Bone Abstracts

Neurofibromatosis type I (NF1) is a monogenetic disorder caused by mutations in the NF1 gene encoding for the Ras-GAP protein neurofibromin. Apart from benign tumour development NF1 is frequently associated with skeletal manifestations such as osteopenia or debilitating focal skeletal dysplasia. To assess a function of Nf1 in osteocytes we here apply a combinatorial approach of biophysical, histological and molecular techniques allowing differential analysis ...

Background: Bone marrow edema (BME) is a localised bone lesion. We hypothesize that structural bone alterations increase the susceptibility to BME. Aim of this study was to analyse bone micro structure, bone mineral density (BMD) and serum fasting bone turnover marker (BTM) values in patients with BME.Methods: We compared 14 nonosteoporotic patients (43.7±19.2 years) with atraumatic BME of lower limb to 35 age-matched healthy controls (HC). HR-pQCT ...

HLA-B27 transgenic rats, developed by inserting into rat genome the gene for HLA-B27, a human Class I major histocompatibility molecule involved in antigen presentation, spontaneously develop arthritis, ankylosing spondylitis, gastrointestinal inflammation, and severe alveolar bone loss, among other signs of a generalized inflammatory response. Clinical manifestations in these rats closely resemble features of HLA-B27–associated diseases in humans. More recently, investig...

Dipeptidyl peptidase 4 (DPP4) modulates activity of proteins by removing two aminoterminal amino acids. DPP4 inhibitors are currently being used to improve glucose tolerance in type 2 diabetes patients by increasing the half-life of DPP4 substrates. It has been shown that these substrates do not only increase pancreatic insulin secretion, but also influence bone cell activity. The potential therapeutic effect of DPP4 inhibition on bone metabolism is thus worth being investigat...

Introduction: Resistance to thyroid hormone (RTH) is a rare disease, characterized by elevated thyroid hormone and not suppressed TSH concentrations. In 85% of cases it is related to TRβ gene mutations.Objectives: To evaluate biochemical and densitometric features of 14 patients with RTH (RTHG: 7 females (4 children) and seven males (2 children)) in comparison to 24 control subjects (CG, 14 females (8 children) and 10 males (4 children)).<p clas...

Introduction: Fracture risk is greater for adults with type 2 diabetes (T2D), despite normal or higher areal bone mineral density (aBMD) compared to controls. Tissue mineral density (TMD), measured by microCT, is more representative of actual mineral density than in vivo aBMD. The aim of this study was to determine whether TMD is greater in adults with T2D, and to investigate the correlates of TMD in adults with T2D.Methods: Using proximal femur...

ASARM peptide (acidic, serine- and aspartate-rich motif) and osteopontin (OPN) fragments accumulate in X-linked hypophosphatemia patients and/or in the Hyp mouse model and, when phosphorylated, potently inhibit mineralization in osteoblast cultures. To investigate this inhibition, we modeled the binding to hydroxyapatite of the human OPN-ASARM peptide (DDSHQSDESHHSDESDEL) using RosettaSurface computational simulations. Peptide binding to hydroxyapatite atomic planes constructe...

Bone metabolism disorders and hypercalcemia occur often in kidney transplant recipients.In 59 kidney recipients (aged 22–74 years, creatinine clearance > 50 ml/min) who were hypercalcemic on more than three consecutive previous visits, the following serum parameters were estimated 1–147 months posttransplant: iPTH, Ca total and ionized, Pi, total and bone alkaline phosphatase, crosslaps, 25(OH)D3, cyclosporine/tacrolimus trough levels. Urin...

Introduction: The RANKL/RANK/OPG system has a key role in bone metabolism. Beyond its role in bone loss, its importance was also documented during inflammation which occurrs in inflammatory bowel disease (IBD). The aim of this study was to investigate the expression of the receptor activator of NF-κB ligand (RANKL) and its receptors RANK as well as its decoy receptor osteoprotegerin (OPG) in the colon during experimantal IBD and following BMP7 or corticosteroid therapy.</...

Deceased donor kidneys are exposed to cold ischemic insult, which makes them particularly susceptible to the effects of cold ischemic injury during hypothermic preservation resulting in high rates of delayed graft function. Although cold storage reduces cellular oxygen demand, ischemia causes the rapid depletion of adenosine triphosphate and accumulation of toxic substances leading to cell death. BMP-7 is a valuable reagent in a field of tissue regeneration and preservation un...

Conventional treatment of hypoparathyroidism with calcium and active vitamin D analogues causes a high renal calcium excretion and over-mineralized bone.We studied 62 patients with hypoPT randomized to 6 months of treatment with either parathyroid hormone (PTH(1-84)) 100 μg/d s.c. or similar placebo, administered as an add-on therapy. Forty-two of the patients had follow-up test performed after 2.5 years; 9 patients had continued daily PTH treatment...

Background: Hypoparathyroidism (HypoPT) is a rare disease, characterized by low plasma levels of Parathyroid hormone and calcium. Furthermore it is characterized by high BMD and very low bone turnover.Aim: We studied risk of fracture in patients with postsurgical HypoPT due to non-malignant diseases compared with an age- and gender-matched control group.Method: We performed a controlled cohort study. Patients diagnosed with HypoPT ...

Introduction: FGF3-associated hypophosphatemic rickets (HR) is a rare disorder caused by excessive renal phosphate wasting. Patients may suffer from limb deformities and low turnover femoral fractures have been described. The aim of this study is to evaluate DXA derived hip geometry of adult HR patients using hip structure analysis (HSA).Materials and methods: Cross-sectional study of HR patients (n=21) at Odense University Hospital compared to ...

In adults, majority of bone marrow (BM) space of long bones is filled with fat tissue. Adipocytes are also present within trabecular bone areas such as vertebral bodies. Despite its prevalence the roles of BM fat in energy and bone metabolism have been largely overlooked. To characterize bone marrow metabolic activity we measured regional glucose uptake in femoral and vertebral bone marrow during fasting and insulin stimulation in normal weight healthy subjects.<p class="a...

Brittle bones have been reported in children, adolescents and adults with cystic fibrosis (CF), independently of sex; this has been termed CF-related bone disease. In CF patients with the F508del mutation in the (Cftr) gene, vertebral fractures and the subsequent dorsal kyphosis decrease pulmonary function, thus accelerating the course of the disease. Mice with the homozygous F508del mutation in CFTR develop a severe osteopenic phenotype early on, in both sexes (Le He...

Mutations in the PHEX gene cause X-linked familial hypophosphatemic rickets (XLH) with severe bone (osteomalacia) and tooth abnormalities being the distinguishing features of this disease. The PHEX mutations lead to an increase in ASARM peptides (acidic serine- and aspartate-rich motif) and osteopontin fragments which inhibit bone extracellular matrix mineralization. MEPE-derived ASARM has been shown to accumulate in tooth dentin of patients with XLH where it may impair dentin...

Objectives: Bone disease is now well described in cystic fibrosis adult patients. CF bone disease is multifactorial but many studies suggested the crucial role of inflammation and chronic pulmonary infection. The objectives of this study were to assess the prevalence of osteoporosis in a current adult CF population and to examine its relationship with infections and inflammation.Methods: Patients were recruited in the adult CF Lyon Centre and assessed in...

Anorexia nervosa (AN) a condition of profound undernutrition, is characterized by alterations in neuroendocrine and metabolic functions. Among the serious pathological consequences of this eating disorder, osteoporosis is often observed and persists after recovery, leading to a high fracture risk.To study particularly bone alterations and recovery, a long term mouse model has been developed. In this model named separation-based anorexia (SBA) – a ch...

The osteoclast-associated receptor (OSCAR), primarily described as a co-stimulatory regulator of osteoclast differentiation, represents a novel link between bone metabolism and vascular biology. Previously, we identified OSCAR on endothelial cells responding to the proatherogenic factor oxidized low density lipoprotein (oxLDL). Additionally, OSCAR expression was increased in the aorta of atherogenic apoE-knock-out (apoE-KO) mice, where it was further induced by feeding a high-...

Aim: We explored the hypothesis that idiopathic hypercalciuria (IH) causes increased bone loss in early post-menopausal women.Materials and methods: We studied 41 postmenopausal women with IH. Inclusion criteria: i) recently (<6 months) diagnosed and untreated IH, ii) postmenopausal status >2 years, and iii) normal renal function. Exclusion criteria: i) all causes of hypercalciuria other than IH and ii) use of any medication for osteoporosis 1-ye...

Autosomal dominant osteopetrosis type II (ADO2) is a rare osteosclerotic disease due heterozygous missense mutations of the CLC7 gene encoding the type seven chloride channel. Our two labs independently generated the first C57 black 6 (B6) mouse model of ADO2 by inserting the pG213R-clc7 mutation. Homozygous mice showed lack of tooth eruption and died within 30 days of age with severe osteopetrosis and central nervous system degenera...

The renal stones found in the mummies of Pandolfo III Malatesta, Lord of Fano (1370–1427) and an anonymous nobleman from Popoli (XVIII century) were investigated using different techniques. Both specimens were examined with binocular stereomicroscopy (BSM) and scanning electron microscopy (SEM), also with energy dispersive X-ray analysis (EDX). Multiple tiny fragments from surface and inner portions were submitted to X-ray diffraction (XRD) analysis. Subsequently, the cal...

Ancient Egyptians were well known for the art of embalming, performed in the belief that preservation of the body was essential for survival in the afterlife. During the mummification process, internal organs were removed and some of them (lungs, stomach, liver, and intestines) washed, dehydrated with natron, perfumed, and stored in so-called canopic jars, buried with the mummy. Each jar had established contents and its own protective deity. To date, a limited number of studie...

Despite mutations in SQSTM1 gene have been detected in up to 50% of patients with familial Paget’s disease of bone (PDB), their prevalence is low in sporadic PDB, likely due to the presence of additional predisposition genes. Recently, at least seven genes were associated with PDB in genome-wide-association studies, including polymorphic variation in OPTN,encoding for optineurin. In particular, a single OPTN variant (rs1561570) was highly associated with...

Backgrounds: Ossification of the posterior longitudinal ligament (OPLL) is characterized by pathological ectopic ossification of the posterior longitudinal ligament. Development of OPLL induces compression myelopathy or radiculopathy by spinal stenosis and the loss of spinal flexibility by ankylosing spinal hyperosteosis (ASH). Although the etiology of OPLL has not been fully elucidated, systemic and local bone formation factors may play a role in the pathogenesis of OPLL. The...

Objectives: The purpose of our study was to investigate RANK/RANKL/OPG system and the concentrations of other markers of bone turn-over in normal pregnancy and pre-eclampsia.Materials and methods: Forty five patients with pre-eclampsia, 78 healthy pregnant women and twenty non-pregnant women were included in the study. Sera concentrations of the markers of bone turn-over: osteoprotegrin (OPG), sRANKL, osteocalcin and CrosLaps – degradation products ...

Cadmium (Cd) is a toxic heavy metal characterized by strong cumulative properties in the human and animals’ organism. Although cadmium accumulation in the bone tissue is lower than in soft tissues such as liver and kidney, the bone-accumulated metal, even at low concentrations, can damage the bone tissue directly. Polyphenols are compounds possessing hydroxyl groups capable of binding divalent metals, including toxic metals, preventing their absorption from the gastrointe...

Introduction: The etiology of Paget’s disease of bone (PDB) is not fully understood, but genetic factors play a clearly important role. Single nucleotide polymorphisms (SNPs) of OPTN gene within PDB6 locus have been highly associated with PDB, but no PDB causal mutation or functional effect on PDB development were reported to date. We aimed to identify functional SNPs associated with this bone disease.Methods: Relevant candidate genes from PDB6 locu...

Background: Zoledronate, a third generation bisphosphonate, has showed high efficacy in the inhibition of bone resorption. The objective of this observational study was to assess short and long-term efficacy and safety of zoledronate in the treatment of active Paget’s disease (PD).Methods: Patients with active PD treated with zoledronate 5 mg were consecutively recruited. Clinical and laboratory parameters were determined before, at 3 and every 6 mo...

Introduction: Paget’s bone disease (PBD) is the second most prevalent metabolic bone disease. Most patients present with pain or fracture but many remain asymptomatic. Evidence suggests a significant reduction both in its prevalence and clinical severity. Recent papers described differences in clinical course and therapeutic options in the last 10–15 years.Objective: To characterize PBD differences between patients having been diagnosed before ...

Introduction: Osteocytes play a major role in the bone remodelling unit (BRU). Thus, we hypothesize that mitochondrial bioenergetics impairment and mitochondrial/peroxisomal fatty acid β-oxidation unbalance is a cause of osteocytes metabolic decline during 17β-estradiol (E2) reduction. E2 and a phytochemical substitute, coumestrol (COU) were used (30 mg/kg during 24 h in ovariectomized rats in order to compare bone loss with sham-operated animal...

Objectives: To evaluate the effect of hormone therapy on the change of bone mineral density in women who showed early menopause after pelvic radiation therapy for uterine cervical cancer.Materials and methods: Through retrospective chart review, the changes of bone mineral density in 63 women with early menopause after pelvic radiation therapy for uterine cervical cancer were evaluated. After the diagnosis of early menopause which was defined as level of...

Objective: The aim of this study was to assess the relationship between renal function (estimated glomerular filtration rate (eGFR) using Cockcroft–Gault (CG) equation and modification of diet in renal disease (MDRD), respectively), bone mineral density (BMD) and both arterial stiffness in Korean postmenopausal women.Materials and methods: From January 2008 until December 2010, among the person who got medical examinations including bone densitometr...

Purpose: Osteoradionecrosis (ORN) of the mandible is a serious complication of radiation therapy, and preceded by 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 PDGF-BB or mesenchymal stem cells (rMSCs) on radiation-induced soft tissue injury.Methods: Rat model was designed to irradiate the skin of SD rats while sparing the body and in...

Introduction: The aim was to examine serum levels of RANKL, OPG and TNF-α before and after curative surgery (PTX) in patients with primary hyperparathyroidism, and their relationship to bone turnover and bone loss.Patients and methods: A 46 patients with rather severe primary hyperparathyroidism (mean PTH=196 pg/ml, mean total Ca=11.4 mg/dl, spine osteoporosis in 50%, hip osteoporosis in a third) mean age of 63.3±12.3 years, 41 women/five males...

Aim: Periodontologists all over the world are more and more interested in connection between pathogenesis of aggressive periodontitis (AP) and calcium and vitamin D metabolic disturbances. Vitamin D besides its direct effect on calcium homeostasis, has immunomodulatory action, that makes interesting the study of vitamin D effect on pathogenesis of AP.Materials and methods: We studied 102 (49 males; 53 females) patients with AP (40.32±1.13), 42 patie...

Objective: Of this study was to investigate the factors influencing fractures in endogenous Cushing’s syndrome (CS) of various etiologies.Materials and methods: The retrospective data of patients, who had received treatment due to endogenous CS, (2001–2011 years) was evaluated. All enrolled patients underwent standard spinal radiographs in lateral positions of the vertebrae Th4-L4. Recent low traumatic non-vertebral fractures were recorded in t...

Objectives: Erythropoietic protoporphyria (EPP) is a rare disease with cutaneous photosensitivity, in which patients avoid sun exposure and use sunscreen. Our purpose was to study bone mineral density (BMD), serum 25-OHD levels and other mineral parameters, to evaluate the impact of these measures in the follow-up of EPP patients.Patients and methods: A ten EPP patients (median age 25; range 22–55, four males and six females), were study for clinica...

Abstract: Osteogenesis imperfecta, also known as ‘brittle bone disease’, is a heterogeneous disorder of connective tissue generally caused by dominant mutations in the genes COL1A1 and COL1A2, encoding the α1 and α2 chains of type I (pro)collagen. Symptomatic patients are usually prescribed bisphosphonates, but this treatment is neither curative nor sufficient. A promising field is gene silencing through RNA interference. In this study, small interfering RN...

Abstract: Paget’s disease of bone (PDB) is characterised by focal lesions of local bone turnover driven by overactive osteoclasts, which often contain nuclear and cytoplasmic inclusion bodies. Mutations affecting the sequestosome-1 (SQSTM1) ubiquitin-associated (UBA) domain have been identified in individuals with PDB. SQSTM1, also known as p62, is a ubiquitously-expressed scaffold protein of 62 kDa that functions in multiple signalling pathways important for cell surviva...

The process of vascular calcification shares many similarities with that of skeletal mineralisation, and involves the deposition of hydroxyapatite crystals in arteries and cardiac muscle. However, the cellular mechanisms responsible have yet to be fully elucidated. BMP-9 has been shown to exert direct effects on both bone development and vascular function. In the present study, we have investigated the role of BMP-9 in vascular smooth muscle cell (VSMC) calcification. Murine V...

Paget’s disease of bone (PDB) is a common metabolic bone disease characterised by increased and disorganised bone remodelling affecting one or more skeletal sites. Bisphosphonates are highly effective at suppressing bone turnover in PDB but it remains unclear whether greater suppression of bone turnover improves clinical outcome. In the PRISM study, we previously reported that PDB patients randomised to ‘intensive’ treatment aimed at normalising alkaline phospha...

The process of vascular calcification shares many similarities with that of skeletal mineralisation, and involves the phenotypic trans-differentiation of vascular smooth muscle cells (VSMCs) to osteoblastic and chondrocytic cells within a calcified environment. Various microRNAs (miRs) are known to regulate cell differentiation, however their role in mediating VSMC calcification has yet to be fully understood.Murine VSMCs were cultured for up to 28 days ...

Osteoclast-poor autosomal recessive osteopetrosis is characterised by susceptibility to fracture despite high bone mineral density as a consequence of an absence of osteoclasts. One of the 12 receptor activator of NF-κB (RANK) mutations associated with this condition is a frameshift mutation encoding a protein that is truncated within the extracellular, N-terminal domain (R110Pfs). We investigated the effect of this mutation on osteoclast formation, receptor localisation ...

This case study is based on the results of the clinical observation of 48 patients aged 22–40 years with toxic necrosis of the jaw bones (28 of whom had a lesion of the mandible, 10 – lesions of the upper jaw, 10 – lesions of both jaws). All patients were observed in the maxillofacial department of Poltava Regional Clinical Hospital. However, only one patient had been referred to the department with the diagnosis ‘toxic osteomyelitis’, 18 – sent w...

Introduction: The purpose of this research was to study the histological structure of albino rats lower incisors of different ages after thymectomy.Materials and methods: The experiment was conducted on 360 white rats of three age groups: immature, mature and senile period. All animals were subjected to surgical thymectomy.Results: In immature rats after thymectomy predentin layer width was less than the control from 30 till 180 da...

Introduction: Osteogenesis imperfecta (OI) is a genetically heterogeneous disorder characterized by bone fragility. OI type V, with autosomal dominant inheritance, is characterized by ossification of the forearm interosseus membrane, radiodense metaphyseal bands, propensity for hyperplastic callus formation, and mesh-like lamellation on bone histology. Type V OI probands are reported to have white sclerae and normal teeth. Recent reports identified the cause of type V OI as a ...

Introduction: Recessive osteogenesis imperfecta (OI) is caused by mutations in genes encoding proteins involved in post-translational interactions with type I collagen. Types VII–IX OI involve defects in the collagen prolyl 3-hydroxylation complex, which modifies α1(I)Pro986. PPIB encodes CyPB, a complex component with PPIase activity and the major isomerase facilitating collagen folding. We investigated the role of CyPB in collagen post-translational modifications a...