Enhancing physical activity and reducing symptoms of patients with osteoarthritis of the knee: a randomized controlled trial of the PrevOP-Psychological Adherence Program.

BACKGROUND: This primary analysis evaluated the "PREVenting the impairment of primary Osteoarthritis by high-impact long-term Physical exercise regimen-Psychological Adherence Program" (PrevOP-PAP), designed to support patients with osteoarthritis of the knee (OAK) to engage in regular moderate-to-vigorous physical activity (MVPA) to reduce OAK symptoms (WOMAC scores). Theory-based on the health action process approach (HAPA), the intervention targeted volitional precursors of MVPA change: action and coping planning, maintenance and recovery self-efficacy, action control, and social network formation. We hypothesized that compared to an active control condition, increases in MVPA at the end of the 12-month intervention would translate into lower WOMAC scores at 24 months in the intervention condition. METHODS: Participants with radiographically verified moderate OAK (N = 241; 62.66% female; M(SD) = 65.60(7.61) years) were randomly assigned to the intervention (51%) or the active control condition. WOMAC scores (24 months) were the primary -, accelerometer-assessed MVPA (12 months) the key secondary outcomes. The PrevOP-PAP was a 12-month intervention with computer-assisted face-to-face and phone-based sessions designed to increase HAPA-proposed volitional precursors of MVPA change (up to 24 months; secondary outcomes). Intent-to-treat analyses included multiple regression and manifest path models. RESULTS: MVPA (12 months) did not mediate effects of the PrevOP-PAP on WOMAC scores (24 months). Compared to the active control condition, WOMAC scores (24 months) were lower in the intervention condition, but this effect did not remain stable in sensitivity analyses (b(SE) = -8.41(4.66), 95%-CI [-17.53; 0.71]). However, exploratory analyses revealed significantly stronger reductions in WOMAC-pain (24 months) in the intervention condition (b(SE) = -2.99(1.18), 95%-CI [-5.36; -0.63]). Groups did not differ in MVPA at 12 months (b(SE) = -3.78(3.42), 95%-CI [-10.80; 2.58]). Of the proposed precursors of MVPA change, action planning was higher in the intervention than in the control condition (24 months; b(SE) = 0.64(0.26), 95%-CI [0.14; 1.15]). CONCLUSIONS: Compared to an active control condition, the PrevOP-PAP did not produce reliable effects on WOMAC scores and none on preceding MVPA. Of the HAPA-proposed volitional precursors, only action planning was sustainably increased. Future interventions should use m-health applications to digitally support long-term changes in proposed volitional precursors of MVPA change. TRIAL REGISTRATION: German Clinical Trials Register; https://drks.de/search/de/trial/DRKS00009677 ; also available at http://apps.who.int/trialsearch/ ; registration number: DRKS00009677; date of registration: 26/01/2016.

Balance and prospective falls in patients with rheumatoid arthritis.

BACKGROUND: Postural control is associated with fall risk. Patients with rheumatoid arthritis (RA) have a higher risk to fall than healthy subjects. The objective of this study was to identify associations between variables of postural control with prospective falls in patients with RA. METHODS: For the baseline, the balance performance of 289 men and women with RA, ages 24-85 years, was evaluated by SPPB, FICSIT-4 and Romberg tests. Postural sway for Romberg, semitandem, tandem and one-leg stands were measured with the Leonardo Mechanograph®. Self-reported disability was assessed using the Health Assessment Questionnaire (HAQ) and the Activity-specific Balance Confidence Scale (ABC-scale). Falls were reported in quarterly reports over a year. Univariate and multiple logistic regression analysis were used to explore any associations with falling. Receiver-operating characteristics were determined, and the area under the curve is reported. RESULTS: A total of 238 subjects completed the 1-year follow-up, 48 (20.2%) experienced at least one fall during the observational period. Age (OR = 1.04, CI 1.01-1.07), HAQ (OR = 1.62, 1.1-2.38), FICSIT-4 scoring 0-4 (OR = 2.38, 1.13-5.0), and one-leg standing (OR = 2.14, 1.06-4.31) showed significant associations with falls. With regard to the SPPB and ABC-scale, no statistically significant associations with falls were found. The quartiles containing the worst results of medio-lateral sway of Romberg (OR = 2.63, CI 1.03-6.69), total sway of semitandem (OR = 3.07, CI 1.10-8.57) and tandem (OR = 2.86, CI 1.06-7.69), and area of sway of semitandem (OR = 2.80, CI 1.11-7.08) stands were associated with falls. CONCLUSIONS: The assessment of a one-leg stand seems to be a good screening tool to discriminate between high and low risk of falls in RA patients in clinical practice. A low FICSIT-4 score and several sway parameters are important predictors of falls. TRIAL REGISTRATION: The study has been registered at the German Clinical Trials Register and the WHO International Clinical Trials Registry Platform (ICTRP) since 16 March 2017 ( DRKS00011873 ).

Cervical spine and muscle adaptation after spaceflight and relationship to herniation risk: protocol from 'Cervical in Space' trial.

BACKGROUND: Astronauts have a higher risk of cervical intervertebral disc herniation. Several mechanisms have been attributed as causative factors for this increased risk. However, most of the previous studies have examined potential causal factors for lumbar intervertebral disc herniation only. Hence, we aim to conduct a study to identify the various changes in the cervical spine that lead to an increased risk of cervical disc herniation after spaceflight. METHODS: A cohort study with astronauts will be conducted. The data collection will involve four main components: a) Magnetic resonance imaging (MRI); b) cervical 3D kinematics; c) an Integrated Protocol consisting of maximal and submaximal voluntary contractions of the neck muscles, endurance testing of the neck muscles, neck muscle fatigue testing and questionnaires; and d) dual energy X-ray absorptiometry (DXA) examination. Measurements will be conducted at several time points before and after astronauts visit the International Space Station. The main outcomes of interest are adaptations in the cervical discs, muscles and bones. DISCUSSION: Astronauts are at higher risk of cervical disc herniation, but contributing factors remain unclear. The results of this study will inform future preventive measures for astronauts and will also contribute to the understanding of intervertebral disc herniation risk in the cervical spine for people on Earth. In addition, we anticipate deeper insight into the aetiology of neck pain with this research project. TRIAL REGISTRATION: German Clinical Trials Register, DRKS00026777. Registered on 08 October 2021.

Longitudinal changes in muscle power compared to muscle strength and mass.

OBJECTIVES: The study reports longitudinal changes in grip strength, muscle mass and muscle power of lower extremities. The aim is to identify early muscular changes to improve the diagnosis and treatment of sarcopenia. METHODS: Grip strength was measured by hand dynamometer, muscle mass by dual-energy X-ray absorptiometry and muscle power by performing a chair rise test and two-leg jumps (2LJP) on the Leonardo Mechanograph®. Longitudinal changes were analysed using paired t-tests by age group and sex. Differences between groups in terms of the annual change were tested by Analysis of Variance and the Dunnett's test. Comparisons between the variables were performed using one sample t-tests. RESULTS: Six-year changes were determined in 318 randomly selected healthy participants aged 20-90 years from Berlin. 2LJP declined significantly earlier in 20-39 years old women (-3.70 W/kg) and men (-5.97 W/kg, both p<0.001). This is an absolute annual decline of -0.46 W/kg in females and -0.75 W/kg in males. In the oldest age group, 2LJP showed the highest absolute annual loss with -0.99 W/kg in women and -0.88 W/kg in men. 2LJP was significantly different compared to all variables of muscle mass and strength (p<0.01). CONCLUSIONS: The results underline the importance of assessing muscle power using 2LJP during aging.

Association between sarcopenia, physical performance and falls in patients with rheumatoid arthritis: a 1-year prospective study.

BACKGROUND: Patients with rheumatoid arthritis (RA) are at increased risk of falls and fractures. Sarcopenia occurs more frequently in RA patients due to the inflammatory processes. Early diagnosis and prevention programmes are essential to avoid serious complications. The present study aims to identify risk factors for falls related to sarcopenia and physical performance. METHODS: In a 1-year prospective study, a total of 289 patients with RA, ages 24-85 years, were followed using quarterly fall diaries to report falls. At the baseline, medical data such as RA disease duration and Disease Activity Score (DAS28CRP) were collected. Self-reported disability was assessed using the Health Assessment Questionnaire (HAQ). Appendicular skeletal mass was determined by Dual X-ray-Absorptiometry (DXA). Physical performance was evaluated by handgrip strength, gait speed, chair rise test, Short Physical Performance Battery, and FICSIT-4. Muscle mechanography was measured with the Leonardo Mechanograph®. Sarcopenia was assessed according to established definitions by the European Working Group on Sarcopenia in Older People (EWGSOP2) and The Foundation for the National Institutes of Health (FNIH). Univariate and multiple logistic regression analysis were used to explore associations with falling. Receiver-operating characteristics (ROC) were performed, and the area under the curve is reported. RESULTS: A total of 238 subjects with RA completed the 1-year follow-up, 48 (20.2%) experienced at least one fall during the observational period. No association was found between sarcopenia and prospective falls. Age (OR = 1.04, CI 1.01-1.07), HAQ (OR = 1.62, 1.1-2.38), and low FICSIT-4 score (OR = 2.38, 1.13-5.0) showed significant associations with falls. CONCLUSIONS: In clinical practice, a fall assessment including age, self-reported activities of daily life and a physical performance measure can identify RA patients at risk of falling. TRIAL REGISTRATION: The study has been registered at the German Clinical Trials Register and the WHO International Clinical Trials Registry Platform (ICTRP) since 16 March 2017 ( DRKS00011873 ).

Effects of single-agent bortezomib as post-transplant consolidation therapy on multiple myeloma-related bone disease: a randomized phase II study.

This phase II study explored the effects of bortezomib consolidation versus observation on myeloma-related bone disease in patients who had a partial response or better after frontline high-dose therapy and autologous stem cell transplantation. Patients were randomized to receive four 35-day cycles of bortezomib 1·6 mg/m2 intravenously on days 1, 8, 15 and 22, or an equivalent observation period, and followed up for disease status/survival. The modified intent-to-treat population included 104 patients (51 bortezomib, 53 observation). There were no meaningful differences in the primary endpoint of change from baseline to end of treatment in bone mineral density (BMD). End-of-treatment rates (bortezomib versus observation) of complete response/stringent complete response were 22% vs. 11% (P = 0·19), very good partial response or better of 80% vs. 68% (P = 0·17), and progressive disease of 8% vs. 23% (P = 0·06); median progression-free survival was 44·9 months vs. 21·8 months (P = 0·22). Adverse events observed ≥15% more frequently with bortezomib versus observation were diarrhoea (37% vs. 0), peripheral sensory neuropathy (20% vs. 4%), nausea (18% vs. 0) and vomiting (16% vs. 0). Compared with observation, bortezomib appeared to have little impact on bone metabolism/health, but was associated with trends for improved myeloma response and survival.

Degenerative inter-vertebral disc disease osteochondrosis intervertebralis in Europe: prevalence, geographic variation and radiological correlates in men and women aged 50 and over.

Objectives: To assess the prevalences across Europe of radiological indices of degenerative inter-vertebral disc disease (DDD); and to quantify their associations with, age, sex, physical anthropometry, areal BMD (aBMD) and change in aBMD with time. Methods: In the population-based European Prospective Osteoporosis Study, 27 age-stratified samples of men and women from across the continent aged 50+ years had standardized lateral radiographs of the lumbar and thoracic spine to evaluate the severity of DDD, using the Kellgren-Lawrence (KL) scale. Measurements of anterior, mid-body and posterior vertebral heights on all assessed vertebrae from T4 to L4 were used to generate indices of end-plate curvature. Results: Images from 10 132 participants (56% female, mean age 63.9 years) passed quality checks. Overall, 47% of men and women had DDD grade 3 or more in the lumbar spine and 36% in both thoracic and lumbar spine. Risk ratios for DDD grades 3 and 4, adjusted for age and anthropometric determinants, varied across a three-fold range between centres, yet prevalences were highly correlated in men and women. DDD was associated with flattened, non-ovoid inter-vertebral disc spaces. KL grade 4 and loss of inter-vertebral disc space were associated with higher spine aBMD. Conclusion: KL grades 3 and 4 are often used clinically to categorize radiological DDD. Highly variable European prevalences of radiologically defined DDD grades 3+ along with the large effects of age may have growing and geographically unequal health and economic impacts as the population ages. These data encourage further studies of potential genetic and environmental causes.

Serum sclerostin and DKK1 in relation to exercise against bone loss in experimental bed rest.

The impact of effective exercise against bone loss during experimental bed rest appears to be associated with increases in bone formation rather than reductions of bone resorption. Sclerostin and dickkopf-1 are important inhibitors of osteoblast activity. We hypothesized that exercise in bed rest would prevent increases in sclerostin and dickkopf-1. Twenty-four male subjects performed resistive vibration exercise (RVE; n = 7), resistive exercise only (RE; n = 8), or no exercise (control n = 9) during 60 days of bed rest (2nd Berlin BedRest Study). We measured serum levels of BAP, CTX-I, iPTH, calcium, sclerostin, and dickkopf-1 at 16 time-points during and up to 1 year after bed rest. In inactive control, after an initial increase in both BAP and CTX-I, sclerostin increased. BAP then returned to baseline levels, and CTX-I continued to increase. In RVE and RE, BAP increased more than control in bed rest (p ≤ 0.029). Increases of CTX-I in RE and RVE did not differ significantly to inactive control. RE may have attenuated increases in sclerostin and dickkopf-1, but this was not statistically significant. In RVE there was no evidence for any impact on sclerostin and dickkopf-1 changes. Long-term recovery of bone was also measured and 6-24 months after bed rest, and proximal femur bone mineral content was still greater in RVE than control (p = 0.01). The results, while showing that exercise against bone loss in experimental bed rest results in greater bone formation, could not provide evidence that exercise impeded the rise in serum sclerostin and dickkopf-1 levels.

Effects of vitamin D3, omega-3 s and a simple strength training exercise program on bone health: the DO-HEALTH randomized controlled trial.

INTRODUCTION: Evidence on the effects of Vitamin D, omega-3 s and exercise on aBMD in healthy older adults is limited. We examined whether vitamin D3, omega-3 s, or a simple home-based exercise program (SHEP), alone or in combination, over three years, improve lumbar spine (LS), femoral neck (FN) or total hip (TH) aBMD assessed by DXA. METHODS: aBMD was a secondary outcome in DO-HEALTH, a 3-year, multicenter, double-blind, randomized 2 × 2 × 2 factorial design trial in generally healthy older adults age ≥ 70 years. The study interventions were vitamin D3 (2000IU/d), omega-3 s (1 g/d), and SHEP (3 × 30 min/wk), applied alone or in combination in 8 treatment arms. Mixed effect models were used adjusting for age, sex, BMI, prior fall, study site and baseline level of the outcome. Main effects were assessed in the absence of an interaction between the interventions. Subgroup analyses by sex, physical activity level, dietary calcium intake, serum 25(OH)D levels, and fracture history were conducted. RESULTS: DXA scans were available for 1493 participants (mean age 75 years; 80.4% were physically active, 44% had 25(OH)D levels <20 ng/ml). At the LS and FN sites, none of the treatments showed a benefit. At the TH, vitamin D vs. no vitamin D treatment showed a significant benefit across 3 years (difference in adjusted means [AM]: 0.0035 [95% CI 0.0011, 0.0059] g/cm2). Furthermore, there was a benefit for vitamin D vs. no vitamin D treatment on LS aBMD in the male subgroup of (interaction P = 0.003; ∆AM: 0.0070 [95% CI 0.0007, 0.0132] g/cm2). CONCLUSIONS: Omega-3 and SHEP had no benefit on aBMD in healthy, active and largely vitamin D replete older adults. Our study suggests a small benefit of 2000 IU vitamin D daily on TH aBMD overall and LS aBMD among men, however, effect sizes were very modest and the clinical impact of these findings is unclear.

Vitamin D, omega-3 fatty acids (omega-3 s) and strength training are simple but promising strategies to improve bone health, however, their effect in healthy older adults over a period of three years was unclear. In this study, we examined whether daily vitamin D supplementation (2000 IU/d), daily omega-3 s supplementation (1 g/d) or a simple strength training program performed three times per week, either applied alone (e.g., only vitamin D supplements) or in combination (e.g., vitamin D and omega-3 s supplements) could improve bone density at the spine, hip or femoral neck. We included 1493 healthy older adults from Switzerland, Germany, France and Portugal who were at least 70 years of age and who had not experienced any major health events in the five years before study start. Taking omega-3 s supplements showed no benefit for bone density. Similarly, the simple strength exercise program showed no benefit. In contrast, participants receiving daily vitamin D supplements experienced a benefit at the hip. However, it should be noted that the effect across three years was very small.

Association Between Visual Acuity and Prospective Fall Risk in Generally Healthy and Active Older Adults: The 3-Year DO-HEALTH Study.

OBJECTIVE: Although aging has a strong impact on visual acuity (VA) and falls, their interaction is understudied in generally healthy older adults. This study aimed to examine if and to what extent baseline VA is associated with an increased risk of all and injurious falls over 3 years in generally healthy community-dwelling older adults. DESIGN: Observational analysis of DO-HEALTH, a double-blind, randomized controlled trial. SETTING AND PARTICIPANTS: Multicenter trial with 7 European centers: Zurich, Basel, Geneva (Switzerland), Berlin (Germany), Innsbruck (Austria), Toulouse (France), and Coimbra (Portugal), including 2157 community-dwelling adults aged 70 years and older without any major health events in the 5 years prior to enrollment, sufficient mobility, and good cognitive status. METHODS: The numbers of all and injurious falls were recorded prospectively by diary and in-person assessment every 3 months. Decreased VA at baseline was defined as better-eye VA lower than 1.0. We applied negative binomial regression models for all and injurious falls, adjusted for age, sex, prior falls, treatment allocation, study site, baseline body mass index, and use of walking aids. RESULTS: Among the 2131 participants included in this analysis (mean age: 74.9 years, 61.7% were women, 82.6% at least moderately physically active), 1464 (68.7%) had decreased VA. Overall, 3290 falls including 2116 injurious falls were recorded over 3 years. Decreased VA at baseline was associated with a 22% increased incidence rate of all falls [adjusted incidence rate ratio (aIRR) = 1.22, 95% CI 1.07, 1.38, P = .003] and 20% increased incidence rate of injurious falls (aIRR = 1.20, 95% CI 1.05, 1.37, P = .007). CONCLUSIONS AND IMPLICATIONS: Our findings suggest that decreased VA is an independent predictor of an about 20% increased risk of all and injurious falls, highlighting the importance of regular eye examinations and VA measurements for fall prevention, even in generally healthy and active older adults.

Grip strength cut-points from the Swiss DO-HEALTH population.

BACKGROUND: While grip strength (GS) is commonly assessed using a Dynamometer, the Martin Vigorimeter was proposed as an alternative method especially in older adults. However, its reference values for Swiss older adults are missing. We therefore aimed to derive sex- and age-specific GS cut-points for the dominant and non-dominant hand (DH; NDH) using the Martin Vigorimeter. Additionally, we aimed to identify clinically relevant weakness and assess convergent validity with key markers of physical function and sarcopenia in generally healthy Swiss older adults. METHODS: This cross-sectional analysis includes baseline data from Swiss participants enrolled in DO-HEALTH, a 3-year randomized controlled trial in community-dwelling adults age 70 + . For both DH and NDH, 4 different definitions of weakness to derive GS cut-points by sex and age category (≤ 75 vs. > 75 years) were used: i) GS below the median of the 1st quintile, ii) GS below the upper limit of the 1st quintile, iii) GS below 2-standard deviation (SD) of the sex- and age-specific mean in DO-HEALTH Swiss healthy agers (i.e. individuals without major chronic diseases, disabilities, cognitive impairment or mental health issues) and iv) GS below 2.5-SD of the sex- and age-specific mean in DO-HEALTH Swiss healthy agers. To assess the proposed cut-points' convergent validity, we assessed their association with gait speed, time to complete the 5 Times Sit-To-Stand (5TSTS) test, and present sarcopenia. RESULTS: In total, 976 participants had available GS at the DH (mean age 75.2, 62% women). According to the 4 weakness definitions, GS cut-points at the DH ranged from 29-42 and 25-39 kPa in younger and older women respectively, and from 51-69 and 31-50 kPa in younger and older men respectively. Overall, weakness prevalence ranged from 2.0% to 19.3%. Definitions of weakness using the median and the upper limit of the 1st GS quintile were most consistently associated with markers of physical performance. Weak participants were more likely to have lower gait speed, longer time to complete the 5TSTS, and sarcopenia, compared to participants without weakness. CONCLUSIONS: In generally healthy Swiss older adults, weakness defined by the median or the upper limit of the 1st GS quintile may serve as reference to identify clinically relevant weakness. Additional research is needed in less healthy populations in order to derive representative population-based cut-points. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01745263.

Association Between Multimorbidity and Rate of Falls: A 3-Year 5-Country Prospective Study in Generally Healthy and Active Community-Dwelling Adults Aged ≥70 Years.

OBJECTIVE: To examine the association between the baseline number of chronic diseases and multimorbidity with regard to the incidence of all and injurious falls over 3 years among European community-dwelling older adults. DESIGN: Observational analysis of DO-HEALTH, a double-blind, randomized controlled trial. SETTING AND PARTICIPANTS: Multicenter trial with 7 European centers: Zurich, Basel, Geneva (Switzerland), Berlin (Germany), Innsbruck (Austria), Toulouse (France), and Coimbra (Portugal), including 2157 community-dwelling adults aged 70 years and older without any major health events in the 5 years prior to enrollment, sufficient mobility, and good cognitive status. METHODS: The main outcomes were the number of all falls and injurious falls experienced over 3 years. The number of chronic diseases and multimorbidity, defined as the presence of 3 or more chronic diseases at baseline, were assessed with the Self-Administered Comorbidity Questionnaire by Sangha et al. RESULTS: Among the 2155 participants included in the analyses (mean age: 74.9 years, 62% were women, 52% were physically active more than 3 times a week), 569 (26.4%) had multimorbidity at baseline. Overall, each 1-unit increase in the baseline number of chronic diseases was linearly associated with a 7% increased incidence rate of all falls [adjusted incidence rate ratio (aIRR) 1.07, 95% CI 1.03-1.12, P < .001] and a 6% increased incidence rate of injurious falls (aIRR 1.06, 95% CI 1.02-1.11, P = .003). Baseline multimorbidity was associated with a 21% increased incidence rate of all falls (aIRR 1.21, 95% CI 1.07-1.37, P = .002) and a 17% increased incidence rate of injurious falls (aIRR 1.17, 95% CI 1.03-1.32, P = .02). CONCLUSIONS AND IMPLICATIONS: Baseline number of prevalent chronic diseases and multimorbidity in generally healthy and active community-dwelling older adults were associated with increased incidence rates of all and injurious falls over 3 years. These findings support that multimorbidity may need consideration as a risk factor for falls, even in generally healthy and active older adults.

Prevalence of sarcopenia in patients with rheumatoid arthritis using the revised EWGSOP2 and the FNIH definition.

OBJECTIVE: In rheumatoid arthritis (RA), chronic inflammation can enhance the development of sarcopenia with a depletion of muscle mass, strength and performance. Currently, a consensus definition for sarcopenia and solid results for the prevalence of sarcopenia in patients with RA are lacking. METHODS: In this cross-sectional study, 289 patients ≥18 years with RA were recruited. Dual X-ray absorptiometry was performed to measure appendicular lean mass. Assessment of muscle function included grip strength, gait speed and chair rise time. Prevalence of sarcopenia was defined using the updated European Working Group on Sarcopenia in Older People (EWGSOP2) and the Foundation for the National Institutes of Health (FNIH) definition. In addition, the RA study population was compared with existing data of healthy controls (n=280). RESULTS: 4.5% of patients (59.4±11.3 years) and 0.4% of controls (62.9±11.9 years) were affected by sarcopenia according to the EWGSOP2 definition. Body weight (OR 0.92, 95% CI 0.86 to 0.97), body mass index (BMI) (OR 0.70, 95% CI 0.57 to 0.87), C reactive protein (CRP) (OR 1.05, 95% CI 1.01 to 1.10), disease duration (OR 1.08, 95% CI 1.02 to 1.36), current medication with glucocorticoids (OR 5.25, 95% CI 2.14 to 24.18), cumulative dose of prednisone equivalent (OR 1.04, 95% CI 1.02 to 1.05) and Health Assessment Questionnaire (HAQ) (OR 2.50, 95% CI 1.27 to 4.86) were associated with sarcopenia in patients with RA. In contrast, the prevalence was 2.8% in patients compared with 0.7% in controls when applying the FNIH definition, and body height (OR 0.75, 95% CI 0.64 to 0.88), BMI (OR 1.20, 95% CI 1.02 to 1.41), CRP (OR 1.06, 95% CI 1.01 to 1.11) and HAQ (OR 2.77, 95% CI 1.17 to 6.59) were associated with sarcopenia. CONCLUSION: Sarcopenia is significantly more common in patients with RA compared with controls using the EWGSOP2 criteria. The FNIH definition revealed sarcopenia in individuals with high BMI and fat mass, regardless of the presence of RA. TRIAL REGISTRATION NUMBER: It was registered at the German Clinical Trials Registry (DRKS) as well as WHO Clinical Trials Registry (ICTRP) (DRKS00011873, registered on 16 March 2017).

Iron metabolism regulation in females and males exposed to simulated microgravity: results from the randomized trial Artificial Gravity Bed Rest-European Space Agency (AGBRESA).

BACKGROUND: Iron metabolism imbalance could contribute to physical deconditioning experienced by astronauts due to its essential role in energy metabolism, cellular respiration, and oxygen transport. OBJECTIVES: In this clinical exploratory study, we wanted to determine whether artificial gravity (AG) training modulated iron metabolism, RBC indices, and body lean mass in healthy male and female participants exposed to head-down tilt (HDT) bed rest, the reference ground-based model of microgravity. METHODS: We recruited 8 healthy female and 16 healthy male participants who were all exposed to HDT bed rest for 60 d. In addition, they were assigned to 3 experimental groups (n = 8/each): controls, continuous AG training in a short-arm centrifuge (1 × 30 min/d), and intermittent AG training (6 × 5 min/d). RESULTS: The iron metabolism responses to simulated microgravity of the AG training groups did not differ significantly from the responses of controls. Independently from AG, we found that both serum iron concentrations (+31.3%, P = 0.027) and transferrin saturation levels (+28.4%, P = 0.009) increased in males after 6 d of HDT bed rest, as well as serum hepcidin concentrations (+36.9%, P = 0.005). The increase of transferrin saturation levels persisted after 57 d of HDT bed rest (+13.5%, P = 0.026), suggesting that long-term exposure to microgravity sustainably increases serum iron availability in males, and consequently the risk of iron excess or misdistribution. In females, 6 and 57 d of HDT bed rest did not significantly change serum iron, transferrin saturation, or hepcidin levels. CONCLUSIONS: The data from this exploratory study suggest that 1) AG training does not influence the iron metabolism responses to microgravity; and 2) iron metabolism parameters, especially iron availability for cells, are significantly increased in males, but not in females, exposed to long-term simulated microgravity. Because of the small sample size of females, we nevertheless must be cautious before concluding that iron metabolism could differently respond to microgravity in females. This trial was registered at https://www.drks.de as DRKS00015677.

Combined Vitamin D, Omega-3 Fatty Acids, and a Simple Home Exercise Program May Reduce Cancer Risk Among Active Adults Aged 70 and Older: A Randomized Clinical Trial.

Objective: The aim of this study was to test the individual and combined benefit of vitamin D, omega-3, and a simple home strength exercise program on the risk of any invasive cancer. Design: The DO-HEALTH trial is a three-year, multicenter, 2 × 2 × 2 factorial design double-blind, randomized-controlled trial to test the individual and combined benefit of three public health interventions. Setting: The trial was conducted between December 2012 and December 2017 in five European countries. Participants: Generally healthy community-dwelling adults ≥70 years were recruited. Interventions: Supplemental 2000 IU/day of vitamin D3, and/or 1 g/day of marine omega-3s, and/or a simple home strength exercise (SHEP) programme compared to placebo and control exercise. Main outcome: In this pre-defined exploratory analysis, time-to-development of any verified invasive cancer was the primary outcome in an adjusted, intent-to-treat analysis. Results: In total, 2,157 participants (mean age 74.9 years; 61.7% women; 40.7% with 25-OH vitamin D below 20 /ml, 83% at least moderately physically active) were randomized. Over a median follow-up of 2.99 years, 81 invasive cancer cases were diagnosed and verified. For the three individual treatments, the adjusted hazard ratios (HRs, 95% CI, cases intervention versus control) were 0.76 (0.49-1.18; 36 vs. 45) for vitamin D3, 0.70 (0.44-1.09, 32 vs. 49) for omega-3s, and 0.74 (0.48-1.15, 35 vs. 46) for SHEP. For combinations of two treatments, adjusted HRs were 0.53 (0.28-1.00; 15 vs. 28 cases) for omega-3s plus vitamin D3; 0.56 (0.30-1.04; 11 vs. 21) for vitamin D3 plus SHEP; and 0.52 (0.28-0.97; 12 vs. 26 cases) for omega-3s plus SHEP. For all three treatments combined, the adjusted HR was 0.39 (0.18-0.85; 4 vs. 12 cases). Conclusion: Supplementation with daily high-dose vitamin D3 plus omega-3s, combined with SHEP, showed cumulative reduction in the cancer risk in generally healthy and active and largely vitamin D-replete adults ≥70 years. Clinical Trial Registration: ClinicalTrials.gov, Identifier: NCT01745263.

Effects of vitamin D, omega-3 fatty acids, and a simple home strength exercise program on fall prevention: the DO-HEALTH randomized clinical trial.

BACKGROUND: The roles of vitamin D, omega-3 fatty acids, and home exercise on fall prevention among generally healthy and active older adults are unclear. OBJECTIVES: We tested the effects of daily supplemental vitamin D, daily supplemental marine omega-3s fatty acids, and a simple home exercise program (SHEP), alone or in combination, on the incidences of total and injurious falls among generally healthy older adults. METHODS: We performed a 2 × 2 × 2 factorial-design randomized controlled trial among 2157 community-dwelling adults aged 70 years and older, who had no major health events in the 5 years prior to enrolment, recruited from Switzerland, Germany, Austria, France, and Portugal between December 2012 and November 2014. Participants were randomly assigned to supplementation with 2000 international units/day of vitamin D3 and/or 1 g/day of marine omega-3s, and/or a SHEP compared with placebo and/or control exercise over 3 years. The primary endpoint for the present fall analysis was the incidence rate of total falls. Falls were recorded prospectively throughout the trial. Since there were no interactions between treatments, the main effects are reported based on a modified intent-to-treat analysis. RESULTS: Of 2157 randomized participants, 1900 (88%) completed the study. The mean age was 74.9 years, 61.7% were women, 40.7% had a serum 25-hydroxyvitamin D concentration < 20 ng/ml, and 83% were at least moderately physically active. In total, 3333 falls were recorded over a median follow-up of 2.99 years. Overall, vitamin D and the SHEP had no benefit on total falls, whilst supplementation with omega-3s compared to no omega-3 supplementation reduced total falls by 10% (incidence rate ratio = 0.90; 95% CI, 0.81-1.00; P = 0.04). CONCLUSIONS: Among generally healthy, active, and vitamin D-replete older adults, omega-3 supplementation may have a modest benefit on the incidence of total falls, whilst a daily high dose of vitamin D or a SHEP had no benefit.

The effects of rehabilitation on the muscles of the trunk following prolonged bed rest.

Microgravity and inactivity due to prolonged bed rest have been shown to result in atrophy of spinal extensor muscles such as the multifidus, and either no atrophy or hypertrophy of flexor muscles such as the abdominal group and psoas muscle. These effects are long-lasting after bed rest and the potential effects of rehabilitation are unknown. This two-group intervention study aimed to investigate the effects of two rehabilitation programs on the recovery of lumbo-pelvic musculature following prolonged bed rest. 24 subjects underwent 60 days of head down tilt bed rest as part of the 2nd Berlin BedRest Study (BBR2-2). After bed rest, they underwent one of two exercise programs, trunk flexor and general strength (TFS) training or specific motor control (SMC) training. Magnetic resonance imaging of the lumbo-pelvic region was conducted at the start and end of bed rest and during the recovery period (14 and 90 days after re-ambulation). Cross-sectional areas (CSAs) of the multifidus, psoas, lumbar erector spinae and quadratus lumborum muscles were measured from L1 to L5. Morphological changes including disc volume, spinal length, lordosis angle and disc height were also measured. Both exercise programs restored the multifidus muscle to pre-bed-rest size, but further increases in psoas muscle size were seen in the TFS group up to 14 days after bed rest. There was no significant difference in the number of low back pain reports for the two rehabilitation groups (p=.59). The TFS program resulted in greater decreases in disc volume and anterior disc height. The SMC training program may be preferable to TFS training after bed rest as it restored the CSA of the multifidus muscle without generating potentially harmful compressive forces through the spine.

Pore-Size Distribution and Frequency-Dependent Attenuation in Human Cortical Tibia Bone Discriminate Fragility Fractures in Postmenopausal Women With Low Bone Mineral Density.

Osteoporosis is a disorder of bone remodeling leading to reduced bone mass, structural deterioration, and increased bone fragility. The established diagnosis is based on the measurement of areal bone mineral density by dual-energy X-ray absorptiometry (DXA), which poorly captures individual bone loss and structural decay. Enlarged cortical pores in the tibia have been proposed to indicate structural deterioration and reduced bone strength in the hip. Here, we report for the first time the in vivo assessment of the cortical pore-size distribution together with frequency-dependent attenuation at the anteromedial tibia midshaft by means of a novel ultrasonic cortical backscatter (CortBS) technology. We hypothesized that the CortBS parameters are associated with the occurrence of fragility fractures in postmenopausal women (n = 55). The discrimination performance was compared with those of DXA and high-resolution peripheral computed tomography (HR-pQCT). The results suggest a superior discrimination performance of CortBS (area under the receiver operating characteristic curve [AUC]: 0.69 ≤ AUC ≤ 0.75) compared with DXA (0.54 ≤ AUC ≤ 0.55) and a similar performance compared with HR-pQCT (0.66 ≤ AUC ≤ 0.73). CortBS is the first quantitative bone imaging modality that can quantify microstructural tissue deteriorations in cortical bone, which occur during normal aging and the development of osteoporosis. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Quantitative assessment of the lumbar intervertebral disc via T2 shows excellent long-term reliability.

Methodologies for the quantitative assessment of the spine tissues, in particular the intervertebral disc (IVD), have not been well established in terms of long-term reliability. This is required for designing prospective studies. 1H water T2 in the IVD ("T2") has attained wider use in assessment of the lumbar intervertebral discs via magnetic resonance imaging. The reliability of IVD T2 measurements are yet to be established. IVD T2 was assessed nine times at regular intervals over 368 days on six anatomical slices centred at the lumbar spine using a spin-echo multi-echo sequence in 12 men. To assess repeatability, intra-class correlation co-efficients (ICCs), standard error of the measurement, minimal detectable difference and co-efficients of variation (CVs) were calculated along with their 95% confidence intervals. Bland-Altman analysis was also performed. ICCs were above 0.93, with the exception of nuclear T2 at L5/S1, where the ICC was 0.88. CVs of the central-slice nucleus sub-region ranged from 4.3% (average of all levels) to 10.1% for L5/S1 and between 2.2% to 3.2% for whole IVD T2 (1.8% for the average of all levels). Averaging between vertebral levels improved reliability. Reliability of measurements was least at L5/S1. ICCs of degenerated IVDs were lower. Test-retest reliability was excellent for whole IVD and good to excellent for IVD subregions. The findings help to establish the long-term repeatability of lumbar IVD T2 for the implementation of prospective studies and determination of significant changes within individuals.

Effects of 8 weeks of bed rest with or without resistance exercise intervention on the volume of the muscle tissue and the adipose tissues of the thigh.

The present study aims to investigate the effects of 8 weeks of bed rest, with or without resistance exercise intervention, on the volumes of muscle tissue and the intramuscular, intermuscular, and subcutaneous adipose tissues of the thigh. Twenty men were included, who were randomly assigned in three groups: resistance exercises group (RE group), resistance exercises with whole-body vibration group (VRE group), and nonexercise control group (CTR group). The RE and VRE groups performed resistance exercises during 8 weeks of bed rest (3 days per week). Additionally, consecutive axial magnetic resonance images were obtained before and after the bed rest. Using these images, the volumes of the muscle tissue and the intramuscular adipose tissue, intermuscular adipose tissue, and subcutaneous adipose tissue of the thigh were evaluated. No significant time-by-group interaction was observed the volumes of the muscle tissue and the intramuscular adipose tissue, intermuscular adipose tissue, and subcutaneous adipose tissue between the RE and VRE groups. Furthermore, the RE and VRE groups were pooled as the resistance exercise intervention group (TR group), wherein their thigh muscle tissue volume was observed to be maintained after the bed rest. However, that of the CTR group significantly decreased. Regarding the thigh intramuscular adipose tissue and intermuscular adipose tissue volumes, no significant difference was observed among the CTR and TR groups. Although subcutaneous adipose tissue volume in the CTR group significantly increased after the bed rest, no changes were observed in that of the TR group. Therefore, the results of the present study suggested that within the 8 weeks of bed rest, adipose tissue adaptation differs depending on the location.