Epigenetic Aging and Musculoskeletal Outcomes in a Cohort of Women Living With HIV.

BACKGROUND: The relationship between accelerated epigenetic aging and musculoskeletal outcomes in women with HIV (WWH) has not been studied. METHODS: We measured DNA methylation age using the Infinium MethylationEPIC BeadChip in a cohort from the Women's Interagency HIV Study (n = 190) with measures of bone mineral density (BMD) and physical function. We estimated 6 biomarkers of epigenetic aging-epigenetic age acceleration (EAA), extrinsic EAA, intrinsic EAA, GrimAge, PhenoAge, and DNA methylation-estimated telomere length-and evaluated associations of epigenetic aging measures with BMD and physical function. We also performed epigenome-wide association studies to examine associations of DNA methylation signatures with BMD and physical function. RESULTS: This study included 118 WWH (mean age, 49.7 years; 69% Black) and 72 without HIV (mean age, 48.9 years; 69% Black). WWH had higher EAA (mean ± SD, 1.44 ± 5.36 vs -1.88 ± 5.07; P < .001) and lower DNA methylation-estimated telomere length (7.13 ± 0.31 vs 7.34 ± 0.23, P < .001) than women without HIV. There were no significant associations between accelerated epigenetic aging and BMD. Rather, measures of accelerated epigenetic aging were associated with lower physical function. CONCLUSIONS: Accelerated epigenetic aging was observed in WWH as compared with women without HIV and was associated with lower physical function in both groups.

Pitavastatin is Well-Tolerated with no Detrimental Effects on Physical Function.

BACKGROUND: Little is known about the potential benefits or harms of statins on physical function among people with HIV (PWH). METHODS: REPRIEVE was a double-blind randomized controlled trial evaluating pitavastatin for primary prevention of major adverse cardiovascular events (MACE) in PWH. Time to complete ten chair rises, 4-meter gait speed, grip strength, and a modified short physical performance test were assessed annually for up to 5 years in the ancillary study PREPARE and analyzed using linear mixed models. FINDINGS: Of 602 PWH, 52% were randomized to pitavastatin and 48% to placebo. Median age was 51 years; 18% were female at birth; 2% transgender; 40% Black, and 18% Hispanic. Median PREPARE follow-up was 4.7 (4.3, 5.0) years. Muscle symptoms (grade ≥3 or treatment-limiting) occurred in 5% of both groups. There was no evidence of decline in chair rise rate in either treatment group, and no difference in the pitavastatin group compared to placebo (estimated difference -0.10 [95% CI: -0.30, 0.10] rises/min/year; p=0.31). Small declines over time were observed in other physical function tests in both treatment groups, with no apparent differences between groups. INTERPRETATION: We observed minimal declines in physical function over 5 years of follow-up among middle-aged PWH, with no differences among PWH randomized to pitavastatin compared to placebo. This finding, combined with low prevalence of myalgias, supports the long-term safety of statin therapy on physical function, when used for primary prevention of MACE among PWH.

Exercise in Octogenarians: How Much Is Too Little?

The global population is rapidly aging, with predictions of many more people living beyond 85 years. Age-related physiological adaptations predispose to decrements in physical function and functional capacity, the rate of which can be accelerated by chronic disease and prolonged physical inactivity. Decrements in physical function exacerbate the risk of chronic disease, disability, dependency, and frailty with advancing age. Regular exercise positively influences health status, physical function, and disease risk in adults of all ages. Herein, we review the role of structured exercise training in the oldest old on cardiorespiratory fitness and muscular strength and power, attributes critical for physical function, mobility, and independent living.

Specific dairy foods and risk of frailty in older women: a prospective cohort study.

BACKGROUND: Dairy contains a complex mixture of lipids, proteins, and micronutrients. Whether habitual dairy consumption is associated with health benefits is not well established. Since dairy is high in nutrients that are potentially protective against frailty, the association between dairy products and the risk of frailty is of interest. METHODS: We analyzed data from 85,280 women aged ≥ 60 years participating in the Nurses' Health Study. Consumption of milk, yogurt, and cheese was obtained from repeated food frequency questionnaires administered between 1980 and 2010. Frailty was defined as having at least three of the following five criteria from the FRAIL scale: fatigue, low strength, reduced aerobic capacity, having ≥ 5 chronic illnesses, and a weight loss of ≥ 5%. The occurrence of frailty was assessed every four years from 1992 to 2018. Cox proportional hazard models were used to examine the association between the intake of dairy foods and frailty. RESULTS: During follow-up we identified 15,912 incident cases of frailty. Consumption of milk or yogurt was not associated with the risk of frailty after adjustment for lifestyle factors, medication use, and overall diet quality. Cheese consumption was positively associated with risk of frailty [relative risk (95% confidence interval) for one serving/day increment in consumption: 1.10 (1.05, 1.16)]. Replacing one serving/day of milk, yogurt, or cheese with one serving/day of whole grains, nuts, or legumes was associated with a significant lower risk of frailty, while replacing milk, yogurt, or cheese with red meat or eggs was associated with an increased risk. When milk was replaced with a sugar-sweetened or artificially sweetened beverage, a greater risk of frailty was observed, while replacing milk with orange juice was associated with a lower risk of frailty. CONCLUSIONS: The results suggest that the association between milk, yogurt, and cheese and frailty partly depends on the replacement product. Habitual consumption of milk or yogurt was not associated with risk of frailty, whereas cheese consumption may be associated with an increased risk.

One leg testing in hip and knee osteoarthritis: A comparison with a two-leg oriented functional outcome measure and self-reported functional measures.

OBJECTIVE: To compare the responsiveness of two unilateral lower-limb performance-based tests, the one-leg rise test and the maximal step-up test, with the bilateral 30-second chair-stand test and the self-reported measure of physical function (HOOS/KOOS). Specific aims were to evaluate responsiveness, floor/ceiling effect and association between the instruments. METHOD: Data was included from 111 participants, mean age 61.3 years (8.3), with clinically verified hip or knee osteoarthritis, who reported less than 150 minutes/week of moderate or vigorous intensity physical activity. Responsiveness, how well the instruments captured improvements, was measured as Cohen's standardised mean difference for effect size, and was assessed from baseline to 12 months following a physical activity intervention. Other assessments were floor and ceiling effects, and correlations between tests. RESULTS: The maximal step-up test had an effect size of 0.57 (95% CI 0.37, 0.77), the 30-second chair-stand 0.48 (95% CI 0.29, 0.68) and the one-leg rise test 0.12 (95% CI 0.60, 0.31). The one-leg rise test had a floor effect as 72% of the participants scored zero at baseline and 63% at 12 months. The correlation between performance-based tests and questionnaires was considered to be minor (r = 0.188 to 0.226) (p = 0.018 to 0.048). CONCLUSION: The unilateral maximal step-up test seems more responsive to change in physical function compared to the bilateral 30-second chair-stand test, although the tests did not differ statistically in effect size. The maximal step-up test provides specific information about each leg for the individual and allows for comparison between the legs.

Mesenchymal stem cells for chronic knee pain secondary to osteoarthritis: A systematic review and meta-analysis of randomized trials.

OBJECTIVE: To assess the effectiveness of mesenchymal stem cells (MSCs) for chronic knee pain secondary to osteoarthritis (OA). METHODS: We searched MEDLINE, EMBASE, CINAHL, and Cochrane Central to September 2023 for trials that (1) enrolled patients with chronic pain associated with knee OA, and (2) randomized them to MSC therapy vs. placebo or usual care. We performed random-effects meta-analysis and used Grading of Recommendations, Assessment, Development, and Evaluation to assess the certainty of evidence. RESULTS: We included 16 trials (807 participants). At 3-6 months, MSC therapy probably results in little to no difference in pain relief (weighted mean difference [WMD] -0.74 cm on a 10 cm visual analog scale [VAS], 95% confidence interval [95%CI] -1.16 to -0.33; minimally important difference [MID] 1.5 cm) or physical functioning (WMD 2.23 points on 100-point 36-item Short Form Survey (SF-36) physical functioning subscale, 95%CI -0.97 to 5.43; MID 10-points; both moderate certainty). At 12 months, injection of MSCs probably results in little to no difference in pain (WMD -0.73 cm on a 10 cm VAS, 95%CI -1.69 to 0.24; moderate certainty) and may improve physical functioning (WMD 19.36 points on 100-point SF-36 PF subscale, 95%CI -0.19 to 38.9; low certainty). MSC therapy may increase risk of any adverse events (risk ratio [RR] 2.67, 95%CI 1.19 to 5.99; low certainty) and pain and swelling of the knee joint (RR 1.58, 95%CI 1.04 to 2.38; low certainty). CONCLUSIONS: Intra-articular injection of MSCs for chronic knee pain associated with OA probably provides little to no improvement in pain or physical function.

Sex differences in osteoarthritis prevalence, pain perception, physical function and therapeutics.

OBJECTIVE: Women have a higher prevalence of osteoarthritis (OA) and worse clinical courses than men. However, the underlying factors and therapeutic outcomes of these sex-specific differences are incompletely researched. This review examines the current state of knowledge regarding sex differences in OA prevalence, risk factors, pain severity, functional outcomes, and use and response to therapeutics. METHODS: PubMed database was used with the title keyword combinations "{gender OR sex} AND osteoarthritis" plus additional manual search of the included papers for pertinent references, yielding 212 references. Additional references were added and 343 were reviewed for appropriateness. RESULTS: Globally, women account for 60% of people with osteoarthritis, with a greater difference after age 40. The higher risk for women may be due to differences in joint anatomy, alignment, muscle strength, hormonal influences, obesity, and/or genetics. At the same radiographic severity, women have greater pain severity than men, which may be explained by biologically distinct pain pathways, differential activation of central pain pathways, differences in pain sensitivity, perception, reporting, and coping strategies. Women have greater limitations of physical function and performance than men independent of BMI, OA severity, injury history, and amount of weekly exercise. Women also have greater use of analgesic medications than men but less use of arthroplasty and poorer prognosis after surgical interventions. CONCLUSIONS: The recognition of sex differences in OA manifestations and management could guide tailoring of sex-specific treatment protocols, and analysis of sex as a biological variable in future research would enhance development of precision medicine.

One-year effectiveness of long-term exercise therapy in people with axial spondyloarthritis and severe functional limitations.

OBJECTIVE: To evaluate the effectiveness of long-term, personalized, supervised exercise therapy on functional ability compared with usual care in people with axial spondyloarthritis (axSpA) and severe functional limitations. METHODS: Participants were randomly 1:1 assigned to the intervention(maximal 64 sessions, with 14 additional optional sessions of supervised active exercise therapy(e.g. aerobic and muscle strengthening) with individualized goal-setting, education and self-management regarding physical activity) or usual care(care determined by clinician(s) and participants themselves). Primary end point was the change in the Patient-Specific Complaints activity ranked 1 (PSC1 (0-10)) at 52 weeks. Secondary endpoints were the PSC activities ranked 2 and 3, the Bath Ankylosing Spondylitis Functional Index, 6-min walk test, Patient Reported Outcome Measurement Information System-Physical Function-10 and the Short Form-36 Physical and Mental Component Summary Score (SF-36 PCS and MCS). Statistical comparisons comprised independent student t-tests and linear mixed models, based on intention-to-treat. RESULTS: 214 participants(49% female, age 52 (SD 12) years), were randomized to the intervention (n = 110) or usual care (N = 104) group. In the intervention group 93% started treatment, using on average 40.5 sessions (SD 15.1). At 52 weeks, the difference in change in PSC1 between groups favored the intervention group (mean difference [95% CI]; -1.8 [-2.4 to -1.2]). additionally, all secondary outcomes, except the SF-36 MSC, showed significantly greater improvements in the intervention group with effect sizes ranging from 0.4-0.7. CONCLUSION: Long-term, supervised exercise therapy proved more effective than usual care in improving functional disability and physical quality of life in people with axSpA and severe functional limitations. CLINICAL TRIAL REGISTER NUMBER: Netherlands Trial Register NL8238, included in the International Clinical Trial Registry Platform (ICTRP) (https://trialsearch.who.int/Trial2.aspx?TrialID=NL8238).

Factors associated with physical function among people with systemic sclerosis: a SPIN cohort cross-sectional study.

OBJECTIVES: To compare physical function in systemic sclerosis (SSc, scleroderma) to general population normative data and identify associated factors. METHODS: Scleroderma Patient-centered Intervention Network Cohort participants completed the Physical Function domain of the Patient-Reported Outcomes Measurement Information System Version 2 upon enrolment. Multivariable linear regression was used to assess associations of sociodemographic, lifestyle, and disease-related variables. RESULTS: Among 2385 participants, the mean physical function T-score (43.7, SD = 8.9) was ∼2/3 of a standard deviation (SD) below the US general population (mean = 50, SD = 10). Factors associated in the multivariable analysis included older age (-0.74 points per SD years, 95% CI -0.78 to -1.08), female sex (-1.35, -2.37 to -0.34), fewer years of education (-0.41 points per SD in years, -0.75 to -0.07), being single, divorced, or widowed (-0.76, -1.48 to -0.03), smoking (-3.14, -4.42 to -1.85), alcohol consumption (0.79 points per SD drinks per week, 0.45-1.14), BMI (-1.41 points per SD, -1.75 to -1.07), diffuse subtype (-1.43, -2.23 to -0.62), gastrointestinal involvement (-2.58, -3.53 to -1.62), digital ulcers (-1.96, -2.94 to -0.98), moderate (-1.94, -2.94 to -0.93) and severe (-1.76, -3.24 to -0.28) small joint contractures, moderate (-2.10, -3.44 to -0.76) and severe (-2.54, -4.64 to -0.44) large joint contractures, interstitial lung disease (-1.52, -2.27 to -0.77), pulmonary arterial hypertension (-3.72, -4.91 to -2.52), rheumatoid arthritis (-2.10, -3.64 to -0.56) and idiopathic inflammatory myositis (-2.10, -3.63 to -0.56). CONCLUSION: Physical function is impaired for many individuals with SSc and is associated with multiple disease factors.

A patient centered assessment of the 2016 ACR-EULAR Myositis Response Criteria: evaluating the meaningfulness of response.

OBJECTIVES: The ACR-EULAR Myositis Response Criteria (Total Improvement Score [TIS]) is a composite measure calculated using changes in myositis core set measures. It is unclear if achieving improvement per TIS reflects improvement in any symptoms of myositis patients. In this study, we examined the association between achieving TIS improvement and patient-centered outcome measures (PCOMs). METHODS: Adults with myositis were enrolled in a prospective study with baseline and 6-month visits. Six core set measures were collected at each visit along with the following PCOMs: Fatigue (visual analogue scale [VAS] and short form 36 [SF36]), pain (VAS, SF36), health-related quality of life (SF-36), physical function (PROMIS-physical function, SF36, sit-to-stand, timed up-and-go, and six-min walk) and physical activity (actigraphy). Mann-Whitney U was used to compare PCOMs between improvement groups. Spearman correlation and regression models were used for correlation and association between TIS and PCOMs, respectively. RESULTS: Of 50 patients (six polymyositis, 24 dermatomyositis, 9 necrotizing myopathy, 11 anti-synthetase syndrome) enrolled (mean age: 52, 60% female), 21 patients satisfied the TIS improvement criteria at 6-months. PCOMs including fatigue, pain, quality of life, physical activity and physical function demonstrated significantly greater improvement in patients who had minimal TIS improvement compared with those with no improvement. Greater PCOM improvements were seen with moderate-major TIS improvement. TIS correlated moderately-strongly with most PCOMs. CONCLUSION: Achieving improvement criteria was accompanied by significant clinical improvements in fatigue, pain, health-related quality of life, physical function, and physical activity. These results support the use of TIS as a clinically meaningful metric of improvement.

Patient reported outcome for physical function in idiopathic inflammatory myopathy.

OBJECTIVES: There is an unmet need to develop patient-reported outcomes (PRO) measures for Idiopathic Inflammatory Myopathies (IIM). To investigate the feasibility, compliance, and psychometric properties of NIH's Patient-Reported Outcomes Measurement Information System (PROMIS) physical function-20 (PF-20) in a large U.S. IIM population. METHODS: "Myositis Patient Centered Tele-Research" (My PACER) is a multicentre prospective observational study of IIM patients, competitively recruited through traditional in-person clinic visits (Center-Based Cohort [CBC]), and remotely using smartphone and web-based technology (Tele-Research Cohort [TRC]). The CBC was further randomly divided (1:1 ratio) into a traditional local sub-cohort, and a remote sub-cohort. Data collected included PRO and other patient self-assessments monthly for 6 months. Clinician-reported outcomes were obtained at baseline and 6 months. RESULTS: 120 IIM patients were enrolled (82 TRC/38 CBC, mean age 55 ± 13.4, 75% females, 81% Caucasians), with similar demographics and mean PROMIS PF-20 score between cohorts. The PROMIS PF-20 score was not associated with age, sex or race. The compliance and completion rates were similar between TRC and CBC as well as sub-cohorts. PROMIS PF-20 showed strong test-retest reliability at 1 month. PROMIS PF-20 was significantly associated with all core set measures except extra-muscular global and CK, as well as with most of symptoms, function and physical activity measures. PROMIS PF-20 illustrated concordant change with myositis response criteria and patient assessment, with a large effect size. CONCLUSIONS: PROMIS PF-20 demonstrates favorable psychometric properties including reliability, validity and responsiveness in a large cohort of myositis patients, with similar adherence in local or remotely enrolled patients.

Physical function trajectory after wrist or lower arm fracture in postmenopausal women: results from the Women's Health Initiative Study.

Long-term physical functioning trajectories following distal forearm fracture are unknown. We found that women with versus those without distal forearm fracture were more likely to experience a 5-year decline in physical functioning, independent of initial physical functioning level. This association was most evident among women 80 years and older. INTRODUCTION: Physical functioning trajectory following lower arm or wrist fracture is not well understood. PURPOSE: This study is to evaluate physical functioning trajectory before vs. after lower arm or wrist fracture, stratified by age. METHODS: We performed a nested case-control study of prospective data from the Women's Health Initiative Study (n = 2097 cases with lower arm or wrist fracture, 20,970 controls). Self-reported fractures and the physical functioning subscale of the RAND 36-item Short-Form Health Survey were assessed annually. We examined three physical functioning trajectory groups: stable, improving, and declining. RESULTS: Mean (SD) number of physical functioning measurements was 5.2 (1.5) for cases and 5.0 (1.4) for controls. Declining physical functioning was observed among 20.4% of cases and 16.0% of controls. Compared to women without lower arm or wrist fracture, women with lower arm or wrist fracture were 33% more likely to experience declining physical functioning (adjusted odds ratio [aOR] 1.33 95% confidence interval [CI] 1.19-1.49, reference group stable or improving physical functioning trajectory). Associations varied by age: age ≥ 80 years aOR 1.56 (95% CI 1.29-1.88); age 70-79 years aOR 1.29 (95% CI 1.09-1.52); age < 70 years aOR 1.15 (95% CI 0.86-1.53) (pinteraction = 0.06). Associations between lower arm or wrist fracture and odds of declining physical functioning did not vary by baseline physical functioning or physical activity level. CONCLUSIONS: Women with lower arm or wrist fracture, particularly those aged 80 and older, were more likely to experience declines in physical functioning than women without such fractures, independent of baseline physical functioning level.

Regular physical activity improves physical function and health-related quality of life among middle-aged and older women who suffered a fragility fracture-a population-based cohort.

Fragility fractures are a major problem in our aging society leading to early death and loss of independence for activities of daily living. Physical activity in a long-term follow-up of Portuguese women over 50 years with a fragility fracture was associated with better physical function and quality of life. PURPOSE: To evaluate the long-term impact of physical activity on physical function and health-related quality of life (HRQoL) in women ≥ 50 years old who suffered a fragility fracture. METHODS: We evaluated the association of physical activity with physical function and HRQoL in women ≥ 50 years old who self-reported at least one low-impact fracture ≥ 40 years old from the EpiDoC cohort, a population-based cohort. Self-reported data regarding sociodemographics, clinical, and lifestyle behaviors were collected through a semi-structured questionnaire at baseline during a face-to-face clinical interview. During a long-term follow-up, a phone interview was conducted to evaluate physical activity (using a non-validated scale developed for the EpiDoC study), physical function (Health Assessment Questionnaire), and HRQoL (European Quality of Life - 5 Dimension). Women were divided into three groups according to the frequency of physical activity (non-frequent = 0 times/week, frequent = 1-2 times/week, or very frequent = ≥ 3 times/week). The association of physical activity frequency (non-frequent, frequent, and very frequent) with physical function and HRQoL over time was assessed through linear mixed models considering varying intercepts for each woman. RESULTS: This study followed 323 post-fracture women, during a mean follow-up of 3.9 ± 3.5 years. Frequent (ß = - 0.1419 [- 0.2783, - 0.0064]) and very frequent (ß = - 0.1908 [- 0.2944, - 0.0881]) physical exercise were associated with improvements in physical function relative to non-frequent physical exercise adjusted for BMI, multimorbidity, hospitalizations, alcohol and smoking habits, and the number of fragility fractures at baseline. As for HRQoL, a positive association was found for exercise frequency, specifically frequent (ß = 0.1305 [0.0646, 0.1958]) and very frequent (ß = 0.1354 [0.0856, 0.1859]) suggesting improvements for HRQoL, in this follow-up period. CONCLUSIONS: These findings based on longitudinal data with long-term follow-up suggest that regular physical activity is associated with better function and HRQol among middle-aged and older post-fracture osteoporotic Portuguese women.

Validity of the Musculoskeletal Tumor Society Score for lower extremity in patients with bone sarcoma or giant cell tumour of bone undergoing bone resection and reconstruction surgery in hip and knee.

BACKGROUND: The Musculoskeletal Tumor Society Score (MSTS) is widely used to evaluate functioning following surgery for bone and soft-tissue sarcoma. However, concerns have been raised about its content validity due to the lack of patient involvement during item development. Additionally, literature reports inconsistent results regarding data quality and structural validity. This study aimed to evaluate content, structural and construct validity of the Danish version of the MSTS for lower extremity (MSTS-LE). METHODS: The study included patients from three complete cohorts (n = 87) with bone sarcoma or giant cell tumour of bone who underwent bone resection and reconstruction surgery in hip and knee. Content validity was evaluated by linking MSTS items to frameworks of functioning, core outcome sets and semi-structured interviews. Data quality, internal consistency and factor analysis were used to assess the underlying structure of the MSTS. Construct validity was based on predefined hypotheses of correlation between the MSTS and concurrent measurements. RESULTS: Content validity analysis revealed concerns regarding the MSTS. The MSTS did not sufficiently cover patient-important functions, the item Emotional acceptance could not be linked to the framework of functioning, the items Pain and Emotional acceptance pertained to domains beyond functioning and items' response options did not match items. A two-factor solution emerged, with the items Pain and Emotional acceptance loading highly on a second factor distinct from functioning. Internal consistency and construct validity showed values below accepted levels. CONCLUSION: The Danish MSTS-LE demonstrated inadequate content validity, internal consistency, and construct validity. In addition, our analyses did not support unidimensionality of the MSTS. Consequently, the MSTS-LE is not a simple reflection of the construct of functioning and the interpretation of a sum score is problematic. Clinicians and researcher should exercise caution when relying solely on MSTS scores for assessing lower extremity function. Alternative outcome measurements of functioning should be considered for the evaluation of postoperative function in this patient group.

Nutrition Interventions on Muscle-Related Components of Sarcopenia in Females: A Systematic Review of Randomized Controlled Trials.

Sarcopenia is a skeletal muscle disease categorized by low muscle strength, muscle quantity or quality, and physical performance. Sarcopenia etiology is multifaceted, and while resistance training is widely agreed upon for prevention and treatment, disease progression is also highly related to poor diet. The incidence of sarcopenia appears sex-specific and may be increased in females, which is problematic because dietary quality is often altered later in life, particularly after menopause. Identifying effective nutrition or supplementation interventions could be an important strategy to delay sarcopenia and related comorbidities in this vulnerable population. This systematic review examined randomized controlled trials (RCTs) of nutrition strategies on muscle-related components of sarcopenia in middle-aged and older females. A protocol was registered (PROSPERO CRD42022382943) and a systematic search of MEDLINE and CINAHL was undertaken. RCTs from 2013 to 2023 that assessed nutrition-only interventions on muscle mass, muscle strength, and physical function in female participants were included. Fourteen RCTs were included based on selection criteria. Study designs and interventions were heterogeneous in supplementation type and amount, age, and duration. Six RCTs reported beneficial effects of protein, Vitamin D, Vitamin D and Magnesium (Mg), and fish oil on muscle protein synthesis, muscle strength, and/or muscle function. Eight studies that examined various protein interventions, VitD alone, Mg alone, and dairy derivatives did not demonstrate any effect. Exercise appeared to modulate results in several studies. Nutrition interventions alone are likely to have a limited but positive effect on muscle-related components of sarcopenia in females. Current evidence suggests that a combination of dietary intervention and exercise is likely to be key to preventing and treating sarcopenia in middle aged and older females and there is a need for well-designed nutrition based studies in this population.

Musculoskeletal Health Worsened from Carnitine Supplementation and Not Impacted by a Novel Individualized Treadmill Training Protocol.

INTRODUCTION: Chronic kidney disease (CKD) negatively affects musculoskeletal health, leading to reduced mobility, and quality of life. In healthy populations, carnitine supplementation and aerobic exercise have been reported to improve musculoskeletal health. However, there are inconclusive results regarding their effectiveness and safety in CKD. We hypothesized that carnitine supplementation and individualized treadmill exercise would improve musculoskeletal health in CKD. METHODS: We used a spontaneously progressive CKD rat model (Cy/+ rat) (n = 11-12/gr): (1) Cy/+ (CKD-Ctrl), (2) CKD-carnitine (CKD-Carn), and (3) CKD-treadmill (CKD-TM). Carnitine (250 mg/kg) was injected daily for 10 weeks. Rats in the treadmill group ran 4 days/week on a 5° incline for 10 weeks progressing from 30 min/day for week one to 40 min/day for week two to 50 min/day for the remaining 8 weeks. At 32 weeks of age, we assessed overall cardiopulmonary fitness, muscle function, bone histology and architecture, and kidney function. Data were analyzed by one-way ANOVA with Tukey's multiple comparisons tests. RESULTS: Moderate to severe CKD was confirmed by biochemistries for blood urea nitrogen (mean 43 ± 5 mg/dL CKD-Ctrl), phosphorus (mean 8 ± 1 mg/dL CKD-Ctrl), parathyroid hormone (PTH; mean 625 ± 185 pg/mL CKD-Ctrl), and serum creatinine (mean 1.1 ± 0.2 mg/mL CKD-Ctrl). Carnitine worsened phosphorous (mean 11 ± 3 mg/dL CKD-Carn; p < 0.0001), PTH (mean 1,738 ± 1,233 pg/mL CKD-Carn; p < 0.0001), creatinine (mean 1 ± 0.3 mg/dL CKD-Carn; p < 0.0001), cortical bone thickness (mean 0.5 ± 0.1 mm CKD-Ctrl, 0.4 ± 0.1 mm CKD-Carn; p < 0.05). Treadmill running significantly improves maximal aerobic capacity when compared to CKD-Ctrl (mean 14 ± 2 min CKD-TM, 10 ± 2 min CKD-Ctrl; p < 0.01). CONCLUSION: Carnitine supplementation worsened CKD progression, mineral metabolism biochemistries, and cortical porosity and did not have an impact on physical function. Individualized treadmill running improved maximal aerobic capacity but did not have an impact on CKD progression or bone properties. Future studies should seek to better understand carnitine doses in conditions of compromised renal function to prevent toxicity which may result from elevated carnitine levels and to optimize exercise prescriptions for musculoskeletal health.

Prevalence of Sarcopenia and Its Defining Components in Non-alcoholic Fatty Liver Disease Varies According to the Method of Assessment and Adjustment: Findings from the UK Biobank.

Sarcopenia may increase non-alcoholic fatty liver disease (NAFLD) risk, but prevalence likely varies with different diagnostic criteria. This study examined the prevalence of sarcopenia and its defining components in adults with and without NAFLD and whether it varied by the method of muscle mass assessment [bioelectrical impedance (BIA) versus dual-energy X-ray absorptiometry (DXA)] and adjustment (height2 versus BMI). Adults (n = 7266) in the UK Biobank study (45-79 years) with and without NAFLD diagnosed by MRI, were included. Sarcopenia was defined by the 2018 European Working Group on Sarcopenia in Older People definition, with low appendicular skeletal muscle mass (ASM) assessed by BIA and DXA and adjusted for height2 or BMI. Overall, 21% of participants had NAFLD and the sex-specific prevalence of low muscle strength (3.6-7.2%) and sarcopenia (0.1-1.4%) did not differ by NAFLD status. However, NAFLD was associated with 74% (males) and 370% (females) higher prevalence of low ASM when adjusted for BMI but an 82% (males) to 89% (females) lower prevalence when adjusted for height2 (all P < 0.05). The prevalence of impaired physical function was 40% (males, P = 0.08) to 123% (females, P < 0.001) higher in NAFLD. In middle-aged and older adults, NAFLD was not associated with a higher prevalence of low muscle strength or sarcopenia but was associated with an increased risk of impaired physical function and low muscle mass when adjusted for BMI. These findings support the use of adiposity-based adjustments when assessing low muscle mass and the assessment of physical function in NAFLD.

Skeletal muscle dysfunction with advancing age.

As a result of advances in medical treatments and associated policy over the last century, life expectancy has risen substantially and continues to increase globally. However, the disconnect between lifespan and 'health span' (the length of time spent in a healthy, disease-free state) has also increased, with skeletal muscle being a substantial contributor to this. Biological ageing is accompanied by declines in both skeletal muscle mass and function, termed sarcopenia. The mechanisms underpinning sarcopenia are multifactorial and are known to include marked alterations in muscle protein turnover and adaptations to the neural input to muscle. However, to date, the relative contribution of each factor remains largely unexplored. Specifically, muscle protein synthetic responses to key anabolic stimuli are blunted with advancing age, whilst alterations to neural components, spanning from the motor cortex and motoneuron excitability to the neuromuscular junction, may explain the greater magnitude of function losses when compared with mass. The consequences of these losses can be devastating for individuals, their support networks, and healthcare services; with clear detrimental impacts on both clinical (e.g., mortality, frailty, and post-treatment complications) and societal (e.g., independence maintenance) outcomes. Whether declines in muscle quantity and quality are an inevitable component of ageing remains to be completely understood. Nevertheless, strategies to mitigate these declines are of vital importance to improve the health span of older adults. This review aims to provide an overview of the declines in skeletal muscle mass and function with advancing age, describes the wide-ranging implications of these declines, and finally suggests strategies to mitigate them, including the merits of emerging pharmaceutical agents.

Physical and psychological distress amongst patients undergoing neoadjuvant chemotherapy for advanced ovarian cancer.

OBJECTIVE: This study compares baseline clinical characteristics, physical function testing, and patient-reported outcomes for patients undergoing primary cytoreductive surgery versus neoadjuvant chemotherapy, with the goal of better understanding unique patient needs at diagnosis. METHODS: Patients with suspected advanced stage (IIIC/IV) epithelial ovarian cancer undergoing either primary cytoreductive surgery or neoadjuvant chemotherapy were enrolled in a single-institution, non-randomized prospective behavioral intervention trial of prehabilitation. Baseline clinical characteristics were abstracted. Physical function was evaluated using the Short Physical Performance Battery, Fried Frailty Index, gait speed, and grip strength. Patient-reported outcomes were evaluated using Patient-Reported Outcomes Measurement Information System metrics and the Perceived Stress Scale. RESULTS: There were no significant differences in demographics or clinical characteristics between cohorts at enrollment, with the exception of performance status, clinical stage, and albumin. While gait speed and grip strength were lower amongst neoadjuvant chemotherapy patients, there were no significant differences in physical function using the Short Physical Performance Battery and Fried Frailty Index. Patients in the neoadjuvant chemotherapy cohort reported decreased perception of physical function and increased fatigue on Patient-Reported Outcomes Measurement Information System metrics. A larger proportion of patients in the neoadjuvant cohort reported severe levels of emotional distress and anxiety, as well as greater perceived stress at diagnosis. CONCLUSIONS: Our findings suggest that patients undergoing neoadjuvant chemotherapy for advanced ovarian cancer present with increased psychosocial distress and decreased perception of physical function at diagnosis and may benefit most from early introduction of supportive care.

Metabolic dysfunction-associated steatotic liver disease in older adults is associated with frailty and social disadvantage.

BACKGROUND & AIMS: The burden of metabolic dysfunction-associated steatotic liver disease (MASLD) is growing rapidly, as is the number of older adults globally. However, relatively few studies have been performed evaluating the prevalence and risk factors for MASLD in older adults. As such, we aimed to identify the prevalence of MASLD in older adults, as well as sociodemographic, clinical, functional and biochemical associations. METHODS: The study population included older adults without a history of cardiovascular disease, dementia or independence-limiting functional impairment who had participated in the ASPirin in Reducing Events in the Elderly (ASPREE) randomised trial. MASLD was defined using the Fatty Liver Index (FLI). Associations were identified using Poisson regression with robust variance for FLI ≥ 60 vs FLI < 30. RESULTS: 9097 Australian participants aged ≥70 years had complete biochemical and anthropometric data to identify MASLD. The study population had a mean age of 75.1 ± 4.3 years and was 45.0% male. Almost one-third (33.0%) had prevalent MASLD, and the prevalence decreased with increasing age (adjusted RR [aRR] 0.96, 95% CI: 0.96-0.97). MASLD was also negatively associated with social advantage (aRR 0.94, 95% CI: 0.90-0.99) and exercise tolerance and was positively associated with diabetes mellitus (aRR: 1.22, 95% CI: 1.16-1.29), hypertension (aRR: 1.31, 95% CI: 1.22-1.41), male sex (aRR: 1.66, 95% CI: 1.57-1.74), pre-frailty (aRR: 1.99, 95% CI: 1.82-2.12) and frailty (aRR: 2.36, 95% CI: 2.16-2.56). MASLD and nonalcoholic fatty liver disease (NAFLD) results were 100% concordant. CONCLUSION: This study in a large cohort of relatively healthy community-dwelling older adults shows that MASLD is common, decreases with age and is associated with poorer metabolic health, social disadvantage and frailty.