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    PTH (1-34) and growth hormone in prevention of disuse osteopenia and sarcopenia in rats.
    Bone 2018 Feb 20. Epub 2018 Feb 20.
    Department of Biomedicine, Aarhus University, Denmark. Electronic address:
    Osteopenia and sarcopenia develops rapidly during disuse. The study investigated whether intermittent parathyroid hormone (1-34) (PTH) and growth hormone (GH) administered alone or in combination could prevent or mitigate disuse osteopenia and sarcopenia in rats. Disuse was achieved by injecting 4 IU botulinum toxin A (BTX) into the right hindlimb musculature of 12-14-week-old female Wistar rats. Read More

    Pathological fracture risk assessment in patients with femoral metastases using CT-based finite element methods. A retrospective clinical study.
    Bone 2018 Feb 20;110:215-220. Epub 2018 Feb 20.
    School of Mechanical Engineering, Tel-Aviv University, Ramat-Aviv, Israel.
    Physician recommendation for prophylactic surgical fixation of a femur with metastatic bone disease (MBD) is usually based on Mirels' criteria and clinical experience, both of which suffer from poor specificity. This may result in a significant number of these health compromised patients undergoing unnecessary surgery. CT-based finite element analyses (CTFEA) have been shown to accurately predict strength in femurs with metastatic tumors in an ex-vivo study. Read More

    Constitutive stimulatory G protein activity in limb mesenchyme impairs bone growth.
    Bone 2018 Feb 19. Epub 2018 Feb 19.
    Endocrine Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA. Electronic address:
    GNAS mutations leading to constitutively active stimulatory G protein alpha-subunit (Gsα) cause different tumors, fibrous dysplasia of bone, and McCune-Albright syndrome, which are typically not associated with short stature. Enhanced signaling of the parathyroid hormone/parathyroid hormone-related peptide receptor, which couples to multiple G proteins including Gsα, leads to short bones with delayed endochondral ossification. It has remained unknown whether constitutive Gsα activity also impairs bone growth. Read More

    Heterotopic ossification and lessons learned from fifteen years at war: A review of therapy, novel research, and future directions for military and civilian orthopaedic trauma.
    Bone 2018 Feb 17. Epub 2018 Feb 17.
    Orthopaedics, USU-Walter Reed Department of Surgery Walter Reed National Military Medical Center, Bethesda, MD, United States.. Electronic address:
    Heterotopic ossification, the formation of bone in soft tissues, is a common complication of the high-energy extremity trauma sustained in modern armed conflict. In the past 15 years, military treatment facilities and aligned laboratories have been in a unique position to study and treat this process due to the high volume of patients with these injuries secondary to blast trauma. The devastating nature of these wounds has limited traditional therapeutic options, necessitating alternative solutions to prophylaxis and initial treatment producing substantial advances in modeling, prophylaxis, detection, and therapy. Read More

    Use of high-dose intermittent systemic glucocorticoids and the risk of fracture in patients with chronic obstructive pulmonary disease.
    Bone 2018 Feb 17. Epub 2018 Feb 17.
    Department of Clinical Pharmacy and Toxicology, Maastricht University Medical Centre, Maastricht, The Netherlands; Department of Pharmacoepidemiology & Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht, The Netherlands; Care and Public Health Research Institute (CAPHRI), Maastricht, The Netherlands; MRC Lifecourse Epidemiology Unit, Southampton General Hospital, Southampton, United Kingdom. Electronic address:
    Introduction: Chronic obstructive pulmonary disease (COPD) is characterised by persistent airflow obstruction and respiratory symptoms. While short course systemic GCs are prescribed in patients with acute COPD exacerbations, little is known of the risk of fractures with intermittent exposure to high-dose GC and the effect of proxies of disease severity.

    Methods: A case-control study was conducted using the Danish National Hospital Discharge Registry (NHDR) between January 1996 to December 2011. Read More

    Osteocyte regulation of bone and blood.
    Bone 2018 Feb 16. Epub 2018 Feb 16.
    Georg-Speyer-Haus, Institute for Tumor Biology and Experimental Therapy, 60596 Frankfurt am Main, Germany.
    This past decade has witnessed a renewed interest in the function and biology of matrix-embedded osteocytes and these cells have emerged as master regulators of bone homeostasis. They secrete two very powerful proteins, sclerostin, a Wnt-inhibitor, that suppresses bone formation, and receptor-activator of NF-kB ligand (RANKL), a cytokine required for osteoclastogenesis. Neutralizing antibodies against these proteins are currently used for the treatment of osteoporosis. Read More

    Regional variations of cortical bone in the humeral head region: A preliminary study.
    Bone 2018 Feb 16;110:194-198. Epub 2018 Feb 16.
    Department of Orthopedics, Tianjin Hospital, Tianjin University, Tianjin, China.
    Background: Incidence of proximal humeral fractures dramatically increased over the last decade due to demographic changes. The goal of this study was to analyze regional characteristics of cortical bone in the humeral head region using cortical bone mapping (CBM) technique.

    Methods: The proximal humerus of 103 healthy volunteers was imaged by clinical computed tomography (CT) scans. Read More

    The paradox of marrow adipose tissue in anorexia nervosa.
    Bone 2018 Feb 16. Epub 2018 Feb 16.
    Neuroendocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.
    Anorexia nervosa (AN) is a psychiatric disorder characterized by inappropriate nutrient intake resulting in low body weight. Multiple hormonal adaptations facilitate decreased energy expenditure in this state of caloric deprivation including non-thyroidal illness syndrome, growth hormone resistance, and hypogonadotropic hypogonadism. Although these hormonal adaptations confer a survival advantage during periods of negative energy balance, they contribute to the long-term medical complications associated with AN, the most common of which is significant bone loss and an increased risk of fracture. Read More

    Antagonists to TRPV1, ASICs and P2X have a potential role to prevent the triggering of regional bone metabolic disorder and pain-like behavior in tail-suspended mice.
    Bone 2018 Feb 14. Epub 2018 Feb 14.
    Department of Orthopaedic Surgery, Sapporo Medical University School of Medicine, South-1, West-16, Chuo-ku, Sapporo 060-8543, Japan.
    Our recent studies demonstrated that regional bone loss in the unloaded hind limbs of tail-suspended mice triggered pain-like behaviors due to the acidic environment in the bone induced by osteoclast activation. The aims of the present study were to examine whether TRPV1, ASIC and P2X (known as nociceptors) are expressed in bone, and whether the antagonists to those receptors affect the expression of osteoblast and osteoclast regulators, and prevent the triggering of not only pain-like behaviors but also high bone turnover conditions in tail-suspension model mice. The hind limb-unloaded mice were subjected to tail suspension with the hind limbs elevated for 14 days. Read More

    Low bone toughness in the TallyHO model of juvenile type 2 diabetes does not worsen with age.
    Bone 2018 Feb 10;110:204-214. Epub 2018 Feb 10.
    Department of Biomedical Engineering, Vanderbilt University, Nashville, TN 37232, United States; Department of Orthopaedic Surgery & Rehabilitation, Vanderbilt University Medical Center, Nashville, TN 37232, United States; Center for Bone Biology, Vanderbilt University Medical Center, Nashville, TN 37232, United States; Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, TN 37212, United States. Electronic address:
    Fracture risk increases as type 2 diabetes (T2D) progresses. With the rising incidence of T2D, in particular early-onset T2D, a representative pre-clinical model is needed to study mechanisms for treating or preventing diabetic bone disease. Towards that goal, we hypothesized that fracture resistance of bone from diabetic TallyHO mice decreases as the duration of diabetes increases. Read More

    YAP1 is essential for osteoclastogenesis through a TEADs-dependent mechanism.
    Bone 2018 Feb 10;110:177-186. Epub 2018 Feb 10.
    Department of Orthopaedic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.. Electronic address:
    Yes-associated protein 1 (YAP1), the core effector of the Hippo signaling pathway, has been identified as a key regulator of tissue homeostasis and organ development by controlling cell proliferation and differentiation. Previous studies have shown that YAP1 regulates multiple steps during skeletal development and bone remodeling, including the self-renewal and differentiation of mesenchymal stem cells (MSCs). However, its role in osteoclastogenesis remains largely unknown. Read More

    High bone mineral density in sickle cell disease: Prevalence and characteristics.
    Bone 2018 Feb 8;110:199-203. Epub 2018 Feb 8.
    Internal Medicine Department, Sickle Cell Referral Center, Georges Pompidou European Hospital, AP-HP, Paris, France; Faculté de Médecine Paris Descartes, Sorbonne Paris-Cité, Paris, France; Laboratory of Excellence GR-Ex, Paris, France.
    Background: Osteosclerosis (OSC) is a rarely studied complication of sickle cell disease (SCD). The objective of our study was to determine the prevalence and characteristics of high bone mineral density (BMD) and its radiological features in adult SCD patients.

    Methods: This prospective observational study was conducted from May 2007 to May 2016 in consecutive patients with steady-state SCD at two university hospitals. Read More

    Bone tissue aging affects mineralization of cement lines.
    Bone 2018 Feb 7;110:187-193. Epub 2018 Feb 7.
    Department of Osteology and Biomechanics, University Medical Center Hamburg-Eppendorf, Lottestr. 55a, 22529 Hamburg, Germany. Electronic address:
    Cement lines are known as thin peripheral boundaries of the osteons. With a thickness below 5 μm their composition of inorganic and organic compounds has been a matter of debate. Here, we hypothesized that cement lines become hypermineralized and their degree of mineralization is not constant but related to the tissue age of the osteon. Read More

    Development of a risk assessment tool for osteoporotic fracture prevention: A claims data approach.
    Bone 2018 Feb 5;110:170-176. Epub 2018 Feb 5.
    Department of Health Economics and Health Services Research, Hamburg Center for Health Economics, University Medical Center Hamburg-Eppendorf, Germany.
    Background: In aging societies osteoporotic fractures are a major health problem with high economic costs. Targeting prevention at individuals at high risk is important to reduce the future burden of fractures. Available risk assessment tools (e. Read More

    Efficacy of anti-IL-23 monotherapy versus combination therapy with anti-IL-17 in estrogen deficiency induced bone loss conditions.
    Bone 2018 Jan 31;110:84-95. Epub 2018 Jan 31.
    Division of Endocrinology and Centre for Research in Anabolic Skeletal Targets in Health and Illness (ASTHI), CSIR-Central Drug Research Institute, B.S. 10/1, Sector-10, Jankipuram, Lucknow, India. Electronic address:
    Recent studies have identified that Interleukin (IL)-23/IL-17 axis plays crucial role in pathogenesis of inflammation and bone destruction. IL-23 is thought to promote joint destruction in arthritis by stimulating Th17 cells. IL-23 directly mediates bone loss by inducing osteoclastogenesis and receptor activator of kappa B ligand (RANKL) expression in T cells. Read More

    Low-intensity pulsed ultrasound promotes spinal fusion and enhances migration and proliferation of MG63s through sonic hedgehog signaling pathway.
    Bone 2018 Feb 2;110:47-57. Epub 2018 Feb 2.
    Department of Orthopedic Surgery, Changhai Hospital, Second Military Medical University, Shanghai, China. Electronic address:
    Low-intensity pulsed ultrasound (LIPUS) has been found to accelerate the healing process of spinal fusion via a process closely related to osteoblast differentiation and migration. Sonic hedgehog (Shh) signaling plays an important role in development and homeostasis, including a critical function in bone formation. However, its role in spinal fusion during LIPUS treatment is still unknown. Read More

    Combination of hindlimb suspension and immobilization by casting exaggerates sarcopenia by stimulating autophagy but does not worsen osteopenia.
    Bone 2018 Feb 2;110:29-37. Epub 2018 Feb 2.
    Department of Orthopaedics and Rehabilitation, The Pennsylvania State University, College of Medicine, Hershey, PA 17033, United States; Department of Biomedical Engineering, Virginia Commonwealth University, Richmond, VA, United States. Electronic address:
    Astronauts in space experience a unique environment that causes the concomitant loss of bone and muscle. However, the interaction between these tissues and how osteopenia and sarcopenia affect each other is unclear. We explored this relationship by exaggerating unloading-induced muscle loss using a unilateral casting model in conjunction with hindlimb suspension (HLS). Read More

    Young female patients with multiple myeloma have low occurrence of osteolytic lesion.
    Bone 2018 Feb 3;110:21-28. Epub 2018 Feb 3.
    Department of Hematology, West China Hospital, Sichuan University, China. Electronic address:
    Objective: Osteolytic lesion (OL) and bone damage are common complications in multiple myeloma (MM). This study aimed to analyze the occurrence of OL in MM patient groups of different ages and genders.

    Patients And Methods: We performed a retrospective study of 762 MM patients admitted to West China Hospital from 2009 to 2014 to investigate the association between OL occurrence with patients' ages and genders. Read More

    The different distribution of enzymatic collagen cross-links found in adult and children bone result in different mechanical behavior of collagen.
    Bone 2018 Feb 1;110:107-114. Epub 2018 Feb 1.
    Department of Physical Therapy, College of Staten Island, USA; New York Center for Biomedical Engineering, City College of New York, USA. Electronic address:
    Enzymatic collagen cross-linking has been shown to play an important role in the macroscopic elastic and plastic deformation of bone across ages. However, its direct contribution to collagen fibril deformation is unknown. The aim of this study is to determine how covalent intermolecular connections from enzymatic collagen cross-links contribute to collagen fibril elastic and plastic deformation of adults and children's bone matrix. Read More

    High-frequency spectral ultrasound imaging (SUSI) visualizes early post-traumatic heterotopic ossification (HO) in a mouse model.
    Bone 2018 Feb 6. Epub 2018 Feb 6.
    Department of Surgery, University of Michigan, Ann Arbor, MI, USA. Electronic address:
    Purpose: Early treatment of heterotopic ossification (HO) is currently limited by delayed diagnosis due to limited visualization at early time points. In this study, we validate the use of spectral ultrasound imaging (SUSI) in an animal model to detect HO as early as one week after burn tenotomy.

    Methods: Concurrent SUSI, micro CT, and histology at 1, 2, 4, and 9weeks post-injury were used to follow the progression of HO after an Achilles tenotomy and 30% total body surface area burn (n=3-5 limbs per time point). Read More

    Stem cells and heterotopic ossification: Lessons from animal models.
    Bone 2018 Jan 31. Epub 2018 Jan 31.
    Department of Molecular & Cell Biology, University of Connecticut Stem Cell Institute, University of Connecticut, Storrs, CT 06269, United States. Electronic address:
    Put most simply, heterotopic ossification (HO) is the abnormal formation of bone at extraskeletal sites. HO can be classified into two main subtypes, genetic and acquired. Acquired HO is a common complication of major connective tissue injury, traumatic central nervous system injury, and surgical interventions, where it can cause significant pain and postoperative disability. Read More

    Accumulation of carboxymethyl-lysine (CML) in human cortical bone.
    Bone 2018 Feb 2;110:128-133. Epub 2018 Feb 2.
    Department of Biomedical Engineering, Rensselaer Polytechnic Institute, Troy, NY 12182, USA; Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY 12182, USA. Electronic address:
    Advanced glycation end-products (AGEs) are a category of post translational modification associated with the degradation of the structural properties of multiple different types of tissues. Typically, AGEs are the result of a series of post-translational modification reactions between sugars and proteins through a process known as non-enzymatic glycation (NEG). Increases in the rate of NEG of bone tissue are associated with type 2 diabetes and skeletal fragility. Read More

    Removal of matrix-bound zoledronate prevents post-extraction osteonecrosis of the jaw by rescuing osteoclast function.
    Bone 2018 Feb 8;110:141-149. Epub 2018 Feb 8.
    Department of Oral Biology, Dental College of Georgia, Augusta University, Augusta, GA, USA. Electronic address:
    Unlike other antiresorptive medications, bisphosphonate molecules accumulate in the bone matrix. Previous studies of side-effects of anti-resorptive treatment focused mainly on systemic effects. We hypothesize that matrix-bound bisphosphonate molecules contribute to the pathogenesis of bisphosphonate-related osteonecrosis of the jaw (BRONJ). Read More

    Teriparatide (human PTH) compensates for impaired fracture healing in COX-2 deficient mice.
    Bone 2018 Feb 3;110:150-159. Epub 2018 Feb 3.
    Department of Orthopaedic Surgery, Washington University School of Medicine, St. Louis, MO, USA. Electronic address:
    Genetic ablation of cyclooxygenase-2 (COX-2) in mice is known to impair fracture healing. To determine if teriparatide (human PTH) can promote healing of Cox-2-deficient fractures, we performed detailed in vivo analyses using a murine stabilized tibia fracture model. Periosteal progenitor cell proliferation as well as bony callus formation was markedly reduced in Cox-2mice at day 10 post-fracture. Read More

    Familial resemblance in trabecular and cortical volumetric bone mineral density and bone microarchitecture as measured by HRpQCT.
    Bone 2018 Jan 31;110:76-83. Epub 2018 Jan 31.
    Menzies Institute for Medical Research, University of Tasmania, Hobart 7000, Australia. Electronic address:
    To estimate the heritability of bone geometry, volumetric bone mineral density (vBMD) and microarchitecture of trabecular (Tb) and cortical (Ct) bone measured by high resolution peripheral quantitative computerised tomography (HRpQCT) at the distal radius and tibia and to investigate the genetic correlations of these measures. Participants were 177 mother-offspring pairs from 162 families (mothers, mean age (SD) = 52.1 (4. Read More

    Novel variant in Sp7/Osx associated with recessive osteogenesis imperfecta with bone fragility and hearing impairment.
    Bone 2018 Jan 31;110:66-75. Epub 2018 Jan 31.
    Institute of Endocrinology and Diabetes, The Children's Hospital at Westmead, Sydney, NSW, Australia; Discipline of Child & Adolescent Health, Sydney Medical School, University of Sydney, Sydney, NSW, Australia.
    Osteogenesis imperfecta (OI) is a connective tissue disorder characterized by low bone density and recurrent fractures with a wide genotypic and phenotypic spectrum. Common features include short stature, opalescent teeth, blue sclerae and hearing impairment. The majority (>90%) of patients with OI have autosomal dominant variants in COL1A1/COL1A2, which lead to defects in type 1 collagen. Read More

    Lactation induces increases in the RANK/RANKL/OPG system in maxillary bone.
    Bone 2018 Jan 31;110:160-169. Epub 2018 Jan 31.
    Department of Anatomy, University of Otago, Dunedin, New Zealand.
    The underlying causes of maxillary bone loss during lactation remain poorly understood. We evaluated the impact of lactation on physiological and mechanically-induced alveolar bone remodeling. Nulliparous non-lactating (N-LAC) and 21-day lactating (LAC) mice underwent mechanically-induced bone remodeling by orthodontic tooth movement (OTM). Read More

    A new open-source tool for measuring 3D osteocyte lacunar geometries from confocal laser scanning microscopy reveals age-related changes to lacunar size and shape in cortical mouse bone.
    Bone 2018 Jan 31;110:115-127. Epub 2018 Jan 31.
    Department of Mechanical Engineering, University of Colorado Boulder, United States. Electronic address:
    Osteocytes can participate in systemic mineral homeostasis through perilacunar maintenance and remodeling, where changes to osteocyte lacunar morphology may affect bone structural integrity, tissue strains, and osteocyte mechanosensitivity. Though aging is associated with both decreased bone quality and altered mineral metabolism, it is not known if osteocyte lacunae undergo age-related changes in geometry. In order to survey lacunar changes with age, we developed an open-source program whereby 3D osteocyte lacunae are automatically segmented and then subsequently reconstructed from confocal laser scanning microscopy (CLSM) depth stacks for quantitative analysis of geometry and orientation. Read More

    Estrogen receptor α- (ERα), but not ERβ-signaling, is crucially involved in mechanostimulation of bone fracture healing by whole-body vibration.
    Bone 2018 Jan 20;110:11-20. Epub 2018 Jan 20.
    Institute of Orthopedic Research and Biomechanics, University Medical Center Ulm, Helmholtzstraße 14, 89081 Ulm, Germany.
    Mechanostimulation by low-magnitude high frequency vibration (LMHFV) has been shown to provoke anabolic effects on the intact skeleton in both mice and humans. However, experimental studies revealed that, during bone fracture healing, the effect of whole-body vibration is profoundly influenced by the estrogen status. LMHFV significantly improved fracture healing in ovariectomized (OVX) mice being estrogen deficient, whereas bone regeneration was significantly reduced in non-OVX, estrogen-competent mice. Read More

    Characterization of the bone marrow adipocyte niche with three-dimensional electron microscopy.
    Bone 2018 Jan 27. Epub 2018 Jan 27.
    Division of Bone and Mineral Diseases, Department of Medicine, Washington University, St. Louis, MO, USA; Department of Cell Biology & Physiology, Washington University, St. Louis, MO, USA. Electronic address:
    Unlike white and brown adipose tissues, the bone marrow adipocyte (BMA) exists in a microenvironment containing unique populations of hematopoietic and skeletal cells. To study this microenvironment at the sub-cellular level, we performed a three-dimensional analysis of the ultrastructure of the BMA niche with focused ion beam scanning electron microscopy (FIB-SEM). This revealed that BMAs display hallmarks of metabolically active cells including polarized lipid deposits, a dense mitochondrial network, and areas of endoplasmic reticulum. Read More

    Development of a 3D bone marrow adipose tissue model.
    Bone 2018 Jan 26. Epub 2018 Jan 26.
    Maine Medical Center Research Institute, Scarborough, ME 04074, USA; University of Maine Graduate School of Biomedical Science and Engineering, Orono, ME 04469, USA; Tufts University School of Medicine, Boston, MA 02111, USA. Electronic address:
    Over the past twenty years, evidence has accumulated that biochemically and spatially defined networks of extracellular matrix, cellular components, and interactions dictate cellular differentiation, proliferation, and function in a variety of tissue and diseases. Modeling in vivo systems in vitro has been undeniably necessary, but when simplified 2D conditions rather than 3D in vitro models are used, the reliability and usefulness of the data derived from these models decreases. Thus, there is a pressing need to develop and validate reliable in vitro models to reproduce specific tissue-like structures and mimic functions and responses of cells in a more realistic manner for both drug screening/disease modeling and tissue regeneration applications. Read More

    Bone marrow adipocytes resist lipolysis and remodeling in response to β-adrenergic stimulation.
    Bone 2018 Jan 26. Epub 2018 Jan 26.
    Department of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI 48105, USA; Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address:
    Bone marrow adipose tissue (BMAT) is preserved or increased in states of caloric restriction. Similarly, we found that BMAT in the tail vertebrae, but not the red marrow in the tibia, resists loss of neutral lipid with acute, 48-hour fasting in rats. The mechanisms underlying this phenomenon and its seemingly distinct regulation from peripheral white adipose tissue (WAT) remain unknown. Read More

    Hypophosphatasia: Biochemical hallmarks validate the expanded pediatric clinical nosology.
    Bone 2018 Jan 31;110:96-106. Epub 2018 Jan 31.
    Center for Metabolic Bone Disease and Molecular Research, Shriners Hospital for Children, St. Louis, MO 63110, USA. Electronic address:
    Hypophosphatasia (HPP) is the inborn-error-of-metabolism due to loss-of-function mutation(s) of the ALPL (TNSALP) gene that encodes the tissue non-specific isoenzyme of alkaline phosphatase (TNSALP). TNSALP represents a family of cell-surface phosphohydrolases differing by post-translational modification that is expressed especially in the skeleton, liver, kidney, and developing teeth. Thus, the natural substrates of TNSALP accumulate extracellularly in HPP including inorganic pyrophosphate (PPi), a potent inhibitor of mineralization, and pyridoxal 5'-phosphate (PLP), the principal circulating form of vitamin B. Read More

    The effects of estrogen deficiency on cortical bone microporosity and mineralization.
    Bone 2018 Jan 20;110:1-10. Epub 2018 Jan 20.
    Department of Biomedical Engineering, The City College of New York, New York, NY 10031, United States. Electronic address:
    Recent studies have demonstrated matrix-mineral alterations in bone tissue surrounding osteocytes in estrogen-deficient animals. While cortical bone porosity has been shown to be a contributor to the mechanical properties of bone tissue, little analysis has been done to investigate the effects of estrogen deficiency on bone's microporosities, including the vascular and osteocyte lacunar porosities. In this study we examined alterations in cortical bone microporosity, mineralization, and cancellous bone architecture due to estrogen deficiency in the ovariectomized rat model of postmenopausal osteoporosis. Read More

    Bone remodelling in vitro: Where are we headed?: -A review on the current understanding of physiological bone remodelling and inflammation and the strategies for testing biomaterials in vitro.
    Bone 2018 Feb 2;110:38-46. Epub 2018 Feb 2.
    Regenerative Biomaterials Group, RAFT Institute, Leopold Muller Building, Mount Vernon Hospital, Northwood HA6 2RN, UK.
    Bone remodelling is a dynamic process required for the maintenance of bone architecture in response to the changing mechanical needs. It is also a vital process during the repair of bone tissue following injury. Clinical intervention in terms of autografting or allografting is often required to heal bone injuries where physiological healing fails. Read More

    Development, regulation, metabolism and function of bone marrow adipose tissues.
    Bone 2018 Jan 16;110:134-140. Epub 2018 Jan 16.
    Department of Molecular & Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI, United States. Electronic address:
    Most adipocytes exist in discrete depots throughout the body, notably in well-defined white and brown adipose tissues. However, adipocytes also reside within specialized niches, of which the most abundant is within bone marrow. Whereas bone marrow adipose tissue (BMAT) shares many properties in common with white adipose tissue, the distinct functions of BMAT are reflected by its development, regulation, protein secretion, and lipid composition. Read More

    Practical considerations for obtaining high quality quantitative computed tomography data of the skeletal system.
    Bone 2018 Jan 12;110:58-65. Epub 2018 Jan 12.
    Human Performance Laboratory, Faculty of Kinesiology, University of Calgary, Calgary, AB, Canada; McCaig Institute for Bone and Joint Health, University of Calgary, Calgary, AB, Canada.
    Quantitative CT (QCT) analysis involves the calculation of specific parameters such as bone volume and density from CT image data, and can be a powerful tool for understanding bone quality and quantity. However, without careful attention to detail during all steps of the acquisition and analysis process, data can be of poor- to unusable-quality. Good quality QCT for research requires meticulous attention to detail and standardization of all aspects of data collection and analysis to a degree that is uncommon in a clinical setting. Read More

    Bone, muscle, and metabolic parameters predict survival in patients with synchronous bone metastases from lung cancers.
    Bone 2018 Mar 11;108:202-209. Epub 2018 Jan 11.
    INSERM UMR1033-LYOS, Université de Lyon, Lyon F-69003, France; Rheumatology Department, Hospices Civils de Lyon, Pierre-Bénite F-69495, France. Electronic address:
    Background: Lung adenocarcinoma regularly induces bone metastases that are responsible for impaired quality of life as well as significant morbidity, including bone pain and fractures. We aimed at identifying whether bone and metabolic biomarkers were associated with the prognosis of lung adenocarcinoma patients with synchronous bone metastases.

    Patients And Methods: POUMOS is a prospective cohort of patients diagnosed with lung adenocarcinoma and synchronous bone metastases. Read More

    Bone matrix microdamage and vascular changes characterize bone marrow lesions in the subchondral bone of knee osteoarthritis.
    Bone 2018 Mar 10;108:193-201. Epub 2018 Jan 10.
    Discipline of Orthopaedics and Trauma, The University of Adelaide, Adelaide, Australia; Bone and Joint Research Laboratory, SA Pathology, Adelaide, Australia. Electronic address:
    Introduction: Bone marrow lesions (BMLs) in the subchondral bone in osteoarthritis (OA) are suggested to be multifactorial, although the pathogenic mechanisms are unknown. Bone metabolism and cardiovascular risk factors associate with BML in epidemiologic studies. However, there are no studies at the tissue level investigating the relationship between these processes and BML. Read More

    Marrow adipose tissue imaging in humans.
    Bone 2018 Jan 10. Epub 2018 Jan 10.
    Department of Radiology, Musculoskeletal Imaging and Interventions, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, United States. Electronic address:
    Bone strength is affected not only by bone mineral density (BMD) and bone microarchitecture but also its microenvironment. Recent studies have focused on the role of marrow adipose tissue (MAT) in the pathogenesis of bone loss. Osteoblasts and adipocytes arise from a common mesenchymal stem cell within bone marrow and many osteoporotic states, including aging, medication use, immobility, over - and undernutrition are associated with increased marrow adiposity. Read More

    Cigarette smoking and hip volumetric bone mineral density and cortical volume loss in older adults: The AGES-Reykjavik study.
    Bone 2018 Mar 10;108:186-192. Epub 2018 Jan 10.
    National Institute on Aging, Intramural Research Program, Laboratory of Epidemiology and Population Sciences, Bethesda, MD, USA.
    This study aimed to explore the relationships of several indicators of cigarette smoking habits (smoking status, pack-years, age at smoking initiation and smoking cessation) with quantitative computed tomographic (QCT)-derived proximal femur bone measures (trabecular vBMD, integral vBMD and the ratio of cortical to total tissue volume (cvol/ivol)) and with subsequent change in these measures over the next five years. A total of 2673 older adults (55.9% women), aged 66-92 years at baseline from the Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study, who had two QCT scans of the hip were studied. Read More

    The regulatory roles of Notch in osteocyte differentiation via the crosstalk with canonical Wnt pathways during the transition of osteoblasts to osteocytes.
    Bone 2018 Mar 10;108:165-178. Epub 2018 Jan 10.
    Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD 4059, Australia; The Australia-China Centre for Tissue Engineering and Regenerative Medicine (ACCTERM), Queensland University of Technology, Brisbane, QLD 4059, Australia. Electronic address:
    Osteocytes comprise more than 90% of the cells in bone and are differentiated from osteoblasts via an unknown mechanism. Recently, it was shown that Notch signaling plays an important role in osteocyte functions. To gain insights into the mechanisms underlying the functions of Notch in regulating the transition of osteoblasts to osteocytes, we performed a luciferase assay by cloning the proximal E11 and dentin matrix acidic phosphoprotein 1 (DMP1) promotor regions into pGluc-Basic 2 vectors, which were subsequently transfected into the IDG-SW3 (osteocytes), MC3T3 (osteoblasts) and 293T (non-osteoblastic cells) cell lines. Read More

    Spatiotemporal characterization of microdamage accumulation in rat ulnae in response to uniaxial compressive fatigue loading.
    Bone 2018 Mar 10;108:156-164. Epub 2018 Jan 10.
    Department of Biomedical Engineering, Fourth Military Medical University, Xi'an, China. Electronic address:
    Repetitive fatigue loading can induce microdamage accumulation in bone matrix, which results in impaired mechanical properties and increased fracture susceptibility. However, the spatial distribution and time-variant process of microdamage accumulation in fatigue-loaded skeleton, especially for linear microcracks which are known to initiate bone remodeling, remain not fully understood. In this study, the time-varying process of the morphology and distribution of microcracks in rat ulnae subjected to uniaxial compressive fatigue loading was investigated. Read More

    SNPs in the vicinity of P2X7R, RANK/RANKL/OPG and Wnt signalling pathways and their association with bone phenotypes in academy footballers.
    Bone 2018 Mar 8;108:179-185. Epub 2018 Jan 8.
    Musculoskeletal Physiology Research Group, Sport, Health and Performance Enhancement Research Centre, Nottingham Trent University, Clifton Lane, Nottingham NG11 8NS, UK. Electronic address:
    Context: Genotype plays an important role in influencing bone phenotypes, such as bone mineral density, but the role of genotype in determining responses of bone to exercise has yet to be elucidated.

    Objective: To determine whether 10 SNPs associated with genes in the vicinity of P2X7R, RANK/RANKL/OPG and Wnt Signalling Pathways are associated with bone phenotypes in elite academy footballers (Soccer players) and to determine whether these genotypes are associated with training induced changes in bone. Design, participants, and methods: 99 elite academy footballers volunteered to participate. Read More

    A case report of mesenteric heterotopic ossification: Histopathologic and genetic findings.
    Bone 2018 Jan 7. Epub 2018 Jan 7.
    Department of Medicine, Mayo Clinic School of Medicine, Mayo Clinic, Rochester, MN, United States. Electronic address:
    Mesenteric heterotopic ossification (MHO) is very rare and occurs in mid- to late-adulthood, usually in the context of prior abdominal surgery. The mechanisms of MHO are unknown. Here we describe the case of a 72-year-old man with MHO. Read More

    Osteopontin regulates dentin and alveolar bone development and mineralization.
    Bone 2018 Feb 5;107:196-207. Epub 2017 Dec 5.
    National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Institutes of Health (NIH), Bethesda, MD, USA.
    The periodontal complex is essential for tooth attachment and function and includes the mineralized tissues, cementum and alveolar bone, separated by the unmineralized periodontal ligament (PDL). To gain insights into factors regulating cementum-PDL and bone-PDL borders and protecting against ectopic calcification within the PDL, we employed a proteomic approach to analyze PDL tissue from progressive ankylosis knock-out (Ank) mice, featuring reduced PP, rapid cementogenesis, and excessive acellular cementum. Using this approach, we identified the matrix protein osteopontin (Spp1/OPN) as an elevated factor of interest in Ankmouse molar PDL. Read More

    Fat mass is positively associated with bone mass acquisition in children with small or normal lean mass: A three-year follow-up study.
    Bone 2018 Feb 5;107:222-227. Epub 2017 Dec 5.
    Department of Public Health, Kindai University Faculty of Medicine, 377-2 Oono-Higashi, Osaka-Sayama 589-8511, Japan.
    The independent impact of fat mass (FM) on bone health is difficult to assess, as FM is correlated with lean soft tissue mass (LSTM). In a previous cross-sectional study, FM was suggested to help promote high bone mass acquisition in adolescents with small LSTM. The present prospective cohort study investigated the effects of FM on bone in pubertal children after stratification by height-normalized index of LSTM (LSTMI). Read More

    Longitudinal changes in bone-testis axis and their associations with insulin resistance in 11- to 12-year-old boys.
    Bone 2018 Mar 5;108:115-120. Epub 2018 Jan 5.
    Department of Paediatrics, Faculty of Medicine, University of Tartu, Tartu, Estonia.
    Purpose: Associations between osteocalcin (OCN), an osteoblast-specific hormone, and different markers of energy metabolism and insulin resistance have been reported in adults, but few studies have investigated this in children. The aim of the current study was to investigate serum OCN levels during pubertal development in normal weight (NW) and overweight (OW) boys, and to evaluate possible associations of OCN with body composition, testosterone, insulin resistance and adipocytokine values during puberty.

    Methods: Ninety 11- to 12-year-old boys were investigated at 12-month intervals over the next 2years. Read More

    Computational and functional characterization of four SNPs in the SOST locus associated with osteoporosis.
    Bone 2018 Mar 4;108:132-144. Epub 2018 Jan 4.
    Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan 430079, China. Electronic address:
    The SOST gene encodes sclerostin, a C-terminal cysteine knot-like domain containing key negative regulator of osteoblastic bone formation that inhibits LRP5/6-mediated canonical Wnt signaling. Numerous single nucleotide polymorphisms (SNPs) in the SOST locus are firmly associated with bone mineral density (BMD) and fracture in genome-wide association studies (GWAS) and candidate gene association studies. However, the validation and mechanistic elucidation of causal genetic variants, especially for SNPs located beyond the promoter-proximal region, remain largely unresolved. Read More

    Variant BMP receptor mutations causing fibrodysplasia ossificans progressiva (FOP) in humans show BMP ligand-independent receptor activation in zebrafish.
    Bone 2018 Jan 4. Epub 2018 Jan 4.
    Department of Cell and Developmental Biology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. Electronic address:
    The large majority of cases of the autosomal dominant human disease fibrodysplasia ossificans progressiva (FOP) are caused by gain-of-function Arg206His mutations in the BMP type I receptor ACVR1 (ALK2). The Arg206His mutation is located in the GS domain of the type I receptor. This region is normally phosphorylated by the BMP type II receptor, which activates the type I receptor to phosphorylate its substrate, the signal transducer Smad1/5/8. Read More

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