoskeletal effects of the recombinant human IGF-I/IGF binding protein-3 complex in osteoporotic patients with proximal femoral fracture: a double-blind, placebo-controlled pilot study

The administration of recombinant human IGF-I complexed with its predominant binding protein IGF binding protein-3 (rhIGF-I/IGFBP-3) may allow the safe administration of higher doses of IGF-I than can be accomplished with rhIGF-I alone. The aim of this randomized, double-blind, placebo- controlled pilot study was to evaluate the short-term safety and musculoskeletal effects of rhIGF-I/IGFBP-3 in older women (aged 65-90 yr) with recent hip fracture. Within 72 h after the event, 30 patients received continuous administration of either placebo (n = 10), 0.5 mg/kg.d rhIGF-I/IGFBP-3 (n = 9), or 1 mg/kg.d rhIGF-I/IGFBP-3 (n = 11). Treatment was administered by sc infusion through a portable mini-pump for a total of 8 wk after hip fracture surgery, with patient follow-up to 6 months after surgery. Efficacy evaluations included a contralateral hip bone density determination, markers of bone turnover (including serum osteocalcin and urinary excretion of N-telopeptide), grip strength, and tests of functional ability. During the administration of rhIGF-I/IGFBP-3, mean serum levels of IGF-I significantly (P < 0.001) increased from 83 ng/ml to 289 ng/ml (0.5 mg/kg.d) and 393 ng/ml (1 mg/kg.d), respectively. Both doses were well tolerated, and no hypoglycemia or other therapy-induced side effects were observed. After an initial loss of hip bone density after hip fracture surgery, patients treated with 1 mg/kg.d rhIGF-I/IGFBP-3 regained a substantial portion of their femoral bone mass. At 6 months postfracture (4 months after the 2-month infusion), they showed a statistically not significant decrease from baseline in hip bone density (-2.6%, P = 0.53). Placebo-treated patients, on the other hand, failed to regain lost bone: at 6 months postfracture, bone density in the placebo group had declined by 6.1% (P = 0.04). Additionally, in patients treated with 1.0 mg/kg.d rhIGF-I/IGFBP-3, grip strength had increased from baseline by 11.4% by the end of the study (P = 0.04) whereas patients on placebo lost 11.6% from baseline (P = 0.16). This increase in muscle strength in the high-dose group was associated with a positive effect on functional recovery. We conclude that a 2-month infusion of rhIGF-I/IGFBP-3 in patients with recent hip fracture is feasible, safe, and well tolerated. Analyzing the effects on bone mass, muscle strength, and functional ability, we observed beneficial trends. In the context of a small exploratory study, these findings should be interpreted with caution, but they support the need for future trials to further assess the therapeutic potential of rhIGF-I/IGFBP-3 in elderly subjects with osteoporosis.     

Is leg muscle strength correlated with functional balance and mobility among inpatients in geriatric rehabilitation?

Determinants of functional balance and mobility have rarely been investigated in geriatric wards. This study examined if leg muscle strength correlates to functional balance and mobility among geriatric inpatients. Fifty inpatients, 29 women and 21 men (mean age 79.6 years) were included. Functional balance was assessed with the Berg Balance Scale (BBS) and mobility was assessed with the Physiotherapy Clinical Outcome Variable Scale (COVS). Strength in the leg extension muscles was measured as 1 Repetition Maximum (1RM) in a leg press and strength in the ankle muscles was measured with Medical Research Council grades (MRC, 0-5). The sum scores, and most of the single items, of the BBS and the COVS significantly correlated to 1RM/body weight, ankle dorsiflexion, and plantar flexion. In a stepwise multiple regression, ankle dorsiflexion and 1RM/body weight together accounted for 39% of the variance of the BBS and 41% of the variance of the COVS. Estimated values of the BBS and the COVS can be calculated from the equation. In clinical work, the knowledge about how leg muscle strength associates with balance and mobility may be useful in analyzing underlying causes of reduced balance and mobility function, and in planning rehabilitation programs.     

Delirium is independently associated with poor functional recovery after hip fracture

OBJECTIVE: To evaluate the role of delirium in the natural history of functional recovery after hip fracture surgery, independent of prefracture status. DESIGN: Prospective cohort study. SETTING: Orthopedic surgery service at a large academic tertiary hospital, with follow-up extending into rehabilitation hospitals, nursing homes, and the community. PARTICIPANTS: One hundred twenty-six consenting subjects older than 65 years (mean age 79 +/- 8 years, 79% women) admitted emergently for surgical repair of hip fracture. MEASUREMENTS: Detailed assessment at enrollment to ascertain prefracture status through interviews with the patient and designated proxy and review of the medical record. Interviews included administration of standardized instruments (Activities of Daily Living (ADL) Scale, Blessed Dementia Rating Scale, Delirium Symptom Interview) and assessment of ambulation, and prefracture living situation. Medical comorbidity, the nature of the hip fracture, and the surgical repair were obtained from the medical record. All subjects underwent daily interviews for the duration of the hospitalization, including the Mini-Mental State Examination and Delirium Symptom Interview, and delirium was diagnosed using the Confusion Assessment Methods algorithm. Patients and proxies were recontacted 1 and 6 months after fracture, and underwent interviews similar to those at enrollment to determine death, persistent delirium, decline in ADL function, decline in ambulation, or new nursing home placement. RESULTS: Delirium occurred in 52/126 (41%) of patients, and persisted in 20/52 (39%) at hospital discharge, 15/52 (32%) at 1 month, and 3/52 (6%) at 6 months. Patients aged 80 years or older, and those with prefracture cognitive impairment, ADL functional impairment, and high medical comorbidity were more likely to develop delirium. However, after adjusting for these factors, delirium was still significantly associated with outcomes indicative of poor functional recovery 1 month after hip fracture: ADL decline (odds ratio (OR) = 2.6; 95% confidence interval (95% CI), 1.1- 6.1), decline in ambulation (OR = 2.6; 95% CI, 1.03-6.5), and death or new nursing home placement (OR = 3.0; 95% CI, 1.1-8.4). Patients whose delirium persisted at 1 month had worse outcomes than those whose delirium had resolved. CONCLUSIONS: Delirium is common, persistent, and independently associated with poor functional recovery 1 month after hip fracture even after adjusting for prefracture frailty. Further research is necessary to identify the mechanisms by which delirium contributes to poor functional recovery, and to determine whether interventions designed to prevent or reduce delirium can improve recovery after hip fracture.