WISE-2005: Bed-rest induced changes in bone mineral density in women during 60 days simulated microgravity☆
Highlights
► Bed-rest results in regional differences in losses of bone in women. ► The greatest effects on bone were seen at the hip and distal tibia. ► Little effect of the countermeasures was seen on bone loss. ► Losses in muscle mass and some changes in body composition were reduced by the exercise countermeasure.
Introduction
In clinical routine the aspects and causes of bone loss are complex. In postmenopausal osteoporosis, for example, there are typically a number of factors contributing to the loss of bone. As such, bone loss causes health care systems worldwide tremendous effort and monetary costs every year, as progressive osteoporosis frequently leads to reduced bone strength, which, when accompanied by falls, can lead to fractures, subsequent immobilisation and further musculoskeletal deconditioning. As part of this, one aspect that can contribute to bone loss is physical inactivity. Bone loss occurs with stroke [1], [2], spinal cord injury[3], [4], and prolonged bed-rest [5], all of which involve some form of inactivity or reduced function. In manned space research bone loss has been detected to be a serious problem. This bone loss can be difficult to prevent with exercise modalities [6], [7], [8] and is presumed to occur as a result of the reduced loading of bone associated with the microgravity environment. Simulated weightlessness, as induced in prolonged bed-rest studies [5], [9], is a valuable tool to evaluate the deconditioning bone occurring in clinical medicine as well as in the manned spaceflight and to define countermeasures to prevent and/or rehabilitate such changes.
Bed-rest studies have to date typically been performed with male subjects. There is of course no guarantee that countermeasures which may, or may not, work for male subjects would necessarily have the same effect on women. The common effects of bed-rest on bone, typically in male subjects, include an increase in bone resorption [10], [11], [12], [13], no significant change [5], [14], [15] or marginal reduction [11], [16], [17], [18], [19], [20], [21] of bone formation, increased calcium excretion [5], [11], [13], and ultimately loss of bone mass and density, predominately from the load-bearing regions of the body [8], [19], [22]. The “Women International Space Simulation for Exploration” (WISE-2005) prolonged bed-rest study was initiated to improve our understanding of the adaptation of female physiology to spaceflight simulation (bed-rest) and to trial countermeasures against the expected deconditioning associated with this simulation in women.
In the WISE-2005 study, in addition to female subjects undergoing strict bed-rest, an exercise countermeasure comprising resistance training and aerobic exercise as well as a high protein and leucine nutrition countermeasure were trialled. As part of our involvement in the WISE-2005 study, we aimed to examine the changes in bone mass at the lower leg (tibia), forearm (radius), hip and lumbar spine and also the effects of the exercise and nutrition countermeasures against these changes.
Section snippets
Bed-rest protocol and subjects
The WISE-2005 study was supported by the European, French, Canadian, German and North American Space agencies (ESA, CNES, Canadian Space Agency, DLR, NASA) and was conducted at the Medes Institute for Space Medicine and Physiology at the Rangueil University Hospital in Toulouse, France (www.spaceflight.esa.int/wise/).
Twenty four healthy female volunteers, 25 to 40 years old participated in this study (Table 1). They were matched according to pre-bed-rest aerobic fitness levels and then randomly
Results
Except for data being unavailable from two subjects in the exercise group at R + 90 and one exercise subject at R + 360, all subjects were measured at all planned points. With the exception of leg sub-region BMD (p = 0.009; whole-body DXA) there was no evidence for differences between groups at baseline for any of the BMD variables (p ≥ 0.10; see Table 3, Table 4, Table 5). Data on changes in bone mineral content (BMC) are presented in online supplementary material (ASM Tables 1–3). The results for BMC
Discussion
Contrary to our expectations, the current study found that in women undergoing 60-days bed-rest, an exercise countermeasure combining high-load resistive and aerobic exercise components did not significantly reduce bone mineral density losses. As expected, however, the nutrition countermeasure, which was mainly targeted at muscle metabolism, had no effect on BMD change compared to control. The nutrition countermeasure, however, had no effect on lean and fat mass changes or on muscle CSA at the
Conclusions
In conclusion, the current study examined regional bone loss in women during 60-days bed-rest. Bone loss was greatest at the distal tibia and proximal femur. The pattern of bone loss was similar to that seen in men in other studies in bed-rest, though the data provide some suggestions of sex-differences, for example at the distal radius. The exercise countermeasure (high-load resistive exercise on the flywheel device with lower-body negative pressure treadmill locomotion) implemented provided
Acknowledgments
We thank the 24 women who volunteered for this bed-rest investigation as well as the nurses, staff, and entire research team at the MEDES Space Clinic (Toulouse Rangueil Hospital) for their exceptional care of the subjects during bed-rest and exercise. The study WISE-2005 (Women International Investigation for Space Exploration) was sponsored by the European Space Agency (ESA), the National Aeronautics and Space Administration of the USA (NASA), the Canadian Space Agency, and the French “Centre
References (62)
- et al.
Comparison of MRI with EMG to study muscle activity associated with dynamic plantar flexion
Magn Reson Imaging
(2003) - et al.
Ambulatory level and asymmetrical weight bearing after stroke affects bone loss in the upper and lower part of the femoral neck differently: bone adaptation after decreased mechanical loading
Bone
(2000) Perspective on the impact of weightlessness on calcium and bone metabolism
Bone
(1998)- et al.
Effect of prolonged bed rest on bone mineral
Metabolism
(1970) - et al.
Bone–muscle strength indices for the human lower leg
Bone
(2000) - et al.
Muscle atrophy and bone loss after 90 days bed rest and the effects of flywheel resistive exercise and pamidronate: results from the LTBR study
Bone
(2005) - et al.
WISE-2005: supine treadmill exercise within lower body negative pressure and flywheel resistive exercise as a countermeasure to bed rest-induced bone loss in women during 60-day simulated microgravity
Bone
(2008) - et al.
Lower body negative pressure treadmill exercise as a countermeasure for bed rest-induced bone loss in female identical twins
Bone
(2007) - et al.
Prevention of bone loss during 56 days of strict bed rest by side-alternating resistive vibration exercise
Bone
(2010) - et al.
Non-invasive axial loading of mouse tibiae increases cortical bone formation and modifies trabecular organization: a new model to study cortical and cancellous compartments in a single loaded element
Bone
(2005)
Modulation of appositional and longitudinal bone growth in the rat ulna by applied static and dynamic force
Bone
Functional adaptation to mechanical loading in both cortical and cancellous bone is controlled locally and is confined to the loaded bones
Bone
Strain rate as a controlling influence on adaptive modeling in response to dynamic loading of the ulna in growing male rats
Bone
Longitudinal study of bone mineral content in the lumbar spine, the forearm and the lower extremities after spinal cord injury
Eur J Clin Invest
Bone mineral density in upper and lower extremities during 12 months after spinal cord injury measured by peripheral quantitative computed tomography
Spinal Cord
Resistance exercise as a countermeasure to disuse-induced bone loss
J Appl Physiol
Bone mineral density in cosmonauts after 4.5–6 month long flights aboard orbital station MIR, Aerospace
Environ Med
Muscle volume, MRI relaxation times (T2), and body composition after spaceflight
J Appl Physiol
Bone mineral and lean tissue loss after long duration space flight
J Musculoskelet Neuronal Interact
Microgravity simulation and analogues
Collagen cross-link excretion during space flight and bed rest
J Clin Endocrinol Metab
Resistive vibration exercise attenuates bone and muscle atrophy in 56 days of bed rest: biochemical markers of bone metabolism
Osteoporosis Int.
The effects of twelve weeks of bed rest on bone histology, biochemical markers of bone turnover, and calcium homeostasis in eleven normal subjects
J Bone Miner Res
Bone resorption is induced on the second day of bed rest: results of a controlled crossover trial
J Appl Physiol
Alendronate as an effective countermeasure to disuse induced bone loss
J Muskuloskel Neuron Interact
Calcium metabolism before, during, and after a 3-mo spaceflight: kinetic and biochemical changes
Am J Physiol Regulatory Integrative Comp Physiol
Effects of 1-week head-down tilt bed rest on bone formation and the calcium endocrine system
Aviat Space Environ Med
Bone mineral loss and recovery after 17 weeks of bed rest
J Bone Miner Res
Calcium absorption, endogenous secretion and endocrine changes during and after long-term bed rest
Bone
Changes in markers of bone formation and resorption in a bed rest model of weightlessness
J Bone Miner Res
Cortical and trabecular bone mineral loss from the spine and hip in long-duration spaceflight
J Bone Miner Res
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Funding sources: WISE: sponsored by the European Space Agency (ESA), the National Aeronautics and Space Administration of the USA (NASA), the Canadian Space Agency, and the French “Centre National d'Etudes Spatiales” (CNES). ADOQ: funded by European Commission under Contract QLK-CT-2002-02363, Key Action n°6: “The ageing population and disabilities”, the Swiss government and ESA. DLR: participation of ADOQ group in WISE was funded by the German AeroSpace Center under Contract 50 WB 0522.