BoneKEy reports最新文献

Osteoporosis presents as increased susceptibility to fractures due to bone loss and compromised bone microstructure. Osteoporosis mainly affects the elderly population, but it is increasingly recognized that compromised bone health with low bone mass and increased fractures may have its onset already in childhood. In such cases, genetic component is likely to contribute more than lifestyle factors to disease onset. During the last decade, our understanding of the genetic determinants of osteoporosis has significantly increased through family studies, candidate gene studies and genome-wide association studies (GWASs). GWASs have led to identification of several genetic loci associated with osteoporosis. A valuable contribution to the research field has been made through studies involving families with childhood-onset rare bone diseases such as osteogenesis imperfecta, osteoporosis-pseudoglioma syndrome and various other skeletal dysplasias with reduced bone mass. Some genes involved in rare low bone mass diseases, such as LRP5 and WNT1, participate in the Wnt/β-catenin pathway, and their discovery has underscored the importance of this pathway for normal skeletal health. The still continuing discovery of gene defects underlying various low bone mass phenotypes contributes to our understanding of normal bone metabolism and enables development of new therapies for osteoporosis.

Bone marrow lesions (BMLs) or using older terminology 'Bone marrow edema' is characterised by excessive water signals in the marrow space on magnetic resonance imaging or ultrasound; BMLs constitute a central component of a wide variety of inflammatory and non-inflammatory rheumatologic conditions affecting the musculoskeletal system: BMLs are not only considered significant sources of pain but also linked to increased disease activity in many musculoskeletal conditions (for example, osteoarthritis, rheumatoid arthritis). The purpose of this review is to summarise current knowledge about the treatment of BMLs, with an emphasis on the clinical and histological features of this entity in inflammatory and non-inflammatory disease. We also try to pair this hypothesis with the apparent beneficial effects of various treatment regimens, mainly within the group of bone antiresorptive drugs (calcitonin, bisphosphonates) on symptoms associated with BMLs.

Paget's disease of bone (PDB) is a common metabolic bone disease characterised by focal areas of increased bone turnover, which primarily affects people over the age of 55 years. Genetic factors have a fundamental role in the pathogenesis of PDB and are probably the main predisposing factor for the disease. The genetic contribution to PDB susceptibility ranges from rare pathogenic mutations in the single gene SQSTM1 to more common, small effect variants in at least seven genetic loci that predispose to the disease. These loci have additive effects on disease susceptibility and interact with SQSTM1 mutations to affect disease severity, making them a potentially useful tool in predicting disease risk and complication and in managing treatments. Many of these loci harbour genes that have important function in osteoclast differentiation such as CSF1, DCSTAMP and TNFRSF11A. Other susceptibility loci have highlighted new molecular pathways that have not been previously implicated in regulation of bone metabolism such as OPTN, which was recently found to negatively regulate osteoclast differentiation. PDB-susceptibility variants exert their effect either by affecting the protein coding sequence such as variants found in SQSTM1 and RIN3 or by influencing gene expression such as those found in OPTN and DCSTAMP. Epidemiological studies indicate that environmental triggers also have a key role in PDB and interact with genetic factors to influence manifestation and severity of the disease; however, further studies are needed to identify these triggers.

Skeletal lesions contribute substantially to morbidity and mortality in patients with cancer. The disease manifestation course during metastatic bone disease is driven by tumour cells in the bone marrow, which alter the functions of bone-resorbing (osteoclasts) and bone-forming (osteoblasts) cells, promoting skeletal destruction. Successful therapeutic strategies for the treatment of metastatic bone disease include bisphosphonates and denosumab that inhibit osteoclast-mediated bone resorption. Inhibitors of cathepsin K, Src and activin A are under clinical investigation as potential anti-osteolytics. In this review, we describe current knowledge and future directions of antiresorptive therapies that may reduce or prevent destructive bone lesions from solid tumours and multiple myeloma.

The bone contains the bone marrow. The functional communication between bone cells and hematopoiesis has been extensively studied in the past decade or so. Osteolineage cells and their modulators, such as the sympathetic nervous system, macrophages and osteoclasts, form a complex unit to maintain the homeostasis of hematopoiesis, called the 'microenvironment'. Recently, bone-embedded osteocytes, the sensors of gravity and mechanical stress, have joined the microenvironment, and they are demonstrated to contribute to whole body homeostasis through the control of immunity and energy metabolism. The inter-organ communication orchestrated by the bone is summarized in this article.