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At least 73 records · Page 4
All sourcesNASA NTRSDOE OSTI
NASA NTRS2025

Magnetic Resonance Imaging (MRI) to Assess Changes to Trabecular Microarchitecture (Trb µArch) of the Hip

BACKGROUND . Calculated loss rates in trabecular (Trb) volumetric bone mineral density (vBMD), in astronauts after return from 6-month long-duration (LD) spaceflight, are rapid relative to menopause-induced loss rates and could contribute to the observed lack of recovery. Perforations in the Trb bony struts, skeletal fragility and fractures [5] have been associated with the rapid rate of bone loss in women due to menopause. The more rapid loss rate observed in astronauts could be inducing similar, irreversible losses of trabecular connectivity as seen in cadaver studies of female skeletons. These changes are not detectable by DXA technology and would not be discovered in astronauts during scheduled, triennial DXA testing for primary osteoporosis. High-resolution-peripheral quantitative computed tomography (HR-pQCT) of the lower leg have detected losses in Trb vBMD (vBMD) and changes in Trb microarchitecture (µArch) in astronauts immediately following routine 6-month spaceflights and continuing in some individuals for 1 or more years postflight with no signs of recovery. Resolution of these microarchitectural changes by whole body QCT, especially in the deeply embedded hip bone, is prohibitive due to excessive and unsafe radiation exposures. While HR-pQCT has sufficient resolution to study Trb µArch at safe and lower radiation exposure testing is restricted only to the lower leg and wrist. Hence, a technology to detect detrimental changes to Trb µArch in astronauts, especially of the hip, is needed to inform type and timing of countermeasures to irreversible deficits (preflight, inflight and postflight). METHODS . This HRP-funded study (2023-2027) will verify the sensitivity of a protocol for MRI scanning (on a 3T Siemens Vida) to detect changes to hip Trb µArch in persons following spinal cord injury (SCI); skeletal immobilization below the spinal lesion will serve as an analog for non-weight-bearing during spaceflight. The study period has been extended by 1 yr due to delayed Richmond IRB approval in Y1. A 3T MRI protocol will characterize serial changes in hip Trb µArch in SCI patients from time of admission at the Richmond VA Medical Center to their scheduled annual exam 12-months later. SCI patients with age, sex, and physical characteristics like ISS astronauts will be consented. The ability of 3T MRI hip scan to discriminate loss of trabecular connectivity subjects with SCI will be compared to age- and sex-matched ambulatory controls. A comparison between HR-pQCT and MRI measurements at the ankle (distal tibia) of study subjects will also be performed. A modified DXA scan analysis (3D-Shaper) will also be verified as a potential method for monitoring concurrent changes in hip Trb bone over 12-month. SIGNIFICANCE . Deliverables: a surveillance method for assessing for irreversible losses of connectivity and how skeletal changes after LD spaceflight(s) would modify the terrestrial risk of primary osteoporosis.

Spinal Cord Injury↗
NASA NTRS2025

Magnetic Resonance Imaging (MRI) to Assess Changes to Trabecular Microarchitecture (Trb µArch) of the Hip

BACKGROUND . Calculated loss rates in trabecular (Trb) volumetric bone mineral density (vBMD), in astronauts after return from 6-month long-duration (LD) spaceflight, are rapid relative to menopause-induced loss rates and could contribute to the observed lack of recovery. Perforations in the Trb bony struts, skeletal fragility and fractures [5] have been associated with the rapid rate of bone loss in women due to menopause. The more rapid loss rate observed in astronauts could be inducing similar, irreversible losses of trabecular connectivity as seen in cadaver studies of female skeletons. These changes are not detectable by DXA technology and would not be discovered in astronauts during scheduled, triennial DXA testing for primary osteoporosis. High-resolution-peripheral quantitative computed tomography (HR-pQCT) of the lower leg have detected losses in Trb vBMD (vBMD) and changes in Trb microarchitecture (µArch) in astronauts immediately following routine 6-month spaceflights and continuing in some individuals for 1 or more years postflight with no signs of recovery. Resolution of these microarchitectural changes by whole body QCT, especially in the deeply embedded hip bone, is prohibitive due to excessive and unsafe radiation exposures. While HR-pQCT has sufficient resolution to study Trb µArch at safe and lower radiation exposure testing is restricted only to the lower leg and wrist. Hence, a technology to detect detrimental changes to Trb µArch in astronauts, especially of the hip, is needed to inform type and timing of countermeasures to irreversible deficits (preflight, inflight and postflight). METHODS . This HRP-funded study (2023-2027) will verify the sensitivity of a protocol for MRI scanning (on a 3T Siemens Vida) to detect changes to hip Trb µArch in persons following spinal cord injury (SCI); skeletal immobilization below the spinal lesion will serve as an analog for non-weight-bearing during spaceflight. The study period has been extended by 1 yr due to delayed Richmond IRB approval in Y1. A 3T MRI protocol will characterize serial changes in hip Trb µArch in SCI patients from time of admission at the Richmond VA Medical Center to their scheduled annual exam 12-months later. SCI patients with age, sex, and physical characteristics like ISS astronauts will be consented. The ability of 3T MRI hip scan to discriminate loss of trabecular connectivity subjects with SCI will be compared to age- and sex-matched ambulatory controls. A comparison between HR-pQCT and MRI measurements at the ankle (distal tibia) of study subjects will also be performed. A modified DXA scan analysis (3D-Shaper) will also be verified as a potential method for monitoring concurrent changes in hip Trb bone over 12-month. SIGNIFICANCE . Deliverables: a surveillance method for assessing for irreversible losses of connectivity and how skeletal changes after LD spaceflight(s) would modify the terrestrial risk of primary osteoporosis.

Risk Surveillance↗
DOE OSTI2021

Improving Bone Health by Optimizing the Anabolic Action of Wnt Inhibitor Multitargeting

Sclerostin antibody (romosozumab) was recently approved for clinical use in the United States to treat osteoporosis. We and others have explored Wnt-based combination therapy to disproportionately improve the anabolic effects of sclerostin inhibition, including cotreatment with sclerostin antibody (Scl-mAb) and Dkk1 antibody (Dkk1-mAb). To determine the optimal ratio of Scl-mAb and Dkk1-mAb for producing maximal anabolic action, the proportion of Scl-mAb and Dkk1-mAb were systematically varied while holding the total antibody dose constant. A 3:1 mixture of Scl-mAb to Dkk1-mAb produced two to three times as much cancellous bone mass as an equivalent dose of Scl-mAb alone. Further, a 75% reduction in the dose of the 3:1 mixture was equally efficacious to a full dose of Scl-mAb in the distal femur metaphysis. The Scl-mAb/Dkk1-mAb combination approach was highly efficacious in the cancellous bone mass, but the cortical compartment was much more subtly affected. The osteoanabolic effects of Wnt pathway targeting can be made more efficient if multiple antagonists are simultaneously targeted.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Estrogen depletion alters osteogenic differentiation and matrix production by osteoblasts in vitro

Highlights: • Estrogen depletion accelerates osteoblast differentiation in static culture. • Mechanical stimulation exacerbated the effects of estrogen depletion on osteoblast differentiation. • Estrogen depletion alters osteoblasts capacity to produce a good quality matrix. Recent studies have revealed that the effects of estrogen deficiency are not restricted to osteoclasts and bone resorption, but that bone matrix composition is altered and osteoblasts exhibit an impaired response to mechanical stimulation. In this study, we test the hypothesis that estrogen depletion alters osteogenic differentiation and matrix production by mechanically stimulated osteoblasts in vitro. MC3T3-E1 cells were pre-treated with estrogen for 14 days, after which estrogen was withdrawn or inhibited with Fulvestrant up to 14 days. Fluid shear stress (FSS) was applied using an orbital shaker. Under estrogen depletion in static culture, osteogenic marker (ALP) and gene expression (Runx2) were decreased at 2 and after 7 days of estrogen depletion, respectively. In addition, up to 7 day the inhibition of the estrogen receptor significantly decreased fibronectin expression (FN1) under static conditions. Under estrogen depletion and daily mechanical stimulation, changes in expression of Runx2 occurred earlier (4 days) and by 14 days, changes in matrix production (Col1a1) were reported. We propose that changes in osteoblast differentiation and impaired matrix production during estrogen depletion may contribute to the altered quality of the bone and act as a contributing factor to increased bone fragility in postmenopausal osteoporosis.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Non-small cell lung cancer cell–derived exosomal miR-17-5p promotes osteoclast differentiation by targeting PTEN

Highlights: • exosomes of SPC-A-1BM cell line prompt osteoclastogenesis. • miR-17-5p increased in exosomes of SPC-A-1BM cell line. • miR-17-5p prompt osteoclastogenesis. • miR-17-5p function through PTEN/PI3K/AKT pathway in osteoclastogenesis in NSCLC. Aberrant activity of bone resorbing osteoclasts plays a key role in the development of osteoporosis and cancer bone metastasis. The identification of novel and specific targets will be helpful for the development of new therapeutic strategies for bone metastasis in lung cancer. Herein, we examined microRNAs in tumor cell-derived exosomes to investigate the communication between the bone environment and tumor cells. TCGA database analysis showed that the level of miR-17-5p increased in non-small cell lung cancer tissues compared with non-tumor tissues. To investigate the function of exosomes in inducing osteoclastogenesis, osteoclast precursors were incubated with exosomes isolated from non-small cell lung cancer cell line, as well as receptor activator of NF-KB ligand and M-CSF to induce osteoclastogenesis. We found that exosomal miR-17-5p is upregulated in a non-small cell lung cancer cell line with bone metastasis compared with the original cell line. Overexpression of miR-17-5p enhanced the osteoclastogenesis of RAW264.7 cells. PTEN was identified as a direct target of miR-17-5p and showed negative effects on osteoclastogenesis. Importantly, treatment of LY294002 (an inhibitor of the PI3K/Akt pathway) attenuated miR-17-5p-mediated osteoclastogenesis effects. Taken together, our findings demonstrated that miR-17-5p promotes osteoclastogenesis through the PI3K/Akt pathway via targeting PTEN in lung cancer.

60 APPLIED LIFE SCIENCES↗
NASA NTRS1995

Estimates of volumetric bone density from projectional measurements improve the discriminatory capability of dual X-ray absorptiometry

To determine whether estimates of volumetric bone density from projectional scans of the lumbar spine have weaker associations with height and weight and stronger associations with prevalent vertebral fractures than standard projectional bone mineral density (BMD) and bone mineral content (BMC), we obtained posteroanterior (PA) dual X-ray absorptiometry (DXA), lateral supine DXA (Hologic QDR 2000), and quantitative computed tomography (QCT, GE 9800 scanner) in 260 postmenopausal women enrolled in two trials of treatment for osteoporosis. In 223 women, all vertebral levels, i.e., L2-L4 in the DXA scan and L1-L3 in the QCT scan, could be evaluated. Fifty-five women were diagnosed as having at least one mild fracture (age 67.9 +/- 6.5 years) and 168 women did not have any fractures (age 62.3 +/- 6.9 years). We derived three estimates of "volumetric bone density" from PA DXA (BMAD, BMAD*, and BMD*) and three from paired PA and lateral DXA (WA BMD, WA BMDHol, and eVBMD). While PA BMC and PA BMD were significantly correlated with height (r = 0.49 and r = 0.28) or weight (r = 0.38 and r = 0.37), QCT and the volumetric bone density estimates from paired PA and lateral scans were not (r = -0.083 to r = 0.050). BMAD, BMAD*, and BMD* correlated with weight but not height. The associations with vertebral fracture were stronger for QCT (odds ratio [QR] = 3.17; 95% confidence interval [CI] = 1.90-5.27), eVBMD (OR = 2.87; CI 1.80-4.57), WA BMDHol (OR = 2.86; CI 1.80-4.55) and WA-BMD (OR = 2.77; CI 1.75-4.39) than for BMAD*/BMD* (OR = 2.03; CI 1.32-3.12), BMAD (OR = 1.68; CI 1.14-2.48), lateral BMD (OR = 1.88; CI 1.28-2.77), standard PA BMD (OR = 1.47; CI 1.02-2.13) or PA BMC (OR = 1.22; CI 0.86-1.74). The areas under the receiver operating characteristic (ROC) curves for QCT and all estimates of volumetric BMD were significantly higher compared with standard PA BMD and PA BMC. We conclude that, like QCT, estimates of volumetric bone density from paired PA and lateral scans are unaffected by height and weight and are more strongly associated with vertebral fracture than standard PA BMD or BMC, or estimates of volumetric density that are solely based on PA DXA scans.

Non-NASA Center↗
DOE OSTI2023

Harnessing Aromatic‐Histidine Interactions through Synergistic Backbone Extension and Side Chain Modification

Abstract Peptide engineering efforts have delivered drugs for diverse human diseases. Side chain alteration is among the most common approaches to designing new peptides for specific applications. The peptide backbone can be modified as well, but this strategy has received relatively little attention. Here we show that new and favorable contacts between a His side chain on a target protein and an aromatic side chain on a synthetic peptide ligand can be engineered by rational and coordinated side chain modification and backbone extension. Side chain modification alone was unsuccessful. Binding measurements, high‐resolution structural studies and pharmacological outcomes all support the synergy between backbone and side chain modification in engineered ligands of the parathyroid hormone receptor‐1, which is targeted by osteoporosis drugs. These results should motivate other structure‐based designs featuring coordinated side chain modification and backbone extension to enhance the engagement of peptide ligands with target proteins.

36 MATERIALS SCIENCE↗
DOE OSTI2023

Harnessing Aromatic‐Histidine Interactions through Synergistic Backbone Extension and Side Chain Modification

Abstract Peptide engineering efforts have delivered drugs for diverse human diseases. Side chain alteration is among the most common approaches to designing new peptides for specific applications. The peptide backbone can be modified as well, but this strategy has received relatively little attention. Here we show that new and favorable contacts between a His side chain on a target protein and an aromatic side chain on a synthetic peptide ligand can be engineered by rational and coordinated side chain modification and backbone extension. Side chain modification alone was unsuccessful. Binding measurements, high‐resolution structural studies and pharmacological outcomes all support the synergy between backbone and side chain modification in engineered ligands of the parathyroid hormone receptor‐1, which is targeted by osteoporosis drugs. These results should motivate other structure‐based designs featuring coordinated side chain modification and backbone extension to enhance the engagement of peptide ligands with target proteins.

36 MATERIALS SCIENCE↗
DOE OSTI2020

Calcitonin Receptor N-Glycosylation Enhances Peptide Hormone Affinity by Controlling Receptor Dynamics

The class B G protein-coupled receptor (GPCR) calcitonin receptor (CTR) is a drug target for osteoporosis and diabetes. N-glycosylation of asparagine 130 in its extracellular domain (ECD) enhances calcitonin hormone affinity with the proximal GlcNAc residue mediating this effect through an unknown mechanism. Here, we present two crystal structures of salmon calcitonin-bound, GlcNAc-bearing CTR ECD at 1.78 and 2.85 Å resolutions and analyze the mechanism of the glycan effect. The N130 GlcNAc does not contact the hormone. Surprisingly, the structures are nearly identical to a structure of hormone-bound, N-glycan-free ECD, which suggested that the GlcNAc might affect CTR dynamics not observed in the static crystallographic snapshots. Hydrogen-deuterium exchange mass spectrometry and molecular dynamics simulations revealed that glycosylation stabilized a β-sheet adjacent to the N130 GlcNAc and the N-terminal α-helix near the peptide-binding site while increasing flexibility of the peptide-binding site turret loop. These changes due to N-glycosylation increased the ligand on-rate and decreased its off-rate. The glycan effect extended to RAMP-CTR amylin receptor complexes and was also conserved in the related CGRP receptor. These results reveal that N-glycosylation can modulate GPCR function by altering receptor dynamics.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Genetic interactions between polycystin-1 and Wwtr1 in osteoblasts define a novel mechanosensing mechanism regulating bone formation in mice

Molecular mechanisms transducing physical forces in the bone microenvironment to regulate bone mass are poorly understood. Here, we used mouse genetics, mechanical loading, and pharmacological approaches to test the possibility that polycystin-1 and Wwtr1 have interdependent mechanosensing functions in osteoblasts. We created and compared the skeletal phenotypes of control Pkd1 flox/+ ;Wwtr1 flox/+ , Pkd1 Oc-cKO , Wwtr1 Oc-cKO , and Pkd1/Wwtr1 Oc-cKO mice to investigate genetic interactions. Consistent with an interaction between polycystins and Wwtr1 in bone in vivo, Pkd1/Wwtr1 Oc-cKO mice exhibited greater reductions of BMD and periosteal MAR than either Wwtr1 Oc-cKO or Pkd1 Oc-cKO mice. Micro-CT 3D image analysis indicated that the reduction in bone mass was due to greater loss in both trabecular bone volume and cortical bone thickness in Pkd1/Wwtr1 Oc-cKO mice compared to either Pkd1 Oc-cKO or Wwtr1 Oc-cKO mice. Pkd1/Wwtr1 Oc-cKO mice also displayed additive reductions in mechanosensing and osteogenic gene expression profiles in bone compared to Pkd1 Oc-cKO or Wwtr1 Oc-cKO mice. Moreover, we found that Pkd1/Wwtr1 Oc-cKO mice exhibited impaired responses to tibia mechanical loading in vivo and attenuation of load-induced mechanosensing gene expression compared to control mice. Finally, control mice treated with a small molecule mechanomimetic, MS2 that activates the polycystin complex resulted in marked increases in femoral BMD and periosteal MAR compared to vehicle control. In contrast, Pkd1/Wwtr1 Oc-cKO mice were resistant to the anabolic effects of MS2. These findings suggest that PC1 and Wwtr1 form an anabolic mechanotransduction signaling complex that mediates mechanical loading responses and serves as a potential novel therapeutic target for treating osteoporosis.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2023

Younger facial looks are associate with a lower likelihood of several age-related morbidities in the middle-aged to elderly

Abstract Background Looking older for one’s chronological age is associated with a higher mortality rate. Yet it remains unclear how perceived facial age relates to morbidity and the degree to which facial ageing reflects systemic ageing of the human body. Objectives To investigate the association between ΔPA and age-related morbidities of different organ systems, where ΔPA represents the difference between perceived age (PA) and chronological age. Methods We performed a cross-sectional analysis on data from the Rotterdam Study, a population-based cohort study in the Netherlands. High-resolution facial photographs of 2679 men and women aged 51.5–87.8 years of European descent were used to assess PA. PA was estimated and scored in 5-year categories using these photographs by a panel of men and women who were blinded for chronological age and medical history. A linear mixed model was used to generate the mean PAs. The difference between the mean PA and chronological age was calculated (ΔPA), where a higher (positive) ΔPA means that the person looks younger for their age and a lower (negative) ΔPA that the person looks older. ΔPA was tested as a continuous variable for association with ageing-related morbidities including cardiovascular, pulmonary, ophthalmological, neurocognitive, renal, skeletal and auditory morbidities in separate regression analyses, adjusted for age and sex (model 1) and additionally for body mass index, smoking and sun exposure (model 2). Results We observed 5-year higher ΔPA (i.e. looking younger by 5 years for one’s age) to be associated with less osteoporosis [odds ratio (OR) 0.76, 95% confidence interval (CI) 0.62–0.93], less chronic obstructive pulmonary disease (OR 0.85, 95% CI 0.77–0.95), less age-related hearing loss (model 2; B = −0.76, 95% CI −1.35 to −0.17) and fewer cataracts (OR 0.84, 95% CI 0.73–0.97), but with better global cognitive functioning (g-factor; model 2; B = 0.07, 95% CI 0.04–0.10). Conclusions PA is associated with multiple morbidities and better cognitive function, suggesting that systemic ageing and cognitive ageing are, to an extent, externally visible in the human face.

Mekić, Selma↗
DOE OSTI2021

Sclerostin Depletion Induces Inflammation in the Bone Marrow of Mice

Romosozumab, a humanized monoclonal antibody specific for sclerostin (SOST), has been approved for treatment of postmenopausal women with osteoporosis at a high risk for fracture. Previous work in sclerostin global knockout (Sost-/- ) mice indicated alterations in immune cell development in the bone marrow (BM), which could be a possible side effect in romosozumab-treated patients. Here, we examined the effects of short-term sclerostin depletion in the BM on hematopoiesis in young mice receiving sclerostin antibody (Scl-Ab) treatment for 6 weeks, and the effects of long-term Sost deficiency on wild-type (WT) long-term hematopoietic stem cells transplanted into older cohorts of Sost-/- mice. Our analyses revealed an increased frequency of granulocytes in the BM of Scl-Ab-treated mice and WT→Sost -/- chimeras, indicating myeloid-biased differentiation in Sost-deficient BM microenvironments. This myeloid bias extended to extramedullary hematopoiesis in the spleen and was correlated with an increase in inflammatory cytokines TNFα, IL-1α, and MCP-1 in Sost-/- BM serum. Additionally, we observed alterations in erythrocyte differentiation in the BM and spleen of Sost-/- mice. Taken together, our current study indicates novel roles for Sost in the regulation of myelopoiesis and control of inflammation in the BM.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS1971

The effect of variable calcium and very low calcium diets on human calcium metabolism

The effects of a very low calcium diet, with variable high and low protein intake, on the dynamics of calcium metabolism and the mechanism of calciuretics, are examined. The experiment, using male subjects, was designed to study the role of intestinal calcium absorption on urinary calcium excretion, and the rate of production of endogeneously secreted calcium in the gastrointestinal tract. The study showed an average of 70% fractional absorption rate during very low calcium intake, and that a decrease in renal tubular reabsorption of calcium is responsible for calciuretic effects of high protein intake. The study also indicates that there is a tendency to develop osteoporosis after long periods of low calcium intake, especially with a concurrent high protein intake.

Chu, J.↗
NASA NTRS1980

Effects of factors of prolonged space flight on conditions of tortoise skeleton

After a 60-90 day space flight mild osteoporosis developed in the epiphyses and metaphyses of long tubular bones of tortoises, which was not attributed to reduced mineral saturation of the preserved bone tissue microstructures. The diminished strength of the cancellous bone of the epiphyses in tortoises after space flight was due to the reduced properties of its structure. The strength of the compact substance did not change under the effect of weightlessness.

Stupakon, G. P.↗
NASA NTRS1980

Changes in bone tissue under conditions of hypokinesia and in connection with age

X-ray micrography was used to study the optical density of the blackening of X-ray photographs made of five bones in 9 young people (ages 24 to 29) before and after strict bed rest for 16 to 37 days. Photometric studies of the X-ray film determined the relative concentration of bone structure before and after hypokinesia. In addition, the bone tissues of 25 cadavers of practically healthy individuals (aged 18 to 70) who died from injuries were investigated using X-ray structural analysis. Results show that the reaction to the state of hypokinesia is not uniform in different individuals and is quite often directly reversed. It was established that pronounced osteoporosis can be found in a relatively short time after conditions of hypokinesia in healthy young individuals. Results show that the stabilization of the crystalline structure of hydroxyapatite, especially its crystal formation, is finished by the age of 20 to 25. From 25 to 60, the crystal lattice remains in stable condition but X-ray analysis shows a reduction in the hydroxyapatite density.

Podrushnyak, E. P.↗
NASA NTRS1980

Effect of six-month hypokinesia in dogs on mineral component, reconstruction and mechanical properties of bone tissue

Ca45 incorporation into the bones of the limbs, particularly in the area of the muscle attachment increased in dogs as a result of 6 month hypokinesia. There were no phenomena of osteoporosis in the cortical layer of the diaphyses; however, changes in the form of osteons, an increase in the number of anastomoses between the channels and the thinning of the subperiosteal layer pointed to disturbances of the bone tissue reconstruction. Mineral saturation of the bone microstructures of the experimental dogs had a tendency to rise. No changes in the mechanical properties of the long bones occurred as a result of hypokinesia in dogs.

Volozhin, A. I.↗
NASA NTRS1983

Skeletal and body composition evaluation

Research on radiation detectors for absorptiometry; analysis of errors affective single photon absorptiometry and development of instrumentation; analysis of errors affecting dual photon absorptiometry and development of instrumentation; comparison of skeletal measurements with other techniques; cooperation with NASA projects for skeletal evaluation in spaceflight (Experiment MO-78) and in laboratory studies with immobilized animals; studies of postmenopausal osteoporosis; organization of scientific meetings and workshops on absorptiometric measurement; and development of instrumentation for measurement of fluid shifts in the human body were performed. Instrumentation was developed that allows accurate and precise (2% error) measurements of mineral content in compact and trabecular bone and of the total skeleton. Instrumentation was also developed to measure fluid shifts in the extremities. Radiation exposure with those procedures is low (2-10 MREM). One hundred seventy three technical reports and one hundred and four published papers of studies from the University of Wisconsin Bone Mineral Lab are listed.

Mazess, R. B.↗