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).     

Low Testosterone,but Not Estradiol,Is Associated With Incident Falls in Older Men: The International MrOS Study

Fracture risk is determined by bone strength and the risk of falls. The relationship between serum sex steroids and bone strength parameters in men is well known, whereas the predictive value of sex steroids for falls is less studied. The aim of this study was to assess the associations between serum testosterone (T) and estradiol (E2) and the likelihood of falls. Older men (aged ≥65 years) from the United States (n = 1919), Sweden (n = 2495), and Hong Kong (n = 1469) participating in the Osteoporotic Fractures in Men Study had baseline T and E2 analyzed by mass spectrometry. Bioavailable (Bio) levels were calculated using mass action equations. Incident falls were ascertained every 4 months during a mean follow‐up of 5.7 years. Associations between sex steroids and falls were estimated by generalized estimating equations. Fall rate was highest in the US and lowest in Hong Kong (US 0.50, Sweden 0.31, Hong Kong 0.12 fall reports/person/year). In the combined cohort of 5883 men, total T (odds ratio [OR] per SD increase = 0.88, 95% confidence interval [CI] 0.86–0.91) and BioT (OR = 0.86, 95% CI 0.83–0.88) were associated with incident falls in models adjusted for age and prevalent falls. These associations were only slightly attenuated after simultaneous adjustment for physical performance variables (total T: OR = 0.94, 95% CI 0.91–0.96; BioT: OR = 0.91, 95% CI 0.89–0.94). E2, BioE2, and sex hormone‐binding globulin (SHBG) were not significantly associated with falls. Analyses in the individual cohorts showed that both total T and BioT were associated with falls in MrOS US and Sweden. No association was found in MrOS Hong Kong, and this may be attributable to environmental factors rather than ethnic differences because total T and BioT predicted falls in MrOS US Asians. In conclusion, low total T and BioT levels, but not E2 or SHBG, are associated with increased falls in older men. © 2017 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals, Inc.     

Effects of a 12-Month Supervised,Community-Based,Multimodal Exercise Program Followed by a 6-Month Research-to-Practice Transition on Bone Mineral Density,Trabecular Microarchitecture,and Physical Function in Older Adults: A Randomized Controlled Trial

Multicomponent exercise programs are recommended to reduce fracture risk; however, their effectiveness in real-world community settings remain uncertain. This 18-month randomized controlled trial investigated the effects of a 12-month, community-based, supervised multicomponent exercise program followed by a 6-month “research-to-practice” transition on areal bone mineral density (BMD), trabecular bone microarchitecture, functional performance, and falls in older adults at increased fracture risk. One-hundred and sixty-two adults aged ≥60 years with osteopenia or at increased falls risk were randomized to the Osteo-cise: Strong Bones for Life multicomponent exercise program (n = 81) or a control group (n = 81). Exercise consisted of progressive resistance, weight-bearing impact, and balance training (3-days/week) performed at community leisure centers. Overall 148 (91%) participants completed the trial, and mean exercise adherence was 59% after 12 months and 45% during the final 6 months. After 12 months, there were significant net beneficial effects of exercise on lumbar spine and femoral neck BMD (1.0% to 1.1%, p < 0.05), muscle strength (10% to 13%, p < 0.05), and physical function (timed stair climb 5%; four-square step test 6%; sit-to-stand 16%, p ranging <0.05 to <0.001), which persisted after the 6-month transition. There were no significant effects of the 18-month intervention on distal femur or proximal tibia trabecular bone microarchitecture or falls incidence, but per protocol analysis (≥66% exercise adherence) revealed there was a significant net benefit of exercise (mean [95% confidence interval] 2.8% [0.2, 5,4]) on proximal tibia trabecular bone volume fraction (Osteo-cise 1.5% [−1.2, 4.2]; controls −1.3% [−2.6, 0.1]) after 18 months due to changes in trabecular number (Osteo-cise 1.7% [−0.9, 4.3]; controls −1.1% [−2.4, 0.2]) but not trabecular thickness (Osteo-cise − 0.2% [−0.5, 0.2]; controls −0.2% [−0.4, 0.0]). In conclusion, this study supports the effectiveness of the Osteo-cise: Strong Bones for Life program as a real-world, pragmatic, evidence-based community exercise program to improve multiple musculoskeletal health outcomes in older adults at increased fracture risk. © 2019 American Society for Bone and Mineral Research.     

High Serum Serotonin Predicts Increased Risk for Hip Fracture and Nonvertebral Osteoporotic Fractures: The MrOS Sweden Study

Because several studies have implicated serotonin as a regulator of bone mass, we here explore its potential association on fracture risk and falls, as on bone mineral density (BMD) and muscle strength, in humans. Serum levels of serotonin were analyzed in 950 men (aged 69 to 81 years), participating in the Gothenburg part of the population‐based study MrOS Sweden. Men taking selective serotonin reuptake inhibitors (SSRIs) had a mean value of 31.2 μg/L compared with 159.4 μg/L in those not taking SSRIs. SSRI users were excluded from further analysis. During 10‐year follow‐up, 224 men exhibited fractures, including 97 nonvertebral osteoporotic fractures (57 hip fractures), and 86 vertebral fractures. Serotonin was associated with hip fracture in linear analysis (hazard ratio [HR] = 1.27, 95% confidence interval [CI] 1.03–1.58) and to all fractures in a nonlinear manner, when quintiles of serotonin was included in quadratic terms (HR = 1.12, 95% CI 1.04–1.21). Men in serotonin quintile 5 had, in multivariable analysis, a HR of 2.30 (95% CI 1.31–4.02) for hip fracture and 1.82 (95% CI 1.17–2.85) for nonvertebral fractures compared with men in quintiles 1 to 4. Men in quintile 1 had, in multivariable analysis, a HR of 1.76 (95% CI 1.03–2.99) for nonvertebral fractures compared with men in quintiles 2 to 4. No association was found with vertebral fractures. Individuals in serotonin quintile 1 had higher prevalence of falls compared with quintiles 2 to 5 (odds ratio = 1.90, 95% CI 1.26–2.87). Serotonin was positively associated with hand‐grip strength (r = 0.08, p = 0.02) and inversely with hip BMD (r = ?0.10, p = 0.003). To assess the association between SSRIs and falls and fractures, the total MrOS Sweden cohort was examined (n = 3014). SSRI users (n = 90) had increased prevalence of falls (16% versus 33%, p = 0.0001) and increased rate of incident fractures (28.0 versus 44.7 per 1000 person‐years, p = 0.018). We present novel data showing that high levels of serotonin predict an increased risk for hip fracture and nonvertebral osteoporotic fractures. © 2018 American Society for Bone and Mineral Research.     

Mild hyponatremia as a risk factor for fractures: The rotterdam study

Recent studies suggest that mild hyponatremia is associated with fractures, but prospective studies are lacking. We studied whether hyponatremia is associated with fractures, falls, and/or bone mineral density (BMD). A total of 5208 elderly subjects with serum sodium assessed at baseline were included from the prospective population‐based Rotterdam Study. The following data were analyzed: BMD, vertebral fractures (mean follow‐up 6.4 years), nonvertebral fractures (7.4 years), recent falls, comorbidity, medication, and mortality. Hyponatremia was detected in 399 subjects (7.7%, 133.4 ± 2.0 mmol/L). Subjects with hyponatremia were older (73.5 ± 10.3 years versus 70.0 ± 9.0 years, p < .001), had more recent falls (23.8% versus16.4%, p < .01), higher type 2 diabetes mellitus prevalence (22.2% versus 10.3%, p < .001), and more often used diuretics (31.1% versus 15.0%, p < .001). Hyponatremia was not associated with lower BMD but was associated with increased risk of incident nonvertebral fractures [hazard ratio (HR) =1.39, 95% confidence interval (CI) 1.11–1.73, p = .004] after adjustment for age, sex, and body mass index. Further adjustments for disability index, use of diuretics, use of psycholeptics, recent falls, and diabetes did not modify results. In the fully adjusted model, subjects with hyponatremia also had increased risk of vertebral fractures at baseline [odds ratio (OR) = 1.78, 95% CI 1.04–3.06, p = .037] but not at follow‐up. Finally, all‐cause mortality was higher in subjects with hyponatremia (HR = 1.21, 95% CI 1.03–1.43, p = .022). It is concluded that mild hyponatremia in the elderly is associated with an increased risk of vertebral fractures and incident nonvertebral fractures but not with BMD. Increased fracture risk in hyponatremia also was independent of recent falls, pointing toward a possible effect on bone quality. © 2011 American Society for Bone and Mineral Research     

Effect of exercise training combined with isoflavone supplementation on bone and lipids in postmenopausal women: A randomized clinical trial

We determined the effects of 2 years of exercise training and soy isoflavone supplementation on bone mass and lipids in postmenopausal women provided with calcium and vitamin D. Women were randomized to four groups: exercise training (Ex); isoflavone supplementation (Iso: 165 mg/d [105 mg/d aglycone equivalent]); combined Ex and Iso (ExIso); and placebo (control). Exercise included resistance training (2 days/week) and walking (4 days/week). Our primary outcomes were lumbar spine and hip bone mineral density (BMD). Secondary outcomes included hip geometry, tibia and radius speed of sound (SOS), dynamic balance (6 m backward tandem walking), blood lipids, mammography, and endometrial thickness. A total of 351 women (Ex = 86, Iso = 90, ExIso = 87, control = 88) were randomized, with 298 analyzed at 2 years (Ex = 77, Iso = 76, ExIso = 72, control = 73). There was a significant interaction for total hip BMD (p < 0.001) such that ExIso had a greater rate of decrease (absolute change [95% confidence interval] = ?0.018 [?0.024, ?0.012] g/cm²) than either the Ex or Iso groups alone (?0.005 [?0.01, 0.001] and ?0.005 [?0.011, 0.001] g/cm², respectively). There were no differences between groups for changes in lumbar spine BMD and minimal significant changes in hip geometric properties and bone SOS. Exercise groups improved dynamic balance as measured by a decrease in backward tandem walking time over 6 m (p = 0.017). Isoflavone groups decreased low density lipoproteins (Iso: ?0.20 [?0.37, ?0.02] mmol/L; ExIso: ?0.23 [?0.40, ?0.06] mmol/L; p = 0.003) compared to non‐isoflavone groups (Ex: 0.01 [?0.16, 0.18] mmol/L; control: ?0.09 [?0.27, 0.08] mmol/L) and had lower adverse reports of menopausal symptoms (14% versus 33%; p = 0.01) compared to non‐isoflavone groups. Isoflavone supplementation did not increase endometrial thickness or abnormal mammograms. We conclude exercise training and isoflavone supplementation maintain hip BMD compared to control, but these two interventions interfere with each other when combined. Isoflavone supplementation decreased LDL and adverse events related to menopausal symptoms. © 2013 American Society for Bone and Mineral Research.     

Integrating lung ultrasound in the hemodynamic evaluation of acute circulatory failure (the fluid administration limited by lung sonography protocol)

In circulatory failure, fluid administration limited by lung sonography protocol uses lung ultrasound artifacts and makes sequential diagnosis of obstructive, cardiogenic, hypovolemic, and septic shock. Lung ultrasound is used along with simple cardiac and vena cava analysis. Whenever echocardiography cannot be performed, fluid administration limited by lung sonography protocol is favored because of its simplicity and could prove contributive. It is based on the presence (B profile) or the absence (A profile) of interstitial pulmonary edema. However, the latter does not represent actual alveolar edema, and transthoracic echocardiography is still used by intensivists as a pivotal hemodynamic measure. Tissue Doppler imaging facilitates the estimation of left ventricular filling pressures, whereas assessing right ventricular function is of prognostic value in states of shock due to massive pulmonary embolism and acute respiratory distress syndrome. In mechanically ventilated patients, poor acoustic windows are evident and performing transesophageal echocardiography may be necessary. Whenever noninvasive hemodynamic measures are inconclusive, in a deteriorating patient, a pulmonary artery catheter may be placed. Ultrasound is not a therapy but a guide for treatment, and physicians should aim to treat underlying pathologies. Despite its limitations, general chest ultrasound (lung and cardiac ultrasound) is a powerful diagnostic and monitoring tool reflecting an era of genuine “visual” medicine.