Advances in the treatment of hypoparathyroidism with PTH 1 –34
Hypoparathyroidism is a rare disorder of calcium metabolism which is treated with calcium and vitamin D analogs. Although conventional therapy effectively raises serum calcium, it bypasses the potent calcium reabsorption effects of PTH on the kidney which leads to hypercalciuria and an increased risk of nephrocalcinosis and renal insufficiency. Twenty-five years ago, we launched the first systematic investigation into synthetic human PTH 1 –34 replacement therapy in both adults and children. These studies led to our current understanding of the complex nature of PTH 1–34 therapy and to the challenges we still face in o...
Source: Bone - September 21, 2018 Category: Orthopaedics Authors: Karen K. Winer Tags: Full Length Article Source Type: research
Long term prognosis of Scheuermann's disease: The association with fragility fracture - The MINOS cohort
The aim was to assess the association of Scheuermann's disease (SCD) with fracture risk (vertebral, peripheral) and bone mineral density (BMD) in older men. SCD was assessed on the baseline lateral spine radiographs using the Berlin criteria in 766 men aged 50 –85. We evaluated the association of SCD and its diagnostic criteria with incident fracture (vertebral over 7.5 years, peripheral over 10 years) and BMD (baseline). SCD prevalence was 25.2%. SCD and its criteria showed inconsistent associations with BMD at different skeletal sites. (Source: Bone)
Source: Bone - September 20, 2018 Category: Orthopaedics Authors: Marine Gaud é, Roland Chapurlat, Jean-Baptiste Pialat, Pawel Szulc Tags: Full Length Article Source Type: research
FRAX is a robust predictor of baseline vertebral fractures in multiple myeloma patients
FRAX is a commonly used tool to evaluate patient fracture risk based on individual patient models that integrate the risks associated with clinical risk factors with or without bone mineral density (BMD) at the femoral neck. Retrospectively, factors identified by the FRAX scoring algorithm were used to predict the risk for vertebral compression fractures at baseline in newly diagnosed multiple myeloma patients. The data were derived from myeloma patients enrolled in Total Therapy Protocols (TT4& TT5) between 8/2008 and 9/2017. (Source: Bone)
Source: Bone - September 19, 2018 Category: Orthopaedics Authors: Shebli Atrash, Isha Dua, Amy F. Buros, Fritz Van Rhee, Larry J. Suva, Sharmilan Thanendrarajan, Carolina Schinke, Faith Davies, Gareth Morgan, Maurizio Zangari Tags: Full Length Article Source Type: research
Understanding age-induced cortical porosity in women: Is a negative BMU balance in quiescent osteons a major contributor?
Cortical bone is remodeled by intracortical basic multicellular units (BMUs), whose end result can be observed as quiescent osteons in histological sections. These osteons offer a unique opportunity to investigate the BMU balance between the magnitude of bone resorption and subsequent bone formation at the BMU level. Our main objective was to investigate whether the latter parameters change between defined categories of osteons and with age, and to which extend these changes contribute to age-induced cortical porosity. (Source: Bone)
Source: Bone - September 18, 2018 Category: Orthopaedics Authors: Christina M. Andreasen, Jean-Marie Delaisse, Bram C.J. van der Eerden, Johannes P.T.M. van Leeuwen, Ming Ding, Thomas Levin Andersen Tags: Full Length Article Source Type: research
Age at menarche and osteoporosis: A Mendelian randomization study
Traditional epidemiological studies suggest that there is an association between age at menarche (years) (AAM) and bone mineral density (BMD) at the sites of the femoral neck and lumbar spine (FNK and LS BMD), indicating a potentially important relationship between AAM and the development of osteoporosis (OP). However, these findings may be influenced by unmeasured confounding factors that can obscure the true relationship between the phenotypic traits. Therefore, we performed Mendelian randomization (MR) analyses to determine whether there is a causal relationship between AAM and BMD (FNK and LS BMD), where late AAM may i...
Source: Bone - September 18, 2018 Category: Orthopaedics Authors: Qiang Zhang, Jonathan Greenbaum, Wei-Dong Zhang, Qing-Chang Sun, Hong-Wen Deng Tags: Full Length Article Source Type: research
Biofidelic finite element models for accurately classifying hip fracture in a retrospective clinical study of elderly women from the AGES Reykjavik cohort
Clinical retrospective studies have only reported limited improvements in hip fracture classification accuracy using finite element (FE) models compared to conventional areal bone mineral density (aBMD) measurements. A possible explanation is that state-of-the-art quasi-static models do not estimate patient-specific loads. A novel FE modeling technique was developed to improve the biofidelity of simulated impact loading from sideways falling. This included surrogate models of the pelvis, lower extremities, and soft tissue that were morphed based on subject anthropometrics. (Source: Bone)
Source: Bone - September 18, 2018 Category: Orthopaedics Authors: W.S. Enns-Bray, H. Bahaloo, I. Fleps, Y. Pauchard, E. Taghizadeh, S. Sigurdsson, T. Aspelund, P. B üchler, T. Harris, V. Gudnason, S.J. Ferguson, H. Palsson, B. Helgason Tags: Full Length Article Source Type: research
TNF- α suppresses osteogenic differentiation of MSCs by accelerating P2Y2 receptor in estrogen-deficiency induced osteoporosis
Tumor Necrosis Factor- α (TNF-α)-inhibited osteogenic differentiation of mesenchymal stem cells (MSCs) contributes to impaired bone formation, which plays a central role in the pathogenesis of postmenopausal osteoporosis. However, the exact mechanisms of TNF-α-inhibited osteoblast differentiation have not been fully el ucidated. Multiple P2 purinoceptor subtypes are expressed in several species of osteoblasts and are confirmed to regulate bone metabolism. The purpose of this study is to investigate whether P2 purinoceptors are involved in TNF-α-inhibited osteoblast differentiation. (Source: Bone)
Source: Bone - September 17, 2018 Category: Orthopaedics Authors: Di Du, Zhibin Zhou, Lei Zhu, Xianteng Hu, Jiajia Lu, Changgui Shi, Fangjing Chen, Aimin Chen Tags: Full Length Article Source Type: research
Influence of demographic and clinical characteristics of elderly patients with a hip fracture on mortality: A retrospective, total cohort study in North-East Spain
The increased mortality after hip fracture (HF) is caused by multiple factors, and large samples are needed to assess the weight of each factor. To date, few studies have investigated these factors through a total cohort approach, and the complexity of underlying medical conditions has not been considered. (Source: Bone)
Source: Bone - September 14, 2018 Category: Orthopaedics Authors: Jose M. Cancio, Emili Vela, Sebasti à Santaeugènia, Montse Clèries, Marco Inzitari, Domingo Ruiz Tags: Full Length Article Source Type: research
Bone health evaluation one year after aromatase inhibitors completion
Breast cancer patients treated with aromatase inhibitors (AIs) experience increased bone loss during their treatment. However, there is little information about bone mineral density (BMD) after completing AI-treatment. The present study aimed to assess BMD changes one year after AI-therapy completion. (Source: Bone)
Source: Bone - September 14, 2018 Category: Orthopaedics Authors: Marta Pineda-Moncus í, Sonia Servitja, Guillem Casamayor, Maria Lourdes Cos, Abora Rial, Jaime Rodriguez-Morera, Ignasi Tusquets, Adolfo Diez-Perez, Natalia Garcia-Giralt, Xavier Nogués Tags: Full Length Article Source Type: research
Glucose dependent miR-451a expression contributes to parathyroid hormone mediated osteoblast differentiation
Parathyroid hormone (PTH; amino acid 1 –34, known as teriparatide) has reported promoting differentiation and glucose uptake in osteoblasts. However, how PTH regulates glucose metabolism to facilitate osteoblast differentiation is not understood. Here, we report that PTH promotes glucose dependent miR-451a expression which stimulates o steoblast differentiation. In addition to glucose uptake, PTH suppresses AMPK phosphorylation via PI3K-mTOR-AKT axis thereby preventing phosphorylation and inactivation of octamer-binding transcription factor 1 (OCT-1) which has been reported to act on the promoter region of miR-451a. (Source: Bone)
Source: Bone - September 13, 2018 Category: Orthopaedics Authors: Anirudha Karvande, Priyanka Kushwaha, Naseer Ahmad, Sulekha Adhikary, Priyanka Kothari, Ashish Kumar Tripathi, Vikram Khedgikar, Ritu Trivedi Tags: Full Length Article Source Type: research
Demethylation of ITGAV accelerates osteogenic differentiation in a blast-induced heterotopic ossification in vitro cell culture model
Trauma-induced heterotopic ossification is an intriguing phenomenon involving the inappropriate ossification of soft tissues within the body such as the muscle and ligaments. This inappropriate formation of bone is highly prevalent in those affected by blast injuries. Here, we developed a simplified model to evaluate the molecular events involved in heterotopic ossification onset that arise from the shock wave component of the disease. We exposed three subtypes of human mesenchymal cells in vitro to a single, high-energy shock wave and observed increased transcription in the osteogenic master regulators, Runx2 and Dlx5, an...
Source: Bone - September 13, 2018 Category: Orthopaedics Authors: Niall J. Logan, Marie Camman, Greg Williams, Claire A. Higgins Tags: Full Length Article Source Type: research
The relationship between estimated bone strength by finite element analysis at the peripheral skeleton to areal BMD and trabecular bone score at lumbar spine
Bone strength, estimated by finite element (FE) analysis based on high resolution peripheral quantitative computed tomography (HR-pQCT) images is an important contributor to understanding risk of fracture. However, it is a peripheral device and cannot be evaluated in vivo at lumbar spine L1 –L4. The aim of this study was to investigate if the axial bone quality can be predicted by strength measurements of peripheral bone.Peripheral bone microarchitecture, areal bone mineral density (aBMD) and trabecular bone score (TBS) were measured in adults individuals (n = 262, 60 years and older; 63% women). (Source: Bone)
Source: Bone - September 13, 2018 Category: Orthopaedics Authors: Jackeline C. Alvarenga, Steven K. Boyd, Rosa M.R. Pereira Tags: Full Length Article Source Type: research
The limitations of using simple definitions of glucocorticoid exposure to predict fracture risk: A cohort study
To evaluate the effects of different definitions of glucocorticoid (GC) exposure on the magnitude and pattern of fracture risk using the same dataset. (Source: Bone)
Source: Bone - September 12, 2018 Category: Orthopaedics Authors: Danielle E. Robinson, Tjeerd P. van Staa, Elaine M. Dennison, Cyrus Cooper, William G. Dixon Tags: Full Length Article Source Type: research
CT analysis of anatomical distribution of melorheostosis challenges the sclerotome hypothesis
Melorheostosis (MEL) is a rare disease of high bone mass with patchy skeletal distribution affecting the long bones. We recently reported somatic mosaic mutations in MAP2K1 in 8 of 15 patients with the disease. The unique anatomic distribution of melorheostosis is of great interest. The disease remains limited to medial or lateral side of the extremity with proximo-distal progression. This pattern of distribution has historically been attributed to sclerotomes (area of bone which is innervated by a single spinal nerve level). (Source: Bone)
Source: Bone - September 12, 2018 Category: Orthopaedics Authors: Smita Jha, Nicholas Laucis, Lauren Kim, Ashkan Malayeri, Abhijit Dasgupta, Georgios Z. Papadakis, Apostolos Karantanas, Miguel Torres, Timothy Bhattacharyya Tags: Full Length Article Source Type: research
Collagen type I degradation fragments act through the collagen receptor LAIR-1 to provide a negative feedback for osteoclast formation
We examined if osteoclast differentiation from murine bone marrow precursors is affected by collagen type I, or by its degradation products produced by human recombinant cathepsin K. Osteoclasts formation was dose-dependently inhibited in the presence of full length collagen type I or its 30 –75 kDa degradation products added to the osteoclast differentiation media for the duration of an experiment. (Source: Bone)
Source: Bone - September 11, 2018 Category: Orthopaedics Authors: Iris Boraschi-Diaz, John S. Mort, Dieter Bromme, Yotis A. Senis, Alexandra Mazharian, Svetlana V. Komarova Tags: Full Length Article Source Type: research
