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Principal Investigator:
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Richard B. Souza, Ph.D.
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Organization:
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University of California, San Francisco
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Project Ended:
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2010
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Long-duration spaceflight leads to bone and muscle loss in astronauts. However it is unclear how living in the reduced-gravity environment of space affects cartilage. Animals that have experienced unloading on the musculoskeletal system have experienced degeneration of cartilage similar to those with osteoarthritis. Dr. Richard Souza is using magnetic resonance technology to measure the changes in cartilage composition during simulated reduced-gravity situations. A secondary objective is to demonstrate how cartilage responds when astronauts return to full gravity.
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Principal Investigator:
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Richard B. Souza, Ph.D.
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Organization:
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University of California, San Francisco
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Project Ended:
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2010
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While several studies have investigated the influence of long-duration spaceflight on muscle and bone tissue, it remains unclear how unloading influences cartilage health. It has been shown in animals that decreased loading results in cartilage deterioration with compositional changes similar to those of osteoarthritis (OA). However, it is unknown if these same changes are experienced in astronauts during spaceflight. If long-duration unloading results in biochemical changes within the cartilage, it may be a medical risk factor for the development of OA later in life. OA is a progressive, degenerative disease that is characterized by changes in proteoglycan and water content.
Recent advancement in magnetic resonance (MR) technology allows for an increased ability to monitor these biochemical levels in vivo. Furthermore, the reversibility reported in animal work with remobilization has yet to be observed in humans. This study utilized state-of-the-art MR techniques to monitor knee cartilage composition with non-weight bearing (simulated zero gravity) and return to full weight bearing (relative increased loading).
Specific Aims- The primary objective is to quantify changes in cartilage composition with loading deprivation using advanced MR techniques (including T2 and T1rho relaxation time mapping).
- A secondary objective is to demonstrate reversibility of compositional changes of articular cartilage associated with OA in vivo.
Eight subjects have successfully completed the study and data have been processed. While the study has not reached completion, some very important findings have been observed. Following approximately six weeks of non-weight-bearing (6.4 ± 0.8 weeks), T1rho values of the tibiofemoral cartilage significantly increased in three out of six compartments. Mean T1rho values for all compartments were greater following the period of non-weight bearing compared to baseline values, but a lack of power resulted in only three statistical differences. The greatest changes were observed in the medial tibia (8 percent change) and lateral tibia (5 percent change). Following four weeks of returning to full-weight bearing (14.4 ± 4.0 weeks post-operative) there were no significant differences in T1rho relaxation times as compared to the pre non-weight bearing time point (p greater than 0.05).
The observation of a transient shift in T1rho relaxation times confirms that cartilage biochemistry is subject to alterations based on loading conditions. Furthermore, the return to baseline levels in T1rho relaxation times following the return to normal loading behavior is promising as this suggests that detrimental changes in cartilage biochemistry are potentially reversible given specific loading conditions. These findings have significant implications for the NSBRI and space travel as it implies that astronauts returning from space have compromised cartilage biochemistry which is associated with reduced cartilage mechanical properties, and need to be carefully monitored following return to Earth. The findings show that these deficits appear to normalize in a fairly brief period of time (4 weeks). Nonetheless, it appears that for at least some time when returning to Earth, astronauts are at risk for serious cartilage injury and further studies are needed to determine the impact of physical activity during the initial days post-flight on long-term cartilage health. Continuation of this research will investigate T2 relaxation times as well as the contralateral knee cartilage which may show signs of overloading.
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Principal Investigator:
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Richard B. Souza, Ph.D.
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Organization:
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University of California, San Francisco
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Project Ended:
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2010
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There are several very important implications from this research to Earth-bound individuals. The obvious first extension of this work is to people undergoing a period of non-weight bearing. The uninvolved joints of the unloaded limb show detrimental effects on the cartilage composition. This is important to know and should be considered when developing accelerated activity protocols as are done with elite athletes. In addition, strategies to provide adequate load to the hip and knee following ankle surgery may be a valuable tool to prevent these negative changes from occurring. Clinically, it often is observed that an individual has several orthopaedic problems on a given side and the contralateral side may be free from injury.
While is would be impossible to determine cause retrospectively, it would be interesting to determine if there are more cartilage lesions and thinning on the lower extremity that has had previous injuries requiring a period of non-weight bearing. A possible prospective study would be to follow the subjects in the current study over a period of time (5-10 years) and evaluate cartilage health bilaterally overtime. However, this would be challenging given the small sample size of the study and would likely be more appropriate for a large database such as the Osteoarthritis Initiative database with over 4,000 quantitative magnetic resonance imaging (MRI) scans.
The second extension of this research performed to Earth-bound populations is related to the range of healthy loading of cartilage. The literature is fairly clear that overloading of cartilage results in detrimental effects leading to cartilage breakdown and osteoarthritis. Forms of overloading include excessive magnitudes of load (e.g., obese individuals), and excessive frequency of loads (e.g., marathon runners). However, this postdoctoral study anchors the opposite spectrum by clearly demonstrating that complete unloading is also damaging to the cartilage and results in the same biochemical alterations associated with cartilage disease. The combination of this study’s data with the current literature suggests that some moderate level of loading is optimal for chondrocyte stimulation and that future studies should closely investigate physical activity levels in subjects prior to initiation of cartilage disease to study the effects of loading on long-term cartilage health.
It is likely that a given level of physical activity will not be appropriate for all people. However, with our ability to quantify cartilage composition, it is a reasonable long-term goal to use a person’s current T1rho and T2 values, along with information such as age, body mass index, gender, and even genetic testing variables to systematically prescribe an appropriate amount of loading to optimize cartilage health. This vision is the primary Earth-based objective of the project’s research line. Work is currently being done with investigators that develop biosensors to fabricate physical activity monitoring devices (with the guidance of Dr. Peter Cavanagh and his team) to accurately monitor behavioral loading patterns across individuals. This technology will be combined with our advanced quantitative MRI analysis of cartilage composition to begin to evaluate the role of physical activity and its specific parameters (magnitude, frequency, volume, etc.) on cartilage disease.
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