Mechanisms of human osteopenia and some peculiarities of bone metabolism in weightlessness conditions

Systematically results and new analysis data on the investigation of human bone system in space flight, the orbital station Mir and International Space Station, are presented. The bone mineral density, bone mineral content, identified as bone mass and body composition using dual energy X-ray absorptiometry were measured. Theoretically, an expected bone mass loss in trabecular tissue of lower skeletal half may by described as a quickly developing but reversible osteopenia and considered as evidence of functional adaptation of bone tissue to the changing mechanical load. A hypothesis of main mechanisms of osteopenia in microgravity is presented. High individual variability of bone mass losses and stability of individual pattern of correlation between bone mass losses in different skeletal segments were found. It is not possible to identify the relationship between bone mass losses and duration of space missions. Therefore it is not a sufficient ground to calculate the probability of reaching the critical level of bone demineralization by prolonged space flight. The same relates to the probability of prognosis of bone quality changes. There is data about dual energy X-ray absorptiometry that is insufficient for this prognosis. The main direction of investigations is presented which might optimize the interplanetary mission from the point of view of skeletal mechanical functions preservation.     

Comparative analysis of changes in the skeleton of cosmonauts in long-term orbital flights and the possibilities of prediction for interplanetary missions

The results of long-term investigations of the bone system of humans during space flights (SFs) on board the Mir orbital station (OS) and international space station (ISS) using osteodensitometry are summarized. Comparative analysis of the results showed the absence of significant differences in changes in the bone mass (BM) in the crew members of both OSs. Theoretically, the expected bone mass losses in the trabecular bone structures of the lower part of the body in the process of a SF (five to seven months) are interpreted in some cases as quickly developing, but reversible, osteopenia and generally interpreted as the evidence of bone functional adaptation to altering mechanical loads on the skeleton. The high individual variability of changes and the stability of the individual character of the BM alteration ratio in different skeletal segments irrespective of the OS type are shown. Owing to the aforementioned individual features, it is not possible to establish a strict relationship between BM changes and the duration of space missions, and, therefore, there is no good reason for calculating the probability of achieving the critical demineralization level when the duration of an SF increases to 1.5–2 years. The probability of prediction of changes in the bone quality (structure) is still less, which, together with BM losses, determines the risk of fractures, and osteodensitometry for such an analysis is insufficient. The main directions of the studies, which could optimize the development of the interplanetary expedition project from the point of view of maintenance of the mechanical function of the skeleton, are considered.     

Study of skeleton gravitation physiology and problem of osteoporosis

Main osteoporosis definitions and some results of bone tissue research in Russian astronauts, patients, and healthy subjects, using modern osteodensitometry, are presented. Bone mineral density (BMD) was regularly decreased at lower segments of skeleton. In the skull bone and some other sites of upper part of skeleton, a tendency was revealed for an increase of the bone mineral content (BMC). The mean value of bone loss was within the normal range and not correlated with duration of space flight; it revealed a high individual variability and in some cases was clinically qualified as local osteopenia. On the ground of analysis of own results and animal and bone cultural experiments data in microgravity conditions, the described changes seem to be reflecting a deceleration of bone formation as an adaptive response of bone tissue to the mechanical unloading. The response is realized mainly on the tissue level. It does not exclude bone resorption activity as a result of changes in hierarchy of water and electrolytes metabolism as reflected by body fluid redistribution in cranial direction. The results obtained broaden our notions on pathogenesis of some types of osteoporosis in clinic.     

Body Composition in a Seasonal Model of Obesity: Longitudinal Measures and Validation of DXA

Objective: Collared lemmings, Dicrostonyx groenlandicus, show rapid changes in body mass on a seasonal basis. The objective of this study was to measure longitudinal changes in body composition in animals undergoing photoperiod-induced weight gain and loss using DXA. Research Methods and Procedures: Adult, female collared lemmings exposed to either long (LD; 22 hours light/2 hours dark) or short (SD; 8 hours light/16 hours dark) photoperiods were anesthetized, and DXA was used to determine fat mass, lean tissue mass (LTM), total-body bone mineral content, and total-bone mineral density. After a baseline scan, one-half of the animals were transferred to the alternate photoperiod (SD-LD, weight loss; LD-SD, weight gain) and one-half remained on the same photoperiod (controls; SD-SD, LD-LD). Body composition was determined by DXA after 4 and 8 weeks. Animals were killed, and body composition was determined by carcass analysis. DXA-derived data were validated by comparing with carcass analysis. Results: Body composition by DXA was highly related to body composition measured by chemical analysis, thereby justifying the use of DXA. Lemmings in the SD-LD group lost weight, and this was reflected in measurable losses of fat and LTM. Lemmings in the LD-SD group gained weight, which was shown by measurable increases in fat, LTM and total-body bone mineral content. Discussion: Comparison of body composition determined by DXA to that by chemical extraction revealed that DXA is useful for measuring body composition. The longitudinal analysis revealed that collared lemmings undergo rapid changes in body composition when exposed to changes in photoperiod.     

Bone mineral and lean tissue loss after long duration space flight

The loss of bone and muscle is a major concern for long duration space flight. In December of 1989, we established a collaboration with Russian colleagues to determine the bone and lean tissue changes in cosmonauts before and after flights on the Mir space station lasting 4-14.4 months. Eighteen crew members received a lumbar spine and hip DEXA scan (Hologic 1000W) before and after flight; 17 crew members received an additional whole body scan. All results were expressed as percent change from baseline per month of flight in order to account for the different flight times. The pre-and post-flight data were analyzed using Hotelling's T(2) for 3 groups of variables: spine, neck of femur, trochanter; whole body BMD and subregions; lean (total, legs, arms) and fat (total only). A paired t-test was used as a follow-up to the Hotelling's T(2) to identify the individual measurements that were significantly different. These data define the rate and extent of bone and lean tissue loss during long duration space flight and indicate that the current in-flight exercise program is not sufficient to completely ameliorate bone and muscle loss during weightlessness.     

Effect of calcium stress on the skeleton mass of intact and ovariectomized rats

Female rats were ovariectomized (Ovx) or sham-operated (control) at 18 weeks and the entire skeleton obtained at 24 weeks (baseline) or after an additional 31 day (28 week) interval on a normal (1.0%) or deficient (0.02%) calcium diet. Ovx rats showed a 42% increase in whole body bone resorption (3H-tetracycline loss) in the absence of calcium stress (1.0% calcium diet) and a 70% increase in resorption with morphological evidence of dramatic loss of cancellous bone mass when placed on calcium-deficient (0.02%) diets. Ovx rats kept on the 1.0% calcium diet showed a significant increase in both their body weight (30.2%) and total bone mass (11.6%) compared to baseline sham-operated controls. However, the total skeleton mass of these animals was significantly reduced (-20%) from that predicted by calculations based on body weight. Maintaining animals on calcium-deficient diets had no significant effect on the total skeleton mass of either control or Ovx rats in comparison with age-matched controls on 1.0% diets. It was further determined that an increase in bone mass between 24 and 28 weeks in rats receiving 1.0% dietary calcium occurred in both the axial and appendicular skeleton and was proportionately similar between control and Ovx groups. However, in animals subjected to dietary calcium stress during this interval, the decreased skeletal growth noted was confined primarily to the axial skeleton. The data indicate that ovariectomy or ovariectomy plus calcium stress does not result in loss of total bone mass during the interval of dramatically increased resorption and rapid loss of cancellous bone. The results suggest that the deterioration in individual bone structural and mechanical integrity due to ovariectomy or dietary calcium deficiency may not be attributed to overt loss in total bone mass but may involve a redistribution of bone mass.     

Muscle volume, MRI relaxation times (T2), and body composition after spaceflight.

Postflight changes in muscle volume, calf muscle transverse relaxation time, and total body composition were measured in 4 crewmembers after a 17-day mission and in 14-16 crewmembers in multiple shuttle/Mir missions of 16- to 28-wk duration. During the 17-day mission, all muscle regions except the hamstrings significantly decreased 3-10% compared with baseline. During the shuttle/Mir missions, there were significant decreases in muscle volume (5-17%) in all muscle groups except the neck. These changes, which reached a new steady state by 4 mo of flight or less, were reversed within 30-60 days after landing. Postflight swelling and elevation of calf muscle transverse relaxation time persisted for several weeks after flight, which suggests possible muscle damage. In contrast to the 17-day flight, in which loss in fat, but not lean body mass, was found (25), losses in bone mineral content and lean body mass, but not fat, were seen after the longer shuttle/Mir missions. The percent losses in total body lean body mass and bone mineral content were similar at approximately 3.4-3.5%, whereas the pelvis demonstrated the largest regional bone loss at 13%.     

Changes in body composition with weight loss: obese subjects randomized to surgical and medical programs

Objective: To assess changes in body composition with weight loss in obese subjects randomized to a laparoscopic adjustable gastric band surgical program or a medical program using a very‐low‐energy diet and orlistat. Research Methods and Procedures: Using body composition measurements by DXA, neutron activation for total body nitrogen, and whole body γ counting for total body potassium, we studied changes in fat mass, fat distribution, fat‐free mass, total bone mineral content, total body protein, and body cell mass at 6 (n = 61 paired) and 24 months (n = 53 paired) after randomization. Results: At 24 months, the surgical group had lost significantly more weight (surgical, 20.3 ± 6.5 kg; medical, 5.9 ± 8.0 kg). There was favorable fat‐free mass to fat mass loss ratios for both groups (surgical, 1:5.5; medical, 1:5.9). Changes in total body nitrogen or potassium were favorable in each group. A small reduction in mean bone mineral content occurred throughout the study but was not associated with extent of weight loss or treatment group. At 6 months, weight loss for both groups was similar (surgical, 14.1 ± 4.5 kg; medical, 13.3 ± 7.3 kg). The medical program subjects lost less fat‐free mass and skeletal muscle and had increased total body protein. The proportion of body fat to limb fat remained remarkably constant throughout the study. Discussion: Weight loss programs used in this study induced fat loss without significant deleterious effects on the components of fat‐free mass.     

Physiological Factors Responsible for the Development of Osteopenia under Conditions of Mechanical Unloading

A summary of results of investigations by the author and a brief review of some literature data on human bone tissue deprived of mechanical loading (spaceflight, hypokinesia) is given. The direction and markedness of changes in bone mass—the bone mineral density and the bone mineral content—in different skeletal segments depend on their position relative to the gravity vector. A theoretically expected bone mass reduction was revealed in the trabecular structures of the bones of the lower part of the skeleton (local osteopenia). In the upper part of the skeleton, an increase in the bone mineral content is observed, which is considered as a secondary response and is due to redistribution of body fluids cephalad. The main cause of osteopenia is mechanical unloading. Arguments are presented that osteocyte osteolysis, delayed osteoblast histogenesis, and osteoclast resorption provoked by rearrangement in the hierarchy of the systems of volume regulation, ion regulation, and the endocrine regulation of calcium homeostasis are the main mechanisms of osteopenia.     

Combination of conjugated linoleic acid with fish oil prevents age-associated bone marrow adiposity in C57Bl/6J mice

The inverse relationship between fat in bone marrow and bone mass in the skeleton of aging subjects is well known. However, there is no precise therapy for the treatment of bone marrow adiposity. We investigated the ability of conjugated linoleic acid (CLA) and fish oil (FO), alone or in combination, to modulate bone loss using 12 months old C57Bl/6J mice fed 10% corn oil diet as control or supplemented with 0.5% CLA or 5% FO or 0.5% CLA+5% FO for 6 months. We found, CLA-fed mice exhibited reduced body weight, body fat mass (BFM) and enhanced hind leg lean mass (HLLM) and bone mineral density (BMD) in different regions measured by dual energy x-ray absorptiometry (DXA); however, associated with fatty liver and increased insulin resistance; whereas, FO fed mice exhibited enhanced BMD, improved insulin sensitivity, with no changes in BFM and HLLM. Interestingly, CLA+FO fed mice exhibited reduced body weight, BFM, peroxisome proliferator-activated receptor gamma and cathepsin K expression in bone marrow with enhanced BMD and HLLM. Moreover, CLA+FO supplementation reduced liver hypertrophy and improved insulin sensitivity with remarkable attenuation of bone marrow adiposity, inflammation and oxidative stress in aging mice. Therefore, CLA with FO combination might be a novel dietary supplement to reduce fat mass and improve BMD.     

Skeletal sensitivity to dietary calcium deficiency is increased in the female compared with the male rat

We investigated potential sex differences in bone resorption and the conservation of whole body bone mass in 24-week-old Sprague-Dawley rats maintained on a 1.0% calcium diet and then fed diets containing 0.02, 0.5, 1.0, or 1.75% calcium for 31 days. Lowering dietary calcium from 1.00% to 0.02% doubled whole skeleton bone resorption (urinary 3H-tetracycline loss). Female rats were more sensitive to calcium stress, exhibiting the maximal resorptive response when fed the 0.5% calcium diet, whereas the 0.02% calcium diet was required to elicit this response in males. Despite the evidence of increased bone resorption, whole skeleton mass was unchanged in females and was significantly increased in males, indicating that switching to even the 0.02% calcium diet did not result in an overt loss of total body bone mass. Compared with controls, the skeleton mass of females (97+/-1.4%) maintained on the 0.02% calcium diet was significantly lower than males (107+/-2.4%), again suggesting a greater impact of calcium deficiency in females. The calculation of the average percentage growth of selected individual bones in male rats indicated a proportional increase in bone mass between the axial and appendicular skeleton of approximately +4% and +18% in animals maintained on 0.02 and 1.75% diets, respectively. By comparison, female rats consuming the 0.02% calcium diet showed an average 14% loss in axial bone and 7.5% gain in appendicular bone mass. The results indicate increased sensitivity to dietary calcium deficiency in female rats which involves a significant loss in axial bone mass not observed in male rats maintained under similar dietary conditions.     

Reproducibility of Dual-Energy X-ray Absorptiometry Measurements in Prepubertal Girls

Objective : Regulation of growth and development, clinical assessment, and obesity are among the areas of nutritionrelated research, wherein accurate assessment of body composition is important. We want to test the hypothesis that dual-energy X-ray absorptiometry (DXA) measurements are reproducible in healthy girls. Research Methods and Procedures : We determined total body composition measurements in healthy prepubertal girls using DXA twice, 6 weeks apart. Results : We studied 61 healthy, normal-weight, prepubertal girls, aged 4.8 years to 10.3 years. The girls' DXA-derived mean weight between visits 1 and 2 significantly increased (27.14 kg vs. 27.80 kg, P<0.0001). The increased weight was due to significant increases in total body fat-free mass (FFM) (19.53 kg vs. 19.89 kg,P<O.001), total body bone mass (1.05 kg vs. 1.07 kg, P<0.0001), and total body fat mass (7.61 kg vs. 7.91 kg,P<0.03). The girls' DXA-derived mean total trunk mass between visits 1 and 2 significantly increased (11.23 kg vs. 11.63 kg, p<<0.0001), as did total leg mass (9.33 kg vs. 9.53 kg, p<<0.001), although no significant differences were observed in total arm mass (2.52 kg vs. 2.54 kg, p< = 0.37). The Pearson coefficient of correlation (r) and total coefficient of variation (CV) for intraindividual measurements by DXA were: weight—r = 0.99, CV= 1.97%; total body FFM—r = 0.96, CV = 2.30%; total body bone mass—r = 0.99, CV = 2.08%; total body fat mass—r = 0.96, CV = 6.55%; percentage total body fat— r = 0.91, CV = 5.69%; total trunk mass—r = 0.96, CV = 3.59%; total arm mass—r = 0.95, CV = 4.09%; and total leg mass—r = 0.99, CV = 2.75%. Discussion : Total body FFM, total body bone mass, total body fat mass, percentage of total body fat mass, as well as regional mass determinations by DXA, were highly reproducible in healthy, normal-weight, prepubertal girls. We highly recommend the use of DXA for total body composition studies in girls aged 5 years to 10 years.     

Benefits of mass reduction for commuting flight with heavy food load in Leach’s storm-petrel,Oceanodroma leucorhoa

When rearing chicks, Leach’s storm-petrels (Oceanodroma leucorhoa) commute between foraging areas and breeding colonies with heavy food loads. At this time they should maximize the size of energy-supplying organs in response to increased energy expenditure but minimize total body mass to decrease the energetic cost of flight. Nineteen storm-petrels were killed to examine the changes in body composition and the masses of energy-supplying organs in birds that were incubating and rearing chicks. Parents lost a mean of 7.95 g in body mass between the stages of incubation and chick-rearing mainly via a loss of skin including subcutaneous adipose tissue, and a small fraction of heart and digestive organs, which are considered energy-supplying organs. This mass loss actually enables them to decrease flight cost by 14.4%. The benefits of decreasing flight costs by reducing total body mass are greater than if the energy-supplying organs of birds are enlarged only.

     

The volume of extracellular fluid under conditions of long-term space flights

The volume of extracellular fluid (the bromine space) was determined in 18 cosmonauts 30 days before the start of a space flight and on the first day after landing. The duration of space flights on the Mir orbital station was from 126 to 438 days. Moreover, the volume of extracellular fluid was determined in seven cosmonauts directly during long-term space flights approximately two weeks before landing. After long-term space flights, the volume of extracellular fluid was decreased in all cosmonauts studied. The bromine space volume was significantly decreased compared to its initial preflight value. A decrease in the volume of extracellular fluid was caused not only by the reduction in the dense mass of the body but also by its dehydration. These processes developed independently of the duration of weightlessness but are mainly determined by the individual features of human beings.     

Intraspecific scaling of flight power in the bat Glossophaga soricina (Phyllostomidae)

Aerodynamic theory predicts that power output during flight should vary with body mass by an exponent of 1.56 when wing morphology remains constant (within an individual), and by an exponent of 1.19 when wing morphology changes with body mass (within a species or between species). I tested these predictions by estimating the power input during horizontal flight in three pregnant and two subadult Glossophaga soricina using a multivariate regression model. This analysis yielded power input during resting and flight as well as the energetic equivalent of change in body mass. A comparison of the estimated flight power for pregnant G. soricina, with published data on flight power of non-pregnant adults, revealed that energy turnover in flight is highest for pregnant G. soricina. Flight power of a 13-g pregnant G. soricina was even higher than that of a 16-g non-pregnant Glossophaga longirostris. A least-squares regression analysis yielded the following equations for the intraspecific scaling of flight power with body mass: power input during horizontal flight (P _f )=24099 body mass (bm; kg)^2.15 (r ²=0.97) for the intra-individual allometry (pregnancy) and P _f =113 bm(kg)^0.95 (r ²=0.99) for the inter-individual allometry (ontogeny). Both mass exponents are not significantly different from the predicted values for the scaling relationship of flight power within an individual (1.56) and within a species (1.19). This is the first measurement of power input during flight for subadult and pregnant bats. Accepted: 11 May 2000     

Lean, fat and bone masses are influenced by orchidectomy in the rat. A densitometric X-ray absorptiometric study

In man, hypogonadism is a risk factor for osteoporosis. Orchidectomy (ORX) in the rat leads to an imbalance between resorption and formation resulting in bone loss. We have measured whole body weight, lean and fat mass, whole bone mass (BMC) in the ORX rat model by dual X-ray densitometry (DXA). Forty-eight male Wistar rats (18-19 weeks old) were studied at 2, 4, 8 and 16 weeks. In each group, 6 rats were ORX and 6 sham-operated were used as control. DXA was performed on the whole body and isolated tibia. The whole body weight of the ORX animals became significantly decreased only at 16 weeks. Whole body BMC was reduced from 8 weeks in the ORX group. The most striking result was a net decrease in lean mass that reached -15.7% at 16 weeks. On the other hand, fat mass remained unchanged during the time series in the ORX animals.     

Bone densitometry: assessing the effects of growth hormone treatment in adults

Dual-energy X-ray absorptiometry (DXA) is the reference method for the measurement of bone mineral mass at different skeletal sites. It has been widely used in recent years to assess the effects of growth hormone (GH) treatment on bone metabolism. In normal individuals, bone mineral content (BMC) and density (BMD), as assessed using DXA, correlate with body size. Therefore, using DXA in patients with congenital GH deficiency (GHD), who have a smaller body frame, would be expected to result in lower bone mass. Thus, comparisons with reference data derived from populations of normal body size are invalid. The evaluation of the effects of GH administration should take into account the possible effects of GH on bone size, not only in children, but also in adults. The enlargement of bone, due to stimulation of the periosteal apposition, may partially mask an increase in BMC, resulting in little or no change in BMD. The ability of GH to affect bone area therefore requires analysis of the possible changes in bone area and BMC, as well as BMD. This issue has been poorly handled in the studies published to date. Lastly, the acceleration of bone turnover induced by GH leads to an increase in bone remodelling space, which in turn is associated with a reduction in BMC and BMD, independent of the net balance between breakdown and formation in each metabolic unit. This bone loss is completely reversible when the remodelling space returns to previous levels. This phenomenon must be taken into account when analysing the effects of GH treatment on bone mass, because a net gain in bone mass may be found in long-term GH treatment or after GH discontinuation, even if bone loss was evident during the first 6 months of treatment. In conclusion, the interpretation of bone density data in patients with GHD, and after GH administration, should take into account some of the methodological aspects of bone densitometry, as well as the specific actions of GH on bone metabolism and body composition.     

Antennae in the hawkmoth Manduca sexta (Lepidoptera, Sphingidae) mediate abdominal flexion in response to mechanical stimuli

Flying insects rely on the integration of feedback signals from multiple sensory modalities. Thus, in addition to the visual input, mechanosensory information from antennae is crucial for stable flight in the hawkmoth Manduca sexta. However, the nature of compensatory reflexes mediated by mechanoreceptors on the antennae is unknown. In this study we describe an abdominal flexion response mediated by the antennal mechanosensory input during mechanical body rotations. Such reflexive abdominal motions lead to shifts in the animal’s center of mass, and therefore changes in flight trajectory. Moths respond with abdominal flexion both to visual and mechanical rotations, but the mechanical response depends on the presence of the mass of the flagellum. In addition, the mechanically mediated flexion response is about 200° out of phase with the visual response and adds linearly to it. Phase-shifting feedback signals in such a manner can lead to a more stable behavioral output response when the animal is faced with turbulent perturbations to the flight path.     

Change of bone mass in postmenopausal Caucasian women with and without hormone replacement therapy is associated with vitamin D receptor and estrogen receptor genotypes

Our purpose is to assess whether genotypes of the vitamin D receptor (VDR) and estrogen receptor (ER) and their interaction influence changes in bone mass in postmenopausal Caucasian women with and without hormone replacement therapy (HRT). A population of 108 US Mid-West women who participated in a study of low-dose continuous estrogen/progestin was genotyped at the VDR BsmI site and the ER XbaI and PvuII sites. Adequate vitamin D and calcium nutritional intakes were assured in all the study subjects. For the 3.5-year duration of the study, we analyzed changes in bone mineral density (BMD) at the spine, femoral neck, distal radius, and the total body (total body bone mineral content, tbBMC). We adjusted for confounding factors, such as age and weight, in the analysis. We found that VDR and/or ER genotypes and/or their interaction generally had significant effects on the changes in the bone mass measurements in both the placebo and HRT groups. When a significant gene-by-gene interaction exists between VDR and ER genotypes, failure to account for them in analyses may yield nonsignificant results, even if significant genotypic effects exist. The amount of variation in changes in bone mass measurements explained by the total genotypic effects of the VDR and ER loci varies from ∼1.0% (for the tbBMC changes in combined placebo and HRT groups) to ∼18.7% (for the spine BMD changes in the HRT group). These results suggest that individual genotypes are important factors in determining changes in bone mass in the elderly with and without HRT and thus may need to be considered with respect to the treatment to preserve bone mass in elderly Caucasian women. Received: 31 July 1998 / Accepted: 11 September 1998     

Validation of DXA Body Composition Estimates in Obese Men and Women

The aim of this study was to determine the accuracy of dual‐energy X‐ray absorptiometry (DXA)‐derived percentage fat estimates in obese adults by using four‐compartment (4C) values as criterion measures. Differences between methods were also investigated in relation to the influence of fat‐free mass (FFM) hydration and various anthropometric measurements. Six women and eight men (age 22–54 years, BMI 28.7–39.9 kg/m², 4C percent body fat (%BF) 31.3–52.6%) had relative body fat (%BF) determined via DXA and a 4C method that incorporated measures of body density (BD), total body water (TBW), and bone mineral mass (BMM) via underwater weighing, deuterium dilution, and DXA, respectively. Anthropometric measurements were also undertaken: height, waist and gluteal girth, and anterior‐posterior (A‐P) chest depth. Values for both methods were significantly correlated (r² = 0.894) and no significant difference (P = 0.57) was detected between the means (DXA = 41.1%BF, 4C = 41.5%BF). The slope and intercept for the regression line were not significantly different (P > 0.05) from 1 and 0, respectively. Although both methods were significantly correlated, intraindividual differences between the methods were sizable (4C‐DXA, range = ?3.04 to 4.01%BF) and significantly correlated with tissue thickness (chest depth) or most surrogates of tissue thickness (body mass, BMI, waist girth) but not FFM hydration and gluteal girth. DXA provided cross‐sectional %BF data for obese adults without bias. However, individual data are associated with large prediction errors (±4.2%BF). This error appears to be associated with tissue thickness indicating that the DXA device used may not be able to accurately account for beam hardening in obese cohorts.