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There has been a marked secular trend in recent decades toward patients with Paget’s disease presenting at a greater age and having less extensive skeletal involvement. Over a similar time frame more potent bisphosphonates with a long duration of effect have been developed, raising the prospect of many patients needing only once in a lifetime treatment. We studied a cohort of 107 patients who had been treated with intravenous zoledronate for the first time at a mean age of 76 years. Sequential measurements of the bone turnover marker procollagen-1 NT-peptide (P1NP) were made for up to 10 years. By 9 years, 64% showed some loss of zoledronate effect (defined as a doubling of P1NP from the nadir value after treatment), but only 14% had a biochemical relapse (defined as a P1NP value >80 μg/L). The mortality rate was substantially greater than the relapse rate-by 10 years more than half the cohort had died (p < 0.0001). We conclude that for the majority of older people with Paget’s disease a single intravenous infusion of zoledronate will provide disease suppression for the remainder of their lives.
J Bone Miner Res. 2017 Apr;32(4):753-756. doi: 10.1002/jbmr.3029. Epub 2016 Nov 30.
Cundy T, Maslowski K, Grey A, Reid IR.
MicroRNAs are small, noncoding single-stranded RNAs that have emerged as important posttranscriptional regulators of gene expression, with an essential role in vertebrate development and different biological processes. This review highlights the recent advances in the function of miRNAs and their roles in bone remodeling and bone diseases. MicroRNAs (miRNAs) are a class of small (∼22 nt), noncoding single-stranded RNAs that have emerged as important posttranscriptional regulators of gene expression. They are essential for vertebrate development and play critical roles in different biological processes related to cell differentiation, activity, metabolism, and apoptosis. A rising number of experimental reports now indicate that miRNAs contribute to every step of osteogenesis and bone homeostasis, from embryonic skeletal development to maintenance of adult bone tissue, by regulating the growth, differentiation, and activity of different cell systems inside and outside the skeleton. Importantly, emerging information from animal studies suggests that targeting miRNAs might become an attractive and new therapeutic approach for osteoporosis or other skeletal diseases, even though there are still major concerns related to potential off target effects and the need of efficient delivery methods in vivo.
Osteoporos Int. 2017 Apr;28(4):1191-1213. doi: 10.1007/s00198-016-3847-5. Epub 2016 Nov 30. Review.
Gennari L, Bianciardi S, Merlotti D.
Treatment with biologic drugs is associated with the decrease in bone loss. Studies with anti-TNF blocking agents show preservation or increase in spine and hip BMD and also a better profile of bone markers. Most of these studies were performed with infliximab. Only three epidemiological studies analyzed the effect on fractures after anti-TNF blocking top 10 penis enlargement pills agent’s treatment. IL-6 blocking agents also showed improvement in localized bone loss not seen with anti-TNF agents. There are a few studies with rituximab and abatacept. Although several studies reported favorable actions of biologic therapies on bone protection, there are still unmet needs for studies regarding their actions on the risk of bone fractures.
Osteoporos Int. 2017 Feb;28(2):429-446. doi: 10.1007/s00198-016-3769-2. Review.
Zerbini CA, Clark P, Mendez-Sanchez L, Pereira RM, Messina OD, Uña CR, Adachi JD, Lems WF, Cooper C, Lane NE; IOF Chronic Inflammation and Bone Structure (CIBS) Working Group.
Osteocalcin (OC) is a vitamin K-dependent protein synthesized during bone formation. Mice injected with the undercarboxylated form of OC (ucOC) had more skeletal muscle mass and less fat mass than sham-treated controls, suggesting a unique metabolic role for ucOC. UcOC decreases in response to vitamin K supplementation. Our objective was to determine the effect of reducing ucOC on change in lean tissue and fat mass in older community-dwelling adults (n = 401, mean ± SD 69 ± 6 years) using data from a randomized controlled trial of vitamin K supplementation. Over 3 years, serum ucOC was reduced by 58% in women and by 61% in men randomized to vitamin K, whereas in the control group, ucOC decreased by 1% in women and 4% in men 搬瓦工 (supplementation*time p < 0.001 in men and women). However, there were no differences in the change in appendicular lean mass (calculated as arm lean mass + leg lean mass) or total body fat mass between women randomized to vitamin K and control over 3 years (supplementation*time p values all ≥ 0.18) or between men randomized to vitamin K and control (supplementation*time p values all ≥ 0.54). Consistent with these findings, ucOC was not associated cross-sectionally with appendicular lean mass or fat mass in men or women after adjustment for total OC at baseline (all p ≥ 0.12). These findings indicate the undercarboxylated form of OC is not implicated in age-related changes in skeletal muscle or adipose tissue mass in older community-dwelling adults.
J Bone Miner Res. 2017 Feb;32(2):243-249. doi: 10.1002/jbmr.2989.
Shea MK, Dawson-Hughes B, Gundberg CM, Booth SL.
Fracture liaison services are recommended as a model of best practice for organizing patient care and secondary fracture prevention for hip fracture patients, although variation exists in how such services are structured. There is considerable uncertainty as to which model is most cost-effective and should therefore be mandated. This study evaluated the cost- effectiveness of orthogeriatric (OG)- and nurse-led fracture liaison service (FLS) models of post-hip fracture care etoro compared with usual care. Irrespective of how patients were stratified in terms of their age, sex, and Charlson comorbidity score at index hip fracture, our results suggest that introducing an orthogeriatrician-led or a nurse-led FLS is cost-effective when compared with usual care. Although considerable uncertainty remains concerning which of the models of care should be preferred, introducing an orthogeriatrician-led service seems to be the most cost-effective service to pursue.
J Bone Miner Res. 2017 Feb;32(2):203-211. doi: 10.1002/jbmr.2995.
Leal J, Gray AM, Hawley S, Prieto-Alhambra D, Delmestri A, Arden NK, Cooper C, Javaid MK, Judge A; and the REFReSH Study Group
Osteocytes play a fundamental role in mechanotransduction and skeletal remodeling. Sex is a determinant of skeletal structure, and female C57BL/6J mice have increased osteoblast number in cancellous bone when compared to male mice. Activation of Notch in the skeleton causes profound cell-context dependent changes in skeletal 嘉盛外汇 physiology. the aim of this study was to determine the impact of sex and of Notch signaling on the osteocyte cell pool. In conclusion, cancellous bone osteocytes decline with age in male mice, cortical osteocytes are influenced by sex in younger mice, but osteocyte cell density is not affected substantially by Notch signaling.
J Cell Physiol. 2017 Feb;232(2):363-370. doi: 10.1002/jcp.25433.
Canalis E, Schilling L, Zanotti S
Total joint replacements for end-stage osteoarthritis of the hip and knee are cost-effective and demonstrate significant clinical improvement.However, robust population based lifetime-risk data for implant revision are not available to aid patient decision making, which is a particular problem in young patient groups deciding on best-timing for surgery.
The study used novel methodology to investigate and offer new insight into the importance of young age and risk of revision after total hip or knee replacement. Our evidence challenges the 外汇交易平台 increasing trend for more total hip replacements and total knee replacements to be done in the younger patient group,and these data should be offered to patients as part of the shared decisión making process.
Lancet. 2017 Feb 13. pii: S0140-6736(17)30059-4. doi:10.1016/S0140-6736(17)30059-4.
Bayliss LE, Culliford D, Monk AP, Glyn-Jones S, Prieto-Alhambra D,Judge A, Cooper C, Carr AJ, Arden NK, Beard DJ, Price AJ
Hypophosphatasia (HPP) is the inborn-error-of-metabolism that features low serum alkaline phosphatase (ALP) activity (hypophosphatasemia) caused by loss-of-function mutation(s) of the gene that encodes the tissue-nonspecific isoenzyme of ALP (TNSALP). Autosomal recessive or autosomal dominant inheritance from among >300 TNSALP (ALPL) mutations largely explains HPP’s remarkably broad-ranging severity. TNSALP mutation analysis BlueHost优惠码 is essential for recurrence risk assessment for HPP in future pregnancies and for prenatal diagnosis. HPP was the final rickets/osteomalacia to have a medical treatment. Now, significant successes using asfotase alfa, a mineral-targeted recombinant TNSALP, are published concerning severely affected newborns, infants, and children. Asfotase alfa was approved by regulatory agencies multinationally in 2015 typically for pediatric-onset HPP.
Bone. 2017 Feb 24. pii: S8756-3282(17)30056-X. doi: 10.1016/j.bone.2017.02.011.
Deletion of connexin (Cx) 37 in mice leads to increased cancellous bone mass due to defective osteoclast differentiation. Paradoxically; however, Cx37-deficient mice exhibit reduced cortical thickness accompanied by higher bone strength,suggesting a contribution of Cx37 to bone matrix composition. Thus, we investigated whether global deletion of Cx37 alters the composition of phentermine organic bone extracellular matrix.m echanistic studies showed Wnt/β-catenin activation in MLO-Y4 osteocytic cells, L5 vertebra, and authentic calvaria-derived osteocytes isolated by fluorescent-activated cell sorter. Our findings demonstrate that altered profile of the bone matrix components in Cx37-deficient mice acts in favor of higher resistance to Fracture in long bones.
Pacheco-Costa R, Kadakia JR, Atkinson EG, Wallace JM, Plotkin LI, Reginato RD