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Decreased RUNX2, RANKL and sost gene expression in transiliac bone biopsies of men with untreated idiopathic osteoporosis
Abstracts / Bone 47 (2010) S72–S241
Most studies report an inverse association between osteoporosis and obesity, generally assessed using body mass index (BMI). However, there is a paucity of data on the association of other body composition parameters with quantitative ultrasound measures as well as prospective fracture risk. We examined these associations in men and women in the European Prospective Investigation into Cancer (EPIC)-Norfolk who had measurements of both heel quantitative ultrasound and percentage body fat (%BF) using a validated impedance technique between 1997 and 2000 and were followed for any incident fracture up to March 2007. From 14,789 participants (6,470 men) aged 42-82 years at baseline, 140 suffered a hip fracture during 114,371 person-years of follow-up (mean 7.7 ± 0.8 years). In sex-specific multivariable linear regression models, age-adjusted heel broadband ultrasound attenuation (BUA) measures were positively associated with %BF (β coefficient = 0.38 for women and 0.19 for men; P < 0.001 for both). However, after inclusion of BMI in the model, the relation between BUA with %BF became significantly negative and remained significant after inclusion of other factors including waist-to-hip ratio, history of fracture, smoking and alcohol intake (β coefficient = -0.11 for women and -0.30 for men; P < 0.001 for both). Women with incident hip fracture during follow-up had significantly lower %BF (36.1% vs. 39.8%) and BMI (25.6 vs. 26.5 kg/m2) compared to women without hip fracture; there were no significant differences for %BF and BMI between men with and without fracture. In sex-specific multivariate Cox proportional-hazard regression models, increasing %BF appeared significantly protective against hip fracture in women (hazard ratio [HR] for 10% increase = 0.55, 95% CI 0.39-0.78; P = 0.001) but not in men (HR = 0.70, 95% CI 0.26-1.83; P = 0.46). BMI became a significant risk factor for hip fracture in the model including %BF for women (HR for 4 kg/m2 = 1.37, 95% CI 1.02-1.85; p = 0.039). The effect of 10% increase in %BF on hip fracture risk was equivalent to about 1 standard deviation increase in BUA and about 7 years decrease in age in women. Understanding differences in relationships between different indices of obesity (such as %BF and BMI), BUA and fracture risk in men and women may help elucidate the metabolic and other underlying mechanisms involved in bone health and fracture risk. Disclosure of Interest: None declared Keywords: BMI, fracture risk assessment, Quantitative Ultrasound doi:10.1016/j.bone.2010.04.429
PP294 Decreased RUNX2, RANKL and sost gene expression in transiliac bone biopsies of men with untreated idiopathic osteoporosis J.M. Patsch1,2,⁎, C. Muschitz3, T. Wögerbauer3, A. Berzlanovich4, K. Wahl2, H. Resch3, P. Pietschmann2 1 Department of Radiology, Medical University of Vienna, Vienna, Austria 2 Center of Physiology, Pathophysiology and Immunology, Medical University of Vienna, Vienna, Austria 3 Medical Department II, St. Vincent Hospital, Vienna, Austria 4 Department of Forensics, Medical University of Vienna Introduction: Male Osteoporosis is a clinically relevant disease which is yet underestimated in its real dimension. Although patients can be treated effectively with certain antiosteoporotic drugs, the detailed pathophysiology of this disease unclear. Bone marker studies suggest a combined osteoblastic and osteoclastic disease Background: However, only few investigations have focused on gene expression in bone tissue of patients affected. The aim of this study was to assess the expression of RANKL, OPG, runx2, osterix, osteocalcin, Wnt10b and SOST in transiliac bone samples of patients with primary male osteoporosis. Patients & Methods: After written informed consent, 11 men with untreated, primary male osteoporosis
S183
underwent transiliac bone biopsy. Metabolic bone diseases other than primary osteoporosis were excluded by clinical work-up, blood testing and routine histology. Age-matched control samples (n = 11) were obtained from forensic autopsies. Samples were transported and stored in RNA-Later until RNA was extracted. Following reverse transcription, samples were submitted to real time PCR to assess RANKL, OPG, osterix, runx2, SOST and wnt10b expression levels. For each sample a mean cycle value was calculated and subtracted by the mean cycle value for GAPDH. Results: Patients were aged 52 ± 16 years and their average body mass index was 26,5 kg/m2. Their mean T-scores were -2,06 at the lumbar spine (L1-L4) and -2,18 at the (total) hip. 90% of patients had a history of peripheral or vertebral fractures. A family history of fractures was present in 45%. When related to GAPDH gene expression, runx2, RANKL and, somewhat surprisingly, SOST expression was significantly lower in patients than in controls. The expression of OPG, osterix and wnt10b did not differ between the groups. Conclusion: Reduced runx2- and RANKL expression indicate an osteoblast defect in male idiopathic osteoporosis. Disclosure of Interest: None declared Keywords: RANKL, runx2, SOST doi:10.1016/j.bone.2010.04.430
PP295 Bone mineral density in postmenopausal women with oteoporotic fractures V. Povoroznyuk⁎, V. Vayda, N. Dzerovych Institute of Gerontology Ams Ukraine, Kyiv, Ukraine This research is aimed at studying the bone mineral density among postmenopausal women with osteoporotic fractures. Object. The total of 160 postmenopausal women 45–79 years old (average age – 63,4 ± 0,7 years; average duration of postmenopausal period – 14,4 ± 0,7 years) were examined. Patients were divided into two groups: group A – women (n = 100, average age – 63,2 ± 0,9 years) without osteoporotic fractures, group B – women (n = 60, average age – 65,5 ± 1,2 years) with osteoporotic fractures in their anamnesis. Methods: The questionnaire; measurement of anthropometrical characteristics (height, mass, body mass index); bone mineral density (BMD), T- and Z-scores of the spine (L1–L4), hip (femoral neck, trochanter and total femur), and forearm (ultradistal, midforearm) were determined by means of Dual-energy X-ray absorptiometer “Prodigy” (GE Medical systems, 2005). Results: All indexes of different skeletal areas measured by DXA in postmenopausal women with osteoporotic fractures were significantly lower (р < 0,001) compared with the data of women without osteoporotic fractures: total body – BMD: 0,999 ± 0,015 g/cm2 and 1,097 ± 0,010 g/cm2, Тscore: -1,59 ± 0,18 and -0,34 ± 0,12, Z-score: -0,81 ± 0,15 and -0,06 ± 0,09; spine (L1–L4) – BMD: 0,909 ± 0,023 g/cm2 and 1,094 ± 0,017 g/cm2, Т-score: -2,26 ± 0,20 and -0,78 ± 0,14, Z-score: -1,18 ± 0,18 and -0,02 ± 0,13; femoral neck – BMD: 0,780 ± 0,016 g/cm2 and 0,886 ± 0,014 g/cm2, Т-score: -1,88 ± 0,11 and -1,09 ± 0,01, Z-score: -0,59 ± 0,10 and -0,05 ± 0,09; trochanter – BMD: 0,696 ± 0,017 g/ cm2 and 0,819 ± 0,016 g/cm2, Т-score: -1,35 ± 0,15 and -0,36 ± 0,12, Z-score: -0,42 ± 0,14 and 0,33 ± 0,11; total femur – BMD: 0,839 ± 0,019 g/cm2 and 0,968 ± 0,016 g/cm2, Т-score: -1,29 ± 0,16 and -0,27 ± 0,12, Z-score: -0,33 ± 0,13 and 0,45 ± 0,11; ultradistal forearm– BMD: 0,299 ± 0,008 g/cm2 and 0,352 ± 0,08 g/cm2, Т-score: -2,12 ± 0,20 and - 0,77 ± 0,19, Z-score: - 0,74 ± 0,21 and 0,39 ± 0,18; midforearm – BMD: 0,562 ± 0,013 g/cm2 and 0,648 ± 0,010 g/cm2, Т-score: - 2,13 ± 0,18 and - 0,96 ± 0,12, Z-score: - 0,69 ± 0,16 and 0,18 ± 0,12, accordingly. Conclusion: Low bone mineral density of different skeletal areas is a significant predictor of osteoporotic fractures in postmenopausal women.
Most studies report an inverse association between osteoporosis and obesity, generally assessed using body mass index (BMI). However, there is a paucity of data on the association of other body composition parameters with quantitative ultrasound measures as well as prospective fracture risk. We examined these associations in men and women in the European Prospective Investigation into Cancer (EPIC)-Norfolk who had measurements of both heel quantitative ultrasound and percentage body fat (%BF) using a validated impedance technique between 1997 and 2000 and were followed for any incident fracture up to March 2007. From 14,789 participants (6,470 men) aged 42-82 years at baseline, 140 suffered a hip fracture during 114,371 person-years of follow-up (mean 7.7 ± 0.8 years). In sex-specific multivariable linear regression models, age-adjusted heel broadband ultrasound attenuation (BUA) measures were positively associated with %BF (β coefficient = 0.38 for women and 0.19 for men; P < 0.001 for both). However, after inclusion of BMI in the model, the relation between BUA with %BF became significantly negative and remained significant after inclusion of other factors including waist-to-hip ratio, history of fracture, smoking and alcohol intake (β coefficient = -0.11 for women and -0.30 for men; P < 0.001 for both). Women with incident hip fracture during follow-up had significantly lower %BF (36.1% vs. 39.8%) and BMI (25.6 vs. 26.5 kg/m2) compared to women without hip fracture; there were no significant differences for %BF and BMI between men with and without fracture. In sex-specific multivariate Cox proportional-hazard regression models, increasing %BF appeared significantly protective against hip fracture in women (hazard ratio [HR] for 10% increase = 0.55, 95% CI 0.39-0.78; P = 0.001) but not in men (HR = 0.70, 95% CI 0.26-1.83; P = 0.46). BMI became a significant risk factor for hip fracture in the model including %BF for women (HR for 4 kg/m2 = 1.37, 95% CI 1.02-1.85; p = 0.039). The effect of 10% increase in %BF on hip fracture risk was equivalent to about 1 standard deviation increase in BUA and about 7 years decrease in age in women. Understanding differences in relationships between different indices of obesity (such as %BF and BMI), BUA and fracture risk in men and women may help elucidate the metabolic and other underlying mechanisms involved in bone health and fracture risk. Disclosure of Interest: None declared Keywords: BMI, fracture risk assessment, Quantitative Ultrasound doi:10.1016/j.bone.2010.04.429
PP294 Decreased RUNX2, RANKL and sost gene expression in transiliac bone biopsies of men with untreated idiopathic osteoporosis J.M. Patsch1,2,⁎, C. Muschitz3, T. Wögerbauer3, A. Berzlanovich4, K. Wahl2, H. Resch3, P. Pietschmann2 1 Department of Radiology, Medical University of Vienna, Vienna, Austria 2 Center of Physiology, Pathophysiology and Immunology, Medical University of Vienna, Vienna, Austria 3 Medical Department II, St. Vincent Hospital, Vienna, Austria 4 Department of Forensics, Medical University of Vienna Introduction: Male Osteoporosis is a clinically relevant disease which is yet underestimated in its real dimension. Although patients can be treated effectively with certain antiosteoporotic drugs, the detailed pathophysiology of this disease unclear. Bone marker studies suggest a combined osteoblastic and osteoclastic disease Background: However, only few investigations have focused on gene expression in bone tissue of patients affected. The aim of this study was to assess the expression of RANKL, OPG, runx2, osterix, osteocalcin, Wnt10b and SOST in transiliac bone samples of patients with primary male osteoporosis. Patients & Methods: After written informed consent, 11 men with untreated, primary male osteoporosis
S183
underwent transiliac bone biopsy. Metabolic bone diseases other than primary osteoporosis were excluded by clinical work-up, blood testing and routine histology. Age-matched control samples (n = 11) were obtained from forensic autopsies. Samples were transported and stored in RNA-Later until RNA was extracted. Following reverse transcription, samples were submitted to real time PCR to assess RANKL, OPG, osterix, runx2, SOST and wnt10b expression levels. For each sample a mean cycle value was calculated and subtracted by the mean cycle value for GAPDH. Results: Patients were aged 52 ± 16 years and their average body mass index was 26,5 kg/m2. Their mean T-scores were -2,06 at the lumbar spine (L1-L4) and -2,18 at the (total) hip. 90% of patients had a history of peripheral or vertebral fractures. A family history of fractures was present in 45%. When related to GAPDH gene expression, runx2, RANKL and, somewhat surprisingly, SOST expression was significantly lower in patients than in controls. The expression of OPG, osterix and wnt10b did not differ between the groups. Conclusion: Reduced runx2- and RANKL expression indicate an osteoblast defect in male idiopathic osteoporosis. Disclosure of Interest: None declared Keywords: RANKL, runx2, SOST doi:10.1016/j.bone.2010.04.430
PP295 Bone mineral density in postmenopausal women with oteoporotic fractures V. Povoroznyuk⁎, V. Vayda, N. Dzerovych Institute of Gerontology Ams Ukraine, Kyiv, Ukraine This research is aimed at studying the bone mineral density among postmenopausal women with osteoporotic fractures. Object. The total of 160 postmenopausal women 45–79 years old (average age – 63,4 ± 0,7 years; average duration of postmenopausal period – 14,4 ± 0,7 years) were examined. Patients were divided into two groups: group A – women (n = 100, average age – 63,2 ± 0,9 years) without osteoporotic fractures, group B – women (n = 60, average age – 65,5 ± 1,2 years) with osteoporotic fractures in their anamnesis. Methods: The questionnaire; measurement of anthropometrical characteristics (height, mass, body mass index); bone mineral density (BMD), T- and Z-scores of the spine (L1–L4), hip (femoral neck, trochanter and total femur), and forearm (ultradistal, midforearm) were determined by means of Dual-energy X-ray absorptiometer “Prodigy” (GE Medical systems, 2005). Results: All indexes of different skeletal areas measured by DXA in postmenopausal women with osteoporotic fractures were significantly lower (р < 0,001) compared with the data of women without osteoporotic fractures: total body – BMD: 0,999 ± 0,015 g/cm2 and 1,097 ± 0,010 g/cm2, Тscore: -1,59 ± 0,18 and -0,34 ± 0,12, Z-score: -0,81 ± 0,15 and -0,06 ± 0,09; spine (L1–L4) – BMD: 0,909 ± 0,023 g/cm2 and 1,094 ± 0,017 g/cm2, Т-score: -2,26 ± 0,20 and -0,78 ± 0,14, Z-score: -1,18 ± 0,18 and -0,02 ± 0,13; femoral neck – BMD: 0,780 ± 0,016 g/cm2 and 0,886 ± 0,014 g/cm2, Т-score: -1,88 ± 0,11 and -1,09 ± 0,01, Z-score: -0,59 ± 0,10 and -0,05 ± 0,09; trochanter – BMD: 0,696 ± 0,017 g/ cm2 and 0,819 ± 0,016 g/cm2, Т-score: -1,35 ± 0,15 and -0,36 ± 0,12, Z-score: -0,42 ± 0,14 and 0,33 ± 0,11; total femur – BMD: 0,839 ± 0,019 g/cm2 and 0,968 ± 0,016 g/cm2, Т-score: -1,29 ± 0,16 and -0,27 ± 0,12, Z-score: -0,33 ± 0,13 and 0,45 ± 0,11; ultradistal forearm– BMD: 0,299 ± 0,008 g/cm2 and 0,352 ± 0,08 g/cm2, Т-score: -2,12 ± 0,20 and - 0,77 ± 0,19, Z-score: - 0,74 ± 0,21 and 0,39 ± 0,18; midforearm – BMD: 0,562 ± 0,013 g/cm2 and 0,648 ± 0,010 g/cm2, Т-score: - 2,13 ± 0,18 and - 0,96 ± 0,12, Z-score: - 0,69 ± 0,16 and 0,18 ± 0,12, accordingly. Conclusion: Low bone mineral density of different skeletal areas is a significant predictor of osteoporotic fractures in postmenopausal women.