Predictive value of sarcopenia components for all-cause mortality: findings from population-based cohorts.

BACKGROUND: Low grip strength and gait speed are associated with mortality. However, investigation of the additional mortality risk explained by these measures, over and above other factors, is limited. AIM: We examined whether grip strength and gait speed improve discriminative capacity for mortality over and above more readily obtainable clinical risk factors. METHODS: Participants from the Health, Aging and Body Composition Study, Osteoporotic Fractures in Men Study, and the Hertfordshire Cohort Study were analysed. Appendicular lean mass (ALM) was ascertained using DXA; muscle strength by grip dynamometry; and usual gait speed over 2.4-6 m. Verified deaths were recorded. Associations between sarcopenia components and mortality were examined using Cox regression with cohort as a random effect; discriminative capacity was assessed using Harrell's Concordance Index (C-index). RESULTS: Mean (SD) age of participants (n = 8362) was 73.8(5.1) years; 5231(62.6%) died during a median follow-up time of 13.3 years. Grip strength (hazard ratio (95% CI) per SD decrease: 1.14 (1.10,1.19)) and gait speed (1.21 (1.17,1.26)), but not ALM index (1.01 (0.95,1.06)), were associated with mortality in mutually-adjusted models after accounting for age, sex, BMI, smoking status, alcohol consumption, physical activity, ethnicity, education, history of fractures and falls, femoral neck bone mineral density (BMD), self-rated health, cognitive function and number of comorbidities. However, a model containing only age and sex as exposures gave a C-index (95% CI) of 0.65(0.64,0.66), which only increased to 0.67(0.67,0.68) after inclusion of grip strength and gait speed. CONCLUSIONS: Grip strength and gait speed may generate only modest adjunctive risk information for mortality compared with other more readily obtainable risk factors.

Sarcopenia prevalence and incidence in older men - a MrOs Sweden study.

INTRODUCTION: The European Working Group on Sarcopenia in Older People (EWGSOP) published a revised definition of sarcopenia in 2018. There are few incidence studies of sarcopenia following the latest definition. OBJECTIVE: To study prevalence, incidence proportion and incidence rate of sarcopenia in a simple random sample of older Swedish men using the EWGSOP2 definition. METHODS: Men aged 69-81 were invited to participate in the Osteoporotic Fractures in Men (MrOs) Sweden study. Of 2,004 included participants, 1,266 participants (mean age 75.1, SD 3.1 years) completed baseline and 5-year follow-up measurements. We assessed muscle strength by measuring grip strength and chair stands test, lean mass by dual energy X-ray absorptiometry and physical performance by gait speed at baseline and follow-up. Sarcopenia prevalence and incidence were calculated according to the EWGSOP2 definition. RESULTS: Sarcopenia prevalence increased from 5.6% at baseline to 12.0% at follow-up. During the mean 5.2-year follow-up period, 9.1% developed sarcopenia (incidence proportion), corresponding to an incidence rate of 1.8 per 100 person-years at risk while 39.4% of the participants with sarcopenia at baseline participating in follow-up reversed to no longer having confirmed sarcopenia at 5-year follow-up. CONCLUSION: The prevalence of sarcopenia defined along EWGSOP2 criteria doubled within 5 years in older men, and more than a third of the study participants with sarcopenia at baseline did not have sarcopenia at follow-up. We conclude that sarcopenia is not a static condition.

Physical function tests predict incident falls: A prospective study of 2969 men in the Swedish Osteoporotic Fractures in Men study.

Aims: Falls are common in the elderly population, and fall-related injuries are a major health issue. We investigated the ability of simple physical tests to predict incident falls. Methods: The Swedish Osteoporotic Fractures in Men (MrOS) study includes 3014 population-based men aged 69-81 years at the start of the study. These men performed five different physical tests at baseline: right-hand grip strength, left-hand grip strength, timed stand test, 6 m walking test (time and steps) and narrow walking test. During the first study year, we asked participants to fill out questionnaires regarding falls 4, 8 and 12 months after baseline. A total of 2969 men completed at least one questionnaire and were included in this study. We used generalised estimating equations and logarithmic regression models to estimate odds ratios for fallers and recurrent fallers (more than one fall during the one-year examination period) in each quartile of men for each physical test. Results: The proportions of fallers and recurrent fallers were higher in the lowest quartile of the physical tests than in the other three quartiles combined for all physical tests. A reduction of one standard deviation in respective physical test resulted in a 13-21% higher risk of becoming a faller and a 13-31% higher risk of becoming a recurrent faller. Conclusions: Low results on simple physical tests is a risk factor for incident falls in elderly Swedish men and may facilitate identification of high-risk individuals suitable for fall-intervention programs.

The fracture predictive ability of a musculoskeletal composite score in old men - data from the MrOs Sweden study.

BACKGROUND: Detection of high-risk individuals for fractures are needed. This study assessed whether level of physical activity (PA) and a musculoskeletal composite score could be used as fracture predictive tools, and if the score could predict fractures better than areal bone mineral density (aBMD). METHODS: MrOs Sweden is a prospective population-based observational study that at baseline included 3014 men aged 69-81 years. We assessed femoral neck bone mineral content (BMC), bone area, aBMD and total body lean mass by dual energy X-ray absorptiometry, calcaneal speed of sound by quantitative ultrasound and hand grip strength by a handheld dynamometer. PA was assessed by the Physical Activity Scale for the Elderly (PASE) questionnaire. We followed the participants until the date of first fracture, death or relocation (median 9.6 years). A musculoskeletal composite score was calculated as mean Z-score of the five measured traits. A Cox proportional hazards model was used to analyze the association between the musculoskeletal traits, the composite score and incident fractures (yes/no) during the follow-up period. Data are presented as hazard ratios (HR) with 95% confidence intervals (95% CI) for fracture for a + 1 standard deviation (SD) change (+ 1 Z-score) in the various musculoskeletal traits as well as the composite score. We used a linear regression model to estimate the association between level of PA, measured as PASE-score and the different musculoskeletal traits as well as the composite score. RESULTS: A + 1 SD higher composite score was associated with an incident fracture HR of 0.61 (0.54, 0.69), however not being superior to aBMD in fracture prediction. A + 1 SD higher PASE-score was associated with both a higher composite score and lower fracture incidence (HR 0.83 (0.76, 0.90)). CONCLUSIONS: The composite score was similar to femoral neck aBMD in predicting fractures, and also low PA predicted fractures. This highlights the need of randomized controlled trials to evaluate if PA could be used as a fracture preventive strategy.

International and ethnic variability of falls in older men.

AIMS: Fallers and especially recurrent fallers are at high risk for injuries. The aim of this study was to evaluate fall epidemiology in older men with special attention to the influence of age, ethnicity and country of residence. METHODS: 10,998 men aged 65 years or above recruited in Hong Kong, the United States (US) and Sweden were evaluated in a cross-sectional retrospective study design. Self-reported falls and fractures for the preceding 12 months were registered through questionnaires. Group comparisons were done by chi-square test or logistic regression. RESULTS: The proportion of fallers among the total population was 16.5% in ages 65-69, 24.8% in ages 80-84 and 43.2% in ages above 90 (P <0.001). The corresponding proportions of recurrent fallers in the same age groups were 6.3%, 10.1% and 18.2%, respectively (P <0.001), and fallers with fractures 1.0%, 2.3% and 9.1%, respectively (P <0.001). The proportion of fallers was highest in the US, intermediate in Sweden and lowest in Hong Kong (in most age groups P <0.05). The proportion of fallers among white men in the US was higher than in white men in Sweden (all comparable age groups P <0.01) but there were no differences in the proportion of fallers in US men with different ethnicity. CONCLUSIONS: The proportion of fallers in older men is different in different countries, and data in this study corroborate with the view that society of residence influences fall prevalence more than ethnicity.

Prevalence and morbidity of neck pain: a cross-sectional study of 3000 elderly men.

BACKGROUND: The purpose of this study is to determine the prevalence and morbidity of neck pain with or without cervical rhizopathy, upper extremity motor deficit and/or thoracolumbar pain in elderly men. METHODS: We conducted a cross-sectional questionnaire study of 3,000 community-dwelling older men with a mean age of 75.4 ± 3.2 years (range 69-81) to determine if they had experienced neck pain with or without cervical rhizopathy/upper extremity motor deficit/thoracolumbar pain (yes/no) during the preceding 12 months, and if so, morbidity with the condition (no/minor/moderate/severe). RESULTS: Among the participants, 865 (29%) reported they had experienced neck and 1,619 (54%) thoracolumbar pain. Among the men with neck pain, 59% had experienced only neck pain, 17% neck pain and cervical rhizopathy and 24% neck pain, rhizopathy and motor deficit. For men with only neck pain, the morbidity was severe in 13%, for men with neck pain and rhizopathy it was 24%, and for men with pain, rhizopathy and motor deficit it was 46% (p < 0.001). Among the men with neck pain, 23% had experienced only neck pain and no thoracolumbar pain; the remaining 77% had both neck and thoracolumbar pain. The morbidity was severe in 10% of the men with neck pain but no thoracolumbar pain and 30% in men with neck and thoracolumbar pain (p < 0.001). CONCLUSION: Neck pain in elderly men is common but symptoms and morbidity vary. For men who only have neck pain, 1/8 rated their morbidity as severe, while almost half who also had cervical rhizopathy and motor deficit and almost 1/3 of those who also had thoracolumbar pain reported severe morbidity.

Recent sarcopenia definitions-prevalence, agreement and mortality associations among men: Findings from population-based cohorts.

BACKGROUND: The 2019 European Working Group on Sarcopenia in Older People (EWGSOP2) and the Sarcopenia Definitions and Outcomes Consortium (SDOC) have recently proposed sarcopenia definitions. However, comparisons of the performance of these approaches in terms of thresholds employed, concordance in individuals and prediction of important health-related outcomes such as death are limited. We addressed this in a large multinational assembly of cohort studies that included information on lean mass, muscle strength, physical performance and health outcomes. METHODS: White men from the Health Aging and Body Composition (Health ABC) Study, Osteoporotic Fractures in Men (MrOS) Study cohorts (Sweden, USA), the Hertfordshire Cohort Study (HCS) and the Sarcopenia and Physical impairment with advancing Age (SarcoPhAge) Study were analysed. Appendicular lean mass (ALM) was ascertained using DXA; muscle strength by grip dynamometry; and usual gait speed over courses of 2.4-6 m. Deaths were recorded and verified. Definitions of sarcopenia were as follows: EWGSOP2 (grip strength <27 kg and ALM index <7.0 kg/m2 ), SDOC (grip strength <35.5 kg and gait speed <0.8 m/s) and Modified SDOC (grip strength <35.5 kg and gait speed <1.0 m/s). Cohen's kappa statistic was used to assess agreement between original definitions (EWGSOP2 and SDOC). Presence versus absence of sarcopenia according to each definition in relation to mortality risk was examined using Cox regression with adjustment for age and weight; estimates were combined across cohorts using random-effects meta-analysis. RESULTS: Mean (SD) age of participants (n = 9170) was 74.3 (4.9) years; 5929 participants died during a mean (SD) follow-up of 12.1 (5.5) years. The proportion with sarcopenia according to each definition was EWGSOP2 (1.1%), SDOC (1.7%) and Modified SDOC (5.3%). Agreement was weak between EWGSOP2 and SDOC (κ = 0.17). Pooled hazard ratios (95% CI) for mortality for presence versus absence of each definition were EWGSOP2 [1.76 (1.42, 2.18), I2 : 0.0%]; SDOC [2.75 (2.28, 3.31), I2 : 0.0%]; and Modified SDOC [1.93 (1.54, 2.41), I2 : 58.3%]. CONCLUSIONS: There was low prevalence and poor agreement among recent sarcopenia definitions in community-dwelling cohorts of older white men. All indices of sarcopenia were associated with mortality. The strong relationship between sarcopenia and mortality, regardless of the definition, illustrates that identification of appropriate management and lifecourse intervention strategies for this condition is of paramount importance.

Inferior physical performance test results of 10,998 men in the MrOS Study is associated with high fracture risk.

BACKGROUND: most fractures are preceded by falls. OBJECTIVE: the aim of this study was to determine whether tests of physical performance are associated with fractures. SUBJECTS: a total of 10,998 men aged 65 years or above were recruited. METHODS: questionnaires evaluated falls sustained 12 months before administration of the grip strength test, the timed stand test, the six-metre walk test and the twenty-centimetre narrow walk test. Means with 95% confidence interval (95% CI) are reported. P < 0.05 is a statistically significant difference. RESULTS: fallers with a fracture performed worse than non-fallers on all tests (all P < 0.001). Fallers with a fracture performed worse than fallers with no fractures both on the right-hand-grip strength test and on the six-metre walk test (P < 0.001). A score below -2 standard deviations in the right-hand-grip strength test was associated with an odds ratio of 3.9 (95% CI: 2.1-7.4) for having had a fall with a fracture compared with having had no fall and with an odds ratio of 2.6 (95% CI: 1.3-5.2) for having had a fall with a fracture compared with having had a fall with no fracture. CONCLUSION: the right-hand-grip strength test and the six-metre walk test performed by old men help discriminate fallers with a fracture from both fallers with no fracture and non-fallers.

Inferior physical performance tests in 10,998 men in the MrOS study is associated with recurrent falls.

BACKGROUND: recurrent fallers are at especially high risk for injuries. OBJECTIVE: to study whether tests of physical performance are associated with recurrent falls. SUBJECTS: a total of 10,998 men aged 65 years or above. METHODS: questionnaires evaluated falls sustained 12 months preceding testing of grip strength, timed stand, 6-m walk and 20-cm narrow walk test. Means with 95% confidence interval (95% CI) are reported. P < 0.01 is a statistically significant difference. RESULTS: in comparison to both occasional fallers and non-fallers, recurrent fallers performed more poorly on all the physical ability tests (all P < 0.001). A score below -2 standard deviations (SDs) in the right-hand grip strength test was associated with an odds ratio of 2.4 (95% CI 1.7, 3.4) for having had recurrent falls compared with having had no fall and of 2.0 (95% CI 1.3, 3.4) for having had recurrent falls compared with having had an occasional fall. CONCLUSION: low performance in physical ability tests are in elderly men associated with recurrent falls.

Greater pQCT Calf Muscle Density Is Associated with Lower Fracture Risk, Independent of FRAX, Falls and BMD: A Meta-Analysis in the Osteoporotic Fractures in Men (MrOS) Study.

We investigated the predictive performance of peripheral quantitative computed tomography (pQCT) measures of both calf muscle density (an established surrogate for muscle adiposity, with higher values indicating lower muscle adiposity and higher muscle quality) and size (cross-sectional area [CSA]) for incident fracture. pQCT (Stratec XCT2000/3000) measurements at the tibia were undertaken in Osteoporotic Fractures in Men (MrOS) United States (US), Hong Kong (HK), and Swedish (SW) cohorts. Analyses were by cohort and synthesized by meta-analysis. The predictive value for incident fracture outcomes, illustrated here for hip fracture (HF), using an extension of Poisson regression adjusted for age and follow-up time, was expressed as hazard ratio (HR) per standard deviation (SD) increase in exposure (HR/SD). Further analyses adjusted for femoral neck (fn) bone mineral density (BMD) T-score, Fracture Risk Assessment Tool (FRAX) 10-year fracture probability (major osteoporotic fracture) and prior falls. We studied 991 (US), 1662 (HK), and 1521 (SW) men, mean ± SD age 77.0 ± 5.1, 73.9 ± 4.9, 80 ± 3.4 years, followed for a mean ± SD 7.8 ± 2.2, 8.1 ± 2.3, 5.3 ± 2.0 years, with 31, 47, and 78 incident HFs, respectively. Both greater muscle CSA and greater muscle density were associated with a lower risk of incident HF [HR/SD: 0.84; 95% confidence interval [CI], 0.72-1.0 and 0.78; 95% CI, 0.66-0.91, respectively]. The pattern of associations was not materially changed by adjustment for prior falls or FRAX probability. In contrast, after inclusion of fn BMD T-score, the association for muscle CSA was no longer apparent (1.04; 95% CI, 0.88-1.24), whereas that for muscle density was not materially changed (0.69; 95% CI, 0.59-0.82). Findings were similar for osteoporotic fractures. pQCT measures of greater calf muscle density and CSA were both associated with lower incidence of fractures in older men, but only muscle density remained an independent risk factor for fracture after accounting for fn BMD. These findings demonstrate a complex interplay between measures of bone, muscle size, and quality, in determining fracture risk. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Sarcopenia Definitions as Predictors of Fracture Risk Independent of FRAX® , Falls, and BMD in the Osteoporotic Fractures in Men (MrOS) Study: A Meta-Analysis.

Dual-energy X-ray absorptiometry (DXA)-derived appendicular lean mass/height2 (ALM/ht2 ) is the most commonly used estimate of muscle mass in the assessment of sarcopenia, but its predictive value for fracture is substantially attenuated by femoral neck (fn) bone mineral density (BMD). We investigated predictive value of 11 sarcopenia definitions for incident fracture, independent of fnBMD, fracture risk assessment tool (FRAX® ) probability, and prior falls, using an extension of Poisson regression in US, Sweden, and Hong Kong Osteoporois Fractures in Men Study (MrOS) cohorts. Definitions tested were those of Baumgartner and Delmonico (ALM/ht2 only), Morley, the International Working Group on Sarcopenia, European Working Group on Sarcopenia in Older People (EWGSOP1 and 2), Asian Working Group on Sarcopenia, Foundation for the National Institutes of Health (FNIH) 1 and 2 (using ALM/body mass index [BMI], incorporating muscle strength and/or physical performance measures plus ALM/ht2 ), and Sarcopenia Definitions and Outcomes Consortium (gait speed and grip strength). Associations were adjusted for age and time since baseline and reported as hazard ratio (HR) for first incident fracture, here major osteoporotic fracture (MOF; clinical vertebral, hip, distal forearm, proximal humerus). Further analyses adjusted additionally for FRAX-MOF probability (n = 7531; calculated ± fnBMD), prior falls (y/n), or fnBMD T-score. Results were synthesized by meta-analysis. In 5660 men in USA, 2764 Sweden and 1987 Hong Kong (mean ages 73.5, 75.4, and 72.4 years, respectively), sarcopenia prevalence ranged from 0.5% to 35%. Sarcopenia status, by all definitions except those of FNIH, was associated with incident MOF (HR = 1.39 to 2.07). Associations were robust to adjustment for prior falls or FRAX probability (without fnBMD); adjustment for fnBMD T-score attenuated associations. EWGSOP2 severe sarcopenia (incorporating chair stand time, gait speed, and grip strength plus ALM) was most predictive, albeit at low prevalence, and appeared only modestly influenced by inclusion of fnBMD. In conclusion, the predictive value for fracture of sarcopenia definitions based on ALM is reduced by adjustment for fnBMD but strengthened by additional inclusion of physical performance measures. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Putative Cut-Points in Sarcopenia Components and Incident Adverse Health Outcomes: An SDOC Analysis.

OBJECTIVES: Analyses performed by the Sarcopenia Definitions and Outcomes Consortium (SDOC) identified cut-points in several metrics of grip strength for consideration in a definition of sarcopenia. We describe the associations between the SDOC-identified metrics of low grip strength (absolute or standardized to body size/composition); low dual-energy x-ray absorptiometry (DXA) lean mass as previously defined in the literature (appendicular lean mass [ALM]/ht2 ); and slowness (walking speed <.8 m/s) with subsequent adverse outcomes (falls, hip fractures, mobility limitation, and mortality). DESIGN: Individual-level, sex-stratified pooled analysis. We calculated odds ratios (ORs) or hazard ratios (HRs) for incident falls, mobility limitation, hip fractures, and mortality. Follow-up time ranged from 1 year for falls to 8.8 ± 2.3 years for mortality. SETTING: Eight prospective observational cohort studies. PARTICIPANTS: A total of 13,421 community-dwelling men and 4,828 community-dwelling women. MEASUREMENTS Grip strength by hand dynamometry, gait speed, and lean mass by DXA. RESULTS: Low grip strength (absolute or standardized to body size/composition) was associated with incident outcomes, usually independently of slowness, in both men and women. ORs and HRs generally ranged from 1.2 to 3.0 for those below vs above the cut-point. DXA lean mass was not consistently associated with these outcomes. When considered together, those who had both muscle weakness by absolute grip strength (<35.5 kg in men and <20 kg in women) and slowness were consistently more likely to have a fall, hip fracture, mobility limitation, or die than those without either slowness or muscle weakness. CONCLUSION: Older men and women with both muscle weakness and slowness have a higher likelihood of adverse health outcomes. These results support the inclusion of grip strength and walking speed as components in a summary definition of sarcopenia. J Am Geriatr Soc 68:1429-1437, 2020.

Identification of Sarcopenia Components That Discriminate Slow Walking Speed: A Pooled Data Analysis.

BACKGROUND: The Sarcopenia Definitions and Outcomes Consortium (SDOC) sought to identify cut points for muscle strength and body composition measures derived from dual-energy x-ray absorptiometry (DXA) that discriminate older adults with slow walking speed. This article presents the core analyses used to guide the SDOC position statements. DESIGN: Cross-sectional data analyses of pooled data. SETTING: University-based research assessment centers. PARTICIPANTS: Community-dwelling men (n = 13,652) and women: (n = 5,115) with information on lean mass by DXA, grip strength (GR), and walking speed. MEASUREMENTS: Thirty-five candidate sarcopenia variables were entered into sex-stratified classification and regression tree (CART) models to agnostically choose variables and cut points that discriminate slow walkers (<0.80 m/s). Models with alternative walking speed outcomes were also evaluated (<0.60 and <1.0 m/s and walking speed treated continuously). RESULTS: CART models identified GR/body mass index (GRBMI) and GR/total body fat (GRTBF) as the primary discriminating variables for slowness in men and women, respectively. Men with GRBMI of 1.05 kg/kg/m2 or less were approximately four times more likely to be slow walkers than those with GRBMI of greater than 1.05 kg/kg/m2 . Women with GRTBF of less than 0.65 kg/kg were twice as likely to be slow walkers than women with GRTBF of 0.65 kg/kg or greater. Models with alternative walking speed outcomes selected only functions of GR as primary discriminators of slowness in both men and women. DXA-derived lean mass measures did not consistently discriminate slow walkers. CONCLUSION: GR with and without adjustments for body size and composition consistently discriminated older adults with slowness. CART models did not select DXA-based lean mass as a primary discriminator of slowness. These results were presented to an SDOC Consensus Panel, who used them and other information to develop the SDOC Position Statements. J Am Geriatr Soc 68:1419-1428, 2020.

The proximal hamstring avulsion clinical trial (PHACT)-a randomised controlled non-inferiority trial of operative versus non-operative treatment of proximal hamstrings avulsions: study protocol.

INTRODUCTION: The treatment of proximal hamstring avulsions is controversial. While several trials have investigated the outcome for patients treated surgically, there is today no prospective trial comparing operative treatment with non-operative treatment. This protocol describes the design for the proximal hamstring avulsion clinical trial (PHACT)-the first randomised controlled trial of operative versus non-operative treatment for proximal hamstring avulsions. METHODS AND ANALYSIS: PHACT is a multicentre randomised controlled trial conducted across Sweden, Norway and Finland. Eligible patients (60 participants/treatment arm) with a proximal hamstring avulsion of at least two of three tendons will be randomised to either operative or non-operative treatment. Participants allocated to surgery will undergo reinsertion of the tendons with suture anchors. The rehabilitation programme will be the same for both treatment groups. When patient or surgeon equipoise for treatment alternatives cannot be reached and randomisation therefore is not possible, patients will be invited to participate in a parallel observational non-randomised cohort. The primary outcome will be the patient-reported outcome measure Perth hamstring assessment tool at 24 months. Secondary outcomes include the Lower Extremity Functional Score, physical performance and muscle strength tests, patient satisfaction and MR imaging. Data analysis will be blinded and intention-to-treat analysis will be preformed. ETHICS AND DISSEMINATION: Ethical approval has been granted by the Ethical Committee of Uppsala University (DNR: 2017-170) and by the Norwegian ethical board (REC: 2017/1911). The study will be conducted in agreement with the Helsinki declaration. The findings will be disseminated in peer-reviewed publications. TRIAL REGISTRATION NUMBER: NCT03311997.

Use of a Swedish T-score reference population for women causes a two-fold increase in the amount of postmenopausal Swedish patients that fulfill the WHO criteria for osteoporosis.

The WHO criteria for osteoporosis are based on bone mineral density (BMD) values in comparison to a reference population of healthy young adults. The aim of this study was to create BMD references for ethnic Swedish women, and to investigate whether the use of these T-score measurements influence the amount of Swedish postmenopausal patients that are diagnosed as having osteoporosis. A bone density reference was created by measuring a population-based sample of 335 randomly selected Swedish women aged 20-39yr. BMD was measured by dual-energy X-ray absorptiometry (DXA) at the lumbar spine, proximal femur, and total body. These locally derived T-score values were subsequently used to diagnose a sample of 300 consecutive postmenopausal Swedish patients referred to the Uppsala Osteoporosis Unit. There was a slight age-dependent decrease in femoral neck BMD, whereas no age effect was seen at other sites such as total hip, lumbar spine, or total body. This suggests that the cohort represents the steady state BMD at the ages of expected peak bone mass in Swedish women. The correlation between BMD measures at different sites differed from r=0.55 (lumbar spine BMD vs femoral neck BMD [FNBMD]) to r=0.92 (total hip BMD vs FNBMD). Central DXA-generated T-scores were calculated from this cohort, and these were significantly higher (0.3-0.5 SD) as compared with manufacturers and NHANESIII reference populations. This indicates that young Swedish women have a higher peak bone mass than the subjects included in the reference populations currently used for clinical measurements. The T-score in total hip derived from the investigated cohort was subsequently used to diagnose 300 clinical patients (mean age 63yr) referred for a DXA scan by their physicians. The use of this locally established and ethnic representative, T-score reference increased the prevalence of osteoporosis in femoral neck and total hip with 53-106%. A Swedish female BMD reference representing peak bone mass has been established and the normative data are presented. Notably, this cohort has considerably higher BMD as compared to the NHANESIII and manufacturer's reference populations. The use of the present T-score reference therefore causes approximately a 2-fold increase in the amount of Swedish postmenopausal women that fulfill the WHO criteria for osteoporosis. This demonstrates the problems with using T-score as diagnostic threshold for osteoporosis and is an argument for future strategies to obtain standardized densitometric cut-offs, for example, mg/cm(2).

Serum DHEA and Its Sulfate Are Associated With Incident Fall Risk in Older Men: The MrOS Sweden Study.

The adrenal-derived hormones dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) are the most abundant circulating hormones and their levels decline substantially with age. Many of the actions of DHEAS are considered to be mediated through metabolism into androgens and estrogens in peripheral target tissues. The predictive value of serum DHEA and DHEAS for the likelihood of falling is unknown. The aim of this study was, therefore, to assess the associations between baseline DHEA and DHEAS levels and incident fall risk in a large cohort of older men. Serum DHEA and DHEAS levels were analyzed with mass spectrometry in the population-based Osteoporotic Fractures in Men study in Sweden (n = 2516, age 69 to 81 years). Falls were ascertained every 4 months by mailed questionnaires. Associations between steroid hormones and falls were estimated by generalized estimating equations. During a mean follow-up of 2.7 years, 968 (38.5%) participants experienced a fall. High serum levels of both DHEA (odds ratio [OR] per SD increase 0.85; 95% CI, 0.78 to 0.92) and DHEAS (OR 0.88, 95% CI, 0.81 to 0.95) were associated with a lower incident fall risk in models adjusted for age, BMI, and prevalent falls. Further adjustment for serum sex steroids or age-related comorbidities only marginally attenuated the associations between DHEA or DHEAS and the likelihood of falling. Moreover, the point estimates for DHEA and DHEAS were only slightly reduced after adjustment for lean mass and/or grip strength. Also, the addition of the narrow walk test did not substantially alter the associations between serum DHEA or DHEAS and fall risk. Finally, the association with incident fall risk remained significant for DHEA but not for DHEAS after simultaneous adjustment for lean mass, grip strength, and the narrow walk test. This suggests that the associations between DHEA and DHEAS and falls are only partially mediated via muscle mass, muscle strength, and/or balance. In conclusion, older men with high DHEA or DHEAS levels have a lesser likelihood of a fall. © 2018 American Society for Bone and Mineral Research.

Measures of Physical Performance and Muscle Strength as Predictors of Fracture Risk Independent of FRAX, Falls, and aBMD: A Meta-Analysis of the Osteoporotic Fractures in Men (MrOS) Study.

Measures of muscle mass, strength, and function predict risk of incident fractures, but it is not known whether this risk information is additive to that from FRAX (fracture risk assessment tool) probability. In the Osteoporotic Fractures in Men (MrOS) Study cohorts (Sweden, Hong Kong, United States), we investigated whether measures of physical performance/appendicular lean mass (ALM) by DXA predicted incident fractures in older men, independently of FRAX probability. Baseline information included falls history, clinical risk factors for falls and fractures, femoral neck aBMD, and calculated FRAX probabilities. An extension of Poisson regression was used to investigate the relationship between time for five chair stands, walking speed over a 6 m distance, grip strength, ALM adjusted for body size (ALM/height2 ), FRAX probability (major osteoporotic fracture [MOF]) with or without femoral neck aBMD, available in a subset of n = 7531), and incident MOF (hip, clinical vertebral, wrist, or proximal humerus). Associations were adjusted for age and time since baseline, and are reported as hazard ratios (HRs) for first incident fracture per SD increment in predictor using meta-analysis. 5660 men in the United States (mean age 73.5 years), 2764 men in Sweden (75.4 years), and 1987 men in Hong Kong (72.4 years) were studied. Mean follow-up time was 8.7 to 10.9 years. Greater time for five chair stands was associated with greater risk of MOF (HR 1.26; 95% CI, 1.19 to 1.34), whereas greater walking speed (HR 0.85; 95% CI, 0.79 to 0.90), grip strength (HR 0.77; 95% CI, 0.72 to 0.82), and ALM/height2 (HR 0.85; 95% CI, 0.80 to 0.90) were associated with lower risk of incident MOF. Associations remained largely similar after adjustment for FRAX, but associations between ALM/height2 and MOF were weakened (HR 0.92; 95% CI, 0.85 to 0.99). Inclusion of femoral neck aBMD markedly attenuated the association between ALM/height2 and MOF (HR 1.02; 95% CI, 0.96 to 1.10). Measures of physical performance predicted incident fractures independently of FRAX probability. Whilst the predictive value of ALM/height2 was substantially reduced by inclusion of aBMD requires further study, these findings support the consideration of physical performance in fracture risk assessment. © 2018 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals Inc.

A TA-repeat polymorphism in the gene for the estrogen receptor alpha does not correlate with muscle strength or body composition in young adult Swedish women.

OBJECTIVES: There are conflicting data in the literature whether estrogens affect muscle strength. Prospective studies with hormone replacement therapy have not been able to convincingly demonstrate a muscular effect and the putative role of estrogen in the development of lean body mass is not established. Both lean mass and fat mass are known to be under strong genetic control and therefore we have investigated the relation between a TA-repeat in the gene for the estrogen receptor alpha (ERalpha) and muscle strength and body composition. METHODS: 175 healthy Swedish women, aged 20-39 were randomly selected from the population registry and included in the study. Body mass measurements (lean mass, fat mass, body weight and BMI) and muscle strength (quadriceps, hamstring and grip strength) were evaluated. The TA-repeat in the ERalpha gene was amplified by polymerase chain reaction. RESULTS: Alleles with a TA-repeat length of 16 repeats or shorter were denoted short (e), and repeat length of 17 repeats or longer were denoted long (E). Women homozygous for the short and long genotype were denoted ee (31%) and EE (21%), respectively, while heterozygous individuals were denoted Ee (48%). The frequencies were in Hardy-Weinberg equilibrium. No associations were found between ERalpha genotypes and muscle strength or body composition. CONCLUSION: The TA-repeat in the human ERalpha gene does not correlate with muscle strength or body mass measurements, indicating that body composition is not as sensitive to genetic variation in this receptor as other target organs for estrogen.

Hyperkyphosis and back pain are not associated with prevalent vertebral fractures in women with osteoporosis.

Vertebral fractures (VFs) are the clinical consequence of spinal osteoporosis and may be associated with back pain and aggravated kyphosis. However, the relative importance of VFs as an underlying cause of kyphosis and chronic back pain is not known. The aim of this study was to investigate the relationship between prevalent VFs and the size of kyphosis, and back pain in osteoporotic women. Thirty-six women, aged 74.6 ± 8.3 years, were consecutively recruited from the osteoporosis unit at Uppsala University Hospital. The patients had 1-9 radiographic verified VFs. Tragus wall distance (TWD) and numeric rating scale were used to measure kyphosis and pain. All patients had a hyperkyphosis (TWD ≥ 10 cm). Notably, there were no associations between numbers or location of VFs versus size of kyphosis (ρ = 0.15, p = 0.4; ρ = -0.27, p = 0.12) or severity of back pain (ρ = -0.08, p = 0.66; ρ = 0.16, p = 0.35). Furthermore, no association was evident between kyphosis and back pain (ρ = -0.02, p = 0.89). There was, however, an association between size of kyphosis and age (R = 0.44, p = 0.008). In conclusion, these data suggest that prevalent VFs are not significantly associated with kyphosis or chronic back pain, in patients with manifest spinal osteoporosis.