In vivo bone remodeling rates determination and compressive stiffness variations before, during 60 days bed rest and two years follow up: A micro-FE-analysis from HR-pQCT measurements of the berlin Bed Rest Study-2

Abstract

Bed rest studies are used for simulation and study of physiological changes as observed in unloading/non-gravity environments. Amongst others, bone mass reduction, similar as occurring due to aging osteoporosis, combined with bio-fluids redistribution and muscle atrophy have been observed and analyzed. Advanced radiological methods of high resolution such as HR-pQCT (XtremeCT) allow 3D-visualizing in vivo bone remodeling processes occurring during absence/reduction of mechanical stimuli (0 to <1 g) as simulated by bed rest. Induced bone micro-structure (e.g. trabecular number, cortical thickness, porosity) and density variations can be quantified. However, these parameters are average values of each sample and important information regarding bone mass distribution and within bone mechanical behaviour is lost. Finite element models with hexa-elements of identical size as the HR-pQCT measurements (0.082 mm×0.082 mm×0.082 mm, ca. 7E6 elements/sample) can be used for subject-specific in vivo stiffness calculation. This technique also allows quantifying if bone microstructural changes represent a risk of mechanical bone collapse (fracture). Materials and methods In the Berlin Bed Rest Study-2, 23 male subjects (20–50 YO) were maintained 60 days under restricted bed rest (6° HDT) aiming to test a - for this study specifically designed - vibration resistive exercise regime for maintenance of bone mass and muscle functionality at normal levels (base line measurements). For comparison a resistive exercise without vibration and a control group were included. Base line HR-pQCT measurements (3 days before bed rest: base line), as well as during 30 days bed rest (BR30 and BR59, 3 days of recovery (R3), R15, R30, R90, R180, R360, and R720 were performed. CT-scan voxels were converted into finite elements (hexa-82 µm edge length) for calculating in vivo compressive stiffness during the experiment duration. Histograms of stresses and strains distributions as well as anatomical regions susceptible for mechanical failure were identified and compared. Results: Resistive vibration exercises (RVE) were able to maintain in the majority of the subjects compressive bone strength as determined after modelling a compressive test using finite element models. Compressive bone stiffness using FEA was monitored through analysis of the internal deformation on the trabecular structures and cortical bone, reaction forces, and minimum principal strains on the in vivo CT measured bone regions during the experiment duration. Stress distributions (main stresses) and von Mises stress distribution remained comparable with those determined in the base line measurements for the RVE-group. However, no major differences were found in the group with resistive exercise training alone. Without mechanical stimuli an increment of bone regions with high stress concentration was observed and a reduction of up to 10% of bone compressive stiffness was quantified by using subject-specific finite-element analysis. Anatomically von Mises stress concentrations, thus bone regions susceptible to fail mechanically, were observed at the center of the cancellous bone and at the antero- posterior region of the cortical bone. Conclusions: Finite element simulations from bed rest studies are an invaluable tool to determine subject-specific in vivo compressive stiffness and anatomical mechanically compromised regions under controlled mechanical conditions (unloading) which - until now - are not possible to be determined with any other method. Vibration exercise combined with a resistive compressive force was able to maintain bone structure and density even during 60 days of bed rest