S240
Abstracts / Bone 48 (2011) S236–S245
PP445-S Hip structure analysis in patients with osteogenesis imperfecta compared with age and sex matched healthy controls L. Folkestad a,b,c,⁎, S. Hansen a,b, C. Ejersted a, J.D. Hald d, B. Langdahl e, J. Gram c, B. Abrahamsen f,g, K. Brixen a,b a Department of Endocrinology, Odense University Hospital, Denmark b Institute of Clinical Research, University of Southern Denmark, Odense, Denmark c Department of Endocrinology, Hospital of South Western Denmark, Esbjerg, Denmark d Department of Endocrinology, Aarhus University Hospital, Aarhus, Denmark e Department of Endocrinology, Aarhus University Hospital, Aarhus, Denmark f Department of Endocrinology, Gentofte Hospital, Gentofte, Denmark g OPEN Institute, University of Southern Denmark, Odense, Denmark Abstract: Background: Osteogenesis Imperfecta (OI) is a group of hereditary, heterogeneous diseases characterized by defects in the biosynthesis of collagen type I resulting in increased risk of fractures. Bone mineral density (BMD) and bone quality are decreased in OI. It is, however, unknown if bone geometry is altered and contributes to the increased risk of fractures. Hip Structure Analysis (HSA) allows measurement of determinants of bone strength, i.e. cross-sectional area (CSA), cross-sectional moment of inertia (CSMI), section modulus (Z), cortical thickness and buckling ratio (BR), from DXAscans of the proximal femur. We compared HSA in OI patients with healthy age and gender matched controls. Methods: A total of 22 OI patients, with DXA-scans within the last 10 years, were identified through our clinical database. All but one patient had type I OI. We excluded one patient due to her bone deformities rendered the HSA impossible. Healthy controls were invited at random from the background population through the central personal registry. Thus, data from 21 patients (11 males and 10 females) aged 18–75 years and 21 controls (11 males and 10 females) aged 22–77 were available for analysis. The HSA was done using the Hologic APEX analysis software. Comparisons were tested using Wilcoxon Signed-Rank test. Results are summarized in Table 1.
Table 1 Region
Variable
OI
Controls
P-value
Total Hip Hip Axis Length Shaft Neck Angle Narrow Neck
BMD (g/cm2) (mm) Degrees (°) CSA (cm2) CSMI (cm4) BR Z (cm3) CSA (cm2) CSMI (cm4) BR (cm3) Z (cm3) CSA (cm2) CSMI (cm4) BR Z
0,77 ± 0,16 108 ± 12 131 ± 6 2,53 ± 0,70 2,68 ± 1,23 14,4 ± 5,0 1,36 ± 0,52 3,76 ± 1,14 10,4 ± 4,4 10,5 ± 3,1 3,39 ± 1,26 3,85 ± 1,08 3,38 ± 1,48 3,09 ± 1,04 2,18 ± 0,77
0,92 ± 0,14 115 ± 12 130 ± 4 3,18 ± 0,65 3,68 ± 1,44 11,3 ± 3,1 4,82 ± 1,55 5,18 ± 1,99 16,3 ± 6,9 8,6 ± 1,8 4,82 ± 1,55 4,67 ± 0,98 4,51 ± 1,59 2,88 ± 0,68 2,73 ± 0,75
0.01 0.04 N.S 0.01 0.046 0.04 0.0001 0.01 0.01 N.S 0.01 0.02 0.046 N.S 0.046
Intertrochanteric
Femoral Shaft
The OI patients had significantly lower BMD and hip axis length compared to healthy age and gender matched controls. At both narrow neck, intertrochanteric and femoral shaft regions CSA, CSMI and section modulus were significantly lower in OI patients compared to the controls. The buckling ratio was, however, only significantly increased at the narrow neck. Conclusion: Patients with OI have significantly lower BMD and altered bone geometry, compared to the controls, indicating decreased bone strength and increased risk of hip fractures. Disclosure of interest: None declared.
Abstract: Staphylococci are the major cause of nosocomial infections related with implanted biomedical devices and still are among the most feared pathogens because of their ability to cause serious infections, including chronic osteomyelitis. The bacterial adherence to biomaterial surface is an important step in the pathogenesis of prosthetic infection because it can lead to the biofilm formation, which enhanced resistance of bacteria against host defense mechanisms and antibiotic treatments. The aim of this study was to evaluate and compare the initial adhesion of S. aureus ATCC 25923 and two clinical strain of S. aureus with phenotype MRSA and MSSA isolated from prosthetic infections, on two different types of nanohydroxyapatite (nanoHA), with heat-treatments at 725 °C and 1000 °C, and to verify the influence of substratum surface roughness and wettability on bacterial adhesion. Adhered cells were evaluated after 60 minutes of adhesion by scanning electron microscopy (SEM) and quantified as colony forming units. The wettability was assessed by contact angle measurements while surface roughness was followed by atomic force microscopy. Concerning nanoHA at 725 °C, significant differences were observed between all strains being the clinical ones who showed more capacity to adhere. NanoHA 1000 °C samples were less susceptible to bacterial adhesion and the results were very similar between the strains. By SEM images were possible to observe the production of slime in the clinical strains, an important virulence factor that contributes towards their pathogenicity. The bacterial adhesion was higher on materials with more hydrophilic surfaces and the different roughnesses of nanoHA surfaces had no effect on the bacterial adherence. This article is part of a Special Issue entitled ECTS 2011. Disclosure of interest: None declared. doi:10.1016/j.bone.2011.03.577
PP447-T Parathyroid hormone and vitamin D — Markers for cardiovascular and all cause mortality in heart failure L.L. Schierbeck a,⁎, T.S. Jensen b, U. Bang c, G. Jensen d, L. Køber e, J.-E.B. Jensen c a Dept. of Endocrinology, Hvidovre Hospital, Copenhagen NV, Denmark b Dept. of Neurosurgery, Århus University Hospital, Århus, Denmark c Dept. of Endocrinology, Hvidovre Hospital, Hvidovre, Denmark d Dept. of Cardiology, Hvidovre HospitaL, Hvidovre, Denmark e Dept. of Cardiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark Abstract: Introduction: Parathyroid Hormone (PTH) and vitamin D have been linked to cardiovascular disease and heart failure (HF). This has mainly been shown in patients with kidney failure or patients with primary hyperparathyroidism. Recently, population based studies have shown similar associations. Aim: To investigate the levels of vitamin D and PTH in a population of HF patients, and whether vitamin D and PTH were related to prognosis. Methods and results: A prospective study of 148 HF outpatients (102 men; 46 women) with follow-up for mortality after 3½ years. NT-proBNP, PTH, 25-OHD and several other biomarkers were examined. Mortality and cardiovascular mortality were analyzed in multivariable regression analyses adjusting for other independent prognostic variables. Mean age was 68 years. Vitamin D deficiency (≤ 50 nmol/l) was prevalent in 43% of the population; 26% had elevated PTH levels; none had primary hyperparathyroidism. We found a strong and significant association between both PTH and vitamin D to mortality, independent of each other and of other clinical important parameters (NT-proBNP, eGFR, age, and left ventricular ejection fraction (LVEF)). Both PTH and vitamin D were significantly associated with all cause mortality. In an adjusted model we found a hazard ratio of 1.9 (CI 1.1–3.4) for vitamin D deficiency and 2.0 (1.0–3.8) for the upper median of PTH, respectively. Conclusion: PTH and vitamin D are independently associated with all cause and cardiovascular mortality in patients with heart failure. This is independent of other known risk factors such as eGFR, LVEF, NT-proBNP and age. This article is part of a Special Issue entitled ECTS 2011. Disclosure of interest: None declared.
doi:10.1016/j.bone.2011.03.578 doi:10.1016/j.bone.2011.03.576
PP446-M Staphylococci adhesion on nanohydroxyapatite L. Grenho a,b,c,⁎, M.P. Ferraz a,b, F.J. Monteiro a,c a INEB - Instituto De Engenharia Biomédica, Universidade Fernando Pessoa, Porto, Portugal b CEBIMED – Centro de Estudos em Biomedicina, Universidade Fernando Pessoa, Porto, Portugal c Departamento de Engenharia Metalúrgica e Materiais, Faculdade de Engenharia - Universidade do Porto, Porto, Portugal
PP448-S Diets high in monounsaturated fatty acids reduce bone mass? M.M. Gonzales Chaves a,⁎, E. Alsina a, E. Macri a, C. Suarez a, E. Lanata b, P. Rodriguez a, S. Zeni a, S. Friedman a a Biochemistry, University of Buenos Aires, Buenos Aires, Argentina b Operative Dentistry, University of Buenos Aires, Buenos Aires, Argentina Abstract: Diets rich in MUFA are indicated for the treatment of nutritional hypercholesterolemia (NHC); however, new sources as high oleic sunflower oil (HOSO, rich in n−9) from sunflower oil have not been adequately studied. Objective: to study in growing healthy rats or with NHC, the effect of diets rich in HOSO on body growth, cardio protective parameters (total
Abstracts / Bone 48 (2011) S236–S245 cholesterol (T-C) triglyceride (TG), HDL-C and noHDL-C), % liver weight/body weight (% LW/BW), % body fat (% BF) and visceral fat % (% VF). Total skeleton bone mineral density (BMD) and content (BMC).Weaning male Wistar rats (n = 24) were randomly assigned to one of three groups. For 8 wks, a control group (CO) received an AIN-93G diet, while another group, a diet rich in HOSO (HOSO). The remained group received for 3 wks a diet rich in saturated fat (SF) and C. Then, for 5 wks (T8) SF was replaced by HOSO (HOSO-C). At T3, serum T-C (mg/dL) and T8, serum T-C (mg/ dL), TG (mg/dL), HDL-C (mg/dL) and noHDL-C (mg/dL) were determined. BMD (g/cm2) and BMC (g) (DXA, Lunar DPX), % LW/BW, %BF, %VF were assayed. Weekly, body size expressed as BW (BWV, g%) and length (BLV, cm/10 cm) velocities and food consumption (g/BW 0.75/d) were recorded. Results (mean ±SD, ANOVA, SNK a posteriori, 5% significance level). At T3, HOSO-C group showed HC (p< 0.001).At T8, food consumption, % LW/BW, % BF, % VF, TG, T-C and noHDL-C were significantly increased in HOSO-C vs. C and HOSO (p < 0.001). Conversely, BWV, HDL-C, BMC, BMC/BW, and BMD were lower in HOSO vs. C and HOSO. The nutritional management of young individuals with NHC would not be appropriate with an n9-rich diet from HOSO, since it reduces both cardio protective parameters and bone mass. Awarded by UBACyT O008 and O015. This article is part of a Special Issue entitled ECTS 2011. Disclosure of interest: None declared.
S241
adenoma, 30 (32.6%) had hyperplasia, and 6 (6,5%), parathyroid cancer. The cure rate after PTX was 95,6%. The prevalence of reduced BMD (less or= 1SD, T-score) was 80%–100% depending on site. 66,3% patients met osteoporosis densitometric criteria. iPTH was higher in patients with osteoporosis than in those with osteopenia (p<0,05). Eighteen patients (19,5%) had a history of bone fracture: ten patients (10,8%) had at least one fracture up to 5 years, and nine patients (9,7%) had a history of at least one fracture during the 10-year period prior to surgery. 1 woman with misdiagnosed brown tumor had come to our department after previous noneffective operations on the maxilla. 3 patients were operated with multi bone fractures and 1 patient in hypercalcemic crisis. Significant increases in any of the indices of BMD from the baseline values were observed within six months after PTX. We found that PTX brings about increases in BMD values as high as 15% in all pHPT patients. In 60 patients after PTX, we presented a prolonged hypocalcemia (in 10 cases — life threatening), due to a severe hungry bone syndrome. Conventional treatment with oral and intravenous calcium and calcitriol supplementation was effective. Conclusions: The systematic performance of bone densitometry has a decisive influence in its appropriate management. We demonstrated that PTX for pHPT led to marked and sustained increases in BMD. This article is part of a Special Issue entitled ECTS 2011. Disclosure of interest: None declared. doi:10.1016/j.bone.2011.03.581
doi:10.1016/j.bone.2011.03.579
PP449-M Ectopic calcification in fetuin-A deficient mice starts in the microvasculature M. Herrmann ⁎, C. Schaefer, A. Kinkeldey, W. Jahnen-Dechent Helmholtz Institute - Biointerface Group, RWTH AACHEN, Aachen, Germany Abstract: The serum protein fetuin-A is a major inhibitor of ectopic calcification acting on the systemic level. Fetuin-A is in vitro highly effective in the formation and stabilization of proteinmineral colloids, referred to as calciprotein particles, CPPs. We had previously confirmed the inhibitory function of fetuin-A in vivo by generating a fetuin-A knockout (KO) mouse model. The backcrossing of fetuin-A KO mice onto two defined inbred strains resulted in two phenotypes. While the Ahsg deficiency on the calcification-resistant C57BL/6 (B6) strain showed no spontaneous calcification phenotype, widespread and systemic ectopic calcification was observed onto the sensitive strain DBA/2 in contrast to DBA/2 wildtype mice. Calcified lesions were detected by computer tomography and histology. The pathology of calcification was analyzed by von Kossa mineral staining, immunohistochemistry and protein analysis. To gain further insight into the molecular mechanisms governing pathological mineralization we performed microarray analysis of DBA/2 wildtype and KO mice. Calcified lesions occurred in myocard, lungs, brown adipose tissue, reproductive organs, kidneys and in subcutaneous fat of the skin. Calcified lesions became visible in histology at age 3 weeks in the most of these soft tissues. The lesions were generally surrounded by a layer of macrophages. Neutrophil granulocytes were occasionally observed. Upon proteomic analysis of lesion material we detected in the lesions serum proteins including osteopontin, adiponectin and serum amyloid P component (SAP). The microarray analysis of brown adipose tissue revealed differentially upregulation of genes linked to extracelluar matrix receptor interaction and cell adhesion. Using immunofluorescence staining of vascular endothelial markers the early stage lesions were invariably detected in small capillaries. We conclude that formation of calcified lesions in fetuin-A deficient DBA/2 mice starts in the lumen of the microvasculature. This article is part of a Special Issue entitled ECTS 2011. Disclosure of interest: None declared.
doi:10.1016/j.bone.2011.03.580
PP450-T Clinical presentation of bone disease in patients with PHP cured in Endocrine Surgery Department in I.M. Sechenov First Moscow State Medical University M.B. Saliba ⁎, A.F. Chernousov, L. Ippolitov, I. Orlova, M. Kiseleva Endocrine Surgery, I.M. Sechenov First Moscow State Medical University, Moscow, Russian Federation Abstract: Primary hyperparathyroidism pHPT is one of the most common endocrine diseases. More than 40–50% patients with pHPT in Russian Federation are symptomatic. pHPT is associated with an increased fracture risk, and decreased bone density thus has been considered an indication for surgery. Bone mineral density BMD takes a growing place in the management of patients. Methods: 92 patients with pHPT were studied. 80 women (87,6%) and 12 males (12,4%). In all cases parathyroidectomy PTX was performed. Bone mineral density BMD was determined in all patients in lumbar spine (LS) and femoral neck by dual-X-Ray absorptiometry DXA. Serum levels of calcium and parathyroid hormone iPTH were determined at the time of the BMD measurement. Results: The mean age of patients was (women 58,9±9,2 year, males 53,1±10,5 year). The mean calcium ionized was 1,54±0,26 mmol/L. iPTH levels were 82–4790 pg/ml: median 250 pg/ml (upper quartile 430 and lower quartile 173). Of the 92 patients, 56 (60.9%) had a single parathyroid
PP451-S Relation between circulation measles virus antibodies and disease severity in Paget's disease: The prism study M. Rios Visconti ⁎, A.L. Langston, Kirsteen Goodman, P.L. Selby, W.D. Fraser, S.H. Ralston Rheumatology Department, University of Edinburgh, Edinburgh, UK Abstract: Paget's disease of bone (PDB) is a common disorder of the skeleton that affects up to 2% of individuals of European ancestry ages 55 years and above. The disease has a strong genetic component but epidemiological studies indicate that environmental factors may also play a role in regulating susceptibility to the disease and disease severity. It has been suggested that chronic low grade infection with measles virus (MV) might act as a susceptibility factor for PDB, but so far as we are aware, no previous studies have been performed to assess the relationship between MV infection and disease severity in PDB. Here we investigated the relationship between circulating IgG antibodies to measles virus (a marker of previous infection) and disease extent and severity in participants who took part in the PRISM study. Relevant data were available from 638 subjects. Severity of PDB was assessed by a disease severity score as previously described (Visconti JMBR 2010) which takes into account the number of bones affected, number of previous treatments, and the presence of complications such as fracture; previous orthopaedic surgery, deafness in patients with skull involvement and bone deformity. Multiple regression analysis showed that age at diagnosis (p<0.001) age (p<0.001) family history of PDB (p=0.003) and the presence of SQSTM1 mutations (p=0.017) were significant independent predictors of disease severity accounting for 29.9% of the variance in severity. Measles virus titre was weakly associated with disease severity but the result was not significant (p=0.079). In view of the weak association between MV titre and disease severity however we performed an exploratory analysis to determine if a threshold level may exist in which MV titre was related to severity. When subjects were categorised into four groups according to MV titres (low, moderate, high, very high) we found that disease extent was higher in the patients with the highest MV titres (n=40) compared with those who had lower MV titres (n=−595) with mean±SD values of 7.32±3.6 vs. 6.13±3.68 (p=0.008). There was no association between MV titre and SQSTM1 mutation status or age at onset. This study has shown evidence of an association between high MV titres and severity of PDB, but only in a subset of patients with the highest MV titres. This raises the possibility that patients with severe PDB may exhibit an exaggerated response to MV infection and that this could influence disease activity. This article is part of a Special Issue entitled ECTS 2011. Disclosure of interest: None declared.
doi:10.1016/j.bone.2011.03.582
PP452-M The vitamin D analog paricalcitol (Pc) upregulates osteocyte fibroblast growth factor 23 (FGF23) and improves the mineralization defect in experimental uremia M. Freundlich a,⁎, E. Bellorin-Font b, R.C. Pereira c, E. Rojas b, E. Alonzo b, B. Rodriguez-Iturbe d, I.B. Salusky c, J.R. Weisinger e a Pediatric Nephrology, University of Miami, Miami, USA b Nephrology and Renal Transplantation, Hospital Universitario, Caracas, Bolivarian Republic of Venezuela c Pediatric Nephrology, UCLA, Los Angeles, USA d Renal Service and IVIC, Hospital Universitario, Maracaibo, Bolivarian Republic of Venezuela e Renal Service and IVIC, Hospital Universitario, Caracas, Bolivarian Republic of Venezuela