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Dual X-ray Absorptiometry (dual + x-ray_absorptiometry)
Selected AbstractsWeight loss, body fat mass, and leptin in Parkinson's disease,MOVEMENT DISORDERS, Issue 6 2009Birgitta Lorefält RNT Abstract Weight loss is a common problem in Parkinson's disease (PD), but the causative mechanisms behind this weight loss are unclear. We compared 26 PD patients with sex and age matched healthy controls. Examinations were repeated at baseline, after one and after two years. Body fat mass was measured by Dual X-ray Absorptiometry (DXA). Seventy three per cent of the PD patients lost body weight. Loss of body fat mass constituted a considerable part of the loss of body weight. In the patients who lost weight, serum leptin levels were lower than in those who did not lose weight. The relationship between low body fat mass and low leptin levels seems to be relevant, at least for female PD patients. It is reasonable to believe that low leptin levels in these patients could be secondary to the decreased body fat mass. © 2009 Movement Disorder Society [source] No association between inhaled corticosteroids and whole body DXA in postmenopausal women,PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 7 2006Sölve Elmståhl MD Abstract Purpose Postmenopausal women treated with corticosteroids are regarded as a high-risk group due to the effect of both natural bone loss and possible adverse effects of treatment with inhaled corticosteroids (IC). Objective To compare bone mineral density (BMD) in postmenopausal women exposed only to IC (IC group, n,=,106) with that of BMD in women not exposed to corticosteroids (n,=,124) and women exposed to oral and/or intra-articular injections in addition to inhaled corticosteroids (OC group, n,=,31). The women were recruited from a population-based prospective cohort study. Methods Dual X-ray absorptiometry (DXA) technique was used to measure BMD in whole body, spine, pelvis and lower extremities. A health questionnaire and an interview about past and present medication use were used. Results The mean duration and dose of IC were 9.5,±,4.5 years and 615,µg daily. Whole body BMD did not significantly differ between the IC group (1.103,g/cm2) and the unexposed group (1.087,g/cm2). Within the IC group, BMD stratified for cumulative dose of IC, duration or current dose above or below 800,µg did not differ. Z -score BMD for tertiles did not differ when comparing the IC and OC groups. Conclusion No difference in BMD was noted between postmenopausal women exposed to inhaled corticosteroids and unexposed controls nor was there any dose response relationship between inhaled corticosteroid therapy and BMD. Copyright © 2006 John Wiley & Sons, Ltd. [source] PSA and body composition by dual X-Ray absorptiometry (DXA) in NHANESTHE PROSTATE, Issue 2 2010Jay H. Fowke Abstract BACKGROUND Obese men are at higher risk for advanced prostate cancer and have a poorer prognosis following treatment. Several studies also report that obese men have lower blood PSA levels, suggesting that obesity may be interfering with the ability to detect early-stage prostate cancer. METHODS Dual X-ray absorptiometry (DXA) is considered a gold-standard measurement of body composition. We investigated the association between PSA levels and body composition measured by DXA among 1,360 men participating in NHANES (2001,2004), a representative sample of the U.S. male population. RESULTS After controlling for age, race, and other factors, PSA concentration was ,15% lower for men with the highest level of total mass, lean mass, fat mass, trunk lean mass, and trunk fat mass (all P for trend <0.05). We then multiplied PSA concentration by estimated plasma volume to calculate the amount of PSA in circulation (i.e., PSA mass). Total body fat mass and fat mass located in the body trunk were not significantly associated with PSA mass, however, PSA mass was ,10,15% higher across low versus high categories of total body lean mass and bone mineral content (all P -trend <0.05). CONCLUSION Our results using DXA to measure body composition confirm that a greater body mass, not just fat mass, is associated with a lower PSA concentration. This is consistent with PSA hemodilution within men with a higher body mass index. The separate associations between measured lean and fat mass on calculated PSA mass require further investigation. Prostate 70: 120,125, 2010. ©2009 Wiley-Liss, Inc. [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] Body composition and its components in preterm and term newborns: A cross-sectional, multimodal investigationAMERICAN JOURNAL OF HUMAN BIOLOGY, Issue 1 2010Irfan Ahmad A prospective, cross-sectional, observational study in preterm and term infants was performed to compare multimodal measurements of body composition, namely, limb ultrasound, bone quantitative ultrasound, and dual X-ray absorptiometry (DXA). One hundred and two preterm and term infants appropriate for gestational age were enrolled from the newborn nursery and neonatal intensive care unit. Infants were included when they were medically stable, in an open crib, on full enteral feeds and within 1 week of anticipated discharge. Correlations among the various measurements of body composition were performed using standard techniques. A comparison between preterm infant (born at 28,32 weeks) reaching term to term-born infants was performed. Limb ultrasound estimates of cross-sectional areas of lean and fat tissue in a region of tissue (i.e., the leg) were remarkably correlated with regional and whole-body estimates of fat-free mass and fat obtained from DXA suggesting the potential usefulness of muscle ultrasound as an investigative tool for studying aspects of body composition in this fragile population. There was a weak but significant correlation between quantitative ultrasound measurements of bone strength and DXA-derived bone mineral density (BMD). Preterm infants reaching term had significantly lower body weight, length, head circumference, muscle and fat cross-sectional area, bone speed of sound, whole-body and regional lean body mass, fat mass, and BMD compared to term-born infants. Current postnatal care and nutritional support in preterm infants is still unable to match the in-utero environment for optimal growth and bone development. The use of relatively simple bedside, noninvasive body composition measurements may assist in understanding how changes in different components of body composition early in life affect later growth and development. Am. J. Hum. Biol. 2010. © 2009 Wiley-Liss, Inc. [source] Volumetric bone mineral density is an important tool when interpreting bone mineralization in healthy childrenACTA PAEDIATRICA, Issue 2 2009Susanne Eriksson Abstract In adults, it is well known that gender influences bone mass, but studies in children have shown contradictory results. Also, conflicting results have been reported regarding bone mineral density in obese children. Objective: To investigate bone parameters in healthy 8-year-old children and relate them to anthropometry and self-reported physical activity (PA). Design: Bone measurements were performed with dual X-ray absorptiometry in 96 children, and questionnaires were used to assess self-reported PA. Results: Bone mineral content and density differed by gender. Eighteen percent of the children were overweight/obese and they had higher bone mineral content and density than children with normal weight. Bone mineral apparent density (g/cm3) of the lumbar spine did not differ, since the vertebral size differed, as was also the case between genders. Self-reported weight-bearing PA influenced bone mass in the hip. Conclusion: PA influenced bone mineralization at this age. The differences in bone mineral content and density in healthy children would mainly be explained by the differences in bone size, reflected in body height and the width of the vertebrae. This indicates the importance of determining volumetric bone mineralization in children. [source] Serum fasting cortisol in relation to bone, and the role of genetic variations in the glucocorticoid receptorCLINICAL ENDOCRINOLOGY, Issue 6 2007N. M. Van Schoor Summary Objective, To examine the relationship between endogenous cortisol and bone, and the role of genetic variations in the glucocorticoid receptor (GR). Design and patients, The Longitudinal Ageing Study Amsterdam (LASA), a population-based cohort study in older men and women. Measurements, Serum fasting cortisol was assessed by competitive immunoassay (n = 1214); bone mineral density (BMD) by dual X-ray absorptiometry (DXA) (n = 502); broadband ultrasound attenuation (BUA) by ultrasound (n = 1209); fractures by self-report (n = 1211); and GR gene polymorphisms (ER22/23EK, N363S, 9beta, BclI) were genotyped by Taqman (n = 858). Results, Higher serum fasting cortisol was significantly associated with lower BMD at all sites and BUA at the heel in women, although most relationships were attenuated by age and body mass index (BMI). The effect on femoral neck BMD remained statistically significant in the fully adjusted model (r = ,0·135, P = 0·04). No significant associations in men were found. Female 9beta G-allele carriers had 50·2 nmol/l lower cortisol and 1·2 lower free cortisol levels than AA homozygotes [P = 0·01 for (free) cortisol]. Furthermore, female BclI GG homozygotes had 54·8 nmol/l higher cortisol levels than C-carriers (P = 0·03). In the total population, BclI GG homozygotes had 0·05 g/cm2 lower trochanteric region BMD (P = 0·03). For the other GR gene polymorphisms, no significant associations were found. Conclusions, Higher cortisol levels are associated with lower femoral neck BMD in elderly women. The G allele of the 9beta polymorphism was associated with lower serum cortisol levels in women. Female BclI GG homozygotes had higher serum cortisol levels, and BclI GG homozygotes had lower trochanteric region BMD in the total population. [source] Functional Impact of Relative Versus Absolute Sarcopenia in Healthy Older WomenJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 11 2007Marcos Estrada MD OBJECTIVES: To determine whether adjustment of muscle mass for height2 or for body mass represents a more-relevant predictor of physical performance. DESIGN: Cross-sectional study, using baseline data from a trial comparing upper- and lower-body training. SETTING: Women recruited from the community and gynecological practices in Connecticut. PARTICIPANTS: One hundred eighty-nine healthy older (aged 67.5 ± 4.8), active women receiving estrogen for osteoporosis over 2 years. MEASUREMENTS: Total and appendicular skeletal muscle (ASM) and fat mass (AFM) were determined using dual x-ray absorptiometry. Physical performance, muscle strength, and fitness measures were obtained at baseline. RESULTS: Adjusting ASM for height2 identifies lean women who are sarcopenic according to published standards yet fails to identify overweight and obese women whose ASM adjusted for body mass is low. ASM divided by body mass (ASM/body mass) is a stronger physical performance predictor, explaining 32.5%, 13.5%, 11.6%, 6.3%, and 6.8% of the variance in maximum time on treadmill, 6-minute walk, gait speed, 8-foot walk, and single leg stance, respectively, whereas ASM divided by height in m2 (ASM/height2) explained only 2.9%, 0.2%, 2.0%, 0.04%, and 0.1%. Multivariate modeling demonstrated considerable overlap in aspects of ASM/body mass and AFM/body mass associated with performance, with ASM/body mass dominant. In contrast, ASM/height2 is a much stronger predictor of leg press 1 repetition maximum and maximum power. CONCLUSION: The results suggest that relative sarcopenia with ASM adjusted for body mass is a better mobility predictor, with absolute sarcopenia a better indicator of isolated muscle group function in healthy postmenopausal women receiving estrogen replacement. [source] Kidney Function as a Predictor of Loss of Lean Mass in Older Adults: Health, Aging and Body Composition StudyJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 10 2007Linda F. Fried MD OBJECTIVES: To assess the association between kidney function and change in body composition in older individuals. DESIGN: Prospective cohort study. SETTING: Two sites, Pittsburgh, Pennsylvania, and Memphis, Tennessee. PARTICIPANTS: Three thousand twenty-six well-functioning, participants aged 70 to 79 in the Health, Aging and Body Composition Study. MEASUREMENTS: Body composition (bone-free lean mass and fat mass) was measured using dual x-ray absorptiometry annually for 4 years. Kidney function was measured at baseline according to serum creatinine (SCr). Comorbidity and inflammatory markers were evaluated as covariates in mixed-model, repeated-measures analysis. RESULTS: High SCr was associated with loss of lean mass in men but not women, with a stronger relationship in black men (P=.02 for difference between slopes for white and black men). In white men, after adjustment for age and comorbidity, higher SCr remained associated with loss of lean mass (,0.07±0.03 kg/y greater loss per 0.4 mg/dL (1 standard deviation (SD)), P=.009) but was attenuated after adjustment for inflammatory factors (,0.05±0.03 kg/y greater loss per SD, P=.10). In black men, the relationship between SCr and loss of lean mass (,0.19±0.04 kg/y per SD, P<.001) persisted after adjustment for inflammation and overall weight change. CONCLUSION: Impaired kidney function may contribute to loss of lean mass in older men. Inflammation appeared to mediate the relationship in white but not black men. Future studies should strive to elucidate mechanisms linking kidney disease and muscle loss and identify treatments to minimize loss of lean mass and its functional consequences. [source] Heritability of bone density: Regional and gender differences in monozygotic twinsJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 2 2009Kevin Y. Tse Abstract Bone mineral density (BMD) is a measure of a person's skeletal mineral content, and assessing BMD by dual x-ray absorptiometry (DEXA) can help to diagnose diseases of low bone density. In this study, we determine the heritability of BMD in male and female monozygotic twin subjects using DEXA in 13 specific anatomical regions. In an attempt to quantify the genetic contribution of gender and skeletal region to BMD heritability, we scanned 14 pairs of identical twins using DEXA and calculated the broad-sense heritability coefficient (H2) in each of the 13 different body regions. The region of the body that was most heritable for both genders was the head (H2,,,95%). When males were compared to females, H2 values for male hip (H2,=,87%) and lower extremities (H2,=,90%) were higher than those in females (H2,=,49% and 56%, respectively). Conversely, H2 value for the female pelvis (H2,=,68%) was higher than that for males (H2,=,26%). These data show that different regions of the skeleton exhibit different degrees of heritability, and that the variation depends on gender. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27:150,154, 2009 [source] Low Bone Mineral Density and Impaired Bone Metabolism in Young Alcoholic Patients Without Liver Cirrhosis: A Cross-Sectional StudyALCOHOLISM, Issue 2 2009Peter Malik Background:, Osteoporosis is regularly mentioned as a consequence of alcoholism. Ethanol,s direct effect on bone-modeling cells as well as alcoholism-related "life-style factors" such as malnutrition, lack of exercise, hormonal changes, and liver cirrhosis are discussed as potential causative factors. Methods:, In a cross-sectional study, we have examined 57 noncirrhotic alcoholic patients (37 male, 20 female) aged 27 to 50 years. Patients suffering from comorbid somatic diseases and with co-medication known to have an influence on bone mineral density (e.g., glucocorticoids, heparin, anticonvulsant agents, oral contraceptives) were excluded. We determined bone mineral density (BMD) by dual x-ray absorptiometry (DXA) in the lumbar spine (L1,L4) and the proximal right femur (femoral neck, total hip) as well as parameters of bone metabolism. Results:, In males but not females, BMD was significantly reduced in the lumbar region, as well as in the proximal femur (femoral neck, total hip). Nine male patients (24.3% of men) and 1 female patient (5% of women) had low BMD (defined as Z -score , ,2.0). As expected, there was a positive correlation between body mass index (BMI) and BMD. Alcohol-related factors (e.g., duration of abuse, consumed amount of alcohol per day) as well as smoking were not associated with a significant effect on BMD. All of the 20 women examined showed elevated estradiol levels, which may have served as a protective factor. In this study, 75.7% of the men and 90% of the women had vitamin D insufficiency or deficiency (plasma levels of 25-hydroxy-vitamin D < 30 ng/ml). Conclusions:, Our study indicates that younger alcoholic patients without other diseases may suffer from an increased risk to develop low BMD and a disturbance of vitamin D metabolism. Nutritional factors or less exposure to sunlight may play an important role in bone loss in young alcoholic patients. BMD measurement and assessment of bone metabolism should be considered in all patients with chronic alcoholism. [source] Generalized bone loss as a predictor of three-year radiographic damage in African American patients with recent-onset rheumatoid arthritisARTHRITIS & RHEUMATISM, Issue 8 2010Jie Zhang Objective To examine the association between baseline bone mineral density (BMD) and radiographic damage at 3 years of disease duration in a longitudinal cohort of African Americans with recent-onset rheumatoid arthritis (RA). Methods African American RA patients with a disease duration of <2 years (n = 141) were included in the study. All patients underwent baseline BMD measurements (femoral neck and/or lumbar spine) using dual x-ray absorptiometry. T scores were calculated using normative data from the general population of African Americans. Patients were categorized as having osteopenia/osteoporosis (T score less than or equal to ,1) or as being healthy. Hand and wrist radiographs, obtained at baseline and at 3 years of disease duration, were scored using the modified Sharp/van der Heijde method. The association between baseline BMD and total radiographic score at 3 years of disease was examined using multivariable negative binomial regression. Results At baseline, the mean age and the mean disease duration were 52.4 years and 14.8 months, respectively; 85.1% of the patients were women. The average total radiographic scores at baseline and at 3 years of disease were 2.4 and 5.7, respectively. In the final reduced multivariable model, adjusting for age, sex, anti,cyclic citrullinated peptide antibody positivity, and the presence of radiographic damage at baseline, the total radiographic score at 3 years disease in patients with osteopenia/osteoporosis of the femoral neck was twice that in patients with normal bone density, and the difference was statistically significant (P = 0.0084). No association between lumbar spine osteopenia/osteoporosis and radiographic score was found. Conclusion Our findings suggest that reduced generalized BMD may be a predictor of future radiographic damage and support the hypothesis that radiographic damage and reduced generalized BMD in RA patients may share a common pathogenic mechanism. [source] Subchondral bone and cartilage damage: A prospective study in older adultsARTHRITIS & RHEUMATISM, Issue 7 2010Dawn Doré Objective There is limited longitudinal evidence relating subchondral bone changes to cartilage damage and loss. The aim of this study was to describe the association between baseline tibial bone area and tibial subchondral bone mineral density (BMD) with tibial cartilage defect development and cartilage volume loss. Methods A total of 341 subjects (mean age 63 years, range 52,79 years) underwent measurement at baseline and ,2.7 years later. Tibial knee cartilage volume, cartilage defects (graded on a scale of 0,4), and bone area were determined using T1-weighted fat suppression magnetic resonance imaging. Tibial subchondral BMD was determined using dual x-ray absorptiometry. Results In multivariable analysis, baseline bone area positively predicted cartilage defect development at the medial and lateral tibial sites (odds ratio [OR] 1.6 per 1 SD increase, 95% confidence interval [95% CI] 1.0, 2.6, and OR 2.4 per 1 SD increase, 95% CI 1.4, 4.0, respectively) and cartilage volume loss at the medial tibial site (, = ,34.9 per 1 SD increase, 95% CI ,49.8, ,20.1). In contrast, baseline subchondral BMD positively predicted cartilage defect development at the medial tibial site only (OR 1.6 per 1 SD increase, 95% CI 1.2, 2.1) and was not associated with cartilage loss. Conclusion The results of this study demonstrated that bone area predicted medial and lateral cartilage defect development and medial cartilage volume loss, while subchondral BMD predicted medial defect development but not cartilage loss. These associations were independent of each other, indicating there are multiple mechanisms by which subchondral bone changes may lead to cartilage damage. [source] Control of Dkk-1 ameliorates chondrocyte apoptosis, cartilage destruction, and subchondral bone deterioration in osteoarthritic kneesARTHRITIS & RHEUMATISM, Issue 5 2010Lin-Hsiu Weng Objective Perturbation of Wnt signaling components reportedly regulates chondrocyte fate and joint disorders. The Wnt inhibitor Dkk-1 mediates remodeling of various tissue types. We undertook this study to examine whether control of Dkk-1 expression prevents joint deterioration in osteoarthritic (OA) knees. Methods Anterior cruciate ligament transection,and collagenase-induced OA in rat knees was treated with end-capped phosphorothioate Dkk-1 antisense oligonucleotide (Dkk-1,AS). Articular cartilage destruction, cartilage degradation markers, bone mineral density (BMD), and subchondral trabecular bone volume of injured knee joints were measured using Mankin scoring, enzyme-linked immunosorbent assay, dual x-ray absorptiometry, and histomorphometry. Dkk-1,responsive molecule expression and apoptotic cells in knee tissue were detected by quantitative reverse transcriptase,polymerase chain reaction, immunoblotting, and TUNEL staining. Results Up-regulated Dkk-1 expression was associated with increased Mankin score and with increased serum levels of cartilage oligomeric matrix protein and C-telopeptide of type II collagen (CTX-II) during OA development. Dkk-1,AS treatment alleviated OA-associated increases in Dkk-1 expression, Mankin score, cartilage fibrillation, and serum cartilage degradation markers. Dkk-1,AS also alleviated epiphyseal BMD loss and subchondral bone exposure associated with altered serum levels of osteocalcin and CTX-I. The treatment abrogated chondrocyte/osteoblast apoptosis and subchondral trabecular bone remodeling in OA. Dkk-1 knockdown increased levels of nuclear ,-catenin and phosphorylated Ser473 -Akt but attenuated expression of inflammatory factors (Toll-like receptor 4 [TLR-4], TLR-9, interleukin-1,, and tumor necrosis factor ,), the apoptosis regulator Bax, matrix metalloproteinase 3, and RANKL in OA knee joints. Conclusion Interference with the cartilage- and bone-deleterious actions of Dkk-1 provides therapeutic potential for alleviating cartilage destruction and subchondral bone damage in OA knee joints. [source] Adenosine A1 receptors regulate bone resorption in mice: Adenosine A1 receptor blockade or deletion increases bone density and prevents ovariectomy-induced bone loss in adenosine A1 receptor,knockout miceARTHRITIS & RHEUMATISM, Issue 2 2010Firas M. Kara Objective Accelerated osteoclastic bone resorption plays a central role in the pathogenesis of osteoporosis and other bone diseases. Because identifying the molecular pathways that regulate osteoclast activity provides a key to understanding the causes of these diseases and developing new treatments, we studied the effect of adenosine A1 receptor blockade or deletion on bone density. Methods The bone mineral density (BMD) in adenosine A1 receptor,knockout (A1R-knockout) mice was analyzed by dual x-ray absorptiometry (DXA) scanning, and the trabecular and cortical bone volume was determined by microfocal computed tomography (micro-CT). The mice were ovariectomized or sham-operated, and 5 weeks after surgery, when osteopenia had developed, several parameters were analyzed by DXA scanning and micro-CT. A histologic examination of bones obtained from A1R-knockout and wild-type mice was carried out. Visualization of osteoblast function (bone formation) after tetracycline double-labeling was performed by fluorescence microscopy. Results Micro-CT analysis of bones from A1R-knockout mice showed significantly increased bone volume. Electron microscopy of bones from A1R-knockout mice showed the absence of ruffled borders of osteoclasts and osteoclast bone resorption. Immunohistologic analysis demonstrated that although osteoclasts were present in the A1R-knockout mice, they were smaller and often not associated with bone. No morphologic changes in osteoblasts were observed, and bone-labeling studies revealed no change in the bone formation rates in A1R-knockout mice. Conclusion These results suggest that the adenosine A1 receptor may be a useful target in treating diseases characterized by excessive bone turnover, such as osteoporosis and prosthetic joint loosening. [source] Extreme obesity due to impaired leptin signaling in mice does not cause knee osteoarthritisARTHRITIS & RHEUMATISM, Issue 10 2009Timothy M. Griffin Objective To test the hypothesis that obesity resulting from deletion of the leptin gene or the leptin receptor gene results in increased knee osteoarthritis (OA), systemic inflammation, and altered subchondral bone morphology. Methods Leptin-deficient (ob/ob) and leptin receptor,deficient (db/db) female mice compared with wild-type mice were studied, to document knee OA via histopathology. The levels of serum proinflammatory and antiinflammatory cytokines were measured using a multiplex bead immunoassay. Cortical and trabecular subchondral bone changes were documented by microfocal computed tomography, and body composition was quantified by dual x-ray absorptiometry. Results Adiposity was increased by ,10-fold in ob/ob and db/db mice compared with controls, but it was not associated with an increased incidence of knee OA. Serum cytokine levels were unchanged in ob/ob and db/db mice relative to controls, except for the level of cytokine-induced neutrophil chemoattractant (keratinocyte chemoattractant; murine analog of interleukin-8), which was elevated. Leptin impairment was associated with reduced subchondral bone thickness and increased relative trabecular bone volume in the tibial epiphysis. Conclusion Extreme obesity due to impaired leptin signaling induced alterations in subchondral bone morphology without increasing the incidence of knee OA. Systemic inflammatory cytokine levels remained largely unchanged in ob/ob and db/db mice. These findings suggest that body fat, in and of itself, may not be a risk factor for joint degeneration, because adiposity in the absence of leptin signaling is insufficient to induce systemic inflammation and knee OA in female C57BL/6J mice. These results imply a pleiotropic role of leptin in the development of OA by regulating both the skeletal and immune systems. [source] Changes in proximal femoral mineral geometry precede the onset of radiographic hip osteoarthritis: The study of osteoporotic fracturesARTHRITIS & RHEUMATISM, Issue 7 2009M. K. Javaid Objective Radiographic hip osteoarthritis (RHOA) is associated with increased hip areal bone mineral density (aBMD). This study was undertaken to examine whether femoral geometry is associated with RHOA independent of aBMD. Methods Participants in the Study of Osteoporotic Fractures in whom pelvic radiographs had been obtained at visits 1 and 5 (mean 8.3 years apart) and hip dual x-ray absorptiometry (DXA) had been performed (2 years after baseline) were included. Prevalent and incident RHOA phenotypes were defined as composite (osteophytes and joint space narrowing [JSN]), atrophic (JSN without osteophytes), or osteophytic (femoral osteophytes without JSN). Analogous definitions of progression were based on minimum joint space and total osteophyte score. Hip DXA scans were assessed using the Hip Structural Analysis program to derive geometric measures, including femoral neck length, width, and centroid position. Relative risks and 95% confidence intervals for prevalent, incident, and progressive RHOA per SD increase in geometric measure were estimated in a hip-based analysis using multinomial logistic regression with adjustment for age, body mass index, knee height, and total hip aBMD. Results In 5,245 women (mean age 72.6 years), a wider femoral neck with a more medial centroid position was associated with prevalent and incident osteophytic and composite RHOA phenotypes (P < 0.05). Increased neck width and centroid position were associated with osteophyte progression (both P < 0.05). No significant geometric associations with atrophic RHOA were found. Conclusion Differences in proximal femoral bone geometry and spatial distribution of bone mass occur early in hip OA and predict prevalent, incident, and progressive osteophytic and composite phenotypes, but not the atrophic phenotype. These bone differences may reflect responses to loading occurring early in the natural history of RHOA. [source] The relationship between focal erosions and generalized osteoporosis in postmenopausal women with rheumatoid arthritisARTHRITIS & RHEUMATISM, Issue 6 2009Daniel 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] Musculoskeletal abnormalities of the tibia in juvenile rheumatoid arthritisARTHRITIS & RHEUMATISM, Issue 3 2007Elena M. O. Felin Objective To characterize local bone geometry, density, and strength, using peripheral quantitative computed tomography (pQCT), compared with general bone characteristics as measured using dual x-ray absorptiometry (DXA), and to assess their relationship to disease-related factors in children with juvenile rheumatoid arthritis (JRA). Methods Forty-eight children ages 4,18 years with JRA (17 pauciarticular, 23 polyarticular, 8 systemic) were compared with age-matched healthy controls (n = 266). Measurements included cortical and trabecular bone geometry, density, and strength at the distal and midshaft tibia determined by pQCT, and whole-body, lumbar spine, and femoral neck measurements by DXA. Results Methotrexate (MTX) was prescribed to 23 of 48 patients (47.9%) and glucocorticoids and MTX were prescribed to 15 of 48 patients (31.3%), with the greatest use in children with systemic JRA. All JRA patients had decreased tibia trabecular bone density, cortical bone size and strength, and muscle mass. Children with systemic JRA had lower femoral neck densities. Systemic JRA was associated with a shorter, less mineralized skeleton, while a narrower, less mineralized skeleton was observed in polyarticular JRA. The tibia diaphysis was narrower with decreased muscle mass, but normal, size-adjusted bone mineral in all subtypes indicated a localized effect of JRA on bone. Patients exposed to glucocorticoids and MTX or to glucocorticoids or MTX alone had greatly reduced trabecular density, cortical bone geometry properties, and bone mineral content, muscle mass, and bone strength. Conclusion Children with JRA have decreased skeletal size, muscle mass, trabecular bone density, cortical bone geometry, and strength. Not surprisingly, these bone abnormalities are more pronounced in children with greater disease severity. [source] Kinetics of bone protection by recombinant osteoprotegerin therapy in Lewis rats with adjuvant arthritisARTHRITIS & RHEUMATISM, Issue 7 2002Giuseppe Campagnuolo Objective To assess the effect of different dosages and treatment schedules of osteoprotegerin (OPG) on joint preservation in an experimental model of adjuvant-induced arthritis (AIA). Methods Male Lewis rats with AIA (6,8 per group) were treated with a subcutaneous bolus of recombinant human OPG according to one of the following schedules: daily OPG (an efficacious regimen) starting at disease onset (days 9,15), early intervention (days 9,11), delayed intervention (days 13,15), and extended therapy (days 9,22). Inflammation (hind paw swelling) was quantified throughout the clinical course; osteoporosis (bone mineral density [BMD], by quantitative dual x-ray absorptiometry) and morphologic appraisals of inflammation, bone damage, intralesional osteoclasts (by semiquantitative histopathologic scoring), and integrity of the articular cartilage matrix (by retention of toluidine blue stain) were determined in histology sections of arthritic hind paws. Results OPG provided dose- and schedule-dependent preservation of BMD and periarticular bone while essentially eliminating intralesional osteoclasts. Dosages ,2.5 mg/kg/day preserved or enhanced BMD and prevented essentially all erosions. A dosage of 4 mg/kg/day protected joint integrity to a comparable degree when given for 7 (days 9,15) or 14 (days 9,22) consecutive days. At this dosage, early intervention (days 9,11) was twice as effective as delayed intervention (days 13,15) at preventing joint dissolution. Erosions and osteoclast scores were greatly decreased for 26 days (measured from the first treatment) after 7 or 14 daily doses of OPG (4 mg/kg/day). OPG treatment also prevented loss of cartilage matrix proteoglycans, an indirect consequence of protecting the subchondral bone. No OPG dosage or regimen alleviated weight loss, inflammation, or periosteal osteophyte production. Conclusion These data indicate that OPG preserves articular bone and (indirectly) articular cartilage in arthritic joints in a dose- and schedule-dependent manner, halts bone erosion when given at any point during the course of arthritis, produces sustained antierosive activity after a short course, and is most effective when initiated early in the disease. [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 therapyARTHRITIS & RHEUMATISM, Issue 5 2002Q. 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] | |||||||||||||