Clinical calcium最新文献

Bisphosphonates are effective in decreasing bone resorption, the incidence of fragility fracure, and pain from bone metastases. Although relatively well tolerated, the initial dose(s)of intravenous or oral monthly aminobisphosphonates can be associated with an acute phase response, a nonspecific physiologic reaction associated with increased levels of inflammatory cytokines, fever, and flu like symptoms including fatigue, nausea, and myalgia within 3 days of dosing and lasting 7 days or less. Nitrogen-BPs(N-BPs)inhibit osteoclast function by acting as potent inhibitors of the enzyme farnesyl diphosphate(FPP)synthase in the mevalonate biosynthetic pathway. Following an intravenous infusion or oral monthly BPs, transient uptake of N-BP into peripheral blood monocytes results in intracellular accumulation of isopentenyl diphosphate(IPP)due to FPP synthase inhibition. Recognition of IPP by γδT cells triggers their activation and expansion, resulting in the release of pro-inflammatory cytokines that cause the flulike symptoms of the acute phase reaction. There is trial evidence that its severity can be reduced by more than half with coadministration of acetaminophen, so the short-term use of these drugs to lessen the APR is advisable in patients receiving their first dosing of N-BPs. Levels of 25(OH)D were negatively correlated with the incidence and severity of APR. Vitamin D reduces the intensity of musculoskeletal pain after dosing of N-BPs for postmenopausal osteoporosis. APR has minimal impact on long-term adherence to therapy. It is less common in subjects who have previously used bisphosphonates. Information of APR to a patient is important before administration.

Exercise and sports are an important means of improving bone health in pre- and postmenopausal women. Generally accepted strategies to improve bone health in this population aim to minimize age-related bone loss. In terms of physical activity, those forms that feature high-impact or weight-bearing activity appear to exert positive influences on bone health. Results of recent meta-analyses have shown that high-impact exercise significantly improves bone mineral density(BMD)in pre- and postmenopausal women. Studies have also shown that walking as an exercise therapy for more than 6 months exerts significant and positive effects on femoral neck BMD in peri- and postmenopausal women. Exercise and sports can be strongly recommended as non-pharmacologic interventions for improving bone health in pre- and postmenopausal women.

Physical activity plays an important role in maintaining or enhancing bone health. Jumping exercise increases bone mineral content(BMC)in prepubescent children(premenarcheal girls). Bone mineral density(BMD)is higher in adolescent athletes who are engaged in weight-bearing activities. Jumping exercise, muscle strengthening exercise, and weight-bearing plus muscle strengthening exercises increase BMD in young adults and premenopausal women. Walking, aerobic weight-bearing exercise, muscle strengthening exercise, and weight-bearing plus muscle strengthening exercises maintain or increase BMD in postmenopausal women. Proper exercise and sports activity at each life stage are important strategies for preventing osteoporosis.

Bisphosphonates have been explored possible combination and/or sequential use with other anti-osteoporotic medications including PTH. Besides with vitamin D(metabolites), combination treatment had been uncommon mainly because there had not been enough anti-fracture evidence. PTH, which can only be used for a certain period over lifetime, requires other anti-osteoporotic medications after and/or before its use. Bisphosphonates have been tried with PTH in various sequential and/or combination ways. Various combination and/or sequential therapy using bisphosphonates will be reviewed in this article.

Cases discontinuing bisphosphonates(BPs)include cases due to adverse effects, non adherence, no effectiveness, and lower risk of fragile fractures. For patients with osteonecrosis of the jaw or atypical femoral fracture, discontinuation of BPs and the switch to Teriparatides may be recommended until the treatments are completed. For the patients of discontinuation of BPs due to lower risk of fractures, the treatment strategy will be determined based on the presence or absence of fracture, the change of bone mineral density and bone resorption markers.

The skeletal muscle has high sensitivity for the mechanical stress. Because it is enlarged by training, whereas it is easily withered by lack of exercise. When we exercise, skeletal muscle cells per se sense mechanical loading, and muscular remodeling and the muscular hypertrophy occur. It has been revealed that the intracellular signaling through PGC-1α participates in the remodeling of the skeletal muscle, while PGC-1α4, an isoform of PGC-1α, and the dystrophin-glycoprotein complex play important roles in muscular hypertrophy. This review describes the impact of physical exercise gives on the remodeling and hypertrophy of muscle through the signaling.

Long-term treatment studies on the use of bisphosphonate(BP)for more than 5 years have been reported for alendronate, risedronate, and zoledronic acid. Bone mineral density(BMD)increases over the long term;however, a large increase has been observed over a 2 to 3 year period after initiation of BP treatment followed by gradual BMD increase and achieving a state of stability. After an initial reduction, the levels of bone remodeling markers remained stable within the premenopausal range during long-term BP treatment. BPs reduce fracture risk over a 5 to 6 year period and residual anti-fracture effects are observed after discontinuation.

Joints are composed of several different tissues(cartilage, capsule, meniscus, and ligament), and articular cartilage plays an important role in maintaining mechanical competence during exercise. Weight-bearing exercise has several benefit, including improved blood and synovial fluid circulation in a given joint. Consistent moderate activities facilitate cycles of anabolism and catabolism. Mechanical stresses are crucial for the maintenance of the morphologic and functional integrity of articular cartilage. Healthy cartilage is exposed by hydrostatic pressure and tensile strain, when cartilage degeneration develops, abnormal cartilage is exposed by shear stress. Moderate(physiological)exercise is characterized by a range of equilibrium between matrix anabolic and catabolic processes, or anabolism beyond catabolism. Joints are susceptible to insufficient or excessive activities, leading to joint degeneration. Lack of exercise is known to induce joint contracture seen clinically as a consequence of disuse changes, and excess mechanical stresses induce joint destruction such as osteoarthritis. Joint diseases resulting from insufficient or excessive activities are new and major challenging issues with our aging population. Thus, it is highly desirable to have an effective and efficient treatment to improve and protect against these joint diseases, and thereby to solve these clearly unanswered issues.

Marx first reported avascular osteonecrosis of the jaw(ONJ)in oncology patients who had used high dose intravenous bisphosphonate(BP)at 2003. Ruggiero et al. also reported BP-related ONJ in osteoporosis patients who had used low dose oral BP at 2004. Since tooth extraction was considered one of risk factors for ONJ, discontinuation of BP before and after tooth extraction was recommended as one of preventive strategy for ONJ, especially in osteoporosis patients. However, recent studies showed that discontinuation of BP did not prevent ONJ, but increased the occurrence of adverse events such as fracture. Best strategies for preventing ONJ include elimination of oral disease such as periodontal and/or periapical diseases prior to initiation of BP, as well as maintenance of good oral hygiene. Development of a strategy for sharing information about ONJ among physicians, dentists, and patients is required to reduce the incidence of ONJ.

From 1990s to 2000s, new drugs for osteoporosis have been developed, and the bone metabolism researches have livened up. In those days, many a people gathered to the meeting from many countries, and the each booth of pharmaceutics was proud of its preeminence. The dedications by the society and its members have had osteoporosis diagnostics developed, the anchor drugs become prevalent, and the number of fractures reduced. Although the brilliant effects of Romosozumab and Abaloparatide were presented in the meeting held this year, the members had to accept the convergence state of new drug developments. But some problems have been still left unsolved, the development of more effective drugs to prevent fragile bone fractures without any adverse events, the safety of long term use of the osteoporosis drugs, and the effectiveness of drugs to prevent from fractures of the oldest old people.