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Methodologies to determine forces on bones and muscles of body segments during exercise, employing compact sensors suitable for use in crowded space vehicles

Work under this grant was carried out by the author and by a graduate research assistant. An instrumented bicycle ergometer was implemented focusing on the stated objective: to estimate the forces exerted by each muscle of the feet, calf, and thigh of an individual while bicycling. The sensors used were light and compact. These were probes to measure muscle EMG activity, miniature accelerometers, miniature load sensors, and small encoders to measure angular positions of the pedal. A methodology was developed and implemented to completely describe the kinematics of the limbs using data from the sensors. This work has been published as a Master's Thesis by the Graduate student supported by the grant. The instrumented ergometer along with the sensors and instrumentation were tested during a KC-135 Zero-Gravity flight in July, 1994. A complete description of the system and the tests performed have been published as a report submitted to NASA Johnson Space Center. The data collected during the KC-135 flight is currently being processed so that a kinematic description of the bicycling experiment will be soon determined. A methodology to estimate the muscle forces has been formulated based on previous work. The methodology involves the use of optimization concepts so that the individual muscle forces that represent variables in dynamic equations of motion may be estimated. Optimization of a criteria (goal) function such as minimization of energy will be used along with constraint equations defined by rigid body equations of motion. Use of optimization principles is necessary, because the equations of motion alone constitute an indeterminate system of equations with respect to the large amount of muscle forces which constitute the variables in these equations. The number of variables is reduced somewhat by using forces measured by the load cells installed on the pedal. These load cells measure pressure and shear forces on the foot. The author and his collaborators at NASA and at the University of Alabama, Tuscaloosa, are continuing the work of reducing the experimental data from the KC-135 flight, and the implementation of the optimization methods to estimate muscle forces. As soon as results from these efforts are available, they will be published in reputable journals. Results of this work will impact studies addressing bone density loss and development of countermeasures to minimize bone loss in zero gravity conditions. By analyzing muscle forces on Earth and in Space during exercise, scientists could eventually formulate new exercises and machines to help maintain bone density. On Earth, this work will impact studies concerning arthritis, and will provide the means to study possible exercise countermeasures to minimize arthritis problems.

Figueroa, Fernando

Elevated 1,25-dihydroxyvitamin D levels in patients with chronic obstructive pulmonary disease treated with prednisone

Glucocorticoid administration is a well established cause of osteopenia. Mechanisms underlying the deleterious effect of glucocorticoids on bone may include direct inhibition of bone formation as well as indirect effects through changes in intestinal calcium absorption, renal calcium excretion, and/or levels of the calciotropic hormones. To further examine the potential role of the calciotropic hormones we measured serum levels of PTH and 1,25 dihydroxyvitamin D [1,25(OH)2D], as well as serum and urine levels of calcium and vertebral bone density in patients with chronic obstructive pulmonary disease being managed with or without prednisone. Patients treated with prednisone had lower spinal bone density (53 vs. 106 mg/cm3) and higher serum calcium (2.40 vs. 2.33 mmol/l), urine calcium (6.9 vs. 2.7 mmol/24h), and 1,25(OH)2D levels (147 vs. 95 pmol/L). Compared to the patients not treated with glucocorticoids. PTH levels also tended to be higher (33 vs. 26 microliters-eq/ml), but the difference was not significant. Serum and urine calcium levels correlated positively with 1,25(OH)2D levels, but none of these measurements correlated with PTH levels. Our results suggest that prednisone treatment alters the regulation of 1,25(OH)2D production, and this may contribute to the loss of bone mineral induced by prednisone.

NASA Discipline Number 40-40

Exercise and osteoporosis: Methodological and practical considerations

Physical activity may have important implications for enhancing bone density prior to the initiation of space flight, for preserving bone density during zero gravity, and for rehabilitating the skeleton upon return to Earth. Nevertheless, the beneficial effects of exercise upon the skeleton have not been proven by controlled trials and no consensus exists regarding the type, duration, and intensity of exercise necessary to make significant alterations to the skeleton. The following sections review our current understanding of exercise and osteoporosis, examine some of the methodological shortcomings of these investigations, and make research recommendations for future clinical trials.

Block, Jon E.

Future human bone research in space

Skylab crewmembers demonstrated negative calcium (Ca) balance reaching about -300 mg/day by flight day 84. Limited bone density (BMD) measurements documented that bone was not lost equally from all parts of the skeleton. Subsequent BMD studies during long duration Russian flights documented the regional extent of bone loss. These studies demonstrated mean losses in the spine, femur neck, trochanter, and pelvis of about 1%-1.6% with large differences between individuals as well as between bone sites in a given individual. Limited available data indicate postflight bone recovery occurred in some individuals, but may require several years for complete restoration. Long duration bedrest studies showed a similar pattern of bone loss and calcium balance (-180 mg/day) as spaceflight. During long duration bedrest, resorption markers were elevated, formation markers were unchanged, 1,25 vitamin D (VitD) and calcium absorption were decreased, and serum ionized Ca was increased. Although this information is a good beginning, additional spaceflight research is needed to assess architectural and subregional bone changes, elucidate mechanisms, and develop efficient as well as effective countermeasures. Space research poses a number of unique problems not encountered in ground-based laboratory research. Therefore, researchers contemplating human spaceflight research need to consider a number of unique problems related to spaceflight in their experimental design.

NASA Center JSC

Irreversibility of advanced osteoporosis: Limited role for pharmacologic intervention

Osteoporosis is of medical interest only because it increases bone fragility and risk of fracture, and except for relief of symptoms, preventing fracture is the only purpose of intervention. To prevent the first fracture, adequate bone density must be accumulated and conserved, but to prevent subsequent fracture, bone density must be augmented so that the supportive function of the skeleton can be restored. Almost 50 years after the recognition of post menopausal osteoporosis as a clinical entity, not one of the many treatments that have been used has been demonstrated to be efficacious in reducing subsequent fracture risk. My purpose is not to recite this chronicle of disappointment, but to account for it in terms of bone biology, to consider some possible exceptions, and to reiterate the importance of preventing damage to the skeleton rather than belatedly attempting its repair.

Parfitt, A. M.

Metabolic energy requirements during manned orbital Skylab missions

The metabolic balance of nine Skylab astronauts was studied during the course of 28-, 59-, and 84-day flights. Control periods of at least three weeks preceding each flight and at least 18 days following each flight were included in the metabolic studies. Results of the investigation indicated that all members lost mass in flight without experiencing an increase in body density. Analysis of bone density, blood and urinary nitrogen levels, and overall calcium and nitrogen balances suggested that lean body mass declined through loss of protein. It thus appeared that despite adequate energy intake, the crew members did not reach equilibrium with the weightless environment within the time periods studied.

Rambaut, P. C.

Effect of low gravity on calcium metabolism and bone formation (L-7)

Recently, attention has been focused on the disorders of bone and calcium metabolism during space flight. The skeletal system has evolved on the Earth under 1-g. Space flights under low gravity appear to cause substantial changes in bone and calcium homeostasis of the animals adapted to 1-g. A space experiment for the First Materials Processing Test (FMPT) was proposed to examine the effects of low gravity on calcium metabolism and bone formation using chick embryos loaded in a space shuttle. This space experiment was proposed based on the following two experimental findings. First, it has been reported that bone density decreases significantly during prolonged space flight. The data obtained from the US Skylab and the U.S.S.R. Salyut-6 cosmonauts have also documented that the degree of bone loss is related to the duration of space flight. Second, the US-Soviet joints space experiment demonstrated that the decrease in bone density under low gravity appears to be due to the decrease in bone formation rather than the increase in bone resorption. The purpose of our space experiment is, therefore, to investigate further the mechanisms of bone growth under low gravity using fertilized chick embryos.

Suda, Tatsuo

Alterations in TNF- and IL-related gene expression in space-flown WI38 human fibroblasts

Spaceflight, just like aging, causes profound changes in musculoskeletal parameters, which result in decreased bone density and muscular weakness. As these conditions decrease our ability to conduct long-term manned space missions, and increase bone frailty in the elderly, the identification of genes responsible for the apparition of these physiological changes will be of great benefit. Thus, we developed and implemented a new microarray approach to investigate the changes in normal WI38 human fibroblast gene expression that arise as a consequence of space flight. Using our microarray, we identified changes in the level of expression of 10 genes, belonging to either the tumor necrosis factor- (TNF) or interleukin- (IL) related gene families in fibroblasts when WI38 cells exposed to microgravity during the STS-93 Space Shuttle mission were compared with ground controls. The genes included two ligands from the TNF superfamily, TWEAK and TNFSF15; two TNF receptor-associated proteins, NSMAF and PTPN13; three TNF-inducible genes, ABC50, PTX3, and SCYA13; TNF-alpha converting enzyme, IL-1 receptor antagonist, and IL-15 receptor alpha chain. Most of these are involved in either the regulation of bone density, and as such the development of spaceflight osteopenia, or in the development of proinflammatory status.

manned

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.

Low Magnitude Mechanical Signals Reduce Risk-Factors for Fracture during 90-Day Bed Rest

Long duration spaceflight leads to multiple deleterious changes to the musculoskeletal system, where loss of bone density, an order of magnitude more severe than that which follows the menopause, combined with increased instability, conspire to elevate the risk of bone fracture due to falls on return to gravitational fields. Here, a ground-based analog for spaceflight is used to evaluate the efficacy of a low-magnitude mechanical intervention, VIBE (Vibrational Inhibition of Bone Erosion), as a potential countermeasure to preserve musculoskeletal integrity in the face of disuse. Twenty-six subjects consented to ninety days of six-degree head-down tilt bed-rest. 18 completed the 90d protocol, 8 of which received daily 10-minute exposure to 30 Hz, 0.3g VIBE, applied in the supine position using a vest elastically coupled to the vibrating platform. The shoulder harness induced a load of 60% of the subjects body weight. At baseline and 90d, Qualitative Ultrasound Scans (QUS) of the calcaneus and CT-scans of the hip and spine were performed to measure changes in bone density. Postural control (PC) was assessed through center of pressure (COP) recordings while subjects stood on a force platform for 4 minutes of quiet stance with eyes closed, and again with eyes opened. As compared to control bedrest subjects,

Muir, J. W.

Ethnic Differences in Bending Stiffness of the Ulna and Tibia

There is considerable information about the variations in bone mass associated with different opportunity to compare a mechanical property of bone in young college women of Caucasian, Hispanic and Asian descent who gave informed consent to participate in an exercise study. The subjects were sedentary, in good health, eumenorrheic, non-smokers and had body mass indices (BMI) less than 30. Measurements acquired were body weight, kg, and height, cm, calcaneal and wrist bone density, g/square cm (PIXI, Lunar GE) and bending stiffness (EI, Nm(exp 2)) in the ulna and tibia. E1 was determined non-invasively with an instrument called the Mechanical Response Tissue Analyzer (MRTA) that delivers a vibratory stimulus to the center of the ulna or tibia and analyzes the response curve based on the equation E1 = k(sub b) L(exp 3)/48 where k, is lateral bending stiffness, L is the length of the bone, E is Young's modulus of elasticity and I, the bending moment of inertia. The error of the test (CV) based on measurements of an aluminum rod with a known E1 was 4.8%, of calcaneal BMD, 0.54%, and of wrist bone density, 3.45%.

Arnaud, S. B.

Altered bone turnover during spaceflight

Modifications in calcium metabolism during spaceflight were studied, using parameters that reflect bone turnover. Bone formation rate, medullary area, bone length, bone density, pore size distribution, and differential bone cell number were evaluated in growing rate both immediately after and 25 days after orbital spaceflights aboard the Soviet biological satellites Cosmos 782 and 936. The primary effect of space flight on bone turnover was a reversible inhibition of bone formation at the periosteal surface. A simultaneous increase in the length of the periosteal arrest line suggests that bone formation ceased along corresponding portions of that surface. Possible reasons include increased secretion of glucocorticoids and mechanical unloading of the skeleton due to near-weightlessness, while starvation and immobilization are excluded as causes.

Turner, R. T.

Stationary Apparatus Would Apply Forces of Walking to Feet

A proposed apparatus would apply controlled cyclic forces to both feet for the purpose of preventing the loss of bone density in a human subject whose bones are not subjected daily to the mechanical loads of normal activity in normal Earth gravitation. The apparatus was conceived for use by astronauts on long missions in outer space; it could also be used by bedridden patients on Earth, including patients too weak to generate the necessary forces by their own efforts. The apparatus (see figure) would be a modified version of a bicycle-like exercise machine, called the cycle ergometer with vibration isolation system (CEVIS), now aboard the International Space Station. Attached to each CEVIS pedal would be a computer-controlled stress/ vibration exciter connected to the heel portion of a special-purpose pedal. The user would wear custom shoes that would amount to standard bicycle shoes equipped with cleats for secure attachment of the balls of the feet to the special- purpose pedals. If possible, prior to use of the apparatus, the human subject would wear a portable network of recording accelerometers, while walking, jogging, and running. The information thus gathered would be fed to the computer, wherein it would be used to make the exciters apply forces and vibrations closely approximating the forces and vibrations experienced by that individual during normal exercise. It is anticipated that like the forces applied to bones during natural exercise, these artificial forces would stimulate the production of osteoblasts (bone-forming cells), as needed to prevent or retard loss of bone mass. In addition to helping to prevent deterioration of bones, the apparatus could be used in treating a person already suffering from osteoporosis. For this purpose, the magnitude of the applied forces could be reduced, if necessary, to a level at which weak hip and leg bones would still be stimulated to produce osteoblasts without exposing them to the full stresses of walking and thereby risking fracture.

Hauss, Jessica

The X-ray attenuation characteristics and density of human calcaneal marrow do not change significantly during adulthood

Changes in the material characteristics of bone marrow with aging can be a significant source of error in measurements of bone density when using X-ray and ultrasound imaging modalities. In the context of computed tomography, dual-energy computed techniques have been used to correct for changes in marrow composition. However, dual-energy quantitative computed tomography (DE-QCT) protocols, while increasing the accuracy of the measurement, reduce the precision and increase the radiation dose to the patient in comparison to single-energy quantitative computed tomography (SE-QCT) protocols. If the attenuation properties of the marrow for a particular bone can be shown to be relatively constant with age, it should be possible to use single-energy techniques without experiencing errors caused by unknown marrow composition. Marrow was extracted by centrifugation from 10 mm thick frontal sections of 34 adult cadaver calcanei (28 males, 6 females, ages 17-65 years). The density and energy-dependent linear X-ray attenuation coefficient of each marrow sample were determined. For purposes of comparing our results, we then computed an effective CT number at two GE CT/i scan voltages (80 and 120 kVp) for each specimen. The coefficients of variation for the density, CT number at 80 kVp and CT number at 120 kVp were each less than 1%, and the parameters did not change significantly with age (p > 0.2, r2 < 0.02, power > 0.8 where the minimum acceptable r2 = 0.216). We could demonstrate no significant gender-associated differences in these relationships. These data suggest that calcaneal bone marrow X-ray attenuation properties and marrow density are essentially constant from the third through sixth decades of life.

NASA Discipline Musculoskeletal

Quantification of Cyclic Ground Reaction Force Histories During Daily Activity in Humans

Theoretical models and experimental studies of bone remodeling suggest that bone density and structure are influenced by local cyclic skeletal tissue stress and strain histories. Estimation of long-term loading histories in humans is usually achieved by assessment of physical activity level by questionnaires, logbooks, and pedometers, since the majority of lower limb cyclic loading occurs during walking and running. These methods provide some indication of the mechanical loading history, but fail to consider the true magnitude of the lower limb skeletal forces generated by various daily activities. These techniques cannot account for individual gait characteristics, gait speed, and unpredictable high loading events that may influence bone mass significantly. We have developed portable instrumentation to measure and record the vertical component of the ground reaction force (GRFz) during normal daily activity. This equipment allows long-term quantitative monitoring of musculoskeletal loads, which in conjunction with bone mineral density assessments, promises to elucidate the relationship between skeletal stresses and bone remodeling.

Breit, G. A.

Cortical bone growth and maturational changes in dwarf rats induced by recombinant human growth hormone

The growth hormone (GH)-deficient dwarf rat was used to investigate recombinant human (rh) GH-induced bone formation and to determine whether rhGH facilitates simultaneous increases in bone formation and bone maturation during rapid growth. Twenty dwarf rats, 37 days of age, were randomly assigned to dwarf plus rhGH (GH; n = 10) and dwarf plus vehicle (n = 10) groups. The GH group received 1.25 mg rhGH/kg body wt two times daily for 14 days. Biochemical, morphological, and X-ray diffraction measurements were performed on the femur middiaphysis. rhGH stimulated new bone growth in the GH group, as demonstrated by significant increases (P < 0.05) in longitudinal bone length (6%), middiaphyseal cross-sectional area (20%), and the amount of newly accreted bone collagen (28%) in the total pool of middiaphyseal bone collagen. Cortical bone density, mean hydroxyapatite crystal size, and the calcium and collagen contents (microgram/mm3) were significantly smaller in the GH group (P < 0.05). Our findings suggest that the processes regulating new collagen accretion, bone collagen maturation, and mean hydroxyapatite crystal size may be independently regulated during rapid growth.

NASA Discipline Musculoskeletal