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Spine BMD (spine + bmd)

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Medical Sciences100%

Kinds of Spine BMD

  • lumbar spine bmd
    		•

    Selected Abstracts

    Proton pump inhibitor omeprazole use is associated with low bone mineral density in maintenance haemodialysis patients

    INTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 2 2009
    A. Kirkpantur
    Summary Objective:, Limited studies have shown that proton pump inhibitor (PPI) therapy may decrease bone density or insoluble calcium reabsorption through induction of hypochlorhydria. However, PPI therapy may also reduce bone resorption via inhibition of osteoclastic vacuolar proton pumps. The aim of this study was to determine whether the opposing effects of PPI therapy may cause clinically important alterations in bone mineral densitometry (BMD) parameters in maintenance haemodialysis patients. Methods:, Sixty-eight maintenance haemodialysis patients were enrolled in this study. Patients were classified into two groups involving users of PPI therapy (omeprazole 20 mg/day, group 1, n = 36 patients) and non-users of acid suppression drugs (group 2, n = 32 patients). Patients had radius, hip and spine BMD assessed by dual-energy X-ray absorptiometry. Results:, The mean duration of PPI therapy with omeprazole was 27 ± 5 months. The users of PPI therapy had lower values of bone mineral density and T -scores at the anatomical regions than non-users of acid suppression drugs. Serum calcium and phosphate levels, calcium-phosphate product and serum intact parathormone levels and the ratio of users of vitamin D therapy were similar among groups. A mutivariable adjusted odds ratio for lower bone density associated with more than 18 months of omeprazole, when all the potential confounders were considered, was 1.31 in the proximal radius, 0.982 in the femur neck, 0.939 in the trochanter and 1.192 in the lumbal spine. Conclusion:, The present data suggest that PPI therapy should be cautiously prescribed in maintenance haemodialysis patients, especially with lower BMD values. [source]

    Head-to-head comparison of risedronate vs. teriparatide on bone turnover markers in women with postmenopausal osteoporosis: a randomised trial

    INTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 6 2008
    A. D. Anastasilakis
    Summary Aims:, We aimed to compare the effect of risedronate (RIS) and teriparatide (TPTD) (recombinant human parathyroid hormone 1,34) on bone turnover markers in women with postmenopausal osteoporosis. Methods:, Forty-four Caucasian women (age 65.1 ± 1.6 years) with postmenopausal osteoporosis were randomly assigned to receive either RIS 35 mg once weekly (n = 22) or TPTD 20 ,g once daily (n = 22) for 12 months. Serum N-terminal propeptide of type 1 collagen (P1NP), C-terminal telopeptide of type 1 collagen (CTx), total alkaline phosphatase (ALP) and intact parathyroid hormone (iPTH) were obtained from all women before, 3 and 6 months after treatment initiation. Lumbar spine bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry before and 12 months after treatment initiation. Results:, P1NP, CTx and total ALP levels decreased in RIS group (p < 0.001) and increased in TPTD group (p < 0.001) throughout the treatment. iPTH increased significantly in RIS group (p < 0.05) and decreased in TPTD group (p < 0.001). Finally, lumbar spine BMD increased significantly in both RIS (p = 0.003) and TPTD groups (p < 0.001) without significant differences between them. Conclusions:, Our data suggest that both serum P1NP and CTx are reliable markers of RIS and TPTD action in women with postmenopausal osteoporosis. In a similar way, serum total ALP can be used as an alternative marker for monitoring both RIS and TPTD action, while iPTH can be used only for TPTD-treated women. The increase in P1NP and CTx after 3 months of treatment with RIS or TPTD can predict the increase in BMD after 12 months of treatment. [source]

    Clinical Characteristics of Flexed Posture in Elderly Women

    JOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 10 2003
    Lara Balzini PT
    Objectives: To investigate the relationships between the severity of flexed posture (FP), skeletal fragility, and functional status level in elderly women. Design: Cross-sectional study. Setting: Geriatric rehabilitation research hospital. Participants: Sixty elderly women (aged 70,93) with FP referred to a geriatric rehabilitation department for chronic back pain without apparent comorbid conditions. Measurements: Multidimensional clinical assessment included the severity of FP (standing occiput-to-wall distance) demographic (age) and anthropometric (height, weight) data, clinical profile (number of falls, pain assessment, Mini-Mental State Examination, Comorbidity Severity Index, Geriatric Depression Scale, Multidimensional Fatigue Inventory), measures of skeletal fragility (number of vertebral fractures by spine radiograph, bone mineral density (BMD), and T-score of lumbar spine and proximal femur), muscular impairment assessment (muscle strength and length), motor performance (Short Physical Performance Battery, Performance Oriented Mobility Assessment, instrumented gait analysis), and evaluation of disability (Barthel Index, Nottingham Extended Activities of Daily Living Index). Results: The severity of FP was classified as mild in 11, moderate in 28, and severe in 21 patients. Although there were no differences between FP groups on the skeletal fragility measurements, the moderate and severe FP groups were significantly different from the mild FP group for greater pain at the level of the cervical and lumbar spine. The severe FP group was also significantly different from the mild but not the moderate FP group in the following categories: clinical profile (greater depression, reduced motivation), muscle impairment (weaker spine extensor, ankle plantarflexor, and dorsiflexor muscles; shorter pectoralis and hip flexor muscles), the motor function performance-based tests (lower scores in the balance and gait subsets of the Performance Oriented Mobility Assessment), the instrumented gait analysis (slower and wider base of support), and disability (lower score on the Nottingham Extended Activities of Daily Living Index). The total number of vertebral fractures was not associated with differences in severity of FP, demographic and anthropometric characteristics, clinical profile, muscular function, performance-based and instrumental measures of motor function, and disability, but it was associated with reduced proximal femur and lumbar spine BMD. Conclusion: The severity of FP in elderly female patients (without apparent comorbid conditions) is related to the severity of vertebral pain, emotional status, muscular impairments, and motor function but not to osteoporosis, and FP has a measurable effect on disability. In contrast, the presence of vertebral fractures in patients with FP is associated with lower BMD but not patients' clinical and functional status. Therefore, FP, back pain, and mobility problems can occur without osteoporosis. Older women with FP and vertebral pain may be candidates for rehabilitation interventions that address muscular impairments, posture, and behavior modification. Randomized controlled trials are needed to support these conclusions. [source]

    Replication of previous genome-wide association studies of bone mineral density in premenopausal American women

    JOURNAL OF BONE AND MINERAL RESEARCH, Issue 8 2010
    Shoji Ichikawa
    Abstract Bone mineral density (BMD) achieved during young adulthood (peak BMD) is one of the major determinants of osteoporotic fracture in later life. Genetic variants associated with BMD have been identified by three recent genome-wide association studies. The most significant single-nucleotide polymorphisms (SNPs) from these studies were genotyped to test whether they were associated with peak BMD in premenopausal American women. Femoral neck and lumbar spine BMD were determined by dual-energy X-ray absorptiometry in two groups of premenopausal women: 1524 white women and 512 black women. In premenopausal white women, two SNPs in the C6orf97/ESR1 region were significantly associated with BMD (p,<,4.8,×,10,4), with suggestive evidence for CTNNBL1 and LRP5 (p,<,.01). Evidence of association with one of the two SNPs in the C6orf97/ESR1 region also was observed in premenopausal black women. Furthermore, SNPs in SP7 and a chromosome 4 intergenic region showed suggestive association with BMD in black women. Detailed analyses of additional SNPs in the C6orf97/ESR1 region revealed multiple genomic blocks independently associated with femoral neck and lumbar spine BMD. Findings in the three published genome-wide association studies were replicated in independent samples of premenopausal American women, suggesting that genetic variants in these genes or regions contribute to peak BMD in healthy women in various populations. © 2010 American Society for Bone and Mineral Research [source]

    Genome-wide pleiotropy of osteoporosis-related phenotypes: The framingham study

    JOURNAL OF BONE AND MINERAL RESEARCH, Issue 7 2010
    David Karasik
    Abstract Genome-wide association studies offer an unbiased approach to identify new candidate genes for osteoporosis. We examined the Affymetrix 500K,+,50K SNP GeneChip marker sets for associations with multiple osteoporosis-related traits at various skeletal sites, including bone mineral density (BMD, hip and spine), heel ultrasound, and hip geometric indices in the Framingham Osteoporosis Study. We evaluated 433,510 single-nucleotide polymorphisms (SNPs) in 2073 women (mean age 65 years), members of two-generational families. Variance components analysis was performed to estimate phenotypic, genetic, and environmental correlations (,P, ,G, and ,E) among bone traits. Linear mixed-effects models were used to test associations between SNPs and multivariable-adjusted trait values. We evaluated the proportion of SNPs associated with pairs of the traits at a nominal significance threshold ,,=,0.01. We found substantial correlation between the proportion of associated SNPs and the ,P and ,G (r,=,0.91 and 0.84, respectively) but much lower with ,E (r,=,0.38). Thus, for example, hip and spine BMD had 6.8% associated SNPs in common, corresponding to ,P,=,0.55 and ,G,=,0.66 between them. Fewer SNPs were associated with both BMD and any of the hip geometric traits (eg, femoral neck and shaft width, section moduli, neck shaft angle, and neck length); ,G between BMD and geometric traits ranged from ,0.24 to +0.40. In conclusion, we examined relationships between osteoporosis-related traits based on genome-wide associations. Most of the similarity between the quantitative bone phenotypes may be attributed to pleiotropic effects of genes. This knowledge may prove helpful in defining the best phenotypes to be used in genetic studies of osteoporosis. © 2010 American Society for Bone and Mineral Research [source]

    Timing of ibuprofen use and bone mineral density adaptations to exercise training

    JOURNAL OF BONE AND MINERAL RESEARCH, Issue 6 2010
    Wendy M Kohrt
    Abstract Prostaglandins (PGs) are essential signaling factors in bone mechanotransduction. In animals, inhibition of the enzyme responsible for PG synthesis (cyclooxygenase) by nonsteroidal anti-inflammatory drugs (NSAIDs) blocks the bone-formation response to loading when administered before, but not immediately after, loading. The aim of this proof-of-concept study was to determine whether the timing of NSAID use influences bone mineral density (BMD) adaptations to exercise in humans. Healthy premenopausal women (n,=,73) aged 21 to 40 years completed a supervised 9-month weight-bearing exercise training program. They were randomized to take (1) ibuprofen (400,mg) before exercise, placebo after (IBUP/PLAC), (2) placebo before, ibuprofen after (PLAC/IBUP), or (3) placebo before and after (PLAC/PLAC) exercise. Relative changes in hip and lumbar spine BMD from before to after exercise training were assessed using a Hologic Delphi-W dual-energy X-ray absorptiometry (DXA) instrument. Because this was the first study to evaluate whether ibuprofen use affects skeletal adaptations to exercise, only women who were compliant with exercise were included in the primary analyses (IBUP/PLAC, n,=,17; PLAC/PLAC, n,=,23; and PLAC/IBUP, n,=,14). There was a significant effect of drug treatment, adjusted for baseline BMD, on the BMD response to exercise for regions of the hip (total, p,<,.001; neck, p,=,.026; trochanter, p,=,.040; shaft, p,=,.019) but not the spine (p,=,.242). The largest increases in BMD occurred in the group that took ibuprofen after exercise. Total-hip BMD changes averaged ,0.2%,±,1.3%, 0.4%,±,1.8%, and 2.1%,±,1.7% in the IBUP/PLAC, PLAC/PLAC, and PLAC/IBUP groups, respectively. This preliminary study suggests that taking NSAIDs after exercise enhances the adaptive response of BMD to exercise, whereas taking NSAIDs before may impair the adaptive response. © 2010 American Society for Bone and Mineral Research [source]

    Sequential Treatment of Severe Postmenopausal Osteoporosis After Teriparatide: Final Results of the Randomized, Controlled European Study of Forsteo (EUROFORS),,

    JOURNAL OF BONE AND MINERAL RESEARCH, Issue 4 2009
    Richard Eastell
    Abstract It is unclear which treatment should be given after stopping teriparatide therapy for severe osteoporosis. In a prospective, randomized, controlled, 2-yr study, we compared BMD effects and clinical safety of three follow-up treatments (anabolic with teriparatide, antiresorptive with raloxifene, or no active treatment) after 1 yr of teriparatide. Postmenopausal women with osteoporosis and a recent fragility fracture received open-label teriparatide (20 ,g/d) for 12 mo before they were randomized (3:1:1) to continue teriparatide (n = 305), switch to raloxifene 60 mg/d (n = 100), or receive no active treatment for the second year (n = 102). All patients received calcium and vitamin D supplementation. Changes in areal BMD from baseline to 24 mo were analyzed using mixed-model repeated measures. Daily teriparatide treatment for 2 yr significantly increased spine BMD by 10.7%. Patients receiving raloxifene in year 2 had no further change in spine BMD from year 1 (change from baseline, 7.9%), whereas patients receiving no active treatment had a BMD decrease of 2.5% in year 2 (change from baseline, +3.8%). At the total hip, BMD increases from baseline at 2 yr were 2.5% with teriparatide, 2.3% with raloxifene, and 0.5% with no active treatment; the respective changes at the femoral neck were 3.5%, 3.1%, and 1.3%. The study had insufficient power to assess antifracture efficacy. In conclusion, BMD increases progressively over 2 yr of teriparatide therapy in women with severe osteoporosis. After discontinuation of teriparatide, raloxifene maintains spine BMD and increases hip BMD. [source]

    Impaired Energetic Metabolism After Central Leptin Signaling Leads to Massive Appendicular Bone Loss in Hindlimb-Suspended Rats,

    JOURNAL OF BONE AND MINERAL RESEARCH, Issue 12 2008
    Aline Martin
    Abstract We previously showed in rats that the leptin effects on bone were dose dependent. Positive effects were observed when serum leptin concentration was in a physiological range. In contrast, important increases in serum leptin levels led to negative effects on bone formation similar to those reported after intracerebroventricular leptin administration in mice. To clarify whether leptin effects on bone depend on administration route and/or animal model, female rats were hindlimb unloaded or not and treated either with intracerebroventricular infusion of leptin or vehicle for 14 days. By increasing cerebrospinal fluid (CSF) leptin concentration, intracerebroventricular infusion of leptin significantly reduced food intake and consequently body weight, abdominal fat, and lean mass of the animals. Leptin infusion inhibited bone elongation over the 14 days and blunted cortical bone thickening at the femoral diaphysis site. Interestingly, leptin effects were site dependent in the cancellous bone envelopes, because tibia metaphysis BMD was lower and lumbar spine BMD was higher under intracerebroventricular leptin. Treated groups showed reduced bone remodeling independently of hindlimb unloading. Multiple downstream pathways were implicated in the mediation of these negative leptin effects on bone including not only stimulation of the sympathetic nervous system but also a decrease in somatotropic axis activity. Therefore, the intracerebroventricular leptin-induced bone loss could be largely related to the concurrent alteration of energetic and metabolic status. In summary, our study supports the hypothesis of a concentration-dependent balance between peripheral and central control of leptin on bone. [source]

    Endogenous Estrogen Levels and the Effects of Ultra-Low-Dose Transdermal Estradiol Therapy on Bone Turnover and BMD in Postmenopausal Women,

    JOURNAL OF BONE AND MINERAL RESEARCH, Issue 11 2007
    Alison J Huang
    Abstract In a randomized controlled trial of a 0.014 mg/d transdermal estradiol patch, serum bone turnover markers decreased to a greater degree in postmenopausal women with lower versus higher endogenous estradiol levels. This suggests that the protective effects of ultra-low-dose estrogen therapy on the postmenopausal skeletal health may depend critically on women's endogenous estrogen levels before treatment. Introduction: Postmenopausal women with very low or undetectable estradiol levels have lower BMD, increased bone turnover, and increased risk of hip and vertebral fracture. We assessed whether the effects of ultra-low-dose 0.014 mg/d transdermal estradiol (Menostar; Berlex, Montvale, NJ, USA) on bone turnover and BMD are influenced by endogenous estradiol levels. Materials and Methods: We analyzed data from postmenopausal women (mean age, 66 yr) randomized to an 0.014-mg/d transdermal estradiol patch or placebo in the ultra-low-dose transdermal estrogen (ULTRA) trial. The free estradiol index (FEI), calculated as the ratio of total estradiol (by mass spectometry) to sex hormone-binding globulin (SHBG; by immunoradiometric assay) × 100, was used to estimate bioavailable estradiol at baseline. Among the 382 women who adhered to ,80% of study medication, we examined change in serum osteocalcin and bone-specific alkaline phosphatase levels at 12 mo and total hip and lumbar spine BMD at 24 mo in each quintile of FEI. Results: Compared with women in the highest quintile of FEI, those in the lowest quintile of FEI had a 26% greater reduction in bone-specific alkaline phosphatase and 15% greater reduction in osteocalcin in response to ultra-low estradiol treatment (p for trend across quintiles < 0.05). There was a trend toward greater improvement in total hip BMD (p = 0.06) but not spine BMD (p = 0.90) in those with lower versus higher FEI levels. Conclusions: The beneficial effects of ultra-low-dose 0.014-mg/d transdermal estrogen therapy on skeletal health may depend critically on women's endogenous estrogen levels before treatment. [source]

    Thyroid-Stimulating Hormone Restores Bone Volume, Microarchitecture, and Strength in Aged Ovariectomized Rats*,,§

    JOURNAL OF BONE AND MINERAL RESEARCH, Issue 6 2007
    T Kuber Sampath PhD
    Abstract We show the systemic administration of low levels of TSH increases bone volume and improves bone microarchitecture and strength in aged OVX rats. TSH's actions are mediated by its inhibitory effects on RANKL-induced osteoclast formation and bone resorption coupled with stimulatory effects on osteoblast differentiation and bone formation, suggesting TSH directly affects bone remodeling in vivo. Introduction: Thyroid-stimulating hormone (TSH) receptor haploinsufficient mice with normal circulating thyroid hormone levels have reduced bone mass, suggesting that TSH directly affects bone remodeling. We examined whether systemic TSH administration restored bone volume in aged ovariectomized (OVX) rats and influenced osteoclast formation and osteoblast differentiation in vitro. Materials and Methods: Sprague-Dawley rats were OVX at 6 months, and TSH therapy was started immediately after surgery (prevention mode; n = 80) or 7 mo later (restoration mode; n = 152). Hind limbs and lumbar spine BMD was measured at 2- or 4-wk intervals in vivo and ex vivo on termination at 8,16 wk. Long bones were subjected to ,CT, histomorphometric, and biomechanical analyses. The direct effect of TSH was examined in osteoclast and osteoblast progenitor cultures and established rat osteosarcoma-derived osteoblastic cells. Data were analyzed by ANOVA Dunnett test. Results: In the prevention mode, low doses (0.1 and 0.3 ,g) of native rat TSH prevented the progressive bone loss, and importantly, did not increase serum triiodothyroxine (T3) and thyroxine (T4) levels in aged OVX rats. In restoration mode, animals receiving 0.1 and 0.3 ,g TSH had increased BMD (10,11%), trabecular bone volume (100,130%), trabecular number (25,40%), trabecular thickness (45,60%), cortical thickness (5,16%), mineral apposition and bone formation rate (200,300%), and enhanced mechanical strength of the femur (51,60%) compared with control OVX rats. In vitro studies suggest that TSH's action is mediated by its inhibitory effects on RANKL-induced osteoclast formation, as shown in hematopoietic stem cells cultivated from TSH-treated OVX rats. TSH also stimulates osteoblast differentiation, as shown by effects on alkaline phosphatase activity, osteocalcin expression, and mineralization rate. Conclusions: These results show for the first time that systemically administered TSH prevents bone loss and restores bone mass in aged OVX rats through both antiresorptive and anabolic effects on bone remodeling. [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]

    Treatment of Skeletally Mature Ovariectomized Rhesus Monkeys With PTH(1-84) for 16 Months Increases Bone Formation and Density and Improves Trabecular Architecture and Biomechanical Properties at the Lumbar Spine,

    JOURNAL OF BONE AND MINERAL RESEARCH, Issue 2 2007
    John Fox PhD
    Abstract Histomorphometric studies of treatments for osteoporosis in humans are restricted to iliac crest biopsies. We studied the effects of PTH(1-84) treatment at the lumbar spine of skeletally mature ovariectomized rhesus monkeys. PTH increased bone turnover, rapidly normalized BMD, and increased vertebral compressive strength. PTH increased trabecular bone volume primarily by increasing trabecular number by markedly increasing intratrabecular tunneling. Introduction: Histomorphometric studies of the anabolic properties of PTH(1-84) (PTH) and related peptides in human bone are restricted to iliac crest biopsies. The ovariectomized (OVX) monkey is an accepted model of human postmenopausal bone loss and was used to study the effects of PTH treatment at clinically relevant skeletal sites. Materials and Methods: Skeletally mature rhesus monkeys were OVX or sham-operated and, after a bone depletion period of 9 months, treated daily for 16 months with PTH (5, 10, or 25 ,g/kg). Markers of bone formation (serum osteocalcin) and resorption (urine N-telopeptide [NTX]) and lumbar spine BMD were measured throughout the study. Trabecular architecture and vertebral biomechanical properties were quantified at 16 months. Results: PTH treatment induced dose-dependent increases in bone turnover but did not increase serum calcium. Osteocalcin was significantly increased above OVX controls by 1 month. NTX was significantly elevated at 1 month with the highest dose, but not until 12 months with the 5 and 10 ,g/kg doses. Lumbar spine BMD was 5% lower in OVX than in sham animals when treatment was started. All PTH doses increased BMD rapidly, with sham levels restored by 3,7 months with 10 and 25 ,g/kg and by 16 months with 5 ,g/kg. PTH treatment increased trabecular bone volume (BV/TV), primarily by increasing trabecular number, and dose-dependently increased bone formation rate (BFR) solely by increasing mineralizing surface. The largest effects on BV/TV and yield load occurred with the 10 ,g/kg dose. The highest dose reduced trabecular thickness by markedly increasing intratrabecular tunneling. Conclusions: PTH treatment of OVX rhesus monkeys increased bone turnover and increased BV/TV, BMD, and strength at the lumbar spine. All PTH doses were safe, but the 10 ,g/kg dose was generally optimal, possibly because the highest dose resulted in too marked a stimulation of bone remodeling. [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]

    Effect of Teriparatide {rhPTH(1-34)} on BMD When Given to Postmenopausal Women Receiving Hormone Replacement Therapy

    JOURNAL OF BONE AND MINERAL RESEARCH, Issue 2 2006
    Louis G Ste-Marie
    Abstract The effects of teriparatide when given in combination with HRT were studied in postmenopausal women with low bone mass or osteoporosis. The data provide evidence that the adverse event profile for combination therapy with teriparatide + HRT together is consistent with that expected for each treatment alone and that the BMD response is greater than for HRT alone. Introduction: Teriparatide {rhPTH(1-34)}, given as a once-daily injection, activates new bone formation in patients with osteoporosis. Hormone replacement therapy (HRT) prevents osteoporosis by reducing bone resorption and formation. Combination therapy with these two compounds, in small clinical trials, increased BMD and reduced vertebral fracture burden. The purpose of this study was to determine whether teriparatide provided additional effect on BMD when given in combination with HRT. Materials and Methods: A randomized, double-blind, placebo-controlled study was conducted in postmenopausal women with either low bone mass or osteoporosis. Patients were randomized to placebo subcutaneous plus HRT (n = 125) or teriparatide 40 ,g/day (SC) plus HRT (TPTD40 + HRT; n = 122) for a median treatment exposure of 13.8 months. Approximately one-half of the patients in each group were pretreated with HRT for at least 12 months before randomization. Patients received 1000 mg calcium and 400,1200 IU of vitamin D daily as oral supplementation. BMD was measured by DXA. Results: Compared with HRT alone, TPTD40 + HRT produced significant (p < 0.001) increases in spine BMD (14% versus 3%), total hip (5.2% versus 1.6%), and femoral neck (5.2% versus 2%) at study endpoint. BMD, in whole body and ultradistal radius, was higher, and in the one-third distal radius was lower, in the combination therapy but not in the HRT group. Serum bone-specific alkaline phosphatase and urinary N-telopeptide/Cr were increased significantly (p < 0.01) in the women receiving TPTD40 + HRT compared with HRT. A similar profile of BMD and bone markers was evident in both randomized patients as well as in subgroups of patients not pretreated or pretreated with HRT. Patients tolerated both the treatments well. Nausea and leg cramps were more frequently reported in the TPTD40 + HRT group. Conclusions: Adding teriparatide, a bone formation agent, to HRT, an antiresorptive agent, provides additional increases in BMD beyond that provided by HRT alone. The adverse effects of teriparatide when added to HRT were similar to the adverse effects described for teriparatide administered alone. Whether teriparatide was initiated at the same time as HRT or after at least 1 year on HRT, the incremental increases over HRT alone were similar. [source]

    Serum TRACP 5b Is a Useful Marker for Monitoring Alendronate Treatment: Comparison With Other Markers of Bone Turnover,

    JOURNAL OF BONE AND MINERAL RESEARCH, Issue 10 2005
    Arja Nenonen MSc
    Abstract We studied clinical performance of serum TRACP 5b and other bone turnover markers, including S-CTX, U-DPD, S-PINP, S-BALP, and S-OC, for monitoring alendronate treatment. TRACP 5b had higher clinical sensitivity, area under the ROC curve, and signal-to-noise ratio than the other markers. Introduction: The purpose of this study was to compare the clinical performance of serum TRACP 5b (S-TRACP5b) with that of other markers of bone turnover in the monitoring of alendronate treatment. Materials and Methods: This double-blinded study included 148 healthy postmenopausal women that were randomly assigned into two groups: one receiving 5 mg alendronate daily (n = 75) and the other receiving placebo (n = 73) for 12 months. All individuals in both groups received calcium and vitamin D daily. The bone resorption markers S-TRACP5b, serum C-terminal cross-linked telopeptides of type I collagen (S-CTX), and total urinary deoxypyridinoline (U-DPD), and the serum markers of bone formation procollagen I N-terminal propeptide (S-PINP), bone-specific alkaline phosphatase (S-BALP), and total osteocalcin (S-OC) were assessed at baseline and at 3, 6, and 12 months after initiation of treatment. Lumbar spine BMD (LBMD) was measured at baseline and 12 months. Results: Compared with the placebo group, LBMD increased, and all bone markers decreased significantly more in the alendronate group (p < 0.001 for each parameter). The decrease of S-TRACP5b after first 3 months of alendronate treatment correlated significantly with the changes of all other markers except S-OC, the best correlation being with S-CTX (r = 0.60, p < 0.0001). The changes of LBMD at 12 months only correlated significantly with the changes of S-TRACP5b (r = ,0.32, p = 0.005) and S-CTX (r = ,0.24, p = 0.037) at 3 months. Based on clinical sensitivity, receiver operating characteristic (ROC) curves, and signal-to-noise ratio, S-TRACP5b, S-CTX, and S-PINP were the best markers for monitoring alendronate treatment. Clinical sensitivity, area under the ROC curve, and signal-to-noise ratio were higher for S-TRACP5b than for the other markers. Conclusion: These results show that S-TRACP5b, S-CTX, and S-PINP are useful markers for monitoring alendronate treatment. [source]

    Monthly Oral Ibandronate Therapy in Postmenopausal Osteoporosis: 1-Year Results From the MOBILE Study

    JOURNAL OF BONE AND MINERAL RESEARCH, Issue 8 2005
    Paul D Miller MD
    Abstract Once-monthly (50/50, 100, and 150 mg) and daily (2.5 mg; 3-year vertebral fracture risk reduction: 52%) oral ibandronate regimens were compared in 1609 women with postmenopausal osteoporosis. At least equivalent efficacy and similar safety and tolerability were shown after 1 year. Introduction: Suboptimal adherence to daily and weekly oral bisphosphonates can potentially compromise therapeutic outcomes in postmenopausal osteoporosis. Although yet to be prospectively shown in osteoporosis, evidence from randomized clinical trials in several other chronic conditions shows that reducing dosing frequency enhances therapeutic adherence. Ibandronate is a new and potent bisphosphonate with antifracture efficacy proven for daily administration and also intermittent administration with a dose-free interval of >2 months. This report presents comparative data on the efficacy and safety of monthly and daily oral ibandronate regimens. Materials and Methods: MOBILE is a 2-year, randomized, double-blind, phase III, noninferiority trial. A total of 1609 women with postmenopausal osteoporosis were assigned to one of four oral ibandronate regimens: 2.5 mg daily, 50 mg/50 mg monthly (single doses, consecutive days), 100 mg monthly, or 150 mg monthly. Results: After 1 year, lumbar spine BMD increased by 3.9%, 4.3%, 4.1%, and 4.9% in the 2.5, 50 /50, 100, and 150 mg arms, respectively. All monthly regimens were proven noninferior, and the 150 mg regimen superior, to the daily regimen. All monthly regimens produced similar hip BMD gains, which were larger than those with the daily regimen. All regimens similarly decreased serum levels of C-telopeptide, a biochemical marker of bone resorption. Compared with the daily regimen, a significantly larger proportion of women receiving the 100 and 150 mg monthly regimens achieved predefined threshold levels for percent change from baseline in lumbar spine (6%) or total hip BMD (3%). All regimens were similarly well tolerated. Conclusions: Monthly ibandronate is at least as effective and well tolerated as the currently approved daily ibandronate regimen in postmenopausal osteoporosis. [source]

    Overweight Postmenopausal Women Lose Bone With Moderate Weight Reduction and 1 g/day Calcium Intake,

    JOURNAL OF BONE AND MINERAL RESEARCH, Issue 3 2005
    Claudia S Riedt
    Abstract Overweight postmenopausal women may be more susceptible to bone loss with weight reduction than previously studied obese women. The influence of energy restriction and Ca intake on BMD was assessed in 66 individuals. Weight reduction resulted in bone loss at several sites in women consuming 1 g Ca/day and was mitigated with higher calcium intake at 1.7 g/day. Introduction: Bone loss is associated with weight loss in obese postmenopausal women and can be prevented with calcium (Ca) supplementation. However, because bone loss caused by weight loss may be greater in overweight than obese women, it is not clear whether Ca supplementation is also beneficial in overweight women. Materials and Methods: We assessed the influence of caloric restriction at two levels of Ca intake on BMD and BMC in 66 overweight postmenopausal women (age, 61 ± 6 years; body mass index, 27.0 ± 1.8 kg/m2). Subjects completed either a 6-month energy-restricted diet (WL, n = 47) and lost 9.3 ± 3.9 % weight or maintained weight (WM; 1 g Ca/day, n = 19). Participants in the WL group were randomly assigned to either normal (1 g/day; WL NL-Ca) or high (1.7 g/day; WL Hi-Ca) Ca intake. Regional BMD and BMC were measured at baseline and after 6 months. Results: During normal Ca intake, trochanter BMD and BMC and total spine BMD were decreased more in WL than WM women (p < 0.05). The WL NL-Ca group lost more trochanter BMD (,4.2 ± 4.1%) and BMC (,4.8 ± 7.1%) than the WL Hi-Ca group (,1.4 ± 5.6% and ,1.1 ± 8.1%, respectively; p < 0.05). There were no significant changes in BMD or BMC at the femoral neck in any group. Weight loss correlated with trochanter BMD loss (r = 0.687, p < 0.001) in the WL NL-Ca group. Conclusion: Despite an intake of 1 g Ca/day, bone loss occurred at some sites because of weight loss. Calcium intake of 1.7 g/day will minimize bone loss during weight loss in postmenopausal overweight women. [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]

    ApoE Gene Polymorphisms, BMD, and Fracture Risk in Elderly Men and Women: The Rotterdam Study,

    JOURNAL OF BONE AND MINERAL RESEARCH, Issue 9 2004
    Mariette WCJ Schoofs
    Abstract To study the association between the ApoE gene polymorphism and osteoporosis, we performed an association study in 5857 subjects from the Rotterdam Study. We did not observe an association between the ApoE polymorphism and osteoporosis in this study, which is thus far the largest study on ApoE and osteoporosis. Introduction: The E4 allele of the E2, E3, E4 protein isoform polymorphism in the gene encoding apolipoprotein E (ApoE) has previously been associated with an increased fracture risk. We investigated the association between the ApoE polymorphism and BMD, bone loss, and incident fractures as part of the Rotterdam Study a prospective population-based cohort study of diseases in the elderly. Materials and Methods: The study population consisted of 5857 subjects (2560 men; 3297 women) for whom data on ApoE genotypes, confounding variables, and follow-up of nonvertebral fractures were available. Data on femoral neck and lumbar spine BMD were available for 4814 participants. Genotype analyses for bone loss (defined as annualized percent change in BMD at the hip and lumbar spine) and BMD were performed using ANOVA. Fractures were analyzed using a Cox proportional-hazards model and logistic regression. All relative risks were adjusted for age and body mass index. Results and Conclusions: The genotype distribution of the study population was in Hardy-Weinberg equilibrium (p = 0.98) and did not differ by gender. At baseline, mean BMD of the lumbar spine and femoral neck did not differ between the ApoE genotypes of men and women. Bone loss (mean follow-up, 2.0 years) did not differ by ApoE genotype for women and men. During a mean follow-up of 6.6 years, 708 nonvertebral fractures (198 hip fractures and 179 wrist fractures) and 149 incident vertebral fractures occurred. No consistent differences in the distribution of alleles could be observed between subjects with or without these fractures. Our data do not support the hypothesis that the ApoE4 risk allele is associated with BMD, increased bone loss, or an increased risk of osteoporotic fractures. [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]

    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]

    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]

    Ibandronate: A Comparison of Oral Daily Dosing Versus Intermittent Dosing in Postmenopausal Osteoporosis

    JOURNAL OF BONE AND MINERAL RESEARCH, Issue 10 2001
    B. J. Riis
    Abstract The objective of this study was to compare efficacy and safety of continuous versus intermittent oral dosing of ibandronate. Two hundred forty women aged 55,75 years with postmenopausal osteoporosis were randomized to active treatment or placebo. Similar total doses of ibandronate were provided by treatment regimens with either continuous 2.5 mg of ibandronate daily (n = 81) or intermittent 20 mg of ibandronate every other day for the first 24 days, followed by 9 weeks without active drug (n = 78). The placebo group (total, n = 81) was crossed over after 12 months to receive either continuous (n = 37) or intermittent ibandronate (n = 35). By 24 months, bone mineral density (BMD) had increased significantly relative to baseline in both active treatment groups. The continuous and intermittent groups showed statistically equivalent increases in lumbar spine BMD of +5.64% (±0.53) and +5.54% (±0.53) and in total hip of +3.35% (±0.40) and +3.41% (±0.40), respectively (per protocol population). Biochemical markers of bone turnover decreased significantly in both treatment groups. The level of marker suppression was similar, although the intermittent group displayed, as expected, more fluctuation over the treatment period. The frequency of adverse events was similar in the treatment groups. In conclusion, the intermittent and continuous regimens showed equivalent changes in BMD and bone turnover. These results confirm previous preclinical findings indicating that the efficacy of ibandronate depends on the total oral dose given rather than on the dosing schedule. This supports development of new flexible dosing regimens targeted to minimize the frequency of dosing, which are expected to improve convenience and lead to enhanced long-term patient compliance. [source]

    Fractal Analysis of Radiographic Trabecular Bone Texture and Bone Mineral Density: Two Complementary Parameters Related to Osteoporotic Fractures

    JOURNAL OF BONE AND MINERAL RESEARCH, Issue 4 2001
    C. L. Benhamou
    Abstract Trabecular bone microarchitecture and bone mineral density (BMD) are two main factors related to osteoporotic fractures. Currently, however, microarchitecture is not evaluated. We have developed and validated a trabecular bone texture analysis from radiographic images. The objective was to determine if the fractal analysis of texture was able to distinguish osteoporotic fracture groups from control groups, either in vertebrae, hip, or wrist fractures, and to determine if this indicator and BMD were independent and complementary. In this cross-sectional unicenter case-control population study in postmenopausal women, 107 fracture cases were enrolled and age-matched with 197 control cases. This population comprised 40 vertebral fractures (with 70 controls), 30 hip fractures (55 controls), and 37 wrist fractures (62 controls). Hip and lumbar spine BMD were measured by double-energy X-ray absorptiometry. Fractal analysis of texture was performed on calcaneus radiographs and the result was expressed as the H parameter (H = 2-fractal dimension). The H parameter showed a lower value (0.679 ± 0.053 SD) in fracture cases versus control cases (0.696 ± 0.030; p = 0.007), the statistical significance persisting after adjustment for age and for lumbar spine (LS) or hip BMD. This result was confirmed in vertebral fractures (p = 0.0001) and hip fractures (p = 0.003) but not wrist fractures (p = 0.07). We determined the threshold between high and low H values and then the odds ratios (OR) of fracture for low H for BMD , ,2.5 SD in T score and for the combinations of both parameters. The OR of fracture for low H was 1.6 (95% CI, 1.1,2.6). For LS BMD , ,2.5 SD the OR of 6.1 (3.4,10.8) shifted to 9.0 (4.0,20.4) when we added low H and for hip BMD it shifted from 5.6 (3.3,9.4) to 8.1 (4.0,16.8). In vertebral, hip, and wrist fracture cases the results were also significant. These data have shown that the fractal analysis of texture on calcaneus radiographs can distinguish osteoporotic fracture groups from control groups. This analysis and BMD provide independent and complementary information. These data suggest that we can improve the fracture risk evaluation by adding information related to microarchitecture, derived from analysis of conventional radiographic images. [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]

    Fitness, fatness and activity as predictors of bone mineral density in older persons

    JOURNAL OF INTERNAL MEDICINE, Issue 5 2002
    K. J. Stewart
    Abstract. Stewart KJ, DeRegis JR, Turner KL, Bacher AC, Sung J, Hees PS, Tayback M, Ouyang P (Johns Hopkins Bayview Medical Center, Johns Hopkins University, School of Medicine, Baltimore, MD, USA). Fitness, fatness, and activity as predictors of bone mineral density in older persons. J Intern Med 2002; 252: 381,388. Objectives. To determine relationships of bone mineral density (BMD) with fitness, physical activity, and body composition and fat distribution. Design. Cross-sectional. Setting. General Clinical Research Center, Johns Hopkins Bayview Medical Center, Baltimore, Maryland. Subjects. Men (n = 38) and women (n = 46), aged 55,75 years with high normal blood pressure or mild hypertension but otherwise healthy. Methods. Aerobic fitness (oxygen uptake) on a treadmill, muscle strength by one-repetition maximum, activity by questionnaire, abdominal obesity by magnetic resonance imaging; anthropometrics, and body composition by dual energy X-ray absorptiometry (DXA) which measured total fat and lean mass, and BMD for the total skeleton, lumbar spine (L1,L4) and total hip. Results. Aerobic fitness did not correlate with BMD. Using multivariate analysis to ascertain independent contributions to the variance in BMD, in women, with adjustment for hormone replacement therapy (HRT), total skeleton BMD was independently related to muscle strength and abdominal total fat; total hip BMD to body weight; lumbar spine BMD to abdominal total fat. HRT also influenced BMD in the lumbar spine. In men, lumbar spine BMD was independently related to abdominal total fat physical activity and total hip BMD related to lower body strength. P < 0.05 for all of these correlations. Conclusions. Abdominal obesity and muscle strength emerge as predominant correlates of BMD in older persons with stronger relationships seen in women. Body weight and HRT also explained portions of the variance in BMD in women. Whether abdominal obesity is simply a marker for general obesity or has independent protective effects on bone is yet to be determined. [source]

    The relationship between focal erosions and generalized osteoporosis in postmenopausal women with rheumatoid arthritis

    ARTHRITIS & RHEUMATISM, Issue 6 2009
    Daniel H. Solomon
    Objective Among rheumatoid arthritis (RA) patients who have had the disease for 10 years, more than half have focal erosions, and the risk of fracture is doubled. However, there is little information about the potential relationship between focal erosions and bone mineral density (BMD). The aim of this study was to determine whether lower BMD is associated with higher erosion scores among patients with RA. Methods We enrolled 163 postmenopausal women with RA, none of whom were taking osteoporosis medications. Patients underwent dual x-ray absorptiometry at the hip and spine and hand radiography, and completed a questionnaire. The hand radiographs were scored using the Sharp method, and the relationship between BMD and erosions was measured using Spearman's correlation coefficients and adjusted linear regression models. Results Patients had an average disease duration of 13.7 years, and almost all were taking a disease-modifying antirheumatic drug. Sixty-three percent were rheumatoid factor (RF) positive. The median modified Health Assessment Questionnaire score was 0.7, and the average Disease Activity Score in 28 joints was 3.8. The erosion score was significantly correlated with total hip BMD (r = ,0.33, P < 0.0001), but not with lumbar spine BMD (r = ,0.09, P = 0.27). Hip BMD was significantly lower in RF-positive patients versus RF-negative patients (P = 0.02). In multivariable models that included age, body mass index, and cumulative oral glucocorticoid dose, neither total hip BMD nor lumbar spine BMD was significantly associated with focal erosions. Conclusion Our results suggest that hip BMD is associated with focal erosions among postmenopausal women with RA, but that this association disappears after multivariable adjustment. While BMD and erosions may be correlated with bone manifestations of RA, their relationship is complex and influenced by other disease-related factors. [source]

    Quantitative computed tomography of the lumbar spine, not dual x-ray absorptiometry, is an independent predictor of prevalent vertebral fractures in postmenopausal women with osteopenia receiving long-term glucocorticoid and hormone-replacement therapy

    ARTHRITIS & RHEUMATISM, Issue 5 2002
    Q. Rehman
    Objective To determine which measurement of bone mineral density (BMD) predicts vertebral fractures in a cohort of postmenopausal women with glucocorticoid-induced osteoporosis. Methods We recruited 114 subjects into the study. All had osteopenia of the lumbar spine or hip, as demonstrated by dual x-ray absorptiometry (DXA), and were receiving long-term glucocorticoids and hormone replacement therapy (HRT). Measurements of BMD by DXA of the lumbar spine, hip (and subregions), and forearm (and subregions), quantitative computed tomography (QCT) of the spine and hip (n = 59), and radiographs of the thoracolumbar spine were performed on all subjects to assess prevalent vertebral fractures. Vertebral fracture prevalence, as determined by morphometry, required a ,20% (or ,4-mm) loss of vertebral body height. Demographic information was obtained by questionnaire. Multiple regression and classification and regression trees (CART) analyses were used to assess predictors of vertebral fracture. Results Twenty-six percent of the study subjects had prevalent fractures. BMD of the lumbar spine, total hip and hip subregions, as measured by QCT, but only the lumbar spine and total hip, as measured by DXA, were significantly associated with prevalent vertebral fractures. However, only lumbar spine BMD as measured by QCT was a significant predictor of vertebral fractures. CART analysis showed that a BMD value <0.065 gm/cm3 was associated with a 7-fold higher risk of fracture than a BMD value ,0.065 gm/cm3. Conclusion In postmenopausal women with osteoporosis induced by long-term glucocorticoid treatment who are also receiving HRT, BMD of the lumbar spine as measured by QCT, but not DXA, is an independent predictor of vertebral fractures. [source]

    Bone metabolism markers and ghrelin in boys at different stages of sexual maturity

    ACTA PAEDIATRICA, Issue 5 2009
    Jaak Jürimäe
    Abstract Aim: To examine the relationship of the markers of bone formation (procollagen type I N-terminal propeptide [PINP]) and bone resorption (type I carboxyterminal telopeptide [ICTP]) with bone mineral content (BMC), bone mineral density (BMD), ghrelin and testosterone in boys during puberty. Methods: Sixty boys were divided in three groups (20 boys in each) based on the pubertal stage (G1, I; G2,G3, II; G4,G5, III). Fasting PINP, ICTP, ghrelin and testosterone were measured. Total body BMD, lumbar BMD, lumbar apparent volumetric BMD (BMAD) and BMC were measured by DXA. Results: PINP and ICTP values peaked at the beginning of puberty (Group II). Ghrelin was lower in Groups II and III compared to less mature boys. PINP and ICTP correlated with each other and were associated with lumbar BMAD in total group of boys. Relationships of PINP and ICTP with total BMD, total BMC and lumbar spine BMD in Group I were observed. PINP and ICTP were also correlated with testosterone in Group II and with lumbar spine BMAD in Group III. Conclusion: These data suggest that testosterone stimulates PINP and ICTP in early puberty, while ghrelin has no direct influence on bone turnover markers in boys at different stages of puberty. [source]