Experiment M-6, bone demineralization
Bone demineralization investigations to determine effects of weightlessness and immobilization on human skeleton
SEARCH · Search NASA
Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
Bone demineralization investigations to determine effects of weightlessness and immobilization on human skeleton
Not Available
An overview of bone demineralization during space flight, observations in bone demineralization and experiments related to bone loss planned for Spacelab flights, and suggestions for further research are investigated. The observations of the working group focused upon the following topics: (1) pathogenesis of bone demineralization, (2) potential for occurrence of renal stones consequent to prolonged hypercalciuria, (3) development of appropriate ground based and inflight models to study bone demineralization, (4) integration of research efforts, and (5) development of effective countermeasures.
Bone demineralization, calcium responses to weightlessness, endocrine responses to weightlessness, mechanisms of bone loss, biomedical research, pathogenesis, and endocrine effects are discussed.
Bone demineralization studies of Gemini IV CREW using radiographic bone densitometry
Space flight effects on bone demineralization of Gemini 4, 5, and 7 crews studied by X ray densitometry
Radiographic densitometry techniques to assess bone demineralization in Gemini 7 astronauts
Bone demineralization of foot and hand of Gemini astronauts during orbital flight
Densitometric evaluations of serial radiographs of "normal" subjects have often shown rather frequent changes in bone mass within relatively short periods of time. For this reason it was decided to make two pre-flight and two post flight radiographs of the Gemini V backup crew. In comparing the changes observed preflight and post flight as the conventional os calcis scanning site between the two crews, it was found that no changes greater than 4 percent were evident in either member of the backup crew. In comparing the changes observed preflight and postflight as the conventional o calcis scanning site between the two crews, it was found that no changes greater than 4 percent were evident in either member of the backup crew. This is in contract to the 15.1 and 8.9 percent losses observed in the prime crew. It has long been known that the skeletal system experiences a general loss of mineral under immobilization or extended bed rest. However, in both Gemini IV and Gemini V studies, bone mass losses were greater in both the os calcis and phalanx than were shown by the TWU bed-rest subjects during the same period of time. Although the bone mass losses in the 8-day Gemini V flight were generally greater than in the 4-day Gemini IV flight, the information to date is still insufficient to conclude that the losses tend to progress linearly with time, or whether a form of physiological adaptation may occur in longer space flights.
As a contribution toward an understanding of the molecular basis of bone loss, mineral imbalance, and increasing fecal calcium under conditions of prolonged space flight, the blood levels of biologically active vitamin D metabolites of flight crew members will be quantitatively measured. Prior to the mission, the refinement of existing and the development of new techniques for the assay of all vitamin D metabolites will provide an arsenal of methods suitable for a wide range of metabolite levels. In terms of practical application, the analysis of human and animal plasma samples, Spacelab crew plasma samples, and flight hardware are envisioned.
Crew members of the Gemini 4, Gemini 5, and Gemini 7 missions were compared regarding skeletal changes in three major anatomic sites with respect to changes in skeletal density during space flight. Bone-mass changes have been found for the command pilot and the pilot of each mission in the conventional os calcis section, in the combined sections covering 60 percent of the os calcis, and in hand phalanges 5-2 and 4-2. Comparison of radiographically determined losses in X-ray absorbence with X-ray absorbence losses in healthy young men subjected to bedrest immobilization for the same length of time showed that losses for the crewmembers exceeded losses for the bedrest subjects in all cases; this was an indication that restriction of body movement did not represent the only factor involved.
The os calcis mineral was measured in the nine Skylab crew members and in eight control subjects, 5 years after the Skylab Program, utilizing a photon absorptiometric technique. These measurements were compared with preflight measurements in an attempt to discover any long-term effects of space flight on the skeletal system. A statistically significant loss of bone mineral was found in the crew members who flew, but caution is urged in the interpretation of this difference. A recommendation to continue studies of this type is made.
The adaptive response of bones to mechanical loading is essential for musculoskeletal development. Despite the importance of collagen in bone mineralization, little is known about how cyclic strain influences physicochemical responses of collagen, especially at the early stage of mineralization when the levels of strain are higher than those in mature bones. The findings in this study show that, without any cell-mediated activity, cyclic strain increases nucleation rates of calcium phosphate (CaP) nanocrystals in highly-organized collagen matrices. The cyclic strain enhances the transport of mineralization fluids with nucleation precursors into the matrix, thus forming more CaP nanocrystals and increasing the elastic modulus of the collagen matrix. The results also suggest that the multiscale spatial distribution of nanocrystals in the fibrous collagen network determines tissue-level mechanical properties more critically than the total mineral content. Furthermore, by linking nano- and micro-scale observations with tissue-level mechanical properties, we provide new insights into designing better biomaterials.
Preflight, inflight, and postflight biochemical analyses of Gemini astronauts body fluids
Bone mineral measurements before and after space missions have shown that weightlessness greatly accelerates bone demineralization. Bone mineral losses as high as 1 to 3 percent per month were reported. Highly precise instrumentation is required to monitor this loss and thereby test the efficacy of treatment. During the last year, a significant improvement was made in Dual-Photon Absorptiometry by replacing the radioactive source with an x ray tube. Advantages of this system include: better precision, lower patient dose, better spacial resolution, and shorter scan times. The high precision and low radiation dose of this technique will allow detection of bone mineral changes of less than 1 percent with measurements conducted directly at the sites of interest. This will allow the required bone mineral studies to be completed in a shorter time with greater confidence.
Under the conditions of microgravity, astronauts lose bone mass at a rate of 1% to 2% a month, particularly in the lower extremities such as the proximal femur [1-3]. The most commonly used countermeasure against bone loss in microgravity has been prescribed exercise [4]. However, data has shown that existing exercise countermeasures are not as effective as desired for preventing bone loss in long duration, 4 to 6 months, spaceflight [1,3,5,6]. This spaceflight related bone loss may cause early onset of osteoporosis to place the astronauts at greater risk of fracture later in their lives. Consequently, NASA seeks to have improved understanding of the mechanisms of bone demineralization in microgravity in order to appropriately quantify this risk, and to establish appropriate countermeasures [7]. In this light, NASA's Digital Astronaut Project (DAP) is working with the NASA Bone Discipline Lead to implement well-validated computational models to help predict and assess bone loss during spaceflight, and enhance exercise countermeasure development. More specifically, computational modeling is proposed as a way to augment bone research and exercise countermeasure development to target weight-bearing skeletal sites that are most susceptible to bone loss in microgravity, and thus at higher risk for fracture. Given that hip fractures can be debilitating, the initial model development focused on the femoral neck. Future efforts will focus on including other key load bearing bone sites such as the greater trochanter, lower lumbar, proximal femur and calcaneus. The DAP has currently established an initial model (Beta Version) of bone loss due to skeletal unloading in femoral neck region. The model calculates changes in mineralized volume fraction of bone in this segment and relates it to changes in bone mineral density (vBMD) measured by Quantitative Computed Tomography (QCT). The model is governed by equations describing changes in bone volume fraction (BVF), and rates of changes in bone cell populations that remove and replace bone in packets within the bone region. The DAP bone model is unique in several respects. In particular in takes former models of volume fraction changes one step higher in fidelity and separates BVF into separate equations for mineralized and osteoid volume fractions governed by a mineralization rate. This more closely follows the physiology of the remodeling unit cycles where bone is first resorbed and then followed by the action of osteoblasts to lay down collagen matrix which eventually becomes mineralized. In another respect, the modules allow the functional description of the time rate of change of other parameters and variables in the model during a computational simulation. More detailed description of the model, preliminary validation results, current limitation and caveats, and planned advancements are provided in sections 2 through 5. The DAP bone model is being developed primarily as a research tool, and not as a clinical tool like QCT. Even if it transitions to a clinical tool, it is not intended to replace QCT or any other clinical tool. Moreover, the DAP bone model does not predict bone fracture. Its purpose is to provide valuable additional data via "forward prediction" simulations for during and after spaceflight missions to gain insight on, (1) mechanisms of bone demineralization in microgravity, and (2) the volumetric changes at the various bone sites in response to in-flight and post-flight exercise countermeasures. This data can then be used as input to the Keyak [8] (or equivalent) FE analysis method to gain insight on how bone strength may change during and after flight. This information can also be useful to help optimize exercise countermeasure protocols to minimize changes in bone strength during flight, and improve regain of bone strength post-flight. To achieve this goal, the bone model will be integrated with DAP's exercise countermeasure models to simulate the effect of exercise prescriptions on preserving bone. More specifically, the model will accept loading history due to muscle and joint force on bone and produce quantified remodeling within the bone region under influence of the applied stress. Furthermore, because they tend to respond differently, the bone remodeling model includes both trabecular bone and cortical bone.
Exposure to reduced gravity during space travel profoundly alters the loads placed on bone and muscle. Astronauts suffer significant losses of muscle and bone strength during weightlessness. Exercise as a countermeasure is only partially effective in remedying severe muscle atrophy and bone demineralization. Similar wasting of muscles and bones affects people on Earth during prolonged bed rest or immobilization due to injury. In the absence of weight bearing activity, atrophy occurs primarily in the muscles that act in low power, routine movements and in maintaining posture. Hormonal disfunction could contribute in part to the loss of muscle and bone during spaceflight. Reduced levels of human Growth Hormone (hGH) were found in astronauts during space flight, as well as reduced GH secretory activity was observed from the anterior pituitary in 7-day space flight rats. Growth hormone has been shown to be required for maintenance of muscle mass and bone mineralization, in part by mediating the biosynthesis IGF-I, a small polypeptide growth factor. IGF biosynthesis and secretion plays an important role in potentiating muscle cell differentiation and has been shown to drive the expression of myogenin, a myogenic specific basic helix-loop-helix factor. IGF-I has also been shown to have an important role in potentiating muscle regeneration, repair and adult muscle hypertrophy.
The effect of micro-gravity on the musculoskeletal system has been well studied. Significant changes in bone and muscle have been shown after long term space flight. Similar changes have been demonstrated due to bed rest. Bone demineralization is particularly profound in weight bearing bones. Much of the current techniques to monitor bone condition use bone mass measurements. However, bone mass measurements are not reliable to distinguish Osteoporotic and Normal subjects. It has been shown that the overlap between normals and osteoporosis is found for all of the bone mass measurement technologies: single and dual photon absorptiometry, quantitative computed tomography and direct measurement of bone area/volume on biopsy as well as radiogrammetry. A similar discordance is noted in the fact that it has not been regularly possible to find the expected correlation between severity of osteoporosis and degree of bone loss. Structural parameters such as trabecular connectivity have been proposed as features for assessing bone conditions. In this report, we use fractal analysis to characterize bone structure. We show that the fractal dimension computed with MRI images and X-Ray images of the patella are the same. Preliminary experimental results show that the fractal dimension computed from MRI images of vertebrae of human subjects before bedrest is higher than during bedrest.