Validation of a Semiautomatic Image Analysis Software for the Quantification of Musculoskeletal Tissues.

Accurate quantification of bone, muscle, and their components is still an unmet need in the musculoskeletal field. Current methods to quantify tissue volumes in 3D images are expensive, labor-intensive, and time-consuming; thus, a reliable, valid, and quick application is highly needed. Tissue Compass is a standalone software for semiautomatic segmentation and automatic quantification of musculoskeletal organs. To validate the software, cross-sectional micro-CT scans images of rat femur (n = 19), and CT images of hip and abdomen (n = 100) from the Osteoporotic Fractures in Men (MrOS) Study were used to quantify bone, hematopoietic marrow (HBM), and marrow adipose tissue (MAT) using commercial manual software as a comparator. Also, abdominal CT scans (n = 100) were used to quantify psoas muscle volumes and intermuscular adipose tissue (IMAT) using the same software. We calculated Pearson's correlation coefficients, individual intra-class correlation coefficients (ICC), and Bland-Altman limits of agreement together with Bland-Altman plots to show the inter- and intra-observer agreement between Tissue Compass and commercially available software. In the animal study, the agreement between Tissue Compass and commercial software was r > 0.93 and ICC > 0.93 for rat femur measurements. Bland-Altman limits of agreement was - 720.89 (- 1.5e+04, 13,074.00) for MAT, 4421.11 (- 1.8e+04, 27,149.73) for HBM and - 6073.32 (- 2.9e+04, 16,388.37) for bone. The inter-observer agreement for QCT human study between two observers was r > 0.99 and ICC > 0.99. Bland-Altman limits of agreement was 0.01 (- 0.07, 0.10) for MAT in hip, 0.02 (- 0.08, 0.12) for HBM in hip, 0.05 (- 0.15, 0.25) for bone in hip, 0.02 (- 0.18, 0.22) for MAT in L1, 0.00 (- 0.16, 0.16) for HBM in L1, and 0.02 (- 0.23, 0.27) for bone in L1. The intra-observer agreement for QCT human study between the two applications was r > 0.997 and ICC > 0.99. Bland-Altman limits of agreement was 0.03 (- 0.13, 0.20) for MAT in hip, 0.05 (- 0.08, 0.18) for HBM in hip, 0.05 (- 0.24, 0.34) for bone in hip, - 0.02 (- 0.34, 0.31) for MAT in L1, - 0.14 (- 0.44, 0.17) for HBM in L1, - 0.29 (- 0.62, 0.05) for bone in L1, 0.03 (- 0.08, 0.15) for IMAT in psoas, and 0.02 (- 0.35, 0.38) for muscle in psoas. Compared to a conventional application, Tissue Compass demonstrated high accuracy and non-inferiority while also facilitating easier analyses. Tissue Compass could become the tool of choice to diagnose tissue loss/gain syndromes in the future by requiring a small number of CT sections to detect tissue volumes and fat infiltration.

Hemoglobin Levels are Low in Sarcopenic and Osteosarcopenic Older Persons.

Anemia is commonly associated with osteoporosis and sarcopenia in older persons. However, there is a common subset of patients identified as osteosarcopenic at a higher risk of adverse outcomes. Whether these patients are also at a higher risk of anemia remains unknown. In this study, we aimed to compare hemoglobin (Hb) levels in osteosarcopenic older subjects versus those with sarcopenia, osteopenia/osteoporosis alone and controls. Cross-sectional study in 558 community-dwelling participants older than 65 (mean age 79 ± 7.5 years) from Western Sydney, Australia. Associations of anemia with sarcopenia, osteopenia/osteoporosis and osteosarcopenia were assessed. Participants were able to mobilize independently, reported a risk/history of falls and were not cognitively impaired. We used the original (EWGOP) and revised (EWGSOP2) European consensus on definition of sarcopenia, and WHO definitions of osteoporosis and osteopenia. Based on both European definitions of sarcopenia prevalence of anemia was the highest among sarcopenic patients (39%), followed by osteosarcopenic (34%), osteoporotic/penic (26%), and controls (24%). Anemia prevalence in total was 176/553 (31.5%). Osteosarcopenic patients on average had 6.3 g/L lower Hb levels compared to controls (p = 0.001), and 3.7 g/L lower Hb than patients with osteoporosis/penia (p < 0.026). Interestingly, levels of Hb did not differ between sarcopenic vs osteosarcopenic patients (p = 0.817) and between osteoporotic/osteopenic patients vs controls (p > 0.259). The higher prevalence of anemia and lower hemoglobin in sarcopenic and osteosarcopenic subjects compared to osteoporotic/penic participants and controls was established. However, the previously reported associations between osteoporosis and anemia were not confirmed. A likely explanation can be inclusion of osteosarcopenic subjects as osteoporotic in previous studies.

The diagnostic value of the Short Physical Performance Battery for sarcopenia.

BACKGROUND: Sarcopenia is defined as the age-related loss of muscle mass, strength, and physical performance. The original European Working Group on Sarcopenia in Older Persons (EWGSOP1) definition, and its revision (EWGSOP2), provide new cut-points and alternate measures for sarcopenia diagnosis. However, sarcopenia is rarely diagnosed in clinical settings owing to its labor-intensive diagnostic process. Given the Short Physical Performance Battery (SPPB) is a quick, easily administrable, and objective measure of muscle strength and physical performance, both of which are key components of sarcopenia, this study examined the diagnostic value of the SPPB for this muscle disease. METHODS: A cross-sectional analysis of 294 community-dwelling older persons (≥65 years) was conducted. Appendicular lean body mass [(ALM) divided by height squared (ALM/h2)], muscle strength (handgrip/sit to stand), and physical performance [gait speed, timed up and go (TUG) and SPPB] were assessed using validated procedures, while participants were diagnosed with sarcopenia following the EWGSOP1 and EWGSOP2 criteria. Diagnostic ability of the SPPB independently and combined with ALM/h2 for sarcopenia was determined using area under the curve (AUC). Potential cut-points were identified, and sensitivity and specificity calculated. RESULTS: Prevalence of sarcopenia ranged from 4 to 16% depending on the definition. The SPPB demonstrated moderate (AUC = 0.644-0.770) value in diagnosing sarcopenia, and a cut-point of ≤8points in SPPB performance resulted in high sensitivity (82-100%) but low specificity (36-41%) for diagnosing those with severe sarcopenia. CONCLUSIONS: The SPPB displayed acceptable value in diagnosing older adults with severe sarcopenia. Moreover, the high sensitivity of the SPPB when using the cut-point of ≤8 suggests it may be a favorable screening tool for sarcopenia in clinical settings where ALM measurements are not available.

Diagnostic Value of Mid-Thigh and Mid-Calf Bone, Muscle, and Fat Mass in Osteosarcopenia: A Pilot Study.

Osteosarcopenia is defined as the concomitant occurrence of osteoporosis and sarcopenia. Current lack of consensus on sarcopenia definitions, combined with the low sensitivity and specificity of screening methodologies, has resulted in varying prevalences of sarcopenia, and consequently osteosarcopenia diagnosis. Previous research indicates that mid-thigh is a potential surrogate region for the assessment of bone, muscle, and fat mass in a single, efficient and low-radiation dual x-ray absorptiometry (DXA) scan. We hypothesized that muscle and bone mass measurements in the mid-thigh region can be used to evaluate bone and muscle health and function. A retrospective study was conducted on community-dwelling older subjects (> 65 y.o., n = 260) who were at risk of falls and fractures. Mid-thigh and mid-calf bone, lean muscle, and fat masses, as well as their association with muscle function, falls, and fractures were compared against conventional measures (hip/spine bone, appendicular lean, and gynoid/android fat masses). Mid-thigh bone, lean, and fat masses showed strong correlation with conventional measures. Mid-thigh lean mass showed similar associations with grip strength, gait speed, and timed up and go (TUG) test as appendicular lean mass. Appendicular, mid-thigh and mid-calf lean masses corrected for body mass index (BMI) showed stronger associations than when corrected for height2. None of the indices were associated with fractures; but fat mass was invariably associated with falls. Those with falls and fractures history had lower bone and muscle mass at mid-thigh. Mid-thigh is a potential new surrogate to study bone, muscle, and fat mass in older people, with comparable ability in predicting muscle performance and falls.

Bone Marrow Adipose Tissue Quantification by Imaging.

PURPOSE OF REVIEW: The significance and roles of marrow adipose tissue (MAT) are increasingly known, and it is no more considered a passive fat storage but a tissue with significant paracrine and endocrine activities that can cause lipotoxicity and inflammation. RECENT FINDINGS: Changes in the MAT volume and fatty acid composition appear to drive bone and hematopoietic marrow deterioration, and studying it may open new horizons to predict bone fragility and anemia development. MAT has the potential to negatively impact bone volume and strength through several mechanisms that are partially described by inflammaging and lipotoxicity terminology. Evidence indicates paramount importance of MAT in age-associated decline of bone and red marrow structure and function. Currently, MAT measurement is being tested and validated by several techniques. However, purpose-specific adaptation of existing imaging technologies and, more importantly, development of new modalities to quantitatively measure MAT are yet to be done.

Marrow Adipose Tissue in Older Men: Association with Visceral and Subcutaneous Fat, Bone Volume, Metabolism, and Inflammation.

Marrow (MAT) and subcutaneous (SAT) adipose tissues display different metabolic profiles and varying associations with aging, bone density, and fracture risk. Using a non-invasive imaging methodology, we aimed to investigate the associations between MAT, SAT, and visceral fat (VAT) with bone volume, bone remodeling markers, insulin resistance, and circulating inflammatory mediators in a population of older men. In this cross-sectional study, 96 healthy men (mean age 67 ± 5.5) were assessed for anthropometric parameters, body composition, serum biochemistry, and inflammatory panel. Using single-energy computed tomography images, MAT (in L2 and L3 and both hips), VAT, and SAT (at the level of L2-L3 and L4-L5) were measured employing Slice-O-Matic software (Tomovision), which enables specific tissue demarcation applying previously reported Hounsfield unit thresholds. MAT volume was similar in all anatomical sites and independent of BMI. In all femoral regions of interest (ROIs) there was a strong negative association between bone and MAT volumes (r = - 0.840 to - 0.972, p < 0.001), with location-dependent variations in the lumbar spine. Unlike VAT and SAT, no associations between MAT and serum glucose, inflammatory markers or insulin resistance indicators were found. Bone decline occurred without red marrow expansion; thus lost bone was mainly (if not exclusively) replaced by MAT. In conclusion, strong inverse correlations between MAT and bone mass, which have been previously observed in women, were also confirmed in older men. However, MAT volume in all ROIs was interrelated and unlike women, mainly independent of VAT or SAT. The lack of strong association between MAT vs VAT/SAT, and its discordant associations with metabolic and inflammatory mediators provide further evidence on MAT's distinct attributes in older men.

Clinical Utility of Thigh and Mid-Thigh Dual-Energy x-Ray Absorptiometry to Identify Bone and Muscle Loss.

Sarcopenia and osteoporosis are highly prevalent syndromes in older people, characterized by loss of muscle and bone tissue, and related to adverse outcomes. Previous reports indicate mid-thigh dual-energy X-ray absorptiometry (DXA) is well suited for the simultaneous assessment of bone, muscle, and fat mass in a single scan. Using cross-sectional clinical data and whole-body DXA images of 1322 community-dwelling adults from the Geelong Osteoporosis Study (57% women, median age 59 years), bone and lean mass were quantified in three unconventional regions of interest (ROIs): (i) a 2.6-cm-thick slice of mid-thigh, (ii) a 13-cm-thick slice of mid-thigh, and (iii) the whole thigh. Conventional indices of tissue mass were also calculated (appendicular lean mass [ALM] and bone mineral density [BMD] of lumbar spine, hip, and femoral neck). The performance of thigh ROIs in identifying osteoporosis, osteopenia, low lean mass and strength, past falls, and fractures was evaluated. All thigh regions (especially whole thigh) performed well in identifying osteoporosis (area under the receiver-operating characteristic [ROC] curve [AUC] > 0.8) and low lean mass (AUC >0.95), but they performed worse in the diagnosis of osteopenia (AUC 0.7-0.8). All thigh regions were equivalent to ALM in discrimination of poor handgrip strength, gait speed, past falls, and fractures. BMD in conventional regions was more strongly associated with past fractures than thigh ROIs. In addition to being faster and easier to quantify, mid-thigh tissue masses can be used for identifying osteoporosis and low lean mass. They are also equivalent to conventional ROIs in their associations with muscle performance, past falls, and fractures; however, further validation is required for the prediction of fractures. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Appendicular and mid-thigh lean mass are associated with muscle strength, physical performance, and dynamic balance in older persons at high risk of falls.

BACKGROUND: Falls in older persons are associated with muscle mass and strength alterations, which may also affect balance parameters. However, the most appropriate combined approach to assess muscle and balance components that predict falls in older persons is still lacking. RESEARCH QUESTION: We hypothesized that appendicular lean and/or mid-thigh mass and muscle strength and performance are positively associated with balance indices and fall risk in older persons. METHODS: Cross-sectional analyses of retrospective data from 260 participants with risk and/or history of falls examined at a Falls and Fracture Clinic. Assessments included a comprehensive clinical exam, bone densitometry and body composition by DXA, grip strength, gait speed, posturography, timed up and go (TUG) and four-square step (FSST) tests. Retrospective falls and fracture history was collected. Associations between appendicular and mid-thigh lean mass and muscle strength/performance vs balance indicators were determined before and after adjusting for age and gender. RESULTS: Mean age of participants was 78 ± 6.7 (65-96) years. Both appendicular and mid-thigh lean masses corrected for BMI (but not for height2), and muscle strength and performance measures are associated with better dynamic balance. Conversely, static balance indicators showed less consistent associations with lean mass. Only TUG and sit to stand time consistently showed significant associations with most static balance indicators. SIGNIFICANCE: Combined with strength and performance parameters, ALM and mid-thigh estimates adjusted by BMI strongly correlate with dynamic balance parameters and could become practical elements of falls risk assessment as well as markers of therapeutic response to falls prevention interventions.

Muscle Volume and Intramuscular Fat of the Tongue Evaluated With MRI Predict Malnutrition in People Living With Dementia: A 5-Year Follow-up Study.

Malnutrition is highly prevalent in older persons with dementia. Therefore, strong predictors of malnutrition in this population are crucial to initiating early interventions. This study evaluates the association between the probability of having malnutrition with the muscle volume and intramuscular fat (iMAT) of the masseter and the tongue in magnetic resonance imaging (MRI) of community-dwelling older persons diagnosed with mild dementia followed up for 5 years. This is a longitudinal study conducted in the western part of Norway. Muscle volume and iMAT of the tongue and masseter were computed from structural head MRI obtained from 65 participants of the Dementia Study of Western Norway using Slice-O-Matic software for segmentation. Malnutrition was assessed using the Global Leadership Initiative on Malnutrition Index. Linear mixed models were conducted. Having malnutrition at baseline was associated with lower muscle volume (odds ratio [OR] 0.60, standard error [SE] 0.20; p = .010) and higher iMAT (OR 3.31, SE 0.46; p = .010) in the tongue. At 5 years follow-up, those with lower muscle volume (OR 0.55, SE 0.20; p = .002) and higher iMAT (OR 2.52, SE 0.40; p = .022) in the tongue had a higher probability of presenting malnutrition. The masseter iMAT and volume were not associated with malnutrition in any of the adjusted models. In people diagnosed with mild dementia, tongue muscle volume and iMAT were associated with baseline malnutrition and the probability of developing malnutrition in a 5-year trajectory. In the masseter, there were no significant associations after adjustments.

Characterization of Skeletal Phenotype and Associated Mechanisms With Chronic Intestinal Inflammation in the Winnie Mouse Model of Spontaneous Chronic Colitis.

BACKGROUND: Osteoporosis is a common extraintestinal manifestation of inflammatory bowel disease (IBD). However, studies have been scarce, mainly because of the lack of an appropriate animal model of colitis-associated bone loss. In this study, we aimed to decipher skeletal manifestations in the Winnie mouse model of spontaneous chronic colitis, which carries a MUC2 gene mutation and closely replicates ulcerative colitis. In our study, Winnie mice, prior to the colitis onset at 6 weeks old and progression at 14 and 24 weeks old, were compared with age-matched C57BL/6 controls. We studied several possible mechanisms involved in colitis-associated bone loss. METHODS: We assessed for bone quality (eg, microcomputed tomography [micro-CT], static and dynamic histomorphometry, 3-point bending, and ex vivo bone marrow analysis) and associated mechanisms (eg, electrochemical recordings for gut-derived serotonin levels, real-time polymerase chain reaction [qRT-PCR], double immunofluorescence microscopy, intestinal inflammation levels by lipocalin-2 assay, serum levels of calcium, phosphorus, and vitamin D) from Winnie (6-24 weeks) and age-matched C57BL6 mice. RESULTS: Deterioration in trabecular and cortical bone microarchitecture, reductions in bone formation, mineral apposition rate, bone volume/total volume, osteoid volume/bone surface, and bone strength were observed in Winnie mice compared with controls. Decreased osteoblast and increased osteoclast numbers were prominent in Winnie mice compared with controls. Upregulation of 5-HTR1B gene and increased association of FOXO1 with ATF4 complex were identified as associated mechanisms concomitant to overt inflammation and high levels of gut-derived serotonin in 14-week and 24-week Winnie mice. CONCLUSIONS: Skeletal phenotype of the Winnie mouse model of spontaneous chronic colitis closely represents manifestations of IBD-associated osteoporosis/osteopenia. The onset and progression of intestinal inflammation are associated with increased gut-derived serotonin level, increased bone resorption, and decreased bone formation.

Evaluating the toxicity of escalating dose of oral picolinic acid in Sprague-Dawley rats.

Picolinic acid (PIC) is a byproduct of tryptophan catabolism through the kynurenine pathway, with anabolic effects on bone in vivo and in vitro. Hence, PIC has been nominated as a possible candidate to treat and/or prevent osteoporosis. However, the effective dose and toxicity of PIC are not known yet. To test the effect of escalating and very high doses of oral PIC, male Sprague-Dawley rats were gavaged PIC: Group 1 (n = 3) received incremental doses of 125, 250 and 500 mg/kg/day PIC on days 1, 3 and 5. Group 2 (n = 3) received 500 mg/kg BID (8 h apart; i.e. 1000 mg/kg/day) PIC on Day 1. Group 3 (n = 3) received 125 mg/kg/day PIC for seven consecutive days. Group 4 (n = 3) received 250 mg/kg/day PIC for seven consecutive days. Groups 1, 3 and 4 rats were euthanized on Day 8. Group 5 (n = 6) received 500 mg/kg/day PIC for two consecutive days and then once a week dose (Days 9, 16 and 23) of 500 mg/kg/dose PIC, until euthanasia (Day 30). Blood and cerebrospinal fluid (CSF) were sampled at euthanasia, and tissues showing abnormalities at necropsy underwent histopathology evaluation. All rats displayed some degree of mild hypercalcemia and hyperkalemia. Rats receiving high doses (500 or 1000 mg/kg/day) of PIC died or were euthanized on humane grounds within the first week after showing clinical neurological signs, with animals later revealed to have brain necrosis and hemorrhage at histopathology. Rats receiving lower doses (125 or 250 mg/kg/day) of PIC completed treatment course without apparent clinical adverse events. In summary, very high doses of PIC (≥500 mg/kg/day) were vascular-neurotoxic. Possible future experiments must consider significantly lower doses.

Sarcopenia Definitions and Outcomes Consortium (SDOC) Criteria are Strongly Associated With Malnutrition, Depression, Falls, and Fractures in High-Risk Older Persons.

OBJECTIVES: Sarcopenia Definitions and Outcomes Consortium (SDOC) provides cut-points based on muscle weakness (low grip strength) and slowness (poor gait speed) for low-risk populations; however, it is unknown if these criteria apply to high-risk populations. We examined the association between SDOC criteria and important health status indicators in high-risk older persons. DESIGN: Cross-sectional study. SETTING AND PARTICIPANTS: 356 community-dwelling older persons (median age: 79 years, interquartile range: 73, 83; 75.2% women) attending a falls and fractures clinic in Melbourne, Australia. METHODS: Grip strength (hydraulic dynamometer) and gait speed (over 4 m) were used to define sarcopenia using SDOC cut-points. Health measures included falls (past 1 year) and fractures (past 5 years) by self-report, and malnutrition, depression, balance confidence, fear of falling, static balance (limits of stability), dynamic balance (Four-Square Step Test), and body composition [body mass index and lean mass, fat mass, and bone density (via dual-energy x-ray absorptiometry)] were assessed using validated procedures. Fasting vitamin D and parathyroid hormone concentrations were measured by immunoassays. Participants were categorized as nonsarcopenic or sarcopenic based on the SDOC cut-points, and multivariate models were used to examine the association between sarcopenia and health status indicators while adjusting for confounding factors. RESULTS: After adjusting for covariates, sarcopenic older persons (n = 162, 45.5%) were positively associated with malnutrition [odds ratio (OR) 3.21, 95% confidence interval (CI) 1.63, 6.32], depression (OR 4.11, 95% CI 2.31, 7.29), fear of falling (OR 1.08, 95% CI 1.06, 1.10) as well as recurrent (2 or more) falls (OR 1.62, 95% CI 1.01, 2.59) and fractures (OR 2.26, 95% CI 1.17, 4.36), and negatively associated with poor balance confidence (OR 0.96, 95% CI 0.95, 0.97) (P < .05 vs nonsarcopenic). CONCLUSIONS AND IMPLICATIONS: SDOC criteria are strongly associated with important health status indicators in high-risk older persons, which strengthens the clinical utility of the SDOC in these populations.

Body composition reference ranges in community-dwelling adults using dual-energy X-ray absorptiometry: the Australian Body Composition (ABC) Study.

BACKGROUND: Reference ranges for lean mass (LM) and fat mass (FM) are essential in identifying soft tissue disorders; however, no such reference ranges exist for the most commonly used Hologic dual-energy X-ray absorptiometry (DXA) machine in Australia. METHODS: Cross-sectional study of community-dwelling adults (aged 18-88 years) who underwent a Hologic DXA scan at one of three commercialized densitometry centres in Australia. Age-specific and sex-specific percentile curves were generated for LM [LM, appendicular lean mass (ALM), ALM adjusted for height squared (ALM/h2 ), and ALM adjusted for body mass index (ALM/BMI)] and FM [FM, FM adjusted for height squared (FM/h2 ), appendicular fat mass, and android and gynoid fat] parameters using the LMS statistical method. Cutpoints equivalent to T-scores of -1, -2, and -2.5 standard deviations below the young mean reference group (20-29 years) were also generated for LM parameters. RESULTS: A total of 15 479 community-dwelling adults (54% men) with a median age of 33 years (interquartile range: 28, 42) were included. LM, ALM, and ALM/h2 remained stable until age 50, after which these parameters started to decline in both sexes. Compared with age 50, median percentiles of LM, ALM, and ALM/h2 declined by -5.9 kg, -3.7 kg, and -0.86 kg/m2 in men and by -2.5 kg, -1.8 kg, and -0.10 kg/m2 in women at age 70, respectively. Adjusting ALM for BMI (rather than height squared) resulted in different trends, with ALM/BMI decreasing from as early as age 20. Compared with age 20, median percentiles of ALM/BMI at age 40 declined by -0.10 kg/kg/m2 in men and by -0.06 kg/kg/m2 in women; and at age 70, ALM/BMI declined by -0.25 kg/kg/m2 in men and by -0.20 kg/kg/m2 in women. Cutpoints equivalent to T-scores of -1, -2, and -2.5 standard deviations for ALM/BMI were 1.01, 0.86, and 0.77 kg/kg/m2 in men and 0.70, 0.59, and 0.53 kg/kg/m2 in women, respectively. All FM parameters progressively increased from age 20 and continued up until age 70. CONCLUSIONS: We developed reference ranges for LM and FM parameters from Hologic DXA machines in a large cohort of Australian adults, which will assist researchers and clinicians in identifying soft tissue disorders such as obesity, sarcopenia, and cachexia.

Uncovering the Bone-Muscle Interaction and Its Implications for the Health and Function of Older Adults (the Wellderly Project): Protocol for a Randomized Controlled Crossover Trial.

BACKGROUND: Bone and muscle are closely linked anatomically, biochemically, and metabolically. Acute exercise affects both bone and muscle, implying a crosstalk between the two systems. However, how these two systems communicate is still largely unknown. We will explore the role of undercarboxylated osteocalcin (ucOC) in this crosstalk. ucOC is involved in glucose metabolism and has a potential role in muscle maintenance and metabolism. OBJECTIVE: The proposed trial will determine if circulating ucOC levels in older adults at baseline and following acute exercise are associated with parameters of muscle function and if the ucOC response to exercise varies between older adults with low muscle quality and those with normal or high muscle quality. METHODS: A total of 54 men and women aged 60 years or older with no history of diabetes and warfarin and vitamin K use will be recruited. Screening tests will be performed, including those for functional, anthropometric, and clinical presentation. On the basis of muscle quality, a combined equation of lean mass (leg appendicular skeletal muscle mass in kg) and strength (leg press; one-repetition maximum), participants will be stratified into a high or low muscle function group and randomized into the controlled crossover acute intervention. Three visits will be performed approximately 7 days apart, and acute aerobic exercise, acute resistance exercise, and a control session (rest) will be completed in any order. Our primary outcome for this study is the effect of acute exercise on ucOC in older adults with low muscle function and those with high muscle function. RESULTS: The trial is active and ongoing. Recruitment began in February 2018, and 38 participants have completed the study as of May 26, 2019. CONCLUSIONS: This study will provide novel insights into bone and muscle crosstalk in older adults, potentially identifying new clinical biomarkers and mechanistic targets for drug treatments for sarcopenia and other related musculoskeletal conditions. TRIAL REGISTRATION: Australia New Zealand Clinical Trials Registry ACTRN12618001756213; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=375925. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/18777.

Associations between osteoporosis, the severity of sarcopenia and fragility fractures in community-dwelling older adults.

PURPOSE: To investigate the association between bone mineral density (BMD) and the severity of sarcopenia using the revised European Working Group on Sarcopenia in Older People (EWGSOP2) definition. METHODS: BMD [dual energy X-ray absorptiometry (DXA)], appendicular lean mass (DXA), handgrip strength (hydraulic dynamometer) and gait speed (over 4-m) were used to screen for osteoporosis and sarcopenia. Participants were categorized as osteoporotic according to the World Health Organization definition (T score ≤ - 2.5), and classified with probable sarcopenia or confirmed sarcopenia according to the EWGSOP2 criteria. Fasting biochemistry profile, fragility fractures, malnutrition index, geriatric depression scale and fear of falling, were also measured using validated procedures. RESULTS: A total of 484 community-dwelling older adults (69.6% women) with a median age of 76 years [Interquartile range (IQR) 70-81] were included in this study. Osteoporosis prevalence increased from 47.6% in non-sarcopenia to 65.5% in probable sarcopenia and 78.1% in those with confirmed sarcopenia (p < 0.05). After adjusting for age, sex and vitamin D in multivariate models, osteoporosis was associated with a greater risk of confirmed sarcopenia [odds ratio (OR) 2.885, 95% CI 1.155, 7.204, p = 0.023]. The number of fragility fractures was also higher in those with confirmed sarcopenia versus those without (p = 0.013), but this finding did not remain significant in adjusted models (p = 0.078). CONCLUSION: Prevalence of osteoporosis increased across the severity of sarcopenia, and osteoporosis was associated with a greater risk of sarcopenia. As such, health care professionals should screen for sarcopenia in those with low BMD.

The Joint Occurrence of Osteoporosis and Sarcopenia (Osteosarcopenia): Definitions and Characteristics.

OBJECTIVES: We sought to examine the associations of osteosarcopenia with physical performance, balance, and falls and fractures in community-dwelling older adults. Additionally, we aimed to determine which clinical outcomes are associated with specific components of osteosarcopenia. DESIGN: Cross-sectional study. SETTING AND PARTICIPANTS: 253 participants (77% women; aged 77.9 ± 0.42 years) who presented for a falls and fractures risk assessment in Melbourne, Australia. METHODS: Participants were mobile, community-dwelling older adults (≥65 years) free of cognitive impairment. Body composition (via dual-energy x-ray absorptiometry), physical performance [via Timed Up and Go (TUG) and Short Physical Performance Battery (SPPB)], and balance [via Four-Square Step test (FSS) and posturography] were examined. Falls in the past year and fractures in the past 5 years were self-reported. Osteosarcopenia was defined as (1) low bone mineral density (BMD) [T score <-1 standard deviation (SD)] combined with sarcopenia and (2) osteoporosis (BMD T score ≤-2.5 SD) combined with severe sarcopenia. For sarcopenia, we employed the criteria of the European Working Group on Sarcopenia in Older People (EWGSOP1), the revised criteria (EWGSOP2), and that of the Foundation for the National Institutes for Health (FNIH). Kruskal-Wallis and logistic regression tests were used for statistical analysis. RESULTS: Osteosarcopenia was associated with worse SPPB, TUG, FSS, limit of stability, and falls and fractures history. Additionally, osteosarcopenia (using the severe sarcopenia classification) conferred an increased rate of falls [odds ratios (ORs) from 2.83 to 3.63; P < .05 for all] and fractures (ORs from 3.86 to 4.38; P < .05 for all) when employing the EWGSOP2 and FNIH definitions, respectively. CONCLUSIONS AND IMPLICATIONS: Compared with the nonosteosarcopenic group, those with osteosarcopenia had greater impairment of physical performance and balance. The EWGSOP2 and FNIH criteria resulted in the strongest associations with physical performance and self-reported falls and fractures.

The effects of dietary fatty acids on bone, hematopoietic marrow and marrow adipose tissue in a murine model of senile osteoporosis.

Purpose: Marrow adipose tissue (MAT) expansion and associated lipotoxicity are important drivers of age-related bone loss and hematopoietic bone marrow (HBM) atrophy. Fish oil and borage oil (rich in ω3 fatty acids) can partially prevent aged-related bone loss in SAMP8 mice. However, whether preservation of bone mass in this progeria model is associated with MAT volumes remains unknown.Results: MAT volume fraction (MAT%) showed a negative association with hematopoietic bone marrow (HBM%;r=-0.836, p<0.001) and bone (bone%;r=-0.344, p=0.013) volume fractions.Adjusting for multiple comparisons, bone% was higher and MAT% was lower in Fish oil (FO)-supplemented groups vs. controls (p<0.001). HBM% did not differ significantly between the four groups. However, in the group supplemented with FO, HBM comprised higher fractions and MAT constituted lower fractions of total marrow vs. controls (p<0.001).Conclusion: Feeding FO-enriched diet prevented age-related bone and HBM loss, by reducing MAT expansion. Our results further emphasize on the role(s) of MAT expansion in bone and HBM atrophy.Methods: SAMP8 mice (n>9 /group) were allocated into 4 categories and fed a control ration, FO-, sunflower oil (SFO)- and borage oil-enriched diets for lifetime. Femurs were scanned using microcomputed tomography (µCT) and bone, MAT, and HBM volumes were determined using an image analysis software.

Changes in Nutritional Status and Musculoskeletal Health in a Geriatric Post-Fall Care Plan Setting.

Understanding how changes in nutritional status influence musculoskeletal recovery after falling remains unclear. We explored associations between changes in nutritional status and musculoskeletal health in 106 community-dwelling older adults aged ≥65 years, who attended the Falls and Fractures Clinic at Sunshine Hospital in St Albans, Australia after falling. At baseline and after 6 months, individuals were assessed for Mini Nutritional Assessment (MNA®), grip strength, gait speed, Timed Up and Go (TUG) test, Short Physical Performance Battery (SPPB), and bone turnover marker levels. Associations were examined using multiple linear regression, adjusted for baseline covariates and post-fall care plans. Over 6 months, the prevalence of malnutrition or risk thereof decreased from 29% to 15% using MNA <24/30. Specifically, 20 individuals (19%) improved, 7 (7%) deteriorated, and 73 (69%) maintained nutritional status, including 65 (61%) who remained well-nourished and 8 (8%) who remained malnourished/at risk. A 1-point increase in MNA score over 6 months was associated with an increase of 0.20 points (95% confidence interval 0.10, 0.31, p < 0.001) in SPPB score. Improvement in nutritional status was associated with improvement in physical performance, providing a basis for interventional studies to ascertain causality and evaluate nutritional models of care for post-fall functional recovery in older adults.

Selective Loss of Levator Ani and Leg Muscle Volumes in Men Undergoing Androgen Deprivation Therapy.

CONTEXT: Androgen deprivation therapy (ADT) for prostate cancer (PCa) leads to a selective loss of leg muscle function during walking. Rodent models of ADT have demonstrated that the levator ani is exquisitely androgen sensitive. OBJECTIVE: To determine whether the high androgen responsiveness of the levator ani muscle documented in rodents is evolutionarily conserved and ADT is associated with a selective loss in leg muscle volume. DESIGN: Prospective longitudinal case-control study. SETTING: Tertiary referral hospital. PARTICIPANTS: Thirty-four men newly beginning ADT and 29 age-matched controls with PCa. MAIN OUTCOME MEASURES: The muscle volumes in liters of the levator ani and primary muscles involved in walking (iliopsoas, quadriceps, gluteus maximus, gluteus medius, calf). RESULTS: Compared with controls, during a 12-month period, men receiving ADT experienced a mean reduction in total testosterone from 14.1 to 0.4 nmol/L and demonstrated greater decreases in levator ani [mean adjusted difference (MAD), -0.005 L; 95% CI, -0.007 to -0.002; P = 0.002; -16% of initial median value], gluteus maximus (MAD, -0.032 L; 95% CI, -0.063 to -0.002; P = 0.017; -5% of initial median value), iliopsoas (MAD, -0.005 L; 95% CI, -0.001 to 0.000; P = 0.013; -5% of initial median value), and quadriceps (MAD, -0.050 L; 95% CI, -0.088 to -0.012; P = 0.031; -3% of initial median value). No substantial differences were observed in the gluteus medius and calf muscles. CONCLUSIONS: The androgen responsiveness of the levator ani appears to be evolutionarily conserved in humans. ADT selectively decreases the volume of muscles that support body weight. Interventional strategies to reduce ADT-related sarcopenia and sexual dysfunction should assess whether targeting these muscle groups, including the pelvic floor, will improve clinical outcomes.

A report of the unusual lesions caused by Thelazia gulosa in cattle.

This is a case report of unusual lesions caused by Thelazia gulosa in cattle. After several ineffective treatments of suspected infectious keratoconjunctivitis in calves and cows, T. gulosa was found associated with retrobulbar granuloma-like masses. The masses with multiple digit-like protrusions on conjunctival surface ejected multiple worms on firm pressure on clinical examination. Samples of tissues that contained worms were surgically removed, fixed in ethanol and submitted to the parasitology and histopathology labs for morphological identification of worms and the nature of the tissue masses, respectively. The infestation was present only in young calves (<3months) and high-producing cows. Histopathology showed fibrovascular granulation tissue, containing a moderate to marked inflammatory infiltrate. Ivermectin treatment (200µg/kg, SC, once) with and without surgical excision resolved the infestation. To the best of our knowledge, this is the first report of tissue invasion by T. gulosa.