Weight-adjusted Bone Mineral Density Research Articles

Bone metabolism, density, and geometry in postmenopausal women with vitamin D insufficiency: a cross-sectional comparison of the effects of elevated parathyroid levels.

In vitamin D insufficiency, elevated parathyroid hormone (PTH) levels may contribute to adverse effect on bone. We assessed effects of PTH responses to vitamin D insufficiency on bone metabolism, density, and geometry. Using a cross-sectional design, we investigated 102 healthy postmenopausal women with low 25-hydroxy-vitamin D (< 50nmol/L) levels, who had either secondary hyperparathyroidism with elevated PTH levels (> 6.9pmol/L, N = 51) or normal PTH levels (N = 51). Bone mineral density (BMD) and bone geometry were assessed by Dual-Energy X-ray absorptiometry (DXA), quantitative computed tomography (QCT) and high-resolution peripheral QCT (HRpQCT) scans. Bone metabolism was assessed by biochemistry including bone turnover markers. Levels of 25(OH)D were 38 (IQR 31-45) nmol/L with no differences between groups. PTH levels were 8.5 (IQR 7.5-9.5) in women with SHPT and 5.2 (4.4-6.6) pmol/L in women with normal PTH (p < 0.001). BMI and eGFR did not differ between groups. SHPT was associated with lower total- and trabecular bone area, lower cortical perimeter, and increased cortical area in tibia and radius. SHPT was associated with a lower weight-adjusted BMD at the lumbar spine (p < 0.05). High compared to normal PTH levels were associated with significantly lower plasma levels of 1,25(OH)2D, phosphate, but higher levels of osteocalcin and borderline higher levels of CTx. PTH correlated to osteocalcin and CTx. High PTH levels are associated with altered bone geometry, increased bone turnover, and reduced BMD at the spine. Whether an increased cortical thickness with a lower trabecular volume is an effect of PTH or not needs further elucidations.

Meta-analysis of genome-wide studies identifies WNT16 and ESR1 SNPs associated with bone mineral density in premenopausal women.

Previous genome-wide association studies (GWAS) have identified common variants in genes associated with variation in bone mineral density (BMD), although most have been carried out in combined samples of older women and men. Meta-analyses of these results have identified numerous single-nucleotide polymorphisms (SNPs) of modest effect at genome-wide significance levels in genes involved in both bone formation and resorption, as well as other pathways. We performed a meta-analysis restricted to premenopausal white women from four cohorts (n = 4061 women, aged 20 to 45 years) to identify genes influencing peak bone mass at the lumbar spine and femoral neck. After imputation, age- and weight-adjusted bone-mineral density (BMD) values were tested for association with each SNP. Association of an SNP in the WNT16 gene (rs3801387; p = 1.7 × 10(-9) ) and multiple SNPs in the ESR1/C6orf97 region (rs4870044; p = 1.3 × 10(-8) ) achieved genome-wide significance levels for lumbar spine BMD. These SNPs, along with others demonstrating suggestive evidence of association, were then tested for association in seven replication cohorts that included premenopausal women of European, Hispanic-American, and African-American descent (combined n = 5597 for femoral neck; n = 4744 for lumbar spine). When the data from the discovery and replication cohorts were analyzed jointly, the evidence was more significant (WNT16 joint p = 1.3 × 10(-11) ; ESR1/C6orf97 joint p = 1.4 × 10(-10) ). Multiple independent association signals were observed with spine BMD at the ESR1 region after conditioning on the primary signal. Analyses of femoral neck BMD also supported association with SNPs in WNT16 and ESR1/C6orf97 (p < 1 × 10(-5) ). Our results confirm that several of the genes contributing to BMD variation across a broad age range in both sexes have effects of similar magnitude on BMD of the spine in premenopausal women. These data support the hypothesis that variants in these genes of known skeletal function also affect BMD during the premenopausal period.

Genome-wide association study of bone mineral density in premenopausal European-American women and replication in African-American women.

Several genome-wide association studies (GWAS) have been performed to identify genes contributing to bone mineral density (BMD), typically in samples of elderly women and men. The objective of the study was to identify genes contributing to BMD in premenopausal women. GWAS using the Illumina 610Quad array in premenopausal European-American (EA) women and replication of the top 50 single-nucleotide polymorphisms (SNPs) for two BMD measures in African-American (AA) women. Subjects included 1524 premenopausal EA women aged 20-45 yr from 762 sibships and 669 AA premenopausal women aged 20-44 yr from 383 sibships. There were no interventions. BMD was measured at the lumbar spine and femoral neck by dual-energy x-ray absorptiometry. Age- and weight-adjusted BMD values were tested for association with each SNP, with P values determined by permutation. SNPs in CATSPERB on chromosome 14 provided evidence of association with femoral neck BMD (rs1298989, P = 2.7 x 10(-5); rs1285635, P = 3.0 x 10(-5)) in the EA women, and some supporting evidence was also observed with these SNPs in the AA women (rs1285635, P = 0.003). Genes identified in other BMD GWAS studies, including IBSP and ADAMTS18, were also among the most significant findings in our GWAS. Evidence of association to several novel loci was detected in a GWAS of premenopausal EA women, and SNPs in one of these loci also provided supporting evidence in a sample of AA women.

Bone mineral density and sex hormone status in intellectually disabled women on progestin‐induced amenorrhea

To evaluate bone mineral density (BMD) and hormonal status in female patients with intellectual disability and a history of progestin-induced amenorrhea. Cross-sectional study. Nursing home. The study included 51 patients with a history of therapeutic amenorrhea (age 23-77 years, mean 45 years); 115 staff members (age 21-64 years, mean 45 years) at the same nursing homes served as controls. Calcaneal BMD was measured for all (Peripheral Instantaneous X-ray Imaging Lunar Bone Densitometer); blood samples for serum levels of estradiol (E(2)), follicle stimulation hormone (FSH) and lutenizing hormone (LH) were obtained only for the patients. The patients showed significantly lower age and weight-adjusted BMD than the controls (0.35 g/cm(2)+/-0.13 vs. 0.53 g/cm(2)+/-0.09, p<0.001). BMD values did not differ between pre- (N=29) and postmenopausal (N=22) patients. Osteoporosis was observed in 57% of the patients and only in 2% of the controls. Four patients (8%) but none of the controls had sustained a bone fracture during the preceding five years. Most premenopausal patients had hypogonadotropic hypogonadism, as shown by low serum E(2), LH and FSH levels in 83%, 69%, and 59% of the cases. Postmenopausal patients showed normal hormonal status for their age. Osteoporosis with concomitant fractures is prevalent in women with intellectual disability on therapeutic amenorrhea. Progestin-induced amenorrhea results in hypogonadism, an established risk factor for osteoporosis. New strategies for the management of menstruation should be considered.

Body composition and bone density in Canadian White and Aboriginal women: The First Nations Bone Health Study

Ethnic variation in soft tissue composition may contribute to observed ethnic differences in bone mineral density (BMD). This analysis was performed to determine whether ethnic differences in body composition affect differences in BMD between Canadian White and Aboriginal women. An age-stratified population-based sample of 206 Aboriginal women and 177 White women underwent multisite bone density measurements and total body soft tissue composition analysis. In univariate analyses, each kg of additional lean mass was associated with a greater increase in BMD than an equal amount of fat mass ( p < .01). When models simultaneously evaluated both soft tissue measurements, lean mass (but not fat mass) was positively correlated with BMD at all measurement sites ( p < .001). Aboriginal women had significantly lower weight-adjusted BMD than White women for two sites (calcaneus, p = .019; total body, p = .026) and lower BMI-adjusted for BMD three sites (calcaneus, p = .0076; distal forearm, p = .047; total body, p = .022). The ratio of lean mass to fat mass was lower in Aboriginal than White women ( p < .001). When BMD was adjusted for body composition variables no significant difference was seen between Aboriginal and White women. Apparent ethnic differences in weight- and BMI-adjusted BMD between Canadian White and Aboriginal women were explained by a lower ratio of lean mass to fat mass in Aboriginal women, combined with a smaller increment in BMD from fat mass versus lean mass in both populations.

Changes in bone mineral density in premenopausal women with rheumatoid arthritis during a two-year follow-up

Objective To ascertain changes in axial bone mineral in premenopausal women with severe rheumatoid arthritis (RA) treated with and without prednisolone (PRED), we conducted a two-year follow-up study of axial bone mineral density (BMD) and bone mineral content (BMC). Methods Premenopausal RA women ( n = 74) attending wards in the Rheumatism Foundation Hospital, Heinola, Finland were consecutively recruited for a follow-up study of BMD. BMD measurements in the lumbar spine and left proximal femur (femoral neck) were performed using dual X-ray absorptiometry at baseline and after two years. BMD is expressed as BMC per projectional area g/cm 2. The Larsen score of 0–100 was assessed at the check-ups. Two RA groups were analyzed: patients receiving prednisolone ( n = 48), RA with PRED group and without prednisolone ( n = 26), RA without PRED group. The control group ( n = 43) comprised age-matched, premenopausal healthy women. Results The patients in the RA with PRED group had lower BMD values than those in the RA without PRED group at commencement of follow-up. The mean weight-adjusted BMD percentage change in the lumbar spine to two years was −1.5% in the RA with PRED group, +0.6% in the RA without PRED group and −0.6% among the controls; a significant difference ( P = 0.030) was found between the RA groups. The mean BMC percentage change to two years in the lumbar spine was −2.2% in the RA with PRED-group ( P = 0.003), +0.0 in the RA without PRED-group and −0.6% in the control group. Accordingly, the mean weight-adjusted BMD percentage change in the femoral neck to two years was −2.6% in the RA with PRED group, +0.4% in the RA without PRED group and −0.9% among the controls; the difference between the RA groups being again significant ( P = 0.049). The mean BMC percentage change to two years in the femoral neck was −1.9% ( P = 0.006), −0.4% and −0.8%, respectively. Mean BMD decreased significantly in both lumbar spine ( P = 0.002) and femoral neck ( P < 0.001) only in the RA with PRED group. However, in spite of statistical findings above, when BMD is expressed as BMC per projectional area there was no statistically significant difference between the three groups in the change in BMC or projectional area in the lumbar spine or femoral neck. There was no significant correlation between the change in BMD in lumbar spine or femoral neck and the change in Larsen score among the RA groups. Conclusions We conclude that according to BMC, premenopausal RA women both with and without prednisolone treatment and controls lost bone statistically similarly. It seems that the role of RA itself in the multifactorial development of axial bone mass during the first decade of severe RA is not the most essential issue. We assume that this role will be less important with better treatment of RA than our patients received. The amount of bone loss during treatment with low-grade prednisolone remains controversial.

Depression and bone mineral density in a community sample of perimenopausal women: Geelong Osteoporosis Study

Reduced bone mineral density (BMD) in women with a history of depressive disorders has been shown in some, but not all studies. This study investigated the association between self-reported depression and BMD in an age-stratified community sample of perimenopausal women residing in the South-Eastern region of Australia. Symptoms of depression in the year between July 2000 and July 2001 were ascertained by a self-report questionnaire based on Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) criteria. Women in the perimenopausal group who had undergone a BMD total hip and spine assessment within the 12-month period after the depression assessment were included in the analysis, resulting in a sample of 78 women aged 45 to 60 years. In this sample, 14 women were identified as depressed. There was no difference in age, hormone therapy (HT) use, or unadjusted BMD at the total hip or spine between the depressed and nondepressed women (P = 0.14, 0.89, 0.57, and 0.70, respectively), but the depressed women tended to be heavier [depressed (median weight, interquartile range = 80 kg, 66-94) vs nondepressed (72 kg, 61-80) P = 0.06]. Whereas there was no significant difference in age-, HT-, and weight-adjusted BMD at the spine [depressed (mean +/- SE = 1.21 +/- 0.05) vs nondepressed (1.28 +/- 0.03 g/cm(2)) P = 0.18], adjusted BMD at the total hip for the depressed women was 7.8% lower than for the nondepressed [depressed (mean +/- SE = 0.957 +/- 0.038) vs nondepressed (1.038 +/- 0.023 g/cm(2)) P = 0.04]. These results suggest that in perimenopausal women, self-reported depression is associated with lower BMD at the hip.

Association of CTR and COLIA1 alleles with BMD values in peri- and postmenopausal women.

The variability of bone mass and bone strength is in part genetically determined. The pathophysiology of the disease is complex and its heritability is almost certainly polygenic. In a large group of women from north eastern Italy, homogeneous for calcium intake and other risk factors for osteoporosis, we investigated three different genetic polymorphic markers that have been associated with bone mineral density (BMD). The study includes 663 postmenopausal (aged 48-85 years) and 52 perimenopausal (aged 47-53 years) women. Lumbar spine and hip BMD were measured by dual energy X-ray absorptiometry (DXA). After DNA extraction, the restriction enzymes utilized were MscI for the SP1 site of the collagen type I regulatory region (COLIA1), AluI for the calcitonin receptor (CTR) gene, and BsmI for the Vitamin D receptor (VDR) gene. COLIA1 genotype was significantly associated with age-adjusted hip BMD, with the highest values in the SS group and the lowest in the ss group (p < 0.05). The COLIA1 effect was not visible until the sixth decade of life, but it increased thereafter with aging, becoming statistically significant also at the lumbar spine in subjects aged >70 years. CTR genotype was also significantly related to bone mass in the CC group, with the lowest age and weight-adjusted BMD values at the spine (p < 0.05). The CTR genotype effect was greater in the younger subset of women. This suggests that the CTR genotype might influence the process of acquiring peak bone mass rather than the process of bone loss along aging. No trend association was found between BMD values and VDR genotype. These findings suggest an association between the COLIA1 gene polymorphism more with the age-related rate of bone loss than with peak bone mass, which apparently is somewhat affected by CTR gene polymorphism.

The BsmI vitamin D receptor restriction fragment length polymorphism (bb) influences the effect of calcium intake on bone mineral density.

Previous studies of the vitamin D receptor (VDR) polymorphisms and bone mineral density (BMD) have suggested that there may be differences in calcium absorption among groups of women with different VDR genotypes, and that the association may be stronger in younger women. To investigate the association between the VDR polymorphisms and BMD, this study was undertaken in the Framingham Study Cohort and a group of younger volunteers. Subjects from the Framingham Study (ages 69-90 years) included those who underwent BMD testing and who had genotyping for the VDR alleles (n = 328) using polymerase chain reaction methods and restriction fragment length polymorphisms with BsmI (B absence, b presence of cut site). A group of younger volunteer subjects (ages 18-68) also underwent BMD testing and VDR genotyping (n = 94). In Framingham Cohort subjects with the bb genotype, but not the Bb or BB genotypes, there were significant associations between calcium intake and BMD at five of six skeletal sites, such that BMD was 7-12% higher in those with dietary calcium intakes greater than 800 mg/day compared with those with intakes < 500 mg/day. The data also suggested that BMD was higher in persons with the bb genotype only in the group with calcium intakes above 800 mg/day. No significant differences were found in the Framingham Cohort for age-, sex-, and weight-adjusted BMD at any skeletal site between those with the BB genotype and those with the bb genotype regardless of 25-hydroxyvitamin D levels or country of origin. In the younger volunteers, BMD of the femoral neck was 5.4% higher (p < 0.05) in the bb genotype group compared with the BB group and 11% higher (p < 0.05) in males with the bb genotype compared with the BB group. There were no significant differences at the lumbar spine. In this study, the association between calcium intake and BMD appeared to be dependent upon VDR genotype. The findings of an association between dietary calcium intake and BMD only in the bb genotype group suggests that the VDR genotype may play a role in the absorption of dietary calcium. Studies that do not consider calcium intake may not detect associations between VDR genotype and BMD. In addition, the association between VDR alleles and BMD may become less evident in older subjects.

Effects of estrogen exposure and reproductive factors on bone mineral density and osteoporotic fractures

The risk of osteoporotic fracture is related to peak bone mass achieved at skeletal maturity and subsequent bone loss. Although premature menopause is a risk factor for osteoporosis, the effect of exposure to endogenous estrogen during a woman's reproductive years is poorly characterized. We analyzed the relationship between reproductive factors and estrogen exposure on bone mineral density (BMD) and incidence of atraumatic fracture in data from 1091 women (age: 70 +/- 7.2 yr; mean +/- SD) participating in the Dubbo Osteoporosis Epidemiology Study. Age- and weight-adjusted BMD among women who had used estrogen replacement therapy (ERT) for more than 5 yr was higher at the lumbar spine and femoral neck by 13.7% and 10.2% (P < 0.001), respectively, compared with women who had used ERT for less than 5 yr or nonusers. Duration of exposure to estrogen (years of menstruation plus postmenopausal ERT use) was associated with higher BMD, such that BMD increased by 2-3% for every 10-yr increase in years of estrogen...

Effects of estrogen exposure and reproductive factors on bone mineral density and osteoporotic fractures.

The risk of osteoporotic fracture is related to peak bone mass achieved at skeletal maturity and subsequent bone loss. Although premature menopause is a risk factor for osteoporosis, the effect of exposure to endogenous estrogen during a woman's reproductive years is poorly characterized. We analyzed the relationship between reproductive factors and estrogen exposure on bone mineral density (BMD) and incidence of atraumatic fracture in data from 1091 women (age: 70 +/- 7.2 yr; mean +/- SD) participating in the Dubbo Osteoporosis Epidemiology Study. Age- and weight-adjusted BMD among women who had used estrogen replacement therapy (ERT) for more than 5 yr was higher at the lumbar spine and femoral neck by 13.7% and 10.2% (P < 0.001), respectively, compared with women who had used ERT for less than 5 yr or nonusers. Duration of exposure to estrogen (years of menstruation plus postmenopausal ERT use) was associated with higher BMD, such that BMD increased by 2-3% for every 10-yr increase in years of estrogen exposure; thus women who menstruated for more than 40 yr had a 6-8% higher BMD than did women who menstruated for less than 30 yr. Higher BMD was also significantly associated with high parity, such that nulliparous women had 5-6% lower BMD than did their peers of the same age and weight. The incidence of atraumatic fractures among non-ERT users was higher than that of ERT-users [odds ratio (OR): 1.06; 95% confidence interval (CI): 0.94-1.16] and was significantly lower among parous women than among nulliparous women (OR 0.94; 95% CI: 0.84-0.98) in univariate analysis. Longer duration of menstruation was associated with lower fracture incidence (OR for 1 SD = 6.6 yr: 0.93; 95% CI: 0.86-1.02). Moreover, when all of these factors were considered simultaneously, parity remained a significant determinant of fracture as well as femoral neck BMD. We conclude that high parity and longer duration of exposure to estrogen, either through natural menstruation or postmenopausal ERT, have protective effects on BMD and are associated with a reduced incidence of atraumatic fracture in a population-based study.