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    The key role of proinflammatory cytokines, matrix proteins, RANKL/OPG and Wnt/β-catenin in bone healing of hip arthroplasty patients.
    Bone 2017 Nov 9. Epub 2017 Nov 9.
    Orthopedic Research Unit, Department of Orthopedic Surgery, Sahlgrenska University Hospital, Mölndal, Sweden; Institution of Clinical Sciences, Göteborg University, Göteborg, Sweden.
    Introduction: We still lack understanding of why some implants fail while most remain stable after decades of use. Proinflammatory cytokines, matrix proteins and bone regulating cytokines of the RANKL/OPG (receptor activator of nuclear factor kappa B ligand/osteoprotegerin) and Wnt/β-catenin pathways are mandatory for normal bone repair but their spatial and temporal role in the healing of primary total hip arthroplasties (THA) has not been previously shown.

    Materials And Methods: Twenty-four osteoarthritis patients with one-sided well-fixed primary THA were prospectively monitored during 18years (18Y) with repeated blood samples, clinical variables and radiographs. Read More

    Dampening of the bone formation response following repeat dosing with sclerostin antibody in mice is associated with up-regulation of Wnt antagonists.
    Bone 2017 Nov 9. Epub 2017 Nov 9.
    UCB Pharma, Slough, UK.
    Administration of antibodies to sclerostin (Scl-Ab) has been shown to increase bone mass, bone mineral density (BMD) and bone strength by increasing bone formation and decreasing bone resorption in both animal studies and human clinical trials. In these studies, the magnitude and rate of increase in bone formation markers is attenuated upon repeat dosing with Scl-Ab despite a continuous and progressive increase in BMD. Here, we investigated whether the attenuation in the bone formation response following repeated administration of Scl-Ab was associated with increased expression of secreted antagonists of Wnt signalling and determined how the circulating marker of bone formation, P1NP, responded to single, or multiple doses, of Scl-Ab four days post-dosing. Read More

    Drosophila models of FOP provide mechanistic insight.
    Bone 2017 Nov 8. Epub 2017 Nov 8.
    Department of Molecular Biology, Cell Biology, and Biochemistry, Brown University, Providence, RI, USA. Electronic address:
    Fibrodysplasia ossificans progressiva (FOP) is a rare bone disease characterized by episodic events of heterotopic ossification (HO). All cases of FOP have been attributed to mutations in the ACVR1 gene that render the encoded BMP type I ALK2 receptor hypersensitive, resulting in the activation of BMP signaling, at inappropriate times in inappropriate locations. The episodic or sporadic nature of HO associated with FOP rests with the occurrence of specific 'triggers' that push the hypersensitive ALK2-FOP receptor into full signaling mode. Read More

    Osteopontin as a novel substrate for the proprotein convertase 5/6 (PCSK5) in bone.
    Bone 2017 Nov 7;107:45-55. Epub 2017 Nov 7.
    Faculty of Dentistry, McGill University, Montreal, QC, Canada; Department of Anatomy and Cell Biology, Faculty of Medicine, McGill University, Montreal, QC, Canada. Electronic address:
    Seven proprotein convertases cleave the basic amino acid consensus sequence K/R-Xn-K/R↓ (where n=0, 2, 4 or 6 variable amino acids) to activate precursor proteins. Despite similarities in substrate specificity, basic amino acid-specific proprotein convertases have a distinct tissue distribution allowing for enzymatic actions on tissue-resident substrates. Proprotein convertase 5/6 (PC5/6) has two splice variants - soluble PC5/6A and membrane-bound PC5/6B - and is expressed during mouse development in many tissues including bone and tooth, but little is known about the substrates for PC5/6 therein. Read More

    Moderate-intensity 4mT static magnetic fields prevent bone architectural deterioration and strength reduction by stimulating bone formation in streptozotocin-treated diabetic rats.
    Bone 2017 Oct 27;107:36-44. Epub 2017 Oct 27.
    Department of Orthopedics, The Affiliated Hospital of Air Force Aviation Medicine Research Institute, Beijing 100089, China. Electronic address:
    Type 1 diabetes mellitus (T1DM) has been associated with deterioration of bone microarchitecture and strength, resulting in increased fracture risk. Substantial studies have revealed the capacity of moderate-intensity static magnetic fields (SMF) on promoting osteoblastogenesis in vitro and stimulating bone growth and bone regeneration in vivo, whereas it is unknown whether SMF can resist T1DM-associated osteopenia/osteoporosis. We herein investigated the potential effects of whole-body SMF exposure with 4mT on bone loss in streptozotocin-induced T1DM rats. Read More

    Degradation of extracellular matrix regulates osteoblast migration: A microfluidic-based study.
    Bone 2017 Oct 26;107:10-17. Epub 2017 Oct 26.
    Multiscale in Mechanical and Biological Engineering, Aragon Institute of Engineering Research, Department of Mechanical Engineering, University of Zaragoza, 50018 Zaragoza, Spain. Electronic address:
    Bone regeneration is strongly dependent on the capacity of cells to move in a 3D microenvironment, where a large cascade of signals is activated. To improve the understanding of this complex process and to advance in the knowledge of the role of each specific signal, it is fundamental to analyze the impact of each factor independently. Microfluidic-based cell culture is an appropriate technology to achieve this objective, because it allows recreating realistic 3D local microenvironments by taking into account the extracellular matrix, cells and chemical gradients in an independent or combined scenario. Read More

    Genetic inhibition of PPARγ S112 phosphorylation reduces bone formation and stimulates marrow adipogenesis.
    Bone 2017 Oct 26;107:1-9. Epub 2017 Oct 26.
    Periodontics & Oral Medicine University of Michigan School of Dentistry, University of Michigan School of Medicine, Ann Arbor, MI, United States; Biological Chemistry, University of Michigan School of Medicine, Ann Arbor, MI, United States. Electronic address:
    A common feature of many skeletal diseases is the accumulation of marrow fat. A reciprocal relationship exists between osteogenesis and adipogenesis in bone marrow that is mediated by the relative activity of PPARγ and RUNX2 transcription factors. The ERK/MAPK pathway is an important inducer of MSC differentiation to osteoblasts and an inhibitor of adipogenesis that functions by phosphorylating RUNX2 and PPARγ. Read More

    Hints on transcriptional control of essential players in heterotopic ossification of Fibrodysplasia Ossificans Progressiva.
    Bone 2017 Oct 31. Epub 2017 Oct 31.
    DINOGMI Department, University of Genova, Genova, Italy; Medical Genetics Unit, Istituto Giannina Gaslini, Genova, Italy.
    Signaling of the Bone Morphogenetic Protein (BMP) pathway is influenced by the level of expression of its components, in particular receptors, intracellular molecules and target genes which largely depends on gene transcription. One peculiar aspect of Fibrodysplasia Ossificans Progressiva (FOP) relates to the cell types in which the genetic mutation exerts its effects, then not only those involved in the heterotopic ossification processes but also others that participate in the inflammatory phases preceding and triggering heterotopic ossification. Such effects are in part detectable as variation in gene expression, which is also variably manifesting in term of time of appearance in different phases of the inflammatory or ossification processes. Read More

    Bibliometric analysis of authorship trends and collaboration dynamics over the past three decades of BONE's publication history.
    Bone 2017 Oct 31;107:27-35. Epub 2017 Oct 31.
    Department of Orthopaedic Surgery, Indiana University School of Medicine, Indianapolis, IN, USA. Electronic address:
    The existence of a gender gap in academia has been a hotly debated topic over the past several decades. It has been argued that due to the gender gap, it is more difficult for women to obtain higher positions. Manuscripts serve as an important measurement of one's accomplishments within a particular field of academia. Read More

    Variable signaling activity by FOP ACVR1 mutations.
    Bone 2017 Oct 31. Epub 2017 Oct 31.
    Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Center for Research in FOP and Related Disorders, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address:
    Most patients with fibrodysplasia ossificans progressiva (FOP), a rare genetic disorder of heterotopic ossification, have the same causative mutation in ACVR1, R206H. However, additional mutations within the ACVR1 BMP type I receptor have been identified in a small number of FOP cases, often in patients with disease of lesser or greater severity than occurs with R206H mutations. Genotype-phenotype correlations have been suggested in patients, resulting in classification of FOP mutations based on location within different receptor domains and structural modeling. Read More

    Effects of bone damage on creep behaviours of human vertebral trabeculae.
    Bone 2017 Nov 3;106:204-210. Epub 2017 Nov 3.
    School of Applied Sciences, London South Bank University, London SE1 0AA, UK. Electronic address:
    A subgroup of patients suffering with vertebral fractures can develop progressive spinal deformities over time. The mechanism underlying such clinical observation, however, remains unknown. Previous studies suggested that creep deformation of the vertebral trabeculae may play a role. Read More

    TNFα blockade mediates bone protection in antigen-induced arthritis by reducing osteoclast precursor supply.
    Bone 2017 Nov 14;107:56-65. Epub 2017 Nov 14.
    Department of Rheumatology, Immunology & Allergology, University Hospital, Bern, Switzerland. Electronic address:
    Bone protective effects of TNFα inhibition in rheumatoid arthritis are thought to be mediated by inhibiting synovial osteoclast differentiation and activity. However, it has not been addressed, if TNFα inhibitors alter the pool of peripheral osteoclast precursor cells (OPCs). Here, we blocked TNFα function in C57BL/6 mice with antigen induced arthritis (AIA) using the soluble TNFα receptor etanercept. Read More

    The effect of switching from teriparatide to anti-RANKL antibody on cancellous and cortical bone in ovariectomized mice.
    Bone 2017 Nov 2;107:18-26. Epub 2017 Nov 2.
    Department of Orthopaedic Surgery, Faculty of Medicine, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033, Japan. Electronic address:
    We examined the effect of teriparatide, and switching from teriparatide to anti-RANKL (receptor activator of nuclear factor κB ligand) monoclonal antibody, in ovariectomized mice. Twelve-week-old female C57BL/6 mice were ovariectomized or sham operated. Four weeks after surgery, ovariectomized mice were subjected to one of the following four treatments: phosphate-buffered saline (PBS) for 8weeks; teriparatide for 4weeks followed by PBS for 4weeks (PTH4W group); teriparatide for 8weeks (PTH8W group); or teriparatide for 4weeks followed by anti-RANKL antibody (single subcutaneous injection of 5mg/kg) (SWITCH group). Read More

    Ex vivo replication of phenotypic functions of osteocytes through biomimetic 3D bone tissue construction.
    Bone 2017 Oct 21;106:148-155. Epub 2017 Oct 21.
    Department of Materials Science and Chemical Engineering, Stevens Institute of Technology, Hoboken, NJ, USA. Electronic address:
    Osteocytes, residing as 3-dimensionally (3D) networked cells in bone, are well known to regulate bone and mineral homeostasis and have been recently implicated to interact with cancer cells to influence the progression of bone metastases. In this study, a bone tissue consisting of 3D-networked primary human osteocytes and MLO-A5 cells was constructed using: (1) the biomimetic close-packed assembly of 20-25μm microbeads with primary cells isolated from human bone samples and MLO-A5 cells and (2) subsequent perfusion culture in a microfluidic device. With this 3D tissue construction approach, we replicated ex vivo, for the first time, the mechanotransduction function of human primary osteocytes and MLO-A5 cells by correlating the effects of cyclic compression on down-regulated SOST and DKK1 expressions. Read More

    Dicer1 ablation in osterix positive bone forming cells affects cortical bone homeostasis.
    Bone 2017 Oct 21;106:139-147. Epub 2017 Oct 21.
    Institute of Biomedicine, University of Turku, Kiinamyllynkatu 10, FI20520 Turku, Finland. Electronic address:
    The RNAse III enzyme Dicer plays a major role in the processing of microRNAs from large pre-miRNAs. Dicer1 processed microRNAs are known to play a comprehensive role in osteoblast differentiation, bone remodeling and skeletal disorders. Targeted deletion of Dicer1 in osteo-progenitor cells is deleterious to fetal survival whereas targeted deletion in mature osteoblasts leads to an increase in bone mass. Read More

    Pharmacological inhibition of tankyrase induces bone loss in mice by increasing osteoclastogenesis.
    Bone 2017 Oct 18;106:156-166. Epub 2017 Oct 18.
    Department of Rheumatology, Kawasaki Medical School, Kurashiki, Japan.
    Tankyrase is a poly (ADP-ribose) polymerase that leads to ubiquitination and degradation of target proteins. Since tankyrase inhibitors suppress the degradation of AXIN protein, a negative regulator of the canonical Wnt pathway, they effectively act as Wnt inhibitors. Small molecule tankyrase inhibitors are being investigated as drug candidates for cancer and fibrotic diseases, in which the Wnt pathways are aberrantly activated. Read More

    Risk of fracture in transfusion-naïve thalassemia population: A nationwide population-based retrospective cohort study.
    Bone 2017 Oct 18;106:121-125. Epub 2017 Oct 18.
    Department of Orthopedics, China Medical University Hospital & School of Medicine, China Medical University,Taichung, Taiwan. Electronic address:
    In thalassemia major or transfusion-dependent thalassemia patients, osteoporosis-related bone complications such as fracture events are common. However, no studies have investigated the risk of fracture in transfusion-naïve thalassemia population. Therefore, we conducted a longitudinal nationwide cohort study to determine whether this population has an increased risk of fracture. Read More

    Skeletal impairment in Pierson syndrome: Is there a role for lamininβ2 in bone physiology?
    Bone 2017 Oct 16;106:187-193. Epub 2017 Oct 16.
    Centre de Référence des Maladies Rénales Rares, Hôpital Femme Mère Enfant, Hospices, Civils de Lyon, 69677 Bron, France; INSERM, UMR 1033, Université Claude Bernard Lyon 1, Lyon, France; Service de Chirurgie Orthopédique Pédiatrique, Hôpital Femme Mère Enfant, Hospices Civils de Lyon, Bron, France; Institute of Human Genetics, University Hospital Magdeburg, Germany; Faculté de Médecine Lyon Est, Université de Lyon, France, Lyon. Electronic address:
    Introduction: Pierson syndrome is caused by a mutation of LAMB2, encoding for laminin β2. Clinical phenotype is variable but usually associates congenital nephrotic syndrome (CNS) and ocular abnormalities. Neuromuscular impairment has also been described. Read More

    Clinical-pathological correlations in three patients with fibrodysplasia ossificans progressiva.
    Bone 2017 Oct 13. Epub 2017 Oct 13.
    Division of Endocrinology, Diabetes, and Metabolism, Institute for Human Genetics, Department of Medicine, University of California, San Francisco, CA, United States. Electronic address:
    Objective: Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare genetic disorder in which heterotopic bone forms in the soft tissues. This often occurs in response to injury or inflammation, leading to joint immobilization and significant disability. There are currently no definitive treatment options for this devastating disease. Read More

    The effect of once-yearly zoledronic acid on hip structural and biomechanical properties derived using computed tomography (CT) in Japanese women with osteoporosis.
    Bone 2017 Oct 12;106:179-186. Epub 2017 Oct 12.
    Japan Osteoporosis Foundation, 2-14 Odenma-cho, Nihonbashi Chuo-ku, Tokyo, Japan.
    The effects of zoledronic acid on hip structural and biomechanical properties were evaluated in Japanese patients with osteoporosis by computed tomography (CT). The subjects included in this study were a subset of female subjects (zoledronic acid group, 49 subjects; placebo group, 53 subjects) in the phase 3 trial (ZONE study) who were available for multi-detector row CT (MDCT) scanning. Eligible subjects were those diagnosed with primary osteoporosis based on the Diagnostic Criteria for Primary Osteoporosis (2000) by the Japanese Society for Bone and Mineral Research and who had between one and four fractured vertebrae located between the fourth thoracic vertebra and the fourth lumbar vertebra. Read More

    CD105 is regulated by hsa-miR-1287 and its expression is inversely correlated with osteopotential in SHED.
    Bone 2017 Oct 13;106:112-120. Epub 2017 Oct 13.
    Departamento de Genética e Evolução, Instituto de Biociências, Universidade de São Paulo, São Paulo, Brazil. Electronic address:
    A more accurate understanding of the molecular mechanisms and signaling pathways underpinning human mesenchymal stem cell (MSC) plasticity and differentiation properties is pivotal for accomplishing solid and diligent translation of MSC-based experimental therapeutics and clinical trials to broad clinical practice. In addition, this knowledge enables selection of MSC subpopulations with increased differentiation potential and/or use of exogenous factors to boost this potential. Here, we report that CD105 (ENG) is a predictive biomarker of osteogenic potential in two types of MSCs: stem cells from human exfoliated deciduous teeth (SHED) and human adipose-derived stem cells (hASC). Read More

    The effect of raloxifene on bone marrow adipose tissue and bone turnover in postmenopausal women with osteoporosis.
    Bone 2017 Oct 11. Epub 2017 Oct 11.
    Leiden University Medical Center, Department of Internal Medicine, Albinusdreef 2, PO Box 9600, 2300RC Leiden, The Netherlands; VU University Medical Center, Department of Clinical Chemistry, The Netherlands. Electronic address:
    In patients with postmenopausal osteoporosis low bone volume is associated with high bone marrow adipose tissue (MAT). Moreover, high MAT is associated with increased fracture risk. This suggests an interaction between MAT and bone turnover, however literature remains equivocal. Read More

    C/EBPα and PU.1 exhibit different responses to RANK signaling for osteoclastogenesis.
    Bone 2017 Oct 11. Epub 2017 Oct 11.
    Department of Pathology, University of Alabama, Birmingham, AL 35294, United States. Electronic address:
    The transcription factors C/EBPα and PU.1 are upregulated by RANKL through activation of its receptor RANK during osteoclastogenesis and are critical for osteoclast differentiation. Herein we investigated the mechanisms underlying how C/EBPα and PU. Read More

    The reduced osteogenic potential of Nf1-deficient osteoprogenitors is EGFR-independent.
    Bone 2017 Oct 12;106:103-111. Epub 2017 Oct 12.
    Department of Orthopedic Surgery, Baylor College of Medicine, Houston, TX, United States; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, United States. Electronic address:
    Neurofibromatosis type 1 (NF1) is a common genetic disorder caused by mutations in the NF1 gene. Recalcitrant bone healing following fracture (i.e. Read More

    A novel bone targeting delivery system carrying phytomolecule icaritin for prevention of steroid-associated osteonecrosis in rats.
    Bone 2017 Oct 10;106:52-60. Epub 2017 Oct 10.
    Musculoskeletal Research Laboratory of Department of Orthopaedics & Traumatology and Innovative Orthopaedic Biomaterial and Drug Translational Research Laboratory of Li Ka Shing Institute of Health, The Chinese University of Hong Kong, Hong Kong, PR China.; Translational Medicine R&D Center, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, PR China.. Electronic address:
    One of the effective strategies for prevention of steroid-associated osteonecrosis (SAON) is to inhibit bone resorption and fat formation and promote bone formation at osteonecrotic sensitive skeletal sites. We identified a novel phytomolecule that showed positive effects on osteogenesis, anti-bone resorption and anti-adipogenesis in vitro and also developed a bone-targeting delivery system (BTDS) for in vivo experimental study. The study investigated if our innovative synthesized BTDS carrying this phytomolecule would be able to effectively prevent SAON in a rat model. Read More

    ALS-associated mutation SOD1(G93A) leads to abnormal mitochondrial dynamics in osteocytes.
    Bone 2017 Oct 10;106:126-138. Epub 2017 Oct 10.
    Kansas City University of Medicine and Bioscience, Kansas City, MO, USA. Electronic address:
    While the death of motor neuron is a pathological hallmark of amyotrophic lateral sclerosis (ALS), defects in other cell types or organs may also actively contribute to ALS disease progression. ALS patients experience progressive skeletal muscle wasting that may not only exacerbate neuronal degeneration, but likely has a significant impact on bone function. In our previous published study, we have discovered severe bone loss in an ALS mouse model with overexpression of ALS-associated mutation SOD1(G93A) (G93A). Read More

    Muscle functions and bone strength are impaired in adolescents with type 1 diabetes.
    Bone 2017 Oct 7;106:22-27. Epub 2017 Oct 7.
    Department of Pediatrics, Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, V Uvalu 84, 150 06 Prague 5, Czech Republic. Electronic address:
    Background: Sarcopenia and osteoporosis are among the late complications of type 1 diabetes (T1D) in adults. Whether and to what extent musculoskeletal impairment is present in childhood and adolescence has yet to be determined. The aim of this study was to assess volumetric bone mineral density (BMD) and dynamic muscle function in adolescents with T1D and to assess the clinical and biochemical predictors of their musculoskeletal system. Read More

    DKK1 and sclerostin are early markers of relapse in multiple myeloma.
    Bone 2017 Oct 6. Epub 2017 Oct 6.
    Centre de rhumatologie, Hopital Purpan, 1 place du docteur Joseph Baylac, 31300 Toulouse, France.
    Recent studies have shown that Dickkopf-related protein (DKK1) and sclerostin decrease when a complete response (CR) is obtained after chemotherapy in myeloma multiple (MM). To study variations in DKK1, sclerostin and P1NP in patients treated for MM, between complete response (CR) and relapse, we carried out a prospective study ancillary to the IFM 2009 protocol (IFM). The aim of IFM was to compare progression-free survival between patients treated with chemotherapy with or without transplantation. Read More

    Determination of sex differences of human cadaveric mandibular condyles using statistical shape and trait modeling.
    Bone 2017 Oct 4;106:35-41. Epub 2017 Oct 4.
    Southwest Research Institute, Mechanical Engineering Division, 6220 Culebra Road, San Antonio, TX 78228, United States. Electronic address:
    The objective of this study was to elucidate sex differences in the anatomy of human temporomandibular joint mandibular condyles using a statistical shape and trait model (SSTM). Mandibles were obtained from 16 human cadavers (79±13years). The condyles were scanned using micro-computed tomography with 27μm resolution. Read More

    Heterotopic ossification and the elucidation of pathologic differentiation.
    Bone 2017 Oct 5. Epub 2017 Oct 5.
    Department of Surgery, University of Michigan Health System, Ann Arbor, MI, USA. Electronic address:
    Tissue regeneration following acute or persistent inflammation can manifest a spectrum of phenotypes ranging from the adaptive to the pathologic. Heterotopic Ossification (HO), the endochondral formation of bone within soft-tissue structures following severe injury serves as a prominent example of pathologic differentiation; and remains a persistent clinical issue incurring significant patient morbidity and expense to adequately diagnose and treat. The pathogenesis of HO provides an intriguing opportunity to better characterize the cellular and cell-signaling contributors to aberrant differentiation. Read More

    Validation of calcaneus trabecular microstructure measurements by HR-pQCT.
    Bone 2017 Oct 3;106:69-77. Epub 2017 Oct 3.
    MRC-Arthritis UK Centre for Integrated research into Musculoskeletal Ageing (CIMA), Department of Oncology and Metabolism, University of Sheffield, Metabolic Bone Centre, Northern General Hospital, Herries Road, Sheffield S5 7AU, UK; Department of Oncology and Metabolism and INSIGNEO Institute for in silico Medicine, University of Sheffield, The Pam Liversidge Building, Sir Robert Hadfield Building, Mappin Street, Sheffield S1 3JD, UK. Electronic address:
    Objective: Assessment of calcaneus microstructure using high-resolution peripheral quantitative computed tomography (HR-pQCT) might be used to improve fracture risk predictions or to assess responses to pharmacological and physical interventions. To develop a standard clinical protocol for the calcaneus, we validated calcaneus trabecular microstructure measured by HR-pQCT against 'gold-standard' micro-CT measurements.

    Methods: Ten human cadaveric feet were scanned in situ using HR-pQCT (isotropic 82μm voxel size) at 100, 150 and 200ms integration times, and at 100ms integration time following removal of the calcaneus from the foot (ex vivo). Read More

    Identification of a novel loss-of-function PHEX mutation, Ala720Ser, in a sporadic case of adult-onset hypophosphatemic osteomalacia.
    Bone 2017 Oct 3;106:30-34. Epub 2017 Oct 3.
    Department of Musculoskeletal Biology, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, UK; Department of Clinical Biochemistry and Metabolic Medicine, Royal Liverpool University Hospital, Liverpool, UK. Electronic address:
    Adults presenting with sporadic hypophosphatemia and elevations in circulating fibroblast growth factor-23 (FGF23) concentrations are usually investigated for an acquired disorder of FGF23 excess such as tumor induced osteomalacia (TIO). However, in some cases the underlying tumor is not detected, and such patients may harbor other causes of FGF23 excess. Indeed, coding-region and 3'UTR mutations of phosphate-regulating neutral endopeptidase (PHEX), which encodes a cell-surface protein that regulates circulating FGF23 concentrations, can lead to alterations in phosphate homeostasis, which are not detected until adulthood. Read More

    Low-1 level mechanical vibration improves bone microstructure, tissue mechanical properties and porous titanium implant osseointegration by promoting anabolic response in type 1 diabetic rabbits.
    Bone 2017 Oct 2;106:11-21. Epub 2017 Oct 2.
    Department of Biomedical Engineering, Fourth Military Medical University, Xi'an, China. Electronic address:
    Type 1 diabetes mellitus (T1DM) is associated with reduced bone mass, increased fracture risk, and impaired bone defect regeneration potential. These skeletal complications are becoming important clinical challenges due to the rapidly increasing T1DM population, which necessitates developing effective treatment for T1DM-associated osteopenia/osteoporosis and bone trauma. This study aims to investigate the effects of whole-body vibration (WBV), an easy and non-invasive biophysical method, on bone microstructure, tissue-level mechanical properties and porous titanium (pTi) osseointegration in alloxan-diabetic rabbits. Read More

    Effects of single or combination therapy of teriparatide and anti-RANKL monoclonal antibody on bone defect regeneration in mice.
    Bone 2017 Oct 1;106:1-10. Epub 2017 Oct 1.
    Department of Orthopedic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
    Objective: The purpose of this study is to investigate the effects of a single or combination therapy of teriparatide (TPTD) and anti-RANKL Ab (anti-murine receptor activator of nuclear factor κB ligand monoclonal antibody) on the regeneration of both cancellous and cortical bone.

    Methods: Nine-week-old mice underwent bone defect surgery on the left femoral metaphysis (cancellous-bone healing model) and right femoral mid-diaphysis (cortical-bone healing model). After surgery, the mice were assigned to 1 of 4 groups to receive 1) saline (5 times a week; CNT group), 2) TPTD (40μg/kg 5 times a week; TPTD group), 3) anti-RANKL Ab (5mg/kg once; Ab group), or 4) a combination of TPTD and anti-RANKL Ab (COMB group). Read More

    Bone replaces articular cartilage in the rat knee joint after prolonged immobilization.
    Bone 2017 Sep 30;106:42-51. Epub 2017 Sep 30.
    Department of Medicine, University of Ottawa, Ontario, Canada; The Ottawa Hospital Rehabilitation Centre, Ottawa, Ontario, Canada. Electronic address:
    Background: Lost joint range of motion (ROM) is common in chronic osteoarthritis, alters regional weight-bearing across the articular surfaces, and contributes to loss of cartilage and bone alterations. Limited data exist on the regional effects on joints subjected to chronic losses of ROM.

    Objective: To characterize the regional replacement by bone as part of articular cartilage degeneration after prolonged immobilization. Read More

    Pulsed electromagnetic fields inhibit human osteoclast formation and gene expression via osteoblasts.
    Bone 2017 Sep 28;106:194-203. Epub 2017 Sep 28.
    Department of Basic Science and Craniofacial Biology, New York University College of Dentistry, New York, NY, USA. Electronic address:
    Pulsed electromagnetic fields (PEMFs) can be effective in promoting the healing of delayed union or nonunion fractures. We previously reported that PEMF (Spinal-Stim® by Orthofix, Inc., Lewisville, TX) stimulated proliferation, differentiation and mineralization of rat calvarial osteoblastic cells in culture. Read More

    Identification of mutations in the prostaglandin transporter gene SLCO2A1 and phenotypic comparison between two subtypes of primary hypertrophic osteoarthropathy (PHO): A single-center study.
    Bone 2017 Sep 28;106:96-102. Epub 2017 Sep 28.
    Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Shuaifuyuan No. 1, Wangfujing, Dongcheng District, Beijing 100730, China. Electronic address:
    Primary hypertrophic osteoarthropathy (PHO) is an inherited disease characterized by digital clubbing, periostosis, and pachydermia. Based on two causative genes, hydroxyprostaglandin dehydrogenase (HPGD) and solute carrier organic anion transporter family member 2A1 (SLCO2A1), PHO is categorized into two subtypes: hypertrophic osteoarthropathy, primary, autosomal recessive 1 (PHOAR1) and hypertrophic osteoarthropathy, primary, autosomal recessive 2 (PHOAR2). In this study, we summarized the clinical manifestations and analyzed SLCO2A1 gene in 23 PHOAR2 patients in our center. Read More

    Cartilage-derived retinoic acid-sensitive protein (CD-RAP): A stage-specific biomarker of heterotopic endochondral ossification (HEO) in fibrodysplasia ossificans progressiva (FOP).
    Bone 2017 Sep 28. Epub 2017 Sep 28.
    Department of Medicine, Mayo Clinic School of Medicine, Mayo Clinic, Rochester, MN, United States. Electronic address:
    Background: Genesis of a cartilaginous scaffold is an obligate precursor to bone formation in heterotopic endochondral ossification (HEO). We tested the hypothesis that cartilage-derived retinoic acid-sensitive protein (CD-RAP) can serve as a plasma biomarker for the pre-osseous cartilaginous stage of HEO. Palovarotene, a retinoic acid receptor-gamma (RARγ) agonist, has been proposed as a possible treatment for fibrodysplasia ossificans progressiva (FOP) and is a potent inhibitor of HEO in mouse models. Read More

    Comparisons of TBS and lumbar spine BMD in the associations with vertebral fractures according to the T-scores: A cross-sectional observation.
    Bone 2017 Dec 28;105:269-275. Epub 2017 Sep 28.
    Department of Internal Medicine, Seoul National University Bundang Hospital and Seoul National University College of Medicine, Seongnam, Republic of Korea.
    Trabecular bone score (TBS) is a parameter of bone quality that has been shown to be related to vertebral fractures. This study aimed to analyze the difference in discriminatory power of TBS for vertebral fractures according to the bone mineral density (BMD) T-score. Areal BMD at the lumbar spine (LS, L1-L4), femur neck (FN) and total hip were assessed using dual x-ray absorptiometry (Discovery W, Hologic, Bedford, MA) in 929 women aged 50years or older. Read More

    Clinical staging of Fibrodysplasia Ossificans Progressiva (FOP).
    Bone 2017 Sep 21. Epub 2017 Sep 21.
    Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States; Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States; The Center for Research in FOP and Related Disorders, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States. Electronic address:
    Fibrodyplasia ossificans progressiva (FOP) is an ultra-rare genetic condition of heterotopic ossification (HO) that results in progressive loss of joint function, ultimately rendering movement impossible. Death is most commonly the result of thoracic insufficiency syndrome, or complications related to recurrent respiratory infections. There are no current treatments for FOP, but early and emerging clinical trials offer hope for this devastating disease. Read More

    A single intraperitoneal injection of bovine fetuin-A attenuates bone resorption in a murine calvarial model of particle-induced osteolysis.
    Bone 2017 Dec 21;105:262-268. Epub 2017 Sep 21.
    University Hospital Essen, Department of Orthopedics and Trauma Surgery, University of Duisburg-Essen, Hufelandstrasse 55, 45147 Essen, Germany.
    Particle-induced osteolysis, which by definition is an aseptic inflammatory reaction to implant-derived wear debris eventually leading to local bone destruction, remains the major reason for long-term failure of orthopedic endoprostheses. Fetuin-A, a 66kDa glycoprotein with diverse functions, is found to be enriched in bone. Besides being an important inhibitor of ectopic calcification, it has been described to influence the production of mediators of inflammation. Read More

    Clcn7(F318L/+) as a new mouse model of Albers-Schönberg disease.
    Bone 2017 Dec 20;105:253-261. Epub 2017 Sep 20.
    Orthopaedic Research Laboratories, Boston Children's Hospital, Boston, MA, USA; Department of Genetics, Harvard Medical School, Boston, MA, USA; Howard Hughes Medical Institute, Boston Children's Hospital, Boston, MA, USA. Electronic address:
    Dominant negative mutations in CLCN7, which encodes a homodimeric chloride channel needed for matrix acidification by osteoclasts, cause Albers-Schönberg disease (also known as autosomal dominant osteopetrosis type 2). More than 25 different CLCN7 mutations have been identified in patients affected with Albers-Schönberg disease, but only one mutation (Clcn7(G213R)) has been introduced in mice to create an animal model of this disease. Here we describe a mouse with a different osteopetrosis-causing mutation (Clcn7(F318L)). Read More

    Ex vivo construction of human primary 3D-networked osteocytes.
    Bone 2017 Dec 21;105:245-252. Epub 2017 Sep 21.
    Department of Materials Science and Chemical Engineering, Stevens Institute of Technology, Hoboken, NJ, USA. Electronic address:
    A human bone tissue model was developed by constructing ex vivo the 3D network of osteocytes via the biomimetic assembly of primary human osteoblastic cells with 20-25μm microbeads and subsequent microfluidic perfusion culture. The biomimetic assembly: (1) enabled 3D-constructed cells to form cellular network via processes with an average cell-to-cell distance of 20-25μm, and (2) inhibited cell proliferation within the interstitial confine between the microbeads while the confined cells produced extracellular matrix (ECM) to form a mechanically integrated structure. The mature osteocytic expressions of SOST and FGF23 genes became significantly higher, especially for SOST by 250 folds during 3D culture. Read More

    Immobilization-induced osteolysis and recovery in neuropathic foot impairments.
    Bone 2017 Dec 20;105:237-244. Epub 2017 Sep 20.
    Dept Orthopaedic Surgery, Campus Box 8233, Foot & Ankle Service, Washington University School of Medicine, Saint Louis, MO, United States. Electronic address:
    Background: Neuropathic foot impairments treated with immobilization and off-loading result in osteolysis. In order to prescribe and optimize rehabilitation programs after immobilization we need to understand the magnitude of pedal osteolysis after immobilization and the time course for recovery.

    Objective: To determine differences in a) foot skin temperature; b) calcaneal bone mineral density (BMD) after immobilization; c) calcaneal BMD after 33-53weeks of recovery; and d) percent of feet classified as osteopenic or osteoporotic after recovery in participants with neuropathic plantar ulcers (NPU) compared to Charcot neuroarthropathy (CNA). Read More

    Combination of PTH (1-34) with anti-IL17 prevents bone loss by inhibiting IL-17/N-cadherin mediated disruption of PTHR1/LRP-6 interaction.
    Bone 2017 Dec 19;105:226-236. Epub 2017 Sep 19.
    Division of Endocrinology, Centre for Research in Anabolic Skeletal Targets in Health and Illness (ASTHI), CSIR-Central Drug Research Institute, B.S. 10/1, Sector-10, Jankipuram Extension, Lucknow, India. Electronic address:
    Combinations of anabolic and anti-resorptive agents have potential to improve bone density more than either agent alone. In this study, we determine the combining effect of anti-IL17 antibody and PTH (1-34) in mitigation of ovariectomy induced bone loss. Ovariectomized BALB/c female mice were treated with anti-IL17 and iPTH monotherapies and their combination. Read More

    A review of sarcopenia: Enhancing awareness of an increasingly prevalent disease.
    Bone 2017 Dec 18;105:276-286. Epub 2017 Sep 18.
    Department of Orthopedic Surgery, Hospital for Special Surgery, New York, NY 10021, United States. Electronic address:
    Sarcopenia is defined as an age associated decline in skeletal muscle mass. The pathophysiology of sarcopenia is multifactorial, with decreased caloric intake, muscle fiber denervation, intracellular oxidative stress, hormonal decline, and enhanced myostatin signaling all thought to contribute. Prevalence rates are as high as 29% and 33% in elderly community dwelling and long-term care populations, respectively, with advanced age, low body mass index, and low physical activity as significant risk factors. Read More

    Corrigendum to "Even with rehydration, preservation in ethanol influences the mechanical properties of bone and how bone responds to experimental manipulation" [Bone 97 (2017) 49-53].
    Bone 2017 Dec 18;105:218. Epub 2017 Sep 18.
    Department of Biomedical Engineering, Indiana University-Purdue University Indianapolis, IN, United States; Department of Orthopaedic Surgery, Indiana University School of Medicine, IN, United States. Electronic address:

    Prevalence and risk factors for fragility fracture in systemic mastocytosis.
    Bone 2017 Dec 14;105:219-225. Epub 2017 Sep 14.
    Department of Dermatology, Mastocytosis Expert Center of Midi-Pyrénées, Paul Sabatier University, Toulouse University Hospital, Toulouse, France. Electronic address:
    Objectives: Systemic mastocytosis (SM) is characterized by the accumulation of mast cells in tissues other than the skin. Bone involvement although frequent has not been thoroughly evaluated. Primary objective was to determine risk factors associated with fragility fractures (FF) in SM. Read More

    Structural basis for the potent and selective binding of LDN-212854 to the BMP receptor kinase ALK2.
    Bone 2017 Sep 12. Epub 2017 Sep 12.
    Structural Genomics Consortium, University of Oxford, Roosevelt Drive, Oxford OX3 7DQ, UK. Electronic address:
    Individuals with the rare developmental disorder fibrodysplasia ossificans progressiva (FOP) experience disabling heterotopic ossification caused by a gain of function mutation in the intracellular region of the BMP type I receptor kinase ALK2, encoded by the gene ACVR1. Small molecule BMP type I receptor inhibitors that block this ossification in FOP mouse models have been derived from the pyrazolo[1,5-a]pyrimidine scaffold of dorsomorphin. While the first derivative LDN-193189 exhibited pan inhibition of BMP receptors, the more recent compound LDN-212854 has shown increased selectivity for ALK2. Read More

    Effect of eplerenone on markers of bone turnover in patients with primary hyperparathyroidism - The randomized, placebo-controlled EPATH trial.
    Bone 2017 Dec 14;105:212-217. Epub 2017 Sep 14.
    Department of Cardiology, Medical University of Graz, Graz, Austria; Medical Clinic V (Nephrology, Hypertensiology, Endocrinology), Medical Faculty Mannheim, Ruperto Carola University Heidelberg, Mannheim, Germany; Bad Gleichenberg Clinic, Bad Gleichenberg, Austria.
    Mineralocorticoid receptor (MR) antagonism may affect bone turnover via direct and indirect pathways involving parathyroid hormone, but randomized controlled trials are lacking. In a pre-specified analysis of the "Eplerenone in primary hyperparathyroidism" placebo-controlled, randomized trial (ISRCTN 33941607), effects of eight weeks MR-blockade with eplerenone on bone turnover markers in 97 patients with primary hyperparathyroidism were tested. Mean age was 67. Read More

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