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DXA
Kinds of DXA Terms modified by DXA Selected AbstractsMinor long-term changes in weight have beneficial effects on insulin sensitivity and ,-cell function in obese subjectsDIABETES OBESITY & METABOLISM, Issue 1 2002A. M. Rosenfalck SUMMARY Aim To evaluate the long-term effect of changes in body composition induced by weight loss on insulin sensitivity (SI), non-insulin mediated glucose disposal, glucose effectiveness (SG) and ,-cell function. Design Glucose metabolism was evaluated before and after participation in a two-year weight loss trial of Orlistat vs. placebo, combined with an energy and fat restricted diet. Subjects Twelve obese patients (11 women, 1 man), age 45.8 ± 10.5 years, body weight (BW) 99.7 ± 13.3 kg, BMI 35.3 ± 2.8 kg/m2. Measurements At inclusion and 2 years later an oral glucose tolerance test (OGTT) and a frequently sampled intravenous glucose tolerance test (FSIGT) were performed. Body composition was estimated by a dual-energy X-ray absorptiometry (DXA) whole body scanning. Results The patients obtained varying changes in BW ranging from a weight loss of 17.8 kg to a weight gain of 6.0 kg. Corresponding changes in fat mass (FM) varied from a 40% reduction to a 19% increase. A significant decrease in both fasting (p =,0.038) and 2 h (p =,0.047) blood glucose at OGTT was found. The improvement in insulin sensitivity (SI) estimated by means of Bergmans Minimal Model, was significantly and linearly correlated to change in total FM (r = , 0.83, p =,0.0026). A multiple regression analysis showed that changes in truncal FM was the strongest predictor of change in SI explaining 67% of the variation. First phase insulin response (AIRg) remained unchanged whereas insulin disposition index increased significantly (p =,0.044). At inclusion five patients had impaired glucose tolerance of which four, who lost weight, were normalized at the retest 2 years later. Conclusion In obese subjects long-term minimal or moderate changes in weight were found to be linearly associated with changes in insulin sensitivity. In obese subjects with impaired glucose tolerance even a minor weight loss was able to normalize glucose tolerance. [source] Low bone mineral density in children and adolescents with inflammatory bowel disease: A population-based study from Western SwedenINFLAMMATORY BOWEL DISEASES, Issue 12 2009Susanne Schmidt MD Abstract Background: Low bone mineral density (BMD) has been recognized as a potential problem in children with inflammatory bowel disease (IBD). The aim of the study was to investigate BMD in Swedish children and adolescents with IBD and to evaluate possible factors affecting BMD. Methods: To evaluate BMD, all patients (n = 144) underwent a dual-energy X-ray absorptiometry (DXA) of the whole body and the spine. BMD values were expressed as Z-scores using normative pediatric data from Lunar (GE Medical Systems). Results: In this population-based study, the lowest BMD values were found in the lumbar spine. The entire IBD group showed significantly lower BMD Z-scores of the lumbar spine (L2,L4) in comparison to healthy references (,0.8 standard deviation [SD], range ,5.9 to 3.7 SD, P < 0.001). Decreased BMD with a Z-score < ,1 SD occurred in 46.7% of the individuals with Crohn's disease (CD) and in 47.0% of those with ulcerative colitis (UC). Low BMD with a Z-score , ,2 SD was present in 26.7% of the patients with CD and in 24.1% of the UC patients. In a multiple regression model with BMD lumbar spine as the depending variable, possible factors associated with lower BMD were male gender, low body mass index (BMI), and treatment with azathioprine. Conclusions: Low BMD is prevalent in Swedish pediatric patients with IBD. Possible risk factors for lower BMD are male gender, low BMI, and treatment with azathioprine, as a probable marker of disease course severity. (Inflamm Bowel Dis 2009) [source] DXA scanning in women over 50 years with distal forearm fracture shows osteoporosis is infrequent until age 65 yearsINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 3 2008H. Lashin Summary Aims:, Women with distal forearm fracture (DFF) may have low bone mineral density (BMD) and merit Dual Energy Xray (DXA) scanning. However patient age at fracture and the database for ,healthy' subjects may influence how many have osteoporosis and require DXA scans. Osteoporosis prevalence in DFF patients by age was investigated using local or nHanes III databases for BMD. Methods:, A total of 186 women over 50 years consecutively referred with DFF over 1 year were audited without exclusion criteria. BMD of L2,4 and femoral neck (Hologic QDR4500A) was measured and T - and Z -scores calculated from a local database or nHanes III. Results:, Of 90 patients aged 50,64 years, 21.1% had femoral neck T -score < ,2.5 and 7.7% < ,3.0 (local) and 8.8% and 4.4% respectively (nHanes III). Patients aged 65,74 years (n = 61) included 19.7% with T -score < ,2.5 (nHanes III = 10%). 41.2% (nHanes III = 28.6%) of patients > 75 years had femoral neck osteoporosis. Including patients with spine T < ,2.5 increased the proportion to 31.1% (50,64 years) and 34.4% (65,74 years) with no extra over 75 years. Weight predicted low BMD ineffectively (area under ROC = 70%). Conclusion:, Osteoporosis is infrequent in women with DFF below 65 years. As fracture prevention treatment yields significant fracture reduction only in patients with T -score < ,2.5, DXA scanning below 65 years is not justified. After 65 years scanning is justified at all ages, as even in the elderly patients osteoporosis is present in < 50% of patients with DFF. Using nHanes III limits the number of DFF patients warranting treatment. Low body weight is unreliable for identifying osteoporosis. [source] Screening for osteoporosis in anorexia nervosa: Prevalence and predictors of reduced bone mineral densityINTERNATIONAL JOURNAL OF EATING DISORDERS, Issue 3 2008Anthony P. Winston MRCPsych Abstract Objective: Decreased bone mineral density (BMD) in anorexia nervosa (AN) can be detected easily by dual-energy X-ray absorptiometry (DXA). This study was designed to assess the prevalence of osteoporosis and osteopenia in AN, identify predictors, and determine the diagnostic yield of screening with DXA. Method: DXA was used to screen 59 unselected adult patients with a history of AN. Results: Osteoporosis was identified in 18 patients (31%) and osteopenia in 30 (51%). The spine had a lower mean T -score than either the hip or femur. BMI significantly predicted T -score (p = 0.0006) and the odds of having osteoporosis (p = 0.0188). There was a significant association between use of oestrogens and the presence of osteoporosis or osteopenia (p = 0.0491). There was no significant association between duration of AN and T -score. A duration of AN of less than 1 year was found in 12% of those with osteoporosis. Conclusion: BMI is a strong predictor of BMD in AN. DXA is an effective screening tool and should probably be offered routinely. © 2007 by Wiley Periodicals, Inc. Int J Eat Disord, 2008 [source] Prevalence and predictors of osteoporosis and the impact of life style factors on bone mineral densityINTERNATIONAL JOURNAL OF RHEUMATIC DISEASES, Issue 3 2007Abdulbari BENER Abstract Aim:, The aim of this study was to determine the prevalence and predictors of osteoporosis and the impact of life style factors on bone mineral density (BMD) in premenopausal and postmenopausal Qatari women. Methods:, This is a cross-sectional study. A total of 821 healthy Qatari women aged 20,70 years had given consent and participated and the study was conducted from June 2005 to December 2006 at the Rumaillah Hospital, Hamad Medical Corporation (HMC), Doha, State of Qatar. All subjects completed a questionnaire on reproductive and life style factors. Height and weight were measured. All subjects underwent dual-energy X-ray absorptiometry (DXA) to determine factors influencing BMD of the spine and femur. The main outcome measures were menopausal status, socio-demographic and lifestyle factors and BMD measurements. Results:, The prevalence of osteoporosis in postmenopausal women was 12.3%. BMI was significantly higher among postmenopausal women (P < 0.001) when compared to premenopausal women. The subjects who regularly consumed dairy products had better BMD at spine, neck and ward sites (P < 0.05). Those doing regular household work for 3,4 h a week had higher BMD at all sites compared to those who did not do their own household work. Multiple regression analysis showed that education level and body mass index were strong positive predictors showing high significance. Conclusion:, The relation between lifestyle and BMD were explored in Qatari women. The prevalence of osteoporosis in Qatari women is comparable to other countries. BMD values were higher in women who were taking diary products regularly, and were involved with household work. [source] Genetic variation in the RANKL/RANK/OPG signaling pathway is associated with bone turnover and bone mineral density in menJOURNAL OF BONE AND MINERAL RESEARCH, Issue 8 2010Delnaz Roshandel Abstract The aim of this study was to determine if single-nucleotide polymorphisms (SNPs) in RANKL, RANK, and OPG influence bone turnover and bone mineral density (BMD) in men. Pairwise tag SNPs (r2,,,0.8) were selected for RANKL, RANK, and OPG and their 10-kb flanking regions. Selected tag SNPs plus five SNPs near RANKL and OPG, associated with BMD in published genome-wide association studies (GWAS), were genotyped in 2653 men aged 40 to 79 years of age recruited for participation in a population-based study of male aging, the European Male Ageing Study (EMAS). N-terminal propeptide of type I procollagen (PINP) and C-terminal cross-linked telopeptide of type I collagen (CTX-I) serum levels were measured in all men. BMD at the calcaneus was estimated by quantitative ultrasound (QUS) in all men. Lumbar spine and total-hip areal BMD (BMDa) was measured by dual-energy X-ray absorptiometry (DXA) in a subsample of 620 men. Multiple OPG, RANK, and RANKL SNPs were associated with bone turnover markers. We also identified a number of SNPs associated with BMD, including rs2073618 in OPG and rs9594759 near RANKL. The minor allele of rs2073618 (C) was associated with higher levels of both PINP (,,=,1.83, p,=,.004) and CTX-I (,,=,17.59, p,=,4.74,×,10,4), and lower lumbar spine BMDa (,,=,,0.02, p,=,.026). The minor allele of rs9594759 (C) was associated with lower PINP (,,=,,1.84, p,=,.003) and CTX-I (,,=,,27.02, p,=,6.06,×,10,8) and higher ultrasound BMD at the calcaneus (,,=,0.01, p,=,.037). Our findings suggest that genetic variation in the RANKL/RANK/OPG signaling pathway influences bone turnover and BMD in European men. © 2010 American Society for Bone and Mineral Research [source] Timing of ibuprofen use and bone mineral density adaptations to exercise trainingJOURNAL OF BONE AND MINERAL RESEARCH, Issue 6 2010Wendy 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] Association with replication between estrogen-related receptor , (ESRR,) Polymorphisms and bone phenotypes in women of European ancestryJOURNAL OF BONE AND MINERAL RESEARCH, Issue 4 2010Latifa Elfassihi Abstract Osteoporosis is a bone disease characterized by low bone mineral density (BMD), a highly heritable polygenic trait. Women are more prone than men to develop osteoporosis owing to a lower peak bone mass and accelerated bone loss at menopause. Lack of estrogen thus is a major risk factor for osteoporosis. In addition to having strong similarity to the estrogen receptor 1 (ESR1), the orphan nuclear estrogen-related receptor , (ESRR,) is widely expressed and shows overlap with ESR1 expression in tissues where estrogen has important physiologic functions. For these reasons, we have undertaken a study of ESRR, sequence variants in association with bone measurements [heel quantitative ultrasound (QUS) by measurements of broadband ultrasound attenuation (BUA), speed of sound (SOS), and stiffness index (SI) and dual-energy X-ray absorptiometry (DXA) at the femoral neck (FN) and lumbar spine (LS)]. A silent variant was found to be associated with multiple bone measurements (LS, BUA, SOS, and SI), the p values ranging from .006 to .04 in a sample of 5144 Quebec women. The region of this variant was analyzed using the HapMap database and the Gabriel method to define a block of 20,kb. Using the Tagger method, eight TagSNPs were identified and genotyped in a sample of 1335 women. Four of these SNPs capture the five major block haplotypes. One SNP (rs2818964) and one haplotype were significantly associated with multiple bone measures. All SNPs involved in the associations were analyzed in two other sample sets with significant results in the same direction. These results suggest involvement of ESRR, in the determination of bone density in women. © 2010 American Society for Bone and Mineral Research [source] Computed tomographic measurements of thigh muscle cross-sectional area and attenuation coefficient predict hip fracture: The health, aging, and body composition studyJOURNAL OF BONE AND MINERAL RESEARCH, Issue 3 2010Thomas Lang Abstract Fatty infiltration of muscle, myosteatosis, increases with age and results in reduced muscle strength and function and increased fall risk. However, it is unknown if increased fatty infiltration of muscle predisposes to hip fracture. We measured the mean Hounsfield unit (HU) of the lean tissue within the midthigh muscle bundle (thigh muscle HU, an indicator of intramuscular fat), its cross-sectional area (CSA, a measure of muscle mass) by computed tomography (CT), bone mineral density (BMD) of the hip and total-body percent fat by dual X-ray absorptiometry (DXA), isokinetic leg extensor strength, and the Short Physical Performance Battery (SPPB) in 2941 white and black women and men aged 70 to 79 years. Sixty-three hip fractures were validated during 6.6 years of follow-up. Proportional hazards regression analysis was used to assess the relative risk (RR) of hip fracture across variations in thigh muscle attenuation, CSA, muscle strength, and physical function for hip fracture. In models adjusted by age, race, gender, body mass index, and percentage fat, decreased thigh muscle HU resulted in increased risk of hip fracture [RR/SD,=,1.58; 95% confidence interval (CI) 1.10,1.99], an association that continued to be significant after further adjustment for BMD. In models additionally adjusted by CSA, muscle strength, and SPPB score, decreased thigh muscle HU but none of the other muscle parameters continued to be associated with an increased risk of hip fracture (RR/SD,=,1.42; 95% CI 1.03,1.97). Decreased thigh muscle HU, a measure of fatty infiltration of muscle, is associated with increased risk of hip fracture and appears to account for the association between reduced muscle strength, physical performance, and muscle mass and risk of hip fracture. This characteristic captures a physical characteristic of muscle tissue that may have importance in hip fracture etiology. © 2010 American Society for Bone and Mineral Research [source] Parathyroid hormone (PTH),induced bone gain is blunted in SOST overexpressing and deficient miceJOURNAL OF BONE AND MINERAL RESEARCH, Issue 2 2010Ina Kramer Abstract Intermittent parathyroid hormone (PTH) treatment is a potent bone anabolic principle that suppresses expression of the bone formation inhibitor Sost. We addressed the relevance of Sost suppression for PTH-induced bone anabolism in vivo using mice with altered Sost gene dosage. Six-month-old Sost overexpressing and 2-month-old Sost deficient male mice and their wild-type littermates were subjected to daily injections of 100,µg/kg PTH(1,34) or vehicle for a 2-month period. A follow-up study was performed in Sost deficient mice using 40 and 80,µg/kg PTH(1,34). Animals were sacrificed 4 hours after the final PTH administration and Sost expression in long bone diaphyses was determined by qPCR. Bone changes were analyzed in vivo in the distal femur metaphysis by pQCT and ex vivo in the tibia and lumbar spine by DXA. Detailed ex vivo analyses of the femur were performed by pQCT, µCT, and histomorphometry. Overexpression of Sost resulted in osteopenia and Sost deletion in high bone mass. As shown before, PTH suppressed Sost in wild-type mice. PTH treatment induced substantial increases in bone mineral density, content, and cortical thickness and in aging wild-type mice also led to cancellous bone gain owing to amplified bone formation rates. PTH-induced bone gain was blunted at all doses and skeletal sites in Sost overexpressing and deficient mice owing to attenuated bone formation rates, whereas bone resorption was not different from that in PTH-treated wild-type controls. These data suggest that suppression of the bone formation inhibitor Sost by intermittent PTH treatment contributes to PTH bone anabolism. © 2010 American Society for Bone and Mineral Research [source] Imputation of 10-year osteoporotic fracture rates from hip fractures: A clinical validation studyJOURNAL OF BONE AND MINERAL RESEARCH, Issue 2 2010William D Leslie Abstract The World Health Organization (WHO) fracture risk assessment system (FRAX) allows for calibration from country-specific fracture data. The objective of this study was to evaluate the method for imputation of osteoporotic fracture rates from hip fractures alone. A total of 38,784 women aged 47.5 years or older at the time of baseline femoral neck bone mineral density (BMD) measurement were identified in a database containing all clinical dual energy X-ray absorptiometry (DXA) results for the Province of Manitoba, Canada. Health service records were assessed for the presence of nontrauma osteoporotic fracture codes after BMD testing (431 hip, 787 forearm, 336 clinical vertebral, and 431 humerus fractures). Ten-year hip and osteoporotic fracture rates were estimated by the Kaplan-Meier method. The population was stratified by age (50 to 90 years, 5-year width strata) and again by femoral neck T -scores (,4.0 to 0.0, 0.5 SD width strata). Within each stratum, the ratio of hip to osteoporotic fractures was calculated and compared with the predicted ratio from FRAX. Increasing age was associated with greater predicted hip-to-osteoporotic ratios (youngest 0.07 versua oldest 0.41) and observed ratios (youngest 0.10 versus oldest 0.48). Lower T -scores were associated with greater predicted (highest 0.04 versus lowest 0.71) and observed ratios (highest 0.06 versus lowest 0.44). There was a strong positive correlation between predicted and observed ratios (Spearman r,=,0.90,0.97, p,<,.001). For 14 of the 18 strata, the predicted ratio was within the observed 95% confidence interval (CI). Since collection of population-based hip fracture data is considerably easier than collection of non,hip fracture data, this study supports the current emphasis on using hip fractures as the preferred site for FRAX model calibration. © 2010 American Society for Bone and Mineral Research [source] Bone and Muscle Development During Puberty in Girls: A Seven-Year Longitudinal Study,,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 10 2009Leiting Xu Abstract The growth of lean mass precedes that of bone mass, suggesting that muscle plays an important role in the growth of bone. However, to date, no study has directly followed the growth of bone and muscle size through puberty and into adulthood. This study aimed to test the hypothesis that the growth of muscle size precedes that of bone size (width and length) and mass during puberty. Bone and muscle properties were measured using pQCT and DXA in 258 healthy girls at baseline (mean age, 11.2 yr) and 1-, 2-, 3,4- and 7-yr follow-up. Growth trends as a function of time relative to menarche were determined from prepuberty to early adulthood for tibial length (TL), total cross-sectional area (tCSA), cortical CSA (cCSA), total BMC (tBMC), cortical volumetric BMD (cBMD), and muscle CSA (mCSA) in hierarchical models. The timings of the peak growth velocities for these variables were calculated. Seventy premenopausal adults, comprising a subset of the girl's mothers (mean age, 41.5 yr), were included for comparative purposes. In contrast to our hypothesis, the growth velocity of mCSA peaked 1 yr later than that of tibial outer dimensions (TL and tCSA) and slightly earlier than tBMC. Whereas TL ceased to increase 2 yr after menarche, tCSA, cCSA, tBMC, and mCSA continued to increase and were still significantly lower than adult values at the age of 18 yr (all p < 0.01). The results do not support the view that muscle force drives the growth of bone size during puberty. [source] Bone Health in Children and Adolescents After Renal Transplantation,,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 10 2009Helena Valta MD Abstract The basis for lifelong bone health is established in childhood and adolescence. Whereas pediatric renal transplant (RTx) patients are at risk for impaired bone mass gain and fractures, scarce data on this subject are available. We performed a cross-sectional and longitudinal study of bone health in a national cohort of 106 pediatric RTx patients (median age, 12.6 yr; median follow-up, 5.1 yr after RTx). The patients underwent clinical evaluation, DXA for BMD, and spinal imaging for vertebral fractures. In longitudinal analysis, the median lumbar spine BMD Z-score was lowest (median, ,1.0) at 1 yr postoperatively but increased to a peak value of ,0.2 at 5 yr. In boys, the lumbar spine BMD Z-score increased also during puberty but decreased in girls. In cross-sectional analysis, the lumbar spine, hip, and whole body BMD Z-scores were < ,2 SD in 4%, 6%, and 6% of the patients, respectively. Sixteen percent had sustained peripheral fractures, and 8% had vertebral fractures. Female sex and age >15 yr (OR, 56.26; 95% CI, 5.17,611.82; p = 0.0007) as well as high plasma PTH levels (OR, 4.03; 95% CI, 1.37,11.85; p = 0.009) were significant predictors for low BMD. Three-year cumulative glucocorticoid dose, outside the immediate post-RTx years, was not associated with BMD parameters. The observed BMD results were satisfactory. However, the high (8%) prevalence of vertebral fractures warrants careful evaluation of bone health in these patients. [source] Severity of Vertebral Fractures Is Associated With Alterations of Cortical Architecture in Postmenopausal Women,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 4 2009Elisabeth Sornay-Rendu Abstract Patients with vertebral fractures (VFx) have trabecular architectural disruption on iliac biopsies. Because cortical bone is an important determinant of bone strength, we assessed cortical and trabecular microarchitecture at peripheral sites in patients with VFx of varying number (N) and severity (S). Bone architecture and volumetric density (vBMD) were assessed at the distal radius and tibia with HR-pQCT (XTreme CT; Scanco Medical, Bassersdorf, Switzerland) in 100 women with VFx (age, 74 ± 9 yr) of different S (GI, n = 23; GII, n = 35; GIII, n = 42) and in 362 women (age, 69 ± 7 yr) without peripheral or VFx (G0) from the OFELY study. Spine areal BMD (aBMD) was assessed by DXA. Among all women, at the radius and after adjustment for age and aBMD, there were significant trends in lower vBMD, cortical thickness (Cort.Th), trabecular number (Tb.N) and thickness (Tb.Th), higher trabecular separation (Tb.Sp), and distribution of separation (Tb.Sp.SD) with greater VFx S and N. Among women with VFx, lower Cort.Th and cortical vBMD (D.Cort) were associated with severe (GIII) and multiple (n > 2) VFx (p < 0.05). The age-adjusted OR for each SD decrease of Cort.Th was 2.04 (95% CI, 1.02,4.00) after adjustment for aBMD. At the tibia, there were trends for lower vBMD, Tb.N, Tb.Th, and higher Tb.Sp and Tb.Sp.SD with greater VFx S and N (p < 0.001). Among women with VFx, lower Cort.Th and D.Cort were associated with severe and multiple (n > 3) VFx (p < 0.01). In postmenopausal women, VFx are associated with low vBMD and architectural decay of trabecular and cortical bone at the radius and tibia, independently of spine aBMD. Severe and multiple VFx are associated with even more alterations of cortical bone. [source] Finite Element Analysis of the Proximal Femur and Hip Fracture Risk in Older Men,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 3 2009Eric S Orwoll Abstract Low areal BMD (aBMD) is associated with increased risk of hip fracture, but many hip fractures occur in persons without low aBMD. Finite element (FE) analysis of QCT scans provides a measure of hip strength. We studied the association of FE measures with risk of hip fracture in older men. A prospective case-cohort study of all first hip fractures (n = 40) and a random sample (n = 210) of nonfracture cases from 3549 community-dwelling men ,65 yr of age used baseline QCT scans of the hip (mean follow-up, 5.6 yr). Analyses included FE measures of strength and load-to-strength ratio and BMD by DXA. Hazard ratios (HRs) for hip fracture were estimated with proportional hazards regression. Both femoral strength (HR per SD change = 13.1; 95% CI: 3.9,43.5) and the load-to-strength ratio (HR = 4.0; 95% CI: 2.7,6.0) were strongly associated with hip fracture risk, as was aBMD as measured by DXA (HR = 5.1; 95% CI: 2.8,9.2). After adjusting for age, BMI, and study site, the associations remained significant (femoral strength HR = 6.5, 95% CI: 2.3,18.3; load-to-strength ratio HR = 4.3, 95% CI: 2.5,7.4; aBMD HR = 4.4, 95% CI: 2.1,9.1). When adjusted additionally for aBMD, the load-to-strength ratio remained significantly associated with fracture (HR = 3.1, 95% CI: 1.6,6.1). These results provide insight into hip fracture etiology and demonstrate the ability of FE-based biomechanical analysis of QCT scans to prospectively predict hip fractures in men. [source] Simplified System for Absolute Fracture Risk Assessment: Clinical Validation in Canadian Women,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 2 2009William D Leslie Abstract Absolute 10-yr fracture risk based on multiple factors is the preferred method for risk assessment. A simplified risk assessment system from sex, age, DXA, and two clinical risk factors (CRFs),prior fracture and systemic corticosteroid (CS) use-has been used in Canada since 2005. This study was undertaken to evaluate this system in the Canadian female population. A total of 16,205 women ,50 yr of age at the time of baseline BMD (1998,2002) were identified in a database containing all clinical DXA test results for the Province of Manitoba, Canada. Basal 10-yr fracture risk from age and minimum T-score (lumbar spine, femur neck, trochanter, total hip) was categorized as low (<10%), moderate (10,20%), or high (>20%). Health service records since 1987 were assessed for prior fracture codes (N = 5224), recent major CS use (N = 616), and fracture codes after BMD testing (mean, 3.1 yr of follow-up) for the hip, vertebrae, forearm, or humerus (designated osteoporotic, N = 757). Fracture risk predicted from age and minimum T-score alone showed a significant gradient in observed fracture rates (low 5.1 [95% CI, 4.1,6.4], moderate 11.5 [95% CI, 10.1,13.0], high 25.4 [95% CI, 23.2,27.9] per 1000 person-years; p -for-trend <0.0001). There was an incremental increase in incident fracture rates from a prior fracture (13.9 [95% CI, 11.3,16.4] per 1000 person-years) or major CS use (11.2 [95% CI, 4.1,18.2] per 1000 person-years). This simplified fracture risk assessment system provides an assessment of fracture risk that is consistent with observed fracture rates. [source] Site-Specific Deterioration of Trabecular Bone Architecture in Men and Women With Advancing AgeJOURNAL OF BONE AND MINERAL RESEARCH, Issue 12 2008Eva-Maria Lochmüller Abstract We tested the hypothesis that the age dependence of trabecular bone microstructure differs between men and women and is specific to skeletal site. Furthermore, we aimed to investigate the microstructural pattern of bone loss in aging. Microstructural properties of trabecular bone were measured in vitro in 75 men and 75 age-matched women (age, 52,99 yr) using ,CT. Trabecular bone samples were scanned at a 26-,m isotropic resolution at seven anatomical sites (i.e., distal radius, T10 and L2 vertebrae, iliac crest, femoral neck and trochanter, and calcaneus). DXA measurements were obtained at the distal radius and proximal femur and QCT was used at T12. No significant decrease in bone density or structure with age was found in men using ,CT, DXA, or QCT at any of the anatomical sites. In women, a significant age-dependent decrease in BV/TV was observed at most sites, which was strongest at the iliac crest and weakest at the distal radius. At most sites, the reduction in BV/TV was associated with an increase in structure model index, decrease in Tb.N, and an increase in Tb.Sp. Only in the calcaneus was it associated with a significant decrease in Tb.Th. In conclusion, a significant, site-specific correlation of trabecular bone microstructure with age was found in women but not in men of advanced age. The microstructural basis by which a loss of BV/TV occurs with age can vary between anatomical sites. [source] Theoretical Implications of the Biomechanical Fracture ThresholdJOURNAL OF BONE AND MINERAL RESEARCH, Issue 10 2008Tony M Keaveny Abstract Because of the dichotomous nature of a bone fracture, when ,, the ratio of the applied impact force to the bone strength, is greater than a critical value,the biomechanical fracture threshold,fracture should occur. We sought to elucidate the conceptual implications of this biomechanical fracture threshold with application to hip fracture. We used data from the PaTH study, a 2-yr clinical trial in postmenopausal women treated with alendronate, PTH, or their combination. Outcomes included the force applied to the hip in a sideways fall as estimated from subject height and weight; femoral strength as determined by QCT-based finite element analysis; the load-to-strength ratio ,; and total hip areal BMD from DXA. Results indicated that those with "very low" femoral strength (<2000 N) invariably had load-to-strength ratio , values well above the theoretical biomechanical fracture threshold (, = 1), but those with "moderately low" femoral strength (2000,4000 N) displayed , values both above and below the theoretical biomechanical fracture threshold. This finding implies that the risk of a hip fracture can be high in those with only moderately low BMD because femoral strength can be low relative to fall impact forces. The observed weak correlation between areal BMD and the load-to-strength ratio , (r2 = 0.14) suggests that consideration of the biomechanical fracture threshold may improve fracture risk assessment, particularly for those in the osteopenic range. Regarding treatment effects, only those subjects having load-to-strength ratio , values within a relatively narrow "transition zone" of ±20% of the assumed biomechanical fracture threshold at baseline were predicted to change fracture status during the trial. In theory, outcomes of fracture trials may be dominated by the responses of those within the "transition zone" at baseline, and treatment benefits in terms of fracture efficacy may depend the patient's baseline status with respect to the biomechanical fracture threshold. We conclude that consideration of the theoretical implications of the biomechanical fracture threshold may lead to new insights and advances in the assessment and treatment of osteoporosis. [source] Recovery of Trabecular and Cortical Bone Turnover After Discontinuation of Risedronate and Alendronate Therapy in Ovariectomized RatsJOURNAL OF BONE AND MINERAL RESEARCH, Issue 10 2008Robyn K Fuchs Abstract Alendronate (ALN) and risedronate (RIS) are bisphosphonates effective in reducing bone loss and fractures associated with postmenopausal osteoporosis. However, it is uncertain how long it takes bone turnover to be re-established after treatment withdrawal, and whether this differs between the two drugs. The objective of this study was to determine the time required to re-establish normal bone turnover after the discontinuation of ALN and RIS treatment in an animal model of estrogen-deficiency osteoporosis. Two hundred ten, 6-mo-old female Sprague-Dawley rats were ovariectomized and 6 wk later were randomized into baseline controls (n = 10) and four treatment groups (n = 50/group): vehicle-treated controls (CON; 0.3 ml sterile water), ALN (2.4 ,g/kg), low-dose RIS (RIS low; 1.2 ,g/kg), and high-dose RIS (RIS high; 2.4 ,g/kg). Treatments were administered 3 times/wk by subcutaneous injection. Baseline controls were killed at the initiation of treatment. Other groups were treated for 8 wk, and subgroups (n = 10/ treatment group) were killed 0, 4, 8, 12, and 16 wk after treatment was withdrawn. Static and dynamic histological analyses were performed for cortical (tibial diaphysis) and trabecular (proximal tibia and L4 vertebrae) bone. DXA and mechanical testing was performed on the L5 vertebra. After 8 wk of treatment, trabecular bone turnover rates were significantly suppressed in all drug-treated animals. Trabecular bone formation rate (BFR/BS) remained significantly lower than vehicle in bisphosphonate-treated animals through 12 wk. Sixteen weeks after treatment withdrawal, trabecular BFR/BS in the proximal tibia was re-established in animals treated with RIS but not in animals treated with ALN compared with controls. BMD of the fifth lumbar vertebra remained significantly higher than controls 16 wk after treatment withdrawal in ALN-treated animals but not in RIS-treated animals. Despite reductions in BMD and increases in bone turnover, ultimate force of the fifth lumbar vertebra remained significantly higher in all drug-treated animals through 16 wk after withdrawal. [source] Bisphosphonate-Induced Osteopetrosis: Novel Bone Modeling Defects, Metaphyseal Osteopenia, and Osteosclerosis Fractures After Drug Exposure Ceases,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 10 2008Michael P Whyte Abstract In 2003, we reported on a 12-yr-old boy who had developed osteopetrosis (OPT) while receiving pamidronate (PMD) for idiopathic bone pain and enigmatic elevation in circulating bone alkaline phosphatase. Now 17 yr of age, he was re-evaluated 6.5 yr after PMD exposure stopped. Our patient described less bone pain but further limb fractures. His growth plates were fused, yet hyperphosphatasemia persisted. Radiographs documented interval fractures of a metacarpal, an osteosclerotic distal radius, and a dense diaphyseal segment of an ulna where a "chalkstick" break remained incompletely healed after 2 yr. There was new L4 spondylolysis, and previous L5 spondylolysis had caused spondylolisthesis. Modeling disturbances of OPT persisted, but partial recovery was shown by metaphyseal surfaces with a unique concave shape. Metaphyseal osteosclerosis had remodeled imperfectly to become focal areas of dense, diaphyseal bone. Newer metaphyseal bone was unexpectedly osteopenic, especially in his distal femurs where cortices were thin and a paucity of trabeculae was documented by CT. Femoral necks had become short and wide with an abnormal contour. A "bone-within-bone" configuration was now present throughout his skeleton. In vertebrae, endplates were thin, and trabecular osteopenia was present central and peripheral to the bands of osteosclerosis. BMD Z-scores assessed by DXA had decreased into the normal range in his spine, hip, and whole body. Iliac crest biopsy showed active bone formation, with much less accumulated primary spongiosa than during the PMD infusions. Osteoclasts that had been dysmorphic, round cells without polarization and off of bone surfaces were now unremarkable in number, location, and appearance. In conclusion, bisphosphonate toxicity during childhood can impair skeletal modeling and remodeling with structural changes that evolve and carry into adult life. [source] Quantitative Trait Loci for BMD in an SM/J by NZB/BlNJ Intercross Population and Identification of Trps1 as a Probable Candidate Gene,,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 9 2008Naoki Ishimori Abstract Identification of genes that regulate BMD will enhance our understanding of osteoporosis and could provide novel molecular targets for treatment or prevention. We generated a mouse intercross population and carried out a quantitative trait locus (QTL) analysis of 143 female and 124 male F2 progeny from progenitor strains SM/J and NZB/BlNJ using whole body and vertebral areal BMD (aBMD) as measured by DXA. We found that both whole body and vertebral aBMD was affected by two loci on chromosome 9: one with a significant epistatic interaction on distal chromosome 8 and the other with a sex-specific effect. Two additional significant QTLs were identified on chromosome 12, and several suggestive ones were identified on chromosomes 5, 8, 15, and 19. The chromosome 9, 12, and 15 loci have been previously identified in other crosses. SNP-based haplotype analysis of the progenitor strains identified blocks within the QTL region that distinguish the low allele strains from the high allele strains, significantly narrowing the QTL region and reducing the possible candidate genes to 98 for chromosome 9, 31 for chromosome 12, and only 2 for chromosome 15. Trps1 is the most probable candidate gene for the chromosome 15 QTL. The sex-specific effects may help to elucidate the BMD differences between males and females. This study shows the power of statistical modeling to resolve linked QTLs and the use of haplotype analysis in narrowing the list of candidates. [source] Assessment of the 10-Year Probability of Osteoporotic Hip Fracture Combining Clinical Risk Factors and Heel Bone Ultrasound: The EPISEM Prospective Cohort of 12,958 Elderly Women,,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 7 2008Didier Hans Abstract This study aimed to develop a hip screening tool that combines relevant clinical risk factors (CRFs) and quantitative ultrasound (QUS) at the heel to determine the 10-yr probability of hip fractures in elderly women. The EPISEM database, comprised of ,13,000 women ,70 yr of age, was derived from two population-based white European cohorts in France and Switzerland. All women had baseline data on CRFs and a baseline measurement of the stiffness index (SI) derived from QUS at the heel. Women were followed prospectively to identify incident fractures. Multivariate analysis was performed to determine the CRFs that contributed significantly to hip fracture risk, and these were used to generate a CRF score. Gradients of risk (GR; RR/SD change) and areas under receiver operating characteristic curves (AUC) were calculated for the CRF score, SI, and a score combining both. The 10-yr probability of hip fracture was computed for the combined model. Three hundred seven hip fractures were observed over a mean follow-up of 3.2 yr. In addition to SI, significant CRFs for hip fracture were body mass index (BMI), history of fracture, an impaired chair test, history of a recent fall, current cigarette smoking, and diabetes mellitus. The average GR for hip fracture was 2.10 per SD with the combined SI + CRF score compared with a GR of 1.77 with SI alone and of 1.52 with the CRF score alone. Thus, the use of CRFs enhanced the predictive value of SI alone. For example, in a woman 80 yr of age, the presence of two to four CRFs increased the probability of hip fracture from 16.9% to 26.6% and from 52.6% to 70.5% for SI Z-scores of +2 and ,3, respectively. The combined use of CRFs and QUS SI is a promising tool to assess hip fracture probability in elderly women, especially when access to DXA is limited. [source] RANKL Inhibition with Osteoprotegerin Increases Bone Strength by Improving Cortical and Trabecular bone Architecture in Ovariectomized Rats,,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 5 2008Michael S Ominsky Abstract Introduction: Ovariectomy (OVX) results in bone loss caused by increased bone resorption. RANKL is an essential mediator of bone resorption. We examined whether the RANKL inhibitor osteoprotegerin (OPG) would preserve bone volume, density, and strength in OVX rats. Materials and Methods: Rats were OVX or sham-operated at 3 mo of age. Sham controls were treated for 6 wk with vehicle (Veh, PBS). OVX rats were treated with Veh or human OPG-Fc (10 mg/kg, 2/wk). Serum RANKL and TRACP5b was measured by ELISA. BMD of lumbar vertebrae (L1,L5) and distal femur was measured by DXA. Right distal femurs were processed for bone histomorphometry. Left femurs and the fifth lumbar vertebra (L5) were analyzed by ,CT and biomechanical testing, and L6 was analyzed for ash weight. Results: OVX was associated with significantly greater serum RANKL and osteoclast surface and with reduced areal and volumetric BMD. OPG markedly reduced osteoclast surface and serum TRACP5b while completely preventing OVX-associated bone loss in the lumbar vertebrae, distal femur, and femur neck. Vertebrae from OPG-treated rats had increased dry and ash weight, with no significant differences in tissue mineralization versus OVX controls. ,CT showed that trabecular compartments in OVX-OPG rats had significantly greater bone volume fraction, vBMD, bone area, trabecular thickness, and number, whereas their cortical compartments had significantly greater bone area (p < 0.05 versus OVX-Veh). OPG improved cortical area in L5 and the femur neck to levels that were significantly greater than OVX or sham controls (p < 0.05). Biomechanical testing of L5 and femur necks showed significantly greater maximum load values in the OVX-OPG group (p < 0.05 versus OVX-Veh). Bone strength at both sites was linearly correlated with total bone area (r2 = 0.54,0.74, p < 0.0001), which was also significantly increased by OPG (p < 0.05 versus OVX). Conclusions: OPG treatment prevented bone loss, preserved trabecular architecture, and increased cortical area and bone strength in OVX rats. [source] Mutations in the Insulin-Like Factor 3 Receptor Are Associated With Osteoporosis,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 5 2008Alberto Ferlin Abstract Introduction: Insulin-like factor 3 (INSL3) is produced primarily by testicular Leydig cells. It acts by binding to its specific G protein,coupled receptor RXFP2 (relaxin family peptide 2) and is involved in testicular descent during fetal development. The physiological role of INSL3 in adults is not known, although substantial INSL3 circulating levels are present. The aim of this study was to verify whether reduced INSL3 activity could cause or contribute to some signs of hypogonadism, such as reduced BMD, currently attributed to testosterone deficiency. Materials and Methods: Extensive clinical, biochemical, and hormonal study, including bone densitometry by DXA, was performed on 25 young men (age, 27,41 yr) with the well-characterized T222P mutation in the RXFP2 gene. Expression analysis of INSL3 and RXFP2 on human bone biopsy and human and mouse osteoblast cell cultures was performed by RT-PCR, quantitative RT-PCR, and immunohistochemistry. Real-time cAMP imaging analysis and proliferation assay under the stimulus of INSL3 was performed on these cells. Lumbar spine and femoral bone of Rxfp2- deficient mice were studied by static and dynamic histomorphometry and ,CT, respectively. Results: Sixteen of 25 (64%) young men with RXFP2 mutations had significantly reduced BMD. No other apparent cause of osteoporosis was evident in these subjects, whose testosterone levels and gonadal function were normal. Expression analyses showed the presence of RXFP2 in human and mouse osteoblasts. Stimulation of these cells with INSL3 produced a dose- and time-dependent increase in cAMP and cell proliferation, confirming the functionality of the RXFP2/INSL3 receptor,ligand complex. Consistent with the human phenotype, bone histomorphometric and ,CT analyses of Rxfp2,/, mice showed decreased bone mass, mineralizing surface, bone formation, and osteoclast surface compared with wildtype littermates. Conclusions: This study suggests for the first time a role for INSL3/RXFP2 signaling in bone metabolism and links RXFP2 gene mutations with human osteoporosis. [source] In Vivo Determination of Bone Structure in Postmenopausal Women: A Comparison of HR-pQCT and High-Field MR Imaging,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 4 2008Galateia J Kazakia PhD Abstract Bone structural measures obtained by two noninvasive imaging tools,3T MRI and HR-pQCT,were compared. Significant but moderate correlations and 2- to 4-fold discrepancies in parameter values were detected, suggesting that differences in acquisition and analysis must be considered when interpreting data from these imaging modalities. Introduction: High-field MRI and high resolution (HR)-pQCT are currently being used in longitudinal bone structure studies. Substantial differences in acquisition and analysis between these modalities may influence the quantitative data produced and could potentially influence clinical decisions based on their results. Our goal was to compare trabecular and cortical bone structural measures obtained in vivo by 3T MRI and HR-pQCT. Materials and Methods: Postmenopausal osteopenic women (n = 52) were recruited for this study. HR-pQCT imaging of the radius and tibia was performed using the XtremeCT scanner, with a voxel size of 82 × 82 × 82 ,m3. MR imaging was performed on a 3T Signa scanner using SSFP imaging sequences, with a pixel size of 156 × 156 ,m2 and slice thickness of 500 ,m. Structure parameters were calculated using standard HR-pQCT and MRI analysis techniques. Relationships between measures derived from HR-pQCT, MRI, and DXA were studied. Results: Significant correlations between HR-pQCT and MRI parameters were found (p < 0.0001) and were strongest for Tb.N (r2 = 0.52), Ct.Th (r2 = 0.59), and site-specific Tb.Sp (r2 = 0.54,0.60). MRI and HR-pQCT provided statistically different values of structure parameters (p < 0.0001), with BV/TV and Tb.Th exhibiting the largest discrepancies (MR/HR-pQCT = 3,4). Although differences in the Tb.N values were statistically significant, the mean differences were on the order of our reproducibility measurements. Systematic differences between MRI and HR-pQCT analysis procedures leading to discrepancies in cortical thickness values were observed, with MRI values consistently higher. Minimal correlations were found between MRI or HR-pQCT parameters and DXA BMD or T-score, except between HR-pQCT measures at the radius and the ultradistal radius T-scores, where moderate correlations were found (r2 = 0.19,0.58). Conclusions: This study provides unique insight into two emerging noninvasive tools for bone structure evaluation. Our findings highlight the significant influence of analysis technique on results of in vivo assessment and underscore the importance of accounting for these differences when interpreting results from these modalities. [source] Growth and Bone Mineral Accretion During Puberty in Chinese Girls: A Five-Year Longitudinal Study,,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 2 2008Kun Zhu Abstract There are few longitudinal data on bone development during puberty in children with low calcium intake. This 5-yr longitudinal study showed that, in Chinese girls, the mean apparent calcium retention efficiency during puberty was 40.9%, PHV occurred at 3,0 yr before menarche, and peak bone mineral accretion occurred 1 yr later than PHV. Chinese girls have high calcium retention efficiency during puberty. Introduction: There are few longitudinal data on bone development during puberty in children with low dietary calcium intake. The aim of this study was to examine the rate of growth and bone mineral accretion and study the predictors of total body BMC during puberty in a 5-yr longitudinal study with Chinese girls. Materials and Methods: Ninety-two girls, 9.5,10.5 yr of age at baseline, from the unsupplemented control group of a school milk intervention trial were included in this analysis. Data on anthropometric measurements, total body BMC as assessed by DXA, and calcium intake as assessed by a 3-day food record were obtained at baseline and 1, 2, 4, and 5 yr. Results: The mean age of menarche was 12.1 ± 1.0 yr. The mean annual rate of bone mineral accretion was 197.4 g/yr during the follow-up period, representing a calcium accretion rate of 162.3 mg/d. This calcium retention rate and the average dietary calcium intake of 444.1 mg/d gave an apparent calcium retention efficiency of 40.9%. Peak height velocity (PHV) occurred at 3,0 yr before menarche. Peak bone mineral accretion occurred 1 yr later than PHV. There was a decrease in size-corrected BMD in the year before menarche. In the linear mixed-effects model analysis containing body size and lifestyle factors, we found that height, body weight, and calcium intake were significant independent predictors of total body BMC. Conclusions: Chinese girls with low habitual dietary calcium intake have high calcium retention efficiency during puberty. Because calcium intake is a significant predictor of total body BMC, increasing dietary calcium intake may have beneficial effects on bone mineral accretion in these girls. [source] Bone Fragility Contributes to the Risk of Fracture in Children, Even After Moderate and Severe Trauma,,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 2 2008Emma M Clark Abstract We prospectively examined whether the relationship between skeletal fragility and fracture risk in children 9.9 ± 0.3 (SD) yr is affected by trauma level. Bone size relative to body size and humeral vBMD showed similar inverse relationships with fracture risk, irrespective of whether fractures followed slight or moderate/severe trauma. Introduction: Fracture risk in childhood is related to underlying skeletal fragility. However, whether this relationship is confined to low-trauma fractures or whether skeletal fragility also contributes to the risk of fracture caused by higher levels of trauma is currently unknown. Materials and Methods: Total body DXA scan results obtained at 9.9 yr of age were linked to reported fractures over the following 2 yr in children from the Avon Longitudinal Study of Parents and Children. DXA scan results that were subsequently derived included total body less head (TBLH) bone size relative to body size (calculated from TBLH area adjusted for height and weight) and humeral volumetric BMD (vBMD; derived from subregional analysis at this site). Trauma level was assigned using the Landin classification based on a questionnaire asking about precipitating causes. Results: Of the 6204 children with available data, 549 (8.9%) reported at least one fracture over the follow-up period, and trauma level was assigned in 280 as follows: slight trauma, 56.1%; moderate trauma, 41.0%; severe trauma, 2.9%. Compared with children without fractures, after adjustment for age, sex, socioeconomic status, and ethnicity, children with fractures from both slight and moderate/severe trauma had a reduced bone size relative to body size (1133 cm2 in nonfractured children versus 1112 cm2 for slight trauma fractures, p < 0.001; 1112 cm2 for moderate/severe trauma fractures, p = 0.001) and reduced humeral vBMD (0.494 g/cm3 in nonfractured children versus 0.484 g/cm3 for slight trauma fractures, p = 0.036; and 0.482g/cm3 for moderate/severe trauma fractures, p = 0.016). Conclusions: Skeletal fragility contributes to fracture risk in children, not only in fractures caused by slight trauma but also in those that result from moderate or severe trauma. [source] Monitoring Teriparatide-Associated Changes in Vertebral Microstructure by High-Resolution CT In Vivo: Results From the EUROFORS Study,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 9 2007Christian Graeff Dipl-Ing Abstract We introduce a method for microstructural analysis of vertebral trabecular bone in vivo based on HRCT. When applied to monitor teriparatide treatment, changes in structural variables exceeded and were partially independent of changes in volumetric BMD. Introduction: Monitoring of osteoporosis therapy based solely on bone densitometry is insufficient to assess anti-fracture efficacy. Assessing bone microstructure in vivo is therefore of importance. We studied whether it is possible to monitor effects of teriparatide on vertebral trabecular microstructure independent of BMD by high-resolution CT (HRCT). Materials and Methods: In a subset of 65 postmenopausal women with established osteoporosis who participated in the EUROFORS study, HRCT scans of T12, quantitative CT of L1,L3, and DXA of L1,L4 were performed after 0, 6, and 12 mo of teriparatide treatment (20 ,g/d). We compared BMD and 3D microstructural variables in three groups of women, based on prior antiresorptive treatment: treatment-naïve; pretreated; and pretreated women showing inadequate response to treatment. Results: We found statistically highly significant increases in most microstructural variables and BMD 6 mo after starting teriparatide. After 12 mo, apparent bone volume fraction (app. BV/TV) increased by 30.6 ± 4.4% (SE), and apparent trabecular number (app. Tb.N.) increased by 19.0 ± 3.2% compared with 6.4 ± 0.7% for areal and 19.3 ± 2.6% for volumetric BMD. The structural changes were partially independent of BMD as shown by a significantly larger standardized increase and a standardized long-term precision at least as good as DXA. Patients who had shown inadequate response to prior osteoporosis treatment did show improvements in BMD and structural measures comparable to treatment-naïve patients. Conclusions: HRCT is a feasible method for longitudinal microstructural analysis of human vertebrae in vivo, offers information beyond BMD, and is sufficiently precise to show profound effects of teriparatide after 12 mo. [source] Bone Loss, Weight Loss, and Weight Fluctuation Predict Mortality Risk in Elderly Men and WomenJOURNAL OF BONE AND MINERAL RESEARCH, Issue 8 2007Nguyen D Nguyen Abstract Low baseline BMD, rate of BMD loss, weight loss, and weight fluctuation are significant predictors of all-cause mortality in elderly men and women, independent of each other and of age, incident fracture, and concomitant diseases. Introduction: Although low BMD has been shown to be associated with mortality in women, the effect of BMD is affected by weight and weight change and the contribution of these factors to mortality risk, particularly in men, is not known. This study examined the association between baseline BMD, rate of bone loss, weight loss, and weight fluctuation and all-cause mortality risk in elderly men and women. Materials and Methods: Data from 1059 women and 644 men, ,60 years of age (as of 1989), of white background who participated in the Dubbo Osteoporosis Epidemiology Study were analyzed. All-cause mortality was recorded annually between 1989 and 2004. BMD at the femoral neck was measured by DXA (GE-LUNAR) at baseline and at approximately every 2 yr afterward. Data on incident osteoporotic fractures and concomitant diseases, including cardiovascular diseases, all types of cancer, and type I/II diabetes mellitus, was also recorded. Results: In the multivariable Cox's proportional hazards model with adjustment for age, incident fractures, and concomitant diseases, the following variables were independent risk factors of all-cause mortality in men: rate of BMD loss of at least 1%/yr, rate of weight loss of at least 1%/yr, and weight fluctuation (defined by the CV) of at least 3%. In women, in addition to the significant factors observed in men, lower baseline BMD was also an independent risk factor of mortality. In both sexes, baseline weight was not an independent and significant predictor of mortality risk. Approximately 36% and 22% of deaths in women and men, respectively, were attributable to the four risk factors. Conclusions: These data suggest that, although low BMD was a risk factor of mortality in women, it was not a risk factor of mortality in men. However, high rates of BMD loss, weight loss, and weight fluctuation were also independent predictors of all-cause mortality in elderly men and women, independent of age, incident fracture, and concomitant diseases. [source] Residual Lifetime Risk of Fractures in Women and Men,,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 6 2007Nguyen D Nguyen Abstract In a sample of 1358 women and 858 men, ,60 yr of age who have been followed-up for up to 15 yr, it was estimated that the mortality-adjusted residual lifetime risk of fracture was 44% for women and 25% for men. Among those with BMD T-scores , ,2.5, the risks increased to 65% in women and 42% in men. Introduction: Risk assessment of osteoporotic fracture is shifting from relative risk to an absolute risk approach. Whereas BMD is a primary predictor of fracture risk, there has been no estimate of mortality-adjusted lifetime risk of fracture by BMD level. The aim of the study was to estimate the residual lifetime risk of fracture (RLRF) in elderly men and women. Materials and Methods: Data from 1358 women and 858 men ,60 yr of age as of 1989 of white background from the Dubbo Osteoporosis Epidemiology Study were analyzed. The participants have been followed for up to 15 yr. During the follow-up period, incidence of low-trauma, nonpathological fractures, confirmed by X-ray and personal interview, were recorded. Incidence of mortality was also recorded. BMD at the femoral neck was measured by DXA (GE-LUNAR) at baseline. Residual lifetime risk of fracture from the age of 60 was estimated by the survival analysis taking into account the competing risk of death. Results: After adjusting for competing risk of death, the RLRF for women and men from age 60 was 44% (95% CI, 40,48) and 25% (95% CI, 19,31), respectively. For individuals with osteoporosis (BMD T-scores , ,2.5), the mortality-adjusted lifetime risk of any fracture was 65% (95% CI, 58,73) for women and 42% (95% CI, 24,71) for men. For the entire cohort, the lifetime risk of hip fracture was 8.5% (95% CI, 6,11%) for women and 4% (95% CI, 1.3,5.4%) for men; risk of symptomatic vertebral fracture was 18% (95% CI, 15,21%) for women and 11% (95% CI, 7,14%) for men. Conclusions: These estimates provide a means to communicate the absolute risk of fracture to an individual patient and can help promote the identification and targeting of high-risk individuals for intervention. [source] | |||||||||||||