Low muscle mass and sarcopenia: common and predictive of osteopenia in inflammatory bowel disease.

BACKGROUND: Body composition is poorly studied in inflammatory bowel disease (IBD). Sarcopenia describes a loss of muscle mass and strength. AIM: To assess the prevalence of low lean mass (LM), sarcopenia and associated morbidity in an adult IBD cohort. METHODS: Cross-sectional data were gathered on pre-menopausal 18- to 50-year-old patients with IBD. Whole-body dual-energy X-ray absorptiometry, anthropometric assessment and grip strength were performed. Low LM was defined as ≥1 s.d. below the population mean for appendicular skeletal muscle index [ASMI (kg)/height (m)²], and sarcopenia as both ASMI and grip strength ≥1 s.d. below population mean. Multivariate regression analyses were performed. RESULTS: Of 137 participants (median age 31 years, BMI 24.8 kg/m(2) ), 56% were male and 69% had Crohn's disease (CD). Low LM and sarcopenia were observed in 21% and 12% of patients, respectively, and osteopenia/osteoporosis in 38% of patients (mean lumbar spine t-score -0.3 ± s.d. 1.1). Grip strength predicted low LM and sarcopenia better than did body mass index (BMI) (OR 4.8 vs. OR 0.7 for low-LM, P < 0.05 both). Normal BMI was falsely reassuring in 72% and 76% of patients with low ASMI and sarcopenia, respectively. Low LM and sarcopenia (OR = 3.6, P = 0.03; OR = 6.3, P = 0.02; respectively), but not BMI nor fat mass, predicted osteopenia/osteoporosis. CONCLUSIONS: Low lean mass and sarcopenia are common in patients with IBD, and important to recognise as they predict osteopenia/osteoporosis. Grip strength testing should be incorporated into routine clinical practice to detect low lean mass deficits, which may go unrecognised using BMI alone.

Validation of the sheep as a large animal model for the study of vertebral osteoporosis.

Rats have long been the animal of choice for research in the field of osteoporosis. In the search for a complementary large animal model the sheep appears useful but hitherto the extent of bone loss from the spine has failed to reach a level that is generally accepted as osteoporotic in humans. Osteoporosis was induced in ten sheep using ovariectomy, low calcium diet and steroid injection for 6 months. Bone samples of iliac crest (IC), lumbar spine (LS), and proximal femur (PF) from the osteoporotic sheep were compared with those from four normal sheep using densitometry, histomorphometry, biochemistry and basic mechanical testing. The differences were examined using an analysis of variance with Tukey-Kramer test. Overall, the bone mineral density at LS and PF decreased more than 25% after treatment. Trabecular bone volume decreased by 29.2, 33.4 and 42.6% in IC, LS and PF, respectively. The failure load of the LS in axial compression was reduced to 2,003 from 6,140 N. The extent of bone loss was sufficient to categorise these sheep as osteoporotic although the pattern of bone loss varied between sites. Reduced mechanical competence in LS confirmed the suitability of this model for evaluation of potential treatments for osteoporosis.

Resting metabolic rate, body composition and aerobic fitness comparisons between active and sedentary 54-71 year old males.

OBJECTIVE: To test the hypothesis that 55-70 y old male longterm exercisers (LE) have higher resting metabolic rates (RMR) than longterm nonexercisers (LNE). DESIGN: A power analysis demonstrated that this cross-sectional study required 12 subjects per group to detect a 10% RMR difference (kJ x kg FFM(-1) x d(-1)) between the LE and LNE (power = 0.8;alpha = 0.05). SUBJECTS: Twelve LE (X +/- s.d.; 63.5+/-3.4 y; 1.75+/-0.06 m; 69.01+/-8.24 kg; 20.4+/-4.9 %BF) and 12 LNE (63.6+/-5.6 y; 1.72+/-0.07 m; 79.44 12.4 kg; 29.6 4.4 %BF) were recruited from advertisements placed in a newspaper and on university and community noticeboards. INTERVENTIONS: Measurements were conducted for: RMR using the Douglas bag technique; body composition via a four compartment model which is based on determination of body density, total body water and bone mineral mass; and aerobic fitness using a submaximal work test on a cycle ergometer. RESULTS: The LE (93.00+/-7.16 kJ x kg(-1) x d(-1)) registered a significantly greater (P = 0.04) RMR than the LNE (84.70+/-11.23 kJ x kg(-1) x d(-1)) when energy expenditure was expressed relative to body mass, but this difference disappeared (P = 0.55) when the data were corrected for the non-zero intercept of the graph of RMR (MJ/d) against body mass. ANCOVA with FFM as the covariate also indicated that the RMR (MJ/d) difference between the groups was not statistically significant (P = 0.28). The adjusted means for the LE and LNE were 6.39 and 6.62 MJ/d, respectively. CONCLUSIONS: There are no RMR (MJ/d) differences between LE and LNE 54-71 y old males when statistical control is exerted for the effect of FFM and the higher value of the former group for RMR normalised to body mass disappears when this ratio is corrected for statistical bias.

Effect of 3 weeks of detraining on the resting metabolic rate and body composition of trained males.

OBJECTIVE: To examine the hypothesis that detraining decreases the resting metabolic rate (RMR) of long-term exercisers. DESIGN: Eight pairs of subjects were matched for age, mass and training volume. They were then randomly allocated to either a control group (continue normal training) or detraining group (stop normal training but continue activities of daily living). SETTING: Exercise Physiology Laboratory, The Flinders University of South Australia. SUBJECTS: Sixteen male subjects (age 23.1 +/- 4.7 y (s.d.); mass 73.73 +/- 8.9 kg; VO2max 60.2 +/- 6.3 ml. kg-1.min-1; height 180.3 +/- 5.0 cm; body fat 14.6 +/- 5.4%) were selected from a pool of respondents to our advertisements. INTERVENTIONS: Each pair of subjects was measured before and after a 3-week experimental period. RESULTS: Two (groups) x 3 (2-, 3-and 4-compartment body composition models) ANOVAs were conducted on the difference between the pre- and post-treatment scores for percentage body fat, fat-free mass (FFM) and relative RMR (kJ.kg FFM-1.h-1). No significant between-group differences were identified except for the detraining group's small decrease in FFM (0.7 kg, P = 0.05). The main effects for body composition model were all significant; but the overall differences between the multicompartment models and the 2-compartment one were less than their technical errors of measurement. No significant interaction (P = 0.51) resulted from a 2 x 2 ANOVA on the pre- and post-treatment absolute RMR data for the control (315.2 and 311.9 kJ/h) and detraining groups (325.4 and 325.5 kJ/h). CONCLUSIONS: 3-weeks detraining is not associated with a decrease in RMR (kJ/h, kJ.kg FFM-1.h-1) in trained males; hence, our data do not support a potentiation of the RMR via exercise training. The greater sensitivity of the multicompartment models to detect changes in body composition was of marginal value.

Comparisons of two-, three-, and four-compartment models of body composition analysis in men and women.

This study compared the traditional two-compartment (fat mass or FM; fat free mass or FFM) hydrodensitometric method of body composition measurement, which is based on body density, with three (FM, total body water or TBW, fat free dry mass)- and four (FM, TBW, bone mineral mass or BMM, residual)-compartment models in highly trained men (n = 12), sedentary men (n = 12), highly trained women (n = 12), and sedentary women (n = 12). The means and variances for the relative body fat (%BF) differences between the two- and three-compartment models [2.2 +/- 1.6 (SD) % BF; n = 48] were significantly greater (P

Body composition changes in elite male bodybuilders during preparation for competition.

Anthropometric profiles together with a 4 compartment criterion model of body composition analysis (total body water, bone mineral, fat and residual masses via a combination of deuterium dilution, dual-energy x-ray absorptiometry and hydrodensitometry) were conducted on 3 elite male bodybuilders 10 wk and then 5 d before competition. A mean body mass reduction from 99.70 (Quetelet's Index = 31.6 kg/m2) to 92.79 kg (Quetelet's Index = 29.2 kg/m2) was accompanied by a decline in the sum of 8 skinfold thicknesses (triceps, subscapular, biceps, iliac crest, supraspinale, abdominal, front thigh and medial calf) from 51.1 to 36.7 mm. The 4 compartment body composition model indicated that there were reductions of: percent body fat (%BF) from 9.1 to 5.0%, fat free mass (FFM) from 90.60 to 88.14 kg and fat mass (FM) from 9.10 to 4.65 kg. Sixty-four percent of the 6.91 kg loss in body mass therefore came from the FM. The 2 compartment hydrodensitometric model yielded higher %BFs (initial = 11.2; final = 7.1) than the 4 compartment model (initial = 9.1; final = 5.0) which is theoretically more valid because it controls for biological variability in the percentages of water and bone mineral in the FFM. Nevertheless, both models registered decreases of 4.1%BF.

Regional bone mineral density interrelationships in normal and osteoporotic postmenopausal women.

We describe a prospective study in which bone mineral density (BMD) was measured in total body and regions, proximal femur, lumbar spine, and forearm in 84 apparently normal postmenopausal women with normal spinal radiographs and in 47 women with 1-10 wedged or compressed vertebrae. There was a history of peripheral fracture in 35 of the 84 controls and 30 of the 47 osteoporotics (p < 0.02) but there was no association between vertebral fracture and wrist fracture. At all sites and regions, the differences in BMD between the "normal"and "osteoporotic" women was highly significant and all but "ribs" and "arms" remained significant after correction for menopausal age. In the whole set, and in both subgroups, the coefficients of correlation between sites and regions were all highly significant (p < 0.001). Nonetheless, some sites discriminated better between the two groups than others. Standardized odds ratios (OR) for vertebral fracture versus no-fracture were calculated by logistic regression and expressed as the rise in OR for each standard deviation (SD) fall in bone density. This ratio was greatest (3.4) in "pelvis" and weakest (1.7) in "ribs" but all were statistically significant. Geometric mean regression equations were calculated for all the 78 possible pairs of sites and regions in the 84 normal subjects and the deviations of the osteoporotic women from these normal slopes calculated. In most pairs of sites and regions, the vertebral fracture cases were scattered around the normal group's slope but fell lower down on both axes. The bone deficits in the osteoporotics compared with young normal women ranged from -14% in "head" to -40% in Ward's triangle and the T-scores ranged from -1.9 in "ribs" to -3.9 in the forearm. Sensitivity ranged from 17% in "ribs" to 36.2% in Ward's triangle. Specificity varied between 88 and 94% and the percent correctly classified ranged from 62.6% in "ribs" to 72.5% in Ward's triangle. We conclude that primary postmenopausal osteoporosis affects the entire skeleton but that some sites discriminate better between vertebral fracture and nonfracture cases regardless of whether they represent cortical or trabecular bone.

Collateral axonal projections from ventrolateral medullary non-catecholaminergic neurons to central nucleus of the amygdala.

Retrograde tract-tracing techniques were used to investigate whether catecholaminergic neurons in the ventrolateral medulla (VLM) send collateral axonal projections to both central nuclei of the amygdala (ACe) in the rat. Rhodamine-labelled latex microspheres or fluorogold (2%) were microinjected into the region of either the right or left ACe. After a survival period of 10-12 days, the rats were sacrificed and transverse sections of the brainstem were processed immunohistochemically for the identification of cell bodies containing the catecholamine biosynthetic enzymes tyrosine hydroxylase (TH) or phenylethanolamine-N-methyltransferase (PNMT). Neuronal perikarya containing the retrogradely transported tracers were observed throughout the rostrocaudal extent of VLM, bilaterally. Approximately 10% of the retrogradely labelled neurons were observed to contain both retrograde tracers. The majority (79 +/- 6.8%) of these double labelled neurons were located within the caudal VLM and their number decreased rostrally. In addition, the proportion of double labelled neurons to single labelled neurons in VLM decreased rostrally; approximately 11% in the caudal VLM and 6% in the rostral VLM. Furthermore, approximately 21% of all VLM neurons that projected to ACe were found to be catecholaminergic: 75% of these were immunoreactive to TH and 25% to PNMT. However, no neurons were found in VLM that contained both retrograde tracers and immunoreactivity to TH or PNMT. These data demonstrate that axons originating from non-catecholaminergic neurons in VLM bifurcate to innervate ACe bilaterally. Although the function of these VLM neurons that project to both ACe is not known, they may be the anatomical substrate by which VLM neurons relay simultaneously autonomic and/or visceral sensory information to influence the activity of ACe.

A comparison of four methods of estimating the body composition of male endurance athletes.

Comparisons were effected of the following four methods of estimating the percent body fat (%BF) of 12 highly trained male endurance athletes (mean +/- SD = 2.20 +/- 4.9 years, 176.8 +/- 5.9 cm 64.2 +/- 6.4 kg): underwater weighing (UWW), total body water (TBW), total body potassium (TBK) and dual-energy X-ray absorptiometry (DEXA). The DEXA mean of 6.8% BF was significantly less (P < 0.05) than those estimated via UWW: 9.7% BF; TBW: 10.6% BF (fat-free mass of FFM = 72.0% H2O); and TBK: 9.7% BF (FFM = 66.6 mmol K.kg-1). Nevertheless, the DEXA % BF correlated 0.746 and 0.737 (both P < 0.01) with those from UWW and TBW, respectively; these were the only correlation coefficients to attain statistical significance (P < or = 0.05). Despite the similar means for UWW, TBW and TBK, 12 of the 36 individual differences between these three methods ranged from 3.2 to 10.4% BF. A critical assumption of UWW, which is regarded by many as the criterion method for the estimation of % BF, is that the FFM has a density of 1.100 g.cm-3. Use of in vivo-measured TBW and bone mineral (via DEXA) for the computation of FFM densities for our subjects, while assuming that the two other components of the FFM (protein and non-bone mineral) remained constant, resulted in scores ranging from 1.09541 to 1.10246 g.cm-3 (mean +/- SD = 1.09881 +/- 0.00254 g.cm-3). FFM and % BF differences between use of a constant FFM density of 1.100 g.cm-3 and the individual values ranged from -1.02 to 0.57 kg (mean +/- SD = -0.28 +/- 0.60 kg) and from -0.9 to 1.7% BF (mean +/- SD = 0.5 +/- 0.9% BF), respectively. It may be concluded that with young male athletes: (1) use of constants based on normal male cadavers yielded similar group means for % BF determined by UWW, TBW and TBK but the DEXA % BF correlated significantly with those from UWW and TBW; and (2) in vivo measurements of individual differences in TBW and bone mineral support the use of conventional UWW for the estimation of % BF.

Correlations between the mechanical properties, radiology and histomorphometry of human femoral bone.

Initial fixation of the femoral components of total hip replacements is related to the mechanical integrity of the bone within the proximal femur. This preliminary study examined the correlations between the mechanical properties, histomorphometry, and radiology of bone core specimens taken from the proximal femora of cadavers and of patients undergoing total hip replacement surgery. Measurements and subjective assessments of the femoral bone from radiographs were shown to have poor correlation with both compressive mechanical properties and bone volume measurements. However, the mechanical properties of the bone core specimens and the histomorphometric measurements correlated well with the bone density measured by single-photon absorptiometry, indicating that this type of imaging technique may be of value in determining bone quality prior to surgery. The prediction of the mechanical properties of the proximal femur by preoperative imaging may have direct bearing on the type of femoral component to be used in total hip replacement. Preoperative assessment of bone quality would allow the surgeon to predict the likely fixation obtainable with different designs.

Normal cytogenetic values for bone marrow based on studies of bone marrow transplant donors.

For individuals suspected of having hematologic neoplasms, interpretation of the clinical significance of sporadic cells with chromosome breakage, structural anomalies, aneuploidy, or polyploidy is often difficult. To help resolve this problem, we established normal cytogenetic values for bone marrow (BM) by investigating 219 BM transplant (BMT) donors using standard techniques for chromosome analysis. The donors ranged in age from 2 to 58 years and were studied for 7 years. The constitutional karyotype for two individuals was 47,XXY; one was mos45,X/46,XX, one was mos46,XX/47,XX, + mar, and 215 were normal. Among other statistics, the median and normal ranges (95th percentile) were determined for any kind of chromosome abnormality, autosomal loss, autosomal gain, sex chromosome loss, sex chromosome gain, chromosome breaks or gaps, major structural abnormalities, and polyploidy. The results suggest that random loss of chromosomes is common in cytogenetic preparations of BM, appears to be largely technical and is inversely proportional to chromosome size. Cells with extra chromosomes or with structural abnormalities are rare in normal BM. No specific sporadic structural abnormalities of chromosomes are associated with normal BM. The widely accepted cytogenetic definition for an abnormal clone appears to be valid, with the possible exception of occasional studies involving loss of smaller autosomes. There may be a correlation between loss of the Y chromosome and age of the patient.

Frequent occurrence of cytogenetic abnormalities in sporadic nonmedullary thyroid carcinoma.

Cytogenetic studies may provide important clues to the molecular pathogenesis of thyroid neoplasia. Thus, the authors attempted cytogenetic studies on 12 thyroid carcinomas: seven papillary, three follicular, and two anaplastic. Successful cytogenetic results were obtained on all 12 tumors; nine (75%) had one or more chromosomally abnormal clones. Four of the papillary carcinomas had a simple clonal karyotype, and three had no apparent chromosome abnormality. All four abnormal papillary tumors contained an anomaly of a chromosome 10q arm. In one instance, an inv(10)(q11.2q21.2) was observed in a Grade 2 papillary carcinoma as the sole acquired abnormality. In another case, an inversion or insertion involving 10q21.2 was found in a Grade 1 papillary tumor. The karyotype of a third tumor, a Grade 1 papillary carcinoma, was 46,XX,der(5)t(5;10)(p15.3;q11),der(9)t(9;?)(q11;?). A fourth abnormal papillary carcinoma, a Grade 1 tumor, had a t(6;10)(q21;q26.1) as the sole abnormality. Each of the five follicular or anaplastic carcinomas had a complex clonal karyotype. The three follicular carcinomas contained an abnormality of 3p25-p21, along with several other chromosome abnormalities.

A cytogenetic study of 53 human gliomas.

Cytogenetic studies were performed on human glioma samples obtained by stereotactic biopsy, stereotactic craniotomy, or routine craniotomy. Using in situ culture and robotic harvesting techniques, we obtained suitable metaphases in 50 (94%) of 53 tumors, including 28 diffuse astrocytomas, four juvenile pilocytic astrocytomas, two gliosarcomas, three other miscellaneous astrocytomas, eight oligodendrogliomas, four mixed oligodendroglioma-astrocytomas, and four ependymomas. Cytogenetic studies were performed only on primary cultures; the mean culture time was 9.6 days (range 1-31 days). One or more chromosomally abnormal clones were observed in 35 (66%) tumors. Eleven (21%) other specimens had random nonclonal chromosome abnormalities. In four (8%) specimens, no chromosome abnormalities were noted. The results of this study suggest that grade 3 and 4 tumors are more likely to contain an abnormal clone than tumors of grade 1 or 2 (p less than 0.01). The most common numeric chromosome abnormalities were -6, +7, -10, -13, -14, -15, -18, and -Y. The most common structural abnormalities involved 1p, 6q, 7q, 8p, 9p, 11p, 11q, 13q, and 19q. Four tumors had two or more independent clones and ten contained subclones demonstrating karyotype evolution. With in situ culture and robotic harvesting techniques, cytogenetic studies can be successful on nearly all human gliomas, including those derived from small stereotactic biopsies.