Comparison of dual-photon absorptiometry systems for total-body bone and soft tissue measurements: dual-energy X-rays versus gadolinium 153.

A total of 81 subjects (41 males and 40 females) were scanned by dual-photon absorptiometry by 153Gd source (DPA; Lunar DP4) and by dual-energy x-ray absorptiometry (DEXA; Lunar-DPX) within a 24 h period. Total-body bone mineral density (TBMD), calcium content (Ca), and soft tissue mass (ST) were determined with a precision of about 1-1.5% using DPA and 0.5-1.0% using DEXA. Measurements of TBMD, Ca, ST, bone area (area), percentage fat, and regional bone mineral densities (BMD) were compared. Paired t-tests showed small but significant differences between all measurements. Correlations (r) for TBMD, Ca, area, ST, percentage fat, arm BMD, leg BMD, and trunk BMD were 0.99, 0.99, 0.97, 0.99, 0.97, 0.99, 0.99, and 0.98. There were small systematic differences for TBMD (less than 1%), calcium (3%), bone area (3%), soft tissue mass (7%), and percentage fat (9%) between the two approaches. Regression equations are given relating these measurements.

Bone mineral density and mass in a cross-sectional study of white and Asian women.

The literature suggests that Asians have lower bone mineral density and mass than whites. It has been proposed that these differences may be due to differences in height, weight, and factors other than ethnicity, but no study has made the appropriate direct comparisons. We compared total-body bone mineral density and mass between Asian and white women while controlling for factors known to be associated with bone mineral density and mass. Measurements were made in 129 Asian (primarily of Chinese ancestry) and 274 white women. A subgroup was formed of women who did not have a history of alcoholism, premenopausal amenorrhea, kidney disease, estrogen use, birth control pill use, thyroid disease, steroid use, hysterectomy, or smoking. In both the main group and the subgroups, bone mineral mass was significantly lower in Asian than in white women, but after analysis of covariance with body weight, height, and age (or years since menopause) as covariates, the differences between ethnic groups disappeared, except in the large group of premenopausal women, in whom average bone mineral density in Asians actually exceeded (p < 0.04) that in whites. The data set was also searched for Asian-white pairs who matched on 17 characteristics related to bone mineral density and mass. In the resulting 16 matched pairs, bone mineral density and mass were not different between ethnic groups. Although Asian women have lower bone mineral mass than white women, when weight, height, and other factors are controlled, bone mineral density and mass do not differ between Asian and white women.

Bone mineral density and mass by total-body dual-photon absorptiometry in normal white and Asian men.

Total body bone mineral density, total body bone mineral mass (TBBM), and bone mineral densities (BMD) in seven different regions of the body were measured in 238 normal men (154 Whites and 84 Asians), age 22-94, using dual-photon absorptiometry. Although Asian men had lower TBBM and BMD in all regions (p less than 0.05) except the arms, when multiple regression was done with body weight, height, and age, no significant differences were found between Asians and Whites for bone measurements. Thus lower bone mineral densities and bone mineral mass in Asian males compared to White males appear to be due to differences in height and weight rather than to ethnic differences. The two groups were combined to derive multiple regression equations for TBBM, total-body BMD, and regional BMD. Age, weight, and height were significant in the multiple regression equations for TBBM, ribs BMD, and legs BMD. Age and weight, but not height, were significant for total-body BMD, trunk BMD, spine BMD, arm BMD, and pelvis BMD. Weight, but neither height nor age, was significant for head BMD. These reference normal bone mineral density and bone mineral mass standards are appropriate for both Asian and White males when adjusted for weight, height, and age.

A multicenter comparison of dual-energy X-ray absorptiometers: in vivo and in vitro measurements of bone mineral content and density.

As part of a multicenter research project, we compared dual-energy X-ray absorptiometry (DXA) instruments at three research centers (sites 1, 2 and 3) to determine both intra- and intersite variability of bone mineral content (BMC), bone mineral density (BMD), and bone area (BA). Scans of the total body and lumbar spine were performed in duplicate on five humans (in vivo), and scans of the total body were performed on two whole body phantoms with artificial skeletons and thickness overlays (in vitro) at all sites over 15 days. The average intrasite variability in two consecutive total body BMD measurements, expressed as a percent difference, was significantly higher in vitro, 1.74 +/- 1.97%, than in vivo, 0.71 +/- 0.38% (p < 0.05). Average intrasite variability of the in vivo lumbar spine BMD was 1.08 +/- 1.12%. The intersite coefficients of variation for all BMD, BMC, and BA measurements were < 2.0%. The total body BMD from site 2 was systematically lower than at sites 1 and 3 both in vivo and in vitro (p < 0.05) with no differences in BMC and BA. Although significant, the total body BMD differences between sites were small (< 1.2%) in vivo compared with in vitro (< 2.6%) and are encouraging for the comparison and pooling of human data from multicenter trials, provided that appropriate standardized cross-calibration and analysis procedures are applied.

In vivo semiquantification of hypothalamic growth hormone-releasing hormone (GHRH) output in humans: evidence for relative GHRH deficiency in aging.

GH secretion declines with aging. The neuroendocrine mechanisms of somatopause are uncertain. To semiquantify endogenous hypothalamic GHRH output, we measured the suppressibility of spontaneous and GHRH-stimulated GH secretion by graded doses of a specific competitive GHRH receptor antagonist (N-Ac-Tyr1,D-Arg2)GHRH-(1-29) in healthy young and elderly men. Nocturnal GH was about 30% lower in the elderly than in the young. Graded boluses of GHRH elicited dose-dependent GH responses, with no difference between the two age groups. Graded infusions of GHRH antagonist suppressed GH responses to GHRH in a dose-dependent manner, but with similar potency in both groups. The degree of inhibition depended on the magnitude of GHRH bolus: the dose-inhibition curves for the low GHRH boluses were shifted to the left compared to those with the high GHRH bolus (P = 0.01). Similarly, the dose-inhibition curve for spontaneous GH secretion was shifted to the left for the elderly compared to the young men (P = 0.01). Thus, the model of graded infusions of GHRH antagonist differentiates between different amounts of GHRH presented to the pituitary, permitting semiquantification of the endogenous hypothalamic GHRH output in vivo. Our data suggest that there is an age-dependent decrease in the endogenous hypothalamic GHRH output contributing to the age-associated GH decline.

Peak bone mass in young healthy men is correlated with the magnitude of endogenous growth hormone secretion.

GH plays a key role during adolescence in longitudinal bone growth and the attainment of peak bone mass. We explored the hypothesis that in early adulthood, bone mineral accretion and/or maintenance in men with normal GH and bone mineral status are related to the magnitude of endogenous GH secretion. Overnight plasma GH concentrations (sampled every 10 min from 2100-0500 h) were measured in 15 healthy, lean, Caucasian men (age, 24+/-1 yr; body mass index, 22.6+/-0.6 kg/m2; mean +/- SE). Total body, femur, and lumbar spine bone mineral mass/density were measured by dual energy x-ray absorptiometry. Total body and femoral bone mineral mass correlated with both total nocturnal GH and maximal GH concentrations even when bone mineral mass was adjusted by height (P = 0.005-0.02; r = 0.58-0.74). Neither spinal nor total body bone mineral density (BMD) correlated with GH. Maximum GH correlated with the BMD of all four femoral sites (P = 0.01-0.04; r = 0.55-0.66), whereas total nocturnal GH correlated with only one (trochanter; P = 0.01; r = 0.64) femoral site. Our data support the hypothesis that GH continues to play a role in the accretion and/or maintenance of bone mass in young men. This relationship is more evident in the bone mineral mass achieved than in the BMD.

Semiquantification of hypothalamic GH-releasing hormone output in women: evidence for sexual dimorphism in the mechanism of the somatopause.

The neuroendocrine mechanisms underlying the decline of GH with aging (somatopause) are uncertain. We recently found that the age-dependent diminution of the hypothalamic GH-releasing hormone (GHRH) output contributes to the somatopause in men. As the regulatory mechanisms of GH secretion are sexually dimorphic, we assessed the suppressibility of spontaneous and GHRH-stimulated GH secretion by graded doses of a specific competitive GHRH receptor antagonist in nine young (20-27 yr old) and eight elderly (65-77 yr old) healthy nonobese women to semiquantify hypothalamic GHRH output. Nocturnal mean GH was lower in elderly women (2.2 +/- 0.4 vs. 0.9 +/- 0.2 microg/liter; P = 0.01). Graded boluses of GHRH-44 resulted in similar GH responses in both populations (P = 0.28). Graded infusions of GHRH antagonist inhibited in a dose-dependent manner the GH responses to GHRH in both groups (P = 0.0001-0.04). The dose-inhibition curve for the lowest GHRH bolus dose was shifted to the left compared with the highest one (P = 0.04). However, the dose-inhibition curves for spontaneous GH secretion were not different in young and elderly women (P = 0.50). Thus, the female somatopause is not associated with a measurable decrease in hypothalamic GHRH output. When the dose-inhibition curves for young men and young women were compared, the latter was shifted to the left (P = 0.009), suggesting that the somatotropic system in women operates with less GHRH. We conclude that the contribution of endogenous GHRH to the maintenance of GH secretion and the neuroendocrine mechanisms of somatopause in humans are sexually dimorphic.

Aging-related growth hormone (GH) decrease is a selective hypothalamic GH-releasing hormone pulse amplitude mediated phenomenon.

BACKGROUND: Aging is accompanied by declining growth hormone (GH) and insulin-like growth factor-I (IGF-I) levels. The neuroendocrine mechanisms of this decline have been studied previously, but the interpretation of the data was confounded by the imprecision in GH measurements and by the intervening variables of altered body composition and decreased gonadal steroid milieu in the elderly subjects of both sexes. METHODS: To study the contribution of aging per se, we evaluated discrete parameters of GH pulsatility in young (n = 8 women, n = 8 men) and elderly (n = 11 women, in 10 men) subjects closely matched for body mass index. Blood samples for GH were obtained every 10 minutes for 24 hours. Plasma GH was measured by a sensitive chemiluminescent assay. GH pulsatility was assessed using cluster analysis. RESULTS: The elderly subjects had plasma IGF-I levels and integrated GH concentrations that were 32% to -56% of their sex-matched younger counterparts. The age-associated attenuation in GH was due to a decrease in GH pulse amplitude, whereas pulse frequency and nadir levels were unchanged. The majority of the young subjects (81%) reached their peak GH during the "lights off" period, whereas the majority of the elderly subjects (62%) peaked during the "lights on" period (p = .01). CONCLUSIONS: We conclude that aging in both sexes is accompanied by profound decreases in GH output and in plasma IGF-I concentrations. This effect is separate from the alterations in body mass index that accompany the normal aging process. Attenuation of GH output associated with aging is related solely to the lower GH and, by inference, GH-releasing hormone (GHRH) pulse amplitude.

A multi-center comparison of dual energy X-ray absorptiometers: in vivo and in vitro soft tissue measurement.

OBJECTIVE: To assess intra- and inter-site soft tissue variability by dual energy X-ray absorptiometry (DXA). DESIGN: Cross-sectional trial. SETTING: Three medical research institutions. SUBJECTS: Five humans (in vivo) and four phantoms (in vitro), configured from two whole body phantoms with artificial skeletons and thickness overlays. INTERVENTIONS: Duplicate total-body DXA scans were performed on all subjects at each institution within a 15 d period. RESULTS: All intra-site coefficients of variation (CV) were < 0.5% for total tissue mass, but in vitro and in vivo Cvs were 7.2% and 2.3% for fat mass (FM) and 2.5% and 0.9% for lean mass (LM), respectively. Several total-body and regional FM and LM measurements were significantly different between sites (P < 0.05), with percent differences between sites ranging from 2.6-13.3% for FM and from 1.6-13.6% for LM. Site 2 was consistently lower for FM and Site 3 was consistently lower for LM. CONCLUSIONS: These results stress the need for both rigorous and standardized cross-calibration procedures for soft tissue measurement by DXA.

Longitudinal changes in body composition in women approaching the midlife.

This population-based longitudinal study describes the 4.5-year changes in body composition and body mass distribution in women aged 20-45 years, and characterizes predictors of these changes. Body weight, waist-to-hip ratio, Quetelet index, fat and lean body mass were measured in 404 white menstruating women aged 20-40 at baseline and 4.5 years later (follow-up). Variables considered for predicting body composition differences were hormonal status, menstrual status, parity, diet and physical activity. Average body weight increased 4.3 kg in 4.5 years (6.4 kg increase in fat and 2.1 kg decrease in lean)--a net increase of 7.1% total body fat. Measured predictors were not significantly associated with weight or Quetelet index; however, they were associated with measured amounts of lean and fat. Longitudinally, women who preserved the most lean body mass tended to be nulliparous, to be still menstruating, to have higher testosterone levels, and to smoke. Physical activity was associated with preserving lean body mass. Increasing age and higher follicle-stimulating hormone levels were associated with increasing waist-to-hip ratio. Average body weight showed a steady increase--characterized by an expanding fat compartment and a shrinking lean compartment--with the older women increasing more in waist girth relative to hip girth than younger women. Predictor variables of these changes included hormonal environment, physical activity, smoking behaviour, parity, and oophorectomy.

Measuring body fat: calibrating the rulers. Intermethod comparisons in 389 normal Caucasian subjects.

A systematic study of 389 normal Caucasians stratified for sex and age compared all of the traditional methods for measuring fat: body water, underwater weighing, body potassium, and anthropometrics and the newer methods of dual-photon absorptiometry, bioimpedance analysis, and total body electrical conductivity. Measurements by all methods are highly intercorrelated, but methods differences show the population means for fat percent to range from 26 to 35% of body weight across eight methods. All methods show increasing fat (as % body weight) with age in both sexes but vary in secular slope. The goal of this report is to provide direct translations between each of the eight methods. Intermethod comparison equations are given as simple linear regressions by using each method both as dependent and independent variable for each sex, permitting translation for results by any method to any other.

Elevated parathyroid hormone-related peptide associated with lactation and bone density loss.

OBJECTIVE: To investigate the hypothesis that parathyroid hormone-related peptide (PRHrP) may be involved with bone loss and recovery as a means of providing adequate calcium and phosphate to infants. DESIGN: An 18-month prospective cohort study. SETTING: General community setting with recruitment occurring at birthing education classes. PARTICIPANTS: Volunteer sample of 115 postpartum healthy women aged 20 to 40 years, and 0 or 1 parity prior to parturition with no intent to breast-feed or intent to breast-feed at least 6 months. MAIN OUTCOME MEASURES: Parathyroid hormone-related peptide, prolactin, estradiol, 1,25-dihydroxyvitamin D, 24-hydroxyvitamin D, femoral bone mineral density, and bone turnover markers were measured in 115 postpartum women at 2 weeks, 2 months, 4 months, 6 months, 12 months, and 18 months postpartum. Lumbar bone mineral density was measured at 2 weeks, 6 months, 12 months, and 18 months postpartum. RESULTS: Elevated PTHrP values were significantly associated (P<.001) with breast-feeding status, elevated prolactin levels, and lower serum estradiol levels, conditions occurring during lactation. Furthermore, elevated PTHrP levels were negatively and significantly associated (P<.01) over time with bone mineral density change at both the spine and the femoral neck, even after accounting for prolactin levels, breast-feeding status, return of menstruation, estradiol levels, PTH levels, 1,25-dihydroxyvitamin D levels, dietary calcium intake, physical activity, and body size. CONCLUSION: These data clearly support the hypothesis that PTHrP is an alternative mechanism associated with bone loss and recovery during and subsequent to lactation.

Generation of growth hormone pulsatility in women: evidence against somatostatin withdrawal as pulse initiator.

To test whether endogenous hypothalamic somatostatin (SRIH) fluctuations are playing a role in the generation of growth hormone (GH) pulses, continuous subcutaneous octreotide infusion (16 microg/h) was used to create constant supraphysiological somatostatinergic tone. Six healthy postmenopausal women (age 67 +/- 3 yr, body mass index 24.7 +/- 1.2 kg/m(2)) were studied during normal saline and octreotide infusion providing stable plasma octreotide levels of 2,567 +/- 37 pg/ml. Blood samples were obtained every 10 min for 24 h, and plasma GH was measured with a sensitive chemiluminometric assay. Octreotide infusion suppressed 24-h mean GH by 84 +/- 3% (P = 0.00026), GH pulse amplitude by 90 +/- 3% (P = 0.00031), and trough GH by 54 +/- 5% (P = 0.0012), whereas GH pulse frequency remained unchanged. The response of GH to GH-releasing hormone (GHRH) was not suppressed, and the GH response to GH-releasing peptide-6 (GHRP-6) was unaffected. We conclude that, in women, periodic declines in hypothalamic SRIH secretion are not the driving force of endogenous GH pulses, which are most likely due to episodic release of GHRH and/or the endogenous GHRP-like ligand.