Search

International audience; 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, red blood cell indices, and body lean mass in male and female healthy participants exposed to head-down tilt (HDT) bed rest, the reference ground-based model of microgravity. METHODS: We recruited 8 female and 16 male healthy participants who were all exposed to HDT bed rest for 60 days. In addition, they were assigned to three experimental groups (n = 8/each): controls, continuous AG training in a short-arm centrifuge (1×30 min/day), and intermittent AG training (6 × 5 min/day). RESULTS: The iron metabolism responses to simulated microgravity of AG training groups do not significantly differ from the responses of controls. Independently from AG, we found that both serum iron (+31.3%, P = 0.027) and transferrin saturation levels (+28.4%, P = 0.009) increased in males after 6 days of HDT bed rest, as well as serum hepcidin levels (+36.9% P = 0.005). The increase of transferrin saturation levels persisted after 57 days 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 days of HDT bed rest did not significantly change serum iron, transferrin saturation, and hepcidin levels. CONCLUSIONS: The data from this exploratory study suggest that 1) AG training does not influence the iron metabolism responses to microgravity; 2) iron metabolism parameters, especially iron availability for cells, are significantly increased in males, but not in females, exposed to long-term simulated microgravity. Due to the small sample size of females, we nevertheless must be cautious before concluding that iron metabolism could differently respond to microgravity in females. Clinical trial registry number: DRKS00015677.

Background: An astronaut’s body is exposed during spaceflight to the peculiar condition of weightlessness, and consequently experiences various adaptive changes, among which bone and muscle loss stand out. Although space agencies nowadays adopt numerous preventive measures against these pathologies, they are presently only able to reduce their entity but not entirely prevent their onset. Hence, alternative countermeasures are currently being investigated, in the hope that they may be more effective and efficient in this setting. Objective: The purpose of this experimental study was to assess the usefulness of a novel form of high-intensity interval training (HIIT), based on the principle of jumping, which could be used aboard the International Space Station (ISS) to prevent musculoskeletal deconditioning in astronauts. The effectiveness of the training has been determined by evaluating its ability in preventing the onset of atrophy in lumbar paraspinal muscles, and chiefly in the multifidus, over the course of a bed-rest study. Materials and Methods: Twenty-three healthy male participants, aged between 21 and 42, selected after an extensive screening procedure, were confined for ninety days in the facilities of the German Aerospace Centre in Cologne. The study was divided in three phases: a 15-day baseline measurement phase, a 60-day 6 head-down-tilt (HDT) bed-rest phase, and a 15-day recovery phase. Participants were oralrandomly allocated to the control group (CTRL, n=11) or the training group (JUMP, n=12). Subjects have been carefully monitored during the whole study, and the dimensions of their lumbar paraspinal muscles has been measured using magnetic resonance imaging at nine points in time, during and after the bed rest. Results: Subjects have tolerated the exercise well, and adherence to the planned protocol has been perfect, despite a few deviations in intensity. No significant difference in lumbar paraspinal muscles atrophy between the training and the control group has emerged at any study-date (p=0.210), whereas a significant reduction in their thickness at the end of the bed rest has been demonstrated in both Groups (-5,05%, p

Objectives: Muscle mass and muscle power considerably decline with aging. The aim of the present study was to determine the association between muscular function using mechanography and sarcopenia, falls and impairment in the activities of daily living (ADL) in a sample of 293 community-dwelling women and men aged 60-85 years in Berlin, Germany. Methods: Muscle function was determined by muscle power per body mass in vertical countermovement jumps (2LJPrel) and the chair rising test (CRTPrel) on a force plate. Sarcopenia status was assessed by estimating appendicular muscle mass with dual-X-ray absorptiometry. Self-reported ADL impairment and falls in the last 12 months were determined. Results: ADL impairment was significantly correlated with all performance tests but not with muscle mass. The 2LJPrel (OR 0.88, 95%-CI 0.79-0.98), the Esslinger Fitness Index (EFI) (OR 0.97, 95%-CI 0.94-1.00) and the maximal velocity of the CRT (OR 0.70, 95%-CI 0.53-0.93) remained significant correlates for sarcopenia independent of age in men but not in women. The EFI could differentiate female individuals who had past fall events (OR 0.96, 95%-CI 0.93-0.98). Conclusion: The results of the present study highlight the importance of assessing muscle power in older individuals as a relevant correlate for functional decline.

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.

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. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved.

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. © 2017 John Wiley & Sons Ltd

BACKGROUND: In the European Prospective Osteoporosis Study (EPOS), a past spine fracture increased risk of an incident fracture 3.6 - 12-fold even after adjusting for BMD. We examined the possibility that biochemical marker levels were associated with this unexplained BMD-independent element of fracture risk. METHODS: Each of 182 cases in EPOS of spine or non-spine fracture that occurred in 3.8 years of follow-up was matched by age, sex and study centre with two randomly assigned never-fractured controls and one case of past fracture. Analytes measured blind were: osteocalcin, bone-specific alkaline phosphatase, total alkaline phosphatase, serum creatinine, calcium, phosphate and albumin, together with the collagen cross-links degradation products serum CTS and urine CTX. Most subjects also had bone density measured by DXA. RESULTS: Cases who had recent fractures did not differ in marker levels from cases who had their last fracture more than 3 years previously. No statistically significant effect of recent fracture was found for any marker except osteocalcin, which was 17.6% lower in recent peripheral cases compared to unfractured controls (p

More severe vertebral fractures have more personal impact. In the European Prospective Osteoporosis Study, more severe vertebral collapse was predictable from prior fracture characteristics. Subjects with bi-concave or crush fractures at baseline had a 2-fold increase in incident fracture size and thus increased risk of a disabling future fracture. Introduction: According to Euler's buckling theory, loss of horizontal trabeculae in vertebrae increases the risk of fracture and suggests that the extent of vertebral collapse will be increased in proportion. We tested the hypothesis that the characteristics of a baseline deformity would influence the size of a subsequent deformity. Methods: In 207 subjects participating in the European Prospective Osteoporosis Study who suffered an incident spine fracture in a previously normal vertebra, we estimated loss of volume (fracture size) from plane film images of all vertebral bodies that were classified as having a new fracture. The sum of the three vertebral heights (anterior, mid-body, and posterior) obtained at follow-up was subtracted from the sum of the same measures at baseline. Each of the summed height loss for vertebrae with a McCloskey-Kanis deformity on the second film was expressed as a percentage. Results and Conclusions: In univariate models, the numbers of baseline deformities and the clinical category of the most severe baseline deformity were each significantly associated with the size of the most severe incident fracture and with the cumulated sum of all vertebral height losses. In multivariate modeling, age and the clinical category of the baseline deformity (crush > bi-concave > uni-concave > wedge) were the strongest determinants of both more severe and cumulative height loss. Baseline biconcave and crush fractures were associated at follow-up with new fractures that were approximately twice as large as those seen with other types of deformity or who previously had undeformed spines. In conclusion, the characteristics of a baseline vertebral deformity determines statistically the magnitude of vertebral body volume lost when a subsequent fracture occurs. Because severity of fracture and number of fractures are determinants of impact, the results should improve prediction of the future personal impact of osteoporosis once a baseline prevalent deformity has been identified.

Summary: In 27 centres across Europe, the prevalence of deforming spinal Scheuermann’s disease in age-stratified population-based samples of over 10,000 men and women aged 50+ averaged 8 % in each sex, but was highly variable between centres. Low DXA BMD was un-associated with Scheuermann’s, helping the differential diagnosis from osteoporosis. Introduction: This study aims to assess the prevalence of Scheuermann’s disease of the spine across Europe in men and women over 50 years of age, to quantitate its association with bone mineral density (BMD) and to assess its role as a confounder for the radiographic diagnosis of osteoporotic fracture. Methods: In 27 centres participating in the population-based European Vertebral Osteoporosis Study (EVOS), standardised lateral radiographs of the lumbar and of the thoracic spine from T4 to L4 were assessed in all those of adequate quality. The presence of Scheuermann’s disease, a confounder for prevalent fracture in later life, was defined by the presence of at least one Schmorl’s node or irregular endplate together with kyphosis (sagittal Cobb angle >40° between T4 and T12) or a wedged-shaped vertebral body. Alternatively, the (rare) Edgren-Vaino sign was taken as diagnostic. The 6-point-per-vertebral-body (13 vertebrae) method was used to assess osteoporotic vertebral shape and fracture caseness. DXA BMD of the L2–L4 and femoral neck regions was measured in subsets. We also assessed the presence of Scheuermann’s by alternative published algorithms when these used the radiographic signs we assessed. Results: Vertebral radiographic images from 4486 men and 5655 women passed all quality checks. Prevalence of Scheuermann’s varied considerably between centres, and based on random effect modelling, the overall European prevalence using our method was 8 % with no significant difference between sexes. The highest prevalences were seen in Germany, Sweden, the UK and France and low prevalences were seen in Hungary, Poland and Slovakia. Centre-level prevalences in men and women were highly correlated. Scheuermann’s was not associated with BMD of the spine or hip. Conclusions: Since most of the variation in population impact of Scheuermann’s was unaccounted for by the radiological and anthropometric data, the search for new genetic and environmental determinants of this disease is encouraged. © 2015, International Osteoporosis Foundation and National Osteoporosis Foundation.

Bed rest studies are an accepted model for simulating bone loss due to microgravity during space flights. In a previous 60 days bed rest study, we investigated the loss of bone mass and the microstructural degeneration at the distal radius and tibia using a high-resolution (HR) pQCT device1. In combination with micro-finite element (micro-FE) analyses, it was possible to also quantify the loss of strength during bed rest2. In that study large variations in loss of bone strength were found between subjects. For some subjects no loss of strength was found whereas for others strength was reduced by 6.5%. Although these values are small and thus may not increase the risk of fracture, it may cause premature age-related osteoporosis and understanding the fundamental nature of the skeletal response to unloading is of great interest to develop countermeasures for overcoming the adverse effects of microgravity during spaceflights. In this study we investigate if the variation in loss of bone strength between subjects as observed in the earlier bed rest study could be related to their activity level prior to the bed rest. Since we expect that subjects that were more active would be more affected by the disuse, we hypothesized that the loss of bone strength is positively correlated to the physical activity of the subjects. As the activity level of the subjects prior to the bed rest study was not known, we used a recently developed method to estimate the bone loading history based on the bone architecture and correlated that with the loss in bone strength measured in the bed rest study to test our hypothesis.

Long-term bed-rest is used to simulate the effect of spaceflight on the human body and test different kinds of countermeasures. The 2nd Berlin BedRest Study (BBR2-2) tested the efficacy of whole-body vibration in addition to high-load resisitance exercise in preventing bone loss during bed-rest. Here we present the protocol of the study and discuss its implementation. Twenty-four male subjects underwent 60-days of six-degree head down tilt bed-rest and were randomised to an inactive control group (CTR), a high-load resistive exercise group (RE) or a high-load resistive exercise with whole-body vibration group (RVE). Subsequent to events in the course of the study (e.g. subject withdrawal), 9 subjects participated in the CTR-group, 7 in the RVE-group and 8 (7 beyond bed-rest day-30) in the RE-group. Fluid intake, urine output and axiallary temperature increased during bed-rest (p=.17). Body weight changes differed between groups (p

The presence of a prevalent vertebral deformity increases the risk of a future vertebral fracture. The aim of this study was to determine whether certain characteristics of the prevalent deformity, including its shape and location in the spine, influenced this effect. The 3100 men and 3500 women who took part in this analysis were recruited from population registers for participation in the European Prospective Osteoporosis Study (EPOS). Subjects had lateral thoracic and lumbar spine x-rays at baseline, and again after a mean interval of 3.8 years. Prevalent morphometric vertebral deformities on the baseline film were identified by the McCloskey-Kanis method. Incident fractures were defined as vertebrae that also satisfied the McCloskey-Kanis criterion for prevalent deformities on the follow-up film, and in addition had at least one height (anterior, mid, or posterior) which had reduced by at least 20% between films. Poisson regression was used to assess the association between various characteristics of the prevalent deformity and the risk of an incident vertebral fracture, with generalised estimating equations used to allow for the fact that each subject contributed several vertebrae to the analysis. The risk of an incident fracture increased with the number of prevalent deformities: relative risk (RR) for one prevalent deformity 3.2 (95% confidence interval (CI); 2.1, 4.8); 9.8 (95% CI;6.1, 15.8) for 2; and 23.3 (95% CI;15.3, 35.4) for 3 or more. Relative risks differed significantly according to the shape of the prevalent deformity, ranging from 5.9 (95% CI; 4.1, 8.6) if the anterior and mid heights were reduced to 1.6 (95% CI;0.8, 3.2) if the posterior and mid heights were reduced. Risks varied also according to the severity of the deformity. There were fivefold differences in relative risk of incident fracture depending on the location of the prevalent deformity within the spine. Compared to vertebrae in subjects with no deformities at baseline, the relative risk of an incident fracture within three vertebrae of a prevalent deformity was greater (7.7 (95% CI;5.6, 10.5)) than the risk in more distant vertebrae (4.0 (95% CI;2.6, 6.0)). In summary, the risk of a subsequent vertebral fracture in individuals with preexisting deformities is importantly influenced by the characteristics of these deformities. © 2003 Elsevier Inc. All rights reserved.

The aim of this analysis was to determine the influence of lifestyle, anthropometric and reproductive factors on the subsequent risk of incident vertebral fracture in men and women aged 50-79 years. Subjects were recruited from population registers from 28 centers across Europe. At baseline, they completed an interviewer-administered questionnaire and had lateral thoraco-lumbar spine radiographs performed. Repeat spinal radiographs were performed a mean of 3.8 years later. Incident vertebral fractures were defined morphometrically and also qualitatively by an experienced radiologist. Poisson regression was used to determine the influence of the baseline risk factor variables on the occurrence of incident vertebral fracture. A total of 3173 men (mean age 63.1 years) and 3402 women (mean age 62.2 years) contributed data to the analysis. In total there were 193 incident morphometric and 224 qualitative fractures. In women, an age at menarche 16 years or older was associated with an increased risk of vertebral fracture (RR = 1.80; 95%CI 1.24, 2.63), whilst use of hormonal replacement was protective (RR=0.58; 95%CI 0.34, 0.99). None of the lifestyle factors studied including smoking, alcohol intake, physical activity or milk consumption showed any consistent associations with incident vertebral fracture. In men and women, increasing body weight and body mass index were associated with a reduced risk of vertebral fracture though, apart from body mass index in men, the confidence intervals embraced unity. For most variables the strengths of the associations observed were similar using the qualitative and morphometric approaches to fracture definition. In conclusion our data suggest that modification of other lifestyle risk factors is unlikely to have a major impact on the population occurrence of vertebral fractures. The important biological mechanisms underlying vertebral fracture risk need to be explored using new investigational strategies.