Monitoring of Bone Loss Biomarkers in Human Sweat: A Non-Invasive, Time Efficient Means of Monitoring Bone Resorption Markers under Micro and Partial Gravity Loading Conditions

We propose to validate that the rate and extent of unloading-induced bone loss in humans can be assessed by monitoring the levels of two bone resorption markers in sweat, namely ionized calcium and collagen break-down products. Initial testing will be carried out in a young healthy population (at rest and during activity) and then in a clinical population undergoing active bone loss, namely spinal cord injury patients. All groups will include both male and female participants. Biomarker concentration will be determined in contemporaneous samples of sweat, blood, and urine collected during both short (24 hr) and long-term studies (multiple sessions over a period of months) to define the relationship between biomarker levels in the respective biological samples. Several different sweat collection techniques will be investigated to determine the most appropriate and efficient means of sample collection suitable for deployment during a space flight mission. These experiments will also include investigation of the most appropriate biomarker analysis techniques that allow for future deployment in micro- or partial gravity environments. This near-real-time monitoring approach may also provide the information required to justify modifying an ineffective bone loss countermeasure prescription during a mission. One of the approaches tested will be a novel, micro-fabricated fluid collection capillary array, known as the micro-fabricated sweat patch (MSP) device, specifically developed for use in microgravity. The MSP technology was initially developed because of its potential to become an autonomous, solid-state collection/analysis device worn on the skin of an astronaut requiring little or no crew interaction to perform its monitoring function.

Loss of bone mass, density, and structural integrity is a significant health risk in a variety of populations such as the elderly, post-menopausal women, young female athletes, and astronauts. Such changes in overall bone quality lead to a greater risk of bone fracture and potentially a reduced rate of bone healing after injury. The ability to monitor biomarkers of bone remodeling (e.g., ionized calcium, collagen cross links) using sweat as an analytical sample provides an attractive alternative to the more invasive and costly measures presently employed such as a bone density scans by dual-energy X-ray absorptiometry (DXA), 24 hour urine collection protocols, or whole blood analyses. The development of a non-invasive, skin-mounted monitoring device which allows the quantitation of ionized calcium and/or collagen cross links in sweat will allow bone loss to be monitored in a wide variety of terrestrial populations that to date have not easily been monitored outside of a clinical setting. This particular project focuses on validating the concept that sweat analysis can be used as a non-invasive means of monitoring bone loss in crew members during periods of mechanical unloading under altered gravitational conditions. In addition, this project is also investigating the best technical approach to collecting a sweat sample which is specifically applicable to the space flight environment while utilizing well-accepted, clinically validated analytical methods. Development of a technology capable of real-time monitoring of biomarkers of bone loss that satisfies the criteria required for use in the space flight environment (i.e., non-invasive/non-intrusive, passive, small, light-weight, low power) has many direct applications in various populations here on Earth.

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