Bone mineral density discordance and exploration of one of its causes.

Discordances between hip and spine areal density T-score values are common and incompletely understood. In a cohort of 1157 postmenopausal women, discordances of greater than 10% occurred in 91%, with spine bone mineral density (BMD) T-scores significantly less negative than femoral neck (FN) T-scores (p<0.001). However, when T-scores based on bone mineral content (BMC) rather than BMD were used, the mean discordance was not significantly different from 0. This was largely because BMC at the FN had seemingly declined with age less rapidly than had BMD at that site. This can be explained by age-related areal expansion at the hip, which would be missed in the reported BMD output. One consequence is that if BMC-based T-scores are used to classify patients, substantially fewer individuals would have been judged osteoporotic in this cohort (two-thirds fewer for spine and three-fourths fewer for hip).

Vitamin D and calcium supplementation reduces cancer risk: results of a randomized trial.

BACKGROUND: Numerous observational studies have found supplemental calcium and vitamin D to be associated with reduced risk of common cancers. However, interventional studies to test this effect are lacking. OBJECTIVE: The purpose of this analysis was to determine the efficacy of calcium alone and calcium plus vitamin D in reducing incident cancer risk of all types. DESIGN: This was a 4-y, population-based, double-blind, randomized placebo-controlled trial. The primary outcome was fracture incidence, and the principal secondary outcome was cancer incidence. The subjects were 1179 community-dwelling women randomly selected from the population of healthy postmenopausal women aged >55 y in a 9-county rural area of Nebraska centered at latitude 41.4 degrees N. Subjects were randomly assigned to receive 1400-1500 mg supplemental calcium/d alone (Ca-only), supplemental calcium plus 1100 IU vitamin D3/d (Ca + D), or placebo. RESULTS: When analyzed by intention to treat, cancer incidence was lower in the Ca + D women than in the placebo control subjects (P < 0.03). With the use of logistic regression, the unadjusted relative risks (RR) of incident cancer in the Ca + D and Ca-only groups were 0.402 (P = 0.01) and 0.532 (P = 0.06), respectively. When analysis was confined to cancers diagnosed after the first 12 mo, RR for the Ca + D group fell to 0.232 (CI: 0.09, 0.60; P < 0.005) but did not change significantly for the Ca-only group. In multiple logistic regression models, both treatment and serum 25-hydroxyvitamin D concentrations were significant, independent predictors of cancer risk. CONCLUSIONS: Improving calcium and vitamin D nutritional status substantially reduces all-cancer risk in postmenopausal women. This trial was registered at clinicaltrials.gov as NCT00352170.

Vitamin D status in a rural postmenopausal female population.

BACKGROUND: Inadequate vitamin D nutritional status is increasingly recognized as common in North American and European populations, but the extent of the shortfall and the parameters of the distribution for populations of interest remain uncertain. PURPOSE: To report the distribution of values for serum 25-hydroxyvitamin D [25(OH)D] in a population of rural postmenopausal women, together with quantification of factors related to vitamin D status. SETTING: Nine largely agrarian counties in eastern Nebraska (approximately 41 degrees N). PARTICIPANTS: A population-based sample of 1,179 women 55 years of age and older recruited into a four-year trial of calcium and vitamin D supplementation. METHODS: Baseline biochemical, dietary, and anthropometric measurements obtained on entry into trial. RESULTS: Serum 25(OH)D concentration at baseline varied cyclically with season, with the solar cycle explaining 2.9% of the total variance (P < 0.001). Mean seasonally adjusted 25(OH)D concentration was 71.1 nmol/L. Serum 25(OH)D also exhibited the expected inverse curvilinear relationship with serum parathyroid hormone (PTH), with the inflection point of the curve located at approximately 80 nmol/L. Supplements containing vitamin D were regularly taken by 59% of the cohort (median dose: 200 IU/d). Nevertheless, approximately 4% of all women had values below the laboratory reference range and more than two-thirds fell below 80 nmol/L. Seasonally adjusted serum 25(OH)D concentration was positively correlated with the size of daily vitamin D supplement dose, and negatively with age, weight, and body mass index (P < 0.01 for all). In stepwise multiple linear regression models, weight, age, and supplement dose were independently correlated with seasonally adjusted serum 25(OH)D, and together explained 19% of the total variance of adjusted 25(OH)D concentration. Women taking supplements had only one-sixth the chance of having a 25(OH)D value below the reference limit of the assay, compared to women who did not use supplements. CONCLUSIONS: Approximately two-thirds of this rural population fell below 80 nmol/L, a value considered to be the lower end of the optimal range. Based on the slope of 25(OH)D on supplement dose observed in these women, it would require an additional vitamin D input of nearly 2000 IU/d to reach the goal of an RDA for vitamin D, i.e., to bring 97.5% of the cohort to levels of 80 nmol/L or higher.

Linkage and association between CA repeat polymorphism of the TNFR2 gene and obesity phenotypes in two independent Caucasian populations.

Previously, our group has reported a suggestive linkage evidence of 1p36 with body mass index (BMI) (LOD = 2.09). The tumor necrosis factor receptor 2 (TNFR2) at 1p36 is an excellent positional and functional candidate gene for obesity. In this study, we have investigated the linkage and association between the TNFR2 gene and obesity phenotypes in two large independent samples, using the quantitative transmission disequilibrium tests (QTDT). The first group was made up of 1,836 individuals from 79 multi-generation pedigrees. The second group was a randomly ascertained set of 636 individuals from 157 US Caucasian nuclear families. Obesity phenotypes tested include BMI, fat mass, and percentage fat mass (PFM). A significant result (P = 0.0056) was observed for linkage with BMI in the sample of the multigenerational pedigrees. Our data support the TNFR2 gene as a quantitative trait locus (QTL) underlying BMI variation in the Caucasian populations.

CA repeat polymorphism of the TNFR2 gene is not associated with bone mineral density in two independent Caucasian populations.

Osteoporosis has a strong genetic component, but the genes involved are poorly defined. Genome-wide scans in multiple populations have identified chromosome 1p36 as one region linked to bone mineral density (BMD). The tumor necrosis factor receptor 2 (TNFR2) at 1p36 is a positional and functional candidate gene in osteoporosis. In this study, we conducted linkage and association tests between the CA repeat polymorphism of the TNFR2 gene and BMD in two large independent samples using the quantitative transmission disequilibrium test (QTDT) program. The first group of subjects was composed of 1836 individuals from 79 multigeneration pedigrees. The second group was a randomly ascertained set of 636 individuals from 157 nuclear families. We found no evidence of association or linkage for spine or hip BMD in the samples of the multigenerational pedigrees or nuclear families. Through testing for association and for linkage, our data do not support the TNFR2 gene as a QTL underlying hip or spine BMD variation in our Caucasian populations.

Calcium supplementation does not augment bone gain in young women consuming diets moderately low in calcium.

In earlier observational work, the dietary calcium:protein ratio was directly related to bone accrual in healthy postadolescent women. In this study, we sought to test the hypothesis that augmented calcium intake would increase postadolescent skeletal consolidation, using a double-blind, randomized, placebo-controlled design. We recruited 152 healthy young women (age 23.1 +/- 2.7 y, BMI 22.5 +/- 3.0 kg/m2); their usual diets, as assessed by 7-d food diaries, were low in calcium (605 +/- 181 mg/d; 15.1 +/- 4.5 mmol/d) and in the calcium:protein ratio (10.1 +/- 2.0 mg/g). The subjects were randomly assigned to supplemental calcium [500 mg calcium (12.5 mmol) as the carbonate, 3 times/d, with meals] or placebo capsules identical in appearance; all participants also took a daily multivitamin, and they were followed for up to 36 mo with bone densitometry (dual energy X-ray absorptiometry; DXA) at 6-mo intervals. A total of 121 subjects remained in the study for at least 12 mo (median time in the study, 35 mo), with a mean compliance level (observed/expected tablet consumption) of 87.7%. DXA data for these 121 subjects indicated modest but significant mean rates of increase (i.e., 0.24 to 1.10%/y) in bone mineral content (BMC; total body, total hip, and lumbar spine) and in lumbar spine bone mineral density (BMD) but no change in total hip BMD. None of these rates of change differed by group, i.e., calcium supplementation did not have any measurable effect on bone mass accrual. By midstudy, the calcium content of the subjects' usual diets for both groups had risen by approximately 15%. The combined effect of improved intakes of dietary calcium and the small amount of calcium added by the multivitamin tablets resulted in a mean calcium intake for the control group > 800 mg (20 mmol)/d, possibly at or near the threshold beyond which additional calcium has no further effect on bone accrual.

Race and sex differences and contribution of height: a study on bone size in healthy Caucasians and Chinese.

Osteoporosis is characterized by a loss of bone strength, of which bone size (BS) is an important determinant. However, studies on the factors determining BS are relatively few. The present study evaluated the independent effects of height, age, weight, sex, and race on areal BS at the hip and spine, measured by dual-energy X-ray absorptiometry, while focusing on the differential contributions of height to BS across sex, race, and skeletal site. The subjects were aged 40 years or older, including 763 Chinese (384 males and 379 females) from Shanghai, People's Republic of China, and 424 Caucasians (188 males and 236 females) from Omaha, Nebraska. Basically, Caucasians had significantly larger BS than Chinese. After adjusting for height, age, and weight, the Chinese had similar spine BS, but significantly larger intertrochanter BS in both sexes and larger total hip BS in females compared with Caucasians. Males had significantly larger BS than females before and after adjustment in both ethnic groups. The effects of age, weight, and race varied, depending on skeletal site. As expected, height had major effects on BS variation in both sexes and races. Height tended to account for larger BS variation at the spine than at the hip (except for Chinese females), and larger BS variation in Caucasians than in Chinese of the same sex (except for the trochanter in females). We conclude that height is a major predictor for BS, and its contributions vary across sex, race, and skeletal site.

Potassium intake and the calcium economy.

BACKGROUND: Dietary potassium intake (K) lowers urinary calcium (Ca) excretion and, in short-term studies, may improve Ca balance. PURPOSE: Our objective was to assess K effects on the Ca economy under steady-state conditions. DESIGN: 8-day, inpatient metabolic studies of nitrogen, phosphorus, and Ca balance, combined with dual isotopic Ca tracer kinetics studies. Study diet matched to prestudy nutrient intakes. SUBJECTS: 191 single women studied from 1-5 times at approximately 5-year intervals, for a total of 644 inpatient studies. Median age at time of study: 50.2 yrs; 301 studies were performed postmenopausally without hormone replacement; 343 were either premenopausal or postmenopausal but on estrogen replacement therapy. RESULTS: Dietary K was highly significantly associated with urinary Ca excretion, with a coefficient of -0.0109 mmol urine Ca/mmol diet K. However, dietary K was negatively correlated with dual-tracer Ca absorption (coefficient for Ca absorption fraction: -0.00094/mmol dietary K), and was not associated with urine Ca after adjustment for Ca absorption. CONCLUSION: While a high K diet (i.e., one rich in fruits, vegetables, and dairy products) has multiple health benefits and clearly lowers urine Ca, it does not seem to exert any appreciable net influence on the Ca economy, largely because the reduced calciuria is offset by reduction of intestinal absorption. We note, however, that since the high K intakes in our studies come more from milk and meat than from fruits and vegetables, we cannot exclude a possible balance effect for different food sources of K.

Genetic dissection of human stature in a large sample of multiplex pedigrees.

Recently, we reported a whole genome scan on a sample of 630 Caucasian subjects from 53 human pedigrees. Several genomic regions were suggested to be linked to height. In an attempt to confirm the identified genomic regions, as well as to identify new genomic regions linked to height, we conducted a whole genome linkage study on an extended sample of 1,816 subjects from 79 pedigrees, which includes the 53 pedigrees containing the original 630 subjects from our previous whole genome study and an additional 128 new subjects, and 26 further pedigrees containing 1,058 subjects. Several regions achieved suggestive linkage signals, such as 9q22.32 [MLS (multipoint LOD score) = 2.74], 9q34.3 [MLS = 2.66], Xq24 [two-point LOD score = 2.64 at the marker DXS8067], and 7p14.2 [MLS = 2.05]. The importance of the above regions is supported either by other whole genome studies or by candidate genes within these regions relevant to linear growth or pathogenesis of short stature. In addition, this study has tentatively confirmed the Xq24 region's linkage to height, as this region was also detected in the previous whole genome study. To date, our study has achieved the largest sample size in the field of genetic linkage studies of human height. Together with the findings of other studies, the current study has further delineated the genetic basis of human stature.

Determinants of endogenous calcium entry into the gut.

BACKGROUND: In addition to food sources, calcium enters the gut by way of digestive secretions and shed mucosa. In health, such entry is as large as or larger than urinary calcium excretion. Because calcium absorption is inefficient, most of this endogenous intestinal calcium is excreted. OBJECTIVE: Our aim was to determine the dietary, anthropometric, and physiologic determinants of calcium entering the digestive stream from endogenous sources. DESIGN: Multiple regression modeling of intake and excretion data was used with 553 metabolic balance and kinetics studies performed in 190 midlife, white women. RESULTS: Endogenous intestinal calcium averaged 3.29 +/- 0.83 mmol/d. Multiple regression models explaining variation in this endogenous intestinal calcium were developed with use of dietary intake, anthropometric, and serum mineral variables. All 3 groups of predictor variables individually explained up to 22% of the variation in measured values for endogenous intestinal calcium. A composite model, incorporating all 3 groups explained 29% of the variation, with phosphorus and meat protein intakes, height, weight, and serum calcium and phosphorus concentrations all independently entering the model. Phosphorus intake dominated over all the other predictors, explaining 20% of the variance all by itself, with endogenous intestinal calcium rising by 0.037 mmol for every 1 mmol of phosphorus ingested. Meat protein (but not nonmeat protein) was the only other significant dietary contributor, exhibiting a negative coefficient. CONCLUSION: As a first approximation, the amount of endogenous calcium entering the digestive stream rises with body size and with the amount of phosphorus-rich food consumed.

A follow-up linkage study for bone size variation in an extended sample.

Bone size, which has strong genetic determination, is an important determinant of bone strength and a risk factor of osteoporotic fractures. We previously reported an approximately 10-cm genome-wide linkage scan in 630 subjects from 53 US Caucasian pedigrees. The strongest evidence of linkage was obtained on chromosome 17q22 near the marker D17S787, with a two-point LOD score of 3.98 and a multipoint maximum LOD score (MLS) of 3.01. Additionally, suggestive linkages (1.54 < MLS < 2.83) were found at the other four chromosomal regions. In the present study, with an attempt to further examine our previous findings, we perform a follow-up linkage analysis in an expanded sample of 79 pedigrees with 1816 subjects. The total sample contains >80,000 informative relative pairs for linkage analyses, including 3846 sib pairs. Fifteen markers covering the above five promising regions are genotyped, narrowing the average genomic distance from approximately 10 to 5 cm. In the total 79 pedigrees, support of linkage was achieved for the wrist bone size at 17q22 with a two-point LOD score of 2.27 (P = 0.0006) and MLS of 1.78 (P = 0.002). The genomic region 17q22 includes COL1A1, a strong candidate gene that is significantly associated with osteoporotic fracture risk. Our data suggest that this region is promising for further exploratory studies.

Bone remodeling increases substantially in the years after menopause and remains increased in older osteoporosis patients.

UNLABELLED: Bone remodeling rates (Ac.f) were measured in transilial biopsy specimens from 50 healthy premenopausal women before and 1 year after menopause, in 34 healthy women 13 years past menopause, and in 89 women with untreated osteoporosis. Ac.f nearly doubled 1 year after menopause, tripled 13 years after menopause, and remained elevated in women with osteoporosis. INTRODUCTION: Increased bone remodeling rates are associated with increased skeletal fragility independent of bone mass, partially accounting for the age-related increase in fracture risk in women that is independent of bone loss. We examined bone remodeling rates before and after menopause and in women with osteoporosis by measurements of activation frequency (Ac.f, #/year) in transilial bone biopsy specimens. MATERIALS AND METHODS: We recruited 75 women, > 46 years old, who had premenopausal estradiol and gonadotropin levels and regular menses. During 9.5 years of observation, 50 women experienced normal menopause and had 2 transilial bone biopsy specimens after tetracycline labeling, one at the beginning of observation and the second 12 months after the last menses, when serum follicle-stimulating hormone (FSH) was > 75 mIU/ml and serum estradiol was < 20 pg/ml. Ac.f was also computed for a group of older healthy postmenopausal women and a group of women with untreated osteoporosis studied earlier by the same biopsy (Bx) and labeling protocol. RESULTS: Median Ac.f rose from 0.13/year to 0.24/year (p < 0.001) across menopause and was greater still in the older normals (p < 0.008) than in the second Bx. Ac.f was not significantly greater in the osteoporosis patients than in the older postmenopausal normals. CONCLUSION: Bone remodeling rates double at menopause, triple 13 years later, and remain elevated in osteoporosis. This change contributes to increases in age-related skeletal fragility in women.

Girls on a high-calcium diet gain weight at the same rate as girls on a normal diet: a pilot study.

OBJECTIVE: To determine whether pubertal girls assigned to calcium-rich diets or their usual calcium intakes differ significantly in weight gain. DESIGN: This is a pilot study conducted on data from an experimental research project. SUBJECTS/SETTING: The sample included 59 girls, 9 years of age, from Omaha metropolitan communities. INTERVENTION: Participants were randomly assigned to a calcium-rich diet supplying at least 1,500 mg of calcium per day or their usual diet. MAIN OUTCOME MEASURE: The outcome measure was change in weight during 2 years of study. STATISTICAL ANALYSES: Data were analyzed using descriptive statistics, Mann-Whitney U, t tests of paired and independent samples, and analysis of covariance. RESULTS: The girls in the calcium-rich diet group had a mean (+/-standard deviation) calcium intake of 1,656+/-191 mg/day, whereas the girls on their usual diets averaged 961+/-268 mg/day. Although the participants in the treatment group consumed nearly twice as much dietary calcium--primarily from dairy foods--they did not have greater increases in body weight, body mass index, or fat or lean mass than the control group. These findings held when the data were grouped by tertile of calcium intake. Compared with girls on their usual diets, the girls who consumed the calcium-rich diet also significantly increased their intake of essential nutrients. CONCLUSION: We conclude that calcium-rich diets do not cause excessive weight gain in pubertal girls but do contribute positively to overall nutrition. These findings provide support for programs to promote calcium-rich diets, which are critical for attaining peak bone mass.

Genome scan for QTLs underlying bone size variation at 10 refined skeletal sites: genetic heterogeneity and the significance of phenotype refinement.

To identify quantitative trait loci (QTLs) underlying variation in bone size, we conducted a whole-genome linkage scan in 53 pedigrees with 630 subjects using 380 microsatellite markers. Lumbar area 1, 2, 3, and 4 at the spine, femoral neck, trochanter, intertrochanter areas at the hip, ultradistal, mid-distal, and one-third distal areas at the wrist were measured by dual-energy X-ray absorptiometry (DXA), and adjusted for age, height, weight, and sex. Two-point and multipoint linkage analyses were performed for skeletal bone size at each site and their composite measurements using the SOLAR package. Two chromosomal regions (1q22 and 10q21) were identified with significant evidence of linkage (LOD > 4.32) to one-third distal area, and three were identified with suggestive evidence of linkage (LOD > 2.93) to bone size in one skeletal site. Our results indicated that the low power of QTLs mapping for composite phenotypic measurements may result from genetic heterogeneity of complex traits.

A follow-up linkage study for quantitative trait loci contributing to obesity-related phenotypes.

We have recently reported a whole-genome scan in a sample of 630 subjects from 53 extended pedigrees, in which several genomic regions that may contain quantitative trait loci (QTLs) for obesity were suggested. In the present study, with an attempt to confirm our previous findings, we performed a follow-up linkage study in an expanded sample of 79 pedigrees with 1816 subjects (including expanded previous 53 pedigrees and 26 newly recruited pedigrees containing 1058 subjects). A new set of microsatellite markers spanning previously identified regions were selected, with the average genomic distance narrowed from approximately 10 cM to approximately 5 cM in this study. Using a variance component method, we performed two- and multipoint linkage analyses in the following three sample sets: expanded previous 53 pedigrees (758 subjects), 26 new pedigrees, and 79 total pedigrees. For body mass index, analyses of the expanded 53 pedigrees attained a LOD score of 2.32 near marker D1S468 in two-point analysis and a maximum LOD score (MLS) of 2.21 in multipoint analysis; 2q14 near marker D2S347 attained a LOD score of 3.42 in two-point analysis and a MLS of 3.93 in multipoint analysis. The linkage peaks at 1p36 and 2q14 were further supported in the analyses of all 79 pedigrees, with multipoint MLS being 1.38 and 0.90, respectively. For fat mass, genomic region 6q27 achieved a LOD score of 1.24 in two-point analysis and an MLS of 0.92 in multipoint analysis in all 79 pedigrees. Our data support that 1p36, 2q14, and 6q27 are promising regions that may harbor QTLs for obesity phenotypes.

Linkage and association of the CA repeat polymorphism of the IL6 gene, obesity-related phenotypes, and bone mineral density (BMD) in two independent Caucasian populations.

Genetic factors play an important role in osteoporosis and obesity, two serious public health problems in the world. We investigated the relationships between obesity-related phenotypes, bone mineral density (BMD) and the CA repeat polymorphism of the IL6 gene in two large independent samples using the quantitative transmission disequilibrium test (QTDT). The first sample consisted of 1,816 individuals from 79 multigenerational pedigrees. Each pedigree was identified through a proband with BMD Z-scores

Human serum 25-hydroxycholecalciferol response to extended oral dosing with cholecalciferol.

BACKGROUND: The cholecalciferol inputs required to achieve or maintain any given serum 25-hydroxycholecalciferol concentration are not known, particularly within ranges comparable to the probable physiologic supply of the vitamin. OBJECTIVES: The objectives were to establish the quantitative relation between steady state cholecalciferol input and the resulting serum 25-hydroxycholecalciferol concentration and to estimate the proportion of the daily requirement during winter that is met by cholecalciferol reserves in body tissue stores. DESIGN: Cholecalciferol was administered daily in controlled oral doses labeled at 0, 25, 125, and 250 micro g cholecalciferol for approximately 20 wk during the winter to 67 men living in Omaha (41.2 degrees N latitude). The time course of serum 25-hydroxycholecalciferol concentration was measured at intervals over the course of treatment. RESULTS: From a mean baseline value of 70.3 nmol/L, equilibrium concentrations of serum 25-hydroxycholecalciferol changed during the winter months in direct proportion to the dose, with a slope of approximately 0.70 nmol/L for each additional 1 micro g cholecalciferol input. The calculated oral input required to sustain the serum 25-hydroxycholecalciferol concentration present before the study (ie, in the autumn) was 12.5 micro g (500 IU)/d, whereas the total amount from all sources (supplement, food, tissue stores) needed to sustain the starting 25-hydroxycholecalciferol concentration was estimated at approximately 96 micro g (approximately 3800 IU)/d. By difference, the tissue stores provided approximately 78-82 micro g/d. CONCLUSIONS: Healthy men seem to use 3000-5000 IU cholecalciferol/d, apparently meeting > 80% of their winter cholecalciferol need with cutaneously synthesized accumulations from solar sources during the preceding summer months. Current recommended vitamin D inputs are inadequate to maintain serum 25-hydroxycholecalciferol concentration in the absence of substantial cutaneous production of vitamin D.

Differences in bone mineral density, bone mineral content, and bone areal size in fracturing and non-fracturing women, and their interrelationships at the spine and hip.

Osteoporotic fractures are a major public health problem, particularly in women. Bone mineral density (BMD), bone mineral content (BMC), and bone size have been regarded as important determinants of osteoporotic fractures. In 1449 women over age 30 years, we studied the detailed relationship, at the spine and hip, between BMD, BMC, and bone areal size (all measured by dual-energy X-ray absorptiometry) and compared their relative magnitudes in fracturing and non-fracturing individuals. We find that, (1) BMD and BMC are significantly higher at the spine and hip in non-fracturing women. Bone areal size is significantly larger at the spine in non-fracturing women; however, the significance disappears when adjustment is made for the significant difference of height (stature) between fracturing and non-fracturing women. In contrast to the spine, bone areal size is always significantly largerin fracturing women at the hip. (2) The relationship among BMD, BMC, and bone areal size is different at the spine and hip. Specifically, at the spine, BMD increases with bone areal size linearly. At the hip, BMD has a quadratic relationship with bone areal size, so that BMD increases at lower bone areal sizes, then (after an intermediate zone of values) decreases with increasing bone areal size. However, BMD adjusted for BMC always decreases with increasing bone areal size, as expected by the definition of BMD. With no adjustment for BMC, the increase in BMD with bone areal size is due to a more rapid increase of BMC than increasing bone areal size, thus explaining the observations of association of both larger BMD and larger bone areal size with stronger bone. (3) At the spine, 86.2% of BMD variation is attributable to BMC and 12.6% to bone areal size. At the hip, 98.0% of BMD variation is due to BMC and 1.1% due to bone areal size. The current study may be important in understanding the relationship among BMD, BMC, and bone size as risk determinants of osteoporotic fractures.

Decline in muscle mass with age in women: a longitudinal study using an indirect measure.

Muscle mass is known to decline with age, but only limited longitudinal data exist to quantify the rate of loss. Using 24-hour urine creatinine, corrected for the contribution of dietary meat intake, we assessed the change with age prospectively in 107 women who provided a minimum of 3 sets of measurements spanning an average interval of 11.9 years, centered around age 55 years. The rate of change in 24-hour urine creatinine at that age averaged -0.94%/yr (95% confidence interval [CI], -1.24% to -0.64%/yr; P <.001). Change in creatinine excretion was directly correlated with change in weight (P <.01), with those gaining weight tending to gain both lean and fat mass. The rate of change in creatinine excretion with age in our subjects is similar to that described in published cross-sectional studies on age-related change in total body potassium and in longitudinal studies using (40)K and dual-energy xray absorptiometry. Our study is the largest longitudinal study reported to date and provides, perhaps, a more secure basis for estimating muscle mass change with age than has been available heretofore.