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Calcified Tissue International

Kathryn Grandfield, Vicky Vuong, Henry P Schwarcz
The ultrastructure of bone has been widely debated, in part due to limitations in visualizing nanostructural features over relevant micrometer length scales. Here, we employ the high resolving power and compositional contrast of high-angle annular dark-field scanning transmission electron microscopy (HAADF STEM) to investigate new features in human bone with nanometer resolution over microscale areas. Using focused ion beam (FIB)-milled sections that span an area of 50 μm2 , we have shown how most of the mineral of cortical human osteonal bone occurs in the form of long, thin polycrystalline plates (mineral lamellae, MLs) which are either flat or curved to wrap closely around collagen fibrils...
July 14, 2018: Calcified Tissue International
Ran Guo, Lang Wu, Qin Fu
Observational studies examining associations of smoking and alcohol consumption with bone mineral density (BMD) have generated inconsistent results and suffer from several methodological limitations. We aim to evaluate whether there are causal associations between smoking, alcohol consumption, and BMD using a Mendelian randomization (MR) design. Genetic variants associated with smoking status (n = 142), no. of cigarettes smoked per day (CPD) (n = 3), smoking initiation (n = 1), and alcohol consumption (n = 6) identified in published genome-wide association studies (GWAS) were used as instruments...
July 14, 2018: Calcified Tissue International
Jean-Yves Reginster, Gary Hattersley, Gregory C Williams, Ming-Yi Hu, Lorraine A Fitzpatrick, E Michael Lewiecki
Abaloparatide (ABL) is a 34-amino acid peptide designed to be a selective activator of the parathyroid hormone receptor type 1 signaling pathway. In the Abaloparatide Comparator Trial In Vertebral Endpoints (ACTIVE), subcutaneous ABL reduced the risk of new vertebral, nonvertebral, clinical, and major osteoporotic fracture compared with placebo and of major osteoporotic fracture compared with teriparatide. To further evaluate the effectiveness of ABL, we calculated the number needed to treat (NNT) to prevent one fracture using ACTIVE data...
June 27, 2018: Calcified Tissue International
Adam Mitchell, Tove Fall, Håkan Melhus, Alicja Wolk, Karl Michaëlsson, Liisa Byberg
Men and women with type 2 diabetes mellitus (T2DM) have higher risk of hip fracture, but the mechanisms are not fully understood. We aimed to investigate how T2DM, glucose, and insulin were associated with femoral bone mineral density (BMD), bone mineral area (BMA), and bone turnover markers. We used two cross-sectional cohorts: the Uppsala Longitudinal Study of Adult Men (ULSAM, n = 452, mean age 82 years) and the Swedish Mammography Cohort Clinical (SMCC, n = 4713, mean age 68 years). We identified men and women with normal fasting glucose (NFG), impaired fasting plasma glucose (IFG), and T2DM...
June 26, 2018: Calcified Tissue International
Tim Rolvien, Julian Stürznickel, Felix N Schmidt, Sebastian Butscheidt, Tobias Schmidt, Björn Busse, Stefan Mundlos, Thorsten Schinke, Uwe Kornak, Michael Amling, Ralf Oheim
Diagnosis and management of adult individuals with low bone mass and increased bone fragility before the age of 50 can be challenging. A number of these patients are diagnosed with mild osteogenesis imperfecta (OI) through detection of COL1A1 or COL1A2 mutations; however, a clinical differentiation from early-onset osteoporosis (EOOP) may be difficult. The purpose of this study was to determine the bone microstructural differences between mild OI and EOOP patients. 29 patients showed mutations in COL1A1 or COL1A2 and were classified as OI...
June 26, 2018: Calcified Tissue International
Nicola Veronese, Luciana La Tegola, Maria Mattera, Stefania Maggi, Giuseppe Guglielmi
PURPOSE: There is evidence that vitamin D may play a role in the osteoarthritis (OA) pathogenesis, but the few data available are limited to X-rays and clinical findings. The aim of this study was to investigate whether a higher intake of vitamin D was associated with a better architecture of the cartilage of the knee, assessed with magnetic resonance (MRI), in a large cohort from North America. METHODS: 783 participants (59.8% females; mean age: 62.3 years) with an MRI assessment from the Osteoarthritis Initiative were included...
June 25, 2018: Calcified Tissue International
M Fiscaletti, C P Coorey, A Biggin, J Briody, D G Little, A Schindeler, C F Munns
Significant fracture history in children is defined as having at least one vertebral fracture, at least 2 fractures by age 10, or at least 3 fractures by age 19. Between September 2011 and December 2014, clinical data were collected on children with a significant fracture history that attended a major Australian children's hospital. Fifty-six patients were identified as having 305 fractures in total, including 44 vertebral fractures. 18% of patients (10/56) were diagnosed with osteogenesis imperfecta (OI) by a bone health expert, molecular testing or both, and they sustained 23% of all fractures (71/305)...
June 25, 2018: Calcified Tissue International
S C Shaw, C M Parsons, N R Fuggle, M H Edwards, S M Robinson, E M Dennison, C Cooper, K A Ward
There are few data describing associations between dietary patterns and bone microarchitecture. This study investigated the relationship between diet quality and HRpQCT and pQCT measures in older adults. Data were available for 184 men and 166 women. Dietary data were collected at baseline (1998-2003) using an administered food frequency questionnaire. A 'prudent' diet score (PDS) was identified using principal component analysis and used as an indicator of dietary quality. HRpQCT and pQCT images were acquired at follow-up in 2012, from the non-dominant distal radius and tibia using Scanco XtremeCT and Stratec XCT2000 instrument scanners, respectively...
June 21, 2018: Calcified Tissue International
Wei Zhao, Xiaodong Li, Yuanzhen Peng, Yiwen Qin, Jiangping Pan, Jiliang Li, Aihua Xu, Michael S Ominsky, Christopher Cardozo, Jian Q Feng, Hua Zhu Ke, William A Bauman, Weiping Qin
To date, no efficacious therapy exists that will prevent or treat the severe osteoporosis in individuals with neurologically motor-complete spinal cord injury (SCI). Recent preclinical studies have demonstrated that sclerostin antibody (Scl-Ab) can prevent sublesional bone loss after acute SCI in rats. However, it remains unknown whether sclerostin inhibition reverses substantial bone loss in the vast majority of the SCI population who have been injured for several years. This preclinical study tested the efficacy of Scl-Ab to reverse the bone loss that has occurred in a rodent model after chronic motor-complete SCI...
June 21, 2018: Calcified Tissue International
A Patel, M H Edwards, K A Jameson, K A Ward, Nicholas Fuggle, C Cooper, E M Dennison
There are few longitudinal data on change in bone structure and muscle mass, strength and function in later life. We report these, and consider bone-muscle interrelationships in older men and women. We studied 188 men and 166 women from the Hertfordshire Cohort Study, who underwent peripheral quantitative computed tomography (pQCT) of the radius and tibia in 2004-2005 and then again in 2011-2012. Grip strength and gait speed were also assessed at both timepoints. Percentage change per year was calculated for grip strength, gait speed, muscle cross-sectional area (mCSA), fat cross-sectional area (fCSA) and diaphyseal bone parameters [total area (Tt...
June 21, 2018: Calcified Tissue International
Lise Sofie Bislev, Lene Langagergaard Rødbro, Lars Rolighed, Tanja Sikjaer, Lars Rejnmark
Vitamin D insufficiency and hyperparathyroidism have been associated with reduced muscle strength, physical performance, postural stability, well-being, and quality of life. In a double-blinded, randomized placebo-controlled trial, we aimed to investigate effects of vitamin D3 supplementation on above-mentioned outcomes in healthy community-dwelling postmenopausal women with plasma levels of 25-hydroxyvitamin D (25(OH)D) below < 50 nmol/l and high parathyroid hormone (PTH) levels. Participants (N = 81) were 1:1 treated with vitamin D3, 70 µg (2800 IU)/day or identical placebo for three months during wintertime (56°N)...
June 21, 2018: Calcified Tissue International
Evelyne Gineyts, Nicolas Bonnet, Cindy Bertholon, Marjorie Millet, Aurélie Pagnon-Minot, Olivier Borel, Sandra Geraci, Edith Bonnelye, Martine Croset, Ali Suhail, Cristina Truica, Nicholas Lamparella, Kim Leitzel, Daniel Hartmann, Roland Chapurlat, Allan Lipton, Patrick Garnero, Serge Ferrari, Philippe Clézardin, Jean-Charles Rousseau
Periostin is an extracellular matrix protein that actively contributes to tumor progression and metastasis. Here, we hypothesized that it could be a marker of bone metastasis formation. To address this question, we used two polyclonal antibodies directed against the whole molecule or its C-terminal domain to explore the expression of intact and truncated forms of periostin in the serum and tissues (lung, heart, bone) of wild-type and periostin-deficient mice. In normal bones, periostin was expressed in the periosteum and specific periostin proteolytic fragments were found in bones, but not in soft tissues...
June 18, 2018: Calcified Tissue International
Yu Shen, Dian Jing, Jin Hao, Ge Tang, Pu Yang, Zhihe Zhao
Collagen cross-linking, as a form of collagen post-translational modification, plays a crucial role in maintaining bone mechanical properties as well as in regulating cell biological functions. Shifts in cross-links profile are found apparently correlated to kinds of skeletal pathology and diseases, whereas little is known about the relationship between collagen cross-links and osteogenesis. Here, we hypothesized that the inhibition of collagen cross-links could impair skeletal microstructure and inhibit osteogenesis...
June 18, 2018: Calcified Tissue International
Nicola Napoli, Bente L Langdahl, Östen Ljunggren, Eric Lespessailles, George Kapetanos, Tomaz Kocjan, Tatjana Nikolic, Pia Eiken, Helmut Petto, Thomas Moll, Erik Lindh, Fernando Marin
This study aimed to describe clinical outcomes in patients prescribed teriparatide and followed up for 18 months after stopping the drug in real-life conditions. The Extended Forsteo® Observational Study analysed incident clinical fractures in 6-month intervals using logistic regression with repeated measures. Changes in back pain (visual analogue scale) and health-related quality of life (HRQoL; EQ-5D questionnaire) were analysed using mixed models for repeated measures. Patients were analysed if they had a post-baseline visit, regardless of whether and for how long they took teriparatide...
June 16, 2018: Calcified Tissue International
M Rotman, C D Andela, B C J Majoor, P D S Dijkstra, N A T Hamdy, A A Kaptein, N M Appelman-Dijkstra
Impairments in quality of life (QoL) have been reported in patients with fibrous dysplasia (FD). Here, we examine coping strategies in FD and assess whether these coping strategies are associated with QoL and disease severity. Ninety-two patients (66% females) filled out the Utrecht Coping List (UCL), Short Form-36, and the Brief Pain Inventory (BPI). Coping strategies of patients with FD were compared with reference data from a random sample of Dutch women and patients with chronic pain. Compared to healthy adults, patients expressed more emotions (p < 0...
June 13, 2018: Calcified Tissue International
Yasuto Shikida, Masahide Mizobuchi, Takashi Inoue, Toma Hamada, Hiroaki Ogata, Fumihiko Koiwa, Takanori Shibata
Fibroblast growth factor 23 (FGF23) is associated with mortality in patients with CKD. However, the mechanisms underlying stimulation of FGF23 remain to be investigated. We examined whether hypercalcemia induced by continuous intravenous (CIV) calcium (Ca) infusion regulates FGF23 levels in normal rats (Normal) and 5/6 nephrectomized uremic rats (Nx). Microinfusion pumps were implanted in the Normal and Nx rats for CIV Ca infusion, and blood, urine, kidney, and tibia were collected. The results showed an increase in serum Ca-stimulated FGF23 independently of serum phosphate (P) and creatinine levels in Normal and Nx rats...
June 7, 2018: Calcified Tissue International
David S Peitgen, Moritz M Innmann, Christian Merle, Tobias Gotterbarm, Babak Moradi, Marcus R Streit
Implant failure and periprosthetic fractures because of periprosthetic bone loss are a major concern in total hip arthroplasty (THA). Hardly any clinical data exist on the long-term evolution of bone mineral density (BMD) around uncemented femoral implants. The question to address is whether relevant bone loss continues into third decade around well-fixed uncemented femoral implants. BMD around stable uncemented straight titanium femoral implants was assessed in a longitudinal cohort study. We included 142 hips of 128 patients and measured the development of the periprosthetic BMD using dual-energy X-ray absorptiometry...
June 1, 2018: Calcified Tissue International
Aya Misawa, Hideo Orimo
HOTAIR is a lncRNA that plays critical role in gene regulation and chromatin dynamics through epigenetic mechanisms. In this work we studied the physiological role of HOTAIR during the process of mineralization using osteoblastic osteosarcoma cells focusing in ALPL (Tissue Non-Specific Alkaline Phosphatase), a pivotal gene that controls bone formation. HOTAIR knockdown resulted in upregulation of ALPL, increase of alkaline phosphatase (ALP) activity, and enhanced mineralization in osteoblastic SaOS-2 cells cultured in mineralizing medium...
May 30, 2018: Calcified Tissue International
Alyson Morse, Tegan L Cheng, Aaron Schindeler, Michelle M McDonald, Sindhu T Mohanty, Michaela Kneissel, Ina Kramer, David G Little
Dickkopf-1 (DKK1) and sclerostin are antagonists of the Wnt/β-catenin pathway and decreased expression of either results in increased bone formation and mass. As both affect the same signaling pathway, we aimed to elucidate the redundancy and/or compensation of sclerostin and DKK1. Weekly sclerostin antibody (Scl-Ab) was used to treat 9-week-old female Dkk1 KO (Dkk1-/- :Wnt3+/- ) mice and compared to Scl-Ab-treated wild-type mice as well as vehicle-treated Dkk1 KO and wild-type animals. While Wnt3 heterozygote (Wnt3+/- ) mice show no bone phenotype, Scl-Ab and vehicle-treated control groups of this genotype were included...
May 29, 2018: Calcified Tissue International
Kazuhiro Shima, Keisuke Kimura, Masahiko Ishida, Akiko Kishikawa, Saika Ogawa, Jiawei Qi, Wei-Ren Shen, Fumitoshi Ohori, Takahiro Noguchi, Aseel Marahleh, Hideki Kitaura
C-X-C motif chemokine 12 (CXCL12) belongs to the family of CXC chemokines. Lipopolysaccharide (LPS) induces inflammation-induced osteoclastogenesis and bone resorption, and in recent years, stimulatory effects of CXCL12 on bone resorption have also been reported. In the present study, we investigated the effects of CXCL12 on LPS-induced osteoclastogenesis and bone resorption. LPS was administered with or without CXCL12 onto mouse calvariae by daily subcutaneous injection. Numbers of osteoclasts and bone resorption were significantly elevated in mice co-administered LPS and CXCL12 compared with mice administered LPS alone...
May 29, 2018: Calcified Tissue International
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