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At least 55 records · Page 3

Predicting Bone Mechanical Properties of Cancellous Bone from DXA, MRI, and Fractal Dimensional Measurements

This project was aimed at making predictions of bone mechanical properties from non-invasive DXA and MRI measurements. Given the bone mechanical properties, stress calculations can be made to compare normal bone stresses to the stresses developed in exercise countermeasures against bone loss during space flight. These calculations in turn will be used to assess whether mechanical factors can explain bone loss in space. In this study we assessed the use of T2(sup *) MRI imaging, DXA, and fractal dimensional analysis to predict strength and stiffness in cancellous bone.

Harrigan, Timothy P.↗

Alendronate and Resistive Exercise Countermeasures Against Bed Rest-Induced Bone Loss: Biochemical Markers of Bone and Calcium Metabolism

Weightlessness-induced bone loss must be counteracted to ensure crew health during extendedduration space missions. Studies were conducted to assess two bone loss countermeasures in a ground-based model: horizontal bed rest. Following a 3-wk ambulatory adaptation period, male and female subjects (aged 21-56 y) completed a 17-wk bed rest protocol. Subjects were assigned to one of three treatments: alendronate (ALEN; 10 mg/d, n=6), resistive exercise (RE; 1.5 h/d, 6 d/wk, n=8), or control (CN; no countermeasure, n=8). Dietary intake was adjusted to maintain body weight. Endocrine and biochemical indices were measured in blood and urine using standard laboratory methods. All data reported are expressed as percent change from individual pre-bedrest data. Serum calcium changed little during bed rest, and tended to decrease (4-8%) in ALEN subjects. In RE subjects, bone alkaline phosphatase and osteocalcin were increased >65 and >30%, respectively, during bed rest, while these were unchanged or decreased in ALEN and CN subjects. Urinary calcium was increased 50% in CN subjects, but was unchanged or decreased in both ALEN and RE groups. Urinary n-telopeptide excretion was increased 40-50% in CN and RE subjects, but decreased 20% in ALEN subjects. Pyridinium crosslink and deoxypyridinoline excretion were increased 20-50% during bed rest. These data suggest that RE countermeasures are effective at increasing markers of bone formation in an analog of weightlessness, while ALEN reduces markers of bone resorption. Counteracting the bone loss of space flight may require both pharmacologic and exercise countermeasures.

Smith, Scott M.↗

Assessment of Long Bone Flexural Properties from Bone Densitometry

While bone densitometry is the accepted non-invasive method of quantifying bone mineral content in bones, its assessment of bone structural properties is less well understood. The objective of our current work is to compare cross-section shape or areal properties of long bones computed from densitometry data with cross-section flexural properties obtained from surface strain measurements.

Whalen, Robert↗

Dependence of Long Bone Flexural Properties on Bone Mineral Distribution

The objective of this study is to assess whether a non-invasive determination of long bone cross-sectional areal properties using bone densitometry accurately estimates true long bone flexural properties. In this study, section properties of two pairs of human female embalmed tibiae were compared using two methods: special analysis of bone densitometry data, and experimental determination of flexural regidities from bone surface strain measurements during controlled loading.

Katz, BethAnn↗

Mapping Bone Mineral Density Obtained by Quantitative Computed Tomography to Bone Volume Fraction

Methods for relating or mapping estimates of volumetric Bone Mineral Density (vBMD) obtained by Quantitative Computed Tomography to Bone Volume Fraction (BVF) are outlined mathematically. The methods are based on definitions of bone properties, cited experimental studies and regression relations derived from them for trabecular bone in the proximal femur. Using an experimental range of values in the intertrochanteric region obtained from male and female human subjects, age 18 to 49, the BVF values calculated from four different methods were compared to the experimental average and numerical range. The BVF values computed from the conversion method used data from two sources. One source provided pre bed rest vBMD values in the intertrochanteric region from 24 bed rest subject who participated in a 70 day study. Another source contained preflight vBMD values from 18 astronauts who spent 4 to 6 months on the ISS. To aid the use of a mapping from BMD to BVF, the discussion includes how to formulate them for purpose of computational modeling. An application of the conversions would be used to aid in modeling of time varying changes in vBMD as it relates to changes in BVF via bone remodeling and/or modeling.

Pennline, James A.↗

Incomplete Bone Recovery at the Distal Tibia in Astronauts with Elevated Markers of Bone Turnover

Determining whether bone recovers after prolonged spaceflight is important for understanding the risks to astronaut long-term skeletal health and the limits of bone adaptation. The primary aim of this study was to use second-generation HR-pQCT to examine recovery of bone microarchitecture, density, and strength after long-duration spaceflight. Secondary aims included examining the effect of mission duration and biochemical measures of bone turnover on bone recovery.

Leigh Gabel↗

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↗

Method of adhering bone to a rigid substrate using a graphite fiber reinforced bone cement

A method is described for adhering bone to the surface of a rigid substrate such as a metal or resin prosthesis using an improved surgical bone cement. The bone cement has mechanical properties more nearly matched to those of animal bone and thermal curing characteristics which result in less traumatization of body tissues and comprises a dispersion of short high modulus graphite fibers within a bonder composition including polymer dissolved in reactive monomer such as polymethylmethacrylate dissolved in methylmethacrylate monomer.

Knoell, A. C.↗

Role of carbonic anhydrase in bone - Plasma acetazolamide concentrations associated with inhibition of bone loss

The effects of acetazolamide and benzolamide on bone formation are examined. Solutions of acetazolamide and benzolamide with 1 M THAM/tris(hydromethyl)aminoethane/ or without 1 M THAM were injected subcutaneous with a minipump and into the food of Sprague-Dawley rats. The data reveal that for 8-day and 12-day infusions only acetazolamide combined with 1 M THAM caused any reduction in bone loss and there were no changes in body weights, food consumption and plasma calcium and phosphorus values. Following 8 days of infusion of acetazolamide with 1 M THAM at infusion rates of 0.5, 5.0, and 50 micrograms/hr, no reduction was detected at 0.5 microgram/hr, a 30 percent reduction occurred at 5.0 micrograms/hr and a 49 percent decrease at 50 micrograms/hr. In the benzolamide experiment it was observed that 0.5 percent of the solution in the food caused no reduction in bone loss; however, infusions with benzolamide plus 1 M THAM resulted in a bone loss reduction of 30 percent at 5.0 micrograms/hr, and a 49 percent decrease at 50 micrograms/hr. Acetazolamide levels in the plasma at 50 micrograms/hr doses are calculated as ranging from 99 ng/ml-223 ng/ml and as 46 ng/ml at 5 micrograms/hr doses.

Kenny, A. D.↗

Bone density in limb-immobilized beagles: An animal model for bone loss in weightlessness

Prolonged weightlessness is man in space flight results in a slow progressive demineralization of bone accompanied by an increased calcium output in the urine resulting in negative calcium balances. This possibly irreversible bone loss may constitute a serious limiting factor to long duration manned space flight. In order to seek and test preventative measures an appropriate ground based animal model simulating weightlessness is necessary. Use of the mature Beagle in limb immobilization has been documented as an excellent model for orthopedic research since this animal most closely simulates the phenomenom of bone loss with regards to growth, remodeling, structure, chemistry and mineralization. The purpose of this project is to develop a research protocol for the study of bone loss in Beagles during and after cast immobilization of a hindleg; research will then be initiated.

Wolinsky, Ira↗

Greater Bone Fomation Induction Occurred in Aged Than Young Cancellous Bone Sites

We have determined the differences in the effects of continual prostaglandin E2 (PGE2) treatment in aged (non-growing) and young (growing) cancellous bone sites in 7 month-old Sprague-Dawley rats. The sites involved are the aged Distal Tibial Metaphysis (DTM) with a closed epiphysis and the young Proximal Tibial Metaphysis (PTM) with a slow growing, open epiphysis. The study involved rats treated with 0, 1, 3 or 6 mg PGE2/kg/d for 60, 120 and 180 days. Static and dynamic histomorphometty of percent trabecular area, and tissue-referent bone formation rate (BFR/TV) were determined in both DTM and PTM. In pretreatment controls, the secondary spongiosa of the two metaphyses contain the same amount of cancellous bone (11% in DTM vs. 13% in PTM), but markedly less bone formation in DTM (0.6%/y in DTM vs. 41.5%/y in PTM). After 60 days of 6 mg PGE2/kg/d treatment, %Tb.Ar was increased 607% in DTM and 199% in PTM, BFR/TV was increased to nearly 14 fold in DTM and only 5 fold in PTM. These results indicated the aged metaphysis of the DTM was much more responsive to PGE2 treatment than young, growing metaphysis of the PTM. The results of 120 and 180 days treatment did not significantly differ from 60 days treatment in both sites, indicating that the effect of continuous daily PGE2 treatment were in equilibrium after 60 days. We concluded that aged metaphysis was much more responsive to PGE2 treatment than young growing metaphysis.

Ke, H. Z.↗

Greater Bone Formation Induction Occurred in Aged than Young Cancellous Bone Sites

We have determined the differences in the effects of continual prostaglandin E(sub 2) (PGE(sub 2) treatment in aged (non-growing) and young (growing) cancellous bone sites in 7-month-old Sprague-Dawley rats. The sites involved are the aged distal tibial metaphysis (DTM) with a closed epiphysis and the young proximal tibial metaphysis (PTM) with a slow growing, open epiphysis. The study involved rats treated with 0, 1, 3 or 6 mg PGE(sub 2)/kg/d for 60, 120 and 180 days. Static and dynamic histomorphometry of percent trabecular area, and tissue-referent bone formation rate (BFR/TV) were determined in both DTM and PTM. In pretreatment controls, the secondary spongiosa of the two metaphyses contain the same amount of cancellous bone (11% in DTM vs. 13% in PTM), but markedly less bone formation in DTM (0.6%/y in DTM vs. 41.5%/y in PTM). After 60 days of 6 mg PGE(sub 2)/kg/d treatment, %Tb.Ar was increased 607% in DTM and 199% in PTM, BFR/TV was increased to nearly 14 fold in DTM and only 5 fold in PTM. These results indicated the aged metaphysis of the DTM was much more responsive to PGE(sub 2) treatment than young, growing metaphysis of the PTM. The results of 120 and 180 days treatment did not significantly differ from 60 days treatment in both sites, indicating that the effect of continuous daily PGE2 treatment were in equilibrium after 60 days. We concluded that aged metaphysis was much more responsive to PGE(sub 2) treatment than young growing metaphysis.

Ke, H. Z.↗

Combined Effects of Spaceflight and Age in Astronauts as Assessed by Areal Bone Mineral Density [BMD] and Trabecular Bone Score

Spaceflight is a potential risk factor for secondary osteoporosis in astronauts. Although lumbar spine (LS) BMD declines rapidly, more than expected for age, there have been no fragility fractures in astronauts that can clearly be attributed to spaceflight. Recently, astronauts have been returning from 6‐month spaceflights with absolute BMD still above young adult mean BMD. In spite of these BMD measurements, we project that the rapid loss in bone mass over long‐duration spaceflight affects the bone microarchitecture of the LS which might predispose astronauts to premature vertebral fractures. Thus, we evaluated TBS, a novel texture index correlated with vertebral bone microarchitecture, as a means of monitoring changes to bone microarchitecture in astronauts as they age. We previously reported that TBS detects an effect of spaceflight (~6‐month duration), independent of BMD, in 51 astronauts (47+/‐4 y) (Smith et al, J Clin Densitometry 2014). Hence, TBS was evaluated in serial DXA scans (Hologic Discovery W) conducted triennially in all active and retired astronauts and more frequently (before spaceflight, after spaceflight and until recovery) in the subset of astronauts flying 4‐6‐ month missions. We used non‐linear models to describe trends in observations (BMD or TBS) plotted as a function of astronaut age. We fitted 1175 observations of 311 astronauts, pre‐flight and then postflight starting 3 years after landing or after astronaut's BMD for LS was restored to within 2% of preflight BMD. Observations were then grouped and defined as follows: 1) LD: after exposure to at least one long‐duration spaceflight > 100 days and 2) SD: before LD and after exposure to at least one short-duration spaceflight < 30 days. Data from males and females were analyzed separately. Models of SD observations revealed that TBS and BMD had similar curvilinear declines with age for both male and female astronauts. However, models of LD observations showed TBS declining with age while BMD appeared stable or trending upward. For females (n=8) LD observations were too few to discern a trend. Notably, models describing trends in TBS appeared to be more sensitive to the effects of age than the models for BMD. We conclude that TBS may provide an additional index for the lumbar spine to monitor the combined changes due to spaceflight and due to aging. This increased knowledge may enhance the ability to identify an intervention trigger for premature vertebral fractures in astronauts.

Sibonga, Jean D.↗

Osteogenic preconditioning in perfusion bioreactors improves vascularization and bone formation by human bone marrow aspirates

Cell-derived extracellular matrix (ECM) provides a niche to promote osteogenic differentiation, cell adhesion, survival, and trophic factor secretion. To determine whether osteogenic preconditioning would improve the bone-forming potential of unfractionated bone marrow aspirate (BMA), we perfused cells on ECM-coated scaffolds to generate naïve and preconditioned constructs, respectively. The composition of cells selected from BMA was distinct on each scaffold. Naïve constructs exhibited robust proangiogenic potential in vitro, while preconditioned scaffolds contained more mesenchymal stem/stromal cells (MSCs) and endothelial cells (ECs) and exhibited an osteogenic phenotype. Upon implantation into an orthotopic calvarial defect, BMA-derived ECs were present in vessels in preconditioned implants, resulting in robust perfusion and greater vessel density over the first 14 days compared to naïve implants. After 10 weeks, human ECs and differentiated MSCs were detected in de novo tissues derived from naïve and preconditioned scaffolds. These results demonstrate that bioreactor-based preconditioning augments the bone-forming potential of BMA.

59 BASIC BIOLOGICAL SCIENCES↗

Prediction of femoral neck and spine bone mineral content from the BMC of the radius or ulna and the relationship between bone strength and BMC

The bone mineral content (BMC) is extensively used to provide information about the status of an entire skeleton. Changes in BMC are employed to evaluate the effect of various drugs, disease states, weightlessness, exercise, renal dialysis and others on the skeleton. Clinical and functional information is discussed that may be derived from the BMC of a limited region of the skeleton. In particular there is a fairly high degree of correlation between the BMC of the radius or ulna and that of the femoral neck, r about 0.85 and a somewhat lower relationship between the BMC of the radius or ulna and the thoracic vertebrae, r about 0.65. Also the BMC is highly related to the strength of bone at that scan site.

Wilson, C. R.↗

Role of carbonic anhydrase in bone - Partial inhibition of disuse atrophy of bone by parenteral acetazolamide

The effectiveness of orally and subcutaneously administered acetazolamide sodium in preventing denervation-induced bone loss in rats is examined. Male Sprague-Dawley rats were treated with acetazolamide either orally by incorporation of 0.2, 0.5, or 1.5 percent concentrations in their diet for 15 days, or subcutaneously by either injection of 0.5 ml/rat of a solution containing either 20 or 100 mg/ml of the drug twice daily for 15 days or by continuous infusion of 5, 50, 500, or 1000 mg/ml of acetazolamide sodium for 8 days using an osmotic minipump. The effects of acetazolamide on body weight, food consumption, and plasma calcium content are evaluated. It is observed that parenteral administration is equally effective as oral administration in partially preventing denervation-induced bone mass changes. The data reveal that approximately 50 percent protection occurs with daily doses of 1094, 129, and 8 mg/kg body weight for the oral, subcutaneous injection, and subcutaneous infusion methods, respectively.

Kenny, A. D.↗

Exercise Countermeasures for Bone Loss During Space Flight: A Method for the Study of Ground Reaction Forces and Their Implications for Bone Strain

The human zero-gravity locomotion simulator and the cadaver simulator offer a powerful combination for the study of the implications of exercise for maintaining bone quality during space flight. Such studies, when compared with controlled in-flight exercise programs, could help in the identification of a strain threshold for the prevention of bone loss during space flight.

Peterman, M.↗

Probabilistic Risk Assessment for Bone Fracture - Bone Fracture Risk Module (BFxRM)

This presentation summarizes the concepts, development, and application of NASA's Bone Fracture Risk Module (BFxRM). The overview includes an assessmnet of strenghts and limitations of the BFxRM and proposes a numebr of discussion questions to the panel regarding future development avenues for this simulation system.

Monte Carlo Method↗