Gisela Beller

Prevention of bone loss during 56 days of strict bed rest by side-alternating resistive vibration exercise

Bed rest is a recognized model for muscle atrophy and bone loss in space flight and in clinical medicine. We hypothesized that whole body vibration in combination with resistive exercise (RVE) would be an effective countermeasure. Twenty healthy male volunteers underwent horizontal bed rest for 56 days and were randomly assigned either to a group that performed RVE 11 times per week or to a group that underwent bed rest only (Ctrl). Bone mineral content (BMC) was assessed by peripheral quantitative computed tomography (pQCT) in the tibia and the radius and by dual x-ray absorptiometry (DXA) in the hip and lumbar spine at baseline and at regular intervals during bed rest and a 12-month follow-up. RVE appeared to protect muscle size and function, and it also prevented bone loss (p-values between <0.001 and 0.01). Bone losses were largest in the distal tibia epiphysis, where BMC declined from 421.8 mg/mm (SD 51.3) to 406.6 mg/mm (SD 52.7) in Ctrl, but only from 411.1 mg/mm (SD 56.6) to 409.6 mg/mm (SD 66.7) in RVE. Most of the BMC losses were recovered by 12-month follow-up. Analyses showed that the epiphyseal cortex, rather than spongiosa, depicted the most pronounced changes during bed rest and recovery. These results suggest that the combined countermeasure applied in this study is effective to prevent bone losses from the tibia. This underlines the importance of mechanical usage for the maintenance of the human skeleton.

Trabecular and cortical bone density and architecture in women after 60 days of bed rest using high-resolution pQCT: WISE 2005

Prolonged bed rest is used to simulate the effects of spaceflight and causes disuse‐related loss of bone. While bone density changes during bed rest have been described, there are no data on changes in bone microstructure. Twenty‐four healthy women aged 25 to 40 years participated in 60 days of strict 6‐degree head‐down tilt bed rest (WISE 2005). Subjects were assigned to either a control group (CON, n = 8), which performed no countermeasures; an exercise group (EXE, n = 8), which undertook a combination of resistive and endurance training; or a nutrition group (NUT, n = 8), which received a high‐protein diet. Density and structural parameters of the distal tibia and radius were measured at baseline, during, and up to 1 year after bed rest by high‐resolution peripheral quantitative computed tomography (HR‐pQCT). Bed rest was associated with reductions in all distal tibial density parameters (p < 0.001), whereas only distal radius trabecular density decreased. Trabecular separation increased at both the distal tibia and distal radius (p < 0.001), but these effects were first significant after bed rest. Reduction in trabecular number was similar in magnitude at the distal radius (p = 0.021) and distal tibia (p < 0.001). Cortical thickness decreased at the distal tibia only (p < 0.001). There were no significant effects on bone structure or density of the countermeasures (p ≥ 0.057). As measured with HR‐pQCT, it is concluded that deterioration in bone microstructure and density occur in women during and after prolonged bed rest. The exercise and nutrition countermeasures were ineffective in preventing these changes.

WISE-2005: Bed-rest induced changes in bone mineral density in women during 60 days simulated microgravity☆

To better understand the effects of prolonged bed-rest in women, 24 healthy women aged 25 to 40 years participated in 60-days of strict 6° head-down tilt bed-rest (WISE-2005). Subjects were assigned to either a control group (CON, n=8) which performed no countermeasure, an exercise group (EXE, n=8) undertaking a combination of resistive and endurance training or a nutrition group (NUT, n=8), which received a high protein diet. Using peripheral quantitative computed tomography (pQCT) and dual X-ray absorptiometry (DXA), bone mineral density (BMD) changes at various sites, body-composition and lower-leg and forearm muscle cross-sectional area were measured up to 1-year after bed-rest. Bone loss was greatest at the distal tibia and proximal femur, though losses in trabecular density at the distal radius were also seen. Some of these bone losses remained statistically significant one-year after bed-rest. There was no statistically significant impediment of bone loss by either countermeasure in comparison to the control-group. The exercise countermeasure did, however, reduce muscle cross-sectional area and lean mass loss in the lower-limb and also resulted in a greater loss of fat mass whereas the nutrition countermeasure had no impact on these parameters. The findings suggest that regional differences in bone loss occur in women during prolonged bed-rest with incomplete recovery of this loss one-year after bed-rest. The countermeasures as implemented were not optimal in preventing bone loss during bed-rest and further development is required.

Impact of oral ibandronate 150 mg once monthly on bone structure and density in post-menopausal osteoporosis or osteopenia derived from in vivo μCT

The effect of ibandronate 150 mg/once monthly in the treatment of post-menopausal osteopenia and osteoporosis on bone micro-structure at the distal tibia and radius has not been considered to date. Seventy post-menopausal women with osteoporosis or osteopenia were recruited. All subjects received calcium and vitamin D supplementation and were randomized to either a group which took 150 mg ibandronate oral monthly or a placebo group over a 12-month period. μCT measures of the distal tibia and radius were conducted every three months, with DXA lumbar spine and hip measurements conducted only pre and post and serum markers of bone formation and resorption measured every 6 months. After 12-months no significant impact of ibandronate on the primary outcome measures bone-volume to tissue-volume and trabecular separation at the distal tibia (p≥0.15) was found. Further multiple regression analyses of the primary end-points indicated a significant effect favoring the ibandronate intervention (p=0.045). Analysis of secondary end-points showed greater increases in distal tibia cortical thickness, cortical density and total density (p≤0.043) with ibandronate and no significant effects at the distal radius, but greater increases of hip DXA-BMD and lumbar spine DXA-BMD (p≤0.017). Ibandronate use resulted in a marked reduction in bone turnover (p<0.001). While ibandronate resulted in greater mineralization of bone, this effect differed from one body region to another. There was some impact of ibandronate on bone structure (cortical thickness) at the distal tibia, but not on bone-volume to tissue-volume or trabecular separation.

Segmentation of bone CT images and assessment of bone structure using measures of complexity

A nondestructive and noninvasive method for numeric characterization (quantification) of the structural composition of human bone tissue has been developed and tested. In order to quantify and to compare the structural composition of bones from 2D computed tomography (CT) images acquired at different skeletal locations, a series of robust, versatile, and adjustable image segmentation and structure assessment algorithms were developed. The segmentation technique facilitates separation from cortical bone and standardizes the region of interest. The segmented images were symbol-encoded and different aspects of the bone structural composition were quantified using six different measures of complexity. These structural examinations were performed on CT images of bone specimens obtained at the distal radius, humeral mid-diaphysis, vertebral body, femoral head, femoral neck, proximal tibia, and calcaneus. In addition, the ability of the noninvasive and nondestructive measures of complexity to quantify trabecular bone structure was verified by comparing them to conventional static histomorphometry performed on human fourth lumbar vertebral bodies. Strong correlations were established between the measures of complexity and the histomorphometric parameters except for measures expressing trabecular thickness. Furthermore, the ability of the measures of complexity to predict vertebral bone strength was investigated by comparing the outcome of the complexity analysis of the CT images with the results of a biomechanical compression test of the third lumbar vertebral bodies from the same population as used for histomorphometry. A multiple regression analysis using the proposed measures including structure complexity index, structure disorder index, trabecular network index, index of a global ensemble, maximal L-block, and entropy of x-ray attenuation distribution revealed an excellent relationship (r=0.959, r2=0.92) between the measures of complexity and compressive bone strength. In conclusion, the image segmentation techniques and the assessment of bone architecture by measures of complexity have been successfully applied to analyze high-resolution peripheral quantitative computed tomography (pQCT) and CT images obtained from the distal radius, humeral mid-diaphysis, third and fourth lumbar vertebral bodies, proximal femur, proximal tibia, and calcaneus. The proposed approach is of broad interest as it can be applied for the quantification of structures and textures originating from different imaging modalities in other fields of science.

Comparative examination of human proximal tibiae in vitro by ultrasonic guided waves and pQCT.

The velocity of ultrasonic guided waves in long bones is dependent upon two determinants of bone strength: the cortical thickness and the material properties. In this study, six human proximal tibiae in vitro were examined to test the efficacy of an ultrasonic method based on guided waves. Peripheral quantitative computed tomography (pQCT) was used as the comparative reference modality. The guided wave velocity (c(F)) was derived from two-dimensional (2-D) spatial-temporal waveform profiles formed by multiple ultrasonic signals acquired along the bones at 100 kHz frequency and passed wavelet processing. The ultrasonic profiles from the examined bones were ranged according to pQCT measurements of cortical thickness (CTh), and cortical bone mineral density (CBMD). Strong correlations between c(F) and CTh (r(S) = 0.83, p < 0.0001) and CBMD (r(S) = 0.88, p < 0.0001) resulted. The study confirmed a potential for guided waves to assess atrophic changes of the proximal tibia.