Bone
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Randomized Controlled Trial
Effect of denosumab on bone density and turnover in postmenopausal women with low bone mass after long-term continued, discontinued, and restarting of therapy: a randomized blinded phase 2 clinical trial.
Denosumab is a fully human monoclonal antibody that inhibits receptor activator of nuclear factor-kappa B ligand (RANKL), an essential mediator of osteoclast formation, function, and survival that has been shown to decrease bone turnover and increase bone mineral density (BMD) in treated patients. We assessed the long-term efficacy and safety of denosumab, and the effects of discontinuing and restarting denosumab treatment in postmenopausal women with low bone mass. ⋯ In postmenopausal women with low BMD, long-term denosumab treatment led to gains in BMD and reduction of BTM throughout the course of the study. The effects on bone turnover were fully reversible with discontinuation and restored with subsequent retreatment.
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Randomized Controlled Trial
Low-intensity pulsed ultrasound increases bone volume, osteoid thickness and mineral apposition rate in the area of fracture healing in patients with a delayed union of the osteotomized fibula.
Low-intensity pulsed ultrasound (LIPUS) accelerates impaired fracture healing, but the exact mechanism is unknown. The aim of this study was to investigate how LIPUS affects bone healing at the tissue level in patients with a delayed union of the osteotomized fibula, by using histology and histomorphometric analysis to determine bone formation and bone resorption parameters. ⋯ Our results suggest that LIPUS accelerates clinical fracture healing of delayed unions of the fibula by increasing osteoid thickness, mineral apposition rate, and bone volume, indicating increased osteoblast activity, at the front of new bony callus formation. Improved stability and/or increased blood flow, but probably not increased angiogenesis, might explain the differences in ossification modes between LIPUS-treated delayed unions and untreated controls.
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Low-trauma fractures of older adults have been recognized as a major public health problem in developed societies with aging populations. However, nationwide information on recent fracture trends is rather scarce. ⋯ The sharp increase in the incidence of low-trauma ankle fracture in Finnish older adults from early 1970s until late 1990s has been followed by stabilized, slightly declining fracture rates. Reasons for this are not known, but a cohort effect toward a healthier aging population with improved functional ability and reduced risk of injurious slips, trips and falls could partly explain the phenomenon.
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Nicotine is the main chemical in cigarettes responsible for the tobacco's pathological effects. The influence of nicotine on bone healing remains controversial. Distraction osteogenesis provides an ideal model to study bone healing and regeneration. ⋯ Frequent appearance of cartilage islands suggested ischemia and low oxygen tension in the distraction regenerate. We concluded that nicotine compromises bone regeneration possibly by causing ischemia and directly inhibitory effect on osteoblastic cells. Nicotine exposure enhances angiogenesis but cannot compensate for the adverse effect of vasoconstriction.
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Pro-inflammatory mediators formed by the kallikrein-kinin system can stimulate bone resorption and synergistically potentiate bone resorption induced by IL-1 and TNF-alpha. We have shown that the effect is associated with synergistically enhanced RANKL expression and enhanced prostaglandin biosynthesis, due to increased cyclooxygenase-2 expression. In the present study, the effects of osteotropic cytokines and different kinins on the expression of receptor subtypes for bradykinin (BK), des-Arg10-Lys-BK (DALBK), IL-1beta and TNF-alpha have been investigated. ⋯ These data show that IL-1beta and TNF-alpha upregulate B1 and B2 receptor expression by mechanisms involving activation of both NF-kappaB and MAP kinase pathways, but that signal transduction pathways are different for IL-1beta and TNF-alpha. The enhanced kinin receptor expression induced by the pro-inflammatory cytokines IL-1beta and TNF-alpha might be one important mechanism involved in the synergistic enhancement of prostaglandin formation caused by co-treatment with kinins and one of the two cytokines. These mechanisms might help to explain the enhanced bone resorption associated with inflammatory disorders, including periodontitis and rheumatoid arthritis.