Home About us Contact
|
Home About us Contact | ||
|
|
||
Cortical Bone (cortical + bone)
Terms modified by Cortical Bone Selected AbstractsThe Effect of NaF In Vitro on the Mechanical and Material Properties of Trabecular and Cortical BoneADVANCED MATERIALS, Issue 4 2009Philipp J. Thurner High doses of sodium fluoride in bones lead to severe softening, by weakening interfacial properties between the inorganic minerals and the organic components, while leaving mineralization unchanged. This leads to reduction of microdamage and associated stress-whitening pointing to a change in failure mode. Accordingly, elastic modulus, failure stress, and indentation-distance increase are decreased, whereas failure strain is increased. [source] Long-Term Protective Effects of Zoledronic Acid on Cancellous and Cortical Bone in the Ovariectomized Rat,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 4 2008Jürg A Gasser PhD Abstract Current bisphosphonate therapies effectively prevent bone loss in postmenopausal women. We studied the effect of a single intravenous dose of ZOL in ovariectomized rats. Protection from bone loss was dose dependent, lasting for up to 32 weeks, supporting the rationale for an annual intravenous dosing regimen of ZOL for treatment of postmenopausal osteoporosis. Introduction: Once-yearly dosing with zoledronic acid (ZOL) 5 mg can increase BMD and reduce fracture rate in postmenopausal women with low BMD. The primary objective of this study was to determine the duration of bone protective effects of a single dose of ZOL in ovariectomized rats, an animal model of postmenopausal osteopenia. Secondary objectives were to determine the effects on bone turnover and mechanical properties. Materials and Methods: Female Wistar rats (10 per group) received single intravenous doses of ZOL 0.8, 4, 20, 100, or 500 ,g/kg, alendronate 200 ,g/kg, or isotonic saline 4 days before bilateral ovariectomy. Sham-operated controls were pretreated with saline. Mass and density of cancellous and cortical bone (pQCT) were measured at 4-wk intervals for 32 wk. Bone architecture (,CT), bone formation dynamics (fluorochrome label-based histomorphometry), and biomechanical strength in compression testing were also assessed at 32 wk. Results: Ovariectomy-associated BMD loss was significantly attenuated for 32 wk by ZOL ,4 ,g/kg for total BMD, ZOL ,20 ,g/kg for cortical BMD, and ZOL ,4 ,g/kg for cancellous BMD (p < 0.01 versus ovariectomized controls). Alendronate 200 ,g/kg was of equivalent potency to ZOL 20 ,g/kg. Ovariectomy-associated decreases in trabecular architectural parameters were dose-dependently attenuated by ZOL. Alendronate 200 ,g/kg was equivalent to ZOL 20 ,g/kg. The bone resorption marker TRACP5b indicated transient suppression of elevated osteoclast activity by ZOL relative to OVX-rats even at the lowest dose of 0.8 ,g/kg, whereas at 100,500 ,g/kg, the effect was significant relative to the OVX control for the entire duration of the study of 32 wk. Bone formation parameters were not significantly affected by ZOL 20 ,g/kg but were significantly reduced by ZOL 100,500 ,g/kg. Alendronate 200 ,g/kg was equivalent to ZOL 100 ,g/kg. ZOL produced dose-related improvements in bone strength parameters after ovariectomy. Alendronate 200 ,g/kg was of similar potency to ZOL 20 ,g/kg. Conclusions: The duration and magnitude of the bone-protecting effect of a single intravenous dose of ZOL in ovariectomized rats is dose dependent and lasts for up to 32 wk. Compared with alendronate, ZOL shows 10-fold higher potency in preventing bone loss. These data support the use of an annual intravenous ZOL dosing regimen for the treatment of osteoporosis. [source] Adrenarche and Bone Modeling and Remodeling at the Proximal Radius: Weak Androgens Make Stronger Cortical Bone in Healthy Children,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 8 2003Thomas Remer Abstract Adrenarche, the physiological increase in adrenal androgen secretion, may contribute to better bone status. Proximal radial bone and 24-h urinary steroid hormones were analyzed cross-sectionally in 205 healthy children and adolescents. Positive adrenarchal effects on radial diaphyseal bone were observed. Obviously, adrenarche is one determinant of bone mineral status in children. Introduction: Increased bone mass has been reported in several conditions with supraphysiological adrenal androgen secretion during growth. However, no data are available for normal children. Therefore, our aim was to examine whether adrenal androgens within their physiological ranges may be involved in the strengthening of diaphyseal bone during growth. Methods: Periosteal circumference (PC), cortical density, cortical area, bone mineral content, bone strength strain index (SSI), and forearm cross-sectional muscle area were determined with peripheral quantitative computed tomography (pQCT) at the proximal radial diaphysis in healthy children and adolescents. All subjects, aged 6,18 years, who collected a 24-h urine sample around the time of their pQCT analysis (100 boys, 105 girls), were included in the present study, and major urinary glucocorticoid (C21) and androgen (C19) metabolites were quantified using gas chromatography-mass spectrometry. Results and Conclusions: We found a significant influence of muscularity, but not of hormones, on periosteal modeling (PC) before the appearance of pubic hair (prepubarche). Similarly, no influence of total cortisol secretion (C21) was seen on the other bone variables. However, positive effects of C19 on cortical density (p < 0.01), cortical area (p < 0.001), bone mineral content (p < 0.001), and SSI (p < 0.001),reflecting, at least in part, reduction in intracortical remodeling,were observed in prepubarchal children after muscularity or age had been adjusted for. This early adrenarchal contribution to proximal radial diaphyseal bone strength was further confirmed for all cortical variables (except PC) when, instead of C19 and C21, specific dehydroepiandrosterone metabolites were included as independent variables in the multiple regression model. During development of pubic hair (pubarche), muscularity and pubertal stage rather than adrenarchal hormones seemed to influence bone variables. Our study shows that especially the prepubarchal increase in adrenal androgen secretion plays an independent role in the accretion of proximal radial diaphyseal bone strength in healthy children. [source] Effects of a New Selective Estrogen Receptor Modulator (MDL 103,323) on Cancellous and Cortical Bone in Ovariectomized Ewes: A Biochemical, Histomorphometric, and Densitometric StudyJOURNAL OF BONE AND MINERAL RESEARCH, Issue 1 2001Pascale Chavassieux Abstract The aims of this study performed in ewes were: (1) to confirm in this animal model the effects on bone of ovariectomy (OVX) alone or associated with Lentaron (L), a potent peripheral aromatase inhibitor, used to amplify the effects of OVX and (2) to evaluate the effects of a new selective estrogen receptor modulator (SERM; MDL 103,323) on bone remodeling. Thirty-nine old ewes were divided into five groups: sham (n = 7); OVX (n = 8); OVX + L (n = 8); OVX + L + MDL; 0.1 mg/kg per day (n = 8); and OVX + L + MDL 1 mg/kg per day (n = 8). The animals were treated for 6 months. Biochemical markers of bone turnover (urinary excretion of type 1 collagen C-telopeptide [CTX], serum osteocalcin [OC], and bone alkaline phosphatase [BAP]) were measured each month. Bone biopsy specimens were taken at the beginning and after death at the end of the experiment. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry (DXA) on the lumbar spine and femur. OVX induced a significant increase in biochemical markers. This effect was the highest after 3 months for CTX (+156% vs. sham) and after 4 months for OC and BAP (+74% and +53% vs. sham, respectively). L tended to amplify the effect of OVX on OC and BAP. OVX induced significant increases in the porosity, eroded, and osteoid surfaces in cortical bone but no effect was observed in cancellous bone. MDL treatment reduced the bone turnover as assessed by bone markers, which returned to sham levels as well as histomorphometry both in cortical and in cancellous bone. Cancellous osteoid thickness decreased by 27% (p < 0.05), mineralizing perimeter by 81% (p < 0.05), and activation frequency by 84% (p < 0.02) versus OVX + L. Femoral and spinal BMD were increased by MDL and tended to return to the sham values. The effects of OVX on bone turnover were different on cortical and cancellous bone. These effects on cortical bone were reflected by changes in biochemical markers. MDL markedly reduces bone turnover and increases BMD suggesting that this new agent may prevent postmenopausal bone loss. [source] Effect of Compromised Cortical Bone on Implant Load DistributionJOURNAL OF PROSTHODONTICS, Issue 8 2008vanç Akça DDS Abstract Purpose: To investigate photoelastically the difference in load distribution of dental implants with different implant neck designs in intact and compromised bone. Materials and Methods: Composite photoelastic models were fabricated using two different resins to simulate trabecular bone and a 1-mm thick layer of cortical bone. The following parallel-sided, threaded implants were centrally located in individual models representing intact and compromised cortical bone: Straumann (4.1-mm diameter × 12-mm length), AstraTech (4.0-mm diameter × 13-mm length), and 3i (3.75-mm diameter × 13-mm length). The compromised cortical bone condition was simulated by contaminating a 1-mm neck portion with Vaseline to impair the implant,resin interface. Vertical and oblique static loads were applied on the abutments, and the resulting stresses were monitored photoelastically and recorded photograhphically. Results: For the fully intact condition, the highest stresses were observed around the crest and apical region for all implant designs under vertical and inclined loads. There were no appreciable differences in magnitude or distribution between implant types. With compromised cortical bone, for all designs and load directions, higher stresses in the supporting structures were observed. Increased stresses were noted especially at the cortical bone,trabecular bone interface. Somewhat lower stress levels were observed with the 3i implant. Conclusions: The condition of implant,cortical bone contact has considerable influence on stress distribution. A compromised cortical bone condition caused higher level stresses for all implant designs tested. [source] Morphometric Analysis of the Canal System of Cortical Bone: An Experimental Study in the Rabbit Femur Carried Out with Standard Histology and Micro-CTANATOMIA, HISTOLOGIA, EMBRYOLOGIA, Issue 1 2010U. E. Pazzaglia Summary The osteonal pattern of cortical bone is gradually built around the intracortical vessels by the progression of the cutting cones (secondary remodelling); therefore, the central canal size can be used as index of the remodelling activity. An experimental model in the rabbit femur was used to investigate, through central canal morphometry and frequency distribution analysis, the remodelling activity, comparing the middle of the diaphysis (mid-shaft) with the extremity (distal-shaft) and at the same level sectors and layers of the cortex in transversal sections. The study documented a higher density of canals in the mid-shaft than in the distal-shaft and a higher remodelling in the distal-shaft. There were no significant differences between dorsal, ventral, medial and lateral sectors at both mid-shaft and distal-shaft levels, while the number of canals was higher in the sub-periosteal layers than in the sub-endosteal. A lower threshold of 40 ,m2 was observed in the central canal area. Sealed osteons in the midshaft were 22.43% of the total number of osteons of the central canal area between 40 and 200 ,m2 and 0.44% of those of the distal-shaft. Micro-CT allowed a 3D reconstruction of the vascular canal system, which confirmed the branched network pattern rather than the trim architecture of the traditional representation. Some aspects like the lower threshold of the central canal size and the sealed osteons documented the plasticity of the system and its capacity for adaptation to changes in the haemodynamic conditions. [source] Bone histology of Silesaurus opolensisDzik, 2003 from the Late Triassic of PolandLETHAIA, Issue 2 2010UCJA FOSTOWICZ-FRELIK Fostowicz-Frelik, ,. & Sulej, T. 2009: Bone histology of Silesaurus opolensisDzik, 2003 from the Late Triassic of Poland. Lethaia, Vol. 43, pp. 137,148. The phylogenetic relationships of Silesaurus opolensis have been the subject of intense debate since its discovery. Silesaurus possesses some features characteristic of ornithischian dinosaurs, such as the presence of a beak at the front of the lower jaw, yet it lacks a number of important femoral and dental synapomorphies of Dinosauria. The microstructure of the long bones (femur, tibia and metatarsal) and ribs of this species reveals a relatively intensive rate of growth, comparable with that seen in small dinosaurs and the gracile crocodylomorph Terrestrisuchus. Cortical bone formed mainly by periosteal tissue with fibro-lamellar matrix (in older specimens parallel fibred) shows very little secondary remodelling and only in one specimen (large tibia ZPAL Ab III/1885) few lines of arrested growth are present in the outermost cortex. The vascularization is relatively dense, mainly longitudinal and ceases towards the periphery, forming almost avascular parallel fibred bone at the bone surface. This indicates maturation and significant decrease in the growth ratio in mature specimens of S. opolensis. The delicate trabeculae exhibit cores formed by the primary cancellous tissue lined with lamellar endosteal bone. The rather intense growth of S. opolensis implies a relatively high metabolic rate. Moreover, evidence from the fibro-lamellar tissue, predominant in the cortex, suggests that this kind of rapid bone deposition could be more typical of Archosauria than previously assumed, a prerequisite for the evolution of the very fast growth rates observed in large ornithischians, sauropods and large theropods. ,Archosauria, Bone histology, Dinosauriformes, Late Triassic, Silesaurus opolensis. [source] Functional behaviour of bone around dental implants,GERODONTOLOGY, Issue 2 2004Clark M. Stanford Achieving a long-term stable implant interface is a significant clinical issue when there is insufficient cortical bone stabilisation at implant placement. Clinical outcomes studies suggest that the higher risk implants are those placed in compromised cortical bone (thin, porous, etc.) in anatomical sites with minimal existing trabecular bone (characterised as type IV bone). In establishing and maintaining an implant interface in such an environment, one needs to consider the impact of masticatory forces, the response of bone to these forces and the impact of age on the adaptive capacity of bone. These forces, in turn, have the potential to create localised changes in interfacial stiffness through viscoelastic changes at the interface. Changes in bone as a function of age (e.g. localised hypermineralised osteopetrosis and localised areas of osteopenia) will alter the communication between osteocytes and osteoblasts creating the potential for differences in response of osteoblastic cells in the older population. A key to understanding the biomechanical and functional behaviour of implants in the older population is to control the anticipated modelling and remodelling behaviour through implant design that takes into account how tissues respond to the mechanically active environment. [source] Inside Front Cover: A Unique Microcracking Process Associated with the Inelastic Deformation of Haversian Bone (Adv. Funct.ADVANCED FUNCTIONAL MATERIALS, Issue 1 2009Mater. Human cortical bone is capable of adapting to the mechanical environment through dynamic remodeling of the Haversian systems. The presence of Haversian canals, however, also introduces stress concentration and could have detrimental effects on the fracture resistance of bone. How is the hierarchical structure in bone designed to alleviate such stress concentrations? On page 57, Vincent Ebacher and Rizhi Wang report a unique and stable microcracking process accompanying the inelastic deformation of Haversian bone. The results lead to the critical role of the well-organized bone lamellae surrounding each Haversian canal. [source] Limitations of previously published systematic reviews evaluating the outcome of endodontic treatmentINTERNATIONAL ENDODONTIC JOURNAL, Issue 8 2009M-K. Wu Abstract The aim of this work was to identify the limitations of previously published systematic reviews evaluating the outcome of root canal treatment. Traditionally, periapical radiography has been used to assess the outcome of root canal treatment with the absence of a periapical radiolucency being considered a confirmation of a healthy periapex. However, a high percentage of cases confirmed as healthy by radiographs revealed apical periodontitis on cone beam computed tomography (CBCT) and by histology. In teeth, where reduced size of the existing radiolucency was diagnosed by radiographs and considered to represent periapical healing, enlargement of the lesion was frequently confirmed by CBCT. In clinical studies, two additional factors may have further contributed to the overestimation of successful outcomes after root canal treatment: (i) extractions and re-treatments were rarely recorded as failures; and (ii) the recall rate was often lower than 50%. The periapical index (PAI), frequently used for determination of success, was based on radiographic and histological findings in the periapical region of maxillary incisors. The validity of using PAI for all tooth positions might be questionable, as the thickness of the cortical bone and the position of the root tip in relation with the cortex vary with tooth position. In conclusion, the serious limitations of longitudinal clinical studies restrict the correct interpretation of root canal treatment outcomes. Systematic reviews reporting the success rates of root canal treatment without referring to these limitations may mislead readers. The outcomes of root canal treatment should be re-evaluated in long-term longitudinal studies using CBCT and stricter evaluation criteria. [source] Analysis of micro fracture in human Haversian cortical bone under transverse tension using extended physical imagingINTERNATIONAL JOURNAL FOR NUMERICAL METHODS IN ENGINEERING, Issue 8 2010É. Budyn Abstract We propose a procedure to investigate local stress intensity factors at the scale of the osteons in human Haversian cortical bone. The method combines a specific experimental setting for a three-point bending millimetric specimen and a numerical method using the eXtended Finite Element Method (X-FEM). The interface between the experimental setting and the numerical method is ensured through an imaging technique that analyses the light microscopy observations to import the geometrical heterogeneity of the Haversian microstructures, the boundary conditions and appearing crack discontinuities into the numerical model. The local mechanical elastic Young's moduli are measured by nano-indentation, and the Poisson ratios are determined by an imaging technique of the stress,strain fields. The model is able to access three scales of measurement: the macro scale of the material level (mm), the micro scale inside the Haversian material for stress,strain fields (10,100µm), and the sub-micro scale for the crack opening profiles (1,10µm ) and fracture parameters (stress intensity factors). The model is applied to several patients at different aging stages. Copyright © 2009 John Wiley & Sons, Ltd. [source] Bone weight: new reference values based on a modern Portuguese identified skeletal collectionINTERNATIONAL JOURNAL OF OSTEOARCHAEOLOGY, Issue 5 2009A. M. Silva Abstract Skeletal weight and/or weight of the different bones of the human skeleton are currently used in a wide range of applications such as archaeological cremations and forensics. Still, few reference values are available that compare the mean weights for the different skeletal parts. In this paper we present new reference values for total skeletal weight, including the weight of the different skeletal bones based on a modern Portuguese Identified Skeletal Collection (CEI) curated in the Museum of Anthropology of the University of Coimbra (Portugal). The mean weight of the entire skeleton for the CEI pooled sample is 3323.8,±,779.6,g. Sex and age differences were investigated. As expected, males display heavier bones, at a statistically significant level. The mean weight of the male skeletons is 3850,g, and 2797.6,g for the female sample. Age differences were found, especially for the female samples in the 29,39 versus 50,59,and/or >60 age groups, probably as a consequence of age-related bone loss in post-menopausal women. For the male sample, no clear age-related trend was observed but for the unexpected result that the second highest bone weight recorded is in the oldest age group (>60 years). This could result from high mechanical loadings and thus greater bone robusticy and amount of cortical bone. The percentage of weight of the different parts of the skeleton was also calculated. These new values can be quite useful in the study of very fragmentary and/or commingled human remains, recovered from historic or forensic contexts, since the complete identification, by side, of the remains is not necessary. Copyright © 2008 John Wiley & Sons, Ltd. [source] A procedural guide to metacarpal radiogrammetry in archaeologyINTERNATIONAL JOURNAL OF OSTEOARCHAEOLOGY, Issue 1 2004R. Ives Abstract The technique of metacarpal radiogrammetry was devised in 1960 as a clinical method to aid in the identification of thinned cortical bone, which may help in diagnosis of osteoporosis. Through taking measurements from radiographs, calculations of the amount of cortical bone can be made. The technique is relatively simple and is not destructive. This paper examines the value of the application of this technique to archaeological remains. A standardized methodology of bone assessment is incorporated to enhance the comparability of future research. Statistical tests demonstrate that the technique is robust, as the position of the bone on the film, radiographic enlargement and use of either the left or right metacarpal will not affect the results obtained. However, differences in film type and measurement position can introduce unacceptable variance into the results. Therefore, guidance is given on future applications of the technique. The technique does have value as a widely available, non-destructive technique for assessing cortical bone loss and the probable prevalence of osteoporosis in archaeological collections. Copyright © 2004 John Wiley & Sons, Ltd. [source] A test of two methods of radiographically deriving long bone cross-sectional properties compared to direct sectioning of the diaphysisINTERNATIONAL JOURNAL OF OSTEOARCHAEOLOGY, Issue 5 2002Jay T. Stock Abstract Numerous studies have made use of cross-sectional geometry to describe the distribution of cortical bone in long bone diaphyses. Several methods can be used to measure or estimate cross-sectional contours. Direct sectioning (DSM) of the diaphysis is not appropriate in most curatorial contexts, and is commonly substituted with methods based upon bi-planar radiography: a latex cast method (LCM) or an eccentric elliptical method (EEM). Previous studies have demonstrated that the EEM provides accurate estimates of area measurements, while providing less accurate estimates of second moments of area (Biknevicius & Ruff, 1992; Runestad et al., 1993; Lazenby, 1997). The LCM has been commonly employed, as a way to estimate section contours more accurately, yet the validity of this method has not been adequately documented. This study measures the agreement of these methods against DSM of long bone diaphyses using 21 sections of canine tibiae derived from a study of total hip arthroplasty. The accuracy and agreement of these methods is evaluated using reduced major axis regression, paired sample t-tests and tests for agreement (Bland & Altman, 1986). The results illustrate that the LCM provides a reasonable estimate of cross-sectional dimensions, producing cross-sectional properties that are on average within 5% of properties derived from the DSM. The EEM is found to provide adequate estimates of true cross-sectional areas, but poor estimates of second moments of area. The use of the LCM is supported for all cross-sectional properties, but the EEM is only accurate in total area, cortical area and percent cortical area estimates. Copyright © 2002 John Wiley & Sons, Ltd. [source] Destruction of microstructure in archaeological bone: a case study from PortugalINTERNATIONAL JOURNAL OF OSTEOARCHAEOLOGY, Issue 6 2001Mary Jackes Abstract Sampling of archaeological human bone may not be justified, contrary to former high expectations regarding adult age assessment based on histomorphometry. The alterations in buried bone as a result of bacterial action are readily visible in the scanning electron microscope (SEM). An understanding of the chemical and structural changes to cortical bone requires work at the level of a few microns. This paper reports on problems encountered during analyses of samples of human bone from Mesolithic (ca. 8000 calbp) shell midden sites at Muge in central Portugal, and the methods used to try and overcome these problems. We believe we have shown that these Mesolithic bones are partly comprised of bacterially reprecipitated mineral, which has had collagen removed, with consequent obliteration of bone microstructure. We conclude that microbial destruction of the structure of archaeological bone can be a serious impediment to analysis of the characteristics of the population represented by those skeletal remains. Copyright © 2001 John Wiley & Sons, Ltd. [source] Porosity of human mandibular condylar boneJOURNAL OF ANATOMY, Issue 3 2007G. A. P. Renders Abstract Quantification of porosity and degree of mineralization of bone facilitates a better understanding of the possible effects of adaptive bone remodelling and the possible consequences for its mechanical properties. The present study set out first to give a three-dimensional description of the cortical canalicular network in the human mandibular condyle, in order to obtain more information about the principal directions of stresses and strains during loading. Our second aim was to determine whether the amount of remodelling was larger in the trabecular bone than in cortical bone of the condyle and to establish whether the variation in the amount of remodelling was related to the surface area of the cortical canals and trabeculae. We hypothesized that there were differences in porosity and orientation of cortical canals between various cortical regions. In addition, as greater cortical and trabecular porosities are likely to coincide with a greater surface area of cortical canals and trabeculae available for osteoblastic and osteoclastic activity, we hypothesized that this surface area would be inversely proportional to the degree of mineralization of cortical and trabecular bone, respectively. Micro-computed tomography was used to quantify porosity and mineralization in cortical and trabecular bone of ten human mandibular condyles. The cortical canals in the subchondral cortex of the condyle were orientated in the mediolateral direction, and in the anterior and posterior cortex in the superoinferior direction. Cortical porosity (average 3.5%) did not differ significantly between the cortical regions. It correlated significantly with the diameter and number of cortical canals, but not with cortical degree of mineralization. In trabecular bone (average porosity 79.3%) there was a significant negative correlation between surface area of the trabeculae and degree of mineralization; such a correlation was not found between the surface area of the cortical canals and the degree of mineralization of cortical bone. No relationship between trabecular and cortical porosity, nor between trabecular degree of mineralization and cortical degree of mineralization was found, suggesting that adaptive remodelling is independent and different between trabecular and cortical bone. We conclude (1) that the principal directions of stresses and strains are presumably directed mediolaterally in the subchondral cortex and superoinferiorly in the anterior and posterior cortex, (2) that the amount of remodelling is larger in the trabecular than in the cortical bone of the mandibular condyle; in trabecular bone variation in the amount of remodelling is related to the available surface area of the trabeculae. [source] Evidence of a hypermineralised calcified fibrocartilage on the human femoral neck and lesser trochanterJOURNAL OF ANATOMY, Issue 2 2001J. E. SHEA Femoral neck fractures are a major cause of morbidity and mortality in elderly humans. In addition to the age-related loss of cancellous bone, changes to the microstructure and morphology of the metaphyseal cortex may be a contributing factor in osteoporotic hip fractures. Recent investigations have identified a hypermineralised tissue on the neck of the femur and trochanteric region that increases in fractional area with advancing age in both males (Boyce & Bloebaum, 1993) and females (Vajda & Bloebaum, 1999). The aim of this study was to determine if the hypermineralised tissue previously observed on the proximal femur is calcified fibrocartilage. Regional variations in the fractional area of hypermineralised tissue, cortical bone, and porosity of the cortical bone along the neck of the femur and lesser trochanter were also quantified. Comparison of back scattered electron and light microscope images of the same area show that regions of hypermineralised tissue correlate with the regions of calcified fibrocartilage from tendon and capsular insertions. The hypermineralised tissue and calcified fibrocartilage had similar morphological features such as the interdigitations of the calcified fibrocartilage into the bone, lacunar spaces, and distinctly shaped pores adjacent to the 2 tissues. Regions of the neck that did not contain insertions were covered with periosteum. There were no regional differences (P > 0.05) on the superior and inferior femoral neck in terms of the percentage area of hypermineralised calcified fibrocartilage, cortical bone, or cortical bone porosity. The lesser trochanter exhibited regional differences in the fractional area of hypermineralised calcified fibrocartilage (P = 0.007) and cortical bone (P = 0.007) but not porosity of the cortical bone (P > 0.05). The effects of calcified fibrocartilage on femoral neck periosteal expansion, repair, and mechanics are unknown, but may play a role in osteoporotic fractures and intracapsular fracture healing. [source] Aged mice have enhanced endocortical response and normal periosteal response compared with young-adult mice following 1 week of axial tibial compressionJOURNAL OF BONE AND MINERAL RESEARCH, Issue 9 2010Michael D Brodt Abstract With aging, the skeleton may lose its ability to respond to positive mechanical stimuli. We hypothesized that aged mice are less responsive to loading than young-adult mice. We subjected aged (22 months) and young-adult (7 months) BALB/c male mice to daily bouts of axial tibial compression for 1 week and evaluated cortical and trabecular responses using micro,computed tomography (µCT) and dynamic histomorphometry. The right legs of 95 mice were loaded for 60 rest-inserted cycles per day to 8, 10, or 12,N peak force (generating mid-diaphyseal strains of 900 to 1900 µ, endocortically and 1400 to 3100 µ, periosteally). At the mid-diaphysis, mice from both age groups showed a strong anabolic response on the endocortex (Ec) and periosteum (Ps) [Ec.MS/BS and Ps. MS/BS: loaded (right) versus control (left), p,<,.05]. Generally, bone formation increased with increasing peak force. At the endocortical surface, contrary to our hypothesis, aged mice had a significantly greater response to loading than young-adult mice (Ec.MS/BS and Ec.BFR/BS: 22 months versus 7 months, p,<,.001). Responses at the periosteal surface did not differ between age groups (p,>,.05). The loading-induced increase in bone formation resulted in increased cortical area in both age groups (loaded versus control, p,<,.05). In contrast to the strong cortical response, loading only weakly stimulated trabecular bone formation. Serial (in vivo) µCT examinations at the proximal metaphysis revealed that loading caused a loss of trabecular bone in 7-month-old mice, whereas it appeared to prevent bone loss in 22-month-old mice. In summary, 1 week of daily tibial compression stimulated a robust endocortical and periosteal bone-formation response at the mid-diaphysis in both young-adult and aged male BALB/c mice. We conclude that aging does not limit the short-term anabolic response of cortical bone to mechanical stimulation in our animal model. © 2010 American Society for Bone and Mineral Research [source] Correlates of trabecular and cortical volumetric bone mineral density of the radius and tibia in older men: The osteoporotic fractures in men studyJOURNAL OF BONE AND MINERAL RESEARCH, Issue 5 2010Kamil E Barbour Abstract Quantitative computed tomography (QCT) can estimate volumetric bone mineral density (vBMD) and distinguish trabecular from cortical bone. Few comprehensive studies have examined correlates of vBMD in older men. This study evaluated the impact of demographic, anthropometric, lifestyle, and medical factors on vBMD in 1172 men aged 69 to 97 years and enrolled in the Osteoporotic Fractures in Men Study (MrOS). Peripheral quantitative computed tomography (pQCT) was used to measure vBMD of the radius and tibia. The multivariable linear regression models explained up to 10% of the variance in trabecular vBMD and up to 9% of the variance in cortical vBMD. Age was not correlated with radial trabecular vBMD. Correlates associated with both cortical and trabecular vBMD were age (,), caffeine intake (,), total calcium intake (+), nontrauma fracture (,), and hypertension (+). Higher body weight was related to greater trabecular vBMD and lower cortical vBMD. Height (,), education (+), diabetes with thiazolidinedione (TZD) use (+), rheumatoid arthritis (+), using arms to stand from a chair (,), and antiandrogen use (,) were associated only with trabecular vBMD. Factors associated only with cortical vBMD included clinic site (,), androgen use (+), grip strength (+), past smoker (,), and time to complete five chair stands (,). Certain correlates of trabecular and cortical vBMD differed among older men. An ascertainment of potential risk factors associated with trabecular and cortical vBMD may lead to better understanding and preventive efforts for osteoporosis in men. © 2010 American Society for Bone and Mineral Research [source] Fluorescent risedronate analogues reveal bisphosphonate uptake by bone marrow monocytes and localization around osteocytes in vivoJOURNAL OF BONE AND MINERAL RESEARCH, Issue 3 2010Anke J Roelofs Abstract Bisphosphonates are effective antiresorptive agents owing to their bone-targeting property and ability to inhibit osteoclasts. It remains unclear, however, whether any non-osteoclast cells are directly affected by these drugs in vivo. Two fluorescent risedronate analogues, carboxyfluorescein-labeled risedronate (FAM-RIS) and Alexa Fluor 647,labeled risedronate (AF647-RIS), were used to address this question. Twenty-four hours after injection into 3-month-old mice, fluorescent risedronate analogues were bound to bone surfaces. More detailed analysis revealed labeling of vascular channel walls within cortical bone. Furthermore, fluorescent risedronate analogues were present in osteocytic lacunae in close proximity to vascular channels and localized to the lacunae of newly embedded osteocytes close to the bone surface. Following injection into newborn rabbits, intracellular uptake of fluorescently labeled risedronate was detected in osteoclasts, and the active analogue FAM-RIS caused accumulation of unprenylated Rap1A in these cells. In addition, CD14high bone marrow monocytes showed relatively high levels of uptake of fluorescently labeled risedronate, which correlated with selective accumulation of unprenylated Rap1A in CD14+ cells, as well as osteoclasts, following treatment with risedronate in vivo. Similar results were obtained when either rabbit or human bone marrow cells were treated with fluorescent risedronate analogues in vitro. These findings suggest that the capacity of different cell types to endocytose bisphosphonate is a major determinant for the degree of cellular drug uptake in vitro as well as in vivo. In conclusion, this study shows that in addition to bone-resorbing osteoclasts, bisphosphonates may exert direct effects on bone marrow monocytes in vivo. © 2010 American Society for Bone and Mineral Research [source] Genetic Hypercalciuric Stone-Forming Rats Have a Primary Decrease in BMD and Strength,,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 8 2009Marc Grynpas Abstract Kidney stone patients often have a decrease in BMD. It is unclear if reduced BMD is caused by a primary disorder of bone or dietary factors. To study the independent effects of hypercalciuria on bone, we used genetic hypercalciuric stone-forming (GHS) rats. GHS and control (Ctl) rats were fed a low Ca (0.02% Ca, LCD) or a high Ca (1.2% Ca, HCD) diet for 6 wk in metabolic cages. All comparisons are to Ctl rats. Urine Ca was greater in the GHS rats on both diets. GHS fed HCD had reduced cortical (humerus) and trabecular (L1,L5 vertebrae) BMD, whereas GHS rats fed LCD had a reduction in BMD similar to Ctl. GHS rats fed HCD had a decrease in trabecular volume and thickness, whereas LCD led to a ,20-fold increase in both osteoid surface and volume. GHS rats fed HCD had no change in vertebral strength (failure stress), ductibility (failure strain), stiffness (modulus), or toughness, whereas in the humerus, there was reduced ductibility and toughness and an increase in modulus, indicating that the defect in mechanical properties is mainly manifested in cortical, rather than trabecular, bone. GHS rat cortical bone is more mineralized than trabecular bone and LCD led to a decrease in the mineralization profile. Thus, the GHS rats, fed an ample Ca diet, have reduced BMD with reduced trabecular volume, mineralized volume, and thickness, and their bones are more brittle and fracture prone, indicating that GHS rats have an intrinsic disorder of bone that is not secondary to diet. [source] Positive Regulation of Adult Bone Formation by Osteoblast-Specific Transcription Factor Osterix,,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 6 2009Wook-Young Baek Abstract Osterix (Osx) is essential for osteoblast differentiation and bone formation, because mice lacking Osx die within 1 h of birth with a complete absence of intramembranous and endochondral bone formation. Perinatal lethality caused by the disruption of the Osx gene prevents studies of the role of Osx in bones that are growing or already formed. Here, the function of Osx was examined in adult bones using the time- and site-specific Cre/loxP system. Osx was inactivated in all osteoblasts by Col1a1-Cre with the activity of Cre recombinase under the control of the 2.3-kb collagen promoter. Even though no bone defects were observed in newborn mice, Osx inactivation with 2.3-kb Col1a1-Cre exhibited osteopenia phenotypes in growing mice. BMD and bone-forming rate were decreased in lumbar vertebra, and the cortical bone of the long bones was thinner and more porous with reduced bone length. The trabecular bones were increased, but they were immature or premature. The expression of early marker genes for osteoblast differentiation such as Runx2, osteopontin, and alkaline phosphatase was markedly increased, but the late marker gene, osteocalcin, was decreased. However, no functional defects were found in osteoclasts. In summary, Osx inactivation in growing bones delayed osteoblast maturation, causing an accumulation of immature osteoblasts and reducing osteoblast function for bone formation, without apparent defects in bone resorption. These findings suggest a significant role of Osx in positively regulating osteoblast differentiation and bone formation in adult bone. [source] Genetic Regulation of Bone Traits Is Influenced by Sex and Reciprocal Cross in F2 Progeny From GK and F344 Rats,,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 6 2009Sofia Lagerholm Abstract A genome-wide linkage analysis to identify quantitative trait loci (QTLs) for bone phenotypes was performed in an F2 intercross of inbred spontaneously type 2 diabetic GK and normoglycemic F344 rats (108 males and 98 females). The aim of the study was to locate genome regions with candidate genes affecting trabecular and cortical bone and to investigate the effects of sex and reciprocal cross. pQCT was used to determine tibial bone phenotypes in the F2 rats, comprising reciprocal crosses with divergent mitochondrial (mt) DNA. Sex and reciprocal cross-separated QTL analyses were performed followed by assessment of specific interactions. Four genome-wide significant QTLs linked to either cortical vBMD, tibia length, body length, or metaphyseal area were identified in males on chromosomes (chr) 1, 8, and 15. In females, three significant QTLs linked to cortical BMC or metaphyseal total vBMD were identified on chr 1 and 2. Several additional suggestive loci for trabecular and cortical traits were detected in both males and females. Four female-specific QTLs on chr 2, 3, 5, and 10 and four reciprocal cross-specific QTLs on chr 1, 10, and 18 were identified, suggesting that both sex and mt genotype influence the expression of bone phenotypes. [source] Severity of Vertebral Fractures Is Associated With Alterations of Cortical Architecture in Postmenopausal Women,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 4 2009Elisabeth Sornay-Rendu Abstract Patients with vertebral fractures (VFx) have trabecular architectural disruption on iliac biopsies. Because cortical bone is an important determinant of bone strength, we assessed cortical and trabecular microarchitecture at peripheral sites in patients with VFx of varying number (N) and severity (S). Bone architecture and volumetric density (vBMD) were assessed at the distal radius and tibia with HR-pQCT (XTreme CT; Scanco Medical, Bassersdorf, Switzerland) in 100 women with VFx (age, 74 ± 9 yr) of different S (GI, n = 23; GII, n = 35; GIII, n = 42) and in 362 women (age, 69 ± 7 yr) without peripheral or VFx (G0) from the OFELY study. Spine areal BMD (aBMD) was assessed by DXA. Among all women, at the radius and after adjustment for age and aBMD, there were significant trends in lower vBMD, cortical thickness (Cort.Th), trabecular number (Tb.N) and thickness (Tb.Th), higher trabecular separation (Tb.Sp), and distribution of separation (Tb.Sp.SD) with greater VFx S and N. Among women with VFx, lower Cort.Th and cortical vBMD (D.Cort) were associated with severe (GIII) and multiple (n > 2) VFx (p < 0.05). The age-adjusted OR for each SD decrease of Cort.Th was 2.04 (95% CI, 1.02,4.00) after adjustment for aBMD. At the tibia, there were trends for lower vBMD, Tb.N, Tb.Th, and higher Tb.Sp and Tb.Sp.SD with greater VFx S and N (p < 0.001). Among women with VFx, lower Cort.Th and D.Cort were associated with severe and multiple (n > 3) VFx (p < 0.01). In postmenopausal women, VFx are associated with low vBMD and architectural decay of trabecular and cortical bone at the radius and tibia, independently of spine aBMD. Severe and multiple VFx are associated with even more alterations of cortical bone. [source] Hip Fractures and the Contribution of Cortical Versus Trabecular Bone to Femoral Neck Strength,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 3 2009Gerold Holzer Abstract Osteoporotic fractures are caused by both cortical thinning and trabecular bone loss. Both are seen to be important for bone fragility. The relative contributions of cortical versus trabecular bone have not been established. The aim of this study was to test the contribution of cortical versus trabecular bone to femoral neck stability in bone strength. In one femur from each pair of 18 human cadaver femurs (5 female; 4 male), trabecular bone was completely removed from the femoral neck, providing one bone with intact and the other without any trabecular structure in the femoral neck. Geometrical, X-ray, and DXA measurements were carried out before biomechanical testing (forces to fracture). Femoral necks were osteotomized, slices were analyzed for cross-sectional area (CSA) and cross-sectional moment of inertia (CSMI), and results were compared with biomechanical testing data. Differences between forces needed to fracture excavated and intact femurs (,F/F mean) was 7.0% on the average (range, 4.6,17.3%). CSA of removed spongiosa did not correlate with difference of fracture load (,F/F mean), nor did BMD. The relative contribution of trabecular versus cortical bone in respect to bone strength in the femoral neck seems to be marginal and seems to explain the subordinate role of trabecular bone and its changes in fracture risk and the effects of treatment options in preventing fractures. [source] Targeted Deletion of the Sclerostin Gene in Mice Results in Increased Bone Formation and Bone Strength,,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 6 2008Xiaodong Li Abstract Introduction: Sclerosteosis is a rare high bone mass genetic disorder in humans caused by inactivating mutations in SOST, the gene encoding sclerostin. Based on these data, sclerostin has emerged as a key negative regulator of bone mass. We generated SOST knockout (KO) mice to gain a more detailed understanding of the effects of sclerostin deficiency on bone. Materials and Methods: Gene targeting was used to inactivate SOST and generate a line of SOST KO mice. Radiography, densitometry, ,CT, histomorphometry, and mechanical testing were used to characterize the impact of sclerostin deficiency on bone in male and female mice. Comparisons were made between same sex KO and wildtype (WT) mice. Results: The results for male and female SOST KO mice were similar, with differences only in the magnitude of some effects. SOST KO mice had increased radiodensity throughout the skeleton, with general skeletal morphology being normal in appearance. DXA analysis of lumbar vertebrae and whole leg showed that there was a significant increase in BMD (>50%) at both sites. ,CT analysis of femur showed that bone volume was significantly increased in both the trabecular and cortical compartments. Histomorphometry of trabecular bone revealed a significant increase in osteoblast surface and no significant change in osteoclast surface in SOST KO mice. The bone formation rate in SOST KO mice was significantly increased for trabecular bone (>9-fold) at the distal femur, as well as for the endocortical and periosteal surfaces of the femur midshaft. Mechanical testing of lumbar vertebrae and femur showed that bone strength was significantly increased at both sites in SOST KO mice. Conclusions:SOST KO mice have a high bone mass phenotype characterized by marked increases in BMD, bone volume, bone formation, and bone strength. These results show that sclerostin is a key negative regulator of a powerful, evolutionarily conserved bone formation pathway that acts on both trabecular and cortical bone. [source] Long-Term Protective Effects of Zoledronic Acid on Cancellous and Cortical Bone in the Ovariectomized Rat,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 4 2008Jürg A Gasser PhD Abstract Current bisphosphonate therapies effectively prevent bone loss in postmenopausal women. We studied the effect of a single intravenous dose of ZOL in ovariectomized rats. Protection from bone loss was dose dependent, lasting for up to 32 weeks, supporting the rationale for an annual intravenous dosing regimen of ZOL for treatment of postmenopausal osteoporosis. Introduction: Once-yearly dosing with zoledronic acid (ZOL) 5 mg can increase BMD and reduce fracture rate in postmenopausal women with low BMD. The primary objective of this study was to determine the duration of bone protective effects of a single dose of ZOL in ovariectomized rats, an animal model of postmenopausal osteopenia. Secondary objectives were to determine the effects on bone turnover and mechanical properties. Materials and Methods: Female Wistar rats (10 per group) received single intravenous doses of ZOL 0.8, 4, 20, 100, or 500 ,g/kg, alendronate 200 ,g/kg, or isotonic saline 4 days before bilateral ovariectomy. Sham-operated controls were pretreated with saline. Mass and density of cancellous and cortical bone (pQCT) were measured at 4-wk intervals for 32 wk. Bone architecture (,CT), bone formation dynamics (fluorochrome label-based histomorphometry), and biomechanical strength in compression testing were also assessed at 32 wk. Results: Ovariectomy-associated BMD loss was significantly attenuated for 32 wk by ZOL ,4 ,g/kg for total BMD, ZOL ,20 ,g/kg for cortical BMD, and ZOL ,4 ,g/kg for cancellous BMD (p < 0.01 versus ovariectomized controls). Alendronate 200 ,g/kg was of equivalent potency to ZOL 20 ,g/kg. Ovariectomy-associated decreases in trabecular architectural parameters were dose-dependently attenuated by ZOL. Alendronate 200 ,g/kg was equivalent to ZOL 20 ,g/kg. The bone resorption marker TRACP5b indicated transient suppression of elevated osteoclast activity by ZOL relative to OVX-rats even at the lowest dose of 0.8 ,g/kg, whereas at 100,500 ,g/kg, the effect was significant relative to the OVX control for the entire duration of the study of 32 wk. Bone formation parameters were not significantly affected by ZOL 20 ,g/kg but were significantly reduced by ZOL 100,500 ,g/kg. Alendronate 200 ,g/kg was equivalent to ZOL 100 ,g/kg. ZOL produced dose-related improvements in bone strength parameters after ovariectomy. Alendronate 200 ,g/kg was of similar potency to ZOL 20 ,g/kg. Conclusions: The duration and magnitude of the bone-protecting effect of a single intravenous dose of ZOL in ovariectomized rats is dose dependent and lasts for up to 32 wk. Compared with alendronate, ZOL shows 10-fold higher potency in preventing bone loss. These data support the use of an annual intravenous ZOL dosing regimen for the treatment of osteoporosis. [source] Construction of the Femoral Neck During Growth Determines Its Strength in Old Age,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 7 2007Roger M D Zebaze Abstract Study of the design of the FN in vivo in 697 women and in vitro in 200 cross-sections of different sizes and shapes along each of 13 FN specimens revealed that strength in old age was largely achieved during growth by differences in the distribution rather than the amount of bone material in a given FN cross-section from individual to individual. Introduction: We studied the design of the femoral neck (FN) to gain insight into the structural basis of FN strength in adulthood and FN fragility in old age. Materials and Methods: Studies in vivo were performed using densitometry in 697 women and in vitro using high-resolution ,CT and direct measurements in 13 pairs of postmortem specimens. Results: The contradictory needs of strength for loading yet lightness for mobility were met by varying FN size, shape, spatial distribution, and proportions of its trabecular and cortical bone in a cross-section, not its mass. Wider and narrower FNs were constructed with similar amounts of bone material. Wider FNs were relatively lighter: a 1 SD higher FN volume had a 0.67 (95% CI, 0.61,0.72) SD lower volumetric BMD (vBMD). A 1 SD increment in height was achieved by increasing FN volume by 0.32 (95% CI, 0.25,0.39) SD with only 0.15 (95% CI, 0.08,0.22) SD more bone, so taller individuals had a relatively lighter FN (vBMD was 0.13 [95% CI, 0.05,0.20 SD] SD lower). Greater periosteal apposition constructing a wider FN was offset by even greater endocortical resorption so that the same net amount of bone was distributed as a thinner cortex further from the neutral axis, increasing resistance to bending and lowering vBMD. This was recapitulated at each point along the FN; varying absolute and relative degrees of periosteal apposition and endocortical resorption focally used the same amount of material to fashion an elliptical FN of mainly cortical bone near the femoral shaft to offset bending but a more circular FN of proportionally more trabecular and less cortical bone to accommodate compressive loads adjacent to the pelvis. This structural heterogeneity was largely achieved by adaptive modeling and remodeling during growth,most of the variance in FN volume, BMC, and vBMD was growth related. Conclusions: Altering structural design while minimizing mass achieves FN strength and lightness. Bone fragility may be the result of failure to adapt bone's architecture to loading, not just low bone mass. [source] Remodeling and Vascular Spaces in BoneJOURNAL OF BONE AND MINERAL RESEARCH, Issue 1 2007Erik Fink Eriksen Abstract In recent years, we have come to appreciate that the close association between bone and vasculature plays a pivotal role in the regulation of bone remodeling and fracture repair. In 2001, Hauge et al. characterized a specialized vascular structure, the bone remodeling compartment (BRC), and showed that the outer lining of this compartment was made up of flattened cells, displaying all the characteristics of lining cells in bone. A decrease in bone turnover leads to a decrease in surfaces covered with remodeling compartments, whereas increased turnover causes an increase. Immunoreactivity for all major osteotropic growth factors and cytokines including osteoprotegerin (OPG) and RANKL has been shown in the cells lining the BRC, which makes the BRC the structure of choice for coupling between resorption and formation. The secretion of these factors inside a confined space separated from the bone marrow would facilitate local regulation of the remodeling process without interference from growth factors secreted by blood cells in the marrow space. The BRC creates an environment where cells inside the structure are exposed to denuded bone, which may enable direct cellular interactions with integrins and other matrix factors known to regulate osteoclast/osteoblast activity. However, the denuded bone surface inside the BRC also constitutes an ideal environment for the seeding of bone metastases, known to have high affinity for bone matrix. Reduction in BRC space brought about by antiresorptive therapies such as bisphosphonates reduce the number of skeletal events in advanced cancer, whereas an increase in BRC space induced by remodeling activators like PTH may increase the bone metastatic burden. The BRC has only been characterized in detail in trabecular bone; there is, however, evidence that a similar structure may exist in cortical bone, but further characterization is needed. [source] Cholesterol-Sensing Receptors, Liver × Receptor , and ,, Have Novel and Distinct Roles in Osteoclast Differentiation and ActivationJOURNAL OF BONE AND MINERAL RESEARCH, Issue 8 2006Kirsten M Robertson Abstract The liver × receptor (,,,) is responsible for regulating cholesterol homeostasis in cells. However, our studies using the LXR,,/,, LXR,,/,, and LXR,,/,,,/, mice show that both LXR, and , are also important for bone turnover, mainly by regulating osteoclast differentiation/activity. Introduction: The liver × receptors (,,,) are primarily responsible for regulating cholesterol homeostasis within cells and the whole body. However, as recent studies show that the role for this receptor is expanding, we studied whether the LXRs could be implicated in bone homeostasis and development. Materials and Methods: pQCT was performed on both male and female LXR,,/,, LXR,,/,, LXR,,/,,,/,, and WT mice at 4 months and 1 year of age. Four-month-old female mice were additionally analyzed with reference to qPCR, immunohistochemistry, histomorphometry, transmission electron microscopy, and serum bone turnover markers. Results: At the mRNA level, LXR, was more highly expressed than LXR, in both whole long bones and differentiating osteoblast-like MC3T3-E1 and osteoclast-like RAW 264.7 cells. Four-month-old female LXR,,/, mice had a significant increase in BMD because of an increase in all cortical parameters. No difference was seen regarding trabecular BMD. Quantitative histomorphometry showed that these mice had significantly more endosteal osteoclasts in the cortical bone; however, these cells appeared less active than normal cells as suggested by a significant reduction in serum levels of cross-linked carboxyterminal telopeptides of type I collagen (CTX) and a reduction in bone TRACP activity. Conversely, the female LXR,,/, mice exhibited no change in BMD, presumably because a significant decline in the number of the trabecular osteoclasts was compensated for by an increase in the expression of the osteoclast markers cathepsin K and TRACP. These mice also had a significant decrease in serum CTX, suggesting decreased bone resorption; however, in addition presented with an increase in the expression of osteoblast associated genes, bone formation markers, and serum leptin levels. Conclusions: Our findings show that both LXRs influence cellular function within the bone, with LXR, having an impact on osteoclast activity, primarily in cortical bone, whereas LXR, modulates trabecular bone turnover. [source] | ||||||||||||||||||||||