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Neck BMD (neck + bmd)

Distribution by Scientific Domains
Medical Sciences95%

Kinds of Neck BMD

  • femoral neck bmd
    		•

    Selected Abstracts

    Calcaneal ultrasonometry in patients with Charcot osteoarthropathy and its relationship with densitometry in the lumbar spine and femoral neck and with markers of bone turnover

    DIABETIC MEDICINE, Issue 6 2001
    A. Jirkovská
    Abstract Aims To assess calcaneal ultrasonometry in Charcot osteoarthropathy (CO) and to compare it with densitometry measured by dual energy X-ray absorptiometry (DEXA) and with bone remodelling markers. Patients and methods A group of 16 diabetic patients in the acute stage of CO with a mean age (± sd) of 51 ± 13 years was compared with 26 sex- and age-matched control subjects. Both calcaneal quantitative ultrasound (QUS) parameter stiffness and bone mineral density (BMD) measured in lumbar spine and femoral neck by DEXA were compared. Collagen type I cross-linked C-telopeptides (ICTP) were used for assessment of bone resorption. Results Patients with acute CO had significantly lower stiffness of the calcaneus in the Charcot and non-Charcot foot (both P < 0.001) and significantly lower femoral neck BMD (P < 0.05) in comparison with the control group. The T-score of stiffness was significantly lower in the Charcot foot compared with the non-Charcot foot (,3.00 ± 1.39 vs. ,2.36 ± 1.12; P < 0.01) and significantly lower than the mean T-score of BMD in the lumbar spine (,0.57 ± 1.28; P < 0.001) and femoral neck (,1.58 ± 1.24; P < 0.05). A significant difference in ICTP (8.49 ± 4.37 vs. 3.92 ± 2.55 ng/ml; P < 0.001) between patients with CO and the control group was found, and a significant correlation was demonstrated between ICTP and the T-score of stiffness (r = ,0.73; P < 0.01). Conclusion The lower calcaneal QUS parameter stiffness in the Charcot foot in comparison with the control group, with the non-Charcot foot and with BMD in the lumbar spine and femoral neck, and its association with increased bone resorption indicate that calcaneal ultrasonometry may be useful in diagnosing the acute stage of CO and in assessing the risk of foot fracture. Diabet. Med. 18, 495,500 (2001) [source]

    Vitamin D receptor FokI genotype influences bone mineral density response to strength training, but not aerobic training

    EXPERIMENTAL PHYSIOLOGY, Issue 4 2005
    Karma M. Rabon-Stith
    To determine the influence of the vitamin D receptor (VDR) gene FokI and BsmI genotype on bone mineral density response to two exercise training modalities, 206 healthy men and women (50,81 years old) were studied before and after ,5,6 months of either aerobic exercise training (AT) or strength training (ST). A totla of 123 subjects completed AT (51 men, 72 women) and 83 subjects completed ST (40 men, 43 women). DNA was extracted from blood samples of all subjects and genotyping was performed at the VDR FokI and BsmI locus to determine its association to training response. Total body, greater trochanter and femoral neck bone mineral density (BMD) were measured before and after both training programmes using dual-energy X-ray absorptiometry. VDR BsmI genotype was not significantly related to BMD at baseline or after ST or AT. However, VDR FokI genotype was significantly related to ST- but not AT-induced changes in femoral neck BMD (P < 0.05). The heterozygotes (Ff) in the ST group approached a significantly greater increase in femoral neck BMD (P= 0.058) compared to f homozygotes. There were no significant genotype relationships in the AT group. These data indicate that VDR FokI genotype may influence femoral neck BMD response to ST, but not AT. [source]

    Zoledronic acid prevents bone loss after allogeneic haemopoietic stem cell transplantation

    INTERNAL MEDICINE JOURNAL, Issue 9 2006
    A. B. D'Souza
    Abstract Allogeneic haemopoietic stem cell transplant (alloHSCT) patients are at increased risk of osteoporosis. Zoledronic acid (ZA) is a potent i.v. bisphosphonate; however, there are few data on ZA use after alloHSCT. The aim of this study is to examine the effect of a single 4 mg ZA infusion in alloHSCT patients with either osteoporosis (T -score < ,2.5) or rapid bone loss post-alloHSCT. An uncontrolled, prospective study of 12 consecutive patients receiving ZA, predominantly within the first year post-HSCT. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry at the spine and proximal femur pretransplant, pre-ZA and post-ZA. The median annualized percentage change in total hip BMD between the pretransplant scan and the scan immediately before ZA was ,13% (range, ,51 to +3.6%). After ZA treatment, the total hip BMD increased by a median of +3.3% (range, ,20.4 to +14.8%) in 75% of patients. The median annualized percentage change in femoral neck BMD between the pretransplant scan and the scan immediately before ZA was ,13.2% (range, ,40 to +1.0%). Post-ZA, femoral neck BMD increased by a median of +1.4% (range, ,22.2 to +33.6%). Only one patient continued to lose bone from the femoral neck post-ZA infusion. The median annualized percentage change in spinal BMD pretransplant was ,12.5% (range, ,38 to +6.9%). Post-ZA, spinal BMD decreased by a median of ,2.8% (range, ,27.6 to +24.4%). Four patients continued to lose bone from the spine post-ZA. ZA reduces bone loss in most patients after alloHSCT. Our data require confirmation in a larger prospective, randomized study. [source]

    Longitudinal Study of Changes in Hip Bone Mineral Density in Caucasian and African-American Women

    JOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 2 2005
    Jane A. Cauley DrPH
    Objectives: To determine whether changes in hip bone mineral density (BMD) differ in Caucasian and African American women. Design: Longitudinal study of changes in hip BMD. Setting: Four U.S. clinical centers. Participants: Six thousand seven Caucasian (mean age 73) and 482 African-American (mean age 75) women enrolled in the Study of Osteoporotic Fractures. Measurements: Total hip and femoral neck BMD were measured an average of 3.5 years apart (Caucasian) and 2.0 years apart (African American). Annual absolute and percentage changes in BMD and bone mineral apparent density (BMAD) were calculated. Results: The multivariate adjusted annual percentage change in BMD was greater in Caucasian than African-American women at the total hip (,0.574%/y vs ,0.334%/y) and femoral neck (,0.515%/y vs ,0.203%/y) (both, P<.001). Similar findings were observed for BMAD. The average annualized rate of BMD loss was twice as high in women aged 75 and older as in women younger than 75 in both ethnic groups. The annual percentage loss in femoral neck BMD in nonusers versus hormone therapy users was (,0.57% vs ,0.22%) in Caucasians and (,0.35% vs 0.64%) in African Americans (interaction P=.03). Conclusion: The average rate of hip BMD loss is approximately twice as great in Caucasian as African-American women and increases with age in both groups. The hormonal and biochemical factors that contribute to ethnic differences and the increase in bone loss with advancing age need to be identified. [source]

    Prevalence and trends in low femur bone density among older US adults: NHANES 2005,2006 compared with NHANES III

    JOURNAL OF BONE AND MINERAL RESEARCH, Issue 1 2010
    Anne C Looker
    Abstract Hip fracture incidence appears to be declining in the United States, but changes in bone mineral density (BMD) of the population have not been evaluated. We used femur BMD data from the National Health and Nutrition Examination Survey (NHANES) 2005,2006 to estimate the prevalence of low femoral BMD in adults age 50 years and older and compared it with estimates from NHANES III (1988,1994). Dual-energy X-ray absorptiometry systems (pencil-beam geometry in NHANES III, fan-beam geometry in NHANES 2005,2006) were used to measure femur BMD, and World Health Organization (WHO) definitions of low BMD were used to categorize skeletal status. In 2005,2006, 49% of older US women had osteopenia and 10% had osteoporosis at the femur neck. In men, 30% had femur neck osteopenia and 2% had femur neck osteoporosis. An estimated 5.3 million older men and women had osteoporosis at the femur neck, and 34.5 million more had osteopenia in 2005,2006. When compared with NHANES III, the age-adjusted prevalence of femur neck osteoporosis in NHANES 2005,2006 was lower in men (by 3 percentage units) and women (by 7 percentage units) overall and among non-Hispanic whites. Changes in body mass index or osteoporosis medication use between surveys did not fully explain the decline in osteoporosis. Owing to the increase in the number of older adults in the US population, however, more older adults had low femur neck BMD (osteoporosis + osteopenia) in 2005,2006 than in 1988,1994. Thus, despite the decline in prevalence, the estimated number of affected older adults in 2005,2006 remained high. Copyright © 2010 American Society for Bone and Mineral Research [source]

    Femoral Neck BMD Is a Strong Predictor of Hip Fracture Susceptibility in Elderly Men and Women Because It Detects Cortical Bone Instability: The Rotterdam Study,

    JOURNAL OF BONE AND MINERAL RESEARCH, Issue 11 2007
    Fernando Rivadeneira
    Abstract We studied HSA measurements in relation to hip fracture risk in 4806 individuals (2740 women). Hip fractures (n = 147) occurred at the same absolute levels of bone instability in both sexes. Cortical instability (propensity of thinner cortices in wide diameters to buckle) explains why hip fracture risk at different BMD levels is the same across sexes. Introduction: Despite the sexual dimorphism of bone, hip fracture risk is very similar in men and women at the same absolute BMD. We aimed to elucidate the main structural properties of bone that underlie the measured BMD and that ultimately determines the risk of hip fracture in elderly men and women. Materials and Methods: This study is part of the Rotterdam Study (a large prospective population-based cohort) and included 147 incident hip fracture cases in 4806 participants with DXA-derived hip structural analysis (mean follow-up, 8.6 yr). Indices compared in relation to fracture included neck width, cortical thickness, section modulus (an index of bending strength), and buckling ratio (an index of cortical bone instability). We used a mathematical model to calculate the hip fracture distribution by femoral neck BMD, BMC, bone area, and hip structure analysis (HSA) parameters (cortical thickness, section modulus narrow neck width, and buckling ratio) and compared it with prospective data from the Rotterdam Study. Results: In the prospective data, hip fracture cases in both sexes had lower BMD, thinner cortices, greater bone width, lower strength, and higher instability at baseline. In fractured individuals, men had an average BMD that was 0.09 g/cm2 higher than women (p < 0.00001), whereas no significant difference in buckling ratios was seen. Modeled fracture distribution by BMD and buckling ratio levels were in concordance to the prospective data and showed that hip fractures seem to occur at the same absolute levels of bone instability (buckling ratio) in both men and women. No significant differences were observed between the areas under the ROC curves of BMD (0.8146 in women and 0.8048 in men) and the buckling ratio (0.8161 in women and 0.7759 in men). Conclusions: The buckling ratio (an index of bone instability) portrays in both sexes the critical balance between cortical thickness and bone width. Our findings suggest that extreme thinning of cortices in expanded bones plays a key role on local susceptibility to fracture. Even though the buckling ratio does not offer additional predictive value, these findings improve our understanding of why low BMD is a good predictor of fragility fractures. [source]

    Association of the VDR Translation Start Site Polymorphism and Fracture Risk in Older Women,,

    JOURNAL OF BONE AND MINERAL RESEARCH, Issue 5 2007
    Susan P Moffett PhD
    Abstract We evaluated the association between the VDR translation start site polymorphism and osteoporotic phenotypes among 6698 older white women. Women with the C/C genotype had lower wrist BMD and an increased risk of wrist and all non-spine/low-trauma fractures. The high frequency of this variant confers a population attributable risk that is similar to several established risk factors for fracture. Introduction: The vitamin D receptor (VDR) is a nuclear receptor that regulates bone formation, bone resorption, and calcium homeostasis. A common C to T polymorphism in exon 2 of the VDR gene introduces a new translation start site and a protein that differs in length by three amino acids (T = 427aa, C = 424aa; rs10735810). Materials and Methods: We conducted genetic association analyses of this polymorphism, BMD, and fracture outcomes in a prospective cohort of 6698 white American women ,65 years of age. Incident fractures were confirmed by physician adjudication of radiology reports. There were 2532 incident nontraumatic/nonvertebral fractures during 13.6 yr of follow-up including 509 wrist and 703 hip fractures. Results: Women with the C/C genotype had somewhat lower distal radius BMD compared with those with the T/T genotype (CC = 0.358 g/cm2, CT = 0.361 g/cm2, TT = 0.369 g/cm2, p = 0.003). The C/C genotype was also associated with increased risk of non-spine, low traumatic fractures (HR: 1.18; 95% CI: 1.04, 1.33) and wrist fractures (HR: 1.33; 95% CI: 1.01, 1.75) compared with the T/T genotype in age-adjusted models. Further adjustments for distal radius BMD only slightly attenuated these associations. The VDR polymorphism was not associated with hip fracture. The population attributable risk (PAR) of the C/C genotype for incident fractures was 6.1%. The PAR for established risk factors for fracture were: low femoral neck BMD (PAR = 16.3%), maternal history of fracture (PAR = 5.1%), low body weight (PAR = 5.3%), corticosteroid use (PAR = 1.3%), and smoking (PAR = 1.6%). Similar PAR results were observed for wrist fractures. Conclusions: The common and potentially functional VDR translation start site polymorphism confers a modestly increased relative risk of fracture among older white women. However, the high frequency of this variant confers a population attributable risk that is similar to or greater than several established risk factors for fracture. [source]

    Meta-Analysis of Genome-Wide Scans Provides Evidence for Sex- and Site-Specific Regulation of Bone Mass,

    JOURNAL OF BONE AND MINERAL RESEARCH, Issue 2 2007
    John PA Ioannidis
    Abstract Several genome-wide scans have been performed to detect loci that regulate BMD, but these have yielded inconsistent results, with limited replication of linkage peaks in different studies. In an effort to improve statistical power for detection of these loci, we performed a meta-analysis of genome-wide scans in which spine or hip BMD were studied. Evidence was gained to suggest that several chromosomal loci regulate BMD in a site-specific and sex-specific manner. Introduction: BMD is a heritable trait and an important predictor of osteoporotic fracture risk. Several genome-wide scans have been performed in an attempt to detect loci that regulate BMD, but there has been limited replication of linkage peaks between studies. In an attempt to resolve these inconsistencies, we conducted a collaborative meta-analysis of genome-wide linkage scans in which femoral neck BMD (FN-BMD) or lumbar spine BMD (LS-BMD) had been studied. Materials and Methods: Data were accumulated from nine genome-wide scans involving 11,842 subjects. Data were analyzed separately for LS-BMD and FN-BMD and by sex. For each study, genomic bins of 30 cM were defined and ranked according to the maximum LOD score they contained. While various densitometers were used in different studies, the ranking approach that we used means that the results are not confounded by the fact that different measurement devices were used. Significance for high average rank and heterogeneity was obtained through Monte Carlo testing. Results: For LS-BMD, the quantitative trait locus (QTL) with greatest significance was on chromosome 1p13.3-q23.3 (p = 0.004), but this exhibited high heterogeneity and the effect was specific for women. Other significant LS-BMD QTLs were on chromosomes 12q24.31-qter, 3p25.3-p22.1, 11p12-q13.3, and 1q32-q42.3, including one on 18p11-q12.3 that had not been detected by individual studies. For FN-BMD, the strongest QTL was on chromosome 9q31.1-q33.3 (p = 0.002). Other significant QTLs were identified on chromosomes 17p12-q21.33, 14q13.1-q24.1, 9q21.32-q31.1, and 5q14.3-q23.2. There was no correlation in average ranks of bins between men and women and the loci that regulated BMD in men and women and at different sites were largely distinct. Conclusions: This large-scale meta-analysis provided evidence for replication of several QTLs identified in previous studies and also identified a QTL on chromosome 18p11-q12.3, which had not been detected by individual studies. However, despite the large sample size, none of the individual loci identified reached genome-wide significance. [source]

    Large-Scale Genome-Wide Linkage Analysis for Loci Linked to BMD at Different Skeletal Sites in Extreme Selected Sibships,

    JOURNAL OF BONE AND MINERAL RESEARCH, Issue 2 2007
    Yi-Hsiang Hsu
    Abstract Few genome-wide linkage studies of osteoporosis have been conducted in the Asian population. We performed a genome-wide scan involving 3093 adult siblings with at least one sib-pair extremely concordant or discordant for hip BMD. Our results indicated four genome-wide significant QTLs for BMD. In comparison with 12 previous reported linkage studies, we reveal novel linkage regions that have reaching global significance. Introduction: The genetic basis for osteoporosis has been firmly established, but efforts to identify genes associated with this complex trait have been incomplete, especially in Asian populations. The purpose of this study was to identify quantitative trait loci (QTLs) for BMD in a Chinese population. Materials and Methods: We performed a genome-wide scan involving 3093 siblings 25,64 years of age from 941 families, with at least one sib-pair extreme concordant or discordant for total hip BMD from a large community-based cohort (n = 23,327) in Anhui, China. Linkage analysis was performed on BMD residuals adjusted for age, height, weight, occupation, cigarette smoking, physical activity, and alcohol consumption using the revised Haseman-Elston regression-based linkage model. Results: Our results revealed significant QTLs on chromosome 7p21.2 for femoral neck BMD (LOD = 3.68) and on chromosome 2q24.3 for total hip BMD (LOD = 3.65). Suggestive linkage regions were found to overlap among different skeletal sites on chromosomes 2q, 7p, and 16q. Sex-specific linkage analysis further revealed a significant QTL for lumbar spine BMD on chromosome 13q21.1 (LOD = 3.62) in women only. When performing multivariate linkage analysis by combining BMDs at four skeletal sites (i.e., whole body, total hip, femoral neck, and lumbar spine BMD), an additional significant QTL was found at chromosome 5q21.2 (LOD = 4.56). None of these significant QTLs found in our study overlapped with major QTLs reported by other studies. Conclusions: This study reveals four novel QTLs in a Chinese population and suggests that BMD at different skeletal sites may also share common genetic determinants. [source]

    Long-Term Fracture Prediction by DXA and QUS: A 10-Year Prospective Study,

    JOURNAL OF BONE AND MINERAL RESEARCH, Issue 3 2006
    Alison Stewart PhD
    Abstract This study investigated the ability of DXA and QUS to predict fractures long term when measured around the time of the menopause. We found both DXA and QUS are able to predict both any fracture and "osteoporotic" fractures and that QUS can predict independently of BMD. Introduction: There are now many treatments available for prevention of osteoporotic fracture. To be cost-effective, we need to target those most at risk. This study examines the ability of DXA and QUS to predict fractures in an early postmenopausal population of women. Materials and Methods: We prospectively measured 3883 women who had been randomly selected from a community-based register. At baseline, they were measured using DXA of spine and hip (Norland XR-26) and QUS of the heel (Walker Sonix UBA 575). Follow-up had a mean of 9.7 ± 1.1 (SD) years. All incident fractures were identified and validated by examination of X-ray reports, and these were compared with those without fracture in a Cox-regression model to calculate hazard ratios (HRs). Results: We found adjusted HRs for any fracture per 1 SD reduction in spine BMD to be 1.61 (1.42-1.83), whereas neck of femur BMD was 1.54 (1.34-1.75). Areas under the curve (AUC) for a receiver operator characteristic (ROC) analysis were 0.62 for spine BMD and 0.59 for neck BMD. In a subgroup where QUS was also measured, the HR for a 1 SD reduction in BMD was 1.69 (1.29-2.22) for spine BMD and 1.55 (1.17-2.06) for neck BMD. The HR for a 1 SD reduction in broadband ultrasound attenuation (BUA) was 1.53 (1.19-1.96), and 1.44 (1.12-1.86) when further adjusted for neck BMD. The AUCs were 0.63 for spine BMD, 0.59 for neck BMD, and 0.62 for BUA. When only osteoporotic fractures were examined, the HRs increased in all situations. BUA showed the highest HR of 2.25 (1.51-3.34), and when further adjusted for neck BMD was 2.12 (1.38-3.28). Conclusions: In conclusion, it may be possible to scan women around the time of the menopause to predict future fractures. It seems that, for "osteoporotic" fractures, BUA may be an improved predictor of fractures in comparison with DXA, because the relative risk is highest for BUA, and independent of BMD. [source]

    Early Changes in Biochemical Markers of Bone Formation Predict BMD Response to Teriparatide in Postmenopausal Women With Osteoporosis,,

    JOURNAL OF BONE AND MINERAL RESEARCH, Issue 6 2005
    Peiqi Chen
    Abstract The relationship between early changes in biochemical markers of bone turnover and the subsequent BMD response to daily teriparatide therapy in women with postmenopausal osteoporosis was studied. Changes in five biochemical markers, obtained from a subset of women enrolled in the Fracture Prevention Trial, were examined. Early increases in the PICP and the PINP were the best predictors of BMD response to teriparatide in this analysis. Introduction: Early reductions in biochemical markers of bone turnover with antiresorptive therapy negatively correlate with subsequent increases in BMD. We undertook this analysis to determine if early changes in biochemical markers with teriparatide therapy predict subsequent increases in BMD. Materials and Methods: In the Fracture Prevention Trial, 1637 postmenopausal women with osteoporosis were randomized to receive daily, self-administered, subcutaneous injections of placebo, teriparatide 20 ,g/day, or teriparatide 40 ,g/day. Serum concentrations of two bone formation markers (bone-specific alkaline phosphatase [bone ALP] and the carboxy-terminal extension peptide of procollagen type 1 [PICP]) and urinary concentrations of two bone resorption markers (free deoxypyridinoline [DPD] and N-terminal telopeptide [NTX]) were assessed in a trial population subset (n = 520) at baseline and at 1, 3, 6, and 12 months. We also assessed serum concentrations of another bone formation marker, the amino-terminal extension peptide of procollagen type 1 (PINP), in a subset of 771 women at baseline and 3 months. Lumbar spine (LS) BMD was measured by DXA at baseline and 18 months. Femoral neck BMD was measured at baseline and 12 months. Results and Conclusion: Baseline bone turnover status correlated positively and significantly with BMD response. The highest correlations occurred for the LS BMD response to teriparatide 20 ,g/day. Among all studied biochemical markers, increases in PICP at 1 month and PINP at 3 months correlated best with increases in LS BMD at 18 months (0.65 and 0.61, respectively; p < 0.05). The relationships between these two biochemical markers and the LS BMD response were stronger than the corresponding relationships for the femoral neck BMD response. Using receiver operator curve analysis, we determined that the increases in PICP at 1 month and PINP at 3 months were the most sensitive and accurate predictors of the LS BMD response. [source]

    Contribution of the LRP5 Gene to Normal Variation in Peak BMD in Women,

    JOURNAL OF BONE AND MINERAL RESEARCH, Issue 1 2005
    Daniel L Koller
    Abstract The role of the LRP5 gene in rare BMD-related traits has recently been shown. We tested whether variation in this gene might play a role in normal variation in peak BMD. Association between SNPs in LRP5 and hip and spine BMD was measured in 1301 premenopausal women. Only a small proportion of the BMD variation was attributable to LRP5 in our sample. Introduction: Mutations in the low-density lipoprotein receptor-related protein 5 (LRP5) gene have been implicated as the cause of multiple distinct BMD-related rare Mendelian phenotypes. We sought to examine whether the LRP5 gene contributes to the observed variation in peak BMD in the normal population. Materials and Methods: We genotyped 12 single nucleotide polymorphisms (SNPs) in LRP5 using allele-specific PCR and mass spectrometry methods. Linkage disequilibrium between the genotyped LRP5 SNPs was measured. We tested for association between these SNPs and both hip and spine BMD (adjusted for age and body weight) in 1301 healthy premenopausal women who took part in a sibling pair study aimed at identifying the genes underlying peak bone mass. Our study used both population-based (ANOVA) and family-based (quantitative transmission disequilibrium test) association methodology. Results and Conclusions: The linkage disequilibrium pattern and haplotype block structure within the LRP5 gene were consistent with that observed in other studies. Although significant evidence of association was found between LRP5 SNPs and both hip and spine BMD, only a small proportion of the total variation in these phenotypes was accounted for. The genotyped SNPs accounted for ,0.8% of the variation in femoral neck BMD and 1.1% of the variation in spine BMD. Results from our sample suggest that natural variation in and around LRP5 is not a major contributor to the observed variability in peak BMD at either the femoral neck or lumbar spine in white women. [source]

    Associations Between Baseline Risk Factors and Vertebral Fracture Risk in the Multiple Outcomes of Raloxifene Evaluation (MORE) Study

    JOURNAL OF BONE AND MINERAL RESEARCH, Issue 5 2004
    Olof Johnell
    Abstract Different risk factors may influence the effectiveness of osteoporosis therapies. The interaction of 30 baseline risk factors and the effectiveness of raloxifene in the MORE study were assessed. The efficacy of raloxifene in reducing vertebral fractures is largely independent of the presence of clinical risk factors for osteoporotic fractures. Introduction: The aim of this analysis was to determine the effect of different risk factors on the effectiveness of raloxifene to reduce vertebral fractures in the Multiple Outcomes of Raloxifene Evaluation (MORE) study using logistic regression models. Materials and Methods: The association was assessed using univariate analyses and a multivariate model between 30 potential risk factors at baseline and the risk of vertebral fractures after 3 years in the placebo group, as well as the interaction of risk factors with raloxifene therapy (at a dose of 60 or 120 mg/day). Results and Conclusions: In the univariate analysis of the placebo group, after adjusting for baseline lumbar spine BMD (LS BMD), short stature (odds ratio [OR] = 1.18), age (OR = 1.38), years since menopause (OR = 1.38), impaired cognitive function, visuospatial capabilities (OR = 1.19), impaired musculoskeletal strength (OR = 1.23), low femoral neck BMD (OR = 1.21), and prior vertebral fracture (OR = 4.95) were significantly associated with the incidence of new vertebral fractures. In the univariate analysis, significant interactions were observed between raloxifene treatment and age (p = 0.04), serum triglycerides (p = 0.03), LS BMD (p = 0.08), and diabetes mellitus (p = 0.04). In the multivariate analysis, the effectiveness of raloxifene was independent of almost all risk factors, with the exception of baseline serum triglyceride level and LS BMD, suggesting an increased efficacy of raloxifene in patients with increased triglyceride levels (p = 0.006) and lower LS BMD values (p = 0.008) at baseline. These data suggest that the efficacy of raloxifene in reducing vertebral fractures is largely independent of the presence of clinical risk factors for osteoporotic fractures. [source]

    Fracture Prediction From Bone Mineral Density in Japanese Men and Women,

    JOURNAL OF BONE AND MINERAL RESEARCH, Issue 8 2003
    Saeko Fujiwara
    Abstract In a cohort of 2356 Japanese elderly, after adjusting for age and prevalent vertebral fracture, baseline BMD predicted the risk of spine and hip fracture with similar RR to that obtained from previous reports in whites. The RR per SD decrease in BMD for fracture declined with age. Introduction: Low bone mineral density (BMD) is one of the most important predictors of a future fracture. However, we are not aware of any reports among Japanese in Japan. Materials and Methods: We examined the association of BMD with risk of fracture of the spine or hip among a cohort of 2356 men and women aged 47,95 years, who were followed up by biennial health examinations. Follow-up averaged 4 years after baseline measurements of BMD that were taken with the use of DXA. Vertebral fracture was assessed using semiquantitative methods, and the diagnosis of hip fracture was based on medical records. Poisson and Cox regression analysis were used. Results: The incidence was twice as high in women as in men, after adjusting for age. After adjusting for baseline BMD and prevalent vertebral fracture, however, the gender difference was no longer significant. Age, baseline BMD of spine and femoral neck, and prior vertebral fracture predicted vertebral fracture and hip fracture. Loss of absolute BMD of the femoral neck predicted spine fracture, after adjusting for baseline BMD; rates of change in percent BMD, weight, height, body mass index, and age at menopause did not. The predictive value of baseline BMD for vertebral fracture risk was similar in men and women. The relative risk (RR) for vertebral fracture and hip fracture per SD decrease in BMD declined with age, after adjustment for prevalent vertebral fractures. Conclusions: Baseline BMD, loss of femoral neck BMD, and prior vertebral fracture predict the risk of spine and hip fracture in Japanese with similar RR to that obtained from previous reports in whites. The RR per SD decrease in BMD for fracture declined with age, suggesting that factors other than BMD might play a greater role in the elderly. [source]

    Genetic and Environmental Determinants of Peak Bone Mass in Young Men and Women

    JOURNAL OF BONE AND MINERAL RESEARCH, Issue 7 2002
    Fiona E. A. Mcguigan Ph.D.
    Abstract Peak bone mass is an important risk factor for the development of osteoporosis in later life. Previous work has suggested that genetic, intrauterine, and environmental factors all contribute to the regulation of bone mass, but the ways in which they interact with each other to do so remain poorly understood. In this study, we investigated the relationship between peak bone mass and polymorphisms of the vitamin D receptor (VDR), estrogen receptor (ER) ,, and collagen type I,1 (COLIA1) genes in relation to other factors such as birth weight, lifestyle diet, and exercise in a population-based cohort of 216 women and 244 men in their early 20s. Stepwise multiple regression analysis showed that body weight was the strongest predictor of bone mineral density (BMD) in women, accounting for 16.4% of the variance in spine BMD and 8.4% of the variance in femoral neck BMD. Other significant predictors were VDR genotype (3.8%) and carbohydrate intake (1.6%) at the spine and vitamin D intake (3.4%) and ER genotype (3.4%) at the femoral neck. Physical activity was the strongest predictor of BMD in men, accounting for 6.7% of the variance at the spine and 5.1% at the hip. Other significant predictors were body weight (5%) and ER PvuII genotype (2.8%) at the spine and weight (3.4%) and alcohol intake (2%) at the femoral neck. Birth weight was not a significant predictor of BMD at either site but COLIA1 genotype significantly predicted birth weight in women, accounting for 4.3% of the variance. We conclude that peak bone mass is regulated by an overlapping but distinct set of environmental and genetic influences that differ in men and women. However, much of the variance in BMD was unexplained by the variables studied here, which suggests that either most of the genes that regulate BMD remain to be discovered or major environmental influences on BMD exist that have not yet been identified. [source]

    Type I Collagen Racemization and Isomerization and the Risk of Fracture in Postmenopausal Women: The OFELY Prospective Study

    JOURNAL OF BONE AND MINERAL RESEARCH, Issue 5 2002
    Patrick Garnero Ph.D.
    Abstract The Asp1211 residue of the1209AHDGGR1214 sequence of the C-terminal cross-linking telopeptide of type I collagen (CTX) can undergo spontaneous post-translational modifications, namely, racemization and isomerization, which result in the formation of four isomers: the native form (,- L) and three age-related forms, that is, an isomerized form (,- L), a racemized form (,- D), and an isomerized/racemized (,- D) form. Previous studies have suggested that changes in the pattern of type I collagen racemization/isomerization, which can be assessed in vivo by measuring the degradation products of the CTX isoforms, may be associated with alterations of bone structure. The aim of this study was to examine prospectively the value of the different urinary CTX isoforms and their related ratio in the prediction of osteoporotic fractures in 408 healthy untreated postmenopausal women aged 50-89 years (mean, 64 years) who were part of the OFELY cohort. During a median 6.8 years follow-up, 16 incident vertebral fractures and 55 peripheral fractures were recorded in 65 women. The baseline levels of the four CTX isoforms in women who subsequently had a fracture were compared with those of the 343 women who did not fracture. At baseline, women with fractures had increased levels of ratios of native ,- L -CTX to age-related isoforms (,- L, ,- D, and ,- D) compared with controls (p < 0.01). In logistic regression analysis after adjustment for age, prevalent fractures, and physical activity, women with levels of ,- L/,- L, ,- L/,- D, and ,- L/,- D -CTX ratios in the highest quartile had a 1.5- to 2-fold increased risk of fractures compared with women with levels in the three lowest quartiles with relative risk (RR) and 95% CI of 2.0 (1.2-3.5), 1.8 (1.02-2.7), and 1.5 (0.9-2.7), respectively. Adjustment of ,- L/,- L and ,- L/,- D -CTX ratios by the level of bone turnover assessed by serum bone alkaline phosphatase (ALP)- or femoral neck bone mineral density (BMD) decreased slightly the RR, which remained significant for the ,- L/,- L -CTX ratio (RR [95%] CI, 1.8 [1.1-3.2] after adjustment for bone ALP, 1.8 [1.03-3.1] after adjustment for BMD, and 1.7 [0.95-2.9] after adjustment for both bone ALP and BMD). Women with both high ,- L/,- L -CTX ratio and high bone ALP had a 50% higher risk of fracture than women with either one of these two risk factors. Similarly, women with both increased CTX ratio and low femoral neck BMD (T score < ,2.5) had a higher risk of fracture with an RR (95% CI) of 4.5 (2.0-10.1). In conclusion, increased urinary ratio between native and age-related forms of CTX, reflecting decreased degree of type I collagen racemization/isomerization, is associated with increased fracture risk independently of BMD and partly of bone turnover rate. This suggests that alterations of type I collagen isomerization/racemization that can be detected by changes in urinary CTX ratios may be associated with increased skeletal fragility. [source]

    Relationships Between Bone Mineral Density and Incident Vertebral Fracture Risk with Raloxifene Therapy,

    JOURNAL OF BONE AND MINERAL RESEARCH, Issue 1 2002
    Somnath Sarkar Ph.D.
    Abstract Although low absolute values of bone mineral density (BMD) predict increased fracture risk in osteoporosis, it is not certain how well increases in BMD with antiresorptive therapy predict observed reductions in fracture risk. This work examines the relationships between changes in BMD after 1 year or 3 years of raloxifene or placebo therapy and the risk for new vertebral fractures at 3 years. In the Multiple Outcomes of Raloxifene Evaluation (MORE) trial, 7705 postmenopausal women with osteoporosis were randomized to placebo or raloxifene 60 mg/day or 120 mg/day. Relationships between baseline BMD and changes in BMD from baseline with the risk of new vertebral fractures were analyzed in this cohort using logistic regression models with the raloxifene doses pooled. As has been observed in other populations, women with the lowest baseline lumbar spine or femoral neck BMD in the MORE cohort had the greatest risk for vertebral fractures. Furthermore, for any percentage change, either increase or decrease in femoral neck or lumbar spine BMD at 1 year or 3 years, raloxifene-treated patients had a statistically significantly lower vertebral fracture risk compared with placebo-treated patients. The decrease in fracture risk with raloxifene was similar across the range of percentage change in femoral neck BMD observed at 3 years; patients receiving raloxifene had a 36% lower risk of vertebral fracture compared with those receiving placebo. At any percentage change in femoral neck and lumbar spine BMD observed at 1 year, raloxifene treatment decreased the risks of new vertebral fractures at 3 years by 38% and 41%, respectively. The logistic regression model showed that the percentage changes in BMD with raloxifene treatment accounted for 4% of the observed vertebral fracture risk reduction, and the other 96% of the risk reduction remains unexplained. The present data show that the measured BMD changes observed with raloxifene therapy are poor predictors of vertebral fracture risk reduction with raloxifene therapy. [source]

    Effects of Current and Discontinued Estrogen Replacement Therapy on Hip Structural Geometry: The Study of Osteoporotic Fractures,

    JOURNAL OF BONE AND MINERAL RESEARCH, Issue 11 2001
    Thomas J. Beck
    Abstract It is assumed that estrogen influences bone strength and risk of fractures by affecting bone mineral density (BMD). However, estrogen may influence the mechanical strength of bones by altering the structural geometry in ways that may not be apparent in the density. Repeated dual energy X-ray absorptiometry (DXA) hip scan data were analyzed for bone density and structural geometry in elderly women participating in the Study of Osteoporotic Fractures (SOF). Scans were studied with a hip structural analysis program for the effects of estrogen replacement therapy (ERT) on BMD and structural geometry. Of the 3964 women with ERT-use data, 588 used ERT at both the start and end of the ,3.5-year study, 1203 had past use which was discontinued by clinic visit 4, and 2163 women had never used ERT. All groups lost BMD at the femoral neck, but the reduced BMD among users of ERT was entirely due to subperiosteal expansion and not bone loss, whereas both bone loss and expansion occurred in past or nonusers. BMD increased 0.8%/year at the femoral shaft among ERT users but decreased 0.8%/year among nonusers. Section moduli increased at both the neck and shaft among ERT users but remained unchanged in past and nonusers. Current, but not past, use of estrogen therapy in elderly women seems to increase mechanical strength of the proximal femur by improving its geometric properties. These effects are not evident from changes in femoral neck BMD. [source]

    Interleukin-6 Gene Polymorphism Is Related to Bone Mineral Density During and After Puberty in Healthy White Males: A Cross-Sectional and Longitudinal Study

    JOURNAL OF BONE AND MINERAL RESEARCH, Issue 10 2000
    Mattias Lorentzon
    Abstract Bone mineral density (BMD) is under strong genetic control and is the major determinant of fracture risk. The cytokine interleukin-6 (IL-6) is an important regulator of bone metabolism and is involved in mediating the effects of androgens and estrogens on bone. Recently, a G/C polymorphism in position ,174 of the IL-6 gene promoter was found. We investigated this genetic polymorphism in relation to BMD during late puberty and to peak bone mass, in healthy white males. We identified the IL-6 genotypes (GG, GC, and CC) in 90 boys, age 16.9 ± 0.3 years (mean ± SD), using polymerase chain reaction (PCR). BMD (g/cm2) at the femoral neck, lumbar spine, and total body was measured using dual energy X-ray absorptiometry. The volumetric BMD (vBMD; mg/cm3) of the lumbar spine was estimated. Differences in BMD in relation to the genotypes were calculated using analysis of variance (ANOVA). Subjects with the CC genotype had 7.9% higher BMD of the femoral neck (p = 0.03), 7.0% higher BMD of the lumbar spine (p < 0.05), and 7.6% higher vBMD of the lumbar spine (p = 0.04), compared with their GG counterparts. Using multiple regression, the IL-6 genotypes were independently related to total body BMD (CC > GG; p = 0.03), humerus BMD (CC > GG; p < 0.05), neck BMD (CC > GG; p = 0.01), spine BMD (CC > GG; p = 0.01), and spine vBMD (CC > GG; p = 0.008). At age 19.3 ± 0.7 years (mean ± SD; 88 men) the IL-6 genotypes were still independent predictors for total body BMD (CC > GG; p = 0.03), humerus BMD (CC > GG; p = 0.03), spine BMD (CC > GG; p = 0.02), and spine vBMD (CC > GG; p = 0.003), while the IL-6 genotypes were not related to the increase in bone density seen after 2 years. We have shown that polymorphism of the IL-6 gene is an independent predictor of BMD during late puberty and of peak bone mass in healthy white men. [source]

    Serum fasting cortisol in relation to bone, and the role of genetic variations in the glucocorticoid receptor

    CLINICAL ENDOCRINOLOGY, Issue 6 2007
    N. M. Van Schoor
    Summary Objective, To examine the relationship between endogenous cortisol and bone, and the role of genetic variations in the glucocorticoid receptor (GR). Design and patients, The Longitudinal Ageing Study Amsterdam (LASA), a population-based cohort study in older men and women. Measurements, Serum fasting cortisol was assessed by competitive immunoassay (n = 1214); bone mineral density (BMD) by dual X-ray absorptiometry (DXA) (n = 502); broadband ultrasound attenuation (BUA) by ultrasound (n = 1209); fractures by self-report (n = 1211); and GR gene polymorphisms (ER22/23EK, N363S, 9beta, BclI) were genotyped by Taqman (n = 858). Results, Higher serum fasting cortisol was significantly associated with lower BMD at all sites and BUA at the heel in women, although most relationships were attenuated by age and body mass index (BMI). The effect on femoral neck BMD remained statistically significant in the fully adjusted model (r = ,0·135, P = 0·04). No significant associations in men were found. Female 9beta G-allele carriers had 50·2 nmol/l lower cortisol and 1·2 lower free cortisol levels than AA homozygotes [P = 0·01 for (free) cortisol]. Furthermore, female BclI GG homozygotes had 54·8 nmol/l higher cortisol levels than C-carriers (P = 0·03). In the total population, BclI GG homozygotes had 0·05 g/cm2 lower trochanteric region BMD (P = 0·03). For the other GR gene polymorphisms, no significant associations were found. Conclusions, Higher cortisol levels are associated with lower femoral neck BMD in elderly women. The G allele of the 9beta polymorphism was associated with lower serum cortisol levels in women. Female BclI GG homozygotes had higher serum cortisol levels, and BclI GG homozygotes had lower trochanteric region BMD in the total population. [source]

    The relationship between serum resistin, leptin, adiponectin, ghrelin levels and bone mineral density in middle-aged men

    CLINICAL ENDOCRINOLOGY, Issue 2 2005
    Ki Won Oh
    Summary Objective Body weight is a significant predictor of bone mass. Hormonal factors such as sex hormones, insulin, leptin and adiponectin are thought to play a role in the mechanisms controlling the association of body weight and fat mass with bone mass. However, contradictory results have been reported for the association between serum adipocytokines and bone mineral density (BMD). We therefore examined whether the serum adipocytokine and ghrelin levels, markers of fat metabolism, are associated with BMD in male adults. Patients and measurements For 80 male adults (average age 54·5 ± 6·4 years; average body mass index (BMI) 24·4 ± 2·5 kg/m2), the correlations between serum resistin, leptin, adiponectin and ghrelin levels with BMD were investigated. Results Among the adipocytokines, serum resistin levels were negatively correlated with lumbar spine BMD (r = ,0·237, P = 0·05). After adjustment was made for age and BMI, log-transformed serum leptin showed a significant negative correlation with lumbar spine BMD, which was not seen on bivariate analysis (r = ,0·237, P = 0·039). Femoral neck BMD was marginally associated only with serum adiponectin levels (r = ,0·226, P = 0·062). In multiple regression analyses, among the adipokines, only resistin was a significant determinant of lumbar spine BMD, although the variance was small (R2 = 0·256). Serum ghrelin levels were not correlated with the BMD of either body site. Conclusions Serum resistin level showed a significant negative correlation with lumbar spine BMD, although the variance was small. Further studies are needed to elucidate the role of adipocytokines in bone metabolism. [source]

    The impact of idiopathic childhood-onset growth hormone deficiency (GHD) on bone mass in subjects without adult GHD

    CLINICAL ENDOCRINOLOGY, Issue 1 2005
    Martin Lange
    Summary objective, Despite seemingly adequate growth hormone (GH) treatment during childhood, children with GH deficiency (GHD) have reduced bone mineral density (BMD) at final height. The aim was to evaluate BMD and bone mineral content (BMC) in adults treated for idiopathic childhood-onset (CO) GHD, 18 years after stopping GH treatment. subjects and methods, Twenty-six (11 females) patients with idiopathic CO GHD participated. All patients but two had been treated for isolated GHD in childhood. The childhood diagnosis was established by an insulin tolerance test (ITT) and reassessed in adulthood by an ITT (N = 21) or arginine test (n = 5), revealing that 10 patients had GHD according to adult criteria. Accordingly, the patient group was divided into (1) patients who did not have persistent GHD in adulthood and (2) patients who did have persistent adult GHD. Twenty-six healthy subjects acted as age-, gender- and body mass index (BMI)-matched controls. results, The patients who did not have persistent GHD had significantly lower IGF-I values and whole-body, femoral neck and lumbar spine BMD compared to controls [0·994 ± 0·10 vs. 1·114 ± 0·11 g/cm2 (P = 0·003), 0·842 ± 0·12 vs. 0·962 ± 0·11 g/cm2 (P = 0·006) and 1·026 ± 0·14 vs. 1·127 ± 0·13 g/cm2 (P = 0·004), respectively]. Femoral neck BMD was significantly reduced in the patients who had persistent GHD, compared to controls (0·842 ± 0·09 vs. 0·938 ± 0·11, P = 0·04). Significant correlations were observed between all bone variables and IGF-I in all subjects, whereas no correlations were observed between bone variables and GH peak levels in the 26 patients. conclusion, In conclusion, we found that (1) patients with idiopathic CO GHD, who at retest in adulthood did not have GHD according to adult criteria, had reduced serum IGF-I and BMD/BMC compared to controls. (2) This observation was also made in the patients who did have persistent GHD in adulthood. The findings may reflect the fact that the present diagnostic criteria for adult GHD (i.e. response to the ITT) do not reflect the clinical consequences of disordered GH,IGF axis in CO GHD young adults who were treated with GH in childhood. Alternatively, despite seemingly adequate GH treatment in childhood an optimal peak bone mass in adolescence may never have been reached in either of the groups. (3) IGF-I levels correlated with clinical signs of the adult GHD syndrome. We believe that further studies on the indications and diagnostic procedures for GH treatment after cessation of linear growth are necessary. [source]