- Email: [email protected]
Denosumab treatment results in significant trabecular and cortical bone improvements at the hip as assessed by QCT
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Abstracts / Bone 48 (2011) S86–S90
OPC05 Identification of a functional variant in the TM7SF4 gene that is associated with susceptibility to paget's disease of bone O.M. Albagha ⁎, S. Wani, S.H. Ralston Molecular Medicine Centre, University of Edinburgh, Edinburgh, UK
Abstract: Paget's disease of bone (PDB) is a common skeletal disorder characterised by focal abnormalities in bone turnover. Genetic factors are important in PDB and mutations in the SQSTM1 gene are found in about 10% of sporadic cases and up to 40% of familial PDB cases. We recently identified variants in the TM7SF4 gene as a genetic risk factors for PDB using a genome wide association study (Albagha et al Nat. Genet. 2010). The most significant association was found for an intronic SNP (P = 7.4 × 10 − 17; OR = 1.4) with no predicted functional effect suggesting that other functional variants are driving the association with PDB risk. TM7SF4 encodes DC-STAMP, a transmembrane protein that plays an essential role in the fusion of osteoclast precursors to form mature osteoclasts. The aim of this study was to identify the functional variant(s) driving the association with PDB risk. The coding region and the putative promoter region of TM7SF4 were sequenced in 50 PDB cases and 10 controls using standard PCR-direct DNA sequencing methods. The identified variants were tested for association with PDB risk in 750 PDB cases and 2700 controls from the UK and significant findings were replicated in a further 500 cases and 500 matched controls. Functional analysis of promoter variants were tested using reporter gene construct experiments. Several variants were identified in the TM7SF4 gene, but a variant in the putative promoter region showed consistent association with PDB risk (combined P = 3.1 × 10 − 8; OR = 1.32). We then investigated the functional effects of this variant using reporter gene construct and results showed that the risk allele increased the expression of a luciferase reporter by 20% compared to the non-risk allele (P = 0.039). In conclusion we have identified a functional variant in the TM7SF4 which was found to enhance reporter gene expression. It is possible that increased DC-STAMP expression could enhance the fusion of osteoclast precursors to form larger and multinucleated osteoclasts which are typically found in Pagetic bone lesions, however further studies will be required to confirm this possibility. This article is part of a Special Issue entitled ECTS 2011. Disclosure of interest: none declared.
doi:10.1016/j.bone.2011.03.120
OPC06 Increased physical activity is associated with optimized development of peak bone mass mainly due to augmented cortical bone size in men: A five year longitudinal study M. Nilsson a, C. Ohlsson a, A. Odén b, D. Mellström a, M. Lorentzon a,⁎ a Institute of Medicine, Sahlgrenska Academy, Centre for Bone and Arthritis Research, Gothenburg University, Sweden b Dept. of Mathematical Sciences, Chalmers University of Technology, Gothenburg, Sweden
Abstract: Aim and background: The role of physical activity on the development of cortical bone geometry and areal bone mineral density (aBMD) in young men has not been established. The aim of this five year longitudinal study of young adult men was to determine whether an increased amount of physical activity was associated with increased bone mass and a favourable development of cortical bone structure. Methods: The original 1068 study subjects, initially included in the Gothenburg Osteoporosis and Obesity study (GOOD), were contacted by letter and telephone and invited to participate in this five year follow-up study. A total of 833 men (78%), 24.1 ± 0.6 years of age, were included. A standardized self administered questionnaire was used to collect information about patterns of physical activity at both the baseline and five year follow-up visit. Areal BMD was measured using dual energy X-ray absorptiometry, whereas volumetric bone mineral density (vBMD) and bone geometry were measured by peripheral quantitative computed tomography. Both baseline and changed (hrs/wk) physical activity were used in a regression model to predict alterations in bone variables. Results: An increased amount of physical activity, between the baseline and follow-up visit, was independently associated with an increase in aBMD of the total body (unstandardized B = 0.002 g/cm 2 per weekly hour increase, p < 0.001) and lumbar spine (B = 0.005, p < 0.001) as well as in cortical cross sectional area at the tibia (B = 0.36 mm 2 per weekly hour increase, p < 0.001). The increased amount of physical activity was also associated with a reduced decrease in aBMD of the total hip (B = 0.004, p < 0.001) as well as in trabecular vBMD (B = 0.590, p < 0.001) at the tibia. Both baseline physical activity and change in physical activity was associated with changes in total hip aBMD (Fig. 1). Conclusion: We found that increased physical activity was related to an advantageous development of cortical bone structure and aBMD in young men, indicating that increased physical activity during this age has the ability to prevent the age dependent decline in aBMD at the hip and increase the cortical envelope, having a positive effect on the attainment of peak bone mass in men.
Fig. 1. This article is part of a Special Issue entitled ECTS 2011. Disclosure of interest: None declared. doi:10.1016/j.bone.2011.03.121
OPC07 (For more information visit the Amgen/GlaxoSmithKline scientific booth) Denosumab treatment results in significant trabecular and cortical bone improvements at the hip as assessed by QCT H.K. Genant a,⁎, K. Engelke b, J.R. Zanchetta c, A. Høiseth d, C.K. Yuen e, S. Stonkus f, M.A. Bolognese g, E. Franek h, T. Fuerst i, H.-S. Radcliffe j, C. Libanati k a UCSF/Synarc, Tiduron, USA b Institute of Medical Physics, University of Erlangen, Erlangen, Germany c Instituto de Investigaciones Metabolicas, Buenos Aires, Argentina d Curato Rtg., Oslo, Norway e SIGMA Canadian Menopause Society, Vancouver, Canada f Klaipeda University Hospital, Klaipeda, Lithuania g Bethesda Health Research, Bethesda, USA h MSWiA, Warsaw, Poland i Synarc Inc., San Francisco, USA j Amgen, Inc., Cambridge, UK k Amgen, Inc., Thousand Oaks, USA Abstract: Denosumab, a fully human monoclonal antibody to RANKL, decreased bone resorption, increased bone mineral density (BMD), and reduced new vertebral, nonvertebral, and hip fractures in postmenopausal women with osteoporosis who participated in the FREEDOM trial (Cummings SR et al, NEJM, 2009:361:756). In FREEDOM, subjects received 60 mg denosumab or placebo every 6 months for 3 years; all subjects received daily supplements of calcium and vitamin D. Hip QCT scans were obtained at baseline and at months 12, 24, and 36, in a subset of women. These scans were analyzed, in a blinded-totreatment manner, using Medical Image Analysis Framework (MIAF) software (University of Erlangen, Germany), which has precision errors of 1.5% to 2.5%. MIAF allows the determination of total, trabecular, subcortical, and cortical BMD for the hip, all of which could influence strength differently. The cortical compartment was divided into the outer half (“periosteal”) and inner half (“endosteal”) subregions. We report the magnitude of
Fig. 1. Total hip BMD and BMC mean percent change and 95% Cl.
Abstracts / Bone 48 (2011) S86–S90 changes from baseline and placebo over the 36 months of denosumab treatment in subjects with evaluable hip QCT scans (denosumab n = 36; placebo n = 26). Baseline mean age was 73 years, mean years since menopause was 25, and mean DXA BMD T-score of the total hip was −1.85. Denosumab resulted in significant improvements in QCT total hip BMD and bone mineral content (BMC) from baseline at 12, 24 and 36 months (Fig. 1). Over 36 months, the mean percent change improvements from baseline in QCT total hip BMD and BMC reached 6.3% and 4.8%, respectively (both p < 0.0001). These gains were accounted for by significant increases in BMD and BMC in all cortical and trabecular compartments (Fig. 2). In the placebo group, total hip BMD and BMC decreased at 36 months from baseline by −1.4% and −2.7%, respectively (both p < 0.05). The differences between denosumab and placebo were also highly significant (p < 0.05 to <0.0001) at 12, 24, and 36 months for total, cortical, and trabecular BMD and BMC. In summary, denosumab results in significant improvements from baseline and placebo in both BMD and BMC, assessed by QCT, across total, trabecular, subcortical, and cortical and hip compartments, as well as periosteal and endosteal cortical subregions.
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(mean of L1-L4), total hip outer (including the trabecular and cortical bone), total hip inner (including only the trabecular bone), femoral neck, and cortical shaft (including only cortical bone) were 0.042± 0.008, 0.013 ± 0.005, 0.015 ±0.006, 0.015 ± 0.005, and 0.009± 0.002 ml. min − 1.ml − 1 respectively. The K1 values were 0.15 ± 0.01, 0.044 ± 0.013, 0.048± 0.018, 0.048± 0.017 and 0.036 ± 0.009 ml.min − 1.ml − 1 respectively. The SUVs were 6.0± 1.5, 2.3 ± 0.7, 2.6± 1.0, 2.7 ±1.1 and 1.8± 0.4 respectively. The differences for Ki at spine and any other hip region were significant (p=0.005). The differences among hip regions were also significant (p<0.05) except between femoral neck and total hip (p>0.05). The differences for K1 were significant between lumbar spine and any other hip regain (p=0.005) with no-significant differences among the hip regions (p> 0.05). Conclusion: This is the first study presenting the dynamic quantification of bone turnover and bone blood flow at the hip. We conclude that the bone turnover, perfusion and SUVs are higher in trabecular bone than in cortical bone. Financial support: this work was funded by the Health Research Board in Ireland under grant No: RP/2007/319. This article is part of a Special Issue entitled entitled ECTS 2011. Disclosure of interest: None declared.
doi:10.1016/j.bone.2011.03.123
OPC09 Thyroid hormone status within the euthyroid range is associated with bone mass and density in healthy young men at the age of peak bone mass G.L.L.E. Roef a,⁎, B. Lapauw a, S. Goemaere b, H.-G. Zmierczak b, T. Fiers c, J.-M. Kaufman a, Y. Taes a a Endocrinology, Ghent University Hospital, Ghent, Belgium b Unit for Osteoporosis and Metabolic bone diseases, Ghent University Hospital, Ghent, Belgium c Dpt. of Clinical Chemistry, Ghent University Hospital, Ghent, Belgium
Fig. 2. Hip BMD and BMC Mean Absolute Change and 95% Cl at 36 Months.
This article is part of a Special Issue entitled ECTS 2011. Disclosure of interest: H. Genant Shareholder of Synarc, Grant / Research Support from Merck, GSK, BMS, Roche, Lilly, Amgen, Novartis, Servier, Genentech, Medtronic, Takeda, Consulting fees from Synarc, Merck, GSK, BMS, Roche, Lilly, Amgen, Novartis, Servier, Genentech, Medtronic, Takeda, K. Engelke Employee of Synarc, Grant / Research Support from German Research Society, NIH, Paid Instructor for German Osteology Society, J. Zanchetta Grant / Research Support from Amgen, Eli Lilly, Merck, Pfizer, Advisory Board Membership of Amgen, Eli Lilly, GSK, Merck, Pfizer, Servier, Consulting fees from Amgen, Eli Lilly, GSK, Merck, Pfizer, Servier, A. Høiseth: None Declared, C. K. Yuen Grant / Research Support from Amgen, Merck, Pfizer, P&G, Novartis, Eli Lilly, Bayer, Speakers Bureau with Amgen, Merck, Pfizer, Advisory Board Membership of Amgen, Pfizer, Consulting fees from Amgen, Pfizer, Speaker Fees from Amgen, Merck, Pfizer, S. Stonkus: None Declared, M. Bolognese Grant / Research Support from Amgen, Roche, TARSA, Lilly, Speakers Bureau with Amgen, Lilly, Roche, E. Franek Grant / Research Support from Amgen, Advisory Board Membership of Amgen, Speaker Fees from Amgen, Novartis, Roche, Servier, T. Fuerst Shareholder of Synarc, Employee of Synarc, H.-S. Radcliffe Employee of Amgen, C. Libanati Shareholder of Amgen, Employee of Amgen. doi:10.1016/j.bone.2011.03.122
Abstract: Context: The hormonal factors involved in the regulation of peak bone mass and geometry in men have not been fully investigated. Aside from gonadal steroids and somatotropic hormones, thyroid hormones are known to affect bone maturation and homeostasis, and are additional candidate determinants of adult bone mass. Objective: We aimed to investigate between-subject physiological variation in free and total thyroid hormone concentrations, thyroid-stimulating hormone (TSH) and thyroid binding globulin (TBG) in relation to parameters of bone mass, geometry and mineral density in healthy men at age of peak bone mass. Design and setting: 677 healthy male siblings aged 25–45 yrs were recruited in a cross-sectional, population-based study. Areal and volumetric bone parameters were determined using dual-energy X-ray absorptiometry (DXA) and peripheral quantitative computed tomography (pQCT). Total (TT3, TT4) and free (FT3, FT4) thyroid hormones, TBG and TSH were determined using immunoassays. Results: Free and total thyroid hormone concentrations were inversely associated with areal bone mineral density (aBMD) and bone mineral content (BMC) at the hip and total body (FT3, TT3, TT4) and at the spine (FT3). Thyroid binding globulin (TBG) was negatively associated with BMC and aBMD at all sites. At the radius, cortical bone area was inversely associated with TT3, TT4 and TBG and trabecular bone density was inversely associated with FT4, TT4 and TBG. We observed inverse associations between cortical bone area at the mid-tibia and FT3, TT3, TT4 and TBG. No associations between TSH and DXA- or pQCT-measurements were found. Conclusion: In healthy men at age of peak bone mass, between-subject variation in thyroid hormone concentrations affects bone density and geometry, with higher levels of FT3, TT3, TT4 and TBG being associated with less favourable bone density and content. This article is part of a Special Issue entitled ECTS 2011. Disclosure of interest: None declared. doi:10.1016/j.bone.2011.03.124
OPC08 Bone turnover at the spine and hip measured using 18F-PET T. Puri a,⁎, G.M. Blake b, M.L. Frost b, M. Siddique b, A.E. Moore b, P.K. Marsden b, I. Fogelman b, K.M. Curran a a University College Dublin, Dublin, Ireland b King's College London, London, UK Abstract: Introduction: The imaging technique of 18F-fluoride positron emission tomography ( 18F-PET) allows the non-invasive assessment of regional bone metabolism at clinically important sites such as the hip and lumbar spine and allows the measurement of a number of parameters relating to bone metabolism, for example, regional bone turnover (Ki) and bone blood flow (K1). Purpose: To compare the differences between the Ki, K1 and standardized uptake values (SUV) at the hip and lumbar spine. Methods: Twelve healthy postmenopausal women had age ranging from 52.3 to 70.6 years, bone mineral density (BMD) T-score ranging from −2.9 to 1.4 at the lumbar spine and from −2.4 to 1.7 at the hip. None had any history of metabolic bone disorder or had taken any medications that affected skeletal metabolism. Dynamic 18F-PET scans at the lumbar spine and hip were performed on two separate occasions. The Ki and K1 values obtained using the Hawkins 3-compartment model were compared using Wilcoxon paired signed rank test. Results: The Ki values at the lumber spine vertebral bodies
OPC10 Βeta2-adrenergic receptor signaling in osteoblasts contributes to the catabolic effect of glucocorticoids on bone F. Elefteriou a,⁎, Y. Ma a, J. Nyman b, H. Tao a, H. Moss a, X. Yang a a Medicine, Vanderbilt University, USA b Veteran Affair Hospital, Nashville, USA Abstract: The sympathetic nervous system is a physiological regulator of bone homeostasis. Autonomic nerves are indeed present in bone, bone cells express the b2adrenergic receptors ,b2AR) and pharmacologic or genetic disruption of sympathetic outflow to bone induces bone gain in rodents. These recent findings implied that conditions that affect b2AR signaling in osteoblasts and/or sympathetic drive to bone may contribute to bone diseases. In this study, we show that dexamethasone stimulates the expression of the b2AR in differentiated primary calvarial osteoblasts, as measured by an increased in Adrb2mRNA and b2AR protein level following short-term dexamethasone treatment. Isoproterenolinduced cAMP accumulation and the expression of the b2AR target gene Rankl were also
Abstracts / Bone 48 (2011) S86–S90
OPC05 Identification of a functional variant in the TM7SF4 gene that is associated with susceptibility to paget's disease of bone O.M. Albagha ⁎, S. Wani, S.H. Ralston Molecular Medicine Centre, University of Edinburgh, Edinburgh, UK
Abstract: Paget's disease of bone (PDB) is a common skeletal disorder characterised by focal abnormalities in bone turnover. Genetic factors are important in PDB and mutations in the SQSTM1 gene are found in about 10% of sporadic cases and up to 40% of familial PDB cases. We recently identified variants in the TM7SF4 gene as a genetic risk factors for PDB using a genome wide association study (Albagha et al Nat. Genet. 2010). The most significant association was found for an intronic SNP (P = 7.4 × 10 − 17; OR = 1.4) with no predicted functional effect suggesting that other functional variants are driving the association with PDB risk. TM7SF4 encodes DC-STAMP, a transmembrane protein that plays an essential role in the fusion of osteoclast precursors to form mature osteoclasts. The aim of this study was to identify the functional variant(s) driving the association with PDB risk. The coding region and the putative promoter region of TM7SF4 were sequenced in 50 PDB cases and 10 controls using standard PCR-direct DNA sequencing methods. The identified variants were tested for association with PDB risk in 750 PDB cases and 2700 controls from the UK and significant findings were replicated in a further 500 cases and 500 matched controls. Functional analysis of promoter variants were tested using reporter gene construct experiments. Several variants were identified in the TM7SF4 gene, but a variant in the putative promoter region showed consistent association with PDB risk (combined P = 3.1 × 10 − 8; OR = 1.32). We then investigated the functional effects of this variant using reporter gene construct and results showed that the risk allele increased the expression of a luciferase reporter by 20% compared to the non-risk allele (P = 0.039). In conclusion we have identified a functional variant in the TM7SF4 which was found to enhance reporter gene expression. It is possible that increased DC-STAMP expression could enhance the fusion of osteoclast precursors to form larger and multinucleated osteoclasts which are typically found in Pagetic bone lesions, however further studies will be required to confirm this possibility. This article is part of a Special Issue entitled ECTS 2011. Disclosure of interest: none declared.
doi:10.1016/j.bone.2011.03.120
OPC06 Increased physical activity is associated with optimized development of peak bone mass mainly due to augmented cortical bone size in men: A five year longitudinal study M. Nilsson a, C. Ohlsson a, A. Odén b, D. Mellström a, M. Lorentzon a,⁎ a Institute of Medicine, Sahlgrenska Academy, Centre for Bone and Arthritis Research, Gothenburg University, Sweden b Dept. of Mathematical Sciences, Chalmers University of Technology, Gothenburg, Sweden
Abstract: Aim and background: The role of physical activity on the development of cortical bone geometry and areal bone mineral density (aBMD) in young men has not been established. The aim of this five year longitudinal study of young adult men was to determine whether an increased amount of physical activity was associated with increased bone mass and a favourable development of cortical bone structure. Methods: The original 1068 study subjects, initially included in the Gothenburg Osteoporosis and Obesity study (GOOD), were contacted by letter and telephone and invited to participate in this five year follow-up study. A total of 833 men (78%), 24.1 ± 0.6 years of age, were included. A standardized self administered questionnaire was used to collect information about patterns of physical activity at both the baseline and five year follow-up visit. Areal BMD was measured using dual energy X-ray absorptiometry, whereas volumetric bone mineral density (vBMD) and bone geometry were measured by peripheral quantitative computed tomography. Both baseline and changed (hrs/wk) physical activity were used in a regression model to predict alterations in bone variables. Results: An increased amount of physical activity, between the baseline and follow-up visit, was independently associated with an increase in aBMD of the total body (unstandardized B = 0.002 g/cm 2 per weekly hour increase, p < 0.001) and lumbar spine (B = 0.005, p < 0.001) as well as in cortical cross sectional area at the tibia (B = 0.36 mm 2 per weekly hour increase, p < 0.001). The increased amount of physical activity was also associated with a reduced decrease in aBMD of the total hip (B = 0.004, p < 0.001) as well as in trabecular vBMD (B = 0.590, p < 0.001) at the tibia. Both baseline physical activity and change in physical activity was associated with changes in total hip aBMD (Fig. 1). Conclusion: We found that increased physical activity was related to an advantageous development of cortical bone structure and aBMD in young men, indicating that increased physical activity during this age has the ability to prevent the age dependent decline in aBMD at the hip and increase the cortical envelope, having a positive effect on the attainment of peak bone mass in men.
Fig. 1. This article is part of a Special Issue entitled ECTS 2011. Disclosure of interest: None declared. doi:10.1016/j.bone.2011.03.121
OPC07 (For more information visit the Amgen/GlaxoSmithKline scientific booth) Denosumab treatment results in significant trabecular and cortical bone improvements at the hip as assessed by QCT H.K. Genant a,⁎, K. Engelke b, J.R. Zanchetta c, A. Høiseth d, C.K. Yuen e, S. Stonkus f, M.A. Bolognese g, E. Franek h, T. Fuerst i, H.-S. Radcliffe j, C. Libanati k a UCSF/Synarc, Tiduron, USA b Institute of Medical Physics, University of Erlangen, Erlangen, Germany c Instituto de Investigaciones Metabolicas, Buenos Aires, Argentina d Curato Rtg., Oslo, Norway e SIGMA Canadian Menopause Society, Vancouver, Canada f Klaipeda University Hospital, Klaipeda, Lithuania g Bethesda Health Research, Bethesda, USA h MSWiA, Warsaw, Poland i Synarc Inc., San Francisco, USA j Amgen, Inc., Cambridge, UK k Amgen, Inc., Thousand Oaks, USA Abstract: Denosumab, a fully human monoclonal antibody to RANKL, decreased bone resorption, increased bone mineral density (BMD), and reduced new vertebral, nonvertebral, and hip fractures in postmenopausal women with osteoporosis who participated in the FREEDOM trial (Cummings SR et al, NEJM, 2009:361:756). In FREEDOM, subjects received 60 mg denosumab or placebo every 6 months for 3 years; all subjects received daily supplements of calcium and vitamin D. Hip QCT scans were obtained at baseline and at months 12, 24, and 36, in a subset of women. These scans were analyzed, in a blinded-totreatment manner, using Medical Image Analysis Framework (MIAF) software (University of Erlangen, Germany), which has precision errors of 1.5% to 2.5%. MIAF allows the determination of total, trabecular, subcortical, and cortical BMD for the hip, all of which could influence strength differently. The cortical compartment was divided into the outer half (“periosteal”) and inner half (“endosteal”) subregions. We report the magnitude of
Fig. 1. Total hip BMD and BMC mean percent change and 95% Cl.
Abstracts / Bone 48 (2011) S86–S90 changes from baseline and placebo over the 36 months of denosumab treatment in subjects with evaluable hip QCT scans (denosumab n = 36; placebo n = 26). Baseline mean age was 73 years, mean years since menopause was 25, and mean DXA BMD T-score of the total hip was −1.85. Denosumab resulted in significant improvements in QCT total hip BMD and bone mineral content (BMC) from baseline at 12, 24 and 36 months (Fig. 1). Over 36 months, the mean percent change improvements from baseline in QCT total hip BMD and BMC reached 6.3% and 4.8%, respectively (both p < 0.0001). These gains were accounted for by significant increases in BMD and BMC in all cortical and trabecular compartments (Fig. 2). In the placebo group, total hip BMD and BMC decreased at 36 months from baseline by −1.4% and −2.7%, respectively (both p < 0.05). The differences between denosumab and placebo were also highly significant (p < 0.05 to <0.0001) at 12, 24, and 36 months for total, cortical, and trabecular BMD and BMC. In summary, denosumab results in significant improvements from baseline and placebo in both BMD and BMC, assessed by QCT, across total, trabecular, subcortical, and cortical and hip compartments, as well as periosteal and endosteal cortical subregions.
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(mean of L1-L4), total hip outer (including the trabecular and cortical bone), total hip inner (including only the trabecular bone), femoral neck, and cortical shaft (including only cortical bone) were 0.042± 0.008, 0.013 ± 0.005, 0.015 ±0.006, 0.015 ± 0.005, and 0.009± 0.002 ml. min − 1.ml − 1 respectively. The K1 values were 0.15 ± 0.01, 0.044 ± 0.013, 0.048± 0.018, 0.048± 0.017 and 0.036 ± 0.009 ml.min − 1.ml − 1 respectively. The SUVs were 6.0± 1.5, 2.3 ± 0.7, 2.6± 1.0, 2.7 ±1.1 and 1.8± 0.4 respectively. The differences for Ki at spine and any other hip region were significant (p=0.005). The differences among hip regions were also significant (p<0.05) except between femoral neck and total hip (p>0.05). The differences for K1 were significant between lumbar spine and any other hip regain (p=0.005) with no-significant differences among the hip regions (p> 0.05). Conclusion: This is the first study presenting the dynamic quantification of bone turnover and bone blood flow at the hip. We conclude that the bone turnover, perfusion and SUVs are higher in trabecular bone than in cortical bone. Financial support: this work was funded by the Health Research Board in Ireland under grant No: RP/2007/319. This article is part of a Special Issue entitled entitled ECTS 2011. Disclosure of interest: None declared.
doi:10.1016/j.bone.2011.03.123
OPC09 Thyroid hormone status within the euthyroid range is associated with bone mass and density in healthy young men at the age of peak bone mass G.L.L.E. Roef a,⁎, B. Lapauw a, S. Goemaere b, H.-G. Zmierczak b, T. Fiers c, J.-M. Kaufman a, Y. Taes a a Endocrinology, Ghent University Hospital, Ghent, Belgium b Unit for Osteoporosis and Metabolic bone diseases, Ghent University Hospital, Ghent, Belgium c Dpt. of Clinical Chemistry, Ghent University Hospital, Ghent, Belgium
Fig. 2. Hip BMD and BMC Mean Absolute Change and 95% Cl at 36 Months.
This article is part of a Special Issue entitled ECTS 2011. Disclosure of interest: H. Genant Shareholder of Synarc, Grant / Research Support from Merck, GSK, BMS, Roche, Lilly, Amgen, Novartis, Servier, Genentech, Medtronic, Takeda, Consulting fees from Synarc, Merck, GSK, BMS, Roche, Lilly, Amgen, Novartis, Servier, Genentech, Medtronic, Takeda, K. Engelke Employee of Synarc, Grant / Research Support from German Research Society, NIH, Paid Instructor for German Osteology Society, J. Zanchetta Grant / Research Support from Amgen, Eli Lilly, Merck, Pfizer, Advisory Board Membership of Amgen, Eli Lilly, GSK, Merck, Pfizer, Servier, Consulting fees from Amgen, Eli Lilly, GSK, Merck, Pfizer, Servier, A. Høiseth: None Declared, C. K. Yuen Grant / Research Support from Amgen, Merck, Pfizer, P&G, Novartis, Eli Lilly, Bayer, Speakers Bureau with Amgen, Merck, Pfizer, Advisory Board Membership of Amgen, Pfizer, Consulting fees from Amgen, Pfizer, Speaker Fees from Amgen, Merck, Pfizer, S. Stonkus: None Declared, M. Bolognese Grant / Research Support from Amgen, Roche, TARSA, Lilly, Speakers Bureau with Amgen, Lilly, Roche, E. Franek Grant / Research Support from Amgen, Advisory Board Membership of Amgen, Speaker Fees from Amgen, Novartis, Roche, Servier, T. Fuerst Shareholder of Synarc, Employee of Synarc, H.-S. Radcliffe Employee of Amgen, C. Libanati Shareholder of Amgen, Employee of Amgen. doi:10.1016/j.bone.2011.03.122
Abstract: Context: The hormonal factors involved in the regulation of peak bone mass and geometry in men have not been fully investigated. Aside from gonadal steroids and somatotropic hormones, thyroid hormones are known to affect bone maturation and homeostasis, and are additional candidate determinants of adult bone mass. Objective: We aimed to investigate between-subject physiological variation in free and total thyroid hormone concentrations, thyroid-stimulating hormone (TSH) and thyroid binding globulin (TBG) in relation to parameters of bone mass, geometry and mineral density in healthy men at age of peak bone mass. Design and setting: 677 healthy male siblings aged 25–45 yrs were recruited in a cross-sectional, population-based study. Areal and volumetric bone parameters were determined using dual-energy X-ray absorptiometry (DXA) and peripheral quantitative computed tomography (pQCT). Total (TT3, TT4) and free (FT3, FT4) thyroid hormones, TBG and TSH were determined using immunoassays. Results: Free and total thyroid hormone concentrations were inversely associated with areal bone mineral density (aBMD) and bone mineral content (BMC) at the hip and total body (FT3, TT3, TT4) and at the spine (FT3). Thyroid binding globulin (TBG) was negatively associated with BMC and aBMD at all sites. At the radius, cortical bone area was inversely associated with TT3, TT4 and TBG and trabecular bone density was inversely associated with FT4, TT4 and TBG. We observed inverse associations between cortical bone area at the mid-tibia and FT3, TT3, TT4 and TBG. No associations between TSH and DXA- or pQCT-measurements were found. Conclusion: In healthy men at age of peak bone mass, between-subject variation in thyroid hormone concentrations affects bone density and geometry, with higher levels of FT3, TT3, TT4 and TBG being associated with less favourable bone density and content. This article is part of a Special Issue entitled ECTS 2011. Disclosure of interest: None declared. doi:10.1016/j.bone.2011.03.124
OPC08 Bone turnover at the spine and hip measured using 18F-PET T. Puri a,⁎, G.M. Blake b, M.L. Frost b, M. Siddique b, A.E. Moore b, P.K. Marsden b, I. Fogelman b, K.M. Curran a a University College Dublin, Dublin, Ireland b King's College London, London, UK Abstract: Introduction: The imaging technique of 18F-fluoride positron emission tomography ( 18F-PET) allows the non-invasive assessment of regional bone metabolism at clinically important sites such as the hip and lumbar spine and allows the measurement of a number of parameters relating to bone metabolism, for example, regional bone turnover (Ki) and bone blood flow (K1). Purpose: To compare the differences between the Ki, K1 and standardized uptake values (SUV) at the hip and lumbar spine. Methods: Twelve healthy postmenopausal women had age ranging from 52.3 to 70.6 years, bone mineral density (BMD) T-score ranging from −2.9 to 1.4 at the lumbar spine and from −2.4 to 1.7 at the hip. None had any history of metabolic bone disorder or had taken any medications that affected skeletal metabolism. Dynamic 18F-PET scans at the lumbar spine and hip were performed on two separate occasions. The Ki and K1 values obtained using the Hawkins 3-compartment model were compared using Wilcoxon paired signed rank test. Results: The Ki values at the lumber spine vertebral bodies
OPC10 Βeta2-adrenergic receptor signaling in osteoblasts contributes to the catabolic effect of glucocorticoids on bone F. Elefteriou a,⁎, Y. Ma a, J. Nyman b, H. Tao a, H. Moss a, X. Yang a a Medicine, Vanderbilt University, USA b Veteran Affair Hospital, Nashville, USA Abstract: The sympathetic nervous system is a physiological regulator of bone homeostasis. Autonomic nerves are indeed present in bone, bone cells express the b2adrenergic receptors ,b2AR) and pharmacologic or genetic disruption of sympathetic outflow to bone induces bone gain in rodents. These recent findings implied that conditions that affect b2AR signaling in osteoblasts and/or sympathetic drive to bone may contribute to bone diseases. In this study, we show that dexamethasone stimulates the expression of the b2AR in differentiated primary calvarial osteoblasts, as measured by an increased in Adrb2mRNA and b2AR protein level following short-term dexamethasone treatment. Isoproterenolinduced cAMP accumulation and the expression of the b2AR target gene Rankl were also