Contextual effects: how to, and how not to, quantify them.

The importance of contextual effects and their roles in clinical care controversial. A Cochrane review published in 2010 concluded that placebo interventions lack important clinical effects overall, but that placebo interventions can influence patient-reported outcomes such as pain and nausea. However, systematic reviews published after 2010 estimated greater contextual effects than the Cochrane review, which stems from the inappropriate methods employed to quantify contextual effects. The effects of medical interventions (i.e., the total treatment effect) can be divided into three components: specific, contextual, and non-specific. We propose that the most effective method for quantifying the magnitude of contextual effects is to calculate the difference in outcome measures between a group treated with placebo and a non-treated control group. Here, we show that other methods, such as solely using the placebo control arm or calculation of a 'proportional contextual effect,' are limited and should not be applied. The aim of this study is to provide clear guidance on best practices for estimating contextual effects in clinical research.

Telemedicine for Patients with Musculoskeletal Pain Lacks High-Quality Evidence on Delivery Modes and Effectiveness: An Umbrella Review.

Background: Musculoskeletal (MSK) pain is the leading cause of disability worldwide. Telemedicine is of growing importance, yet impacts on treatment efficacy remain unclear. Objective: This umbrella review (CRD42022298047) examined the effectiveness of telemedicine interventions on pain intensity, disability, psychological function, quality of life, self-efficacy, and adverse events in MSK pain. Methods: PubMed, SPORTDiscus, Cochrane Library, EMBASE, and CINAHL were searched from inception to August 9, 2022, for systematic reviews with meta-analysis, including telemedicine-delivered exercise, education, and psychological interventions, in randomized controlled trials (RCTs). AMSTAR-2 was implemented. Standardized mean differences (SMDs; negative favors telemedicine) were extracted as effect estimates. Results: Of 1,135 records, 20 reviews (RCTs: n = 97, participants: n = 15,872) were included. Pain intensity SMDs were -0.66 to 0.10 for mixed pain (estimates: n = 16), -0.64 to -0.01 for low-back pain (n = 9), -0.31 to -0.15 for osteoarthritis (n = 7), -0.29 for knee pain (n = 1), -0.66 to -0.58 for fibromyalgia (n = 2), -0.16 for back pain (n = 1), and -0.09 for rheumatic disorders (n = 1). Disability SMDs were -0.50 to 0.10 for mixed pain (n = 14), -0.39 to 0.00 for low-back pain (n = 8), -0.41 to -0.04 for osteoarthritis (n = 7), -0.22 for knee pain (n = 1), and -0.56 for fibromyalgia (n = 1). Methodological quality was "critically low" for 17 reviews. Effectiveness tended to favor telemedicine for all secondary outcomes. Conclusions: Primary RCTs are required that compare telemedicine interventions with in-person delivery of the intervention (noninferiority trials), consider safety, assess videoconferencing, and combine different treatment approaches.

Does adding exercise or physical activity to pharmacological osteoporosis therapy in patients with increased fracture risk improve bone mineral density and lower fracture risk? A systematic review and meta-analysis.

This prospectively registered systematic review and meta-analysis examines whether exercise (EX) training has an additive effect to osteoanabolic and/or antiresorptive pharmacological therapy (PT) in people with osteoporosis on bone mineral density (BMD), bone turnover markers (BTMs), fracture healing, and fractures. Four databases (inception to 6 May 2022), 5 trial registries, and reference lists were searched. Included were randomized controlled trials comparing the effect of EX + PT vs. PT with regard to BMD, BTM, fracture healing, and fractures. Risk of bias was assessed using the Cochrane RoB2 and certainty of evidence by the GRADE approach. Random-effects meta-analysis with Hartung-Knapp-Sidik-Jonkman adjustment was used to estimate standardized mean differences and 95% confidence intervals. Out of 2593 records, five RCTs with 530 participants were included. Meta-analysis showed with very low certainty evidence and wide confidence intervals that EX + PT compared to PT had larger effect sizes for BMD at 12 months at the hip (SMD [95%CI]: 0.18 [- 1.71; 2.06], n = 3 studies), tibia (0.25 [- 4.85; 5.34], n = 2), lumbar spine (0.20 [- 1.15; 1.55], n = 4), and forearm (0.05 [- 0.35; 0.46], n = 3), but not femoral neck (- 0.03 [- 1.80; 1.75], n = 3). Furthermore, no improvement was revealed for BTM such as bone ALP (- 0.68 [- 5.88; 4.53], n = 3), PINP (- 0.74 [- 10.42; 8.93], n = 2), and CTX-I (- 0.69 [- 9.61; 8.23], n = 2), but with very wide confidence intervals. Three potentially relevant ongoing trials were identified via registries. No data were found for fracture healing or fracture outcomes. It remains unclear whether EX has an additive impact to PT in people with osteoporosis. High-quality, adequately powered, targetted RCTs are required. PROTOCOL REGISTRATION: PROSPERO CRD42022336132.

Interventions for promoting evidence-based guideline-consistent surgery in low back pain: a systematic review and meta-analysis of randomised controlled trials.

PURPOSE: Examine the effectiveness of interventions to approach guideline-adherent surgical referrals for low back pain assessed via systematic review and meta-analysis. METHODS: Five databases (10 September 2021), Google Scholar, reference lists of relevant systematic reviews were searched and forward and backward citation tracking of included studies were implemented. Randomised controlled/clinical trials in adults with low back pain of interventions to optimise surgery rates or referrals to surgery or secondary referral were included. Bias was assessed using the Cochrane ROB2 tool and evidence certainty via Grading of Recommendations Assessment, Development and Evaluation (GRADE). A random effects meta-analysis with a Paule Mandel estimator plus Hartung-Knapp-Sidik-Jonkman method was used to calculate the odds ratio and 95% confidence interval, respectively. RESULTS: Of 886 records, 6 studies were included (N = 258,329) participants; cluster sizes ranged from 4 to 54. Five studies were rated as low risk of bias and one as having some concerns. Two studies reporting spine surgery referral or rates could only be pooled via combination of p values and gave evidence for a reduction (p = 0.021, Fisher's method, risk of bias: low). This did not persist with sensitivity analysis (p = 0.053). For secondary referral, meta-analysis revealed a non-significant odds ratio of 1.07 (95% CI [0.55, 2.06], I2 = 73.0%, n = 4 studies, Grading of Recommendations Assessment, Development and Evaluation [GRADE] evidence certainty: very low). CONCLUSION: Few RCTs exist for interventions to improve guideline-adherent spine surgery rates or referral. Clinician education in isolation may not be effective. Future RCTs should consider organisational and/or policy level interventions. PROSPERO REGISTRATION: CRD42020215137.

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.

Primary surgery versus primary rehabilitation for treating anterior cruciate ligament injuries: a living systematic review and meta-analysis.

OBJECTIVE: Compare the effectiveness of primarily surgical versus primarily rehabilitative management for anterior cruciate ligament (ACL) rupture. DESIGN: Living systematic review and meta-analysis. DATA SOURCES: Six databases, six trial registries and prior systematic reviews. Forward and backward citation tracking was employed. ELIGIBILITY CRITERIA: Randomised controlled trials that compared primary reconstructive surgery and primary rehabilitative treatment with or without optional reconstructive surgery. DATA SYNTHESIS: Bayesian random effects meta-analysis with empirical priors for the OR and standardised mean difference and 95% credible intervals (CrI), Cochrane RoB2, and the Grading of Recommendations Assessment, Development and Evaluation approach to judge the certainty of evidence. RESULTS: Of 9514 records, 9 reports of three studies (320 participants in total) were included. No clinically important differences were observed at any follow-up for self-reported knee function (low to very low certainty of evidence). For radiological knee osteoarthritis, we found no effect at very low certainty of evidence in the long term (OR (95% CrI): 1.45 (0.30 to 5.17), two studies). Meniscal damage showed no effect at low certainty of evidence (OR: 0.85 (95% CI 0.45 to 1.62); one study) in the long term. No differences were observed between treatments for any other secondary outcome. Three ongoing randomised controlled trials were identified. CONCLUSIONS: There is low to very low certainty of evidence that primary rehabilitation with optional surgical reconstruction results in similar outcome measures as early surgical reconstruction for ACL rupture. The findings challenge a historical paradigm that anatomic instability should be addressed with primary surgical stabilisation to provide optimal outcomes. PROSPERO REGISTRATION NUMBER: CRD42021256537.

Increased Joint Mobility Is Associated With Impaired Transversus Abdominis Contraction.

ABSTRACT: Mitchell, UH, Owen, PJ, Rantalainen, T, and Belavý, DL. Increased joint mobility is associated with impaired transversus abdominis contraction. J Strength Cond Res 36(9): 2472-2478, 2022-Increased joint mobility is a risk factor for joint injury, but muscle function may be able to compensate for it. Current evidence suggests reduced force production capacity in people with hypermobility. However, little is known about the lumbar spine. The purpose of this cross-sectional study was to assess whether there was a link between joint mobility and transverse abdominis and multifidus muscles contraction, muscles ascribed a core-stability role. Using a modified quantitative version of the Beighton scale (BOM score), we measured joint mobility of 30 middle-aged individuals without low back pain. These scores were correlated with magnetic resonance imaging-derived measures of transverse abdominis and multifidus muscle contraction during a spinal loading maneuver. The level of significance was set for p ≤ 0.05. The results showed greater joint mobility (a higher BOM score) correlated ( r = 0.468; p = 0.009) with reduced transversus abdominis (TrA) shortening during contraction (i.e., less muscle shortening in people with greater joint mobility). The trunk subdomain score exhibited a correlation of 0.354 with TrA length change, but this did not reach statistical significance ( p = 0.055). The subdomains of the BOM score did not correlate significantly with each other ( p ≥ 0.097). No association was seen between multifidus contraction and joint mobility. The results suggest that greater general joint mobility is associated with impaired contraction of the TrA muscle. This should be considered when coaching athletes or treating patients with (functional) spinal instability. The quantitative approach we developed to measure joint mobility could be used in the future studies of global flexibility.

Count- versus MAD-based accelerometry-assessed movement behaviors and associations with child adiposity and fitness.

Estimations of time spent sedentary and in various physical activity intensities may vary according to data reduction methods applied. This study compared associations between children's accelerometer data and adiposity and fitness markers using open source (mean amplitude deviation, MAD) and proprietary (counts) data reduction methods. Complete-case accelerometer, adiposity (Body Mass Index z-score, waist circumference), and fitness (cardiorespiratory, musculoskeletal) data from 118 children (10.4 ± 0.6 years, 49% girls) were analyzed. Estimates of sedentary behavior, light-, moderate-, vigorous- (VPA), and moderate- to vigorous-intensity (MVPA) physical activity were calculated using count- and MAD-based data reduction methods. Linear regression models between time in movement behaviours and fitness and adiposity markers were conducted. Significant differences in estimates of time spent in all intensities were observed between MAD-based and count-based methods. Both methods produced evidence to suggest that sedentary behavior was detrimentally, and physical activity (any intensity) was beneficially, associated with waist circumference. MVPA and VPA were beneficially associated with fitness markers using both data reduction measures. Overall, findings suggest that estimates of sedentary time and physical activity were not comparable. However, the strength and direction of the associations obtained between the different data reduction methods and adiposity and fitness outcomes were fairly comparable, with both methods finding stronger associations for VPA compared to MVPA. This suggests that future studies may be able to pool data using different data reduction approaches when examining associations between activity and health risk factors, albeit with caution.

Physical activity accumulation along the intensity spectrum differs between children and adults.

PURPOSE: Detailed exploration of physical activity accumulation with fine grading along the intensity spectrum has indicated the potential pragmatic utility of such an approach. However, it is currently unclear what sorts of accumulation patterns along particular intensity bands are found in the children and adult populations. Therefore, we conducted a comparison of activity accumulation in specific intensity bands between four distinct populations: children, adults with sedentary lifestyles, habitual joggers, habitual marathon runners. METHODS: Free-living waist-worn accelerometry records from 28 children aged 7 to 11, and 61 adults aged 25 to 35 were analysed. Activity intensity was evaluated in 5 s non-overlapping epochs as mean amplitude deviation (MAD) and normalised to acceleration intensities corresponding to walking at 3 metabolic equivalents of a task (METs). Adult data were normalised to 0.091 g MAD based on literature, and data from children to 0.170 g MAD based on laboratory experimentation. The normalised epoch values were divided into 100 intensity gradations. RESULTS: Children accumulated more activity in 0.74 to 1.58 normalised acceleration intensities (all p < 0.005) compared to adults. Adult joggers/runners accumulated more activity in normalised acceleration intensities from 7.1 to 11.1 compared to the other groups (p < 0.008). CONCLUSION: The primary bulk of children's free-living activities are of relatively low intensity not likely to provoke cardiometabolic improvement. These sorts of explorations could be used in informing intervention development aiming at optimising healthy development. Evidence is mounting to justify randomised controlled trials based on intervention targets identified based on exploring the intensity spectrum.

Exercise for the intervertebral disc: a 6-month randomised controlled trial in chronic low back pain.

BACKGROUND CONTEXT: Muscle, bone and tendon respond anabolically to mechanical forces. Whether the intervertebral disc (IVD) can benefit from exercise is unclear. PURPOSE: To examine whether exercise can beneficially affect IVD characteristics. STUDY DESIGN/SETTING: This is a single-blinded 6-month randomised controlled trial (ACTRN12615001270505) in an exercise and physiotherapy clinic. PATIENT SAMPLE: Forty patients with chronic non-specific low back pain (NSCLBP) are included in this study. OUTCOME MEASURES: The primary outcome was lumbar IVD T2 time (MRI). Secondary outcomes included IVD diffusion coefficient and IVD expansion with short-duration lying. METHODS: Twenty patients progressively loaded their lumbar IVDs (exercise) via an exercise programme involving progressive upright aerobic and resistance exercises targeting the trunk and major muscle groups and were compared to twenty patients who performed motor control training and manual therapy (control). Testing occurred at baseline, 3 months and 6 months. RESULTS: Seventeen exercise and fifteen control patients completed the interventions. There were no group-by-time differences in T2 time of the entire IVD (exercise 94.1 ± 10.0 ms vs. control 96.5 ± 9.3 ms, p = 0.549). Exercise patients had shorter T2 time in the posterior annulus at 6 months (82.7 ± 6.8 ms vs. 85.1 ± 8.0 ms, p = 0.028). Exercise patients showed higher L5/S1 apparent diffusion coefficients and decreased IVD height at 3 months (both p ≤ 0.050). After adjustments for multiple comparisons, differences lost statistical significance. Per-protocol and intent-to-treat analyses yielded similar findings. CONCLUSIONS: This trial found that 6 months of exercise did not benefit the IVD of people with NSCLBP. Based on this index study, future studies could investigate the effect of exercise on IVD in different populations, with different types, durations and/or intensities of exercise, and using different IVD markers. These slides can be retrieved under Electronic Supplementary Material.

Which specific modes of exercise training are most effective for treating low back pain? Network meta-analysis.

OBJECTIVE: Examine the effectiveness of specific modes of exercise training in non-specific chronic low back pain (NSCLBP). DESIGN: Network meta-analysis (NMA). DATA SOURCES: MEDLINE, CINAHL, SPORTDiscus, EMBASE, CENTRAL. ELIGIBILITY CRITERIA: Exercise training randomised controlled/clinical trials in adults with NSCLBP. RESULTS: Among 9543 records, 89 studies (patients=5578) were eligible for qualitative synthesis and 70 (pain), 63 (physical function), 16 (mental health) and 4 (trunk muscle strength) for NMA. The NMA consistency model revealed that the following exercise training modalities had the highest probability (surface under the cumulative ranking (SUCRA)) of being best when compared with true control: Pilates for pain (SUCRA=100%; pooled standardised mean difference (95% CI): -1.86 (-2.54 to -1.19)), resistance (SUCRA=80%; -1.14 (-1.71 to -0.56)) and stabilisation/motor control (SUCRA=80%; -1.13 (-1.53 to -0.74)) for physical function and resistance (SUCRA=80%; -1.26 (-2.10 to -0.41)) and aerobic (SUCRA=80%; -1.18 (-2.20 to -0.15)) for mental health. True control was most likely (SUCRA≤10%) to be the worst treatment for all outcomes, followed by therapist hands-off control for pain (SUCRA=10%; 0.09 (-0.71 to 0.89)) and physical function (SUCRA=20%; -0.31 (-0.94 to 0.32)) and therapist hands-on control for mental health (SUCRA=20%; -0.31 (-1.31 to 0.70)). Stretching and McKenzie exercise effect sizes did not differ to true control for pain or function (p>0.095; SUCRA<40%). NMA was not possible for trunk muscle endurance or analgesic medication. The quality of the synthesised evidence was low according to Grading of Recommendations Assessment, Development and Evaluation criteria. SUMMARY/CONCLUSION: There is low quality evidence that Pilates, stabilisation/motor control, resistance training and aerobic exercise training are the most effective treatments, pending outcome of interest, for adults with NSCLBP. Exercise training may also be more effective than therapist hands-on treatment. Heterogeneity among studies and the fact that there are few studies with low risk of bias are both limitations.

Domains of Chronic Low Back Pain and Assessing Treatment Effectiveness: A Clinical Perspective.

Nonspecific chronic low back pain (CLBP) is a common clinical condition that has impacts at both the individual and societal level. Pain intensity is a primary outcome used in clinical practice to quantify the severity of CLBP and the efficacy of its treatment; however, pain is a subjective experience that is impacted by a multitude of factors. Moreover, differences in effect sizes for pain intensity are not observed between common conservative treatments, such as spinal manipulative therapy, cognitive behavioral therapy, acupuncture, and exercise training. As pain science evolves, the biopsychosocial model is gaining interest in its application for CLBP management. The aim of this article is to discuss our current scientific understanding of pain and present why additional factors should be considered in conservative CLBP management. In addition to pain intensity, we recommend that clinicians should consider assessing the multidimensional nature of CLBP by including physical (disability, muscular strength and endurance, performance in activities of daily living, and body composition), psychological (kinesiophobia, fear-avoidance, pain catastrophizing, pain self-efficacy, depression, anxiety, and sleep quality), social (social functioning and work absenteeism), and health-related quality-of-life measures, depending on what is deemed relevant for each individual. This review also provides practical recommendations to clinicians for the assessment of outcomes beyond pain intensity, including information on how large a change must be for it to be considered "real" in an individual patient. This information can guide treatment selection when working with an individual with CLBP.

Intervertebral disc status is associated with vertebral marrow adipose tissue and muscular endurance.

PURPOSE: Low back pain is a major public health issue. Identifying factors associated with better intervertebral disc (IVD) characteristics gives insight into IVD metabolism and highlights intervention targets for improvement of IVD health. This cross-sectional study investigates whether IVD T2-relaxation time on magnetic resonance imaging (MRI) is associated with vertebral fat fraction (VFF; to quantify marrow adipose tissue), trunk muscle cross-sectional area (CSA), muscle function and physical activity (PA). METHODS: Seventy-nine healthy subjects (35 males, 44 females) without history of spinal disease were included. Lumbar IVDs T2-relaxation time, lumbar VFF and CSA of multifidus, erector spinae, quadratus lumborum, and psoas muscles were quantified via MRI. Isometric trunk flexion and extension endurance times as well as habitual PA levels and exposure to occupational spine risk factors were documented. Pearson-partial correlations adjusted for anthropometric differences by controlling for vertebral body height. RESULTS: Higher IVD T2-time correlated with: (a) lower VFF (r = - 0.27, p < 0.05), (b) greater trunk extensor muscle endurance (r = 0.37, p < 0.01), and (c) greater trunk flexor muscle endurance (r = 0.30, p < 0.01) but not with muscle CSA. Lower VFF also correlated with greater extensor muscle endurance (r = - 0.26, p < 0.05) and habitual PA (MET-mins per week) (r = - 0.24, p < 0.05). CONCLUSION: This is the first study to show that better IVD hydration is associated with lower VFF and that greater physical activity is associated with favourable levels of vertebral marrow adipose tissue in young healthy individuals. Reduced vertebral marrow adipose tissue may specifically improve IVD hydration via improved nutrient supply. These slides can be retrieved under Electronic Supplementary Material.

Are habitual runners physically inactive?

The World Health Organisation's (WHO) physical activity guidelines recommend 150min/week of moderate- to vigorous-intensity physical activity (MVPA) accumulated in 10 min bouts. To see whether people performing habitual exercise for recreation meet these guidelines, 25 long-distance runners [mean 67 km/wk], 25 joggers [mean 28 km/wk], and 20 sedentary adults wore an ActiGraph GT3X+ accelerometer for 7 days. Sedentary time and bouts were similar in runners and sedentary adults (p > 0.46). Sedentary adults performed 20 ± 16 min/day of MVPA (usual bout duration (W50%): 9.53 ± 3.45min), with joggers and runners performing 45 ± 31min (W50%: 16.92 ± 9.53min) and 83 ± 58min (W50%: 20.35 ± 8.85min), respectively (p ≤ 0.001 versus sedentary group). Data showed that 65% of the sedentary group, 32% of joggers and 4% of long-distance runners did not meet the WHO guideline for MVPA. Failure to meet the guideline was most prominent in, but not restricted to, runners who reported ≤50km running per week. Self-reported running does not ensure adults meet physical activity guidelines or offset daily sedentary behaviours. On the other hand, the sedentary group was very close in accumulating recommended bouts of MVPA in incidental activities. Future studies should assess whether modification of work and leisure physical activity would be more fruitful than encouraging recreational exercise per se in meeting physical activity guidelines.

Hypertrophy and Explosive-Reactive Functioning in Sedentary Men After 10 Weeks of Whole-Body Vibration.

Ebing, J, Gast, U, Hauptmann, C, Felsenberg, D, and Belavý, DL. Hypertrophy and explosive-reactive functioning in sedentary men after 10 weeks of whole-body vibration. J Strength Cond Res 32(1): 27-36, 2018-The objective of this study was to determine the impact of vertical (Power-plate; POW) and side-alternating (Galileo; GAL) whole-body vibration exercise on muscle mass and lower-limb neuromuscular function. Forty-three sedentary male subjects (18-30 year) randomized into 3 groups underwent 2 upper-body exercise sessions per week for 10 weeks. Two groups of subjects underwent additional squat exercises on the GAL (N = 15) or POW (N = 14) devices. The third group was control. On magnetic resonance imaging, volume of the thigh muscles was measured. Countermovement jump, multiple one-leg hopping, drop jump, landing test, 15-m sprint, and grip strength were performed. Measurements were performed at baseline, and at 5 and 10 weeks. Significantly greater increases in vasti volume were seen in the GAL (+4.15%; p = 0.00076 vs. control) and POW (+4.81%; p = 0.0074 vs. control) groups than in the control group (-1.22%) at 10 weeks. The adductor magnus volume increased in the GAL (+2.24%; p = 0.00038 vs. baseline) and POW (+2.33%; p = 0.00038 vs. baseline) groups at 10 weeks, but this was not significantly different from the control (-0.67%; p = 0.54 vs. baseline). Hamstring volume decreased in GAL (-1.85%; p = 0.00038 vs. baseline) at 5 weeks with the reduction in the POW group at 5 weeks (-1.73%; p = 0.17 vs. baseline) not reaching significance. There were no significant differences between the POW and GAL groups (p ≥ 0.084) and no significant changes in neuromuscular performance. Twice weekly squat exercises with whole-body vibration, progressing from 3- to 5-minute time under tension, lead to thigh muscle hypertrophy but no improvements in explosive-reactive function.

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.

Disc herniations in astronauts: What causes them, and what does it tell us about herniation on earth?

PURPOSE: Recent work showed an increased risk of cervical and lumbar intervertebral disc (IVD) herniations in astronauts. The European Space Agency asked the authors to advise on the underlying pathophysiology of this increased risk, to identify predisposing factors and possible interventions and to suggest research priorities. METHODS: The authors performed a narrative literature review of the possible mechanisms, and conducted a survey within the team to prioritize research and prevention approaches. RESULTS AND CONCLUSIONS: Based on literature review the most likely cause for lumbar IVD herniations was concluded to be swelling of the IVD in the unloaded condition during spaceflight. For the cervical IVDs, the knowledge base is too limited to postulate a likely mechanism or recommend approaches for prevention. Basic research on the impact of (un)loading on the cervical IVD and translational research is needed. The highest priority prevention approach for the lumbar spine was post-flight care avoiding activities involving spinal flexion, followed by passive spinal loading in spaceflight and exercises to reduce IVD hyper-hydration post-flight.