Approximately 50% of women experience at least one bone fracture postmenopause. Current screening approaches target anti-fracture interventions to women aged >60 years who satisfy clinical risk and ...bone mineral density criteria for osteoporosis. Intervention is only recommended in 7-25% of those women screened currently, well short of the 50% who experience fractures. Large screening trials have not shown clinically significant decreases in the total fracture numbers. By contrast, six large clinical trials of anti-resorptive therapies (for example, bisphosphonates) have demonstrated substantial decreases in the number of fractures in women not identified as being at high risk of fracture. This finding suggests that broader use of generic bisphosphonates in women selected by age or fracture risk would result in a reduction in total fracture numbers, a strategy likely to be cost-effective. The utility of the current bone density definition of osteoporosis, which neither corresponds with who suffers fractures nor defines who should be treated, requires reappraisal.
The goal of osteoporosis management is to prevent fractures. Several pharmacological agents are available to lower fracture risk, either by reducing bone resorption or by stimulating bone formation. ...Bisphosphonates are the most widely used anti-resorptives, reducing bone turnover markers to low premenopausal concentrations and reducing fracture rates (vertebral by 50–70%, non-vertebral by 20–30%, and hip by ~40%). Bisphosphonates bind avidly to bone mineral and have an offset of effect measured in months to years. Long term, continuous use of oral bisphosphonates is usually interspersed with drug holidays of 1–2 years, to minimise the risk of atypical femoral fractures. Denosumab is a monoclonal antibody against RANKL that potently inhibits osteoclast development and activity. Denosumab is administered by subcutaneous injection every 6 months. Anti-fracture effects of denosumab are similar to those of the bisphosphonates, but there is a pronounced loss of anti-resorptive effect from 7 months after the last injection, which can result in clusters of rebound vertebral fractures. Two classes of anabolic drugs are now available to stimulate bone formation. Teriparatide and abaloparatide both target the parathyroid hormone-1 receptor, and are given by daily subcutaneous injection for up to 2 years. Romosozumab is an anti-sclerostin monoclonal antibody that stimulates bone formation and inhibits resorption. Romosozumab is given as monthly subcutaneous injections for 1 year. Head-to-head studies suggest that anabolic agents have greater anti-fracture efficacy and produce larger increases in bone density than anti-resorptive drugs. The effects of anabolic agents are transient, so transition to anti-resorptive drugs is required. The optimal strategy for cycling anabolics, anti-resorptives, and off-treatment periods remains to be determined.
In this article, we tackle the problem of depth estimation from single monocular images. Compared with depth estimation using multiple images such as stereo depth perception, depth from monocular ...images is much more challenging. Prior work typically focuses on exploiting geometric priors or additional sources of information, most using hand-crafted features. Recently, there is mounting evidence that features from deep convolutional neural networks (CNN) set new records for various vision applications. On the other hand, considering the continuous characteristic of the depth values, depth estimation can be naturally formulated as a continuous conditional random field (CRF) learning problem. Therefore, here we present a deep convolutional neural field model for estimating depths from single monocular images, aiming to jointly explore the capacity of deep CNN and continuous CRF. In particular, we propose a deep structured learning scheme which learns the unary and pairwise potentials of continuous CRF in a unified deep CNN framework. We then further propose an equally effective model based on fully convolutional networks and a novel superpixel pooling method, which is about 10 times faster, to speedup the patch-wise convolutions in the deep model. With this more efficient model, we are able to design deeper networks to pursue better performance. Our proposed method can be used for depth estimation of general scenes with no geometric priors nor any extra information injected. In our case, the integral of the partition function can be calculated in a closed form such that we can exactly solve the log-likelihood maximization. Moreover, solving the inference problem for predicting depths of a test image is highly efficient as closed-form solutions exist. Experiments on both indoor and outdoor scene datasets demonstrate that the proposed method outperforms state-of-the-art depth estimation approaches.
Fat and bone Reid, Ian R.
Archives of biochemistry and biophysics,
11/2010, Letnik:
503, Številka:
1
Journal Article
Recenzirano
Body weight is a principal determinant of bone density and fracture risk, and adipose tissue mass is a major contributor to this relationship. In contrast, some recent studies have argued that “fat ...mass after adjustment for body weight” actually has a deleterious effect on bone, but these analyses are confounded by the co-linearity between the variables studied, and therefore have produced misleading results. Mechanistically, fat and bone are linked by a multitude of pathways, which ultimately serve the function of providing a skeleton appropriate to the mass of adipose tissue it is carrying. Adiponectin, insulin/amylin/preptin, leptin and adipocytic estrogens are all likely to be involved in this connection. In the clinic, the key issues are that obesity is protective against osteoporosis, but underweight is a major preventable risk factor for fractures.
Summary Background Findings from recent meta-analyses of vitamin D supplementation without co-administration of calcium have not shown fracture prevention, possibly because of insufficient power or ...inappropriate doses, or because the intervention was not targeted to deficient populations. Despite these data, almost half of older adults (older than 50 years) continue to use these supplements. Bone mineral density can be used to detect biologically significant effects in much smaller cohorts. We investigated whether vitamin D supplementation affects bone mineral density. Methods We searched Web of Science, Embase, and the Cochrane Database, from inception to July 8, 2012, for trials assessing the effects of vitamin D (D3 or D2, but not vitamin D metabolites) on bone mineral density. We included all randomised trials comparing interventions that differed only in vitamin D content, and which included adults (average age >20 years) without other metabolic bone diseases. We pooled data with a random effects meta-analysis with weighted mean differences and 95% CIs reported. To assess heterogeneity in results of individual studies, we used Cochran's Q statistic and the I2 statistic. The primary endpoint was the percentage change in bone mineral density from baseline. Findings Of 3930 citations identified by the search strategy, 23 studies (mean duration 23·5 months, comprising 4082 participants, 92% women, average age 59 years) met the inclusion criteria. 19 studies had mainly white populations. Mean baseline serum 25-hydroxyvitamin D concentration was less than 50 nmol/L in eight studies (n=1791). In ten studies (n=2294), individuals were given vitamin D doses less than 800 IU per day. Bone mineral density was measured at one to five sites (lumbar spine, femoral neck, total hip, trochanter, total body, or forearm) in each study, so 70 tests of statistical significance were done across the studies. There were six findings of significant benefit, two of significant detriment, and the rest were non-significant. Only one study showed benefit at more than one site. Results of our meta-analysis showed a small benefit at the femoral neck (weighted mean difference 0·8%, 95% CI 0·2–1·4) with heterogeneity among trials ( I2 =67%, p<0·00027). No effect at any other site was reported, including the total hip. We recorded a bias toward positive results at the femoral neck and total hip. Interpretation Continuing widespread use of vitamin D for osteoporosis prevention in community-dwelling adults without specific risk factors for vitamin D deficiency seems to be inappropriate. Funding Health Research Council of New Zealand.
Progress continues to be made in the development of therapeutics for fracture prevention. Bisphosphonates are now available orally and intravenously, often as inexpensive generics, and remain the ...most widely used interventions for osteoporosis. The major safety concern associated with the use of bisphosphonates is the development of femoral shaft stress fractures and, although rare, this adverse event affords the principal rationale for restricting bisphosphonate therapy to those individuals with femoral T-scores <-2.5, and for providing drug holidays in those individuals requiring therapy for >5 years. Newer antiresorptive therapies, in the form of denosumab and cathepsin K inhibitors, might increase efficacy and possibly circumvent some of the safety concerns associated with bisphosphonate use (for example, gastrointestinal and renal complications). The combination of teriparatide with antiresorptives markedly increases effects on BMD; new anabolic agents are also very promising in this regard. However, whether or not these changes in BMD translate into improved efficacy of fracture prevention remains to be determined. Vitamin D is important for the prevention of osteomalacia, but does not influence BMD or fracture risk in patients not deficient in vitamin D. The balance of risks and benefits of calcium supplementation is contentious, but patients should be encouraged to adhere to a balanced diet aimed at maintaining a healthy body weight. Consideration of a patient's risk of falling, and its mitigation, are also important. In this Review, I summarize the short-term and long-term effects of osteoporosis therapies.
Effects of Leptin on the Skeleton Reid, Ian R; Baldock, Paul A; Cornish, Jillian
Endocrine reviews,
2018-December, Letnik:
39, Številka:
6
Journal Article
Recenzirano
Odprti dostop
Abstract
Leptin originates in adipocytes, including those in bone marrow, and circulates in concentrations 20 to 90 times higher than those in the cerebrospinal fluid. It has direct anabolic effects ...on osteoblasts and chondrocytes, but it also influences bone indirectly, via the hypothalamus and sympathetic nervous system, via changes in body weight, and via effects on the production of other hormones (e.g., pituitary). Leptin's role in bone physiology is determined by the balance of these conflicting effects. Reflecting this inconsistency, the leptin-deficient mouse has reduced length and bone mineral content of long bones but increased vertebral trabecular bone. A consistent bone phenotype in human leptin deficiency has not been established. Systemic leptin administration in animals and humans usually exerts a positive effect on bone mass, and leptin administration into the cerebral ventricles usually normalizes the bone phenotype in leptin-deficient mice. Reflecting the role of the sympathetic nervous system in mediating the central catabolic effects of leptin on the skeleton, β-adrenergic agonists and antagonists have major effects on bone in mice, but this is not consistently seen in humans. The balance of the central and peripheral effects of leptin on bone remains an area of substantial controversy and might vary between species and according to other factors such as body weight, baseline circulating leptin levels, and the presence of specific pathologies. In humans, leptin is likely to contribute to the positive relationship observed between adiposity and bone density, which allows the skeleton to respond appropriately to changes in soft tissue mass.
Objective To determine whether increasing calcium intake from dietary sources affects bone mineral density (BMD) and, if so, whether the effects are similar to those of calcium supplements.Design ...Random effects meta-analysis of randomised controlled trials.Data sources Ovid Medline, Embase, Pubmed, and references from relevant systematic reviews. Initial searches were undertaken in July 2013 and updated in September 2014.Eligibility criteria for selecting studies Randomised controlled trials of dietary sources of calcium or calcium supplements (with or without vitamin D) in participants aged over 50 with BMD at the lumbar spine, total hip, femoral neck, total body, or forearm as an outcome.Results We identified 59 eligible randomised controlled trials: 15 studied dietary sources of calcium (n=1533) and 51 studied calcium supplements (n=12 257). Increasing calcium intake from dietary sources increased BMD by 0.6-1.0% at the total hip and total body at one year and by 0.7-1.8% at these sites and the lumbar spine and femoral neck at two years. There was no effect on BMD in the forearm. Calcium supplements increased BMD by 0.7-1.8% at all five skeletal sites at one, two, and over two and a half years, but the size of the increase in BMD at later time points was similar to the increase at one year. Increases in BMD were similar in trials of dietary sources of calcium and calcium supplements (except at the forearm), in trials of calcium monotherapy versus co-administered calcium and vitamin D, in trials with calcium doses of ≥1000 versus <1000 mg/day and ≤500 versus >500 mg/day, and in trials where the baseline dietary calcium intake was <800 versus ≥800 mg/day.Conclusions Increasing calcium intake from dietary sources or by taking calcium supplements produces small non-progressive increases in BMD, which are unlikely to lead to a clinically significant reduction in risk of fracture.
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