Digital Astronaut: Bone Remodeling Model

Background

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. The most commonly used countermeasure against bone loss in microgravity has been prescribed exercise. However, data has shown that existing exercise countermeasures are not as effective as desired for preventing bone loss in long duration spaceflight. 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.

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.

Methods

The model consists of three major research areas: (1) the orthopedic science or mechanics of the removal and replacement of bone packets via remodeling units, (2) the biology and physiology of cellular dynamics of remodeling units, and (3) mechanotransduction which describes the function of skeletal loading and its role in maintaining bone health. The basic biological assumption used in the cellular physiology can be stated as such: Cell proliferation or anti-proliferation is respectively either directly proportional or inversely proportional to receptor occupancy ratio.

In implementation, the bone remodeling model is based on a first principles physiological and mathematical description of the components of bone physiology, including responses by the endocrine, biochemical, autocrine, and paracrine systems. The model mathematically formulates the key elements based on well-accepted knowledge and experimental studies of bone. In particular, the model uses the RANK-RANKL-OPG signaling pathway to describe the cellular dynamics. For skeletal loading, the model includes the effects of nitric oxide (NO) and prostaglandin E2 (PGE2). In the computational model, reduced skeletal loading triggers a decrease in NO and PGE2, which in turn triggers an imbalance in the pathway in favor of resorption. This leads to a decrease in mineralized volume M and osteoid volume O, and hence a decrease in bone volume fraction (BVF). The loading portion of the model is based on the concept of a minimum effective strain stimulus, which takes into consideration strain rate as opposed to strain magnitude only.

Specific Aims

1. For individuals in the age range of the astronaut corps, predict changes in trabecular and cortical volumetric bone mineral fraction and density as a function of time since measurement, gravity level, and applied loads

2. Support the bone fracture standard by accepting and providing data in the same form as that of a Quantitative Computed Tomography (QCT) scan.

The discoveries made through this work can have spin-off benefits to terrestrial healthcare by providing fundamental methods that can be further built upon to:

(1) Gain further insight on the mechanisms and influence on the bone remodeling process and its implications in bone health and other health risks to patients who are bed-ridden or immobilized due to:

* Long term illnesses; * Post-op surgery; * Limb fractures; and/or * Spinal injury, to name a few

(2) Design exercise prescriptions for patients who have experienced bone demineralization from bed-ridden or immobilized disuse indicated in 1, in order to help them recover bone and minimize bone fracture.

(3) Investigate the level of regular activity or exercise people should be engaged in to ensure healthy bones throughout their lives, particularly in minimizing or preventing age related osteoporosis.

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