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Decreased Bone Mass (decreased + bone_mass)
Selected AbstractsIBD and skeletal health: Children are not small adults!INFLAMMATORY BOWEL DISEASES, Issue 11 2005Francisco A Sylvester MD Abstract Patients with inflammatory bowel disease often have decreased bone mass, and fragility fractures can occur. Multiple disease- and treatment related factors, including malnutrition, inflammation, malabsorption, decreased weight-bearing physical activity, and corticosteroids negatively influence bone metabolic activity. Because low-impact fracture is the pathologic expression of critically reduced bone mass and bone quality, knowing the relative risk of fractures in patients with IBD is of great interest. The absolute risk for incident fractures in these patients is still being debated. Clinical and laboratory research is clarifying mechanisms by which IBD can affect the function of osteoblasts and osteoclasts. In this concise review, we aim to provide an update on this topic, with focus on how pediatric IBD affects bone health. [source] Mutations in the Insulin-Like Factor 3 Receptor Are Associated With Osteoporosis,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 5 2008Alberto Ferlin Abstract Introduction: Insulin-like factor 3 (INSL3) is produced primarily by testicular Leydig cells. It acts by binding to its specific G protein,coupled receptor RXFP2 (relaxin family peptide 2) and is involved in testicular descent during fetal development. The physiological role of INSL3 in adults is not known, although substantial INSL3 circulating levels are present. The aim of this study was to verify whether reduced INSL3 activity could cause or contribute to some signs of hypogonadism, such as reduced BMD, currently attributed to testosterone deficiency. Materials and Methods: Extensive clinical, biochemical, and hormonal study, including bone densitometry by DXA, was performed on 25 young men (age, 27,41 yr) with the well-characterized T222P mutation in the RXFP2 gene. Expression analysis of INSL3 and RXFP2 on human bone biopsy and human and mouse osteoblast cell cultures was performed by RT-PCR, quantitative RT-PCR, and immunohistochemistry. Real-time cAMP imaging analysis and proliferation assay under the stimulus of INSL3 was performed on these cells. Lumbar spine and femoral bone of Rxfp2- deficient mice were studied by static and dynamic histomorphometry and ,CT, respectively. Results: Sixteen of 25 (64%) young men with RXFP2 mutations had significantly reduced BMD. No other apparent cause of osteoporosis was evident in these subjects, whose testosterone levels and gonadal function were normal. Expression analyses showed the presence of RXFP2 in human and mouse osteoblasts. Stimulation of these cells with INSL3 produced a dose- and time-dependent increase in cAMP and cell proliferation, confirming the functionality of the RXFP2/INSL3 receptor,ligand complex. Consistent with the human phenotype, bone histomorphometric and ,CT analyses of Rxfp2,/, mice showed decreased bone mass, mineralizing surface, bone formation, and osteoclast surface compared with wildtype littermates. Conclusions: This study suggests for the first time a role for INSL3/RXFP2 signaling in bone metabolism and links RXFP2 gene mutations with human osteoporosis. [source] ,-Arrestin2 Regulates the Differential Response of Cortical and Trabecular Bone to Intermittent PTH in Female Mice,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 4 2005Mary L Bouxsein PhD Abstract Cytoplasmic arrestins regulate PTH signaling in vitro. We show that female ,-arrestin2,/, mice have decreased bone mass and altered bone architecture. The effects of intermittent PTH administration on bone microarchitecture differed in ,-arrestin2,/, and wildtype mice. These data indicate that arrestin-mediated regulation of intracellular signaling contributes to the differential effects of PTH at endosteal and periosteal bone surfaces. Introduction: The effects of PTH differ at endosteal and periosteal surfaces, suggesting that PTH activity in these compartments may depend on some yet unidentified mechanism(s) of regulation. The action of PTH in bone is mediated primarily by intracellular cAMP, and the cytoplasmic molecule ,-arrestin2 plays a central role in this signaling regulation. Thus, we hypothesized that arrestins would modulate the effects of PTH on bone in vivo. Materials and Methods: We used pDXA, ,CT, histomorphometry, and serum markers of bone turnover to assess the skeletal response to intermittent PTH (0, 20, 40, or 80 ,g/kg/day) in adult female mice null for ,-arrestin2 (,-arr2,/,) and wildtype (WT) littermates (7-11/group). Results and Conclusions: ,-arr2,/, mice had significantly lower total body BMD, trabecular bone volume fraction (BV/TV), and femoral cross-sectional area compared with WT. In WT females, PTH increased total body BMD, trabecular bone parameters, and cortical thickness, with a trend toward decreased midfemoral medullary area. In ,-arr2,/, mice, PTH not only improved total body BMD, trabecular bone architecture, and cortical thickness, but also dose-dependently increased femoral cross-sectional area and medullary area. Histomorphometry showed that PTH-stimulated periosteal bone formation was 2-fold higher in ,-arr2,/, compared with WT. Osteocalcin levels were significantly lower in ,-arr2,/, mice, but increased dose-dependently with PTH in both ,-arr2,/, and WT. In contrast, whereas the resorption marker TRACP5B increased dose-dependently in WT, 20-80 ,g/kg/day of PTH was equipotent with regard to stimulation of TRACP5B in ,-arr2,/,. In summary, ,-arrestin2 plays an important role in bone mass acquisition and remodeling. In estrogen-replete female mice, the ability of intermittent PTH to stimulate periosteal bone apposition and endosteal resorption is inhibited by arrestins. We therefore infer that arrestin-mediated regulation of intracellular signaling contributes to the differential effects of PTH on cancellous and cortical bone. [source] Glucocorticoid Excess During Adolescence Leads to a Major Persistent Deficit in Bone Mass and an Increase in Central Body FatJOURNAL OF BONE AND MINERAL RESEARCH, Issue 10 2001Veronica Abad Abstract Endogenous Cushing's syndrome (CS) in children causes growth retardation, decreased bone mass, and increased total body fat. No prospective controlled studies have been performed in children to determine the long-term sequelae of CS on peak bone mass and body composition. A 15-year-old girl with Cushing disease (CD), and her healthy identical co-twin, were followed for 6 years after the CD was cured. At the 6-year follow-up both twins had areal bone mineral density (BMD) and body composition determined by dual-energy X-ray absorptiometry (DXA) and three-dimensional quantitative computed tomography (3DQCT). Z scores for height, weight, and body mass index (BMI) were ,2.3, ,0.8 and 0.2, and 1.2, 0.2, and ,0.6, in the twin with CD and her co-twin, respectively. In the twin with CD, areal BMD and bone mineral apparent density (BMAD) at different sites varied from 0.7 to 3 SD below her co-twin. Volumetric lumbar spine bone density Z score was ,0.75 and 1.0, and total body, abdominal visceral, and subcutaneous fat (%) was 42, 10, and 41 versus 26, 4, and 17 in the twin with CD and her co-twin, respectively. The relationship between total body fat and L2-L4 BMAD was inverse in the twin with CD (p < 0.05), which by contrast in her co-twin was opposite and direct (p < 0.001). In the twin with CD, despite cure, there was a persistent deficit in bone mass and increase in total and visceral body fat. These observations suggest that hypercortisolism (exogenous or endogenous) during adolescence may have persistent adverse effects on bone and fat mass. [source] Stat1-mediated cytoplasmic attenuation in osteoimmunologyJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 2 2005Hiroshi Takayanagi Abstract Signal transducer and activator of transcription 1 (Stat1) is a critical mediator of gene transcription in type I interferon (IFN-,/,) signaling that is essential for host defense against viruses. In the skeletal system, type I IFNs (IFN-,/,) also play an important physiological role in the inhibition of receptor activator of NF-,B ligand (RANKL)-induced osteoclast differentiation and bone resorption: mice deficient in IFN signaling exhibit decreased bone mass accompanied by the activation of osteoclastogenesis. On the other hand, an unexpected increase in bone mass was observed in Stat1-deficient mice, indicating that Stat1 has a hitherto unknown function in the regulation of bone formation. Indeed, Stat1 was found to have a unique, non-canonical function as a cytoplasmic attenuator of Runx2, a key transcription factor for osteoblast differentiation. Thus, the loss of Stat1 results in excessive activation of Runx2 and osteoblast differentiation, thereby tipping the balance in favor of bone formation over bone resorption. This is an interesting example in which a latent transcription factor attenuates the activity of another transcription factor in the cytoplasm, and reveals a novel regulatory mechanism of bone remodeling by immunomodulatory molecules. Here, we summarize recent advances in the study of Stat1 and IFNs in the context of osteoimmunology, including latest reports that question whether the inhibitory function of Stat1 in chondrocytes is responsible for dwarfism in achondroplasia. © 2004 Wiley-Liss, Inc. [source] Assessment of Bone Mineralization Following Renal Transplantation in Children: Limitations of DXA and the Confounding Effects of Delayed Growth and DevelopmentAMERICAN JOURNAL OF TRANSPLANTATION, Issue 3 2001Mary B. Leonard Pediatric renal transplantation recipients have numerous risk factors for decreased bone mass, including the underlying renal disease, nutritional deficits, decreased physical activity, inflammation and exposure to steroid therapy. The assessment of bone mineralization in children following renal transplantation is fraught with difficulty. Dual energy x-ray absorptiometry (DXA) is the most commonly employed tool to assess bone mineralization. However, DXA has important limitations in children and in individuals with renal disease. This brief review will examine the expected gains in bone size and bone mass during growth and the mechanisms by which renal failure and steroid therapy interrupt these process. In addition, the limitations of DXA for detecting impaired bone mineralization in children with renal disease are reviewed and alternative approaches explored. [source] | ||||||||||