Areal BMD (areal + bmd)

Distribution by Scientific Domains


Selected Abstracts


A Bivariate Whole Genome Linkage Study Identified Genomic Regions Influencing Both BMD and Bone Structure,

JOURNAL OF BONE AND MINERAL RESEARCH, Issue 11 2008
Xiao-Gang Liu
Abstract Areal BMD (aBMD) and areal bone size (ABS) are biologically correlated traits and are each important determinants of bone strength and risk of fractures. Studies showed that aBMD and ABS are genetically correlated, indicating that they may share some common genetic factors, which, however, are largely unknown. To study the genetic factors influencing both aBMD and ABS, bivariate whole genome linkage analyses were conducted for aBMD-ABS at the femoral neck (FN), lumbar spine (LS), and ultradistal (UD)-forearm in a large sample of 451 white pedigrees made up of 4498 individuals. We detected significant linkage on chromosome Xq27 (LOD = 4.89) for LS aBMD-ABS. In addition, we detected suggestive linkages at 20q11 (LOD = 3.65) and Xp11 (LOD = 2.96) for FN aBMD-ABS; at 12p11 (LOD = 3.39) and 17q21 (LOD = 2.94) for LS aBMD-ABS; and at 5q23 (LOD = 3.54), 7p15 (LOD = 3.45), Xq27 (LOD = 2.93), and 12p11 (LOD = 2.92) for UD-forearm aBMD-ABS. Subsequent discrimination analyses indicated that quantitative trait loci (QTLs) at 12p11 and 17q21 may have pleiotropic effects on aBMD and ABS. This study identified several genomic regions that may contain QTLs important for both aBMD and ABS. Further endeavors are necessary to follow these regions to eventually pinpoint the genetic variants affecting bone strength and risk of fractures. [source]


The COMT val158met Polymorphism Is Associated With Peak BMD in Men,

JOURNAL OF BONE AND MINERAL RESEARCH, Issue 12 2004
Mattias Lorentzon
Abstract The associations between the functional val158met polymorphism of the estrogen-degrading COMT enzyme and skeletal properties in young men were investigated. BMD was associated with COMT genotype. Introduction: Peak BMD is an important predictor of future risk of osteoporosis, and it is to a large extent determined by genetic factors. Estrogens are involved in the accretion of bone mass during puberty. Catechol- O -methyltransferase (COMT) is involved in the degradation of estrogens. There is a functional polymorphism in the COMT gene (val158met), resulting in a 60,75% difference in enzyme activity between the val (high activity [H]) and met (low activity [L]) variants. The aim of this cross-sectional study was to investigate the associations between this polymorphism and peak BMD in young men. Materials and Methods: A total of 458 healthy men (mean age, 19 ± 0.6 years) were genotyped and classified as COMTLL, COMTHL, or COMTHH. Areal BMD (aBMD) was measured by DXA. Cortical and trabecular volumetric BMD (vBMD) were measured by pQCT. The associations between COMT genotype and skeletal phenotypes were determined. Results and Conclusions: Regression models using physical activity, height, weight, age, and COMT genotype as covariates showed that COMT genotype was an independent predictor of aBMD in the total body and in all femur locations investigated, but not in the spine. The values for COMTHL and COMTHH were very similar, and therefore, they were pooled into one group. aBMD at Ward's triangle, trochanter, and total femur were 4.9%, 4.5%, and 3.7% lower, respectively, in the COMTLL than in the COMTHL/HH group (p < 0.01). pQCT analyses showed that COMT genotype was an independent predictor of trabecular vBMD of the tibia, radius, and fibula. Trabecular vBMD of the radius and fibula in COMTLL was 5.3% and 7.4% lower, respectively, than that of the combined COMTHL/HH group. COMT genotype was associated with cortical vBMD but not with cortical cross-sectional area in the tibia. These findings show that the COMT polymorphism is associated with BMD in young adult men. [source]


Generalized Low Areal and Volumetric Bone Mineral Density in Adolescent Idiopathic Scoliosis,

JOURNAL OF BONE AND MINERAL RESEARCH, Issue 8 2000
J. C. Y. Cheng
Abstract Adolescent idiopathic scoliosis (AIS) may be associated with generalized low bone mineral status. The bone mineral density (BMD) of 75 girls of 12,14 years of age and diagnosed as having AIS were compared with 94 age-matched female control subjects. Areal BMD (aBMD) of the lumbar spine (L2-L4) and the bilateral proximal femur were measured using -energy X-ray absorptiometry (DEXA), and volumetric BMD (vBMD) of the nondominant distal radius and bilateral distal tibias was measured with peripheral quantitative computer tomography (pQCT). Relevant anthropometric parameters and the severity of the spinal deformity (Cobb's angle) also were evaluated and correlated with the BMD measurements. Results revealed the presence of a generalized lower bone mineral status in AIS patients. Detailed analysis showed that the aBMD and vBMD measured at the bilateral lower extremities were significantly lower in AIS patients when compared with the same in the normal controls. The most significant effect was seen in the trabecular BMD (tBMD) of the distal tibias. Of all the AIS girls, 38% of the aBMD and 36% of the vBMD were below ,1 SD of the normal. BMD was found to correlate better with "years since menarche" (YSM) than with chronological age. When the BMD was evaluated for the 3 YSM groups, aBMD of the proximal femur and tBMD of distal tibias were found to be significantly lower in the AIS patients. Neither the aBMD nor the vBMD of AIS patients was found to be associated with the severity of spinal deformity. In addition, anthropometric measurements showed significantly longer arm span and lower extremities in the AIS girls. We concluded that the AIS girls had generalized lower aBMDs and vBMDs. [source]


Bone mass in young adults with Down syndrome

JOURNAL OF INTELLECTUAL DISABILITY RESEARCH, Issue 3 2008
M. Guijarro
Abstract Background Down syndrome (DS) is a frequent cause of intellectual disability. With the increasing life expectancy of these patients, concerns have been raised about the risk of osteoporosis. In fact, several investigators have reported a reduced bone mass in DS. However, the results may be confounded by comorbid diseases, and differences in lifestyle habits and body size. Therefore, we planned to determine anthropometric and lifestyle factors influencing bone mineral density (BMD) in young adults with DS. Methods Thirty-nine patients with DS (mean age 26 years) and 78 controls were studied. Areal BMD was measured by dual x-ray decsitometry (DXA); volumetric BMD at the lumbar spine and femoral neck was estimated with published formulae. Results DS patients had lower areal BMD than controls at all regions (spine, hip and total body). Height and projected bone area were also lower. There were no differences between both groups regarding estimated volumetric BMD at the femoral neck. However, spine volumetric BMD was also lower in DS than controls. In multivariate analysis, DS, male sex, little physical activity and low sunlight exposure were associated with lower spine volumetric BMD; on the other hand, fat mass and sunlight exposure were associated with femoral neck volumetric BMD. Conclusion This study shows that patients with DS had a reduced areal BMD, but it is in part a consequence of the reduced body size, particularly at the femoral neck. Physical activity and sunlight exposure are associated to volumetric BMD and should be stimulated in order to maintain an adequate bone mass in these patients. [source]


Genetic variation in the RANKL/RANK/OPG signaling pathway is associated with bone turnover and bone mineral density in men

JOURNAL OF BONE AND MINERAL RESEARCH, Issue 8 2010
Delnaz 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]


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

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


Severity of Vertebral Fractures Is Associated With Alterations of Cortical Architecture in Postmenopausal Women,

JOURNAL OF BONE AND MINERAL RESEARCH, Issue 4 2009
Elisabeth 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 2009
Eric 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]


Theoretical Implications of the Biomechanical Fracture Threshold

JOURNAL OF BONE AND MINERAL RESEARCH, Issue 10 2008
Tony 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]


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 2008
Naoki 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]


Low Skeletal Muscle Mass Is Associated With Poor Structural Parameters of Bone and Impaired Balance in Elderly Men,The MINOS Study,

JOURNAL OF BONE AND MINERAL RESEARCH, Issue 5 2005
Pawel Szulc MD
Abstract In 796 men, 50-85 years of age, decreased relative skeletal muscle mass index was associated with narrower bones, thinner cortices, and a consequent decreased bending strength (lower section modulus), as well as with impaired balance and an increased risk of falls. Introduction: In men, appendicular skeletal muscle mass (ASM) is correlated positively with BMC and areal BMD (aBMD). In elderly men, low muscle mass and strength (sarcopenia) is associated with difficulties in daily living activities. The aim of this study was to evaluate if ASM is correlated with bone size, mechanical properties of bones, balance, and risk of falls in elderly men. Materials and Methods: This study used 796 men, 50-85 years of age, belonging to the MINOS cohort. Lifestyle factors were evaluated by standardized questionnaires. Estimates of mechanical bone properties were derived from aBMD measured by DXA. ASM was estimated by DXA. The relative skeletal muscle mass index (RASM) was calculated as ASM/(body height)2.3. Results: After adjustment for age, body size, tobacco smoking, professional physical activity, and 17,-estradiol concentration, RASM was correlated positively with BMC, aBMD, external diameter, and cortical thickness (r = 0.17-0.34, p < 0.0001) but not with volumetric BMD. Consequently, RASM was correlated with section modulus (r = 0.29-0.39, p < 0.0001). Men in the lowest quartile of RASM had section modulus of femoral neck and distal radius lower by 12-18% in comparison with men in the highest quartile of RASM. In contrast, bone width was not correlated with fat mass, reflecting the load of body weight (except for L3), which suggests that the muscular strain may exert a direct stimulatory effect on periosteal apposition. After adjustment for confounding variables, a decrease in RASM was associated with increased risk of falls and of inability to accomplish clinical tests of muscle strength, static balance, and dynamic balance (odds ratio per 1 SD decrease in RASM, 1.31-2.23; p < 0.05-0.001). Conclusions: In elderly men, decreased RASM is associated with narrower bones and thinner cortices, which results in a lower bending strength. Low RASM is associated with impaired balance and with an increased risk of falls in elderly men. It remains to be studied whether low RASM is associated with decreased periosteal apposition and with increased fracture risk in elderly men, and whether the difference in skeletal muscle mass between men and women contributes to the between-sex difference in fracture incidence. [source]


Evaluation of a Prediction Model for Long-Term Fracture Risk,

JOURNAL OF BONE AND MINERAL RESEARCH, Issue 4 2005
L Joseph Melton III MD
Abstract The NOF cost-effectiveness model, based on clinical risk factors and femoral neck aBMD, predicted overall fracture risk in a cohort of postmenopausal women followed for up to 22 years. Introduction: To assess the ability of a statistical model to predict long-term fracture risk for a population of postmenopausal women, we compared observed fractures to those predicted by the National Osteoporosis Foundation's (NOF) cost-effectiveness model. Materials and Methods: In this population-based study, 393 postmenopausal Rochester, MN, women had baseline measurements of femoral neck areal BMD (aBMD) and assessment of the clinical risk factors (personal fracture history, family history of osteoporotic fracture, low body weight, and smoking status) that were included in the NOF model. They were then followed prospectively for up to 22 years. Fractures were ascertained by periodic interview and review of community medical records. Standardized incidence ratios (SIRs) compared observed fractures to predicted numbers. Results: During 4782 person-years of follow-up, 212 women experienced 503 fractures, two-thirds of which were caused by moderate trauma. When undiagnosed (incidentally noted) vertebral and rib fractures were excluded, there was general concordance between observed and predicted fractures of the hip (SIR, 0.78; 95% CI, 0.56-1.01), distal forearm (SIR, 1.22; 95% CI, 0.86-1.68), spine (SIR, 0.76; 95% CI, 0.50-1.11), and all other sites combined (SIR, 1.18; 95% CI, 0.97-1.42). Fracture prediction by the NOF model was about as good after 10 years as it was earlier during follow-up. Conclusions: This study validates the ability of a statistical model based on femoral neck aBMD and common clinical risk factors to predict the actual occurrence of fractures in a cohort of postmenopausal white women. [source]


Mapping Quantitative Trait Loci for Vertebral Trabecular Bone Volume Fraction and Microarchitecture in Mice,

JOURNAL OF BONE AND MINERAL RESEARCH, Issue 4 2004
Mary L Bouxsein
Abstract BMD, which reflects both cortical and cancellous bone, has been shown to be highly heritable; however, little is known about the specific genetic factors regulating trabecular bone. Genome-wide linkage analysis of vertebral trabecular bone traits in 914 adult female mice from the F2 intercross of C57BL/6J and C3H/HeJ inbred strains revealed a pattern of genetic regulation derived from 13 autosomes, with 5,13 QTLs associated with each of the traits. Ultimately, identification of genes that regulate trabecular bone traits may yield important information regarding mechanisms that regulate mechanical integrity of the skeleton. Introduction: Both cortical and cancellous bone influence the mechanical integrity of the skeleton, with the relative contribution of each varying with skeletal site. Whereas areal BMD, which reflects both cortical and cancellous bone, has been shown to be highly heritable, little is known about the genetic determinants of trabecular bone density and architecture. Materials and Methods: To identify heritable determinants of vertebral trabecular bone traits, we evaluated the fifth lumbar vertebra from 914 adult female mice from the F2 intercross of C57BL/6J (B6) and C3H/HeJ (C3H) progenitor strains. High-resolution ,CT was used to assess total volume (TV), bone volume (BV), bone volume fraction (BV/TV), trabecular thickness (Tb.Th), separation (Tb.Sp), and number (Tb.N) of the trabecular bone in the vertebral body in the progenitors (n = 8/strain) and female B6C3H-F2 progeny (n = 914). Genomic DNA from F2 progeny was screened for 118 PCR-based markers discriminating B6 and C3H alleles on all 19 autosomes. Results and Conclusions: Despite having a slightly larger trabecular bone compartment, C3H progenitors had dramatically lower vertebral trabecular BV/TV (,53%) and Tb.N (,40%) and higher Tb.Sp (71%) compared with B6 progenitors (p < 0.001 for all). Genome-wide quantitative trait analysis revealed a pattern of genetic regulation derived from 13 autosomes, with 5,13 quantitative trait loci (QTLs) associated with each of the vertebral trabecular bone traits, exhibiting adjusted LOD scores ranging from 3.1 to 14.4. The variance explained in the F2 population by each of the individual QTL after adjusting for contributions from other QTLs ranged from 0.8% to 5.9%. Taken together, the QTLs explained 22,33% of the variance of the vertebral traits in the F2 population. In conclusion, we observed a complex pattern of genetic regulation for vertebral trabecular bone volume fraction and microarchitecture using the F2 intercross of the C57BL/6J and C3H/HeJ inbred mouse strains and identified a number of QTLs, some of which are distinct from those that were previously identified for total femoral and vertebral BMD. Identification of genes that regulate trabecular bone traits may ultimately yield important information regarding the mechanisms that regulate the acquisition and maintenance of mechanical integrity of the skeleton. [source]


Glucocorticoid Excess During Adolescence Leads to a Major Persistent Deficit in Bone Mass and an Increase in Central Body Fat

JOURNAL OF BONE AND MINERAL RESEARCH, Issue 10 2001
Veronica Abad
Abstract Endogenous Cushing's syndrome (CS) in children causes growth retardation, decreased bone mass, and increased total body fat. No prospective controlled studies have been performed in children to determine the long-term sequelae of CS on peak bone mass and body composition. A 15-year-old girl with Cushing disease (CD), and her healthy identical co-twin, were followed for 6 years after the CD was cured. At the 6-year follow-up both twins had areal bone mineral density (BMD) and body composition determined by dual-energy X-ray absorptiometry (DXA) and three-dimensional quantitative computed tomography (3DQCT). Z scores for height, weight, and body mass index (BMI) were ,2.3, ,0.8 and 0.2, and 1.2, 0.2, and ,0.6, in the twin with CD and her co-twin, respectively. In the twin with CD, areal BMD and bone mineral apparent density (BMAD) at different sites varied from 0.7 to 3 SD below her co-twin. Volumetric lumbar spine bone density Z score was ,0.75 and 1.0, and total body, abdominal visceral, and subcutaneous fat (%) was 42, 10, and 41 versus 26, 4, and 17 in the twin with CD and her co-twin, respectively. The relationship between total body fat and L2-L4 BMAD was inverse in the twin with CD (p < 0.05), which by contrast in her co-twin was opposite and direct (p < 0.001). In the twin with CD, despite cure, there was a persistent deficit in bone mass and increase in total and visceral body fat. These observations suggest that hypercortisolism (exogenous or endogenous) during adolescence may have persistent adverse effects on bone and fat mass. [source]


Bone mass in young adults with Down syndrome

JOURNAL OF INTELLECTUAL DISABILITY RESEARCH, Issue 3 2008
M. Guijarro
Abstract Background Down syndrome (DS) is a frequent cause of intellectual disability. With the increasing life expectancy of these patients, concerns have been raised about the risk of osteoporosis. In fact, several investigators have reported a reduced bone mass in DS. However, the results may be confounded by comorbid diseases, and differences in lifestyle habits and body size. Therefore, we planned to determine anthropometric and lifestyle factors influencing bone mineral density (BMD) in young adults with DS. Methods Thirty-nine patients with DS (mean age 26 years) and 78 controls were studied. Areal BMD was measured by dual x-ray decsitometry (DXA); volumetric BMD at the lumbar spine and femoral neck was estimated with published formulae. Results DS patients had lower areal BMD than controls at all regions (spine, hip and total body). Height and projected bone area were also lower. There were no differences between both groups regarding estimated volumetric BMD at the femoral neck. However, spine volumetric BMD was also lower in DS than controls. In multivariate analysis, DS, male sex, little physical activity and low sunlight exposure were associated with lower spine volumetric BMD; on the other hand, fat mass and sunlight exposure were associated with femoral neck volumetric BMD. Conclusion This study shows that patients with DS had a reduced areal BMD, but it is in part a consequence of the reduced body size, particularly at the femoral neck. Physical activity and sunlight exposure are associated to volumetric BMD and should be stimulated in order to maintain an adequate bone mass in these patients. [source]


Total body bone measurements: A cross-sectional study in children with acute lymphoblastic leukemia during and following completion of therapy

PEDIATRIC BLOOD & CANCER, Issue 1 2009
Kara M. Kelly MD
Abstract Background Abnormalities in bone mineral density (BMD) occur in children treated for acute lymphoblastic leukemia (ALL). However, BMD estimates have been performed using varied instruments, reference data, and interpretations. This exploratory cross sectional study to evaluate bone mass in children with ALL, uses an algorithm that serially adjusts for variables known to affect pediatric bone measures by dual energy X-ray absorptiometry (DXA), based on models developed in 1,218 healthy children and adolescents. Procedure Anthropometry, DXA scans, and factors with possible influence on bone mass were evaluated in 21 ALL patients receiving chemotherapy and 20 in the follow-up phase. Main outcome was treatment group differences in Z -scores for total body bone mineral content (BMC), bone area (Area), and areal BMD (aBMD). Results Mean Z -scores for the entire study population for BMC, Area, and aBMD were significantly less than zero. Among possible contributing factors, only calcium intake was a significant co-variate. Comparison between treatment groups showed that least-square mean Z -scores for patients on-therapy for at least 12 months were significantly lower than those off therapy for at least 12 months (P: 0.0008,0.044), except for BMC at last step of the algorithm (adjusted for sex, age, ethnicity, height, weight, and bone area). Conclusions Evaluation of total body DXA by this algorithm is consistent with better general bone status in those off-therapy. However, in this small exploratory study, the lack of significant difference between Z -scores for fully adjusted BMC in on- versus off-therapy groups suggests possible risk of low peak bone mass. Additional longitudinal evaluation is warranted. Pediatr Blood Cancer 2009;52:33,38. © 2008 Wiley-Liss, Inc. [source]