25May 2017
MPubmed

This study has as objectives: To estimate the preferences of osteoporotic patients for medication attributes, and analyse data from seven European countries.

In total, 1124 patients completed the experiment, with a sample of between 98 and 257 patients per country. They found statistically significant differences in patients’ preferences for anti-osteoporosis medications between countries, especially for the mode of administration. Our findings emphasized that international treatment recommendations should allow for local adaptation, and that understanding individual preferences is important if we want to improve the quality of clinical care for patients with osteoporosis.

Rheumatology (Oxford). 2017 Apr 6. doi: 10.1093/rheumatology/kex071

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Hiligsmann M, Dellaert BG, Dirksen CD, Watson V, Bours S, Goemaere S, Reginster JY, Roux C, McGowan B, Silke C, Whelan B, Diez-Perez A), Torres E, Papadakis G, Rizzoli R, Cooper C,Pearson G, Boonen A

25May 2017
MPubmed

Bone has recently emerged as a pleiotropic endocrine organ that secretes at least two hormones, FGF23 and osteocalcin, which regulate kidney function and glucose homeostasis, respectively. These findings have raised the question of whether other bone-derived hormones exist and what their potential functions are. Here we identify, through molecular and genetic analyses in mice, lipocalin 2 (LCN2) as an osteoblast-enriched, secreted protein. Loss- and gain-of-function experiments in mice demonstrate that osteoblast-derived LCN2 maintains glucose homeostasis by inducing insulin secretion and improves glucose tolerance and insulin sensitivity. In addition, osteoblast-derived LCN2 inhibits food intake. LCN2 crosses the blood-brain barrier, binds to the melanocortin 4 receptor (MC4R) in the paraventricular and ventromedial neurons of the hypothalamus and activates an MC4R-dependent anorexigenic (appetite-suppressing) pathway. These results identify LCN2 as a bone-derived hormone with metabolic regulatory effects, which suppresses appetite in a MC4R-dependent manner, and show that the control of appetite is an endocrine function of bone.

Nature. 2017 Mar 16;543(7645):385-390. doi: 10.1038/nature21697. Epub 2017 Mar 8.

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Mosialou I, Shikhel S, Liu JM, Maurizi A, Luo N, He Z, Huang Y, Zong H, Friedman RA, Barasch J, Lanzano P, Deng L, Leibel RL, Rubin M, Nicholas T, Chung W, Zeltser LM, Williams KW, Pessin JE, Kousteni S.

25May 2017
MPubmed

Periostin is an extracellular matrix protein, and in bone is expressed most highly in the periosteum. It increases bone formation through osteoblast differentiation, cell adhesion, Wnt signalling and collagen cross-linking. We hypothesised that serum periostin would be high at times of life when cortical modeling is active, in early adulthood and in older age, and that it would correlate with cortical bone measures, bone turnover and hormones that regulate cortical modeling. We conducted a cross-sectional observational study of 166 healthy men and women at three skeletal stages; the end of longitudinal growth (16-18years), peak bone mass (30-32years) and older age (over 70years). We measured serum periostin with a new ELISA optimised for human serum and plasma which recognises all known splice variants (Biomedica). We measured the distal radius and distal tibia with HR-pQCT, and measured serum PINP, CTX, sclerostin, PTH, IGF-1, estradiol and testosterone. Periostin was higher at age 16-18 than age 30-32 (1253 vs 842pmol/l, p<0.001), but not different between age 30-32 and over age 70. Periostin was inversely correlated with tibia cortical thickness and density (R -0.229, -0.233, both p=0.003). It was positively correlated with PINP (R 0.529, p<0.001), CTX (R 0.427, p<0.001) and IGF-1 (R 0.440, p<0.001). When assessed within each age group these correlations were only significant at age 16-18, except for PINP which was also significant over age 70. We conclude that periostin may have a role in IGF-1 driven cortical modeling and consolidation in young adults, but it may not be an important mediator in older adults.

Bone. 2017 Jun;99:8-13. doi: 10.1016/j.bone.2017.03.041. Epub 2017 Mar 16.

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Walsh JS, Gossiel F, Scott JR, Paggiosi MA, Eastell R.

25May 2017
Watch Movie Online It (2017)
  • It (2017)

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    135 mins
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    Thriller, Horror, Drama.
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    September 5, 2017
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Andy Muschietti.

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Seth Grahame-Smith, David Katzenberg, Roy Lee, Dan Lin, Barbara Muschietti.

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Chase Palmer, Gary Dauberman, Cary Fukunaga.

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New Line Cinema, Vertigo Entertainment, Lin Pictures, RatPac-Dune Entertainment, KatzSmith Productions.

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25May 2017
Watch and Download Full Movie Blade Runner 2049 (2017)
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    163 mins
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    October 4, 2017
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    English.
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    United States of America.
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Movie ‘Blade Runner 2049’ was released in October 4, 2017 in genre Action. Denis Villeneuve was directed this movie and starring by Ryan Gosling. This movie tell story about Thirty years after the events of the first film, a new blade runner, LAPD Officer K, unearths a long-buried secret that has the potential to plunge what’s left of society into chaos. K’s discovery leads him on a quest to find Rick Deckard, a former LAPD blade runner who has been missing for 30 years.

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Denis Villeneuve.

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Broderick Johnson, Andrew A. Kosove, Ridley Scott, Cynthia Sikes, Bud Yorkin.

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Alcon Entertainment, Scott Free Productions, Warner Bros., Thunderbird Films, Torridon Films.

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27Abr 2017
MPubmed

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.

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Cundy T, Maslowski K, Grey A, Reid IR.

27Abr 2017
MPubmed

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.

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Gennari L, Bianciardi S, Merlotti D.

23Mar 2017
MPubmed

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.

23Mar 2017
MPubmed

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.

23Mar 2017
MPubmed

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