The Potential of Whole Body Vibration Training during 14-Days of 6°-Head Down Tilt Bed Rest to Counteract Effects on Muscle Performance, Balance and Articular Cartilage

Im Rahmen der ‚Vibration-Bed-Rest-Study’ (VBR-Studie) wurde der Einsatz von Vibrationstraining als Gegenmaßnahme für die degenerativen Auswirkungen von Bettruhe in 6°-Kopftieflage (6°-head-down-tilt (6°-HDT)) untersucht. Dazu wurden 8 Probanden für 14 Tage in Bettruhe mit 6°-HDT immobilisiert. Die Auswirkungen von Bettruhe mit und ohne Einsatz von Vibrationstraining auf unterschiedliche Gewebe und Organe wurden untersucht, darunter z.B. die muskuläre Leistungsfähigkeit, die Gleichgewichtsfähigkeit, sowie Gelenkknorpel im Knie. Gegenstand der Untersuchung waren die folgenden allgemeinen Hypothesen: a) 14 Tage HDT-Bettruhe führen zu einer allgemeinen Dekonditionierung des menschlichen Körpers. b) Die Anwendung von Vibrationstraining während 14-tägiger Bettruhe in 6°-HDT kann dieser Dekonditionierung entgegenwirken. Das zeigt sich in einer Verlangsamung oder Aufhebung der zuvor beobachteten Effekte. In dieser Dissertation werden die Ergebnisse der folgenden Untersuchungen präsentiert und diskutiert: - Muskuläre Leistungsfähigkeit der unteren Extremität (Kapitel 4) - Gleichgewichtsfähigkeit (Kapitel 5) - Gelenkknorpelbiologie und –morphologie (Kapitel 6) Acht gesunde männliche Probanden (Alter: 26 ± 5 Jahre; Gewicht: 78 ± 10 kg; Größe: 179 ± 10 cm) nahmen an der VBR-Studie teil, die im ‚Crossover-Design’ mit zwei Studienphasen durchgeführt wurde. Jeder Proband erhielt in einer Phase Vibrationstraining und in der zweiten Phase eine Kontrollintervention. Während der Trainingsintervention in der Bettruhephase trainierten die Probanden 2 mal täglich für 5 mal 60 Sekunden auf der Vibrationsplatte (Galileo900) bei ein Frequenz von 20 Hz und einer Amplitude von ~ 3 mm. Die Strecke zum und vom Trainingsraum wurde zweimal täglich gegangen. Die Abläufe waren identisch für die Kontroll- und die Trainingsintervention, lediglich die Vibrationsplatte wurde während der Kontrollintervention nicht angestellt. Dieses Studiendesign ermöglichte es daher, den isolierten „Vibrations-Effekt“ zu untersuchen. Die Experimente zur muskulären Leistungsfähigkeit, Gleichgewichtsfähigkeit und Kniegelenksknorpel wurden jeweils vor und nach der Bettruheintervention durchgeführt. Blutabnahmen für Biomarker fanden in regelmäßigen Abständen während der gesamten Untersuchung statt. Die Kraftleistungsdiagnostik zeigte keine Veränderungen in der Maximalkraft der Kniebeuger und Kniestrecker durch Bettruhe. Vibrationstraining führte zu einer Verschlechterung der Maximalkraft in den Kniebeugern, nicht aber in den Kniestreckern. Die maximale Leistung zeigte in den Kniebeugern keine Veränderung durch Bettruhe, Vibrationstraining veränderte das Ergebnis nicht. In den Kniestreckern nahm die maximale Leistung nach Bettruhe signifikant ab, was durch Vibrationstraining aufgehalten werden konnte. Die Ergebnisse zeigten, dass eine Veränderung der Maximalkraft sowie der maximalen Leistung nach einer 14-tägigen Bettruhe unter den gegebenen kontrollierten Bedingungen sehr muskel- und probandenspezifisch auftritt, was an der initialen Leistungsfähigkeit liegen kann. Betrachtet man die maximale Leistung, so konnte Vibrationstraining den Bettruheeffekt für die Kniestrecker signifikant beeinflussen. Die Gleichgewichtsfähigkeit wurde mit Hilfe des Posturomed® untersucht, die Messgrößen waren die Haltezeit und die Auslenkung des Posturomed® bei der Ausübung vorgegebener Übungen. Bettruhe führte zu keiner generellen Veränderung in beiden Parametern. Wurde Vibrationstraining angewendet, so verschlechterten sich Haltezeit und Auslenkung signifikant. Beide Ergebnisse stützen die Ausgangshypothese nicht, dass Bettruhe zu einer Abnahme der Gleichgewichtsfähigkeit führt. Im Gegenteil, Vibrationstraining verschlechterte den Bettruhe-Effekt. Als Grund kann der frühe Messzeitpunkt genannt werden, der keine adäquate Zeit zu einer Trainingsanpassung zuließ, zusätzlich zu der relativ kurzen Bettruhe- und Trainingsintervention. Außerdem stellt Vibrationstraining einen sehr komplexen und anspruchsvollen Reiz für die Propriozeptoren und das zentrale Nervensystem dar, was zu einer akuten Irritation führen kann. Knorpeldicke wurde mit Hilfe der bildgebenden Magnet Resonanz (Magnet Resonance Imaging (MRI)) gemessen. Zusätzlich wurden die Serum-Konzentrationen von ‚Cartilage Oligometric Matrix Protein’ (COMP) untersucht. Eine Abnahme der mittleren sowie der maximalen Knorpeldicke nach 14.Tagen Bettruhe konnte an den Tibia-Kondylen festgestellt werden, nicht aber für den Femur. Vibrationstraining führte zu einer Zunahme der mittleren und maximalen Knorpeldicken. Serum-COMP-Konzentrationen nahmen nach 24 Stunden in Bettruhe signifikant ab und stiegen direkt nach der Bettruhe wieder auf das Ausgangsniveau an. Vibrationstraining veränderte diese Reaktion nicht. Die Ergebnisse der Knorpeluntersuchungen zeigten eine Abnahme der Knorpeldicke in der Tibia und eine Umkehr des Effektes durch Vibrationstraining, was auf eine Veränderung in den mechanischen Eigenschaften von Knorpel durch die Kontroll- sowie die Trainingsintervention zurückzuführen sein könnte. Die Veränderungen der Serum-COMP-Konzentration ist möglicherweise auf veränderte Transportbedingungen der Fragmente aus dem Gelenk zurückzuführen und könnte auf eine Veränderung im Knorpelstoffwechsel durch die mangelnde mechanische Belastung in Bettruhe hinweisen. Zusammenfassend konnten die allgemeinen Hypothesen der Untersuchung nicht vollständig bestätigt werden. Degenerative Veränderungen durch 14 Tage in HDT-Bettruhe konnten für muskuläre Leistungsfähigkeit, Gleichgewichtsfähigkeit und Kniegelenksknorpel mit den hier angewendeten Methoden nicht in dem erwarteten Ausmaß festgestellt werden, beziehungsweise waren parameter- und probanden-spezifisch sehr unterschiedlich. Die Gründe dafür können vielfältig sein, beigetragen dazu haben sicher die sehr kontrollierten Bedingungen, der ausgeglichene Energiehaushalt, das Aufstehen, um zum Trainingsraum zu laufen, sowie der initiale Trainingszustand der Probanden. Das Vibrationstraining wurde in seiner Intensität so gewählt, dass es Organe und Gewebe vor Degeneration bewahren oder den Prozess verlangsamen sollte. Die zum Teil ausbleibende Degeneration führte dazu, dass der Trainingsreiz unter Umständen nicht mehr angemessen war. Wenn Bettruhe keinen negativen Effekt auf das jeweilige System hatte, so konnte Vibrationstraining dann auch nicht mehr als Gegenmaßnahme wirken. Die zum Teil gefundenen negativen Effekte waren so nicht erwartet worden. Auf Grundlage der hier vorgestellten Ergebnisse kann isoliertes Vibrationstraining nicht generell als Gegenmaßnahme für Effekte von Bettruhe in 6°-HDT auf muskuläre Leistungsfähigkeit, Gleichgewichtsfähigkeit und Gelenkknorpel empfohlen werden. Dennoch sollten weitere Untersuchungen folgen, um die Kombination von Vibrationstraining mit herkömmlichen Krafttrainingsmethoden im Rahmen von Bettruhestudien zu untersuchen, und um die Ergebnisse für Gelenkknorpel zu spezifizieren. Dabei sollte schon im Auswahlprozess der Probanden dem initialen Trainingsniveau gesteigerte Beachtung geschenkt werden. Wünschenswert wäre eine bezüglich des Leistungsniveaus homogene Probandengruppe. Generell sind höhere Intensitäten in der Trainingsplanung empfehlenswert und im Weiteren sollte der Schwerpunkt zukünftig auf eine individuellere, progressive Steigerung der Trainingsintensität im Rahmen von Bettruhestudien gelegt werden. The Vibration-Bed-Rest-Study (VBR-Study) was performed to investigate the potential of whole body vibration training to counteract degenerative effects of 14 days of 6° head down tilt bed rest (6°-HDT bed rest) on the human body. The effects of immobilization with and without vibration training on different tissues and organs, including skeletal muscle performance, balance performance and articular cartilage, were determined. The following general hypotheses were tested: a) 14 days of 6°-HDT bed rest lead do a general deconditioning of the human body b) Vibration training has the potential to counteract deconditioning during 14- days of 6°-HDT bed rest in terms of slowing down the effects or even preventing them. In this thesis, the results of the following experiments were presented and discussed: Skeletal Muscle Performance (Chapter 4), Balance Performance (Chapter 5), Cartilage biology and morphology (Chapter 6). Eight healthy male subjects (age: 26 ± 5 years; mass: 78 ± 10 kg; height: 179 ± 10 cm) participated in the study after giving their informed consent. The study was performed in a cross-over-design where each subject received vibration training in one phase and a control intervention in the other. During the training intervention, subjects trained 2 x 5 minutes per day at 20 Hz with ~ 3 mm amplitude on a vibration plate (Galileo 900). Subjects walked a defined path to the training room and back twice daily. The schedules during the control and the vibration intervention were identical except for the vibration of the plate. By this study design we were able to interpret the real ‘vibration effect’. The experiments on muscle performance, balance performance and cartilage morphology were scheduled before and after the 14 days of 6°-HDT bed rest. Blood sampling for the analysis of biomarkers was done regularly at predefined times during the whole study. Muscle performance was measured in maximum voluntary contraction (MVC) and maximal power. MVC did not change due to bed rest for the knee flexor and knee extensor muscles. When subjects received vibration training there was a significant decrease in MVC for the knee flexor muscles, but not for the knee extensor muscles. Maximal power did not change due to bed rest for the knee flexor muscles. However, there was a significant decrease in maximal power of the knee flexors when subjects received vibration training. In the knee extensors, bed rest lead to a significant decrease in maximal power which could be prevented by vibration training. The results indicated that changes in MVC and power after 14 days of 6°-HDT bed rest under the given conditions were muscle and subject specific and may have depended on their initial physical status. In reference to the power of the knee extensors, the used training protocol was sufficient to cause a significant difference in bed rest effects with and without training. Thus, vibration training with the protocol used had the potential to affect the response of muscle to bed rest induced immobilization. Balance performance was measured with the Posturomed® device, using the parameters ‘holding time’ and ‘displacement’. Bed rest did not lead to a general deterioration in both parameters. Vibration training lead to a significant decrease in holding time and an increased in displacement of the Posturomed®, which reflected a decline in the performance level. The results may have been impacted by the early point in time of the measurement, which did not allow for adaptation to the training process, in addition to the relatively short duration of the bed rest and the training period. Also, vibration training is a very complex and demanding input for our postural receptor system and the central nervous system, which may possibly have caused an acute disorientation that lead to the results. Articular cartilage thickness was measured using magnet resonance imaging (MRI) of the right knee. Additionally, serum concentrations of ‘Cartilage oligometric matrix protein’ (COMP) were analysed from 10 blood samples taken throughout the study. Decreases in average and maximum cartilage thickness after bed rest were observed for the tibial condyle and the effects inverted into an increase when subjects received vibration training. No changes were obtained for the femoral condyle. After 24h of 6°-HDT bed rest, serum COMP concentration decreased significantly and the values returned to baseline after bed rest. Vibration training did not alter the response of serum COMP concentrations. This study showed that decreases in cartilage thickness after a 14-day bed rest can be observed and that vibration training may be able to counteract this effect. Changes in cartilage thickness could reflect a change in mechanical properties of articular cartilage due to the bed rest and the control intervention. Bed rest resulted in a reduction of serum COMP concentrations within less than two days which might have been caused by decreased diffusion of COMP molecules from the cartilage into serum due and / or might reflect a change in cartilage metabolism in response to a lack of exposure of the joint to mechanical loading. Summarizing the results, our general hypotheses were not completely substantiated. It can be stated that the degenerative effects of immobilization did not reach the degree that was previously expected. Amongst others, the effect of the very controlled study conditions, the normo-caloric diet and the allowance to stand up and walk to the training room and back twice a day might have contributed to this outcome. Also, the pre-study training status may impact the bed rest effects more than expected. The training intensity was chosen in order to prevent or decelerate the de-conditioning of the human body due to bed rest. As this deconditioning was missing in some parts, the training intensity was not appropriate to impact the bed rest effects anymore. The observed decline in performance due to the vibration training has not been expected before. Based on the findings of the VBR-Study, we cannot recommend generally pure vibration training as a countermeasure for changes in muscle performance, balance performance and articular cartilage morphology. For the latter, our results showed that cartilage in the knee joint is responsive to both unloading and vibration training. However, further research is encouraged in order to specify the responses. It is likely that the combination of whole body vibration with resistance training will lead to more promising results. Additionally, we suggest considering the initial training status when recruiting and screening subjects. With this in focus, a homogeneous group of subjects should be aspired. Generally, higher training intensities are recommended, in addition to an individually tailored vibration training protocol for each subject with a progressively increasing training intensity

Framework for modulating ambulatory load in the context of in vivo mechanosensitivity of articular cartilage

Objective: Different stress modalities have been used to provoke a load induced mechanoresponse in blood markers of articular cartilages. The challenge in in vivo experiments is to alter specific loading characteristics. Here, we aimed to develop a load modification framework that changes ambulatory load magnitude without changing load frequency or joint kinematics. Design: Spatiotemporal parameters, sagittal joint kinematics and vertical ground reaction force (vGRF) of 24 healthy participants were recorded while walking with reduced (80%), normal (100%) and increased (120%) bodyweight (BW) on three separate test days in a block randomized cross-over design. The reduced and increased load conditions were compared to the normal load condition using paired sample t-tests for spatiotemporal pa- rameters and statistical parametric mapping for vGRF and joint kinematics. Results: Load modification resulted in measured vGRF differences of 19.5%BW (reduced) and þ16.8%BW (increased). Spatiotemporal parameters with reduced and increased load did not differ from normal load except of a shorter stance time under reduced load (21 ms). Joint kinematics for both conditions did not differ from normal load except of decreased ankle dorsiflexion (maximum 5.9) and increased knee flexion (maximum þ6.5) for the reduced load condition during pre-swing when the support limb is already unloaded. Conclusion: Overall, we did not observe relevant differences in spatiotemporal parameters or joint kinematics between loading conditions. Mean absolute joint angle deviations below 4.1 demonstrate that the proposed load modification framework changes ambulatory load magnitude without changing load frequency or joint kinematics

Sensitivity of serum concentration of cartilage biomarkers to 21-days of bed rest

The objective of the study was to test the hypothesis that serum levels of cartilage oligomeric matrix protein (COMP) would decrease and serum levels of tumor-necrosis factor alpha (TNF-α) and selected matrix metalloproteinases (MMPs) would increase in response to bed rest (BR) and that these changes are unaffected by the intake of potassium bicarbonate or whey protein. Seven and nine healthy male subjects participated in two 21-day 6° head down tilt crossover BR-studies with nutrition interventions. Serum samples were taken before, during, and after BR and biomarker concentrations were measured using commercial enzyme-linked immunosorbent assays. MMP-3 during BR was significantly lower than at baseline (reduction greater 20%; p < 0.001). MMP-3 increased significantly from 14 to 21 days of BR (+7%; p = 0.049). COMP during BR was significantly lower than at baseline (reduction greater 20%; p < 0.001). MMP-3 and COMP returned to baseline within 1 day after BR. MMP-9 on day 3 of BR was significantly lower than at baseline (-31%; p < 0.033) and on days 3, 5, and 14 of BR significantly lower than at the end of and after BR (reduction greater 35%; p < 0.030). The nutritional countermeasures did not affect these results. The observed changes in cartilage biomarkers may be caused by altered cartilage metabolism in response to the lack of mechanical stimulus during BR and inflammatory biomarkers may play a role in changes in biomarker levels.; Immobilization independently from injury can cause altered cartilage biomarker concentration. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res

Musculoskeletal research in human space flight - unmet needs for the success of crewed deep space exploration

Based on the European Space Agency (ESA) Science in Space Environment (SciSpacE) community White Paper "Human Physiology - Musculoskeletal system", this perspective highlights unmet needs and suggests new avenues for future studies in musculoskeletal research to enable crewed exploration missions. The musculoskeletal system is essential for sustaining physical function and energy metabolism, and the maintenance of health during exploration missions, and consequently mission success, will be tightly linked to musculoskeletal function. Data collection from current space missions from pre-, during-, and post-flight periods would provide important information to understand and ultimately offset musculoskeletal alterations during long-term spaceflight. In addition, understanding the kinetics of the different components of the musculoskeletal system in parallel with a detailed description of the molecular mechanisms driving these alterations appears to be the best approach to address potential musculoskeletal problems that future exploratory-mission crew will face. These research efforts should be accompanied by technical advances in molecular and phenotypic monitoring tools to provide in-flight real-time feedback

Effect of disease-modifying anti-rheumatic drugs on bone structure and strength in psoriatic arthritis patients

Objectives To address whether the use of methotrexate (MTX) and biological disease-modifying anti-rheumatic drugs (bDMARDs) impacts bone structure and biomechanical properties in patients with psoriatic arthritis (PsA). Methods This is a cross-sectional study in PsA patients receiving no DMARDs, MTX, or bDMARDs. Volumetric bone mineral densities (vBMDs), microstructural parameters, and biomechanical properties (stiffness/failure load) were determined by high-resolution peripheral quantitative CT and micro-finite element analysis in the respective groups. Bone parameters were compared between PsA patients with no DMARDs and those receiving any DMARDs, MTX, or bDMARDs, respectively. Results One hundred sixty-five PsA patients were analyzed, 79 received no DMARDs, 86 received DMARDs, of them 52 bDMARDs (TNF, IL-17- or IL-12/23 inhibitors) and 34 MTX. Groups were balanced for age, sex, comorbidities, functional index, and bone-active therapy, while disease duration was longest in the bDMARD group (7.8 ± 7.4 years), followed by the MTX group (4.6 ± 7.4) and the no-DMARD group (2.9 ± 5.2). No difference in bone parameters was found between the no-DMARD group and the MTX group. In contrast, the bDMARD group revealed significantly higher total (p = 0.001) and trabecular vBMD (p = 0.005) as well as failure load (p = 0.012) and stiffness (p = 0.012). In regression models, age and bDMARDs influenced total vBMD, while age, sex, and bDMARDs influenced failure load and stiffness. Conclusion Despite longer disease duration, bDMARD-treated PsA patients benefit from higher bone mass and better bone strength than PsA patients receiving MTX or no DMARDs. These data support the concept of better control of PsA-related bone disease by bDMARDs

Sclerostin and DKK1 levels during 14 and 21 days of bed rest in healthy young men

Objectives: Wnt signaling pathway may be crucial in the pathogenesis of disuse-induced bone loss. Sclerostin and DKK1, antagonists of the Wnt signaling pathway, were assessed during immobilization by bed rest in young, healthy people. Methods: Two bed rest studies were conducted at the German Aerospace Center in Cologne. 14 days of 6° head-down-tilt bed rest were applied to eight healthy young male test subjects in study 1 and 21 days of head-down-tilt bed rest to seven healthy male subjects in study 2. Results: Sclerostin levels increased in both studies during bed rest (study 1, 0.64±0.05 ng/ml to 0.69±0.04 ng/ml, P=0.014; study 2, 0.42±0.04 ng/ml to 0.47±0.04 ng/ml, P=0.008) and they declined at the end of the 14- and 21-day bed rest periods. DKK1 decreased during the bed rest period in study 1 (P<0.001) but increased during bed rest in study 2 (P=0.006). As expected, bone formation marker PINP decreased (study 1, P=0.013; study 2, P<0.001) and bone resorption marker NTX increased during bed rest (P<0.001). Conclusion: Data suggest that the Wnt signaling pathway is involved in disuse-induced bone loss in young, healthy humans

Task-specific recruitment of motor units for vibration damping

Vibrations occur within the soft tissues of the lower extremities due to the heel-strike impact during walking. Increases in muscle activity in the lower extremities result in increased damping to reduce this vibration. The myoelectric intensity spectra were compared using principal component analysis from the tibialis anterior and lateral gastrocnemius of 40 subjects walking with different shoe conditions. The soft insert condition resulted in a significant, simultaneous increase in muscle activity with a shift to higher myoelectric frequencies in the period 0-60 ms after heel-strike which is the period when the greater vibration damping occurred. These increases in myoelectric frequency match the spectral patterns which indicate increases in recruitment of faster motor units. It is concluded that fast motor units are recruited during the task of damping the soft-tissue resonance that occurs following heel-strike

Locomotion replacement exercise cannot counteract cartilage biomarker response to 5 days of immobilization in healthy adults

Biomarkers of cartilage metabolism are sensitive to changes in the biological and mechanical environment and can indicate early changes in cartilage homeostasis. The purpose of this study was to determine if a daily locomotion replacement program can serve as a countermeasure for changes in cartilage biomarker serum concentration caused by immobilization. Ten healthy male subjects (mean ± 1 standard deviation, age: 29.4±5.9 years; body mass: 77.7±4.1 kg) participated in the cross-over 5 days bed rest study with three interventions: control (CON), standing (STA) and locomotion replacement training (LRT). Serum samples were taken before, during, and after bed rest. Biomarker concentrations were measured using commercial enzyme-linked immunosorbent assays. Cartilage oligomeric matrix protein (COMP) levels after 24hrs of bed rest decreased independently of the intervention (-16.8 to -9.8%) and continued to decreased until 72hrs of bed rest (minimum, -23.2 to -20.6%). LRT and STA did not affect COMP during bed rests (p=0.056) but there was a strong tendency for a slower decrease with LRT (-9.4%) and STA (-11.7%) compared to CON (-16.8%). MMP-3 levels decreased within the first 24hrs of bed rest (CON: -22.3%; STA: -14.7%; LRT: -17%) without intervention effect. Both COMP and MMP-3 levels recovered to baseline levels during the 6 days recovery period. MMP-1, MMP-9 and TNF-alpha levels were not affected by immobilization or intervention. COMP and MMP-3 are mechanosensitive cartilage biomarkers affected by immobilization, and simple interventions such as standing upright or LRT during bed rest cannot prevent these changes. Clinical significance: Simple locomotion interventions cannot prevent cartilage biomarker change during bed rest

EMG and Heart Rate Responses Decline within 5 Days of Daily Whole-Body Vibration Training with Squatting

In this study, we examined the acute effects of a 5-day daily whole-body vibration (WBV) training on electromyography (EMG) responses of the m. rectus femoris and m. gastrocnemius lateralis, heart rate (HR, continuously recorded), and blood lactate levels. The purpose of the study was to investigate the adaptation of muscle activity, heart rate and blood lactate levels during 5 days of daily training. Two groups of healthy male subjects performed either squat exercises with vibration at 20 Hz on a side alternating platform (SE+V, n = 20, age = 31.9 (+/-) 7.5 yrs., height = 178.8 (+/-) 6.2 cm, body mass = 79.2 (+/-) 11.4 kg) or squat exercises alone (SE, n = 21, age = 28.4 (+/-) 7.3 years, height = 178.9 (+/-) 7.4 cm, body mass = 77.2 (+/-) 9.7 kg). On training day 1, EMG amplitudes of the m. rectus femoris were significantly higher (P,0.05) during SE+V than during SE. However, this difference was no longer statistically significant on training days 3 and 5. The heart rate (HR) response was significantly higher (P<0.05) during SE+V than during SE on all training days, but showed a constant decline throughout the training days. On training day 1, blood lactate increased significantly more after SE+V than after SE (P<0.05). On the following training days, this difference became much smaller but remained significantly different. The specific physiological responses to WBV were largest on the initial training day and most of them eclined during subsequent training days, showing a rapid neuromuscular and cardiovascular adaptation to the vibration stimulus