Long Non-coding RNA XIST May Influence Cervical Ossification of the Posterior Longitudinal Ligament Through Regulation of miR-17-5P/AHNAK/BMP2 Signaling Pathway
This study was conducted to investigate the role and mechanism of lncRNA X inactive specific transcript (XIST) in the occurrence of cervical ossification of the posterior longitudinal ligament (OPLL). Here, primary human ligament fibroblasts cells (LFCs) were isolated from 30 cases of OPLL and 30 normal cervical posterior longitudinal ligament (non-OPLL) tissues to perform the qPCR and Western blot assay. We found that the mRNA level of lncRNA XIST was significantly increased in OPLL LFCs compared to non-OPLL LFCs. By bioinformatics analysis, we found that lncRNA XIST has four binding sites for miR-17-5p and found that the...
Source: Calcified Tissue International - September 11, 2019 Category: Orthopaedics Source Type: research

Functional Measures of Sarcopenia: Prevalence, and Associations with Functional Disability in 10,892 Adults Aged 65  Years and Over from Six Lower- and Middle-Income Countries
AbstractIdentification of sarcopenia in lower- and middle-income countries (LMICs) is limited by access to technologies that assess muscle mass. We investigated associations between two functional measures of sarcopenia, grip strength and gait speed (GS), with functional disability in adults from six LMICs. Data were extracted from the World Health Organization (WHO) Study on global AGEing and adult health Wave 1 (2007 –2010) for adults (≥ 65 years) from China, Mexico, Ghana, India, Russia and South Africa (n = 10,892, 52.8% women). We calculated country-specific prevalence of low grip st...
Source: Calcified Tissue International - September 10, 2019 Category: Orthopaedics Source Type: research

Understanding Patients ’ Perspectives and Educational Needs by Type of Osteoporosis in Men and Women and People with Glucocorticosteroid-Induced Osteoporosis: A Qualitative Study to Improve Disease Management
AbstractThe aim of the study was to investigate similarities and differences in health beliefs, experiences and educational needs by type of osteoporosis (OP), particularly in people with glucocorticoid-induced OP (GIOP) and men. A qualitative study was conducted via focus groups involving post-menopausal women with or without osteoporotic fractures, osteoporotic men and people with GIOP. Fifty-three participants were included in eight groups. A wide range of health beliefs was found for all types of OP. Osteoporosis was considered a natural consequence of ageing except in men or conversely a serious disease associated wit...
Source: Calcified Tissue International - September 10, 2019 Category: Orthopaedics Source Type: research

The Effect of Dried Beancurd on Bone Mineral Density in Postmenopausal Chinese Women: A 2-Year Randomized Controlled Trial
AbstractSoy foods contain several components such as isoflavones, calcium and protein that potentially modulate bone turnover and increase bone mineral density (BMD) in postmenopausal women. The study is to evaluate the effect of dried beancurd supplementation on skeletal health in postmenopausal Chinese women. Three hundred postmenopausal women aged 50 –65 years were assigned into two groups, receiving 100 g dried beancurd or rice cake a day for 2 years. BMD at the lumbar spine and right proximal femur were measured with a dual-energy X-ray absorptiometry. The bone turnover biomarkers of serum alkalin...
Source: Calcified Tissue International - September 5, 2019 Category: Orthopaedics Source Type: research

Multiple Fractures and Impaired Bone Fracture Healing in a Patient with Pycnodysostosis and Hypophosphatasia
AbstractPycnodysostosis (PYCD) is a rare recessive inherited skeletal disease, characterized by short stature, brittle bones, and recurrent fractures, caused by variants in the Cathepsin K encoding gene that leads to impaired osteoclast-mediated bone resorption. Hypophosphatasia (HPP) is a dominant or recessive inherited condition representing a heterogeneous phenotype with dental symptoms, recurrent fractures, and musculoskeletal problems. The disease results from mutation(s) in the tissue non-specific alkaline phosphate encoding gene with reduced activity of alkaline phosphatase and secondarily defective mineralization o...
Source: Calcified Tissue International - September 5, 2019 Category: Orthopaedics Source Type: research

Earlier Onset in Autosomal Dominant Hypophosphatemic Rickets of R179 than R176 Mutations in Fibroblast Growth Factor 23: Report of 20 Chinese Cases and Review of the Literature
AbstractAutosomal dominant hypophosphatemic rickets (ADHR) is a rare hereditary disorder characterized by variant onset ages and diverse phenotypes. Our aim is to explore the genotype –phenotype correlations between ADHR patients with R176 and R179 mutations inFGF23 gene. Clinical manifestations, laboratory examinations, and genetic analyses were collected from 20 patients in six Chinese ADHR kindreds in our hospital. Previously published ADHR literatures were reviewed. Among 20 Chinese ADHR mutation carriers, 11 patients revealed overt symptoms. 10/11 (90.9%) of which were females. Patients with R179 mutations prese...
Source: Calcified Tissue International - September 5, 2019 Category: Orthopaedics Source Type: research

The Effect of Recombinant Undercarboxylated Osteocalcin on Endothelial Dysfunction
AbstractLow circulating levels of undercarboxylated osteocalcin (ucOC) is associated with a higher risk of cardiovascular disease, yet whether ucOC has a direct effect on endothelium-dependent vasorelaxation, or in proximity to its postulated receptor, the class CG protein-coupled receptor (GPCR6A), in blood vessels remains unclear. Immunohistochemistry and proximity ligation assays were used to localize the presence of ucOC and GPRC6A and to determine the physical proximity (
Source: Calcified Tissue International - September 4, 2019 Category: Orthopaedics Source Type: research

Associations of Smoking and Alcohol and Coffee Intake with Fracture and Bone Mineral Density: A Mendelian Randomization Study
AbstractThe causal associations of smoking and alcohol and coffee intake with fracture and bone mineral density are unknown. We investigated the associations using Mendelian randomization (MR). Summary-level data from UK Biobank for bone fractures (main outcome) (53,184 cases; 373,611 non-cases) and estimated bone mineral density (eBMD) (n = 426,824 individuals) were used. Single-nucleotide polymorphisms associated with smoking initiation (n = 378) and alcohol (n = 99) and coffee (n = 15) intake at the genome-wide significance threshold (P  =  5 &...
Source: Calcified Tissue International - September 4, 2019 Category: Orthopaedics Source Type: research

Substrate Strain Mitigates Effects of β-Aminopropionitrile-Induced Reduction in Enzymatic Crosslinking
This study evaluated dose-dependent effects of BAPN on osteoblast gene expression of type I collagen, LOX, and genes associated with crosslink formation. The second objective was to characterize collagen produced in vitro after exposure to BAPN, and to explore changes to collagen properties under continuous cyclical substrate strain. To evaluate dose-dependent effects, osteoblasts were exposed to a range of BAPN dosages (0–10 mM) for gene expression analysis and cell proliferation. Results showed significant upregulation ofBMP-1,POST, andCOL1A1 and change in cell proliferation. Results also showed that  whi...
Source: Calcified Tissue International - September 3, 2019 Category: Orthopaedics Source Type: research

The Effect of Caffeine on Calcitriol-Inducible Vitamin D Receptor-Controlled Gene Expression in Intestinal and Osteoblastic Cells
AbstractSome epidemiological studies suggested caffeine consumption as the cause for bone mineral density loss. Certain genes involved in this process are regulated by vitamin D receptor (VDR). Therefore, we investigated if caffeine can affect inducible expression of VDR-regulated genes, some of them being involved in bone mineralization process. By employing reporter gene assay, polymerase chain reaction, and western blotting, we monitored the VDR activity and expression in cell cultures of intestinal (LS180), osteosarcoma (HOS), and normal human osteoblasts in vitro. While caffeine stimulated calcitriol-inducible VDR-dep...
Source: Calcified Tissue International - August 30, 2019 Category: Orthopaedics Source Type: research

Non-lethal Raine Syndrome in a Middle-Aged Woman Caused by a Novel FAM20C Mutation
AbstractRaine syndrome is a rare hereditary disease caused by mutations in theFAM20C gene. Only 18 non-lethal cases have been reported, the majority of them being children and young adults aged up to 30. Due to the rarity of the disease, genotype –phenotype correlations are not available and patient life expectancy is unknown, thus making descriptions of each novel case of particular importance. In this article, we describe a case of an Armenian woman, living in Russia, who was followed-up from age 36 to 39, presenting with pain in the ext remities, osteosclerosis with periosteal bone formation, multiple calcificatio...
Source: Calcified Tissue International - August 30, 2019 Category: Orthopaedics Source Type: research

Jump Exercise and Food Restriction on Bone Parameters in Young Female Rats
We examined the effect of jump exercise on bone parameters in young female rats under food restriction. Seven-week-old female rats were divided into four groups: a sedentary and ad libitum feeding group (n = 10), a jump exercise and ad libitum feeding group (n = 9), a sedentary and 30% food restriction group (n = 9), and a jump exercise and 30% food restriction group (n = 10). The jump groups jumped 20 times/day, 5 times/week. The experiment lasted for 13 weeks. There were no interactions of jump exercise and food restriction on bone. Jump exercise under food res...
Source: Calcified Tissue International - August 29, 2019 Category: Orthopaedics Source Type: research

Asiatic Acid Attenuates Bone Loss by Regulating Osteoclastic Differentiation
This study is to examine the effect of Asiatic acid (AA) in osteoclastic differentiation, and further to investigate its effect on bone quality in animals. Effect of AA on osteoclastic differentiation was measured by Tartrate-resistant acid phosphatase stain, bone resorption pit assays, and quantitative real-time polymerase chain reaction. Nuclear factor kappa-light-chain-enhancer of activated B cells (NF- κB) and transforming growth factor-β (TGF-β) signaling were measured by western blot before and after AA treatment. Ovariectomized (OVX) wild-type or Smad7 partially knock out mice were used to evaluate t...
Source: Calcified Tissue International - August 21, 2019 Category: Orthopaedics Source Type: research

No Signature of Osteocytic Osteolysis in Cortical Bone from Lactating NMRI Mice
AbstractThe roles of osteocytes in bone homeostasis have garnered increasing attention since it has been realized that osteocytes communicate with other organs. It has long been debated whether and/or to which degree osteocytes can break down the bone matrix surrounding them in a process called osteocytic osteolysis. Osteocytic osteolysis has been indicated to be induced by a number of skeletal challenges including lactation in CD1 and C57BL/6 mice, whereas immobilization-induced osteocytic osteolysis is still a matter of controversy. Motivated by the wish to understand this process better, we studied osteocyte lacunae in ...
Source: Calcified Tissue International - August 15, 2019 Category: Orthopaedics Source Type: research

Autophagy Regulates Craniofacial Bone Acquisition
In this study, we investigated the effect of autophagy suppression on craniofacial bone acquisition by deletingFip200 orAtg5, two essential autophagy genes, usingOsterix-Cre (Osx-Cre). We found that theOsx-Cre transgene mildly decreased the bone mass of parietal bone but not frontal bone, and did not affect cranial base bone mass in adult mice. In the cranial vault,Fip200 orAtg5 deletion similarly decreased 50% bone mass of neural crest-derived frontal bone;Atg5 deletion decreased 50% andFip200 deletion decreased 30% bone mass of mesoderm-derived parietal bone. In the cranial base,Fip200 orAtg5 deletion similarly decreased...
Source: Calcified Tissue International - August 1, 2019 Category: Orthopaedics Source Type: research

Glucocorticoid Enhanced the Expression of Ski in Osteonecrosis of Femoral Head: The Effect on Adipogenesis of Rabbit BMSCs
AbstractGlucocorticoid (GC)-induced osteonecrosis has been considered as the most serious side effect in long-term or over-dose steroid therapy. The decreased bone mass and increased marrow fat tissue demonstrated that GC can destroy the normal differentiation of bone marrow mesenchymal stem cells (BMSCs), which accelerates adipogenesis but not osteogenesis. However, the underlying mechanisms are still unclear. Ski, an evolutionary conserved protein, is a multifunctional transcriptional regulator that involved in regulating signaling pathways associated with adipogenesis differentiation, but the concrete function remains u...
Source: Calcified Tissue International - July 30, 2019 Category: Orthopaedics Source Type: research

Targeting Vitamin D Deficiency to Limit Exacerbations in Respiratory Diseases: Utopia or Strategy With Potential?
AbstractPatients with respiratory diseases such as cystic fibrosis, chronic obstructive pulmonary disease, or asthma often experience an acute worsening of respiratory symptoms, termed exacerbations. Although the course of exacerbations is disease specific, they are mostly triggered by a respiratory infection. Exacerbations often require hospitalization and are an important cause of mortality. Treatments of exacerbations aim to minimize the negative impact and to prevent subsequent events. Despite many existing therapy options, many patients do not benefit from therapy and suffer from recurrent events. Vitamin D deficiency...
Source: Calcified Tissue International - July 26, 2019 Category: Orthopaedics Source Type: research

The Local and Systemic Interactions Between Muscle and Bone in Postmenopausal Korean Women
AbstractDespite many studies about local and systemic interactions between bone and muscle, the more dominant interaction remains unclear. We aimed to compare the association of skeletal muscle mass with bone mineral density (BMD) at the femur, which seemed more likely affected by local interaction, and the association of skeletal muscle mass with BMD at the lumbar spine (LS-BMD) and the trabecular bone score (TBS), which seemed more likely affected by systemic interaction. In 279 women, we measured the femoral neck BMD (FN-BMD), total hip BMD (TH-BMD), LS-BMD, and TBS. Appendicular skeletal muscle mass (ASM), lean mass (L...
Source: Calcified Tissue International - July 25, 2019 Category: Orthopaedics Source Type: research

The Relationship Between Omega-3, Omega-6 and Total Polyunsaturated Fat and Musculoskeletal Health and Functional Status in Adults: A Systematic Review and Meta-analysis of RCTs
AbstractWe conducted a systematic review and meta-analysis to assess the effects of increasing dietary omega-3, omega-6 and mixed polyunsaturated fatty acids (PUFA) on musculoskeletal health, functional status, sarcopenia and risk of fractures. We searched Medline, Embase, The Cochrane library, ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP) databases for Randomised Controlled Trials (RCTs) of adults evaluating the effects of higher versus lower oral omega-3, omega-6 or mixed PUFA for  ≥ 6 months on musculoskeletal and functional outcomes. We included 28 RCTs (72...
Source: Calcified Tissue International - July 25, 2019 Category: Orthopaedics Source Type: research

A Vitamin D, Calcium and Leucine-Enriched Whey Protein Nutritional Supplement Improves Measures of Bone Health in Sarcopenic Non-Malnourished Older Adults: The PROVIDE Study
AbstractAlterations in musculoskeletal health with advanced age contribute to sarcopenia and decline in bone mineral density (BMD) and bone strength. This decline may be modifiable via dietary supplementation. To test the hypothesis that a specific oral nutritional supplement can result in improvements in measures of bone health. Participants (n 380) were participants of the PROVIDE study, a 13-week, multicenter, randomized, controlled, double-blind, 2 parallel-group study among non-malnourished older participants ( ≥ 65 years) with sarcopenia [determined by Short Physical Performance Battery (SPPB; 0-12) sc...
Source: Calcified Tissue International - July 23, 2019 Category: Orthopaedics Source Type: research

Correction to: Is There Enough Evidence for Osteosarcopenic Obesity as a Distinct Entity? A Critical Literature Review
The original version of this article unfortunately contained a mistake in one of the co-author's name. The co-author Cyrus Cooper's degree “FMedSci” was incorrectly tagged as family name. This has been corrected with this erratum. (Source: Calcified Tissue International)
Source: Calcified Tissue International - July 23, 2019 Category: Orthopaedics Source Type: research

Bone-Bound Bisphosphonates Inhibit Proliferation of Breast Cancer Cells
In conclusion, bone-bound zoledronate inhibits breast cancer cell proliferation, an activity that may contribute to its clinical anti-tumour effects. (Source: Calcified Tissue International)
Source: Calcified Tissue International - July 19, 2019 Category: Orthopaedics Source Type: research

Hyaluronic Acid Stimulates Osseointegration of β-TCP in Young and Old Ewes
AbstractCross-linked hyaluronic acid (HyAR) increases the local concentration of growth factors. We compared β-TCP osseointegration in old and young ewes with/without HyAR addition. A blind tunnel was drilled on the medial femoral condyle of each knee in nine young and nine old ewes and was filled with β-TCP, β-TCP + HyAR or left unfilled. Double labeling with calcein allowed histodynamic analysis. Ewes were sacrificed at 84 days and the knees were harvested. MicroCT provided histomorphometric parameters: trabecular bone volume, residual volume of biomaterial. Histodynamic parameters were:...
Source: Calcified Tissue International - July 18, 2019 Category: Orthopaedics Source Type: research

Does Use of Androgen Deprivation Therapy (ADT) in Men with Prostate Cancer Increase the Risk of Sarcopenia?
AbstractAndrogen deprivation therapy (ADT) for prostate cancer (PCa) can compromise muscle health. Hence, we aimed to quantify the prevalence of sarcopenia (i.e., compromised lean mass, muscle strength, and physical function) in ADT-treated (>  12 week) men (n = 70) compared to similarly aged non-ADT-treated PCa (n = 52) and healthy controls (n = 70). Lean and fat mass were quantified by dual-energy X-ray absorptiometry. Muscle strength and function were measured using handgrip dynamometry and gait speed, respectively. Sarcopenia was defined as low adjusted appendicu...
Source: Calcified Tissue International - July 17, 2019 Category: Orthopaedics Source Type: research

Renal Tubular Function, Bone Health and Body Composition in Wilson ’s Disease: A Cross-Sectional Study from India
AbstractThere is limited literature from India with regard to the prevalence and magnitude of renal tubular and bone manifestations in Wilson ’s disease (WD). Thus, we studied the prevalence of renal tubular acidosis among Indian patients with WD and also evaluated bone health and body composition in them. It was a cross-sectional study conducted at a south Indian tertiary care center. Twenty-five consecutive patients with WD aged more than 12 years attending the hepatology and neurology departments and 50 age, sex and BMI-matched controls were recruited. After clinical assessment, they underwent biochemical tes...
Source: Calcified Tissue International - July 17, 2019 Category: Orthopaedics Source Type: research

Vitamin D and Skeletal Muscle: Emerging Roles in Development, Anabolism and Repair
AbstractThis special issue article will focus on morphologic and functional roles of vitamin D in muscle, from strength to contraction to development and ageing and will characterise the controversy of VDR ’s expression in skeletal muscle, central to our understanding of vitamin D’s effects on this tissue. (Source: Calcified Tissue International)
Source: Calcified Tissue International - July 16, 2019 Category: Orthopaedics Source Type: research

Diagnostic Value of Mid-Thigh and Mid-Calf Bone, Muscle, and Fat Mass in Osteosarcopenia: A Pilot Study
AbstractOsteosarcopenia is defined as the concomitant occurrence of osteoporosis and sarcopenia. Current lack of consensus on sarcopenia definitions, combined with the low sensitivity and  specificity of screening methodologies, has resulted in varying prevalences of sarcopenia, and consequently osteosarcopenia diagnosis. Previous research indicates that mid-thigh is a potential surrogate region for the assessment of bone, muscle, and fat mass in a single, efficient and low-radiati on dual x-ray absorptiometry (DXA) scan. We hypothesized that muscle and bone mass measurements in the mid-thigh region can be used t...
Source: Calcified Tissue International - July 10, 2019 Category: Orthopaedics Source Type: research

Vitamin D, Autoimmune Disease and Rheumatoid Arthritis
AbstractVitamin D has been reported to influence physiological systems that extend far beyond its established functions in calcium and bone homeostasis. Prominent amongst these are the potent immunomodulatory effects of the active form of vitamin D, 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3). The nuclear vitamin D receptor (VDR) for 1,25-(OH)2D3 is expressed by many cells within the immune system and resulting effects include modulation of T cell phenotype to suppress pro-inflammatory Th1 and Th17 CD4+ T cells and promote tolerogenic regulatory T cells. In addition, antigen-presenting cells have been shown to express the enzy...
Source: Calcified Tissue International - July 8, 2019 Category: Orthopaedics Source Type: research

Long-Term Stable Bone Mineral Density in HIV-Infected Men Without Risk Factors for Osteoporosis Treated with Antiretroviral Therapy
ConclusionsBMD remained stable over 12  years in middle-aged and older HIV-infected men treated with ART. Monitoring BMD in men established on ART who do not have risk factors for BMD loss is not necessary. (Source: Calcified Tissue International)
Source: Calcified Tissue International - June 27, 2019 Category: Orthopaedics Source Type: research

Bazedoxifene Ameliorates Homocysteine-Induced Apoptosis via NADPH Oxidase-Interleukin 1 β and 6 Pathway in Osteocyte-like Cells
AbstractHomocysteine (Hcy) increases oxidation and inflammation; however, the mechanism of Hcy-induced bone fragility remains unclear. Because selective estrogen modulators (SERMs) have an anti-oxidative effect, SERMs may rescue the Hcy-induced bone fragility. We aimed to examine whether oxidative stress and pro-inflammatory cytokines such as interleukin (IL)-1 β and IL-6 are involved in the Hcy-induced apoptosis of osteocytes and whether bazedoxifene (BZA) inhibits the detrimental effects of Hcy. We used mouse osteocyte-like cell lines MLO-Y4-A2 and Ocy454. Apoptosis was examined by DNA fragmentation ELISA and TUNEL ...
Source: Calcified Tissue International - June 27, 2019 Category: Orthopaedics Source Type: research

Increased Cellular Presence After Sciatic Neurectomy Improves the Bone Mechano-adaptive Response in Aged Mice
We examined bone adaptation in four groups of female C57BL/6J mice, 20 –22 months old: (1) sham surgery + 9N loading; (2) sciatic neurectomy, sacrificed after 5 days; (3) sciatic neurectomy, sacrificed after 19 days; (4) sciatic neurectomy + 9N loading. We examined changes in bone cross sectional properties with micro-CT images, and static and dynamic hist omorphometry with histological sections taken at the midpoint between tibiofibular junctions. The response to loading at 9N was not detectable with quantitative micro-CT data, but surface-specific histomorphometry captured...
Source: Calcified Tissue International - June 26, 2019 Category: Orthopaedics Source Type: research

Coordination of Fusion and Trafficking of Pre-osteoclasts at the Marrow –Bone Interface
AbstractFusion is the final osteoclast differentiation step leading to bone resorption. In healthy trabecular bone, osteoclast fusion is restricted to bone surfaces undergoing resorption, and necessarily requires site-specific recruitment of mononucleated pre-osteoclasts originating from the bone marrow. However, the spatiotemporal mechanism coordinating recruitment and fusion is poorly investigated. Herein we identify a collagen/vascular network as a likely structure supporting this mechanism. We therefore used multiplex immunohistochemistry and electron microscopy on human iliac crest bone samples, in combination with fu...
Source: Calcified Tissue International - June 25, 2019 Category: Orthopaedics Source Type: research

Role of Nrf2 in Fracture Healing: Clinical Aspects of Oxidative Stress
AbstractFracture healing is a natural process that recapitulates embryonic skeletal development. In the early phase after fracture, reactive oxygen species (ROS) are produced under inflammatory and ischemic conditions due to vessel injury and soft tissue damage, leading to cell death. Usually, such damage during the course of fracture healing can be largely prevented by protective mechanisms and functions of antioxidant enzymes. However, intrinsic oxidative stress can cause excessive toxic radicals, resulting in irreversible damage to cells associated with bone repair during the fracture healing process. Clinically, patien...
Source: Calcified Tissue International - June 24, 2019 Category: Orthopaedics Source Type: research

Vitamin D Status in Paget Disease of Bone and Efficacy –Safety Profile of Cholecalciferol Treatment in Pagetic Patients with Hypovitaminosis D
AbstractAdequate vitamin D status is essential for skeletal health. Paget ’s disease of bone (PDB) is a common metabolic skeletal disorder, but data regarding the vitamin D status in PDB patients are lacking. We performed a case–control study to estimate vitamin D status in 708 PDB patients and in 1803 healthy controls from Italy and an observational prospective study to evaluate the efficacy–safety profile of oral cholecalciferol treatment [400.000 International Units (UI) of cholecalciferol administered in cycles of 8 weeks until 25OHD levels reaches 70 nmol/L as primary therapy and 50.000&nbs...
Source: Calcified Tissue International - June 24, 2019 Category: Orthopaedics Source Type: research

Recombinant Human Bone Morphogenetic Protein 7 Exerts Osteo-Catabolic Effects on Bone Grafts That Outweigh Its Osteo-Anabolic Capacity
This study aimed to investigate the effects of recombinant human bone morphogenetic protein (rhBMP-7) on human cancellous bone grafts (BGs) while differentiating between anabolic and catabolic events. Human BGs alone or supplemented with rhBMP-7 were harvested 14  weeks after subcutaneous implantation into NOD/Scid mice, and studied via micro-CT, histomorphometry, immunohistochemistry and flow cytometry. Immunohistochemical staining for human-specific proteins made it possible to differentiate between grafted human bone and newly formed murine bone. Only BG s implanted with rhBMP-7 formed an ossicle containing a funct...
Source: Calcified Tissue International - June 18, 2019 Category: Orthopaedics Source Type: research

The Role of Osteoprotegerin in Vascular Calcification and Bone Metabolism: The Basis for Developing New Therapeutics
AbstractOsteoporosis (OP) and cardiovascular diseases (CVD) are both important causes of mortality and morbidity in aging patients. There are common mechanisms underlying the regulation of bone remodeling and the development of smooth muscle calcification; a temporal relationship exists between osteoporosis and the imbalance of mineral metabolism in the vessels. Vascular calcification appears regulated by mechanisms that include both inductive and inhibitory processes. Multiple factors are implicated in both bone and vascular metabolism. Among these factors, the superfamily of tumor necrosis factor (TNF) receptors includin...
Source: Calcified Tissue International - June 13, 2019 Category: Orthopaedics Source Type: research

Cluster Analysis of Finite Element Analysis and Bone Microarchitectural Parameters Identifies Phenotypes with High Fracture Risk
AbstractHigh-resolution peripheral quantitative computed tomography (HRpQCT) is increasingly used for exploring associations between bone microarchitectural and finite element analysis (FEA) parameters and fracture. We hypothesised that combining bone microarchitectural parameters, geometry, BMD and FEA estimates of bone strength from HRpQCT may improve discrimination of fragility fractures. The analysis sample comprised of 359 participants (aged 72 –81 years) from the Hertfordshire Cohort Study. Fracture history was determined by self-report and vertebral fracture assessment. Participants underwent HRpQCT scans...
Source: Calcified Tissue International - June 11, 2019 Category: Orthopaedics Source Type: research

Reversal of Osteopenia in Ovariectomized Rats by Pentoxifylline: Evidence of Osteogenic and Osteo-Angiogenic Roles of the Drug
AbstractPentoxifylline (PTX) is a non-selective phosphodiesterase inhibitor and is used for the management of intermittent claudication. We tested whether PTX has oral efficacy in stimulating new bone formation. Rat calvarial osteoblasts (RCO) were used to study the effect of PTX on osteoblast differentiation and angiogenesis. Pharmacokinetic and pharmacodynamic studies were carried out in rats to determine an oral dose of PTX. In ovariectomized (OVX) rats with osteopenia, the effect of PTX on various skeletal parameters was studied, and compared with teriparatide. Effect of PTX on angiogenic signaling was studied by immun...
Source: Calcified Tissue International - June 7, 2019 Category: Orthopaedics Source Type: research

MicroRNAs Involved in the Regulation of Angiogenesis in Bone Regeneration
AbstractMicroRNAs (miRNAs) as a newly founded and thriving non-coding endogenous class of molecules which regulate many cellular pathways after transcription have been extensively investigated in regenerative medicine. In this systematic review, we sought to analyze miRNAs-mediated therapeutic approaches for influencing angiogenesis in bone tissue/bone regeneration. An electronic search in MEDLINE, Scopus, EMBASE, Cochrane library, web of science, and google scholar with no time limit were done on English publications. All types of original articles which a miRNA for angiogenesis in bone regeneration were included in our r...
Source: Calcified Tissue International - June 7, 2019 Category: Orthopaedics Source Type: research

Cost-Effectiveness of the Screening for the Primary Prevention of Fragility Hip Fracture in Spain Using FRAX ®
AbstractTo assess the cost-effectiveness of the primary prevention of fragility hip fractures through opportunistic risk-based screening using FRAX® among women aged 70 to 89  years, and the subsequent treatment with alendronate in women at high-risk, from the Spanish national health system perspective. We performed a discrete-event simulation model. Women were categorized in low, intermediate and high-risk of fragility hip fracture through screening based on the FRAX® risk assessment tool score (Spanish version). Low-risk women received lifestyle recommendations whereas the high-risk group was assigned to ale...
Source: Calcified Tissue International - June 6, 2019 Category: Orthopaedics Source Type: research

Continued Beneficial Effects of Burosumab in Adults with X-Linked Hypophosphatemia: Results from a 24-Week Treatment Continuation Period After a 24-Week Double-Blind Placebo-Controlled Period
This report describes the efficacy and safety of burosumab during the open-label treatment period. From weeks 24–48, serum phosphorus concentrations remained normal in 83.8% of participants who re ceived burosumab throughout and were normalized in 89.4% who received burosumab after placebo. By week 48, 63.1% of baseline fractures/pseudofractures healed fully with burosumab, compared with 35.2% with burosumab after placebo. In both groups, burosumab was associated with clinically significant a nd sustained improvement from baseline to week 48 in scores for patient-reported outcomes of stiffness, pain, physical functio...
Source: Calcified Tissue International - June 4, 2019 Category: Orthopaedics Source Type: research

Dehydroepiandrosterone Sulfate and Free Testosterone but not Estradiol are Related to Muscle Strength and Bone Microarchitecture in Older Adults
AbstractThe study aimed to elucidate the relationship between sex steroids and muscle mass, muscle strength, and trabecular bone score (TBS) in a community-dwelling aged population. We analyzed 922 men  >  60 years of age and 1244 postmenopausal women. Weak muscle strength was defined as hand grip strength 
Source: Calcified Tissue International - June 4, 2019 Category: Orthopaedics Source Type: research

Melorheostosis and Osteopoikilosis Clinical and Molecular Description of an Italian Case Series
In this study, we described the clinical, radiological and molecular findings of 19 individuals with MEL and 8 with OPK and compared the results to the medical literature. The molecular analyses of this case series corroborate the available data in the medical literature, indicating thatLEMD3 germline mutations are not a major cause of isolated MEL and reporting five further cases of OPK caused byLEMD3 germline mutations. (Source: Calcified Tissue International)
Source: Calcified Tissue International - May 25, 2019 Category: Orthopaedics Source Type: research

Long-Term Effects of Teriparatide Followed by Antiresorptive Therapy on Clinical Outcomes in Patients with Severe Spinal Osteoporosis
AbstractTeriparatide (TPTD) is the most widely used anabolic agent in the treatment of patients with osteoporosis although its use is restricted in many countries. A recent randomised trial confirmed that TPTD was superior to risedronate at preventing vertebral fractures over a 2-year period. There is limited information on the relative effectiveness of TPTD compared with standard care in routine clinical practice. In this paper, we report the results of an extended observational study of 724 women referred to a specialist clinic with severe osteoporosis over an 11.5-year period, who were considered for TPTD therapy. Of th...
Source: Calcified Tissue International - May 21, 2019 Category: Orthopaedics Source Type: research

The Association of Aromatic Amino Acids with Incident Hip Fracture, aBMD, and Body Composition from the Cardiovascular Health Study
We examined the relationship between a one-tim e estimate of daily dietary AAA intake with risk of incident hip fractures over a median of 13.2 years of fracture follow-up. A subset (n  =  1336) who had dual energy X-ray absorptiometry (DXA) performed were included in a cross-sectional analysis of the association of dietary AAA intake with aBMD of the total hip and measurements of body composition. In multivariable models adjusted for demographic and clinical variables, medication use, and diet, higher dietary AAA intake was not significantly associated with incident hip fractures. All hazard ratios (HR)...
Source: Calcified Tissue International - May 21, 2019 Category: Orthopaedics Source Type: research

Is There Enough Evidence for Osteosarcopenic Obesity as a Distinct Entity? A Critical Literature Review
AbstractThe co-existence of impaired bone health (osteopenia/osteoporosis), reduced muscle mass and strength (sarcopenia), and increased adiposity (obesity) in middle-aged and older people has been identified in recent studies, leading to a proposal for the existence of “osteosarcopenic obesity” as a distinct entity. Evidence for the pathophysiological overlap of these conditions is mounting, although a causal relationship is yet to be established. Each component condition occurs frequently with increasing age, and with shared risk factors in many instances, th us, an overlap of these three conditions is not su...
Source: Calcified Tissue International - May 16, 2019 Category: Orthopaedics Source Type: research

Vitamin D, and Maternal and Child Health
AbstractVitamin D has important roles in calcium metabolism and in the prevention of rickets and osteomalacia; low levels of 25-hydroxyvitamin D are common in the general population and amongst pregnant women. Whilst there is a wealth of observational evidence linking vitamin D deficiency to a wide range of disease outcomes, there are currently few high-quality randomised controlled trials to confirm any causal associations, although many are currently in progress. Furthermore, currently, the vast majority of published guidelines recommend standard supplemental vitamin D doses for children and pregnant women, yet there is ...
Source: Calcified Tissue International - May 14, 2019 Category: Orthopaedics Source Type: research

Long Noncoding RNA Analyses for Osteoporosis Risk in Caucasian Women
In this study, microarray analyses of monocytes were performed using Affymetrix exon 1.0 ST arrays in 73 Caucasian females (age: 47 –56). LncRNA profile was generated by re-annotating exon array for lncRNAs detection, which yielded 12,007 lncRNAs mapped to the human genome.Results575 lncRNAs were differentially expressed between the two groups. In the high BMD subjects, 309 lncRNAs were upregulated and 266 lncRNAs were downregulated (nominally significant, rawp-value  
Source: Calcified Tissue International - May 9, 2019 Category: Orthopaedics Source Type: research

Focal and Osteosclerotic Bone Diseases
(Source: Calcified Tissue International)
Source: Calcified Tissue International - May 9, 2019 Category: Orthopaedics Source Type: research

Fibrogenesis Imperfecta Ossium
AbstractFibrogenesis imperfecta ossium (FIO) is an extremely uncommon fatal bone disorder of poorly understood etiology. The pathogenesis of FIO is not well known. The fundamental skeletal defect appears to be an abnormality in organic matrix of bone characterized by defective mineralization of the abnormal collagen. FIO clinically manifests in middle-aged adults presenting with fracture and bone pain. Elevated serum alkaline phosphatase is the only and the most consistent biochemical abnormality. Although paraproteinemia is observed in one-third of cases, the pathogenic link to the disease process is unclear. Limited info...
Source: Calcified Tissue International - May 8, 2019 Category: Orthopaedics Source Type: research