[The effect of intensified training therapy on axial spondylarthritis in day care units]. / Der Effekt intensivierter Trainingstherapie bei axialer Spondyloarthritis im teilstationären Setting.

BACKGROUND: Day care units are an essential part of psychiatric treatment in Germany. In rheumatology they are also regularly used. Axial spondylarthritis (axSpA) is an inflammatory rheumatic disease that causes pain, diminished quality of life, limitations in activities of daily living and ability to work, especially if insufficiently treated. The multimodal rheumatologic complex treatment with at least 14 days of inpatient care is an established tool to control exacerbated disease activity. The feasibility and effect of an equivalent treatment in a day care setting has not yet been evaluated. METHODS: The effect of a therapy in a day care unit comparable to the inpatient multimodal rheumatologic complex treatment was investigated using clinically established patient reported outcomes (NAS pain, FFbH, BASDAI, BASFI). RESULTS: Selected subgroups of axSpA patients can routinely and effectively be treated in day care units. Intensified multimodal as well as nonintensified treatment forms lead to reduced disease activity. Additionally, compared to nonintensified treatment, the intensified multimodal treatment approach leads to significantly reduced pain, and disease-related and functional limitations in daily life. CONCLUSION: If available, treatment in a day care unit can complement the established inpatient treatment modalities in selected axSpA patients. In cases with high disease activity and suffering, intensified multimodal treatment should be preferred due to better outcomes.

[Frequency and severity of sarcopenia in patients with inflammatory and noninflammatory musculoskeletal diseases : Results of a monocentric study in a tertiary care center]. / Häufigkeit und Schweregrad von Sarkopenie bei Patient*innen mit entzündlichen und nichtentzündlichen muskuloskeletalen Erkrankungen : Ergebnisse einer monozentrischen Studie in einem tertiären Zentrum.

INTRODUCTION: Sarcopenia (SP) is defined as the pathological loss of muscle mass and function. This is a clinically relevant problem, especially in geriatric patients, because SP is associated with falls, frailty, loss of function, and increased mortality. People with inflammatory and degenerative rheumatic musculoskeletal disorders (RMD) are also at risk for developing SP; however, there is little research on the prevalence of this health disorder in this patient group using currently available SP criteria. OBJECTIVE: To investigate the prevalence and severity of SP in patients with RMD. METHODS: A total of 141 consecutive patients over 65 years of age with rheumatoid arthritis (RA), spondylarthritis (SpA), vasculitis, and noninflammatory musculoskeletal diseases were recruited in a cross-sectional study at a tertiary care center. The European Working Group on Sarcopenia in Older People (EWGSOP 1 and 2) definitions of presarcopenia, SP, and severe SP were used to determine the prevalence. Lean mass as a parameter of muscle mass and bone density were measured by dual X­ray absorptiometry (DXA). Handgrip strength and the short physical performance battery (SPPB) were performed in a standardized manner. Furthermore, the frequency of falls and the presence of frailty were determined. Student's T-test and the χ2-test were used for statistics. RESULTS: Of the patients included 73% were female, the mean age was 73 years and 80% had an inflammatory RMD. According to EWGSOP 2, 58.9% of participants probable had SP due to low muscle function. When muscle mass was added for confirmation, the prevalence of SP was 10.6%, 5.6% of whom had severe SP. The prevalence was numerically but not statistically different between inflammatory (11.5%) and noninflammatory RMD (7.1%). The prevalence of SP was highest in patients with RA (9.5%) and vasculitis (24%), and lowest in SpA (4%). Both osteoporosis (40% vs. 18.5%) and falls (15% vs. 8.6%) occurred more frequently in patients with SP than those without SP. DISCUSSION: This study showed a relatively high prevalence of SP, especially in patients with RA and vasculitis. In patients at risk, measures to detect SP should routinely be performed in a standardized manner in the clinical practice. The high frequency of muscle function deficits in this study population supports the importance of measuring muscle mass in addition to bone density with DXA to confirm SP.

Defining an international cut-off of two-legged countermovement jump power for sarcopenia and dysmobility syndrome.

We aimed to establish jump power cut-offs for the composite outcome of either sarcopenia (EWGSOP2) or dysmobility syndrome using Asian and Caucasian cohorts. Estimated cut-offs were sex specific (women: < 19.0 W/kg; men: < 23.8 W/kg) but not ethnicity specific. Jump power has potential to be used in definitions of poor musculoskeletal health. PURPOSE: Weight-corrected jump power measured during a countermovement jump may be a useful tool to identify individuals with poor musculoskeletal health, but no cut-off values exist. We aimed to establish jump power cut-offs for detecting individuals with either sarcopenia or dysmobility syndrome. METHODS: Age- and sex-matched community-dwelling older adults from two cohorts (University of Wisconsin-Madison [UW], Korean Urban Rural Elderly cohort [KURE], 1:2) were analyzed. Jump power cut-offs for the composite outcome of either sarcopenia defined by EWGSOP2 or dysmobility syndrome were determined. RESULTS: The UW (n = 95) and KURE (n = 190) cohorts were similar in age (mean 75 years) and sex distribution (68% women). Jump power was similar between KURE and UW women (19.7 vs. 18.6 W/kg, p = 0.096) and slightly higher in KURE than UW in men (26.9 vs. 24.8 W/kg, p = 0.050). In UW and KURE, the prevalence of sarcopenia (7.4% in both), dysmobility syndrome (31.6% and 27.9%), or composite of either sarcopenia or dysmobility syndrome (32.6% and 28.4%) were comparable. Low jump power cut-offs for the composite outcome differed by sex but not by ethnicity (< 19.0 W/kg in women; < 23.8 W/kg in men). Low jump power was associated with elevated odds of sarcopenia (adjusted odds ratio [aOR] 4.07), dysmobility syndrome (aOR 4.32), or the composite of sarcopenia or dysmobility syndrome (aOR 4.67, p < 0.01 for all) independent of age, sex, height, and ethnicity. CONCLUSION: Sex-specific jump power cut-offs were found to detect the presence of either sarcopenia or dysmobility syndrome in older adults independent of Asian or Caucasian ethnicity.

[Evaluation of the trabecular bone score (TBS) in routine clinical care of patients with inflammatory rheumatic and non-inflammatory diseases : Correlation with conventional bone mineral density measurement and prevalence of vertebral fractures]. / Evaluation des Trabecular Bone Score (TBS) in der täglichen Praxis bei Patienten mit entzündlich rheumatischen und nichtentzündlichen Erkrankungen : Korrelation mit konventioneller Knochendichtemessung und Prävalenz von Wirbelkörperfrakturen.

BACKGROUND: Osteoporosis-related fractures are common in patients with rheumatoid arthritis (RA). Bone mineral density (BMD) measurements using dual-energy x­ray absorptiometry (DXA) alone has only a limited value for predicting the risk of fractures. The trabecular bone score (TBS) is a surrogate parameter for trabecular microarchitecture of bone and a predictor of fracture risk independent of BMD. AIM: To examine the prevalence of BMD, TBS and osteoporosis-related vertebral fractures (VF) in patients with RA in comparison to controls with non-inflammatory musculoskeletal diseases. METHODS: Data from patients with RA diagnosed by a rheumatologist and with TBS and DXA measurements, who were assessed in this hospital between 2006 and 2014 were retrospectively analyzed. The RA patients were matched with controls with non-inflammatory musculoskeletal diseases. "Reduced bone health" was defined as a T­score <-1.0 and/or a TBS value <-1.31. Statistical analyses were carried out using the Mann-Whitney test and the Wilcoxon test. RESULTS: Data from 143 patients with RA (age 72.1 ± 11.1 years, 72% female) and 106 controls (age 69.6 ± 12.6 years, 75% female) were included. The RA patients more frequently had low BMD (n = 102, 71.3%) and low TBS values (n = 125, 87.4%) compared to controls (n = 63, 59.4% and n = 79, 74.5%, p = 0.049 and p = 0.009, respectively). The RA patients had more VF (n = 52, 36.4%) than controls (n = 24, 22.6%, p = 0.02). A total of 20 patients with VF (26.3%) had normal lumbar spine BMD and 9 (11.8%) also had a normal hip BMD. In patients with VF the combination of low TBS with normal spine BMD was more common than a normal TBS and low spine BMD (p = 0.008 for patients with RA, p = 0.025 for controls). DISCUSSION: It is known that VF can occur in patients with normal BMD. In patients with VF, a low TBS with normal spine BMD is found more frequently than normal TBS and low spine BMD. These results suggest that measurement of the TBS has the potential to be a useful tool to detect increased fracture risk in patients with RA and normal spine BMD.

[Biosimilars and the nocebo effect]. / Biosimilars und der Nocebo-Effekt.

Biosimilars have been approved for use in Germany for many years and in the meantime also in rheumatology but only a few years ago. Biosimilars, which are biotechnologically manufactured products the same as reference biologicals, have actually now achieved a substantial proportion of the market in some regions but there are still doubters among patients and physicians who fear a loss of quality even if there is no evidence for this. A part of this problem can be explained by the nocebo effect but which furthermore also has a substantial medical importance. This effect is described and explained in this article. Psychosocial and context-related factors, such as the relationship between patient and physician, previous experience with treatment and treatment expectations can either improve or impair the efficacy of treatment interventions. These phenomena are commonly known as placebo and nocebo effects. As placebo and nocebo effects can influence the development of symptoms, the frequency of undesired events and the efficacy of treatment, it is decisive to know these effects and to develop strategies for prevention in order to optimize the treatment results. Although in recent years experimental studies have achieved substantial progress in the clarification of the psychosocial and neurobiological mechanisms of placebo effects, detailed mechanisms of nocebo effects are still widely unexplored. An improved understanding of these mechanisms promises the development of user-friendly strategies for the clinical care to improve treatment results and patient satisfaction.

DXA Errors Are Common and Reduced by Use of a Reporting Template.

OBJECTIVE: High quality dual energy X-ray absorptiometry (DXA) acquisition, analysis, and reporting demands technical and interpretive excellence. We hypothesized that DXA errors are common and of such magnitude that incorrect clinical decisions might result. In this 2-phase study, we evaluated DXA technical and interpretation error rates in a clinical population and subsequently assessed if implementing an interpretation template reduced errors. METHODS: In phase 1, DXA scans of 345 osteoporosis clinic referrals were reviewed by International Society for Clinical Densitometry-certified technologists (n = 3) and physicians (n = 3). Technologists applied International Society for Clinical Densitometry performance standards to assess technical quality. Physicians assessed reporting compliance with published guidance, relevance of technical errors and determined overall and major error prevalence. Major errors were defined as "provision of inaccurate information that could potentially lead to incorrect patient care decisions." In phase 2, a DXA reporting template was implemented at 2 clinical DXA sites after which the 3 physicians reviewed 200 images and reports as above. The error prevalence was compared with the 298 patients in phase 1 from these sites. RESULTS: In phase 1, technical errors were identified in 90% of patients and affected interpretation in 13%. Interpretation errors were present in 80% of patients; 42% were major. The most common major errors were reporting incorrect information on bone mineral density change (70%) and incorrect diagnosis (22%). In phase 2, at these 2 clinical sites, major errors were present in 37% before and 17% after template implementation. Template usage reduced the odds of major error by 66% (odds ratio 0.34, 95% confidence interval 0.21, 0.53, and p < 0.0001). CONCLUSION: DXA technical and interpretation errors are extremely common and likely adversely affect patient care. Implementing a DXA reporting template reduces major errors and should become common practice. Additional interventions, such as requiring initial and ongoing training and/or certification for technologists and interpreters, are suggested.

[Differential diagnosis of axial spondyloarthritis-axSpA mimics]. / Differenzialdiagnose axiale Spondyloarthritis ­ "axSpA mimics".

The classification of axial spondyloarthritis (axSpA) comprises the classical ankylosing spondylitis (AS), which is characterized by already existing structural changes in the sacroiliac joints, and the so-called non-radiographic axSpA (nr-axSpA), in which by definition such changes are not present. This distinction is based on the ASAS classification criteria for axSpA, which are however not suitable for a diagnosis. According to the current classification, spondyloarthritis (SpA) includes axSpA, which can be associated with psoriasis and/or chronic inflammatory bowel diseases (CED), such as Crohn's disease and ulcerative colitis, and peripheral SpA, which is further divided into SpA associated with psoriasis, partially synonymous with psoriatic arthritis (PsA), reactive SpA, partially synonymous with reactive arthritis (ReA) and SpA associated with CED, partially synonymous with arthritis associated with CED (e.g. Crohn's disease, ulcerative colitis) and peripheral undifferentiated SpA, which by definition is not associated with any of the above. In this article only the most important differential diagnoses are discussed, i. e. diffuse idiopathic skeletal hyperostosis (DISH), fractures and infections in the axial skeleton. In addition, the frequency of certain musculoskeletal findings in the normal population examined by magnetic resonance imaging (MRI) are also discussed.

[Rheumatological care in the Rheumazentrum Ruhrgebiet Rheumatism Center-a model for conurbations]. / Rheumatologische Versorgung im Rheumazentrum Ruhrgebiet ­ ein Modell für Ballungszentren.

The Ruhrgebiet Rheumatism Center, which is highly specialized for rheumatic diseases, is the largest of its kind in Germany. For many years it has fulfilled all the requirements for structural quality required by the Association of Rheumatological Acute Clinics (VRA) including regular participation in the KOBRA benchmarking project. Therefore, the center regularly receives the VRA seal for quality of care. In 2018 more than 7500 patients were treated as inpatients. Within the framework of care according to §116b (ASV since May 2019) there were nearly 25,000 outpatient patient contacts. Furthermore, an early screening program (triage) was established 5 years ago in order to be able to identify patients with musculoskeletal complaints on a potentially inflammatory rheumatic basis. This functions in the sense of an early diagnosis and treatment in accordance with the treat-to-target concept within less than 4 weeks (initially) on an outpatient basis with respect to the required urgency, in order to subsequently provide sound diagnostic support. In the last 2 years 2017 and 2018, this deadline was met in more than 90% of cases. Within the scope of inpatient care approximately one third of patients were treated in recent years with a defined rheumatological complex therapy and 10% with pain complex therapy. Approximately 3% were treated with geriatric complex therapy and 65% were short-stay patients (<4 days), i.e. patients who received the necessary diagnostics and treatment on an inpatient basis at short notice. The overall structure of the rheumatism center, the cooperation with rheumatologists in private practice, many cooperation partners, referring physicians and patients represents a model for rheumatological care in large conurbations. The care of large numbers of patients also enables the further training of many assistants and this is essential for the future of good rheumatological medicine.

Could bioelectric impedance spectroscopy (BIS) measured appendicular intracellular water serve as a lean mass measurement in sarcopenia definitions? A pilot study.

DXA lean mass measurement for sarcopenia diagnosis is not always possible. Bioelectric impedance spectroscopy (BIS), a portable technology, is a potential alternative to DXA-measured lean mass. This pilot study explores the possibility and proposes an arbitrarily chosen potential cut-point for appendicular intracellular water corrected by height (aICW/ht2). INTRODUCTION: Sarcopenia definitions often include DXA lean mass measurement. However, DXA is not always available. We explored the potential of a less-expensive mobile method, bioelectric impedance spectroscopy (BIS), to assess lean mass for sarcopenia determination. We hypothesized that BIS-measured appendicular intracellular water (aICW/ht2) would correlate with DXA-measured appendicular lean mass (ALM)/ht2 and with functional parameters. If so, establishing an aICW/ht2 cut-point in sarcopenia definitions may be feasible. METHODS: Sixty-one community-dwelling women, mean age 79.9, had BIS and DXA lean mass, grip strength, gait speed, and jumping mechanography assessments. BIS aICW was calculated using limb length and intracellular water resistance. aICW/ht2 was compared to DXA-measured ALM/ht2 by linear regression. The European Working Group ALM/ht2 and an exploratory aICW/ht2 cut-point were utilized. RESULTS: In this cohort, ALM/ht2 and aICW/ht2 were moderately correlated, R2 = 0.55, p < 0.0001. Lean mass was low in 7 and normal in 44 by BIS and DXA. Those with low aICW/ht2 had lower grip strength (p = 0.04) and jump power (p = 0.0002) than those with normal aICW/ht2 and ALM/ht2. Subjects with low ALM/ht2 had lower jump power (p = 0.0006) but were not different in gait speed or grip strength. CONCLUSIONS: BIS aICW is correlated with DXA-measured ALM directly, and when height adjusted. An aICW/ht2 cut-point of 6.5 L/m2 identified 70% of women with low ALM/ht2. Women with low lean mass by DXA and BIS had poorer function measured by jump power. These pilot data support further evaluation of BIS measurement inclusion into sarcopenia definitions.

Comparison of muscle/lean mass measurement methods: correlation with functional and biochemical testing.

DXA-measured lean mass is often used to assess muscle mass but has limitations. Thus, we compared DXA lean mass with two novel methods-bioelectric impedance spectroscopy and creatine (methyl-d3) dilution. The examined methodologies did not measure lean mass similarly and the correlation with muscle biomarkers/function varied. INTRODUCTION: Muscle function tests predict adverse health outcomes better than lean mass measurement. This may reflect limitations of current mass measurement methods. Newer approaches, e.g., bioelectric impedance spectroscopy (BIS) and creatine (methyl-d3) dilution (D3-C), may more accurately assess muscle mass. We hypothesized that BIS and D3-C measured muscle mass would better correlate with function and bone/muscle biomarkers than DXA measured lean mass. METHODS: Evaluations of muscle/lean mass, function, and serum biomarkers were obtained in older community-dwelling adults. Mass was assessed by DXA, BIS, and orally administered D3-C. Grip strength, timed up and go, and jump power were examined. Potential muscle/bone serum biomarkers were measured. Mass measurements were compared with functional and serum data using regression analyses; differences between techniques were determined by paired t tests. RESULTS: Mean (SD) age of the 112 (89F/23M) participants was 80.6 (6.0) years. The lean/muscle mass assessments were correlated (.57-.88) but differed (p < 0.0001) from one another with DXA total body less head being highest at 37.8 (7.3) kg, D3-C muscle mass at 21.1 (4.6) kg, and BIS total body intracellular water at 17.4 (3.5) kg. All mass assessment methods correlated with grip strength and jump power (R = 0.35-0.63, p < 0.0002), but not with gait speed or repeat chair rise. Lean mass measures were unrelated to the serum biomarkers measured. CONCLUSIONS: These three methodologies do not similarly measure muscle/lean mass and should not be viewed as being equivalent. Functional tests assessing maximal muscle strength/power (grip strength and jump power) correlated with all mass measures whereas gait speed was not. None of the selected serum measures correlated with mass. Efforts to optimize muscle mass assessment and identify their relationships with health outcomes are needed.

[Becoming older with axial spondyloarthritis]. / Älter werden mit axialer Spondyloarthritis.

The combination of physiological age-related changes (e. g. reduction in muscle mass and function, reduction in organ function and degenerative changes in joints) and disease-specific changes of ankylosing spondylitis (AS), make older AS patients vulnerable for additional diseases. In this patient population various processes lead to a reduction in physical function, changes in posture, osteoporosis and sarcopenia, which then can result in falls and fractures, especially vertebral fractures. Mortality is increased in patients with AS, particularly in men due to an increase in cardiovascular mortality. Although the standardized assessment of cardiovascular risk factors in patients with inflammatory rheumatic diseases (independent of age) has been recommended for years, it is rarely done in clinical practice. Overall, data on comorbidities and risk factors are only available for AS patients and are lacking for other forms of spondyloarthritides.

Reproducibility of jumping mechanography and traditional measures of physical and muscle function in older adults.

SUMMARY: Improved approaches to assess functional change over time are needed to optimally reduce fall/fracture risk; jumping mechanography (JM) may be one such methodology. In this study, JM parameters were more reproducible than traditional functional tests. JM may be better able to demonstrate efficacy of interventions to mitigate sarcopenia. INTRODUCTION: Jumping mechanography (JM), a tool using maximal countermovement jumps performed on a force plate, may more reliably assess muscle function than traditional methods. The purpose of this study was to examine JM retest reliability in older adults compared with commonly used muscle and physical function assessments. METHODS: Community-dwelling individuals age≥70 years performed physical and muscle function assessments including the short physical performance battery (SPPB), grip strength, and JM on multiple occasions over 3 months. JM parameters included body weight-corrected peak power and jump height. Appendicular lean mass was measured by dual energy x-ray (DXA). Mixed effects linear regression models were used to estimate between- and within-person variability summarized as intra-class correlation coefficients (ICC). RESULTS: Ninety-seven individuals (49 females, 48 males, mean age 80.7 years) participated. All testing was well tolerated; no participant sustained injury. Jump power, height, and grip strength were greater (p<0.0001) in men than women. Grip strength, jump power, and height had excellent ICCs (0.95, 0.93, and 0.88, respectively); chair rise, SPPB score, and gait speed had lower ICCs (0.81, 0.77, and 0.76, respectively). CONCLUSION: In older adults, JM has excellent retest reliability, is stable over time, and can be performed safely. JM retest reliability was comparable to grip strength and possibly better than SPPB and gait speed. JM is a promising tool for muscle function assessment in older adults. Comparison of this approach with traditional assessment tools in longitudinal interventional studies is needed.

Definitions of Sarcopenia: Associations with Previous Falls and Fracture in a Population Sample.

Sarcopenia is common in later life and may be associated with adverse health outcomes such as disability, falls and fracture. There is no consensus definition for its diagnosis although diagnostic algorithms have been proposed by the European Working Group for Sarcopenia in Older People (EWGSOP), the International Working Group on Sarcopenia (IWGS) and the Foundation for the National Institutes of Health Sarcopenia Project (FNIH). More recently, Binkley and colleagues devised a score-based system for the diagnosis of "dysmobility syndrome" in an attempt to combine adverse musculoskeletal phenotypes, including sarcopenia and osteoporosis, in order to identify older individuals at particular risk. We applied these criteria to participants from the Hertfordshire Cohort Study to define their prevalence in an unselected cohort of UK community-dwelling older adults and assess their relationships with previous falls and fracture. Body composition and areal bone mineral density were measured using dual-energy X-ray absorptiometry, gait speed was determined by a 3-m walk test and grip strength was assessed with a Jamar hand-held dynamometer. Researcher-administered questionnaires were completed detailing falls and fracture history. The prevalence of sarcopenia in this cohort was 3.3, 8.3 and 2.0% using the EWGSOP, IWGS and related definition of FNIH, respectively; 24.8% of individuals had dysmobility syndrome. Individuals with dysmobility reported significantly higher number of falls (last year and since the age of 45 years) (p < 0.01) than those without it, but no increased fracture rate was observed in this group (p = 0.96). Those with sarcopenia as defined by the IWGS reported significantly higher falls in the last year and prevalent fractures (falls in the last year: OR 2.51; CI 1.09-5.81; p = 0.03; fractures OR 2.50; CI 1.05-5.92; p = 0.04) but these significant associations were not seen when the EWGSOP definition was applied. The IWGS definition of sarcopenia appears to be an effective means of identifying individuals at risk of prevalent adverse musculoskeletal events.

Effect of age and sex on jumping mechanography and other measures of muscle mass and function.

OBJECTIVES: Sarcopenia increases falls and fracture risk. Sarcopenia clinical trials require robust quantitative tools to evaluate muscle function; jumping mechanography (JM) is likely one such tool. However, US data comparing JM with traditional tests across the lifespan is limited. This study evaluated the effect of age and sex on JM compared with traditional function tests and lean mass. METHODS: US adults (213 women/119 men; mean age 65.4 years, range 27-96) performed functional tests including JM, Short Physical Performance Battery (SPPB) and grip strength (GS). Appendicular lean mass (ALM) was measured using DXA. RESULTS: Men had higher relative jump power [mean (SD) 28.5 (10.52) vs. 21.9 (7.11) W/kg], GS [35.5 (9.84) vs. 22.7 (6.98) kg] and ALM/ht(2) [8.25 (1.35) vs. 6.99 (1.38) kg/m2] (all p<0.0001); no difference was observed for SPPB components. JM parameters were more strongly correlated with age than traditional tests (R2=0.38-0.61 vs. R2=0.01-0.28) and weakly with GS and chair rise time (R2=0.30-0.36). CONCLUSION: JM parameters are correlated with GS and chair rise time and demonstrate stronger correlations with age. JM shows promise as a valuable tool to evaluate and monitor interventions for sarcopenia as it could potentially detect change in muscle function more precisely than existing tools.

What's in a name revisited: should osteoporosis and sarcopenia be considered components of "dysmobility syndrome?".

Sarcopenia and osteoporosis are age-related declines in the quantity and quality of muscle and bone respectively, with shared pathogeneses and adverse health consequences. Both absolute and relative fat excess, i.e., obesity and sarcopenic obesity, contribute to disability, falls, and fractures. Rather than focusing on a single component, i.e., osteoporosis, sarcopenia, or obesity, we realized that an opportunity exists to combine clinical factors, thereby potentially allowing improved identification of older adults at risk for disability, falls, and fractures. Such a combination could be termed dysmobility syndrome, analogous to the approach taken with metabolic syndrome. An arbitrary score-based approach to dysmobility syndrome diagnosis is proposed and explored in a small cohort of older adults. Further evaluation of such an approach in large population-based and prospective studies seems warranted.

Myostatin--the holy grail for muscle, bone, and fat?

Myostatin, a member of the transforming growth factor beta (TGF-ß) superfamily, was first described in 1997. Since then, myostatin has gained growing attention because of the discovery that myostatin inhibition leads to muscle mass accrual. Myostatin not only plays a key role in muscle homeostasis, but also affects fat and bone. This review will focus on the impact of myostatin and its inhibition on muscle mass/function, adipose tissue and bone density/geometry in humans. Although existing data are sparse, myostatin inhibition leads to increased lean mass and 1 study found a decrease in fat mass and increase in bone formation. In addition, myostatin levels are increased in sarcopenia, cachexia and bed rest whereas they are increased after resistance training, suggesting physiological regulatory of myostatin. Increased myostatin levels have also been found in obesity and levels decrease after weight loss from caloric restriction. Knowledge on the relationship of myostatin with bone is largely based on animal data where elevated myostatin levels lead to decreased BMD and myostatin inhibition improved BMD. In summary, myostatin appears to be a key factor in the integrated physiology of muscle, fat, and bone. It is unclear whether myostatin directly affects fat and bone, or indirectly via muscle. Whether via direct or indirect effects, myostatin inhibition appears to increase muscle and bone mass and decrease fat tissue-a combination that truly appears to be a holy grail. However, at this time, human data for both efficacy and safety are extremely limited. Moreover, whether increased muscle mass also leads to improved function remains to be determined. Ultimately potential beneficial effects of myostatin inhibition will need to be determined based on hard outcomes such as falls and fractures.

Vertebral fracture assessment: impact of instrument and reader.

PURPOSE: Many osteoporotic vertebral fractures are not clinically recognized but increase fracture risk. We hypothesized that a newer generation densitometer increases the number of evaluable vertebrae and vertebral fractures detected. We also explored the impact of reader experience on vertebral fracture assessment (VFA) interpretation. METHODS: VFA images obtained using Prodigy and iDXA densitometers in 103 older adults were evaluated for vertebral visualization and fracture presence in the T4-L5 region. A "true" read for each densitometer was achieved by consensus. If readers disagreed, the evaluation of a third expert physician was taken as true. Main outcomes were evaluable vertebrae, vertebral fractures, and intrareader/interreader reproducibility. RESULTS: Using the "true" reads, 92% of vertebrae were visualized on iDXA and 76% on Prodigy. Numerically, more fractures were identified with iDXA; the "true" reads found 43 fractures on iDXA and 21 on Prodigy. The experienced reader had better intrareader and interreader reproducibility than the inexperienced reader when compared with the "true" read. CONCLUSIONS: Using the newer iDXA densitometer for VFA analysis improves vertebral body visualization and fracture detection. Training and experience enhance result reproducibility.

Normative Values of Muscle Power using Force Plate Jump Tests in Men Aged 77-101 Years: The Osteoporotic Fractures in Men (MrOS) Study.

OBJECTIVE: To determine normative values for weight-bearing, countermovement leg extension ("jump") tests in the oldest men and characteristics of those not completing vs. completing tests. DESIGN: 2014-16 cross-sectional exam. SETTING: Six U.S. sites from the Osteoporotic Fractures in Men (MrOS) Study. PARTICIPANTS: Community-dwelling men (N=1,841) aged 84.5±4.2 (range: 77-101) years. INTERVENTIONS: N/A. MEASUREMENTS: Jump tests on a force plate measured lower-extremity muscle peak power/kg, velocity and force/kg at peak power, with normative values for 5-year age groups and by limitations in moderate-intensity activities of daily living (ADLs) and climbing several flights of stairs. RESULTS: Jump completion was 68.9% (N=1,268/1,841) and 98% (1,242/1,268) had ≥1 analyzable trial/participant. Exclusions primarily were due to poor mobility and/or balance: 24.8% (456/1,841) prior to and 6.4% (N=117/1,841) after attempting testing. Peak power was 20.8±5.3 W/kg, with 1.2±0.3 m/s for velocity, and 16.7±1.9 N/kg for force at peak power. Each 5-year age group >80 years had subsequently 10% lower power/kg, with 30% lower power/kg at >90 vs. ≤80 years (all p<0.05). Velocity and force/kg at peak power were 24% and 9% lower respectively, at >90 vs. ≤80 years (all p<0.05). Limitations in both moderate ADLs and climbing several flights of stairs were associated with 16% lower age-adjusted power/kg, equivalent to 5-10 years of aging, with 11% and 6% lower age-adjusted velocity and force/kg respectively, vs. those without limitation (all p<0.05). Men not completing vs. completing jumps had older age, higher BMI, lower physical activity, more comorbidities, worse cognition, more IADLs/ADLs and more falls in the past year (all p<0.05). Post-jump pain occurred in 4.6% (58/1,268), with 2 participants stopping testing due to pain. Only 24/1,242 (2%) had all trials/participant without flight (i.e., inability to lift feet), with 323/1,242 having ≥1 trial/participant without flight (total of 28%). No serious adverse safety events (e.g., injury) occurred. CONCLUSIONS: A multicenter cohort of oldest men with a range of function had higher declines in jump power/kg and velocity vs. force/kg across each 5-year age group >80 years. Future research should examine age- and functional-related declines in jump measures related to physical performance decline, falls, fractures, and disability.

Changes in lower extremity muscle function after 56 days of bed rest.

Preservation of muscle function, known to decline in microgravity and simulation (bed rest), is important for successful spaceflight missions. Hence, there is great interest in developing interventions to prevent muscle-function loss. In this study, 20 males underwent 56 days of bed rest. Ten volunteers were randomized to do resistive vibration exercise (RVE). The other 10 served as controls. RVE consisted of muscle contractions against resistance and concurrent whole-body vibration. Main outcome parameters were maximal isometric plantar-flexion force (IPFF), electromyography (EMG)/force ratio, as well as jumping power and height. Measurements were obtained before and after bed rest, including a morning and evening assessment on the first day of recovery from bed rest. IPFF (-17.1%), jumping peak power (-24.1%), and height (-28.5%) declined (P < 0.05) in the control group. There was a trend to EMG/force ratio decrease (-20%; P = 0.051). RVE preserved IPFF and mitigated the decline of countermovement jump performance (peak power -12.2%; height -14.2%). In both groups, IPFF was reduced between the two measurements of the first day of reambulation. This study indicates that bed rest and countermeasure exercises differentially affect the various functions of skeletal muscle. Moreover, the time course during recovery needs to be considered more thoroughly in future studies, as IPFF declined not only with bed rest but also within the first day of reambulation. RVE was effective in maintaining IPFF but only mitigated the decline in jumping performance. More research is needed to develop countermeasures that maintain muscle strength as well as other muscle functions including power.