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Women with anorexia nervosa (AN) have increased marrow fat despite severe depletion of body fat. Recent studies have suggested that marrow fat composition may serve as a biomarker for bone quality. The purpose of our study was to investigate marrow fat composition of the femur using proton MR spectroscopy ( 1 H MRS), and the relationship between measures of marrow fat composition and BMD and...
The strength of trabecular bone depends on its microarchitecture and its tissue level properties. However, the interrelation between these two determinants of bone quality and their relation to age remain to be clarified. Iliac crest bone cores (n=152) from individuals aged 30–90years were analyzed by quantitative backscattered electron imaging. Univariate and multivariate analyses were conducted...
Calcification of end plate chondrocytes is a major cause of intervertebral disc (IVD) degeneration. However, the underlying molecular mechanism of end plate chondrocyte calcification is still unclear. The aim of this study was to clarify whether autophagy in end plate chondrocytes could protect the calcification of end plate chondrocytes. Previous studies showed that intermittent cyclic mechanical...
Icariin, a prenylated flavonol glycoside isolated from Epimedii herba, has been found to be a potent stimulator of osteogenic differentiation and has potential application in preventing bone loss. However, the signaling pathway underlying its osteogenic effect remains unclear. We hypothesized that the osteogenic activity of icariin is related to the nitric oxide (NO) signal pathway and PI3K/AKT pathway...
Data for fibroblast growth factor 23 (FGF23) and particularly for Klotho in healthy children are limited. We aimed to investigate the relationship between FGF23 and Klotho with age and TmP/GFR and to evaluate parameters that might affect FGF23 and Klotho. In 159 healthy children (82 boys) with a mean±SD age of 8.78±3.47years we measured FGF23 (intact FGF23/iFGF23 and C-terminal FGF23/cFGF23) and soluble...
Osteoarthritis (OA) is a non-rheumatoid joint disease characterized by progressive degeneration of extra-cellular cartilage matrix (ECM), enhanced subchondral bone remodeling, osteophyte formation and synovial thickening. Alendronate (ALN) is a potent inhibitor of osteoclastic bone resorption and results in reduced bone remodeling. This study investigated the effects of pre-emptive use of ALN on OA...
Cathepsin K (CatK) is a cysteine protease, expressed predominantly in osteoclasts (OC) which degrades demineralized bone matrix. Novel selective inhibitors of CatK are currently being developed for the treatment of postmenopausal osteoporosis. Pharmacological inhibition of CatK reduces OC resorption activity while preserving bone formation in preclinical models. Disruption of the CatK gene in mice...
Osteogenesis imperfecta is a genetic disorder resulting in bone fragility. The mechanisms behind this fragility are not well understood. In addition to characteristic bone mass deficiencies, research suggests that bone material properties are compromised in individuals with this disorder. However, little data exists regarding bone properties beyond the microstructural scale in individuals with this...
Several factors associated with bone mineral density (BMD) increase are reported with daily teriparatide treatment, but there has been no systematic analysis to summarize these associations. The purpose of this study was to investigate the clinical determinants associated with BMD increase to daily teriparatide treatment.This was a retrospective study. We performed an analysis of 306 patients diagnosed...
Subchondral cysts are deeply related to the pathogenesis of osteoarthritis (OA), but the factors contributing to cyst formation are not well known. A three-dimensional analysis of subchondral cysts at the micro-structural level was conducted using a high-resolution peripheral quantitative CT (HR-pQCT), and their relationships with cartilage attrition and subchondral bone microstructure were investigated...
Osteogenesis imperfecta (OI) is a heritable bone fragility disorder that is usually caused by mutations affecting collagen type I production in osteoblasts. Stimulation of bone formation through sclerostin antibody treatment (Sost-ab) has shown promising results in mouse models of relatively mild OI. We assessed the effect of once-weekly intravenous Sost-ab injections for 4weeks in male Col1a1 ...
The in vivo mouse tibial loading model has been increasingly used to understand the mechanisms governing the mechanobiological responses of cancellous and cortical bone tissues to physical stimuli. Accurate characterization of the strain environment throughout the tibia is fundamental in relating localized mechanobiological processes to specific strain stimuli in the skeleton. MicroCT-based finite...
Atypical femoral fractures (AFFs) are stress-related fractures that are speculated to associate with long-term treatment with bisphosphonates for osteoporosis. A history of AFF is a high risk factor for the development of a subsequent AFF in the same location of the contralateral femur, suggesting that a patient's individual anatomical factor(s) are related to the fracture site of AFFs. In this study,...
Cortical bone is typically regarded as “MR invisible” with conventional clinical magnetic resonance imaging (MRI) pulse sequences. However, recent studies have demonstrated that free water in the microscopic pores of cortical bone has a short T2* but a relatively long T2, and may be detectable with conventional clinical spin echo (SE) or fast spin echo (FSE) sequences. In this study we describe the...
Metastatic bone disease has a major impact on the morbidity and mortality of breast cancer patients, and studies on bone metastasis biology have led to the development of the most widely used drugs for bone metastases treatment: zoledronate (Zol) and denosumab (Den). The aim of the present study was to assess the effect of soluble mediators produced by breast cancer cells on human osteoclast maturation...
Mechanical loading can increase cortical bone mass by shifting the balance between bone formation and resorption towards increased formation. With advancing age resorption outpaces formation resulting in a net loss in cortical bone mass. How cortical bone (re)modeling – especially resorption – responds to mechanical loading with aging remains unclear. In this study, we investigated age-related changes...
In pediatric surgeries, cutaneous scarring is frequently accompanied by an arrest in skeletal growth. The molecular mechanisms responsible for this effect are not understood. Here, we investigated the relationship between scar contracture and osteogenesis. An excisional cutaneous wound was made on the tail of neonatal mice. Finite element (FE) modeling of the wound site was used to predict the distribution...
The aim of this study is to investigate how bone strength in the distal femur and proximal tibia are related to local muscle volume in ambulant individuals with bilateral spastic cerebral palsy (CP).Twenty-seven participants with CP (mean age: 14.6±2.9years; Gross Motor Function Classification System (GMFCS) levels I-III) and twenty-two typically developing (TD) peers (mean age: 16.7±3.3years) took...
Runx2 and Axin2 regulate skeletal development. We recently determined that Axin2 and Runx2 molecularly interact in differentiating osteoblasts to regulate intramembranous bone formation, but the relationship between these factors in endochondral bone formation was unresolved. To address this, we examined the effects of Axin2 deficiency on the cleidocranial dysplasia (CCD) phenotype of Runx2 +/−...
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