21Jun 2017
MPubmed

The relative efficacy and harms of balloon kyphoplasty (BK) for treating vertebral compression fractures (VCF) are uncertain. The clinical importance of the greater improvements with BK versus NSM is unclear, may be due to placebo effect, and may not counterbalance short-term AE risks. Outcomes appeared similar between BK and other surgical interventions.Well-conducted randomized trials comparing BK with sham would help resolve remaining ncertainty about the relative benefits and harms of BK.

J Bone Miner Res. 2017 May 17. doi: 10.1002/jbmr.3170. [Epub ahead of print]

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Rodriguez AJ, Fink HA, Mirigian L, Guañabens N, Eastell R, Akesson K, Bauer DC, Ebeling PR

 

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
MPubmed

Adults with low concentrations of 25-hydroxyvitamin D (25[OH]D) in blood have an increased risk of falls and fractures, but randomised trials of vitamin D supplementation have had inconsistent results. We aimed to assess the effect of high-dose vitamin D supplementation on fractures and falls.

The Vitamin D Assessment (ViDA) Study was a randomised, double-blind, placebo-controlled trial of healthy volunteers aged 50-84 years conducted at one centre in Auckland, New Zealand. Participants were randomly assigned to receive either an initial oral dose of 200 000 IU (5·0 mg) colecalciferol (vitamin D3) followed by monthly 100 000 IU (2·5 mg) colecalciferol or equivalent placebo dosing.

Between April 5, 2011, and Nov 6, 2012, 5110 participants were recruited and randomly assigned either colecalciferol (n=2558) or placebo (n=2552). The mean age of participants was 65·9 years (SD 8·3) and 2971 (58%) were men. The mean concentration of 25(OH)D in blood was 63 nmol/L (SD 24) at baseline, with 1534 (30%) having 25(OH)D concentrations lower than 50 nmol/L. Follow-up was until July 31, 2015, with a mean treatment duration of 3·4 years (SD 0·4, range 2·5-4·2). During follow-up, 2638 participants reported having a fall, 1312 (52%) of 2539 in the vitamin D group compared with 1326 (53%) of 2517 in the placebo group. The HR for falls-adjusted for age, sex, ethnic origin, history of recent fall, physical activity, and baseline 25(OH)D-was 0·99 (95% CI 0·92-1·07; p=0·82) for vitamin D compared with placebo. Non-vertebral fractures were reported in 292 individuals, 156 (6%) of 2558 in the vitamin D group and 136 (5%) of 2550 in the placebo group. The adjusted HR for fractures was 1·19 (95% CI 0·94-1·50; p=0·15) for vitamin D compared with placebo. 123 (2%) people died during the trial, 65 assigned vitamin D and 58 allocated placebo; the difference between treatment groups was not significant.

Conclusion: High-dose bolus vitamin D supplementation of 100 000 IU colecalciferol monthly over 2·5-4·2 years did not prevent falls or fractures in this healthy, ambulatory, adult population. Further research is needed to ascertain the effects of daily vitamin D dosing, with or without calcium.

Lancet Diabetes Endocrinol. 2017 Apr 28. pii: S2213-8587(17)30103-1. doi: 10.1016/S2213-8587(17)30103-1.

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Khaw KT, Stewart AW, Waayer D, Lawes CMM, Toop L, Camargo CA Jr, Scragg R.

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.