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Evaluating Daily Load Stimulus Formulas in Relating Bone Response to Exercise

Six formulas representing what is commonly referred to as "daily load stimulus" are identified, compared and tested in their ability to relate skeletal mechanical loading to bone maintenance and osteogenic response. Particular emphasis is placed on exercise- induced skeletal loading and whether or not the formulas can adequately capture the known experimental observations of saturation of continuous cyclic loading, rest insertion between repetitions (cycles), recovery of osteogenic potential following saturation, and multiple shorter bouts versus a single long bout of exercise. To evaluate the ability of the formulas to capture these characteristics, a set of exercise scenarios with type of exercise bout, specific duration, number of repetitions, and rest insertion between repetitions is defined. The daily load values obtained from the formulas for the loading conditions of the set of scenarios is illustrated. Not all of the formulas form estimates of daily load in units of stress or in terms of strain at a skeletal site due to the loading force from a specific exercise prescription. The comparative results show that none of the formulas are able to capture all of the experimentally observed characteristics of cyclic loading. However, the enhanced formula presented by Genc et al. does capture several characteristics of cyclic loading that the others do not, namely recovery of osteogenic potential and saturation. This could be a basis for further development of mathematical formulas that more adequately approximates the amount of daily stress at a skeletal site that contributes to bone adaptation.

Pennline, James A.↗

Using the Enhanced Daily Load Stimulus Model to Quantify the Mechanical Load and Bone Mineral Density Changes Experienced by Crew Members on the International Space Station

Despite the use of exercise countermeasures during long-duration space missions, bone mineral density (BMD) and predicted bone strength of astronauts continue to show decreases in the lower extremities and spine. This site-specific bone adaptation is most likely caused by the effects of microgravity on the mechanical loading environment of the crew member. There is, therefore, a need to quantify the mechanical loading experienced on Earth and on-orbit to define the effect of a given "dose" of loading on bone homeostasis. Gene et al. recently proposed an enhanced DLS (EDLS) model that, when used with entire days of in-shoe forces, takes into account recently developed theories on the importance of factors such as saturation, recovery, and standing and their effects on the osteogenic response of bone to daily physical activity. This algorithm can also quantify the tinting and type of activity (sit/unload, stand, walk, run or other loaded activity) performed throughout the day. The purpose of the current study was to use in-shoe force measurements from entire typical work days on Earth and on-orbit in order to quantify the type and amount of loading experienced by crew members. The specific aim was to use these measurements as inputs into the EDLS model to determine activity timing/type and the mechanical "dose" imparted on the musculoskeletal system of crew members and relate this dose to changes in bone homeostasis.

Genc, K. O.↗

Computational Analysis of Artificial Gravity as a Possible Countermeasure to Spaceflight Induced Bone Loss

During exploration class missions, such as to asteroids and Mars, astronauts will be exposed to reduced gravity for extended periods. Data has shown that astronauts lose bone mass at a rate of 1% to 2% a month in microgravity, particularly in lower extremities such as the proximal femur. Exercise countermeasures have not completely eliminated bone loss from long duration spaceflight missions, which leaves astronauts susceptible to early onset osteoporosis and greater risk of fracture. Introduction of the Advanced Resistive Exercise Device and other large exercise devices on the International Space Station (ISS), coupled with improved nutrition, has further minimized bone loss. However, unlike the ISS, exploration vehicles will have very limited volume and power available to accommodate such capabilities. Therefore, novel concepts like artificial gravity systems are being explored as a means to provide sufficient load stimulus to the musculoskeletal system to mitigate bone changes that may lead to early onset osteoporosis and increased risk of fracture. Currently, there is minimal data available to drive further research and development efforts to appropriately explore such options. Computational modeling can be leveraged to gain insight on the level of osteoprotection that may be achieved using artificial gravity produced by a spinning spacecraft or centrifuge. With this in mind, NASA's Digital Astronaut Project (DAP) has developed a bone remodeling model that has been validated for predicting volumetric bone mineral density (vBMD) changes of trabecular and cortical bone both for gravitational unloading condition and the equivalent of 1g daily load stimulus. Using this model, it is possible to simulate vBMD changes in trabecular and cortical bone under different gravity conditions. In this presentation, we will discuss our preliminary findings regarding if and how artificial gravity may be used to mitigate spaceflight induced bone loss.

Mulugeta, L.↗

Integration of a Finite Element Model with the DAP Bone Remodeling Model to Characterize Bone Response to Skeletal Loading

NASA's Digital Astronaut Project (DAP) has developed a bone remodeling model that has been validated for predicting volumetric bone mineral density (vBMD) changes of trabecular and cortical bone in the absence of mechanical loading. The model was recently updated to include skeletal loading from exercise and free living activities to maintain healthy bone using a new daily load stimulus (DLS). This new formula was developed based on an extensive review of existing DLS formulas, as discussed in the abstract by Pennline et al. The DLS formula incorporated into the bone remodeling model utilizes strains and stress calculated from finite element model (FEM) of the bone region of interest. The proximal femur was selected for the initial application of the DLS formula, with a specific focus on the femoral neck. METHODS: The FEM was generated from CAD geometry of a femur using de-identified CT data. The femur was meshed using linear tetrahedral elements Figure (1) with higher mesh densities in the femoral neck region, which is the primary region of interest for the initial application of the DLS formula in concert with the DAP bone remodeling model. Nodal loads were applied to the femoral head and the greater trochanter and the base of the femur was held fixed. An L2 norm study was conducted to reduce the length of the femoral shaft without significantly impacting the stresses in the femoral neck. The material properties of the FEM of the proximal femur were separated between cortical and trabecular regions to work with the bone remodeling model. Determining the elements with cortical material properties in the FEM was based off of publicly available CT hip scans [4] that were segmented, cleaned, and overlaid onto the FEM.

Bone Remodeling↗

Mini Treadmill for Musculoskeletal Health

Because NASA's approach to space exploration calls for long-term extended missions, there is a pressing need to equip astronauts with effective exercise regimens that will maintain musculoskeletal and cardiovascular health. ZIN Technologies, Inc., has developed an innovative miniature treadmill for use in both zero-gravity and terrestrial environments. The treadmill offers excellent periodic impact exercise to stimulate cardiovascular activity and bone remodeling as well as resistive capability to encourage full-body muscle maintenance. A novel speed-control algorithm allows users to modulate treadmill speed by adjusting stride, and a new subject load device provides a more Earth-like gravity replacement load. This new and compact treadmill offers a unique approach to managing astronaut health while addressing the inherent and stringent challenges of space flight. The innovation also has the potential to offer numerous terrestrial applications, as a real-time daily load stimulus (DLS) measurement feature provides an effective mechanism to combat or manage osteoporosis, a major public health threat for 55 percent of Americans over the age of 50.

Humphreys, Bradley↗

Life Sciences Implications of Lunar Surface Operations

The purpose of this report is to document preliminary, predicted, life sciences implications of expected operational concepts for lunar surface extravehicular activity (EVA). Algorithms developed through simulation and testing in lunar analog environments were used to predict crew metabolic rates and ground reaction forces experienced during lunar EVA. Subsequently, the total metabolic energy consumption, the daily bone load stimulus, total oxygen needed, and other variables were calculated and provided to Human Research Program and Exploration Systems Mission Directorate stakeholders. To provide context to the modeling, the report includes an overview of some scenarios that have been considered. Concise descriptions of the analog testing and development of the algorithms are also provided. This document may be updated to remain current with evolving lunar or other planetary surface operations, assumptions and concepts, and to provide additional data and analyses collected during the ongoing analog research program.

Chappell, Steven P.↗

Development of Bone Remodeling Model for Spaceflight Bone Physiology Analysis

Current spaceflight exercise countermeasures do not eliminate bone loss. Astronauts lose bone mass at a rate of 1-2% a month (Lang et al. 2004, Buckey 2006, LeBlanc et al. 2007). This may lead to early onset osteoporosis and place the astronauts at greater risk of fracture later in their lives. NASA seeks to improve understanding of the mechanisms of bone remodeling and demineralization in 1g in order to appropriately quantify long term risks to astronauts and improve countermeasures. NASA's Digital Astronaut Project (DAP) is working with NASA's bone discipline to develop a validated computational model to augment research efforts aimed at achieving this goal.

Microgravity↗

A method for continuous monitoring of the Ground Reaction Force during daily activity

Theoretical models and experimental studies of bone remodeling have identified peak cyclic force levels (or cyclic tissue strain energy density), number of daily loading cycles, and load (strain) rate as possible contributors to bone modeling and remodeling stimulus. To test our theoretical model and further investigate the influence of mechanical forces on bone density, we have focused on the calcaneus as a model site loaded by calcaneal surface tractions which are predominantly determined by the magnitude of the external ground reaction force (GRF).

Whalen, Robert↗

Prediction of human gait parameters from temporal measures of foot-ground contact

Investigation of the influence of human physical activity on bone functional adaptation requires long-term histories of gait-related ground reaction force (GRF). Towards a simpler portable GRF measurement, we hypothesized that: 1) the reciprocal of foot-ground contact time (1/tc); or 2) the reciprocal of stride-period-normalized contact time (T/tc) predict peak vertical and horizontal GRF, loading rates, and horizontal speed during gait. GRF data were collected from 24 subjects while they walked and ran at a variety of speeds. Linear regression and ANCOVA determined the dependence of gait parameters on 1/tc and T/tc, and prediction SE. All parameters were significantly correlated to 1/tc and T/tc. The closest pooled relationship existed between peak running vertical GRF and T/tc (r2 = 0.896; SE = 3.6%) and improved with subject-specific regression (r2 = 0.970; SE = 2.2%). We conclude that temporal measures can predict force parameters of gait and may represent an alternative to direct GRF measurements for determining daily histories of habitual lower limb loading quantities necessary to quantify a bone remodeling stimulus.

NASA Center ARC↗

Non-Invasive Investigation of Bone Adaptation in Humans to Mechanical Loading

Experimental studies have identified peak cyclic forces, number of loading cycles, and loading rate as contributors to the regulation of bone metabolism. We have proposed a theoretical model that relates bone density to a mechanical stimulus derived from average daily cumulative peak cyclic 'effective' tissue stresses. In order to develop a non-invasive experimental model to test the theoretical model we need to: (1) monitor daily cumulative loading on a bone, (2) compute the internal stress state(s) resulting from the imposed loading, and (3) image volumetric bone density accurately, precisely, and reproducibly within small contiguous volumes throughout the bone. We have chosen the calcaneus (heel) as an experimental model bone site because it is loaded by ligament, tendon and joint contact forces in equilibrium with daily ground reaction forces that we can measure; it is a peripheral bone site and therefore more easily and accurately imaged with computed tomography; it is composed primarily of cancellous bone; and it is a relevant site for monitoring bone loss and adaptation in astronauts and the general population. This paper presents an overview of our recent advances in the areas of monitoring daily ground reaction forces, biomechanical modeling of the forces on the calcaneus during gait, mathematical modeling of calcaneal bone adaptation in response to cumulative daily activity, accurate and precise imaging of the calcaneus with quantitative computed tomography (QCT), and application to long duration space flight.

Whalen, R.↗

Skeletal Adaptation to Daily Activity: A Biochemical Perspective

Musculoskeletal forces generated by normal daily activity on Earth maintain the functional and structural properties of muscle and bone throughout most of one's adult life. A reduction in the level of cumulative daily loading caused by space flight, bed rest or spinal cord injury induces rapid muscle atrophy, functional changes in muscle, and bone resorption in regions subjected to the reduced loading. Bone cells in culture and bone tissue reportedly respond to a wide variety of non-mechanical and mechanical stimuli ranging, from electromagnetic fields, and hormones to small amplitude, high frequency vibrations, fluid flow, strain rate, and stress/strain magnitude. However, neither the transduction mechanism that transforms the mechanical input into a muscle or bone metabolic response nor the characteristics, of the loading history that directly or indirectly stimulates the cell is known. Identifying the factors contributing to the input stimulus will have a major impact on the design of effective countermeasures for long duration space flight. This talk will present a brief overview of current theories of bone remodeling and functional adaptation to mechanical loading. Work from our lab will be presented from the perspective of daily cumulative loading on Earth and its relationship to bone density and structure. Our objective is to use the tibia and calcaneus as model bone sites of cortical and cancellous bone adaptation, loaded daily by musculoskeletal forces in equilibrium with the ground reaction force. All materials that will be discussed are in the open scientific literature.

Whalen, Robert T.↗