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Skeletal Sites (skeletal + site)
Kinds of Skeletal Sites Selected AbstractsLarge-Scale Genome-Wide Linkage Analysis for Loci Linked to BMD at Different Skeletal Sites in Extreme Selected Sibships,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 2 2007Yi-Hsiang Hsu Abstract Few genome-wide linkage studies of osteoporosis have been conducted in the Asian population. We performed a genome-wide scan involving 3093 adult siblings with at least one sib-pair extremely concordant or discordant for hip BMD. Our results indicated four genome-wide significant QTLs for BMD. In comparison with 12 previous reported linkage studies, we reveal novel linkage regions that have reaching global significance. Introduction: The genetic basis for osteoporosis has been firmly established, but efforts to identify genes associated with this complex trait have been incomplete, especially in Asian populations. The purpose of this study was to identify quantitative trait loci (QTLs) for BMD in a Chinese population. Materials and Methods: We performed a genome-wide scan involving 3093 siblings 25,64 years of age from 941 families, with at least one sib-pair extreme concordant or discordant for total hip BMD from a large community-based cohort (n = 23,327) in Anhui, China. Linkage analysis was performed on BMD residuals adjusted for age, height, weight, occupation, cigarette smoking, physical activity, and alcohol consumption using the revised Haseman-Elston regression-based linkage model. Results: Our results revealed significant QTLs on chromosome 7p21.2 for femoral neck BMD (LOD = 3.68) and on chromosome 2q24.3 for total hip BMD (LOD = 3.65). Suggestive linkage regions were found to overlap among different skeletal sites on chromosomes 2q, 7p, and 16q. Sex-specific linkage analysis further revealed a significant QTL for lumbar spine BMD on chromosome 13q21.1 (LOD = 3.62) in women only. When performing multivariate linkage analysis by combining BMDs at four skeletal sites (i.e., whole body, total hip, femoral neck, and lumbar spine BMD), an additional significant QTL was found at chromosome 5q21.2 (LOD = 4.56). None of these significant QTLs found in our study overlapped with major QTLs reported by other studies. Conclusions: This study reveals four novel QTLs in a Chinese population and suggests that BMD at different skeletal sites may also share common genetic determinants. [source] Normative data of bone mineral density in an unselected adult Austrian populationEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 4 2003S. Kudlacek Abstract Background There is increasing evidence that correct interpretation of bone mineral density (BMD) measurements by dual energy X-ray absorptiometry (DEXA) requires a population-specific reference range. We therefore collected data on age-related BMD in a random sample of the normal adult Austrian population to establish an appropriate normative database. Methods We measured BMD by DEXA at five different skeletal sites in 1089 subjects, i.e. 654 females and 435 males, aged between 21,76 years, who had been recruited by 17 centres across Austria. Results Age-related bone loss was observed until age 65 years with significant changes at the lumbar spine (r = ,0·23), total hip (r = ,0·07), trochanter (r = ,0·10), femoral neck (r = ,0·30) and Ward's triangle (r = ,0·40) in the women but only at the femoral neck (r = ,0·23) and at Ward's triangle (r = ,0·40) in the men. When we calculated T scores from the BMD data of the young normal adult study population and used the T score set points according to the WHO classification of osteopenia and osteoporosis, we found that, depending on the skeletal site measured, 7·6,27·4% of the women and 16,41% of the men in our study group had low bone mass, whereas 0·6,2·7% of the female and 0·2,1·0% of the male study population were osteoporotic. However, osteoporosis was indicated in 4,9-fold more females and 5,15-fold more males when we based our estimates on the normative data provided by the manufacturers of the DEXA systems. Conclusion Our data underscore the importance of using a population-specific reference range for DEXA measurements to avoid overdiagnosis of osteoporosis. [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] Ovariectomy-Induced Bone Loss Varies Among Inbred Strains of Mice,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 7 2005Mary L Bouxsein PhD Abstract There is a subset of women who experience particularly rapid bone loss during and after the menopause. However, the factors that lead to this enhanced bone loss remain obscure. We show that patterns of bone loss after ovariectomy vary among inbred strains of mice, providing evidence that there may be genetic regulation of bone loss induced by estrogen deficiency. Introduction: Both low BMD and increased rate of bone loss are risk factors for fracture. Bone loss during and after the menopause is influenced by multiple hormonal factors. However, specific determinants of the rate of bone loss are poorly understood, although it has been suggested that genetic factors may play a role. We tested whether genetic factors may modulate bone loss subsequent to estrogen deficiency by comparing the skeletal response to ovariectomy in inbred strains of mice. Materials and Methods: Four-month-old mice from five inbred mouse strains (C3H/HeJ, BALB/cByJ, CAST/EiJ, DBA2/J, and C57BL/6J) underwent ovariectomy (OVX) or sham-OVX surgery (n = 6-9/group). After 1 month, mice were killed, and ,CT was used to compare cortical and trabecular bone response to OVX. Results: The effect of OVX on trabecular bone varied with mouse strain and skeletal site. Vertebral trabecular bone volume (BV/TV) declined after OVX in all strains (,15 to ,24%), except for C3H/HeJ. In contrast, at the proximal tibia, C3H/HeJ mice had a greater decline in trabecular BV/TV (,39%) than C57BL/6J (,18%), DBA2/J (,23%), and CAST/EiJ mice (,21%). OVX induced declines in cortical bone properties, but in contrast to trabecular bone, the effect of OVX did not vary by mouse strain. The extent of trabecular bone loss was greatest in those mice with highest trabecular BV/TV at baseline, whereas cortical bone loss was lowest among those with high cortical bone parameters at baseline. Conclusions: We found that the skeletal response to OVX varies in a site- and compartment-specific fashion among inbred mouse strains, providing support for the hypothesis that bone loss during and after the menopause is partly genetically regulated. [source] How Many Women Have Osteoporosis?JOURNAL OF BONE AND MINERAL RESEARCH, Issue 5 2005L. Joseph Melton III Osteoporosis is widely viewed as a major public health concern, but the exact magnitude of the problem is uncertain and likely to depend on how the condition is defined. Noninvasive bone mineral measurements can be used to define a state of heightened fracture risk (osteopenia), or the ultimate clinical manifestation of fracture can be assessed (established osteoporosis). If bone mineral measurements more than 2 standard deviations below the mean of young normal women represent osteopenia, then 45% of white women aged 50 years and over have the condition at one or more sites in the hip, spine, or forearm on the basis of population-based data from Rochester, Minnesota. A smaller proportion is affected at each specific skeletal site: 32% have bone mineral values this low in the lumbar spine, 29% in either of two regions in the proximal femur, and 26% in the midradius. Although this overall estimate is substantial, some other serious chronic diseases are almost as common. More importantly, low bone mass is associated with adverse health outcomes, especially fractures. The lifetime risk of any fracture of the hip, spine, or distal forearm is almost 40% in white women and 13% in white men from age 50 years onward. If the enormous costs associated with these fractures are to be reduced, increased attention must be given to the design and implementation of control programs directed at this major health problem. [source] Mapping Quantitative Trait Loci for Vertebral Trabecular Bone Volume Fraction and Microarchitecture in Mice,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 4 2004Mary 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] Effect of 8-Month Vertical Whole Body Vibration on Bone, Muscle Performance, and Body Balance: A Randomized Controlled Study,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 5 2003Saila Torvinen MD Abstract Recent animal studies have given evidence that vibration loading may be an efficient and safe way to improve mass and mechanical competence of bone, thus providing great potential for preventing and treating osteoporosis. Randomized controlled trials on the safety and efficacy of the vibration on human skeleton are, however, lacking. This randomized controlled intervention trial was designed to assess the effects of an 8-month whole body vibration intervention on bone, muscular performance, and body balance in young and healthy adults. Fifty-six volunteers (21 men and 35 women; age, 19-38 years) were randomly assigned to the vibration group or control group. The vibration intervention consisted of an 8-month whole body vibration (4 min/day, 3-5 times per week). During the 4-minute vibration program, the platform oscillated in an ascending order from 25 to 45 Hz, corresponding to estimated maximum vertical accelerations from 2g to 8g. Mass, structure, and estimated strength of bone at the distal tibia and tibial shaft were assessed by peripheral quantitative computed tomography (pQCT) at baseline and at 8 months. Bone mineral content was measured at the lumbar spine, femoral neck, trochanter, calcaneus, and distal radius using DXA at baseline and after the 8-month intervention. Serum markers of bone turnover were determined at baseline and 3, 6, and 8 months. Five performance tests (vertical jump, isometric extension strength of the lower extremities, grip strength, shuttle run, and postural sway) were performed at baseline and after the 8-month intervention. The 8-month vibration intervention succeeded well and was safe to perform but had no effect on mass, structure, or estimated strength of bone at any skeletal site. Serum markers of bone turnover did not change during the vibration intervention. However, at 8 months, a 7.8% net benefit in the vertical jump height was observed in the vibration group (95% CI, 2.8-13.1%; p = 0.003). On the other performance and balance tests, the vibration intervention had no effect. In conclusion, the studied whole body vibration program had no effect on bones of young, healthy adults, but instead, increased vertical jump height. Future human studies are needed before clinical recommendations for vibration exercise. [source] More Broken Bones: A 4-Year Double Cohort Study of Young Girls With and Without Distal Forearm FracturesJOURNAL OF BONE AND MINERAL RESEARCH, Issue 10 2000A. Goulding Abstract Predictors of childhood fractures have not been investigated previously. This study was undertaken to determine whether a previous history of forearm fracture, low bone mineral density (BMD; both areal bone mineral density [aBMD, g/cm2] and volumetric bone mineral apparent density [BMAD, g/cm3]), or anthropometry, influence fracture risk in young girls. At baseline, two cohorts of girls, aged 3,15 years, were evaluated: 100 had recently broken a forearm (group 1) and 100 were fracture free (group 2). Four years later we restudied 170 of these girls (82 from group l and 88 from group 2). We now report the relationships of previous fracture history, baseline BMD (measured by dual-energy X-ray absorptiometry), baseline weight, and height to risk of new fracture. More new fractures occurred in group l (37 fractures in 24 girls) than in group 2 (8 fractures in 7 girls; p = 0.0007). The independent predictors for occurrence of a new fracture at any skeletal site in a multivariate model adjusting for age, weight, total body aBMD, and fracture history were previous fracture (hazard ratio [HR], 3.28; 95% CI, 1.41-7.64); age (HR per l-year increase, 0.91; 95% CI, 0.84-0.99); total body aBMD (HR per l SD decrease, 1.92; 95% CI, 1.31-2.81); and body weight (HR per l SD increase, 1.49; 95% CI, 1.06-2.08). Girls with two risk factors together had substantially greater fracture risk: previous fracture and low spinal BMAD (HR, 9.4; 95% CI, 2.8-32.0), previous fracture and high body weight (HR, 10.2; 95% CI, 2.8-37.6), or previous fracture and low total body aBMD (HR, 13.0; 95% CI, 3.9-43.1). We conclude that previous forearm fracture, low total body aBMD, low spinal BMAD, and high body weight each increase risk of new fractures within 4 years in young girls. Interventions to reduce the risk of fractures, particularly forearm fractures, in girls warrant further study. [source] Race and sex differences and contribution of height: A study on bone size in healthy Caucasians and ChineseAMERICAN JOURNAL OF HUMAN BIOLOGY, Issue 5 2005Yuan-Yuan Zhang Osteoporosis is characterized by a loss of bone strength, of which bone size (BS) is an important determinant. However, studies on the factors determining BS are relatively few. The present study evaluated the independent effects of height, age, weight, sex, and race on areal BS at the hip and spine, measured by dual-energy X-ray absorptiometry, while focusing on the differential contributions of height to BS across sex, race, and skeletal site. The subjects were aged 40 years or older, including 763 Chinese (384 males and 379 females) from Shanghai, People's Republic of China, and 424 Caucasians (188 males and 236 females) from Omaha, Nebraska. Basically, Caucasians had significantly larger BS than Chinese. After adjusting for height, age, and weight, the Chinese had similar spine BS, but significantly larger intertrochanter BS in both sexes and larger total hip BS in females compared with Caucasians. Males had significantly larger BS than females before and after adjustment in both ethnic groups. The effects of age, weight, and race varied, depending on skeletal site. As expected, height had major effects on BS variation in both sexes and races. Height tended to account for larger BS variation at the spine than at the hip (except for Chinese females), and larger BS variation in Caucasians than in Chinese of the same sex (except for the trochanter in females). We conclude that height is a major predictor for BS, and its contributions vary across sex, race, and skeletal site. Am. J. Hum. Biol. 17:568,575, 2005. © 2005 Wiley-Liss, Inc. [source] Normative data of bone mineral density in an unselected adult Austrian populationEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 4 2003S. Kudlacek Abstract Background There is increasing evidence that correct interpretation of bone mineral density (BMD) measurements by dual energy X-ray absorptiometry (DEXA) requires a population-specific reference range. We therefore collected data on age-related BMD in a random sample of the normal adult Austrian population to establish an appropriate normative database. Methods We measured BMD by DEXA at five different skeletal sites in 1089 subjects, i.e. 654 females and 435 males, aged between 21,76 years, who had been recruited by 17 centres across Austria. Results Age-related bone loss was observed until age 65 years with significant changes at the lumbar spine (r = ,0·23), total hip (r = ,0·07), trochanter (r = ,0·10), femoral neck (r = ,0·30) and Ward's triangle (r = ,0·40) in the women but only at the femoral neck (r = ,0·23) and at Ward's triangle (r = ,0·40) in the men. When we calculated T scores from the BMD data of the young normal adult study population and used the T score set points according to the WHO classification of osteopenia and osteoporosis, we found that, depending on the skeletal site measured, 7·6,27·4% of the women and 16,41% of the men in our study group had low bone mass, whereas 0·6,2·7% of the female and 0·2,1·0% of the male study population were osteoporotic. However, osteoporosis was indicated in 4,9-fold more females and 5,15-fold more males when we based our estimates on the normative data provided by the manufacturers of the DEXA systems. Conclusion Our data underscore the importance of using a population-specific reference range for DEXA measurements to avoid overdiagnosis of osteoporosis. [source] Regional variability in secondary remodeling within long bone cortices of catarrhine primates: the influence of bone growth historyJOURNAL OF ANATOMY, Issue 3 2008Shannon C. McFarlin Abstract Secondary intracortical remodeling of bone varies considerably among and within vertebrate skeletons. Although prior research has shed important light on its biomechanical significance, factors accounting for this variability remain poorly understood. We examined regional patterning of secondary osteonal bone in an ontogenetic series of wild-collected primates, at the midshaft femur and humerus of Chlorocebus (Cercopithecus) aethiops (n = 32) and Hylobates lar (n = 28), and the midshaft femur of Pan troglodytes (n = 12). Our major objectives were: 1) to determine whether secondary osteonal bone exhibits significant regional patterning across inner, mid-cortical and outer circumferential cortical rings within cross-sections; and if so, 2) to consider the manner in which this regional patterning may reflect the influence of relative tissue age and other circumstances of bone growth. Using same field-of-view images of 100-µm-thick cross-sections acquired in brightfield and circularly polarized light microscopy, we quantified the percent area of secondary osteonal bone (%HAV) for whole cross-sections and across the three circumferential rings within cross-sections. We expected bone areas with inner and middle rings to exhibit higher %HAV than the outer cortical ring within cross-sections, the latter comprising tissues of more recent depositional history. Observations of primary bone microstructural development provided an additional context in which to evaluate regional patterning of intracortical remodeling. Results demonstrated significant regional variability in %HAV within all skeletal sites. As predicted,%HAV was usually lowest in the outer cortical ring within cross-sections. However, regional patterning across inner vs. mid-cortical rings showed a more variable pattern across taxa, age classes, and skeletal sites examined. Observations of primary bone microstructure revealed that the distribution of endosteally deposited bone had an important influence on the patterning of secondary osteonal bone across rings. Further, when present, endosteal compacted coarse cancellous bone always exhibited some evidence of intracortical remodeling, even in those skeletal sites exhibiting comparatively low %HAV overall. These results suggest that future studies should consider the local developmental origin of bone regions undergoing secondary remodeling later in life, for an improved understanding of the manner in which developmental and mechanical factors may interact to produce the taxonomic and intraskeletal patterning of secondary bone remodelling in adults. [source] Morphologic changes associated with functional adaptation of the navicular bone of horsesJOURNAL OF ANATOMY, Issue 5 2007V. A. Bentley Abstract Failure of functional adaptation to protect the skeleton from damage is common and is often associated with targeted remodeling of bone microdamage. Horses provide a suitable model for studying loading-related skeletal disease because horses are physically active, their exercise is usually regulated, and adaptive failure of various skeletal sites is common. We performed a histologic study of the navicular bone of three groups of horses: (1) young racing Thoroughbreds (n = 10); (2) young unshod ponies (n = 10); and (3) older horses with navicular syndrome (n = 6). Navicular syndrome is a painful condition that is a common cause of lameness and is associated with extensive remodeling of the navicular bone; a sesamoid bone located within the hoof which articulates with the second and third phalanges dorsally. The following variables were quantified: volumetric bone mineral density; cortical thickness (Ct.Th); bone volume fraction, microcrack surface density; density of osteocytes and empty lacunae; and resorption space density. Birefringence of bone collagen was also determined using circularly polarized light microscopy and disruption of the lacunocanalicular network was examined using confocal microscopy. Remodeling of the navicular bone resulted in formation of transverse secondary osteons orientated in a lateral to medial direction; bone collagen was similarly orientated. In horses with navicular syndrome, remodeling often led to the formation of intracortical cysts and development of multiple tidemarks at the articular surface. These changes were associated with high microcrack surface density, low bone volume fraction, low density of osteocytes, and poor osteocyte connectivity. Empty lacunae were increased in Thoroughbreds. Resorption space density was not increased in horses with navicular syndrome. Taken together, these data suggest that the navicular bone may experience habitual bending across the sagittal plane. Consequences of cumulative cyclic loading in horses with navicular syndrome include arthritic degeneration of adjacent joints and adaptive failure of the navicular bone, with accumulation of microdamage and associated low bone mass, poor osteocyte connectivity, and low osteocyte density, but not formation of greater numbers of resorption spaces. [source] Genome-wide pleiotropy of osteoporosis-related phenotypes: The framingham studyJOURNAL OF BONE AND MINERAL RESEARCH, Issue 7 2010David Karasik Abstract Genome-wide association studies offer an unbiased approach to identify new candidate genes for osteoporosis. We examined the Affymetrix 500K,+,50K SNP GeneChip marker sets for associations with multiple osteoporosis-related traits at various skeletal sites, including bone mineral density (BMD, hip and spine), heel ultrasound, and hip geometric indices in the Framingham Osteoporosis Study. We evaluated 433,510 single-nucleotide polymorphisms (SNPs) in 2073 women (mean age 65 years), members of two-generational families. Variance components analysis was performed to estimate phenotypic, genetic, and environmental correlations (,P, ,G, and ,E) among bone traits. Linear mixed-effects models were used to test associations between SNPs and multivariable-adjusted trait values. We evaluated the proportion of SNPs associated with pairs of the traits at a nominal significance threshold ,,=,0.01. We found substantial correlation between the proportion of associated SNPs and the ,P and ,G (r,=,0.91 and 0.84, respectively) but much lower with ,E (r,=,0.38). Thus, for example, hip and spine BMD had 6.8% associated SNPs in common, corresponding to ,P,=,0.55 and ,G,=,0.66 between them. Fewer SNPs were associated with both BMD and any of the hip geometric traits (eg, femoral neck and shaft width, section moduli, neck shaft angle, and neck length); ,G between BMD and geometric traits ranged from ,0.24 to +0.40. In conclusion, we examined relationships between osteoporosis-related traits based on genome-wide associations. Most of the similarity between the quantitative bone phenotypes may be attributed to pleiotropic effects of genes. This knowledge may prove helpful in defining the best phenotypes to be used in genetic studies of osteoporosis. © 2010 American Society for Bone and Mineral Research [source] Identification of genes influencing skeletal phenotypes in congenic P/NP ratsJOURNAL OF BONE AND MINERAL RESEARCH, Issue 6 2010Imranul Alam Abstract We previously showed that alcohol-preferring (P) rats have higher bone density than alcohol-nonpreferring (NP) rats. Genetic mapping in P and NP rats identified a major quantitative trait locus (QTL) between 4q22 and 4q34 for alcohol preference. At the same location, several QTLs linked to bone density and structure were detected in Fischer 344 (F344) and Lewis (LEW) rats, suggesting that bone mass and strength genes might cosegregate with genes that regulate alcohol preference. The aim of this study was to identify the genes segregating for skeletal phenotypes in congenic P and NP rats. Transfer of the NP chromosome 4 QTL into the P background (P.NP) significantly decreased areal bone mineral density (aBMD) and volumetric bone mineral density (vBMD) at several skeletal sites, whereas transfer of the P chromosome 4 QTL into the NP background (NP.P) significantly increased bone mineral content (BMC) and aBMD in the same skeletal sites. Microarray analysis from the femurs using Affymetrix Rat Genome arrays revealed 53 genes that were differentially expressed among the rat strains with a false discovery rate (FDR) of less than 10%. Nine candidate genes were found to be strongly correlated (r2,>,0.50) with bone mass at multiple skeletal sites. The top three candidate genes, neuropeptide Y (Npy), , synuclein (Snca), and sepiapterin reductase (Spr), were confirmed using real-time quantitative PCR (qPCR). Ingenuity pathway analysis revealed relationships among the candidate genes related to bone metabolism involving ,-estradiol, interferon-,, and a voltage-gated calcium channel. We identified several candidate genes, including some novel genes on chromosome 4 segregating for skeletal phenotypes in reciprocal congenic P and NP rats. © 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] Effects of denosumab on bone mineral density and bone turnover in postmenopausal women transitioning from alendronate therapyJOURNAL OF BONE AND MINERAL RESEARCH, Issue 1 2010David L Kendler Abstract Patients treated with bisphosphonates for osteoporosis may discontinue or require a switch to other therapies. Denosumab binds to RANKL and is a potent inhibitor of bone resorption that has been shown to increase bone mineral density (BMD) and decrease fracture risk in postmenopausal women with osteoporosis. This was a multicenter, international, randomized, double-blind, double-dummy study in 504 postmenopausal women,,,55 years of age with a BMD T- score of ,2.0 or less and ,4.0 or more who had been receiving alendronate therapy for at least 6 months. Subjects received open-label branded alendronate 70,mg once weekly for 1 month and then were randomly assigned to either continued weekly alendronate therapy or subcutaneous denosumab 60,mg every 6 months and were followed for 12 months. Changes in BMD and biochemical markers of bone turnover were evaluated. In subjects transitioning to denosumab, total hip BMD increased by 1.90% at month 12 compared with a 1.05% increase in subjects continuing on alendronate (p,<,.0001). Significantly greater BMD gains with denosumab compared with alendronate also were achieved at 12 months at the lumbar spine, femoral neck, and 1/3 radius (all p,<,.0125). Median serum CTX levels remained near baseline in the alendronate group and were significantly decreased versus alendronate (p,<,.0001) at all time points with denosumab. Adverse events and serious adverse events were balanced between groups. No clinical hypocalcemic adverse events were reported. Transition to denosumab produced greater increases in BMD at all measured skeletal sites and a greater reduction in bone turnover than did continued alendronate with a similar safety profile in both groups. Copyright © 2010 American Society for Bone and Mineral Research [source] Comparison of the Effect of Denosumab and Alendronate on BMD and Biochemical Markers of Bone Turnover in Postmenopausal Women With Low Bone Mass: A Randomized, Blinded, Phase 3 Trial,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 1 2009Jacques P Brown Abstract Denosumab is a fully human monoclonal antibody that inhibits bone resorption by neutralizing RANKL, a key mediator of osteoclast formation, function, and survival. This phase 3, multicenter, double-blind study compared the efficacy and safety of denosumab with alendronate in postmenopausal women with low bone mass. One thousand one hundred eighty-nine postmenopausal women with a T-score , ,2.0 at the lumbar spine or total hip were randomized 1:1 to receive subcutaneous denosumab injections (60 mg every 6 mo [Q6M]) plus oral placebo weekly (n = 594) or oral alendronate weekly (70 mg) plus subcutaneous placebo injections Q6M (n = 595). Changes in BMD were assessed at the total hip, femoral neck, trochanter, lumbar spine, and one-third radius at 6 and 12 mo and in bone turnover markers at months 1, 3, 6, 9, and 12. Safety was evaluated by monitoring adverse events and laboratory values. At the total hip, denosumab significantly increased BMD compared with alendronate at month 12 (3.5% versus 2.6%; p < 0.0001). Furthermore, significantly greater increases in BMD were observed with denosumab treatment at all measured skeletal sites (12-mo treatment difference: 0.6%, femoral neck; 1.0%, trochanter; 1.1%, lumbar spine; 0.6%, one-third radius; p , 0.0002 all sites). Denosumab treatment led to significantly greater reduction of bone turnover markers compared with alendronate therapy. Adverse events and laboratory values were similar for denosumab- and alendronate-treated subjects. Denosumab showed significantly larger gains in BMD and greater reduction in bone turnover markers compared with alendronate. The overall safety profile was similar for both treatments. [source] Calcifications in the Abdominal Aorta Predict Fractures in Men: MINOS Study,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 1 2008Pawel Szulc MD In a cohort of 781 men ,50 yr of age followed up for 10 yr, extended calcifications in the abdominal aorta were associated with a 2- to 3-fold increase in the risk of osteoporotic fractures regardless of BMD and falls. Introduction: Cardiovascular disease and osteoporotic fractures are public health problems that frequently coexist. Materials and Methods: We assessed the relation of the severity of aortic calcifications with BMD and the risk of fracture in 781 men ,50 yr of age. During a 10-year follow-up, 66 men sustained incident clinical fractures. Calcifications in the abdominal aorta expressed as an aortic calcification score (ACS) were assessed by a semiquantitative method. BMD was measured at the lumbar spine, hip, whole body, and distal forearm. Results: ACS > 2 was associated with a 2-fold increase in the mortality risk after adjustment for age, weight, smoking, comorbidity, and medications. After adjustment for age, body mass index (BMI), smoking, and comorbidity, men in the highest quartile of ACS (>6) had lower BMD of distal forearm, ultradistal radius, and whole body than men in the lower quartiles. Log-transformed ACS predicted fractures when adjusted for age, BMI, age by BMI interaction, prevalent fractures, BMD, and history of two or more falls (e.g., hip BMD; OR = 1.44; p < 0.02). ACS, BMD at all the skeletal sites, and history of two or more falls were independent predictors of fracture. Men with ACS > 6 had a 2- to 3-fold increased risk of fracture after adjustment for confounding variables (OR = 2.54-3.04; p < 0.005-0.001 according to the site). Conclusions: This long-term prospective study showed that elevated ACS (>6) is a robust and independent risk factor for incident fracture in older men regardless of age, BMI, BMD, prevalent fractures, history of two or more falls, comorbidities, and medications. [source] Large-Scale Genome-Wide Linkage Analysis for Loci Linked to BMD at Different Skeletal Sites in Extreme Selected Sibships,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 2 2007Yi-Hsiang Hsu Abstract Few genome-wide linkage studies of osteoporosis have been conducted in the Asian population. We performed a genome-wide scan involving 3093 adult siblings with at least one sib-pair extremely concordant or discordant for hip BMD. Our results indicated four genome-wide significant QTLs for BMD. In comparison with 12 previous reported linkage studies, we reveal novel linkage regions that have reaching global significance. Introduction: The genetic basis for osteoporosis has been firmly established, but efforts to identify genes associated with this complex trait have been incomplete, especially in Asian populations. The purpose of this study was to identify quantitative trait loci (QTLs) for BMD in a Chinese population. Materials and Methods: We performed a genome-wide scan involving 3093 siblings 25,64 years of age from 941 families, with at least one sib-pair extreme concordant or discordant for total hip BMD from a large community-based cohort (n = 23,327) in Anhui, China. Linkage analysis was performed on BMD residuals adjusted for age, height, weight, occupation, cigarette smoking, physical activity, and alcohol consumption using the revised Haseman-Elston regression-based linkage model. Results: Our results revealed significant QTLs on chromosome 7p21.2 for femoral neck BMD (LOD = 3.68) and on chromosome 2q24.3 for total hip BMD (LOD = 3.65). Suggestive linkage regions were found to overlap among different skeletal sites on chromosomes 2q, 7p, and 16q. Sex-specific linkage analysis further revealed a significant QTL for lumbar spine BMD on chromosome 13q21.1 (LOD = 3.62) in women only. When performing multivariate linkage analysis by combining BMDs at four skeletal sites (i.e., whole body, total hip, femoral neck, and lumbar spine BMD), an additional significant QTL was found at chromosome 5q21.2 (LOD = 4.56). None of these significant QTLs found in our study overlapped with major QTLs reported by other studies. Conclusions: This study reveals four novel QTLs in a Chinese population and suggests that BMD at different skeletal sites may also share common genetic determinants. [source] Treatment of Skeletally Mature Ovariectomized Rhesus Monkeys With PTH(1-84) for 16 Months Increases Bone Formation and Density and Improves Trabecular Architecture and Biomechanical Properties at the Lumbar Spine,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 2 2007John Fox PhD Abstract Histomorphometric studies of treatments for osteoporosis in humans are restricted to iliac crest biopsies. We studied the effects of PTH(1-84) treatment at the lumbar spine of skeletally mature ovariectomized rhesus monkeys. PTH increased bone turnover, rapidly normalized BMD, and increased vertebral compressive strength. PTH increased trabecular bone volume primarily by increasing trabecular number by markedly increasing intratrabecular tunneling. Introduction: Histomorphometric studies of the anabolic properties of PTH(1-84) (PTH) and related peptides in human bone are restricted to iliac crest biopsies. The ovariectomized (OVX) monkey is an accepted model of human postmenopausal bone loss and was used to study the effects of PTH treatment at clinically relevant skeletal sites. Materials and Methods: Skeletally mature rhesus monkeys were OVX or sham-operated and, after a bone depletion period of 9 months, treated daily for 16 months with PTH (5, 10, or 25 ,g/kg). Markers of bone formation (serum osteocalcin) and resorption (urine N-telopeptide [NTX]) and lumbar spine BMD were measured throughout the study. Trabecular architecture and vertebral biomechanical properties were quantified at 16 months. Results: PTH treatment induced dose-dependent increases in bone turnover but did not increase serum calcium. Osteocalcin was significantly increased above OVX controls by 1 month. NTX was significantly elevated at 1 month with the highest dose, but not until 12 months with the 5 and 10 ,g/kg doses. Lumbar spine BMD was 5% lower in OVX than in sham animals when treatment was started. All PTH doses increased BMD rapidly, with sham levels restored by 3,7 months with 10 and 25 ,g/kg and by 16 months with 5 ,g/kg. PTH treatment increased trabecular bone volume (BV/TV), primarily by increasing trabecular number, and dose-dependently increased bone formation rate (BFR) solely by increasing mineralizing surface. The largest effects on BV/TV and yield load occurred with the 10 ,g/kg dose. The highest dose reduced trabecular thickness by markedly increasing intratrabecular tunneling. Conclusions: PTH treatment of OVX rhesus monkeys increased bone turnover and increased BV/TV, BMD, and strength at the lumbar spine. All PTH doses were safe, but the 10 ,g/kg dose was generally optimal, possibly because the highest dose resulted in too marked a stimulation of bone remodeling. [source] An In Vitro Study of the Ultrasonic Axial Transmission Technique at the Radius: 1-MHz Velocity Measurements Are Sensitive to Both Mineralization and Intracortical Porosity,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 9 2004Emmanuel Bossy Abstract The ultrasonic axial transmission technique allows for investigating skeletal sites such as the cortical layer of long bones (radius, tibia, phalanges). Using synchrotron radiation ,CT, we investigated, in vitro, the relationships between 1-MHz axial transmission SOS measurements at the radius and site-matched measurements of C.Th, POR, MIN, and vBMD. Introduction: The ultrasonic axial transmission technique allows for investigating skeletal sites such as the cortical layer of long bones (radius, tibia, phalanges). Materials and Methods:Using synchrotron radiation ,CT, we investigated, in vitro, the relationships between 1-MHz axial transmission speed of sound (SOS) measurements at the radius and site-matched measurements of cortical thickness (C.Th), intracortical porosity (POR), tissue mineralization (MIN), and volumetric BMD (vBMD). SOS measurements were based on bidirectional axial transmission and were performed with a 1-MHz proprietary probe on 39 excised human radii. Results: The highest correlations between SOS values and bone parameters (R2SOS/POR = 0.28, p < 10,3; R2SOS/MIN = 0.38, p < 10,4; R2SOS/vBMD = 0.57, p < 10,3) were found for bone parameters assessed in a 1-mm-thick periosteal region of the cortex rather than throughout the whole cortex. The observed moderate correlation between SOS and C.Th values (R2SOS/C.Th = 0.20, p < 10,2) disappeared when controlled for other variables. The two best multilinear predictive models, including either BMD alone or the pair of dependent variables MIN and POR (all assessed in the periosteal cortex), were equally accurate in predicting SOS values (R2SOS/(POR,MIN) = 0.59, p < 10,5; R2SOS/vBMD = 0.57, p < 10,5). Conclusion: For the first time, the respective adjusted contributions of POR (,24 m/s%,1) and tissue mineralization (+3.5 m/s/mg/cm,3) to SOS values were assessed. These results suggest potential sensitivity of axial transmission SOS values to changes in cortical bone status under different pathological conditions or treatments affecting POR and/or tissue mineralization. [source] Bone Strength at Clinically Relevant Sites Displays Substantial Heterogeneity and Is Best Predicted From Site-Specific Bone DensitometryJOURNAL OF BONE AND MINERAL RESEARCH, Issue 1 2002Felix Eckstein Ph.D. Abstract In this study we test the hypotheses that mechanical bone strength in elderly individuals displays substantial heterogeneity among clinically relevant skeletal sites, that ex situ dual-energy X-ray absorptiometry (DXA) provides better estimates of bone strength than in situ DXA, but that a site-specific approach of bone densitometry is nevertheless superior for optimal prediction of bone failure under in situ conditions. DXA measurements were obtained of the lumbar spine, the left femur, the left radius, and the total body in 110 human cadavers (age, 80.6 ± 10.5 years; 72 female, 38 male), including the skin and soft tissues. The bones were then excised, spinal and femoral DXA being repeated ex situ. Mechanical failure tests were performed on thoracic vertebra 10 and lumbar vertebra 3 (compressive loading of a functional unit), the left and right femur (side impact and vertical loading configuration), and the left and right distal radius (fall configuration, axial compression, and 3-point-bending). The failure loads displayed only very moderate correlation among sites (r = 0.39 to 0.63). Ex situ DXA displayed slightly higher correlations with failure loads compared with those of in situ DXA, but the differences were not significant and relatively small. Under in situ conditions, DXA predicted 50-60% of the variability in bone failure loads at identical (or closely adjacent) sites, but only around 20-35% at distant sites, advocating a site-specific approach of densitometry. These data suggest that mechanical competence in the elderly is governed by strong regional variation, and that its loss in osteoporosis may not represent a strictly systemic process. [source] Changes in Bone Density During Childhood and Adolescence: An Approach Based on Bone's Biological OrganizationJOURNAL OF BONE AND MINERAL RESEARCH, Issue 4 2001Frank Rauch Abstract Bone densitometry has great potential to improve our understanding of bone development. However, densitometric data in children rarely are interpreted in light of the biological processes they reflect. To strengthen the link between bone densitometry and the physiology of bone development, we review the literature on physiological mechanisms and structural changes determining bone mineral density (BMD). BMD (defined as mass of mineral per unit volume) is analyzed in three levels: in bone material (BMDmaterial), in a bone's trabecular and cortical tissue compartments (BMDcompartment), and in the entire bone (BMDtotal). BMDmaterial of the femoral midshaft cortex decreases after birth to a nadir in the first year of life and thereafter increases. In iliac trabecular bone, BMDmaterial also increases from infancy to adulthood, reflecting the decrease in bone turnover. BMDmaterial cannot be determined with current noninvasive techniques because of insufficient spatial resolution. BMDcompartment of the femoral midshaft cortex decreases in the first months after birth followed by a rapid increase during the next 2 years and slower changes thereafter, reflecting changes in both relative bone volume and BMDmaterial. Trabecular BMDcompartment increases in vertebral bodies but not at the distal radius. Quantitative computed tomography (QCT) allows for the determination of both trabecular and cortical BMDcompartment, whereas projectional techniques such as dual-energy X-ray absorptiometry (DXA) can be used only to assess cortical BMDcompartment of long bone diaphyses. BMDtotal of long bones decreases by about 30% in the first months after birth, reflecting a redistribution of bone tissue from the endocortical to the periosteal surface. In children of school age and in adolescents, changes in BMDtotal are site-specific. There is a marked rise in BMDtotal at locations where relative cortical area increases (metacarpal bones, phalanges, and forearm), but little change at the femoral neck and midshaft. BMDtotal can be measured by QCT at any site of the skeleton, regardless of bone shape. DXA allows the estimation of BMDtotal at skeletal sites, which have an approximately circular cross-section. The system presented here may help to interpret densitometric results in growing subjects on a physiological basis. [source] Pubertal Maturation Characteristics and the Rate of Bone Mass Development Longitudinally Toward MenarcheJOURNAL OF BONE AND MINERAL RESEARCH, Issue 4 2001Silvia C. C. M. Van Coeverden Abstract To assess risks for osteoporosis and to compare bone mass in different groups of healthy children or children with diseases, it is important to have knowledge of their sexual maturation status during puberty. The aim of our study was to evaluate bone mass formation longitudinally in relation to pubertal maturation characteristics in healthy white girls. We investigated the bone mineral content (BMC) and the bone mineral density (BMD) at different skeletal sites in 151 girls with increasing pubertal stages in relation with their chronological age and with an early or late onset of puberty or menarche and with a slow or fast maturation. Bone mass was measured at the onset of puberty, during puberty, and at menarche. We conclude the following: (1) from midpuberty to menarche, the increase in bone mass formation is highest at all skeletal sites in white girls; (2) early mature girls at the onset of puberty have slightly but definitely lower bone masses at all skeletal sites and at all pubertal stages than late mature girls, whereas the average bone mass formation from the onset of puberty to menarche is similar in both groups; (3) girls with a slow rate of pubertal maturation have lower bone mass values 2 years after the onset of puberty, but at menarche bone mass is similar compared with fast maturers; and (4) it cannot be confirmed that there is an effect of menarcheal age on bone mass values at menarche. [source] Protein Undernutrition-Induced Bone Loss Is Associated with Decreased IGF-I Levels and Estrogen DeficiencyJOURNAL OF BONE AND MINERAL RESEARCH, Issue 4 2000Patrick Ammann M.D. Abstract Protein undernutrition is a known factor in the pathogenesis of osteoporotic fracture in the elderly, but the mechanisms of bone loss resulting from this deficiency are still poorly understood. We investigated the effects of four isocaloric diets with varying levels of protein content (15, 7.5, 5, and 2.5% casein) on areal bone mineral density (BMD), bone ultimate strength, histomorphometry, biochemical markers of bone remodeling, plasma IGF-I, and sex hormone status in adult female rats. After 16 weeks on a 2.5% casein diet, BMD was significantly decreased at skeletal sites containing trabecular or cortical bone. Plasma IGF-I was decreased by 29,34% and no estrus sign in vaginal smear was observed. To investigate the roles of estrogen deficiency and protein undernutrition, the same protocol was used in ovariectomized (OVX) or sham-operated (SHAM) rats, pair-fed isocaloric diets containing either 15 or 2.5% casein. Trabecular BMD was decreased by either manipulation, with effects appearing to be additive. Cortical BMD was decreased only in rats on a low-protein diet. This was accompanied by an increased urinary deoxypyridinoline excretion without any change in osteocalcin levels, suggesting an uncoupling between resorption and formation. Isocaloric protein undernutrition decreased bone mineral mass and strength. This effect might be related to decreased plasma IGF-I and/or estrogen deficiency with a consequent imbalance in bone remodeling. [source] Bone mineral content and bone metabolism in young adults with severe periodontitisJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 6 2001Nina Von Wowern Abstract Objectives: To clarify in young adults with severe periodontitis (1) whether the bone mineral content (BMC) or density (BMD) in the mandible/other skeletal sites and the systemic bone metabolism differed from normal and (2) whether mandibular/forearm BMC did change during the 5 to 10-year follow-up. Material and Methods: 24 young otherwise normal patients with verified severe periodontitis were included, of which 20 attended the follow-up visit. Mandibular/forearm BMC was measured at both visits by dual-photon absorptiometry, supplemented with femoral neck/lumbar spine BMD measurements at follow-up visit by dual-energy X-ray absorptiometry. Serum alkaline phosphatase/ionized calcium, urinary excretion of pyridinoline/deoxy-pyridinoline were analysed at the follow-up visit. A conventional periodontal examination was performed at both visits. Results: Mandibular BMC was significantly below normal mean BMC at both visits. The mandibular Z-scores were ,2.00 in 33.3% (8/24). BMC/BMD in the remaining sites and the values for bone markers did not differ from normal. Mandibular/forearm BMC was stable while a significant aggravation of alveolar bone loss occurred during the trial without change of probing depth. Conclusions: Severe periodontitis in young adults seems to be a local disorder associated with relatively low BMC in the jaws without systemic alterations of BMC/BMD and bone metabolism. Zusammenfassung Zielsetzung: Abklärung ob bei jungen Erwachsenen mit schwerer Parodontitis (1) der Mineralgehalt und die Dichte des Knochens im Unterkiefer bzw. anderen Teilen des Skeletts sowie deer Knochenstoffwechsel sich von normalen Verhältnissen unterscheiden und (2) ob sich der Mineralgehalt des Unterkiefer- bzw. des Unterarmknochens während eines Beobachtungszeitraums von 5 bis 10 Jahren verändern. Material und Methoden: 24 allgemein gesunde Patienten mit schwerer Parodontitis nahmen an der Studie teil von denen 20 an der Nachuntersuchung teilnahme. Der Mineralgehalt des Unterkiefer- bzw. Unterarmknochens wurde bei beiden Untersuchungen mittels Dual-Photonen-Absorptiometrie bestimmt. Zusätzlich wurden bei der Nachuntersuchung die Knochendichte des Obserschenkelhalses und der Lendenwirbel mittels Dual-Energie-Röntgen-Absorptiometrie erfaßt. Die Serumkonzentrationen alkalischer Phosphatase sowie der Kalzium-Ionen und die Ausscheidung von Pyridinolin sowie Desoxypyridinolin im Urin wurden bei der Nachuntersuchung analysiert. Zu jedem Untersuchungstermin fand eine klinische Untersuchung der parodontalen Verhältnisse statt. Ergebnisse: Der Mineralgehalt des Unterkieferknochens lag zu beiden Untersuchungsterminen unter den mittleren Normalwerten. Die Z-Werte des Unterkiefers lagen in 8 von 24 Fällen (33.3%) ,2.00. Der Mineralgehalt und die Dichte des Knochens der übrigen Regionen und die Werte der Knochenmarker unterschieden sich nicht von den Normalwerten. Der Mineralgehalt des Unterkiefer- und Unterarmknochens verhielt sich während des Untersuchungszeitraumes stabil, während es zu einer deutlichen Verschlimmerung des alveolären Knochenabbaus ohne Veränderung der Sondierungstiefen kam. Schlußfolgerungen: Bei schwerer Parodontitis bei jungen Erwachsenen scheint es sich um eine lokale Störung mit relativ geringem Mineralgehalt der Kieferknochen zu handeln ohne systemische Veränderungen von Mineralgehalt und Dichte des Knochens bzw. des Knochenstoffwechsels. Résumé Le but de cette étude était de connaître chez les jeunes adultes souffrant de parodontite sévère (1) si le contenu en minéraux osseux (BMC) ou la densité (BMD) dans des sites mandibulaires ou du squelette et le métabolisme osseux systémique étaient différents par rapport à ceux de personnes normales et (2) si le BMC de la mandibule ou de l'avant-bras changeait durant une période de suivi de 5 à 10 années. 24 patients normaux mais souffrant de parodontite sévère ont été inclus dans cette investigation mais seul 20 ont poursuivi l'étude. Le BMC de la mandibule et de l'avant-bras ont été mesurés aux 2 sites par absorptiométrie par photon double, avec également des mesures BMD au niveau du fémur et de la colonne vertébrale lors de la visite de suivi par absorptiométrie par RX àénergie double. Le calcium ionisé par phosphatase alcaline sérique et l'excrétion urinaire de pyridinoline/deoxypyridinoline ont été analysés lors de l'examen de suivi. Un examen parodontal conventionnel a été effectué aux 2 visites. Le BMC mandibulaire était significativement inférieur au BMC moyen normal lors des deux visites. Les scores Z mandibulaires étaient ,2.00 dans 33.3% (8/24) des cas. BMC/BMD dans les sites restants et les valeurs des marqueurs osseux ne différaient pas des normaux. BMC mandibulaire/avant-bras était stable tandis qu'une aggravation significative de la perte osseuse alvéolaire se produisait durant l'étude sans changement de la profondeur au sondage. La parodontite sévère chez les jeunes adultes semble être un désordre local associéà un BMC relativement bas dans les mâchoires sans altération systémique de BMC/BMD ni du métabolisme osseux. [source] Effectiveness of raloxifene on bone mineral density and serum lipid levels in post-menopausal women with low BMD after discontinuation of hormone replacement therapyJOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 5 2006E. K. Song MS Summary Objective:, To evaluate the effect of raloxifene on bone mineral density (BMD) and serum lipid levels in post-menopausal women who had discontinued hormone replacement therapy (HRT). Methods:, Thirty-four post-menopausal women with low BMD who had taken 60 mg of raloxifene daily for 12 months after discontinuing HRT were evaluated retrospectively. Information about their demographics, fracture history, BMD, lipid profiles and adverse events were collected from medical records and intranet database. The outcome measures were changes in the spine (L2,L4) and femur BMD, serum lipid concentrations, fracture rate and tolerability. Results:, The post-menopausal women had a significant increase in their spine (L2,L4) and femur BMD from their baseline BMD [spine, 2·9 ± 4·6% (P < 0·001); femur, 3·0 ± 6·6% (P = 0·01)]. Serum low-density lipoprotein (LDL) cholesterol was significantly reduced by 22·6% below baseline after 12 months (P = 0·007). No fractures were observed during therapy. Raloxifene was well tolerated. The most common adverse event was hot flash, which was generally mild. Conclusions:, Raloxifene increases BMD at important skeletal sites, and lowers LDL cholesterol with tolerable adverse events. [source] Preventing osteoporotic fractures with antiresorptive therapy: implications of microarchitectural changesJOURNAL OF INTERNAL MEDICINE, Issue 1 2004S. Boonen Abstract. Prospective studies have demonstrated that low bone mass correlates well with increased risk of osteoporotic fractures at various skeletal sites. Trials have likewise confirmed that enhancing bone mass with antiresorptive therapy reduces fracture incidence in individuals at risk. However, correlation of bone mineral density (BMD) increases with therapeutic risk reduction has proved less consistent than correlation of BMD decreases with greater fracture risk in the untreated. Indeed, various analyses have indicated that , even during treatment with potent bisphosphonates like alendronate and risedronate , BMD changes from baseline account for <30% of the reduction in vertebral fractures in treated women. It is clearly, therefore, that factors other than BMD are involved in the reduction of fracture risk achieved by antiresorptive therapies. According to recent micro-computed tomography imaging and other studies, antiresorptive therapy can help rebuild the microarchitecture of bone as well as strengthen the materials that go into it. When treating individuals with osteoporosis, these microarchitectural changes contribute to the reduction of fracture risk achieved by antiresorptive therapies. [source] Ovariectomy stimulates and bisphosphonates inhibit intracortical remodeling in the mouse mandibleORTHODONTICS & CRANIOFACIAL RESEARCH, Issue 4 2010DJ Kubek To cite this article: Kubek DJ, Burr DB, Allen MR: Ovariectomy stimulates and bisphosphonates inhibit intracortical remodeling in the mouse mandible Orthod Craniofac Res 2010;13:214,222 Structured Abstract Authors,,, Kubek DJ, Burr DB, Allen MR Objective,,, The pathophysiology of osteonecrosis of the jaw (ONJ) is thought to be linked to suppression of intracortical remodeling. The aim of this study was to determine whether mice, which normally do not undergo appreciable amounts of intracortical remodeling, could be stimulated by ovariectomy to remodel within the cortex of the mandible and if bisphosphonates (BPs) would suppress this intracortical remodeling. Material and Methods,,, Skeletally mature female C3H mice were either ovariectomized (OVX) or SHAM operated and treated with two intravenous doses of zoledronic acid (ZOL, 0.06 mg/kg body weight) or vehicle (VEH). This ZOL dose corresponds to the dose given to patients with cancer on a mg/kg basis, adjusted for body weight. Calcein was administered prior to sacrifice to label active formation sites. Dynamic histomorphometry of the mandible and femur was performed. Results,,, Vehicle-treated OVX animals had significantly higher (eightfold) intracortical remodeling of the alveolar portion of the mandible compared to sham , this was significantly suppressed by ZOL treatment. At all skeletal sites, overall bone formation rate was lower with ZOL treatment compared to the corresponding VEH group. Conclusions,,, Under normal conditions, the level of intracortical remodeling in the mouse mandible is minimal but in C3H mice it can be stimulated to appreciable levels with ovariectomy. Based on this, if the suppression of intracortical remodeling is found to be part of the pathophysiology of ONJ, the ovariectomized C3H mouse could serve as a useful tool for studying this condition. [source] Effect of Environmental Factors and Gender on the Heritability of Bone Mineral Density and Bone SizeANNALS OF HUMAN GENETICS, Issue 4 2006M. Y. M. Ng Summary Bone mineral density (BMD), a risk factor for osteoporosis, is believed to be under genetic control. The effect of environmental factors and gender on the heritability of BMD and bone size is ill-defined. In this study, heritability estimates (h2) were determined in 3,320 southern Chinese subjects from 1,019 families using the variance components model. The h2 for age, weight and height-adjusted BMD was 0.63,0.71 for females, and 0.74,0.79 for males; and for bone size, 0.44,0.64 for females and 0.32,0.86 for males. Adjustment for lifestyle factors including calcium and phytoestrogen intake, exercise, smoking and alcohol consumption altered the h2 differently in males and females. The proportion of variance in BMD and bone size explained by all covariates varied between skeletal sites, but was consistently greater in females than males. A significant gender difference was observed in the genetic variance of BMD and bone size at the hip but not the spine. In conclusion, a gender difference was observed in the degree of heritability of BMD and bone size at specific skeletal sites. Environmental influences contributed variably at different sites in the two sexes. [source] | |||||||||||||