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Exploration of mitochondrial defects in sarcopenic hip fracture patients.

ABSTRACT: Severe cases of age-related loss of muscle function and mass are clinically unique to sarcopenia. Mitochondrial dysfunction has been associated with aging and sarcopenia, but the causal connection in this context is not well eluded. Here we investigated different aspects of mitochondrial respiration in sarcopenia. Open muscle biopsies were taken from a total of 31 hip fracture patients, older than 70 years. Patients were assigned a sarcopenia Z-score based on EWGSOP2 criteria. Primary myoblast cultures were generated from the muscle tissue samples and used for real time metabolic measurement. Muscle and serum samples showed correlation of high Z-scores with reduced mitochondrial complex I activity, increased tricarboxylic acid cycle (TCA) metabolites, reduced vitamin D₃ levels, and signs of an altered iron metabolism. Primary myoblast cultures gained from the same muscle biopsies did not show significant mitochondrial defects. We hypothesize that a sum of external consequences, including vitamin D₃ deficiency and iron deficiency caused by disturbances in the iron metabolism, result in complex I deficiency, which in turn affects the TCA and contributes to muscle weakness and loss.

SUBMITTER: Hintze S

PROVIDER: S-EPMC9593198 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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Exploration of mitochondrial defects in sarcopenic hip fracture patients.

Hintze Stefan S Baber Lisa L Hofmeister Fabian F Jarmusch Stefanie S Todorow Vanessa V Mehaffey Stefan S Tanganelli Fabiana F Ferrari Uta U Neuerburg Carl C Teupser Daniel D Bidlingmaier Martin M Marques Jair Gonzalez JG Koletzko Berthold B Schoser Benedikt B Drey Michael M Meinke Peter P

Heliyon 20221019 10

Severe cases of age-related loss of muscle function and mass are clinically unique to sarcopenia. Mitochondrial dysfunction has been associated with aging and sarcopenia, but the causal connection in this context is not well eluded. Here we investigated different aspects of mitochondrial respiration in sarcopenia. Open muscle biopsies were taken from a total of 31 hip fracture patients, older than 70 years. Patients were assigned a sarcopenia Z-score based on EWGSOP2 criteria. Primary myoblast c ...[more]

PMID: 36303924

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Project description:Background and purposePreventing subsequent falls in persons recovering from hip fracture is paramount. The Four Square Step Test (FSST) is a fast, easy measure of dynamic balance, with times more than 15 seconds previously associated with multiple fall risk in older adults. This study investigates among hip fracture patients (1) FSST performance, and how (2) unique population characteristics (such as fracture side) and (3) cognition impact FSST performance.MethodsPatients with hip fracture (n = 40) 60 years and older came from an ancillary study to a larger randomized controlled trial testing two 16-week in-home physical therapy interventions after completion of usual care rehabilitation. Baseline measurers included: FSST, demographics, fracture characteristics, Modified Mini-Mental State Examination (3MS), Hooper Visual Organization Test (HVOT), and Trails Making Tests (TMT) A and B.ResultsOf 40 patients with hip fracture, 13 did not complete the FSST at baseline and were significantly older (P = .040) and performed worse on cognitive tests (3MS, HVOT, TMT-B; P < .05). Mean FSST time was 24.3 ± 13.1 seconds for the other 27, of whom 7 finished in less than 15 seconds. A significant 3-way interaction was observed, such that those with left-side pertrochanteric fractures who performed poorly on the HVOT did significantly worse on the FSST (P < .01, R2 = 0.93).DiscussionAlmost one-third of patients with hip fracture could not perform the FSST after completing usual care rehabilitation. Inability to perform the FSST was not random, as those without the FSST were physically and cognitively worse than those who did perform the FSST. Among those who could attempt the FSST, few performed well. Cognitive ability related to spatial orientation and fracture characteristics such as fracture side and fracture type has a synergistic effect on FSST performance.ConclusionsThis is one of the first studies to assess the FSST in a population with hip fracture. At 4 months after hip fracture, most patients cannot perform the FSST in less than 15 seconds. Fracture side and fracture type appear important to FSST performance, as does cognition. More work needs to be done longitudinally to study the FSST in patients with hip fracture.

Project description:Background: Osteoporotic fractures are associated with a loss of quality of life, but only few patients receive an appropriate therapy. Therefore, the present study aims to investigate the awareness of musculoskeletal patients to participate in osteoporosis assessment and to evaluate whether there are significant differences between acute care patients treated for major fractures of the hip compared to elective patients treated for hip joint replacement.; Methods: From May 2015 to December 2016 patients who were undergoing surgical treatment for proximal femur fracture or total hip replacement due to osteoarthritis and were at risk for an underlying osteoporosis (female > 60 and male > 70 years) were included in the study and asked to complete a questionnaire assessing the awareness for an underlying osteoporosis. ASA Score, FRAX Score, and demographic information have also been examined. Results: In total 268 patients (female = 194 (72.0%)/male = 74 (28%)), mean age 77.7 years (±7.7) undergoing hip surgery were included. Of these, 118 were treated for fracture-related etiology and 150 underwent total hip arthroplasty in an elective care setting. Patients were interviewed about their need for osteoporosis examination during hospitalization. Overall, 76 of 150 patients receiving elective care (50.7%) considered that an examination was necessary, whereas in proximal femur fracture patients the awareness was lower, and the disease osteoporosis was assessed as threatening by significantly fewer newly fractured patients. By comparison, patients undergoing trauma surgery had a considerably greater risk of developing another osteoporotic fracture than patients undergoing elective surgery determined by the FRAX® Score (p ≤ 0.001).; Conclusions: The patients' motivation to endure additional osteoporosis diagnostic testing is notoriously low and needs to be increased. Patients who underwent acute care surgery for a fragility proximal femur fracture, although acutely affected by the potential consequences of underlying osteoporosis, showed lower awareness than the elective comparison population that was also on average 6.1 years younger. Although elective patients were younger and at a lower risk, they seemed to be much more willing to undergo further osteoporosis assessment. In order to better identify and care for patients at risk, interventions such as effective screening, early initiation of osteoporosis therapy in the inpatient setting and a fracture liaison service are important measures.

Project description:BackgroundAgeing is associated with a decline in skeletal muscle mass and function (strength and power), known as sarcopenia. Inadequate dietary protein and inactivity have been shown to accelerate sarcopenia outcomes, occurring at different rates in males and females. Regardless, active older adults who often exceed the exercise guidelines still show signs of sarcopenia. This study aimed to explore the link between age, physical activity, protein intake, and biological sex with skeletal muscle mass, strength, power, and physical capacity/performance in active older adults. Fifty-four active older adults were recruited from this trial and grouped according to age (middle aged: 50-59 years, and older age: ≥ 60 years), exercise volume (low: ≥ 90-149 min/week, moderate: ≥ 150-299 min/week, and high: ≥ 300 min/week), protein intake (low: < 0.8 g/kg body mass (BM), moderate: ≥ 0.8-1.19g /kg BM, and high: ≥ 1.2 g/kg BM), and biological sex (males and females). Skeletal muscle and fat mass (dual X-ray absorptiometry), strength (1-repetition maximum using leg press, chest press, lateral pull down, and hand grip), power (counter movement jump), and general fitness (cardiorespiratory capacity and gait speed) were assessed. Data were grouped based on variables, and a general linear model (ANCOVA) or an independent t test was used to determine between group differences.ResultsFifty three of the total participants' data were analysed. The middle-aged group had 18%, 11%, and 10% higher leg press, chest press, and lateral pull down, respectively, compared to the older-aged group (p < .05). There were no significant differences between different levels of training volume and any of the outcomes. Higher protein intakes were associated with significantly less body fat mass (p = .005) and a trend towards a higher leg press (p = .053) and higher relative power (W/kg) (p = .056) compared with the moderate and low protein intake groups. Significant differences based on biological sex were observed for all outcomes except for gait speed (p = .611) and cardiorespiratory fitness (p = .147).ConclusionsContributions of age, physical activity, daily protein intake, and biological sex can explain the individual variation in outcomes related to changes in body composition, strength, power, and/or cardiorespiratory fitness in a cohort of active older adults. The preprint version of this work is available on Research Square: https://www.researchsquare.com/article/rs-51873/v1 .Trial registrationThis trial is registered in the ANZCTR.org.au, no. ACTRN12618001088235 ( https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=375286 ).

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Exploration of mitochondrial defects in sarcopenic hip fracture patients.

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Exploration of mitochondrial defects in sarcopenic hip fracture patients.

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