Bone Abstracts

Osteogenesis imperfecta (OI) is a hereditary disease with a generalized involvement of the connective tissue caused by collagen type 1 mutations. The clinical appearance is broad with fractures as the key symptom. Only few genotype–phenotype correlations have been established. We aim to characterize the Danish OI population thoroughly including DXA and HRpQCT, anthropometry, patient history, and genetic background.This cross-sectional study includes...

Background: Hypophosphatasia (HPP) results from inactivating mutation(s) in the gene for tissue non-specific alkaline phosphatase (TNSALP). Substantial improvement has been reported in skeletal mineralization and physical function in patients (pts) with life-threatening perinatal and infantile HPP treated for 48 weaks with asfotase alfa, a bone-targeted recombinant human TNSALP.Objective: To evaluate long-term efficacy and tolerability of asfotase alfa i...

Background: Hypophosphatasia (HPP) is caused by inactivating mutation(s) in the gene for tissue non-specific alkaline phosphatase. Extracellular accumulation of inorganic pyrophosphate can lead to profound hypomineralization resulting in limb and chest deformity, respiratory complications and vitamin B6-dependent seizures in the severe forms of HPP. The natural history of HPP is poorly understood, but the perinatal and infantile forms are often considered lethal.<p class="...

Renal osteodystrophy encompasses the bone histologic abnormalities seen in patients with chronic kidney disease (CKD). The bone-specific alkaline phosphatase (BALP) isoform B1x is exclusively found in serum of some CKD patients. The aim of this study was to examine the relationship between serum BALP isoforms and histologic abnormalities of bone in patients with CKD on chronic dialysis (CKD-5D).Anterior iliac crest bone samples from 40 CKD-5D patients we...

Background: Pathophysiological calcification in the vasculature is a risk factor for cardiovascular disease (CVD). CVD are among the most common causes of death in patients with chronic kidney disease and crucial for kidney transplantation (RTX) outcomes.Aim: The aim of this study is to identify differences in the pattern and the onset of expression of regulators of calcification (RC) in atherosclerosis (AS) and media sclerosis (MS).<p class="abstext...

Osteogenesis imperfect (OI) is an inheritable bone disease with low bone mass, fragility, deformity and multiple fractures in skeletal tissues. Modulation of Wnt signalling components reportedly alleviates excessive bone and joint remodelling in various skeletal disorders. This study is undertaken to explore whether loss of Wnt inhibitor Dickkopf-1 (Dkk1) action affects bone formation or skeletal homeostasis in OI. In clinical vignettes, OI patients had severe osteoporosis (<e...

Acute phase reaction (APR) is the most frequent side effect following i.v. nitrogen-containing bisphosphonates (N-BPs) infusion. A recent observation in osteoporotic women treated with N-BPs evidenced a negative association between 25(OH)D levels and APR, likely due to the immuno-modulatory effects of vitamin D on γδTcells. However, this association remains to be demonstrated in patients with Paget’s disease of bone (PDB). Moreover whether vitamin D supplementat...

Mutations of the ALPL-gene are closely related to hypophosphatasia (HPP), an inherited disorder of bone and mineral metabolism with clinically heterogeneous symptoms. To date 278 different mutations have been described, leading to reduction or completely loss of enzymatic activity of the tissue nonspecific alkaline phosphatase (TNAP).We present the case of a 6-year-old boy with clinical features and laboratory results consistent with infantile H...

Paget’s disease of Bone (PDB) is caused by mutations in the gene encoding Sequestosome-1 (Q17STM1 or p62) that affect the C-terminal Ubiquitin-Associated (UBA) domain. A second isoform of Q17STM1 exists (referred to hereafter as 55kDa-Q17STM1), which lacks the N-terminal Phox and Bem1 (PB1) domain and has previously been reported to be ~45x more abundant than Q17STM1/p62 in osteoclasts. Mutations in the UBA domain will also occur in this isoform. Several of the UBA mutati...

Spinal cord injury (SCI) has been associated with marked bone loss and an increased risk of fractures under the SCI level. The aim of the study was to analyze the effect of recent complete SCI on bone turnover and bone mineral density (BMD) evolution and factors related to bone loss.Methods: Prospective study including patients with complete motor SCI (ASIA A or B) (<6 months). Bone turnover markers (bone formation: P1NP, bone ALP and resorption: sCT...

Recent studies have demonstrated the role of osteocalcin in energy metabolism regulation having a connection between this and bone metabolism. According to this, anti-osteoporotic drugs may exert different effects on energy metabolism. Thereby, our aim is to evaluate the effects of antiresorptive (Denosumab) and osteoanabolic (Teriparatide) drugs that reduce or increase respectively osteocalcin levels, on energy and bone metabolism by assessing of undercarboxilated osteocalcin...

Gla-rich protein (GRP) is a vitamin K-dependent protein, characterized by a high density of γ-carboxylated Glu residues and high calcium binding affinity. It was shown to accumulate in mouse and sturgeon cartilage and in sites of skin and vascular calcification in humans. Four alternatively spliced transcripts of the GRP gene (GRP–F1, F2, F3 and F4) were described in mouse chondrocytes and zebrafish. Osteoarthritis (OA) is a common degenerative joint disease...

Background: The prevalence and severity of Paget’s disease of bone (PDB) have fallen over recent years but it is unclear if this has impacted on disease presentation. Here we evaluated the presentation of PDB in a contemporary cohort and conducted a systematic review of MEDLINE on the mode of presentation.Methods: The presenting features of PDB were recorded in 87 patients who had presented to a specialist clinic between 2005 and 2013. The systemati...

Vascular calcification has a marked impact on arterial heterogeneity and plaque stability. Based on a cohort of 116 patients (carotid and femoral endarterectomies), the aim of the present study was to determine the influence of the bone-like vascular calcification and of osteoprotegerin (OPG) on plaque stability.Seventy-three carotid and 43 femoral plaques along with plasma were harvested and analyzed in a single center study. The presence of osteoid met...

We sought to elucidate the effects of dietary caloric alterations on bone marrow adiposity and the effects of β-adrenergic signaling on marrow stromal cells’ adipogenic differentiation. Male 6-week-old C57BL/6 mice were assigned into three groups: an ad-libitum fed control diet (CON; 10 kcal% fat), a high calorie diet (HIGH; 60 kcal% fat) and a low calorie diet (LOW; 30% kcal restriction vs CON diet). In each diet group, mice were treated with vehicle (VEH: ...

Objective: Minimally invasive parathyroidectomy (MIP) has become a frequently used strategy but it requires a precise preoperative localization and the use of intraoperative PTH to fulfill its benefits. The current localization techniques (ultrasonography, MIBI scan) have shortcomings and intraoperative PTH is not available in our country.Case presentation: We report the cases of two patients, females (63 and 55 years old), with clinical and biochemical ...

Bisphosphonates (BPs) are widely used as antiresorptive drugs. However, one of most potent BPs, zoledronic acid (ZA) can cause BP-related osteonecrosis of the jaws (BRONJ) with a poorly understood pathophysiology. The aim of this study was to find a clue for the development of BRONJ by evaluating the cytotoxic effects of ZA on osteoblasts and examining the action mechanism of ZA on osteoclast differentiation. Jaw bone osteoblasts (JB-OBs), long bone osteoblasts (LB-OBs), and b...

Purpose: Osteoradionecrosis (ORN) of the mandible is a serious complication of radiation therapy, and accompanies soft tissue damage before bone loss appears. However, there is still no adequate treatment to heal the soft tissue damage of ORN. This study investigated the effect of platelet-derived growth factor (PDGF) or rat mesenchymal stem cells (rMSCs) on the healing of radiation-induced soft tissue injury by varying administration timing.Methods: Rat...

Hypophosphatasia (HPP) is a rare disease characterized by low enzymatic activity of tissue-nonspecific alkaline phosphatase (TNSALP) resulting in an accumulation of its endogenous substrates like pyridoxal phosphate (PLP) and inorganic pyrophosphate (PPi). The ectoenzyme plays an important role during bone mineralization and might contribute to proper function of kidney and muscle. Neurological symptoms of HPP like seizures, anxiety disorders and depression provide ...

Tea is the second most consumed beverage in the world, next to water. The popularity of tea is determined by healthy properties connected with the presence of antioxidants, hence tea can be classified as functional food. Cadmium (Cd) and lead (Pb) are toxic metals commonly occurring in the human environment with exposure ~5 and 35 mg/kg Bw per week respectively.Thirty growing male Wistar rats (12 weeks old, 326.4±31.0 g) were used. Rat were fed ...

Fibrodysplasia ossificans progressiva (FOP) is a rare, extremely disabling genetic disorder characterized by progressive heterotopic ossification preceded by episodic inflammatory soft tissue swellings (flare ups) leading to early death. There is no proven effective treatment yet. We aimed to develop an in vitro system to investigate the working mechanism of flare ups induced ossification.Skin biopsies were obtained from four patients with FOP. ...

Introduction: Calcification of vessels, especially media calcification, in combination with bone demineralization and disturbed bone metabolism is abundant in patients suffering from end stage renal disease (ESRD). In this project, we compare biomarkers of calcification with a focus on microRNAs from ESRD patients listed for renal transplantation (RTX) and healthy controls.Methods: Samples are collected from kidney transplant patients. At the same time t...

Objective: Vascular calcification contributes to the pathogenesis of atherosclerosis, hypercholesterolemia, end stage renal disease, and diabetes, and is caused by genetic ablation of matrix Gla protein (MGP) in mice. Genetic ablation of MGP in mice results in excessive calcification of the vessel wall associated with a chondrocyte-like trans-differentiation in smooth muscle cells (VSMCs). Canonical β-catenin signaling is activated in the calcified arterial Mgp&#8722...

Objective: To find whether treatment with cholecalciferol and calcium in a group of vitamin D deficient women is associated with changes in muscular function, musculoskeletal pain, and fatigue.Design: Prospective interventional cohort study.Sample: A study group of 25 post partum women recruited and diagnosed with hypovitaminosis D during pregnancy.Setting: The study group was recruited 2006–2009 at two ...

Background: Risk of fracture in chronic kidney disease (CKD) population is high and it is associated with increased mortality. CKD affects bone quality through changes in bone turnover, microarchitecture, and mineralization. Secondary hyperparathyroidism has different effects on cortical and trabecular bone but dual-energy X-ray absorptiometry (DXA) is unable to effectively differentiate these bone compartments. High resolution peripheral quantitative computed tomography (HRpQ...

Introduction: Heterotopic ossification (HO) means deposition of bone within the soft tissue around peripheral joints, first described by Guy Patin in 1692. This may occurs in up to 50% of spinal cord injury (SCI) patients. HO begins at mean of 12 weeks after injury. Only 10–20% of patients have clinical symptoms with decreased range of motion and inflammatory symptoms in the affected joints. The large joints below the levels of injury are typically affected, most commonly...

Aim: We present the case of a 36y female patient with multiple fragility fractures after the age of 21 and mutations in COL1A1, COL1A2 and GNAS genes.Material and methods: A 36y female patient with multiple fractures of the axial and appendicular skeleton was referred to us for consultation. The patient was born with hexadactyly of the left foot and had a history of mild thoracolumbar scoliosis (10°) and medium height (165 cm) with no other history ...

Background: Primary hyperparathyroidism (PHPT) has evolved into an asymptomatic disease in the west. In contrast classic symptoms of PHPT have been reported to be common in the East with as many as 80–100% of PHPT patients presenting with bone manifestations in India.Objective: To describe clinical and biochemical profile of patients diagnosed with PHPT between years 2009 and 2012.Methodology: This was a retrospective study co...

Introduction: Gaucher disease (GD), the most prevalent glycolipid storage disease, is an autosomal recessive metabolic disorder that is caused by an inherited deficiency of the lysosomal enzyme, glycocerebrosidase. This defect leads to reduce enzyme activity, resulting in the accumulation of glucosylceramide in cells of the monocyte-macrophages linage, known as Gaucher cells. Common presenting features include anemia, thrombocytopenia, hepatosplenomegaly and bone abnormalities...

Background and objectives: The association between excess calcium intake and cardiovascular mortality has been reported, but the association has not yet been explored according to serum vitamin D status. Thus, we investigated the relation of dietary calcium intake and Framingham risk score (FRS) according to serum 25-hydroxyvitamin D (25(OH)D) status.Methods: A total of 7809 subjects (3452 males and 4357 female) aged over 40 years from the data of the Ko...

Evaluation of time-related changes of serum biochemical bone metabolism markers was performed in male pigs. Control group (n=7) received saline. NanoCa group (n=7) received nanopartical calcium per os (Ace Nano Calcium, NanoTechWorld, Korea). Dex group (n=7) received dexamethasone (1 mg/kg/48 hr i.m.). NanoCa/Dex group (n=6) received simultaneously nanopartical calcium and dexamethasone the same as the groups NanoCa and Dex...

Introduction: Niemann–Pick disease (NPD) is a rare autosomal recessive lysosomal lipid storage disorder. It is caused by mutations of genes which products are involved in the metabolism of sphingolipids. Their dysfunction causes sphingomyelin to accumulate in different organs which leads to progressive multisystemic disorder. Types A and B NPD are caused by mutations in sphingomyelin phosphodiesterase-1 gene with deficiency of acid sphingomyelinase (ASM). Types C and D NP...

Zinc (Zn) has a number of key roles relating to cell signalling, cell activation, gene expression, protein synthesis, apoptosis and is crucial for the development of immune cells. Damage to the linings of the gastrointestinal tract is observed during Zn deficiency. Since a few years it has been suggested the existence of the novel interrelationship between bone and gut:gut–bone axis.The aim was to establish changes of morphological, geometric and me...

Poor vitamin K intake is associated with markedly increased cardiovascular risk and mortality. The molecular mechanism underlying this association is suggested to be the vitamin K-dependent carboxylation of vascular matrix Gla-protein (MGP), a potent calcification inhibitor. The carboxylation step is essential for its activation, and uncarboxylated MGP, produced during poor vitamin K status, is inactive.The IDS-iSYS inaKtiv MGP assay is the auto...

Melorheostosis together with osteopoikilosis, ostepathia striata and Buschke–Ollendorfov’s syndrom belongs to mesodermal sclerotic dysplasia. Melorheostosis is a very rare disease with an incidence of 1:1 000 000, which was firstly described by French neurologist Léri in 1922. Hyperdense bands prominent upon the outer cortex niveau are visible on X-rays of long bones diaphysis reminding flowing wax of a candle. This disease is connected with contractures of soft...

Background and objective: Recent studies have demonstrated that higher serum 25-hydroxyvitamin D (25(OH)D) had a favorable effect on bone health. Osteocalcin, however, according to its serum concentration showed different outcomes for bone and aortic calcification. The aim of this cross-sectional study was to compare the bone mineral density (BMD) and coronary artery calcification score (CACS) according to the serum concentration of 25-hydroxyvitamin D and osteocalcin.<p c...

The aim of this study was to investigate BMD of affected femur in patients with hemiplegic stroke.Medical records of 153 patients with stroke who admitted a rehabilitation clinic from January 2011 to March 2013 were retrospectively reviewed. We excluded the patients with non-hemiplegia, diseases which can affect the BMD such as diabetes mellitus, thyroid disease and anti-epileptic drugs. We also excluded the patients who did not check both femur BMD. Tot...

Background: The optimal level of 25-hydroxyvitamin D2 (25(OH) D) for a healthy bone is not clear, nor the effects of treatment with vitamin D. Few previous studies have measured treatment effect on BMD in young deficient individuals.Materials and methods: A treatment group of vitamin D deficient immigrant women and a control group of ethnic Swedish women were recruited during pregnancy. A treatment of 800–1600 IU cholecalciferol and 500–1000 mg...

A 20-year-old male presented following a fall down. He was diagnosed with a C5–C7 burst fracture and underwent a cervical fixation surgery. He was transferred to inpatient rehabilitation with C6 ASIA A tetraplegia.70 days after the operation, he began to have intermittent mild fever with a temperature of 37.4 oC. On postoperative day 72, left thigh was noted to be edematous. The circumferential difference between the lower extremities mea...

Objectives: We investigated bone mineral density (BMD) in women as this is related to a history of previous pregnancies and miscarriage and according to age.Materials and methods: We performed retrospective study on 1043 women who had their BMD in a university hospital. We analyzed the BMD and the previous obstetric history according to age and the clinical characteristics.Results: The mean age of the study subjects was 56.7±5...

Vitamin D (vit D) plays an important role in the regulation of mineral homeostasis. Vit D insufficiency leads to decreased calcium and phosphorous intestinal absorption, parathyroid glands (PG) stimulation with consequent development of secondary hyperparathyroidism (HPT) and bone mineralization defect. We present a clinical case of a patient with tertiary HPT as a consequence of severe vit D deficiency.A clinical case: A woman 59 years old considered he...

The aim of this study was to evaluate the adsorption of salivary proteins on giomer (Beautifil II) and composite resin (Filtek Z350).Three discs (5 mm diameter and 1 mm height) were prepared for each material. Three discs were immersed in 1 ml? of human saliva within polyethylene tube and stored at room temperature. Evaluations were performed by Bradford method and SDS gel electrophoresis for analysis of salivary protein adsorbed on giomer and composite ...

Background: Adult GH Deficiency (GHD) is associated with decreased bone mass and increased fracture risk. Recombinant human GH (rhGH) replacement therapy leads to progressive increases in bone mineral density (BMD) for up to 7 years of treatment, but little is known on longer term effects of rhGH therapy on bone mass or fracture risk.Methods: 230 GHD patients (mean age 47.1 years, 52.6% female) on rhGH replacement therapy for ≥5 years were included...

In autosomal recessive osteopetrosis due to mutations of the TNFSF11 gene, deficiency of the pro-osteoclastogenic cytokine RANKL prevents osteoclast formation. RANKL is a membrane-bound protein cleaved into active soluble (s)RANKL by various enzymes, including metalloproteinase 14 (MMP14). We created a bio-device that released sRANKL and induced osteoclastogenesis in tnfsf11−/− mice. We tested various RANKL cell sources, and used mouse primary calvarial osteoblasts...