Age-Related Increases in Marrow Fat Volumes have Regional Impacts on Bone Cell Numbers and Structure
In this study, we hypothesize that areas of bone marrow with high fat volumes are associated with significant changes in cell number within a similar region of interest (ROI). Inbred albino Louvain (LOU) rats, originating from the Wistar strain, have been described as a model of healthy aging with the absence of obesity but expressing the typical features of age-related bone loss. We compared local changes in distal femur cellularity and structure in specific ROI of undecalcified bone sections from 4- and 20-month-old male and female LOU rats and Wistar controls. Our results confirmed that older LOU rats exhibited signific...
Source: Calcified Tissue International - July 9, 2020 Category: Orthopaedics Source Type: research

The Use of Collagen-Induced Arthritis Animal Model on Studying Bone Metabolism
AbstractCIA is a well-studied animal model of autoimmune arthritis. It resembles rheumatoid arthritis as far as histopathological changes and molecular pathogenesis are concerned. CIA is induced by immunization with collagen type II in susceptible strains. The purpose of this review is to assess the use of CIA animal model on bone metabolism and the potential therapeutic agents that could reverse this effect. A database search from their inception to 2019 was conducted to identify experimental animal studies pertinent to CIA model and bone examination. Studies including ovariectomy or without a direct comparison between co...
Source: Calcified Tissue International - July 9, 2020 Category: Orthopaedics Source Type: research

Dapagliflozin and Liraglutide Therapies Rapidly Enhanced Bone Material Properties and Matrix Biomechanics at Bone Formation Site in a Type 2 Diabetic Mouse Model
This study hi ghlighted that these two molecules are effective in improving bone material properties and modulating matrix biomechanics at bone formation site. This study also highlighted that the resulting effects on bone material properties are not identical between dapagliflozin and liraglutide and not only me diated by lower blood glucose. (Source: Calcified Tissue International)
Source: Calcified Tissue International - July 8, 2020 Category: Orthopaedics Source Type: research

Functional Analysis of Calcium-Sensing Receptor Variants Identified in Families Provisionally Diagnosed with Familial Hypocalciuric Hypercalcaemia
AbstractIdentification of variants in the calcium-sensing receptor (CASR) gene is an important means of distinguishing between familial hypocalciuric hypercalcaemia (FHH) and primary hyperparathyroidism. However, identification and bioinformatics analysis of genetic variants alone is now considered insufficient as definitive proof; additional functional assessment is required to diagnose FHH with certainty. We identified two novel variants, D433Y and C739Y, and one previously reported variant G509R in theCASR of four kindreds provisionally diagnosed with FHH and aimed to functionally characterise these variants to confirm ...
Source: Calcified Tissue International - July 8, 2020 Category: Orthopaedics Source Type: research

Prevalence of Frailty in Older Men and Women: Cross-Sectional Data from the Geelong Osteoporosis Study
This study determined the prevalence of frailty in a population-based sample of older adults and examined the relationship between frailty and comorbid conditions. Men (n = 347) and women (n = 360) aged ≥ 60 year from the Geelong Osteoporosis Study (GOS) were assessed between 2016–2019 and 2011–2014, respectively. Frailty was identified using a modified Fried frailty phenotype. Prevalence estimates were standardised to the 2011 Australian population. Kruskal–Wallis test a ndχ2 test were used to analyse data. For women, mean standardised prevalence estimates were 1...
Source: Calcified Tissue International - July 2, 2020 Category: Orthopaedics Source Type: research

Effects of C-Peptide Replacement Therapy on Bone Microarchitecture Parameters in Streptozotocin-Diabetic Rats
AbstractC-peptide therapy protects against diabetic micro- and macrovascular damages and neuropatic complications. However, to date, the role of C-peptide in preventing diabetes-related bone loss has not been investigated. Our aim was to evaluate if C-peptide infusion improves bone quality in diabetic rats. Twenty-three male Wistar rats were randomly divided into three groups: normal control group; sham diabetic control group; diabetic plus C-peptide group. Diabetes was induced by streptozotocin injection and C-peptide was delivered subcutaneously for 6  weeks. We performed micro-CT and histological testing to assess ...
Source: Calcified Tissue International - June 30, 2020 Category: Orthopaedics Source Type: research

Three-Dimensional Microstructural Basis for Differential Occurrence of Subcapital versus Basicervical Hip Fractures in Men
AbstractWe analyzed the bone microarchitecture of the subcapital and basicervical subregions of the femoral neck in men, to determine whether microarchitectural differences of cortical or trabecular bone can explain differential frequency of subcapital vs. basicervical fractures, especially in aged persons. The study sample encompassed twenty male proximal femora obtained during autopsy. They were divided in two age groups: young (  60 years,n = 10). Micro-computed tomography was used to evaluate cortical and trabecular microarchitecture of the subcapital and basicervical regions of the superolate...
Source: Calcified Tissue International - June 29, 2020 Category: Orthopaedics Source Type: research

The Distinct Role of the Extra-Large G Protein ɑ-Subunit XLɑs
AbstractGNAS is one of the most complex gene loci in the human genome and encodes multiple gene products includingGs α,XL αs,NESP55,A/B, andAS transcripts. XL αs, the extra-large G protein ɑ-subunit, is paternally expressed.XL ɑs andGs ɑ share the common 2 –13 exons with different promoters and first exons. Therefore, XLɑs contains most of the functional domains of Gsα including receptor and effector binding sites. In vitro studies suggest a “Gsɑ”-like function of XLɑs regarding the stimulation of cAMP generation in response to receptor acti vation with different cellular act...
Source: Calcified Tissue International - June 28, 2020 Category: Orthopaedics Source Type: research

Successful Intravascular Treatment of an Intraosseous Arteriovenous Fistula in Fibrous Dysplasia
We describe a case of an aggressive occipital lesion that presented with pain associated with diplopia and tinnitus, raising concern for malignant transformation. A massive intraosseous arteriovenous fistula was identified giving rise to an anomalous vein coursing to the cavernous sinus with compression of the abducens nerve. The vascular anomaly was mapped and after embolization symptoms resolved; a biopsy with extensive genetic analyses excluded malignancy. The differential diagnosis for expanding FD lesions includes aggressive FD, malignant transformation, and secondary vascular anomalies. In cases when traditional radi...
Source: Calcified Tissue International - June 17, 2020 Category: Orthopaedics Source Type: research

New Therapies for Hypophosphatemia-Related to FGF23 Excess
AbstractFGF23 is a hormone produced by osteocytes in response to an elevation in the concentration of extracellular phosphate. Excess production of FGF23 by bone cells, or rarely by tumors, is the hormonal basis for several musculoskeletal syndromes characterized by hypophosphatemia due to renal phosphate wasting. FGF23-dependent chronic hypophosphatemia causes rickets and osteomalacia, as well as other skeletal complications. Genetic disorders of FGF23-mediated hypophosphatemia include X-linked hypophosphatemia (XLH), autosomal dominant hypophosphatemic rickets (ADHR), autosomal recessive hypophosphatemic rickets (ARHR), ...
Source: Calcified Tissue International - June 5, 2020 Category: Orthopaedics Source Type: research

Tumor-Induced Osteomalacia
AbstractTumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome caused by tumoral production of fibroblast growth factor 23 (FGF23). The hallmark biochemical features include hypophosphatemia due to renal phosphate wasting, inappropriately normal or frankly low 1,25-dihydroxy-vitamin D, and inappropriately normal or elevated FGF23. TIO is caused by typically small, slow growing, benign phosphaturic mesenchymal tumors (PMTs) that are located almost anywhere in the body from the skull to the feet, in soft tissue or bone. The recent identification of fusion genes in a significant subset of PMTs has provided importa...
Source: Calcified Tissue International - June 5, 2020 Category: Orthopaedics Source Type: research

Do Older Adults with Low Muscle Mass or Strength, in the Presence of Obesity, Have an Increased Risk of Joint Replacement Over 13 Years?
This study aims to assess whether older adults with low muscle mass or strength, in the presence of obesity, have an increased risk of knee (TKR) and hip replacement (THR) over 13  years. 1082 community-dwelling older adults (51% women; mean age 62.9 ± 7.5 years) were studied at baseline and multiple time points over 13 years. The incidence of TKR and THR was determined by data linkage to National Joint Replacement Registry. Appendicular lean and fat mass were measure d using DXA. Lower-limb muscle strength (LMS) was assessed by dynamometer. Low muscle mass and strength were defined as t...
Source: Calcified Tissue International - June 3, 2020 Category: Orthopaedics Source Type: research

The Predictive Value of Sarcopenia and Falls for 2-Year Major Osteoporotic Fractures in Community-Dwelling Older Adults
AbstractTo evaluate the associations of sarcopenia and previous falls with 2-year major osteoporotic fractures (MOFs) in community-dwelling older adults. Four thousand Chinese men and women  ≥ 65 years recruited from Hong Kong communities were prospectively followed up. Measures of muscle mass, grip strength, gait speed and falls in the previous year were recorded at baseline, the 2nd year and the 4th year visit for each subject. The associations of fall history, sarcopenia and its components with 2-year MOFs were evaluated using generalized linear mixed models. Poor grip strength and poor gait speed ...
Source: Calcified Tissue International - May 30, 2020 Category: Orthopaedics Source Type: research

Effect of Metformin vs. Placebo in Combination with Insulin Analogues on Bone Markers P1NP and CTX in Patients with Type 2 Diabetes Mellitus
AbstractPreclinical studies have shown a potential osteoanabolic effect of metformin but human studies of how metformin affects bone turnover are few. A post hoc sub-study analysis of an 18-month multicenter, placebo-controlled, double-blinded trial in type 2 diabetes mellitus (T2DM), randomizing participants to metformin versus placebo both in combination with different insulin analogue regimens (Metformin  + Insulin vs. Placebo + Insulin). Patients were not treatment naive at baseline, 83% had received metformin, 69% had received insulin, 57.5% had received the combination of metformin and ins...
Source: Calcified Tissue International - May 28, 2020 Category: Orthopaedics Source Type: research

Roles of Olfactomedin 1 in Muscle and Bone Alterations Induced by Gravity Change in Mice
In conclusion, we first showed that OLFM1 suppresses osteoclast formation and RANKL expression in mouse cells. (Source: Calcified Tissue International)
Source: Calcified Tissue International - May 27, 2020 Category: Orthopaedics Source Type: research

Unloading-Induced Cortical Bone Loss is Exacerbated by Low-Dose Irradiation During a Simulated Deep Space Exploration Mission
In conclusion, we show that low-dose radiation exposure negatively influences bone physiology beyond that induced by microgravity alone. (Source: Calcified Tissue International)
Source: Calcified Tissue International - May 25, 2020 Category: Orthopaedics Source Type: research

Bisphosphonate Therapy and Tooth Development in Children and Adolescents with Osteogenesis Imperfecta
AbstractOsteogenesis imperfecta (OI) is a heterogeneous connective tissue disorder characterized by repeated fractures and skeletal disorders. At present, bisphosphonate (BP) therapy is the gold standard for OI treatment. The present retrospective study evaluated the effect of BP therapy on tooth development and eruption of permanent teeth in a cohort of children receiving pamidronate. Three groups were studied: patients with OI who were treated with BPs (n = 45), patients with OI who were not treated with BPs (n = 117), and age- and gender-matched healthy controls (n = 121). Denta...
Source: Calcified Tissue International - May 25, 2020 Category: Orthopaedics Source Type: research

Hemoglobin Levels are Low in Sarcopenic and Osteosarcopenic Older Persons
In this study, we aimed to compare hemoglobin (Hb) levels in osteosarcopenic older subjects versus those with sarcopenia, osteopenia/osteoporosis alone and controls. Cross-sectional study in 558 community-dwelling participants older than 65 (mean age 79  ± 7.5 years) from Western Sydney, Australia. Associations of anemia with sarcopenia, osteopenia/osteoporosis and osteosarcopenia were assessed. Participants were able to mobilize independently, reported a risk/history of falls and were not cognitively impaired. We used the original (EWGOP) an d revised (EWGSOP2) European consensus on definition of...
Source: Calcified Tissue International - May 21, 2020 Category: Orthopaedics Source Type: research

Prolonged 25-OH Vitamin D Deficiency Does Not Impair Bone Mineral Density in Adult Patients With Vitamin D 25-Hydroxylase Deficiency ( CYP2R1 )
AbstractVitamin D-dependent rickets type 1B (VDDR1B) is an autosomal semidominant genetic disorder caused by a deficiency inCYP2R1, which encodes vitamin D 25-hydroxylase, an enzyme that plays a crucial role in the conversion of vitamin D to 25-dihydroxyvitamin D3. VDDR1B is a severe form of rickets that occurs during infancy and which is responsive to 25-OH vitamin D supplementation. We studied three adult patients from a multi-consanguineous family with VDDR1B. They have been diagnosed with pseudo-nutritional rickets and treated during their adolescence with 25-OH vitamin D. These patients stopped their treatments at the...
Source: Calcified Tissue International - May 19, 2020 Category: Orthopaedics Source Type: research

Where Two Common Conditions of Aging Meet: Osteoarthritis and Sarcopenia
AbstractOsteoarthritis and sarcopenia are the most frequently described musculoskeletal disorders in older persons but the intertwining of these conditions and of their functional and cellular causes is complex. This narrative review aims to identify the links between osteoarthritis and sarcopenia described 1-in clinical studies, 2-in in vitro studies, and 3-the available treatment strategies for both conditions. Electronic databases were used for the literature search of all studies investigating the relationship between sarcopenia and the presence of concomitant osteoarthritis. This review identified a limited number of ...
Source: Calcified Tissue International - May 18, 2020 Category: Orthopaedics Source Type: research

Congenital Conditions of Hypophosphatemia Expressed in Adults
AbstractThe main congenital conditions of hypophosphatemia expressed in adulthood include several forms of hereditary hypophosphatemic rickets and a congenital disorder of vitamin D metabolism characterized by osteomalacia and hypophosphatemia in adult patients. Hypophosphatemia in adults is defined as serum phosphate concentration  
Source: Calcified Tissue International - May 14, 2020 Category: Orthopaedics Source Type: research

The Genetic Epidemiology of Joint Shape and the Development of Osteoarthritis
AbstractCongruent, low-friction relative movement between the articulating elements of a synovial joint is an essential pre-requisite for sustained, efficient, function. Where disorders of joint formation or maintenance exist, mechanical overloading and osteoarthritis (OA) follow. The heritable component of OA accounts for  ~ 50% of susceptible risk. Although almost 100 genetic risk loci for OA have now been identified, and the epidemiological relationship between joint development, joint shape and osteoarthritis is well established, we still have only a limited understanding of the contribution that genetic ...
Source: Calcified Tissue International - May 11, 2020 Category: Orthopaedics Source Type: research

Osteoarthritis: Current Molecular Biomarkers and the Way Forward
AbstractThe ultimate hope of researchers and patients is a pathway to development of treatments for osteoarthritis to modify the disease process in addition to the symptoms. However, development of disease modifying drugs requires objective endpoints such as measures of joint structure, joint tissue homeostasis and/or joint survival –measures such as provided by imaging biomarkers, molecular biomarkers and joint replacement frequency, respectively. Although biomarkers supporting investigational drug use and drug approval include surrogate endpoints that may not necessarily reflect or directly correlate with the clini...
Source: Calcified Tissue International - May 4, 2020 Category: Orthopaedics Source Type: research

The Association Between Muscle Mass and Strength in Relation to Bone Measures in a Paediatric Population: Sex-Specific Effects
AbstractPost-puberty, bone mass displays clear sex-specific patterns. However, research has suggested that a sexual dimorphism in bone mass is evident in younger children and is likely attributable to differences in lean mass. Thus, we aimed to determine whether the association with both overall muscle mass and/or muscle strength was different between the sexes in a paediatric population. Participants were recruited as part of the Vitamin D in Pregnancy Study, Australia. There were 209/402 (52.3%) children at the 11-year follow-up, and 172 had complete data. Children were assessed for bone mineral content (BMC), bone miner...
Source: Calcified Tissue International - May 2, 2020 Category: Orthopaedics Source Type: research

The lncRNA GAS5 Inhibits the Osteogenic Differentiation and Calcification of Human Vascular Smooth Muscle Cells
AbstractVascular calcification (VC), which is associated with high cardiovascular morbidity and mortality in patients with chronic kidney disease, is promoted by the osteoblastic differentiation of vascular smooth muscle cells (VSMCs). The present study explored the functional roles and molecular mechanisms of the long noncoding RNA growth arrest-specific transcript 5 (GAS5) in VC. Our results indicated that GAS5 was clearly downregulated in calcified human aortic vascular smooth muscle cells (HASMCs). Functionally, we found that overexpression of GAS5 significantly attenuated the osteogenic differentiation and calcificati...
Source: Calcified Tissue International - April 28, 2020 Category: Orthopaedics Source Type: research

A Rare Cause of Hypophosphatemia: Raine Syndrome Changing Clinical Features with Age
AbstractRaine Syndrome (RS) is caused by biallelic loss-of-function mutations inFAM20C gene and characterized by hypophosphatemia, typical facial and skeletal features. Subperiosteal bone formation and generalized osteosclerosis are the most common radiological findings. Here we present a new case with RS. A 9-month-old male patient on a home-type ventilator was referred for hypophosphatemia. He was born with a weight of 3800  g to non-consanguineous parents. Prenatal ultrasound had demonstrated nasal bone agenesis. A large anterior fontanel, frontal bossing, exophthalmos, hypoplastic nose, high arched palate, low set...
Source: Calcified Tissue International - April 27, 2020 Category: Orthopaedics Source Type: research

Congenital Conditions of Hypophosphatemia in Children
This article will review the pathophysiologic causes of congenital hypophosphatemia, their clinical consequences and medical therapy. (Source: Calcified Tissue International)
Source: Calcified Tissue International - April 23, 2020 Category: Orthopaedics Source Type: research

A Case of a Heterozygous Inactivating CASR Variant with Adult-Onset Symptomatic Hypercalcemia Requiring Extensive Surgery
We describe the case of an adult female patient with symptomatic familial hypocalciuric hypercalcemia requiring a step-wise therapeutic approach and the eventual need for a total parathyroidectomy and thyroidectomy to cure symptoms. Genetic analysis demonstrated a heterozygous R227L inactivatingCASR gene variant, previously only described in neonatal severe hyperparathyroidism. Post-operative histology showed diffuse hyperplasia of all four parathyroid glands along with the presence of intrathyroidal parathyroid tissue. With regard to clinical management this case suggests that familial hypocalciuric hypercalcemia should b...
Source: Calcified Tissue International - April 19, 2020 Category: Orthopaedics Source Type: research

Correction to: Identifying Scoliosis in Population ‑Based Cohorts: Automation of a Validated Method Based on Total Body Dual Energy X‑ray Absorptiometry Scans
In the original version of the article, the co-author would like to add to the acknowledgements section to highlight their funding stream (EPSRC). The revised acknowledgements is given below. (Source: Calcified Tissue International)
Source: Calcified Tissue International - April 18, 2020 Category: Orthopaedics Source Type: research

JZL184, A Monoacylglycerol Lipase Inhibitor, Induces Bone Loss in a Multiple Myeloma Model of Immunocompetent Mice
AbstractMultiple myeloma (MM) patients develop osteolysis characterised by excessive osteoclastic bone destruction and lack of osteoblast bone formation. Pharmacological manipulation of monoacylglycerol lipase (MAGL), an enzyme responsible for the degradation of the endocannabinoid 2-arachidonoyl glycerol (2-AG), reduced skeletal tumour burden and osteolysis associated with osteosarcoma and advanced breast and prostate cancers. MM and hematopoietic, immune and bone marrow cells express high levels of type 2 cannabinoid receptor and osteoblasts secrete 2-AG. However, the effects of MAGL manipulation on MM have not been inve...
Source: Calcified Tissue International - April 13, 2020 Category: Orthopaedics Source Type: research

The Causes of Hypo- and Hyperphosphatemia in Humans
AbstractPhosphate homeostasis involves several major organs that are the skeleton, the intestine, the kidney, and parathyroid glands. Major regulators of phosphate homeostasis are parathormone, fibroblast growth factor 23, 1,25-dihydroxyvitamin D, which respond to variations of serum phosphate levels and act to increase or decrease intestinal absorption and renal tubular reabsorption, through the modulation of expression of transcellular transporters at the intestinal and/or renal tubular level. Any acquired or genetic dysfunction in these major organs or regulators may induce hypo- or hyperphosphatemia. The causes of hypo...
Source: Calcified Tissue International - April 13, 2020 Category: Orthopaedics Source Type: research

Glucocorticoids Enhanced Osteoclast Autophagy Through the PI3K/Akt/mTOR Signaling Pathway
AbstractAutophagy is an evolutionarily conserved dynamic process and present in variety of cells at basal levels to maintain homeostasis and to promote cell survival in response to stresses. The early bone loss with excessive glucocorticoids (GCs) was reported to be related with the extension of the life span of osteoclasts. However, the connection between GCs induced bone loss and osteoclast autophagy remains to be elucidated. Autophagy was detected in a Dexamethasone (Dex) induced osteoporotic mice model and primary osteoclast cultures by autophagosome detection kit, and autophagy-related proteins were assayed by Western...
Source: Calcified Tissue International - April 9, 2020 Category: Orthopaedics Source Type: research

Phosphate Metabolism in Health and Disease
AbstractPhosphorus, a 5A element with atomic weight of 31, comprises just over 0.6% of the composition by weight of plants and animals. Three isotopes are available for studying phosphorus metabolism and kinetics.31P is stable, whereas the radioactive isotope33P has a half-life of 25  days and32P has a half-life of 14  days. Phosphate ester and phosphoanhydride are common chemical linkages and phosphorus is a key element in organic molecules involved in a wide variety of essential cellular functions. These include biochemical energy transfer via adenosine triphosphate (ATP), maintenance of genetic information wi ...
Source: Calcified Tissue International - April 7, 2020 Category: Orthopaedics Source Type: research

Medications as a Risk Factor for Fragility Hip Fractures: A Systematic Review and Meta-analysis
AbstractFragility hip fractures and their associated morbidity and mortality pose a global healthcare problem. Several pharmaceutical products have been postulated to alter bone architecture and contribute to fragility hip fractures. We searched four electronic databases from inception to September 2017. Inclusion criteria were the following: (1) adult patients with fragility hip fractures, (2) full text in English, (3) minimum one-year follow-up, and (4) reporting of at least one risk factor. To minimize heterogeneity among the studies, we performed subgroup analyses. Whenever heterogeneity remained significant, we employ...
Source: Calcified Tissue International - April 7, 2020 Category: Orthopaedics Source Type: research

Identification of a 22  bp DNA cis Element that Plays a Critical Role in Colony Stimulating Factor 1-Dependent Transcriptional Activation of the SPHK1 Gene
AbstractSphingosine-1-phosphate (S1P) is an anabolic clastokine. Colony Stimulating Factor 1 (CSF1) induces expression of the rate limiting enzyme required for S1P synthesis, sphingosine kinase 1 (SPHK1) in bone in vivo, and in osteoclasts in vitro. To study the mechanism of CSF1-induced SPHK1 gene expression, a 2608  bp fragment of the murine SPHK1 gene (− 2497 to + 111 bp relative to the transcription start site) was cloned and transfected into pZen cells (murine fibroblasts engineered to express c-fms). SPHK1 promoter activity was assessed using a dual-luciferase reporter assay system. By a...
Source: Calcified Tissue International - April 3, 2020 Category: Orthopaedics Source Type: research

Are Bisphosphonates Associated with Adverse Metabolic and Cognitive Effects? A Study in Intact Rats and Rat-Fed High-Fat High-Fructose Diet
AbstractOsteocalcin, known as a bone gla protein, is considered a regulator of energy metabolism and behavior in its undercarboxylated form (ucOC). Antiresorptive drugs, such as alendronate, reduce serum level of ucOC. The purpose of the current study was to verify if alendronate might impact on energy metabolism and animal behavior by reducing ucOC level and to find out if the presence of metabolic alterations would further worsen these potential adverse effects. Four groups of male Wistar rats (12 per group) were used: a control group, a group receiving high-fat high-fructose diet (HFHF), a group treated with alendronate...
Source: Calcified Tissue International - March 24, 2020 Category: Orthopaedics Source Type: research

HNGF6A Inhibits Oxidative Stress-Induced MC3T3-E1 Cell Apoptosis and Osteoblast Phenotype Inhibition by Targeting Circ_0001843/miR-214 Pathway
In this study, we aimed to investigate the effects of HNGF6A, an analogue of HN, on osteoblast apoptosis and differentiation and the underlying mechanisms. Cell proliferation of murine osteoblastic cell line MC3TC-E1 was examined by CCK8 assay and Edu staining. Cell apoptosis was detected by Annexin V assay under H2O2 treatment. The differentiation of osteoblast was determined by Alizarin red S staining. We also tested the expression of osteoblast phenotype related protein by real-time PCR and Western blot. The interaction between Circ_0001843 and miR-214, miR-214 and TAFA5 was examined by luciferase report assay. Circ_000...
Source: Calcified Tissue International - March 18, 2020 Category: Orthopaedics Source Type: research

Urban –Rural Differences in Bone Mineral Density and its Association with Reproductive and Menstrual Factors Among Older Women
ConclusionMore older women in rural areas had osteoporosis. Later menarche, less years from menarche to menopause and higher parity might partially contribute to decreased BMD among women in rural areas. More attention should be paid to women in rural areas to prevent bone loss and further bone and health impairment. (Source: Calcified Tissue International)
Source: Calcified Tissue International - March 16, 2020 Category: Orthopaedics Source Type: research

Increased Risk of Hip Fracture in Patients with Lymphoma, a Swedish Population Study of 37,236 Lymphoma Patients
AbstractIncreased bone loss has been noted in lymphoma patients; however, the incidence of hip fracture is not known. The aim of our study was to explore the risk for hip fracture in patients with lymphoma compared with the entire Swedish population. The risk of hip fracture was determined in a retrospective population cohort study of adult Swedish lymphoma patients (n = 37,236), diagnosed 1995–2015 and compared with the entire Swedish population during the same period. The incidence of hip fracture in lymphoma patients was higher in women than in men, increased by age, and decreased by calendar year as...
Source: Calcified Tissue International - March 13, 2020 Category: Orthopaedics Source Type: research

Distribution of Prevalent and Incident Vertebral Fractures and Their Association with Bone Mineral Density in Postmenopausal Women in the Teriparatide Versus Risedronate VERO Clinical Trial
AbstractVertebral fractures (VFx) occur most frequently in the mid-thoracic and thoraco-lumbar regions, which experience the highest mechanical loading along the spine. The prevalence and incidence of VFx by their location and severity, and their relationship with bone mineral density (BMD), are seldom reported in randomized clinical trial cohorts. The VERO trial randomized 1360 postmenopausal women with at least two moderate or one severe VFx to receive either teriparatide or risedronate for up to 24  months. In this post hoc analysis, we describe the centrally read distribution and severity of prevalent and incident...
Source: Calcified Tissue International - March 10, 2020 Category: Orthopaedics Source Type: research

Self-perceived Fracture Risk in the Global Longitudinal Study of Osteoporosis in Women: Its Correlates and Relationship with Bone Microarchitecture
AbstractThe purpose of this study is to examine correlates of self-perceived fracture risk (SPR) and relationships between SPR and subsequent bone density and microarchitecture in the UK arm of the Global Longitudinal Study of Osteoporosis in Women. 3912 women completed baseline questionnaires detailing medical history and SPR; 492 underwent HRpQCT scans of the radius and tibia and DXA scans of total body, hip, femoral neck and lumbar spine a median of 7.5  years later. Correlates of SPR were examined and a cluster analysis of potential predictors of SPR performed. SPR in relation to HRpQCT and aBMD parameters was exa...
Source: Calcified Tissue International - March 5, 2020 Category: Orthopaedics Source Type: research

Modulation of Transient Receptor Potential Channels 3 and 6 Regulates Osteoclast Function with Impact on Trabecular Bone Loss
AbstractEnhanced osteoclast formation and function is a fundamental cause of alterations to bone structure and plays an important role in several diseases impairing bone quality. Recent work revealed that TRP calcium channels 3 and 6 might play a special role in this context. By analyzing the bone phenotype of TRPC6-deficient mice we detected a regulatory effect of TRPC3 on osteoclast function. These mice exhibit a significant decrease in bone volume per tissue volume, trabecular thickness and -number together with an increased number of osteoclasts found on the surface of trabecular bone. Primary bone marrow mononuclear c...
Source: Calcified Tissue International - March 5, 2020 Category: Orthopaedics Source Type: research

Wnt16 Overexpression in Osteoblasts Increases the Subchondral Bone Mass but has no Impact on Osteoarthritis in Young Adult Female Mice
AbstractEpidemiological studies have shown that high bone mineral density (BMD) is associated with an increased risk of osteoarthritis (OA), but the causality of this relationship remains unclear. Both bone mass and OA have been associated with the WNT signaling pathway in genetic studies, there is thus an interest in studying molecular partners of the WNT signaling pathway and OA. Female mice overexpressing WNT16 in osteoblasts (Obl-Wnt16 mice) have an increased bone mass. We aimed to evaluate if the high bone mass inObl-Wnt16 mice leads to a more severe experimental OA development than in WT control mice. We induced expe...
Source: Calcified Tissue International - March 5, 2020 Category: Orthopaedics Source Type: research

Long-term rates of change in musculoskeletal aging and body composition: findings from the Health, Aging and Body Composition Study
AbstractMusculoskeletal disorders are common among older people. Preventive strategies require understanding of age-related changes in strength, function and body composition, including how they interrelate. We have described, and examined associations between, 9-year changes in these parameters among 2917 Health, Aging and Body Composition Study participants (aged 70 –79 years). Appendicular lean mass (ALM), whole body fat mass and total hip BMD were ascertained using DXA; muscle strength by grip dynamometry; and muscle function by gait speed. For each characteristic annualised percentage changes were calculate...
Source: Calcified Tissue International - March 3, 2020 Category: Orthopaedics Source Type: research

Characterization of Skeletal Muscle Endocrine Control in an In Vitro Model of Myogenesis
AbstractSkeletal muscle has remarkable regenerative abilities regulated by a highly orchestrated process involving the activation of cellular and molecular responses, which are dependent on satellite cells. These cells maintain the stem cell population and provide numerous myogenic cells that proliferate, differentiate, fuse and lead to new myofiber formation for a functional contractile tissue. We have isolated and characterized satellite cells obtained from human biopsies and established an in vitro model of myogenesis, evaluating muscle regeneration, monitoring the dynamic increases of the specific myogenic regulatory f...
Source: Calcified Tissue International - February 27, 2020 Category: Orthopaedics Source Type: research

Exosomes Secreted by Young Mesenchymal Stem Cells Promote New Bone Formation During Distraction Osteogenesis in Older Rats
This study aimed to evaluate the effects of MSC-Exos on bone regeneration during DO in older rats. Exosomes were isolated from the supernatants of young bone marrow mesenchymal stem cells (BMSCs) through ultra-centrifugation, and characterized using transmission electron microscopy, western blot, and tunable resistive pulse sensing analysis. The effects of MSC-Exos on the proliferation and differentiation of older BMSCs were evaluated using CCK-8 assay, ALP and ARS staining, and qRT-PCR. Unilateral tibial DO model was established on older Sprague –Dawley rats and MSC-Exos or phosphate buffer saline was locally inject...
Source: Calcified Tissue International - February 26, 2020 Category: Orthopaedics Source Type: research

Clinical Significance of Hypophosphatasemia in Children
In conclusion, reflected persistent hypophosphatasemia frequency was 1/1552 (0.06%) in this large pediatric cohort and,ALPL gene mutations were detected in 13.5% (5/37) of the studied cases. Although biochemical hypophosphatasemia is not uncommon, clinically significant HPP is rare. (Source: Calcified Tissue International)
Source: Calcified Tissue International - February 22, 2020 Category: Orthopaedics Source Type: research

Hyponatremia, Hypokalemia, and Fragility Fractures in Old Patients: More than an Association?
This study is divided in two parts: one retrospective and one prospective. We retrospectively collected data on urgently admitted patients for femoral fragility fractures (Fx) or for acute myocardial infarction (AMI), and patients admitted for elective hip/knee replacement surgery for osteoarthrosis (OA). Age, sex, serum sodium, potassium, creatinine, and comorbidities were recorded. We enrolled prospectively in-patients from our unit: age, sex, comorbidities, drugs, and fragility fractures were recorded. Blood electrolytes were measured. Cognitive function, nutrition, muscular strength, and balance were evaluated by stand...
Source: Calcified Tissue International - February 19, 2020 Category: Orthopaedics Source Type: research

High-Level Expression of Alkaline Phosphatase by Adeno-Associated Virus Vector Ameliorates Pathological Bone Structure in a Hypophosphatasia Mouse Model
AbstractHypophosphatasia (HPP) is a systemic skeletal disease caused by mutations in the gene encoding tissue-nonspecific alkaline phosphatase (TNALP). We recently reported that survival of HPP model mice can be prolonged using an adeno-associated virus (AAV) vector expressing bone-targeted TNALP with deca-aspartate at the C terminus (TNALP-D10); however, abnormal bone structure and hypomineralization remained in the treated mice. Here, to develop a more effective and clinically applicable approach, we assessed whether transfection with TNALP-D10 expressing virus vector at a higher dose than previously used would ameliorat...
Source: Calcified Tissue International - February 19, 2020 Category: Orthopaedics Source Type: research

Models of Osteoarthritis: Relevance and New Insights
AbstractOsteoarthritis (OA) is a progressive and disabling musculoskeletal disease affecting millions of people and resulting in major healthcare costs worldwide. It is the most common form of arthritis, characterised by degradation of the articular cartilage, formation of osteophytes, subchondral sclerosis, synovial inflammation and ultimate loss of joint function. Understanding the pathogenesis of OA and its multifactorial aetiology will lead to the development of effective treatments, which are currently lacking. Two-dimensional (2D) in vitro tissue models of OA allow affordable, high-throughput analysis and stringent c...
Source: Calcified Tissue International - February 15, 2020 Category: Orthopaedics Source Type: research