Clinical calcium最新文献

Biologics made a big paradigm shift in the treatment for rheumatoid arthritis(RA). In the next step, current research for RA shifts from traditional approach for average patients to precision medicine using huge omics data from patients. Multiomics analysis for the specimen from patients will play an important role for the establishment of precision medicine for RA.

Previous studies demonstrated that patients undergoing chronic dialysis therapy showed several times higher risks for hip fracture compared to those of healthy subjects. Their bone tissue would be vulnerable because of the bone loss and poor quality. In addition, volume and strength of the muscle are decreased and the ratio of sarcopenia or frailty is increased among these patients, accordingly leading to higher risks for falls and bone fractures. Considering the pathophysiology of bone fracture in dialysis patients, it is a matter of course that one wonders how effective recently developed medicine for"classical" osteoporosis is. However, evidence to guide us is currently lacking. Therefore, it is crucial for us to construct evidence by observational and interventional studies.

As of February 2018, 5 originator TNF inhibitors(infliximab, etanercept, adalimumab, golimumab and certolizumab pegol)and biosimilar agents of infliximab and etanercept are available for rheumatoid arthritis(RA)in Japan. The effectiveness of TNF inhibitors considerably improves with concomitant methotrexate regardless of their immunogenicity. The Japan College of Rheumatology guideline for TNF inhibitor use in RA has been updated in March 2017 according to recent evidences. During the remission induction phase, maintenance of drug trough level above effective blood concentration is paramount, while the tapering and withdrawal of TNF inhibitors may be considered after achieving sustained remission.

Osteoarthritis(OA)of the knee is a joint disease that is primarily affected by articular cartilage and also affected by subchondral bone and meniscus, leading to walking pain and impairing moving ability and as a result, disability. Knee OA is diagnosed by plain radiograph, however, it is not sensitive enough to detect the association between the pathophysiology and symptom of the disease. Treatment target of knee OA is to improve symptom, mainly pain. A conservative treatment is the principle of knee OA treatment, in which the combination of non-pharmacological and pharmacological treatment is primarily recommended. When the conservative treatment is ineffective, surgical treatment could be selected. It is estimated that there are 25 million people with radiographic knee OA in Japan. Recent researches using MRI and biomarkers, in addition to radiograph, have been revealed the precise mechanisms of pathophysiology of knee OA. Recently, it has been suggested that the pathophysiologies associated with pain in knee OA are altered depending upon the severity of disease. It has been expected that the pathophysiology of early stage knee OA will also be clarified.

Frailty and sarcopenia present significant risks for adverse outcomes such as disability, falls, and mortality in Japanese older adults. Among community-dwelling Japanese older adults, the prevalence of frailty, which was characterized using three or more limitations(shrinking, exhaustion, low activity, slowness, and weakness), was 5.2% and 12.0% in men and women, respectively. The prevalence of sarcopenia based on a diagnosis of low appendicular muscle mass, low grip strength, and low gait speed was 9.6% in men and 7.7% in women. Further, the prevalence of frailty with comorbidity of sarcopenia was 21.6% and 52.2% in men and women, respectively, and the prevalence of sarcopenia with comorbidity of frailty was 28.6% and 34.4% in men and women, respectively. The estimated number of prevalent cases of frailty, pre-frailty, and sarcopenia in Japanese older adults was approximately 3,090,000, 17,950,000, and 2,710,000, respectively.

The antirickets factor vitamin D exhibits its action through activation of vitamin D receptor(VDR). The active form of vitamin D, 1α,25-dihydroxyvitamin D3[1,25(OH)2D3], is a potent VDR ligand, and contributes to the maintenance of calcium homeostasis by enhancing intestinal calcium absorption, renal calcium reabsorption and bone resorption. 1,25(OH)2D3 also regulates bone formation, phosphorus metabolism and vitamin D metabolism. Experimental and epidemiological evidence has shown vitamin D actions on cellular proliferation and differentiation, immunity and inflammation, and cardiovascular function. Vitamin D derivatives and VDR ligands may be useful for the treatment of osteoporosis, malignancy, autoimmune and inflammatory disease and cardiovascular disease as well as rickets and osteomalacia.

Bones are the most frequent sites in patients with progressive prostate cancer. Spinal column and pelvic bone are vulnerable for metastasis, and osteoblastic lesions are frequently observed. Imaging evaluation is performed using bone scintigrapy with 99mTc, CT or MRI. Extent of disease is categorized as EOD score, and it is still used for evaluation of bone metastasis in clinical trials. Clinical guidelines recommend the uses of bone modifying agents including zoledronic acid and denosumab for bone metastasis in patients with castration-resistant prostate cancer. New androgen targeted agents, enzalutamide and abiraterone, or taxans, docetaxel and cabazitaxel, show clinical efficacy for bone metastasis of prostate cancer. Recently, metastasis free survival(MFS)has been approved as a primary endpoint for nonmetastatic castration-resistant prostate cancer. For this category, enzalutamide and apalutamide have been approved for patients with nonmetastatic castration-resistant prostate cancer. Treatment and follow-up strategy is now dramatically changed in the area of bone metastasis of prostate cancer.

Recently, it has been found that systemic metabolic disorders are associated with the onset and progression of various joint diseases. Although osteoarthritis(OA)is mainly a degradative condition of the articular cartilage induced by mechanical stress, there is a growing body of data demonstrating the involvement of metabolic factors including fat metabolism. Recent studies have revealed that adipokines including adiponectin and leptin are associated with inflammation of rheumatoid arthritis. A better understanding of these relationships may lead to new strategies to treat or prevent joint disease such as OA.

Bone tissue is a hard tissue, it was difficult to observe the interior of the bone tissue alive. With the progress of microscopic technology and fluorescent probe technology in recent years, it becomes possible to observe various activities of various cells forming bone society. On the other hand, the quantitative increase in data and the diversification and complexity of the images makes it difficult to perform quantitative analysis by visual inspection. It has been expected to develop a methodology for processing microscopic images and data analysis. In this article, we introduce the research field of bioimage informatics which is the boundary area of biology and information science, and then outline the basic image processing technology for quantitative analysis of live imaging data of bone.

Osteoblasts are bone-forming cells which produce bone matrix proteins and control calcium and mineral deposition. It is still unknown how osteoblasts work through the processes actually, because most of bone researches use static images of sections. Recently developed intravital imaging system with multiphoton microscopy can enable dynamic observation of living individual cells without making sections. This technique has so high-resolution in the Z direction that it is particularly useful for observation of deep tissues like bones. Here we introduce our data about osteoblast live cell imaging in vivo and in vitro including intravital imaging and summarize the latest reports about it.