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Atypical femoral fractures: Radiographic and histomorphometric features in 9 patients
S110
Abstracts
PP146 The (S1486T/C) promoter polymorphism of the TLR-9 gene is associated with knee osteoarthritis in a Chinese population S.-L. Sua,⁎, D.M. Salterb, H.-S. Leec a School of Public Health, National Defense Medical Center, Taipei, Taiwan b Osteoarticular Research Group, University of Edinburgh, Edinburgh, UK c Department of Pathology, Tri-Service General Hospital, Taipei, Taiwan Abstract: Based on the recent observation that Toll-like receptors (TLRs) may be involved in the pathogenesis of osteoarthritis (OA), we explored the possibility that human TLR gene polymorphisms are associated with OA. Two separate populations were studied in a twostage case–control study with a total of 503 OA patients and 428 healthy controls. The TLR-2, TLR-4, and TLR-9 genotypes were assessed by real-time polymerase chain reaction. Our data demonstrated a lack of association among TLR-2, TLR-4, and TLR-9 (T-1237C) polymorphisms and the risk of developing OA in both stages of the study. T-1486C was significantly associated with OA in both populations with G1635A of TLR-9 gene was found to be significantly associated with OA when the two populations were combined. Stratifying the samples by K–L score there were significant differences in the genotype of the TLR-9T-1486C and G1635A between OA of the knee grade 4 and controls. In haplotype analyses, the haplotype TTG and TTA revealed higher risk of OA and TCA confers a lower risk of OA in combined population. The present results demonstrate that TLR-9 polymorphisms, in particular T-1486C is significantly associated with OA. TLR-9 gene polymorphisms may play a role in the etiology of knee OA. This article is part of a Special Issue entitled ECTS 2012. Disclosure of interest: None declared. doi:10.1016/j.bone.2012.02.335
PP147 Genetic parallels between periodontitis and an osteoporosis V.G. Atrushkevicha,⁎, A. Zinovyevaa, A. Polyakovb a Periodontology, Moscow State University of Medicine and Dentistry, Russian Federation b DNA-Diagnostics Laboratory, the Research Centre for Medical Genetics, Moscow, Russian Federation Abstract: Introduction: Aggressive Periodontitis (AP) is characterized by severe alveolar bone resorption and early loss of teeth. Pathologic mechanisms of AP also develop on a genetic level. Materials and methods: 203 patients participated in the study. There were 47 patients with AP, 40 with osteoporosis (OP), 52 healthy patients (control-1) and 64 randomized patients (control-2 — only for genetic study). We studied condition of hard dental tissue according to quantity of carious teeth (C), extracted teeth (E), filled teeth (F), periodontal indexes (HI, PBI, GI, CAL, mobility), orthopantomography (assessment of severity of alveolar bone resorption (SR)), and data of X-ray densitometry (DEXA) (assessment of bone mineral density (BMD)). Peripheral blood DNA was studied. We defined (PCR diagnostics) genes involved in the process of bone remodelling (Calcitonin receptor gene (CALCR), parathyroid hormone receptor type 1(PTHR1), and collagen type one alpha-1 (COL1A1)). Results: There were more F and E in AP patients than in control-1 (p=0.005 and p=0.04 accordingly) but fewer than in OP patients (p=0.04 and p=0.00006 accordingly). Periodontal indexes were higher in AP patients than in OP and control-1 groups (pb 0.05). The highest SR was noted in patients with AP (pb 0.05). BMD in AP patients was in normal limits. Occurrence rate (OR) is 6.1 times higher if two or three predisposing genotypes of genes CALCR, PTHR1, and COL1A1 (p=0.001) are present. In case genotype T/T of gene COL1A1 is present, OR of AP is increased by 7 times (p=0.002). SR is the highest in patients with genotype T/T (p=0.04 for maxilla, p=0.03 for mandible). Conclusions: All three genes predispose to AP. The presence of genotype T/T of COL1A1 maximally increases the occurrence rate of AP and results in the most severe bone resorption. We suggest using c.140-441GbT of gene COL1A1 as a marker for an early diagnosis of AP, treatment planning and treatment prognosis. This article is part of a Special Issue entitled ECTS 2012. Disclosure of interest: None declared. doi:10.1016/j.bone.2012.02.336
PP148 Molecular mechanisms of lipid uptake into the skeleton A. Bartelta,b,⁎, B. Freundb, O.T. Brunsc, J. Heerenb, A.C. Niemeiera,b a Department of Orthopedics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany b Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany c Department of Chemistry, Massachusetts Institute of Technology, Boston, MA, USA
Abstract: Objective: Lipids are transported via lipoproteins, which in the circulation can be either processed by lipoprotein lipase to release lipid constituents or can be taken up as whole particles. Next to triglycerides and cholesterol, also lipophilic vitamin K is delivered by lipoproteins. However, the contribution of the skeleton as a lipid storage organ to lipoprotein metabolism is poorly understood. Here we analyze the molecular basis of lipoprotein uptake into bone and quantify the contribution of the skeleton to systemic lipid metabolism. Methods: 59Fe-nanocrystals and 3H-triolein-labeled lipoproteins were injected to follow lipoprotein particle and fatty acid uptake simultaneously. Uptake was determined by scintillation counting. The fate of dietary lipids was followed in an oral fat tolerance test with tracer amounts of 3 H-triolein. Animal models of defective lipoprotein function were used to elucidate molecular pathways responsible for lipid entry into bone. Results: In comparison to liver and brown adipose tissue, which alongside muscle represents the major organs involved in dietary fat clearance, the lipid uptake per mg of organ weight is relatively low in calvaria, femur cortex and vertebra. However, the skeleton is the fourth most important organ involved in lipid uptake. Furthermore, bone marrow displays a strong specific fatty acid uptake for 3H-triolein which is independent of the lipoprotein receptor ligand apolipoprotein E and is not blocked by pre-treatment with natural lipoproteins. In contrast to fatty acids, uptake of 59Fe-nanocrystal label is low, and is blocked by pre-treatment with lipoproteins. Conclusion: The majority of lipids are taken-up by 1. initial binding of lipoproteins, 2. hydrolysis of triglycerides by lipoprotein lipase and uptake of fatty acids and 3. clearance of remnant particles by liver and brown adipose tissue. Of note, the skeleton is among the top four organs involved in dietary fat clearance (next to muscle, liver and brown fat). As the close relationship between obesity, insulin resistance and diabetes and different adipose depots is established, the contribution of “skeletal adipose tissue” to metabolic disease seems to be largely unvalued in face of its quantitative importance for lipid metabolism. Our results suggest that bone marrow adipocytes not only manipulate the microenvironment in bone and thus bone homeostasis but also are linked to systemic energy metabolism and thus to metabolic disease. This article is part of a Special Issue entitled ECTS 2012. Disclosure of interest: None declared. doi:10.1016/j.bone.2012.02.337
PP149 Atypical femoral fractures: Radiographic and histomorphometric features in 9 patients A. Khan⁎ Endocrinology and Geriatrics, McMaster University, Hamilton, Canada Abstract: Purpose: this study describes the patient characteristics and histomorphometric and radiographic features of atypical femoral fractures (AFF) as seen in 9 cases referred for evaluation. Methods: All patients referred for evaluation of AFF were reviewed. Patients meeting the ASBMR criteria for AFF were further evaluated and tetracycline labelled bone biopsies were completed. Radiographs were reviewed by a musculoskeletal radiologist. Results: All fracture lines were transverse or short oblique with thickened cortices. We report 9 cases of AFF in patients on long term bisphosphonate (bp) therapy. 6 of 7 fractures occurred without a fall or direct trauma to the femur with 1 case occurring after a fall from standing height. All patients were female; average age was 67 yrs (range 54–80 yrs). 2 of the 9 cases were of Chinese descent, 2 were East Indian with 3 being Caucasian. Average bp duration of us was 8.5 years (range 7–14 years), 5 of 9 patients were on alendronate alone, and 2 patients were on risedronate. 1 patient had received 18 months of teriparatide, 3 years prior to the AFF and had received a total of 10 years of bp use prior to teriparatide. Prodromal thigh or groin pain was seen in 5 of the 9 patients for 3 to 12 months prior to fracture. Proton pump inhibitor use was present in 1 patient for the previous 2 years. 1 patient was on prednisone for rheumatoid arthritis. Rheumatoid arthritis was present in 2 cases. Diabetes was not present in any of the 9 cases. Bilaterality occurred in 1 patient with the second AFF occurring 1 month after the first AFF. Renal function was well preserved with an estimated glomerular filtration rate N 60 ml/min in all cases. 25 hydroxy vitamin D levels were 75 nmol/l in 5 cases. 2 cases had mild vitamin D insufficiency (N 50nmol/l). Summary: A large number of the AFF occurred in women of Asian descent (4 of 9). 6 of the 9 AFF occurred in the absence of a fall. Prodromal pain was commonly seen. Proton pump inhibitors were used in only 1 patient. Histomorphometric features included evidence of mineralization abnormalities and decreased bone formation. Conclusion: AFF in association with long term bp use are being seen in disproportionately a large number of Asian women. Further evaluation of all AFF with identification of predisposing key clinical risk factors is needed. Improved understanding of the pathophysiology may be gained with further histomorphometric data in larger numbers of patients. This article is part of a Special Issue entitled ECTS 2012. Disclosure of interest: None declared. doi:10.1016/j.bone.2012.02.338
Abstracts
PP146 The (S1486T/C) promoter polymorphism of the TLR-9 gene is associated with knee osteoarthritis in a Chinese population S.-L. Sua,⁎, D.M. Salterb, H.-S. Leec a School of Public Health, National Defense Medical Center, Taipei, Taiwan b Osteoarticular Research Group, University of Edinburgh, Edinburgh, UK c Department of Pathology, Tri-Service General Hospital, Taipei, Taiwan Abstract: Based on the recent observation that Toll-like receptors (TLRs) may be involved in the pathogenesis of osteoarthritis (OA), we explored the possibility that human TLR gene polymorphisms are associated with OA. Two separate populations were studied in a twostage case–control study with a total of 503 OA patients and 428 healthy controls. The TLR-2, TLR-4, and TLR-9 genotypes were assessed by real-time polymerase chain reaction. Our data demonstrated a lack of association among TLR-2, TLR-4, and TLR-9 (T-1237C) polymorphisms and the risk of developing OA in both stages of the study. T-1486C was significantly associated with OA in both populations with G1635A of TLR-9 gene was found to be significantly associated with OA when the two populations were combined. Stratifying the samples by K–L score there were significant differences in the genotype of the TLR-9T-1486C and G1635A between OA of the knee grade 4 and controls. In haplotype analyses, the haplotype TTG and TTA revealed higher risk of OA and TCA confers a lower risk of OA in combined population. The present results demonstrate that TLR-9 polymorphisms, in particular T-1486C is significantly associated with OA. TLR-9 gene polymorphisms may play a role in the etiology of knee OA. This article is part of a Special Issue entitled ECTS 2012. Disclosure of interest: None declared. doi:10.1016/j.bone.2012.02.335
PP147 Genetic parallels between periodontitis and an osteoporosis V.G. Atrushkevicha,⁎, A. Zinovyevaa, A. Polyakovb a Periodontology, Moscow State University of Medicine and Dentistry, Russian Federation b DNA-Diagnostics Laboratory, the Research Centre for Medical Genetics, Moscow, Russian Federation Abstract: Introduction: Aggressive Periodontitis (AP) is characterized by severe alveolar bone resorption and early loss of teeth. Pathologic mechanisms of AP also develop on a genetic level. Materials and methods: 203 patients participated in the study. There were 47 patients with AP, 40 with osteoporosis (OP), 52 healthy patients (control-1) and 64 randomized patients (control-2 — only for genetic study). We studied condition of hard dental tissue according to quantity of carious teeth (C), extracted teeth (E), filled teeth (F), periodontal indexes (HI, PBI, GI, CAL, mobility), orthopantomography (assessment of severity of alveolar bone resorption (SR)), and data of X-ray densitometry (DEXA) (assessment of bone mineral density (BMD)). Peripheral blood DNA was studied. We defined (PCR diagnostics) genes involved in the process of bone remodelling (Calcitonin receptor gene (CALCR), parathyroid hormone receptor type 1(PTHR1), and collagen type one alpha-1 (COL1A1)). Results: There were more F and E in AP patients than in control-1 (p=0.005 and p=0.04 accordingly) but fewer than in OP patients (p=0.04 and p=0.00006 accordingly). Periodontal indexes were higher in AP patients than in OP and control-1 groups (pb 0.05). The highest SR was noted in patients with AP (pb 0.05). BMD in AP patients was in normal limits. Occurrence rate (OR) is 6.1 times higher if two or three predisposing genotypes of genes CALCR, PTHR1, and COL1A1 (p=0.001) are present. In case genotype T/T of gene COL1A1 is present, OR of AP is increased by 7 times (p=0.002). SR is the highest in patients with genotype T/T (p=0.04 for maxilla, p=0.03 for mandible). Conclusions: All three genes predispose to AP. The presence of genotype T/T of COL1A1 maximally increases the occurrence rate of AP and results in the most severe bone resorption. We suggest using c.140-441GbT of gene COL1A1 as a marker for an early diagnosis of AP, treatment planning and treatment prognosis. This article is part of a Special Issue entitled ECTS 2012. Disclosure of interest: None declared. doi:10.1016/j.bone.2012.02.336
PP148 Molecular mechanisms of lipid uptake into the skeleton A. Bartelta,b,⁎, B. Freundb, O.T. Brunsc, J. Heerenb, A.C. Niemeiera,b a Department of Orthopedics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany b Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany c Department of Chemistry, Massachusetts Institute of Technology, Boston, MA, USA
Abstract: Objective: Lipids are transported via lipoproteins, which in the circulation can be either processed by lipoprotein lipase to release lipid constituents or can be taken up as whole particles. Next to triglycerides and cholesterol, also lipophilic vitamin K is delivered by lipoproteins. However, the contribution of the skeleton as a lipid storage organ to lipoprotein metabolism is poorly understood. Here we analyze the molecular basis of lipoprotein uptake into bone and quantify the contribution of the skeleton to systemic lipid metabolism. Methods: 59Fe-nanocrystals and 3H-triolein-labeled lipoproteins were injected to follow lipoprotein particle and fatty acid uptake simultaneously. Uptake was determined by scintillation counting. The fate of dietary lipids was followed in an oral fat tolerance test with tracer amounts of 3 H-triolein. Animal models of defective lipoprotein function were used to elucidate molecular pathways responsible for lipid entry into bone. Results: In comparison to liver and brown adipose tissue, which alongside muscle represents the major organs involved in dietary fat clearance, the lipid uptake per mg of organ weight is relatively low in calvaria, femur cortex and vertebra. However, the skeleton is the fourth most important organ involved in lipid uptake. Furthermore, bone marrow displays a strong specific fatty acid uptake for 3H-triolein which is independent of the lipoprotein receptor ligand apolipoprotein E and is not blocked by pre-treatment with natural lipoproteins. In contrast to fatty acids, uptake of 59Fe-nanocrystal label is low, and is blocked by pre-treatment with lipoproteins. Conclusion: The majority of lipids are taken-up by 1. initial binding of lipoproteins, 2. hydrolysis of triglycerides by lipoprotein lipase and uptake of fatty acids and 3. clearance of remnant particles by liver and brown adipose tissue. Of note, the skeleton is among the top four organs involved in dietary fat clearance (next to muscle, liver and brown fat). As the close relationship between obesity, insulin resistance and diabetes and different adipose depots is established, the contribution of “skeletal adipose tissue” to metabolic disease seems to be largely unvalued in face of its quantitative importance for lipid metabolism. Our results suggest that bone marrow adipocytes not only manipulate the microenvironment in bone and thus bone homeostasis but also are linked to systemic energy metabolism and thus to metabolic disease. This article is part of a Special Issue entitled ECTS 2012. Disclosure of interest: None declared. doi:10.1016/j.bone.2012.02.337
PP149 Atypical femoral fractures: Radiographic and histomorphometric features in 9 patients A. Khan⁎ Endocrinology and Geriatrics, McMaster University, Hamilton, Canada Abstract: Purpose: this study describes the patient characteristics and histomorphometric and radiographic features of atypical femoral fractures (AFF) as seen in 9 cases referred for evaluation. Methods: All patients referred for evaluation of AFF were reviewed. Patients meeting the ASBMR criteria for AFF were further evaluated and tetracycline labelled bone biopsies were completed. Radiographs were reviewed by a musculoskeletal radiologist. Results: All fracture lines were transverse or short oblique with thickened cortices. We report 9 cases of AFF in patients on long term bisphosphonate (bp) therapy. 6 of 7 fractures occurred without a fall or direct trauma to the femur with 1 case occurring after a fall from standing height. All patients were female; average age was 67 yrs (range 54–80 yrs). 2 of the 9 cases were of Chinese descent, 2 were East Indian with 3 being Caucasian. Average bp duration of us was 8.5 years (range 7–14 years), 5 of 9 patients were on alendronate alone, and 2 patients were on risedronate. 1 patient had received 18 months of teriparatide, 3 years prior to the AFF and had received a total of 10 years of bp use prior to teriparatide. Prodromal thigh or groin pain was seen in 5 of the 9 patients for 3 to 12 months prior to fracture. Proton pump inhibitor use was present in 1 patient for the previous 2 years. 1 patient was on prednisone for rheumatoid arthritis. Rheumatoid arthritis was present in 2 cases. Diabetes was not present in any of the 9 cases. Bilaterality occurred in 1 patient with the second AFF occurring 1 month after the first AFF. Renal function was well preserved with an estimated glomerular filtration rate N 60 ml/min in all cases. 25 hydroxy vitamin D levels were 75 nmol/l in 5 cases. 2 cases had mild vitamin D insufficiency (N 50nmol/l). Summary: A large number of the AFF occurred in women of Asian descent (4 of 9). 6 of the 9 AFF occurred in the absence of a fall. Prodromal pain was commonly seen. Proton pump inhibitors were used in only 1 patient. Histomorphometric features included evidence of mineralization abnormalities and decreased bone formation. Conclusion: AFF in association with long term bp use are being seen in disproportionately a large number of Asian women. Further evaluation of all AFF with identification of predisposing key clinical risk factors is needed. Improved understanding of the pathophysiology may be gained with further histomorphometric data in larger numbers of patients. This article is part of a Special Issue entitled ECTS 2012. Disclosure of interest: None declared. doi:10.1016/j.bone.2012.02.338