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    Prevalence and risk factors for fragility fracture in systemic mastocytosis.
    Bone 2017 Sep 14. 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 Sep 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

    Obesity and type 2 diabetes, not a diet high in fat, sucrose, and cholesterol, negatively impacts bone outcomes in the hyperphagic Otsuka Long Evans Tokushima Fatty rat.
    Bone 2017 Sep 9;105:200-211. Epub 2017 Sep 9.
    Department of Nutrition and Exercise Physiology, University of Missouri, Columbia, MO, United States. Electronic address:
    Background: Obesity and type 2 diabetes (T2D) increase fracture risk; however, the association between obesity/T2D may be confounded by consumption of a diet high in fat, sucrose, and cholesterol (HFSC).

    Objective: The study objective was to determine the main and interactive effects of obesity/T2D and a HFSC diet on bone outcomes using hyperphagic Otuska Long Evans Tokushima Fatty (OLETF) rats and normophagic Long Evans Tokushima Otsuka (LETO) controls.

    Methods: At 8weeks of age, male OLETF and LETO rats were randomized to either a control (CON, 10 en% from fat as soybean oil) or HFSC (45 en% from fat as soybean oil/lard, 17 en% sucrose, and 1wt%) diet, resulting in four treatment groups. Read More

    Secular trends of use of anti-osteoporosis treatments in Spain: A population-based cohort study including over 1.5million people and more than 12years of follow-up.
    Bone 2017 Sep 7. Epub 2017 Sep 7.
    BIFAP, Division of Pharmacoepidemiology and Pharmacovigilance, Spanish Agency of Medicines and Medical Devices (AEMPS), Madrid, Spain.
    Objective: Different regulatory actions for anti-osteoporosis medication (AOM) were taken during the last years, including marketing of new drugs, safety warnings, or restrictions on the indications. We aimed to characterise the secular trends of AOM use in Spain from 2001 to 2013.

    Methods: A cohort study using the Spanish Database for Pharmacoepidemiological Research in Primary Care (BIFAP), was performed. Read More

    GNAS mutations and heterotopic ossification.
    Bone 2017 Sep 6. Epub 2017 Sep 6.
    Endocrine Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, United States. Electronic address:
    GNAS is a complex imprinted gene encoding the alpha-subunit of the stimulatory heterotrimeric G protein (Gsα). GNAS gives rise to additional gene products that exhibit exclusively maternal or paternal expression, such as XLαs, a large variant of Gsα that shows exclusively paternal expression and is partly identical to the latter. Gsα itself is expressed biallelically in most tissues, although the expression occurs predominantly from the maternal allele in a small set of tissues, such as renal proximal tubules. Read More

    Evidence of disordered calcium metabolism in adolescent girls with type 1 diabetes: An observational study using a dual-stable calcium isotope technique.
    Bone 2017 Sep 4;105:184-190. Epub 2017 Sep 4.
    Department of Pediatrics, Golisano Children's Hospital, The University of Rochester School of Medicine and Dentistry, 601 Elmwood Ave, Box 690, Rochester, NY 14642, USA. Electronic address:
    Type 1 diabetes (T1D) is associated with skeletal abnormalities including low bone density and increased fracture risk. The pathophysiology underlying T1D related skeletal fragility remains unknown. The objective of this study was to use a dual-stable calcium isotope method to investigate the effects of T1D on calcium absorption and estimated calcium retention in adolescent females. Read More

    Automatic registration of 2D histological sections to 3D microCT volumes: Trabecular bone.
    Bone 2017 Sep 1;105:173-183. Epub 2017 Sep 1.
    Computer-assisted Applications in Medicine, ETH Zürich, Switzerland.
    Histomorphometry and microCT are the two dominant imaging techniques to study bone structure and quality to evaluate repair, regeneration, and disease. These two methods are complementary; where histology provides highly resolved tissue properties on a cellular level in 2D, microCT provides spatial information of bone micro-structure in 3D. For this reason, both of these modalities are commonly used in bone studies. Read More

    Etelcalcetide (AMG 416), a peptide agonist of the calcium-sensing receptor, preserved cortical bone structure and bone strength in subtotal nephrectomized rats with established secondary hyperparathyroidism.
    Bone 2017 Sep 1;105:163-172. Epub 2017 Sep 1.
    Department of Cardiometabolic Disorders, Amgen Inc., Thousand Oaks, CA, USA.
    Sustained elevation of parathyroid hormone (PTH) is catabolic to cortical bone, as evidenced by deterioration in bone structure (cortical porosity), and is a major factor for increased fracture risk in chronic kidney disease (CKD). Etelcalcetide (AMG 416), a novel peptide agonist of the calcium-sensing receptor, reduces PTH levels in subtotal nephrectomized (Nx) rats and in hemodialysis patients with secondary hyperparathyroidism (SHPT) in clinical studies; however, effects of etelcalcetide on bone have not been determined. In a rat model of established SHPT with renal osteodystrophy, etelcalcetide or vehicle was administered by subcutaneous (s. Read More

    Overlapping functions of bone sialoprotein and pyrophosphate regulators in directing cementogenesis.
    Bone 2017 Sep 1;105:134-147. Epub 2017 Sep 1.
    Biosciences Division, College of Dentistry, The Ohio State University, Columbus, OH, USA. Electronic address:
    Although acellular cementum is essential for tooth attachment, factors directing its development and regeneration remain poorly understood. Inorganic pyrophosphate (PPi), a mineralization inhibitor, is a key regulator of cementum formation: tissue-nonspecific alkaline phosphatase (Alpl/TNAP) null mice (increased PPi) feature deficient cementum, while progressive ankylosis protein (Ank/ANK) null mice (decreased PPi) feature increased cementum. Bone sialoprotein (Bsp/BSP) and osteopontin (Spp1/OPN) are multifunctional extracellular matrix components of cementum proposed to have direct and indirect effects on cell activities and mineralization. Read More

    The FOP Connection Registry: Design of an international patient-sponsored registry for Fibrodysplasia Ossificans Progressiva.
    Bone 2017 Aug 30. Epub 2017 Aug 30.
    International FOP Association, 1520 Clay St, Suite H2, North Kansas City, MO 64116, USA. Electronic address:
    The Fibrodysplasia Ossificans Progressiva (FOP) Connection Registry is an international, voluntary, observational study that directly captures demographic and disease information initially from patients with FOP (the patient portal) and in the near future from treating physicians (the physician portal) via a secure web-based tool. It was launched by the International FOP Association (IFOPA) with a guiding vision to develop and manage one unified, global, and coordinated Registry allowing the assembly of the most comprehensive data on FOP. This will ultimately facilitate greater access and sharing of patient data and enable better and faster development of therapies and tracking their long-term treatment effectiveness and safety. Read More

    Fatty acid metabolism by the osteoblast.
    Bone 2017 Aug 30. Epub 2017 Aug 30.
    Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Baltimore Veterans Administration Medical Center, Baltimore, MD, USA. Electronic address:
    The emergence of bone as an endocrine organ able to influence whole body metabolism, together with comorbid epidemics of obesity, diabetes, and osteoporosis, have prompted a renewed interest in the intermediary metabolism of the osteoblast. To date, most studies have focused on the utilization of glucose by this specialized cell, but the oxidation of fatty acids results in a larger energy yield. Osteoblasts express the requisite receptors and catabolic enzymes to take up and then metabolize fatty acids, which appears to be required during later stages of differentiation when the osteoblast is dedicated to matrix production and mineralization. Read More

    The prenylflavonoid Icaritin enhances osteoblast proliferation and function by signal transducer and activator of transcription factor 3 (STAT-3) regulation of C-X-C chemokine receptor type 4 (CXCR4) expression.
    Bone 2017 Aug 31;105:122-133. Epub 2017 Aug 31.
    Department of Obstetrics & Gynaecology, National University of Singapore, Singapore. Electronic address:
    In this study, we examined the effects of a natural prenylflavonoid Icaritin (ICT), on human osteoblast proliferation and osteogenic function. We observed that ICT dose-dependently enhanced osteoblast proliferation by ~15% over a 7day period. This increase in cell proliferation was associated with corresponding increases in osteoblast functions as measured by ALP secretion, intracellular calcium ions influx and calcium deposition. Read More

    Regulatory elements driving the expression of skeletal lineage reporters differ during bone development and adulthood.
    Bone 2017 Aug 31;105:154-162. Epub 2017 Aug 31.
    Laboratory of Clinical and Experimental Endocrinology, Department of Clinical and Experimental Medicine, KU Leuven, Leuven, Belgium; Prometheus, Division of Skeletal Tissue Engineering, KU Leuven, Leuven, Belgium. Electronic address:
    To improve bone healing or regeneration more insight in the fate and role of the different skeletal cell types is required. Mouse models for fate mapping and lineage tracing of skeletal cells, using stage-specific promoters, have advanced our understanding of bone development, a process that is largely recapitulated during bone repair. However, validation of these models is often only performed during development, whereas proof of the activity and specificity of the used promoters during the bone regenerative process is limited. Read More

    Heterotopic ossification: Mechanistic insights and clinical challenges.
    Bone 2017 Aug 27. Epub 2017 Aug 27.
    Department of Developmental Biology, Harvard School of Dental Medicine, 188 Longwood Ave. Boston, MA 02215, USA. Electronic address:
    Bone formation is exquisitely controlled both spatially and temporally. Heterotopic ossification (HO) is pathological bone formation in soft tissues that often leads to deleterious outcomes. Inherited genetic forms of HO can be life-threatening and can happen as early as in infancy. Read More

    Mast cell inhibition as a therapeutic approach in fibrodysplasia ossificans progressiva (FOP).
    Bone 2017 Aug 26. Epub 2017 Aug 26.
    Department of Medicine, Mayo Clinic School of Medicine, Mayo Clinic, Rochester, MN, United States. Electronic address:
    Background: Episodic flare-ups of fibrodysplasia ossificans progressiva (FOP) are characterized clinically by severe, often posttraumatic, connective tissue swelling and intramuscular edema, followed histologically by an intense and highly angiogenic fibroproliferative reaction. This early inflammatory and angiogenic fibroproliferative response is accompanied by the presence of abundant mast cells far in excess of other reported myopathies.

    Results: Using an injury-induced, constitutively-active transgenic mouse model of FOP we show that mast cell inhibition by cromolyn, but not aprepitant, results in a dramatic reduction of heterotopic ossification. Read More

    Effects of reduced energy availability on bone metabolism in women and men.
    Bone 2017 Aug 25;105:191-199. Epub 2017 Aug 25.
    Musculoskeletal Physiology Research Group, Sport, Health and Performance Enhancement Research Centre, School of Science and Technology, Nottingham Trent University, UK. Electronic address:
    Background: The short-term effects of low energy availability (EA) on bone metabolism in physically active women and men are currently unknown.

    Purpose: We evaluated the effects of low EA on bone turnover markers (BTMs) in a cohort of women and a cohort of men, and compared effects between sexes.

    Methods: These studies were performed using a randomised, counterbalanced, crossover design. Read More

    The skeletal vascular system - Breathing life into bone tissue.
    Bone 2017 Aug 26. Epub 2017 Aug 26.
    Laboratory of Clinical and Experimental Endocrinology, Department of Chronic Diseases, Metabolism and Ageing, KU Leuven, 3000 Leuven, Belgium; Prometheus, Division of Skeletal Tissue Engineering, KU Leuven, 3000 Leuven, Belgium. Electronic address:
    During bone development, homeostasis and repair, a dense vascular system provides oxygen and nutrients to highly anabolic skeletal cells. Characteristic for the vascular system in bone is the serial organization of two capillary systems, each typified by specific morphological and physiological features. Especially the arterial capillaries mediate the growth of the bone vascular system, serve as a niche for skeletal and hematopoietic progenitors and couple angiogenesis to osteogenesis. Read More

    Glucose metabolism in bone.
    Bone 2017 Aug 24. Epub 2017 Aug 24.
    Department of Orthopaedic Surgery, Department of Developmental Biology, Washington University School of Medicine, St Louis, MO 63131, USA. Electronic address:
    The adult human skeleton is a multifunctional organ undergoing constant remodeling through the opposing activities of the bone-resorbing osteoclast and the bone-forming osteoblast. The exquisite balance between bone resorption and bone formation is responsible for bone homeostasis in healthy adults. However, evidence has emerged that such a balance is likely disrupted in diabetes where systemic glucose metabolism is dysregulated, resulting in increased bone frailty and osteoporotic fractures. Read More

    Femoral head trabecular micro-architecture in patients with osteoporotic hip fractures: Impact of bisphosphonate treatment.
    Bone 2017 Aug 24;105:148-153. Epub 2017 Aug 24.
    Department of Orthopedics & Joint Center, CHA Bundang Medical Center, Seongnam, South Korea. Electronic address:
    Introduction: Bisphosphonates are effective in preventing osteoporotic fractures. However, their limited efficacy of bisphosphonates has been suggested as a result of these drugs, which prevent the resorption of bone without improving bone connectivity. The trabecular microarchitecture in patients with osteoporotic hip fractures was evaluated according to their history of bisphosphonate treatment (BT). Read More

    Associations between body mass index across adult life and hip shapes at age 60 to 64: Evidence from the 1946 British birth cohort.
    Bone 2017 Aug 24;105:115-121. Epub 2017 Aug 24.
    MRC Unit for Lifelong Health and Ageing at UCL, 33 Bedford Place, London WC1B 5JU, UK.
    Objective: To examine the associations of body mass index (BMI) across adulthood with hip shapes at age 60-64years.

    Methods: Up to 1633 men and women from the MRC National Survey of Health and Development with repeat measures of BMI across adulthood and posterior-anterior dual-energy X-ray absorptiometry bone mineral density images of the proximal femur recorded at age 60-64 were included in analyses. Statistical shape modelling was applied to quantify independent variations in hip mode (HM), of which the first 6 were examined in relation to: i) BMI at each age of assessment; ii) BMI gain during different phases of adulthood; iii) age first overweight. Read More

    Determinants of short term fracture risk in patients with a recent history of low-trauma non-vertebral fracture.
    Bone 2017 Aug 22. Epub 2017 Aug 22.
    Paris Descartes University, Cochin Hospital, Department of Rheumatology, Paris, France; U1153 Institut National de la Santé et de la Recherche Médicale, PRESS Sorbonne Paris Cité, Paris Descartes University, Cochin Hospital, Department of Rheumatology, Paris, France.
    Low-trauma fractures tend to cluster in time, and subsequent fractures have a role in increased morbidity and mortality in osteoporotic patients. The aim of this study was to identify the risk factors of short-term subsequent non-vertebral fracture (NVF). Patients were included from the Fracture Liaison Service (FLS) which provides assessment for osteoporosis to all in-hospital patients admitted for a low-trauma NVF in the Orthopaedics department. Read More

    The fracture toughness of small animal cortical bone measured using arc-shaped tension specimens: Effects of bisphosphonate and deproteinization treatments.
    Bone 2017 Aug 18;105:67-74. Epub 2017 Aug 18.
    Department of Aerospace and Mechanical Engineering, University of Notre Dame, Notre Dame, IN 46556, USA. Electronic address:
    Small animal models, and especially transgenic models, have become widespread in the study of bone mechanobiology and metabolic bone disease, but test methods for measuring fracture toughness on multiple replicates or at multiple locations within a single small animal bone are lacking. Therefore, the objective of this study was to develop a method to measure cortical bone fracture toughness in multiple specimens and locations along the diaphysis of small animal bones. Arc-shaped tension specimens were prepared from the mid-diaphysis of rabbit ulnae and loaded to failure to measure the radial fracture toughness in multiple replicates per bone. Read More

    ARQ 087 inhibits FGFR signaling and rescues aberrant cell proliferation and differentiation in experimental models of craniosynostoses and chondrodysplasias caused by activating mutations in FGFR1, FGFR2 and FGFR3.
    Bone 2017 Aug 18;105:57-66. Epub 2017 Aug 18.
    Department of Biology, Faculty of Medicine, Masaryk University, 62500 Brno, Czech Republic; International Clinical Research Center, St. Anne's University Hospital, 65691 Brno, Czech Republic. Electronic address:
    Tyrosine kinase inhibitors are being developed for therapy of malignancies caused by oncogenic FGFR signaling but little is known about their effect in congenital chondrodysplasias or craniosynostoses that associate with activating FGFR mutations. Here, we investigated the effects of novel FGFR inhibitor, ARQ 087, in experimental models of aberrant FGFR3 signaling in cartilage. In cultured chondrocytes, ARQ 087 efficiently rescued all major effects of pathological FGFR3 activation, i. Read More

    Retinoid roles and action in skeletal development and growth provide the rationale for an ongoing heterotopic ossification prevention trial.
    Bone 2017 Aug 19. Epub 2017 Aug 19.
    Translational Research Program in Pediatric Orthopaedics, Division of Orthopaedic Surgery, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, United States. Electronic address:
    The majority of skeletal elements develop via endochondral ossification. This process starts with formation of mesenchymal cell condensations at prescribed sites and times in the early embryo and is followed by chondrogenesis, growth plate cartilage maturation and hypertrophy, and replacement of cartilage with bone and marrow. This complex stepwise process is reactivated and recapitulated in physiologic conditions such as fracture repair, but can occur extraskeletally in pathologies including heterotopic ossification (HO), Ossification of the Posterior Longitudinal Ligament (OPLL) and Hereditary Multiple Exostoses (HME). Read More

    [18F]NaF PET/CT scan as an early marker of heterotopic ossification in fibrodysplasia ossificans progressiva.
    Bone 2017 Aug 18. Epub 2017 Aug 18.
    Department of Radiology & Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands.
    Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disease with a progressive course characterized by episodically local flare-ups, which often but not always leads to heterotopic bone formation (HO). Recently, we showed that [18F]NaF PET/CT may be the first tool to monitor progression of a posttraumatic flare-up leading to new HO, which was demonstrated in a patient with FOP who underwent a maxillofacial surgery. This paper evaluates [18F]NaF PET/CT as a marker of FOP disease activity, comparing its use with other imaging modalities known in literature. Read More

    Unsaturation level decreased in bone marrow fat of postmenopausal women with low bone density using high resolution magic angle spinning (HRMAS) (1)H NMR spectroscopy.
    Bone 2017 Aug 18;105:87-92. Epub 2017 Aug 18.
    Maine Medical Center Research Institute, Scarborough, USA.
    There are increasing evidences suggesting bone marrow adiposity tissue (MAT) plays a critical role in affecting both bone quantity and quality. However, very limited studies that have investigated the association between the composition of MAT and bone mineral density (BMD). The goal of this study was to quantify MAT unsaturation profile of marrow samples from post-menopausal women using ex vivo high-resolution magic angle spinning (HRMAS) proton nuclear magnetic resonance ((1)H NMR) spectroscopy, and to investigate the relationship between MAT composition and BMD. Read More

    Imaging assessment of fibrodysplasia ossificans progressiva: Qualitative, quantitative and questionable.
    Bone 2017 Aug 16. Epub 2017 Aug 16.
    Department of Radiology, Division of Musculoskeletal Imaging and Intervention, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, United States. Electronic address:
    Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare autosomal dominant genetic disorder of heterotopic ossification (HO) characterized by skeletal anomalies and episodic soft tissue swelling (flare-ups) that can transform into heterotopic bone. The progressive development of heterotopic bone and progressive arthropathy leads to significant limitation of mobility. This paper will review various imaging modalities used in evaluating episodic soft tissue swelling (flare-ups), heterotopic bone and skeletal anomalies. Read More

    Acute unilateral hip pain in fibrodysplasia ossificans progressiva (FOP).
    Bone 2017 Aug 16. Epub 2017 Aug 16.
    Department of Medicine, Mayo Clinic School of Medicine, Mayo Clinic, Rochester, MN, United States. Electronic address:
    Background: Flare-ups of the hips are among the most feared and disabling complications of fibrodysplasia ossificans progressiva (FOP) and are poorly understood. In order to better understand the nature of hip flare-ups in FOP, we evaluated 25 consecutive individuals with classic FOP (14 males, 11 females; 3-56years old, median age, 17years old) who presented with acute unilateral hip pain.

    Results: All 25 individuals were suspected of having a flare-up of the hip based on clinical history and a favorable response to a four day course of high-dose oral prednisone. Read More

    Galectin-3 as a novel regulator of osteoblast-osteoclast interaction and bone homeostasis.
    Bone 2017 Aug 16;105:35-41. Epub 2017 Aug 16.
    Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Department of Internal Medicine 3 - Rheumatology and Immunology, Universitätsklinikum Erlangen, Erlangen, Germany. Electronic address:
    Bone tissue undergoes permanent and lifelong remodeling with a concerted action of bone-building osteoblasts and bone-resorbing osteoclasts. A precise cooperation between those two cell types is critical in the complex process of bone renewal. Galectin-3 is a member of the β-galactoside-binding lectin family playing multiple roles in cell growth, differentiation and aggregation. Read More

    Spontaneous mutation of Dock7 results in lower trabecular bone mass and impaired periosteal expansion in aged female Misty mice.
    Bone 2017 Aug 15;105:103-114. Epub 2017 Aug 15.
    Maine Medical Center Research Institute, Maine Medical Center, Scarborough, ME 04074, United States; University of Maine Graduate School of Biomedical Science and Engineering, Orono, ME 04469, United States.
    Misty mice (m/m) have a loss of function mutation in Dock7 gene, a guanine nucleotide exchange factor, resulting in low bone mineral density, uncoupled bone remodeling and reduced bone formation. Dock7 has been identified as a modulator of osteoblast number and in vitro osteogenic differentiation in calvarial osteoblast culture. In addition, m/m exhibit reduced preformed brown adipose tissue innervation and temperature as well as compensatory increase in beige adipocyte markers. Read More

    Hyperglycemia is associated with increased bone mineral density and decreased trabecular bone score in elderly Japanese men: The Fujiwara-kyo osteoporosis risk in men (FORMEN) study.
    Bone 2017 Aug 15;105:18-25. Epub 2017 Aug 15.
    Nara Medical University School of Medicine, 840 Shijocho, Kashihara, Nara 634-8521, Japan.
    Purpose: Patients with type 2 diabetes mellitus (T2DM) have an increased fracture risk despite having higher areal bone mineral density (aBMD). This study aimed to clarify the association between glycemic and insulin resistance status and bone microarchitecture, and whether pentosidine and bone turnover markers play any roles in the association.

    Methods: A total of 2012 community-dwelling men aged ≥65years completed baseline measurements of spine aBMD, fasting plasma glucose (FPG) and serum insulin, hemoglobin A1c (HbA1c), osteocalcin, type I procollagen N-terminal propeptide, type I collagen C-terminal crosslinking telopeptide, tartrate-resistant acid phosphatase isoenzyme 5b, pentosidine, height and weight and an interview regarding past disease history. Read More

    Globular adiponectin reverses osteo-sarcopenia and altered body composition in ovariectomized rats.
    Bone 2017 Aug 12;105:75-86. Epub 2017 Aug 12.
    Division of Endocrinology and Center for Research in Anabolic Skeletal Target in Health and Illness (ASTHI), Central Drug Research Institute (CDRI), Council of Scientific and Industrial Research (CSIR), Lucknow 226031, India; AcSIR, CSIR-Central Drug Research Institute Campus, Lucknow 226031, India. Electronic address:
    Adiponectin regulates various metabolic processes including glucose flux, lipid breakdown and insulin response. We recently reported that adiponectin receptor1 (adipoR1) activation by a small molecule reverses osteopenia in leptin receptor deficient db/db (diabetic) mice. However, the role of adiponectin in bone metabolism under the setting of post-menopausal (estrogen-deficiency) osteopenia and associated metabolic derangements has not been studied. Read More

    Activated FGFR3 promotes bone formation via accelerating endochondral ossification in mouse model of distraction osteogenesis.
    Bone 2017 Aug 10;105:42-49. Epub 2017 Aug 10.
    Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine, Japan.
    Achondroplasia (ACH) is one of the most common short-limbed skeletal dysplasias caused by gain-of-function mutations in the fibroblast growth factor receptors 3 (FGFR3) gene. Distraction osteogenesis (DO) is a treatment option for short stature in ACH in some countries. Although the patients with ACH usually show faster healing in DO, details of the newly formed bone have not been examined. Read More

    The impact of peripheral serotonin on leptin-brain serotonin axis, bone metabolism and strength in growing rats with experimental chronic kidney disease.
    Bone 2017 Aug 7;105:1-10. Epub 2017 Aug 7.
    Department of Monitored Pharmacotherapy, Medical University of Bialystok, Bialystok, Poland. Electronic address:
    Chronic kidney disease (CKD) results in decreased bone strength. Serotonin (5-HT) is one of the critical regulators of bone health, fulfilling distinct functions depending on its synthesis site: brain-derived serotonin (BDS) favors osteoblast proliferation, whereas gut-derived serotonin (GDS) inhibits it. We assessed the role of BDS and peripheral leptin in the regulation of bone metabolism and strength in young rats with 5/6 nephrectomy. Read More

    Discontinuation of Denosumab therapy for osteoporosis: A systematic review and position statement by ECTS.
    Bone 2017 Aug 5;105:11-17. Epub 2017 Aug 5.
    Bone Center, Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands. Electronic address:
    Introduction: The optimal duration of osteoporosis treatment is controversial. As opposed to bisphosphonates, denosumab does not incorporate into bone matrix and bone turnover is not suppressed after its cessation. Recent reports imply that denosumab discontinuation may lead to an increased risk of multiple vertebral fractures. Read More

    Differential responses of mechanosensitive osteocyte proteins in fore- and hindlimbs of hindlimb-unloaded rats.
    Bone 2017 Aug 3;105:26-34. Epub 2017 Aug 3.
    Department of Health and Kinesiology, Texas A&M University, College Station, TX 77843, United States. Electronic address:
    Osteocytes are believed to be the primary mechanosensors of bone tissue, signaling to osteoblasts and osteoclasts by releasing specific proteins. Sclerostin, interleukin-6 (IL-6), and insulin-like growth factor-I (IGF-I) are osteocyte proteins that signal to osteoblasts. The primary objective of this study was to determine if osteocyte protein response to mechanical unloading is restricted to the unloaded bone using the hindlimb unloading (HU) rodent model. Read More

    Shared ACVR1 mutations in FOP and DIPG: Opportunities and challenges in extending biological and clinical implications across rare diseases.
    Bone 2017 Aug 2. Epub 2017 Aug 2.
    Division of Neurosurgery, The Children's Hospital of Philadelphia, Colket Translational Research Building Room 4052, 3501 Civic Center Blvd, Philadelphia 19104, PA, United States; Department of Biomedical and Health Informatics, The Children's Hospital of Philadelphia, Colket Translational Research Building Room 4052, 3501 Civic Center Blvd, Philadelphia 19104, PA, United States; Center for Data Driven Discovery in Biomedicine, The Children's Hospital of Philadelphia, Colket Translational Research Building Room 4052, 3501 Civic Center Blvd, Philadelphia 19104, PA, United States; Center for Childhood Cancer Research, The Children's Hospital of Philadelphia, Colket Translational Research Building Room 4052, 3501 Civic Center Blvd, Philadelphia 19104, PA, United States; Department of Neurosurgery, Perelman School of Medicine at the University of Pennsylvania, 3501 Civic Center Blvd, Room 4052, Philadelphia 19104, PA, United States. Electronic address:
    Gain-of-function mutations in the Type I Bone Morphogenic Protein (BMP) receptor ACVR1 have been identified in two diseases: Fibrodysplasia Ossificans Progressiva (FOP), a rare autosomal dominant disorder characterized by genetically driven heterotopic ossification, and in 20-25% of Diffuse Intrinsic Pontine Gliomas (DIPGs), a pediatric brain tumor with no effective therapies and dismal median survival. While the ACVR1 mutation is causal for FOP, its role in DIPG tumor biology remains under active investigation. Here, we discuss cross-fertilization between the FOP and DIPG fields, focusing on the biological mechanisms and principles gleaned from FOP that can be applied to DIPG biology. Read More

    Phantomless calibration of CT scans for measurement of BMD and bone strength-Inter-operator reanalysis precision.
    Bone 2017 Oct 1;103:325-333. Epub 2017 Aug 1.
    Department of Mechanical Engineering, University of California, Berkeley, CA, USA; Department of Bioengineering, University of California, Berkeley, CA, USA. Electronic address:
    Patient-specific phantomless calibration of computed tomography (CT) scans has the potential to simplify and expand the use of pre-existing clinical CT for quantitative bone densitometry and bone strength analysis for diagnostic and monitoring purposes. In this study, we quantified the inter-operator reanalysis precision errors for a novel implementation of patient-specific phantomless calibration, using air and either aortic blood or hip adipose tissue as internal calibrating reference materials, and sought to confirm the equivalence between phantomless and (traditional) phantom-based measurements. CT scans of the spine and hip for 25 women and 15 men (mean±SD age of 67±9years, range 41-86years), one scan per anatomic site per patient, were analyzed independently by two analysts using the VirtuOst software (O. Read More

    Impact of FRAX-based osteoporosis intervention using real world data.
    Bone 2017 Oct 2;103:318-324. Epub 2017 Aug 2.
    Tel Aviv University, Faculty of Management, Israel; Tel Aviv Souraski Medical Center, Gastroenterology and Liver Diseases Institute, Israel.
    Objectives: To estimate the implications and accuracy of the most common fracture prevention strategies: (1) fixed threshold by the National Osteoporosis Foundation (NOF), (2) age-dependent threshold by the National Osteoporosis Guideline Group (NOGG) and (3) osteoporotic bone mineral density (BMD).

    Methods: A retrospective cohort of all 50-90years old female members in a nationally representative payer provider healthcare organization in Israel, with 10years of follow-up on incident events of major osteoporotic fractures. Since events are less frequent than non-events, balanced accuracy (the average between the accuracy obtained for patients with and without events) was used to measure performance. Read More

    Stable sulforaphane protects against gait anomalies and modifies bone microarchitecture in the spontaneous STR/Ort model of osteoarthritis.
    Bone 2017 Oct 1;103:308-317. Epub 2017 Aug 1.
    Skeletal Biology Group, Comparative Biomedical Sciences, The Royal Veterinary College, Royal College Street, London, NW1 0TU, UK.
    Osteoarthritis (OA), affecting joints and bone, causes physical gait disability with huge socio-economic burden; treatment remains palliative. Roles for antioxidants in protecting against such chronic disorders have been examined previously. Sulforaphane is a naturally occurring antioxidant. Read More

    Tissue-specific mineralization defects in the periodontium of the Hyp mouse model of X-linked hypophosphatemia.
    Bone 2017 Oct 29;103:334-346. Epub 2017 Jul 29.
    EA2496, Faculty of Dentistry, Paris Descartes University, Montrouge, France. Electronic address:
    X-linked hypophosphatemia (XLH) is a dento-osseous disorder caused by inactivating mutations in the PHEX gene, leading to renal phosphate wasting and hypophosphatemia, and impaired mineralization of bones and teeth. In the oral cavity, recent reports suggest a higher susceptibility of XLH patients to periodontitis, where patients present with impaired tooth cementum - a bone-like tissue involved in tooth attachment to the jaw bones and post-eruption tooth positioning - and a higher frequency of intrabony defects. In the present study, the pathobiology of alveolar bone and tooth cementum was investigated in the Hyp mouse, the murine analog of XLH. Read More

    Heterotopic bone induction via BMP signaling: Potential therapeutic targets for fibrodysplasia ossificans progressiva.
    Bone 2017 Jul 25. Epub 2017 Jul 25.
    Division of Pathophysiology, Research Center for Genomic Medicine, Saitama Medical University, 1397-1 Yamane, Hidaka-shi, Saitama 350-1241, Japan.
    More than 50years ago, Marshal M. Urist detected "heterotopic bone-inducing activity" in demineralized bone matrix. This unique activity was referred to as "bone morphogenetic protein (BMP)" because it was sensitive to trypsin digestion. Read More

    Deficiency of DGCR8 increases bone formation through downregulation of miR-22 expression.
    Bone 2017 Oct 21;103:287-294. Epub 2017 Jul 21.
    Department of Biochemistry, BK21 PLUS Program for Creative Veterinary Science Research and Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul, South Korea. Electronic address:
    MicroRNAs (miRNA) significantly contribute to bone formation by post-transcriptional regulation of gene expression. Mature miRNAs are generated following sequential cleavage by DROSHA/DGCR8 and DICER. However, recent studies have identified that some miRNAs require only one of these enzymes. Read More

    Neutron tomographic imaging of bone-implant interface: Comparison with X-ray tomography.
    Bone 2017 Oct 22;103:295-301. Epub 2017 Jul 22.
    Division of Geotechnical Engineering, Lund University, Sweden. Electronic address:
    Metal implants, in e.g. joint replacements, are generally considered to be a success. Read More

    Comparison of non-invasive assessments of strength of the proximal femur.
    Bone 2017 Jul 21;105:93-102. Epub 2017 Jul 21.
    Center for Advanced Orthopedic Studies, Beth Israel Deaconess Medical Center, Boston, MA, USA; Department of Orthopedic Surgery, Harvard Medical School, Boston, MA, USA.
    It is not clear which non-invasive method is most effective for predicting strength of the proximal femur in those at highest risk of fracture. The primary aim of this study was to compare the abilities of dual energy X-ray absorptiometry (DXA)-derived aBMD, quantitative computed tomography (QCT)-derived density and volume measures, and finite element analysis (FEA)-estimated strength to predict femoral failure load. We also evaluated the contribution of cortical and trabecular bone measurements to proximal femur strength. Read More

    In vitro osteoclastogenesis from Gaucher patients' cells correlates with bone mineral density but not with Chitotriosidase.
    Bone 2017 Oct 20;103:262-269. Epub 2017 Jul 20.
    IIFP, Universidad Nacional de La Plata, CONICET, Facultad de Ciencias Exactas, Departamento de Ciencias Biológicas, 47 y 115, 1900 La Plata, Argentina. Electronic address:
    Gaucher disease (GD) is caused by mutations on the gene encoding for the lysosomal enzyme glucocerebrosidase. Type I GD (GD1) patients present anemia, hepatosplenomegaly and bone alterations. In spite of treatment, bone alterations in GD patients persist, including poor bone mineral density (BMD). Read More

    Early clinical observations on the use of imatinib mesylate in FOP: A report of seven cases.
    Bone 2017 Jul 20. Epub 2017 Jul 20.
    Department of Medicine, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, MN 55905, United States. Electronic address:
    Background: Fibrodysplasia ossificans progressiva (FOP) is an ultrarare genetic disorder of progressive, disabling heterotopic ossification (HO) for which there is presently no definitive treatment. Research studies have identified multiple potential targets for therapy in FOP, and novel drug candidates are being developed for testing in clinical trials. A complementary approach seeks to identify approved drugs that could be re-purposed for off-label use against defined targets in FOP. Read More

    Exogenous hedgehog antagonist delays but does not prevent fracture healing in young mice.
    Bone 2017 Oct 19;103:241-251. Epub 2017 Jul 19.
    Department of Orthopaedic Surgery and Musculoskeletal Research Center, Washington University School of Medicine, Saint Louis, MO, United States.
    Fracture healing recapitulates many aspects of developmental osteogenesis. The hedgehog (Hh) signaling pathway, essential to skeletal development, is upregulated during fracture healing, although its importance is unclear. Our goal was to assess the functional importance of Hh signaling in endochondral fracture healing. Read More

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