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Icaritin scaffolds for repairing steroid-associated osteonecrosis lesion
Abstracts / Bone 45 (2009) S59–S111
PF-29 Abnormally high bone mineralization in children with osteogenesis imperfecta is neither associated with specific collagen mutations nor with clinical severity of the disease N. Fratzl-Zelmana, P. Roschgera, B.M. Misofa, F. Rauchb, F.H. Glorieuxb, K. Klaushofera a Ludwig Boltzmann Institute of Osteology, Hanusch Hospital of WGKK and AUVA Trauma Centre Meidling, 4th Medical Dept., Hanusch Hospital, Vienna, Austria b Genetic Unit, Shriners Hospital for Children and McGill University, Montreal, Canada Osteogenesis imperfecta (OI) is a genetically and clinically heterogeneous disease with low bone mass and increased bone fragility. The disorder is often caused by mutations of the type I collagen genes leading to different clinical severity (OI I–IV). At the clinical level, OI-I represents the mild non-deforming form that results either from quantitative mutations that lead to a decreased amount of normal collagen or qualitative mutations where structural aberrant collagen chains are generated. OI-III and OI-IV represent the severe and moderately deforming phenotype respectively. More recently, new forms of OIs with no primary collagen defect have been defined (types V–VII). In particular, OI type VII was characterized as moderately to severely deforming form of OI, resulting from a severe reduction in the expression of cartilage-associated protein (CRTAP) a cofactor, which is crucial for the proper post-translational chain synthesis and helix formation of collagen. The phenotypic consequences of a particular mutation at the bone material level are not fully understood. In the present study, we compared bone mineralization density distribution (BMDD, measured by quantitative backscattered electron imaging) in bone biopsies from affected children (N = 34, age 2 to 17.5 years) with specimens from a control population (N = 54, age 1.5 to 23 years). The analyses revealed that the mean calcium content (Ca Mean) in each group was significantly higher than in controls: OI type I, quantitative mutation, N = 13: + 7.4%, p < 0.001; OI-I, qualitative mutation, N = 6; + 6.4%, p < 0.001; OI-III, N = 3: +7.3%, p < 0.01; OIIV, N = 8: +7.9%, p < 0.001; OI-VII, N = 4: +3.3%, p < 0.05. In addition, there was no statistical difference between both OI-I forms and between OI-III, IV and VII and OI-1. The results show that bone matrix in children with OI is abnormally highly mineralized, and that this effect is independent of type I collagen alterations, and clinical severity. doi:10.1016/j.bone.2009.04.175
PF-30 In vitro release of osteoinductive molecule Icaritin from porous PLGA/TCP/Icaritin scaffolds for repairing steroid-associated osteonecrosis lesion X.-L. Wanga, G. Zhanga, X.-H. Xiea, K.-M. Leea, G. Lia, X.-O. Wangb, X.-S. Yaoc, Y. Lengd, K.-S. Leunga, L. Qina a Musculoskeletal Research Laboratory, Department of Orthopaedics and Traumatology, the Chinese University of Hong Kong, Shatin, N.T., Hong Kong b Department of Mechanical Engineering, Centre of Laser Rapid Forming, Tsinghua University, Beijing, China c Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy, Jinan University, Guangzhou, China d Department of Physics and the Institute of Nano Science and Technology, The Hong Kong University of Science and Technology, Kowloon, Hong Kong Introduction: Tissue engineering strategy for repairing steroidassociated osteonecrosis lesion requires both qualified platform and
S105
factor for osteogenesis. Our pilot study showed that PLGA/TCP (poly lactic-co-glycolic acid and tricalcium phosphate) was a promising porous scaffold biomaterial with needed mechanical strength for orthopaedics applications. On the other hand, bone strengthening herb-derived small molecule Icaritin with stable chemical property (compared to BMP) demonstrated osteoinductive potential, evidenced by the finding in our recently finished muscle pouch model. Taken together, the investigators produced PLGA/TCP composite material with incorporation of Icaritin before employing it for repairing steroid-associated osteonecrosis lesion. However, the release behaviour of Icaritin from PLGA/TCP/Icaritin composite scaffold remained unclear. The aim of the study was to address the question. Methods: Approximately 25 mg of scaffold at three different Icaritin concentrations (7 × 10− 4 M, 7 × 10− 5 M, 7 × 10− 6 M) was added to a test tube with 5 ml phosphate buffered saline (PBS, pH 7.4) inside, respectively. The resultant mixture was placed in an orbital shaker bath at 37 °C, 120 rpm. One millilitre of sample mixture was extracted at specific time intervals from each test tube within 60 days, and an equal volume of fresh buffer was for supplement. HPLC was used to test the concentration of Icaritin inside the PBS solutions at 270 nm. Results: During the 60 days examined, the first phase was described as an initial burst lasting about 5 days, which was attributed to the diffusion of Icaritin from the PLGA/TCP scaffold. Following the initial phase, there was a slow and constant Icaritin release due to the erosion of the PLGA/TCP scaffold. The behaviour of both the release amount and release rate showed dose-dependent pattern. Conclusion: Icaritin could be controlled and sustained release from the PLGA/TCP/Icaritin scaffold, which is essential to facilitate achieving the tissue engineering strategy for repairing steroidassociated osteonecrosis lesion. doi:10.1016/j.bone.2009.04.176
PF-31 A randomised trial investigating an exercise programme to prevent reduction of bone mineral density and impairment of motor performance during treatment for childhood acute lymphoblastic leukaemia M.L. te Winkela, A. Hartmana, R.D. van Beeka, S.M.P.F. de Muinck Keizer-Schramaa, H.C.G. Kemperb, W. Hopc, M.M. van den HeuvelEibrinka, R. Pietersa a Erasmus MC-Sophia Children's Hospital, Rotterdam, Netherlands b EMGO Institute VU University Medical Center, Amsterdam, Netherlands c Erasmus MC, Rotterdam, Netherlands Reduced bone mineral density (BMD), altered body composition, impaired motor performance and passive ankle dorsiflexion are side effects of acute lymphoblastic leukaemia (ALL) treatment. We performed a randomised study investigating whether an exercise programme could prevent these side effects. At diagnosis, 51 ALL patients (median age: 5.4 years) were randomised into a group receiving a two-year exercise programme (including twice-daily highintensity weight-bearing activities) or a control group receiving standard care. BMD of total body (BMDTB), lumbar spine (BMDLS) and body composition were measured using dual energy X-ray absorptiometry. Motor performance was measured with Bayley Scales of Infant Development/Movement-ABC, and passive ankle dorsiflexion with a goniometer. The investigator was blinded to the randomisation. Repeated measurements analysis (ANOVA) was used. Body fat increased equally during treatment in both the intervention and control group (Δfat: 1.04 SDS vs. 1.56 SDS, p = 0.25). One year after
PF-29 Abnormally high bone mineralization in children with osteogenesis imperfecta is neither associated with specific collagen mutations nor with clinical severity of the disease N. Fratzl-Zelmana, P. Roschgera, B.M. Misofa, F. Rauchb, F.H. Glorieuxb, K. Klaushofera a Ludwig Boltzmann Institute of Osteology, Hanusch Hospital of WGKK and AUVA Trauma Centre Meidling, 4th Medical Dept., Hanusch Hospital, Vienna, Austria b Genetic Unit, Shriners Hospital for Children and McGill University, Montreal, Canada Osteogenesis imperfecta (OI) is a genetically and clinically heterogeneous disease with low bone mass and increased bone fragility. The disorder is often caused by mutations of the type I collagen genes leading to different clinical severity (OI I–IV). At the clinical level, OI-I represents the mild non-deforming form that results either from quantitative mutations that lead to a decreased amount of normal collagen or qualitative mutations where structural aberrant collagen chains are generated. OI-III and OI-IV represent the severe and moderately deforming phenotype respectively. More recently, new forms of OIs with no primary collagen defect have been defined (types V–VII). In particular, OI type VII was characterized as moderately to severely deforming form of OI, resulting from a severe reduction in the expression of cartilage-associated protein (CRTAP) a cofactor, which is crucial for the proper post-translational chain synthesis and helix formation of collagen. The phenotypic consequences of a particular mutation at the bone material level are not fully understood. In the present study, we compared bone mineralization density distribution (BMDD, measured by quantitative backscattered electron imaging) in bone biopsies from affected children (N = 34, age 2 to 17.5 years) with specimens from a control population (N = 54, age 1.5 to 23 years). The analyses revealed that the mean calcium content (Ca Mean) in each group was significantly higher than in controls: OI type I, quantitative mutation, N = 13: + 7.4%, p < 0.001; OI-I, qualitative mutation, N = 6; + 6.4%, p < 0.001; OI-III, N = 3: +7.3%, p < 0.01; OIIV, N = 8: +7.9%, p < 0.001; OI-VII, N = 4: +3.3%, p < 0.05. In addition, there was no statistical difference between both OI-I forms and between OI-III, IV and VII and OI-1. The results show that bone matrix in children with OI is abnormally highly mineralized, and that this effect is independent of type I collagen alterations, and clinical severity. doi:10.1016/j.bone.2009.04.175
PF-30 In vitro release of osteoinductive molecule Icaritin from porous PLGA/TCP/Icaritin scaffolds for repairing steroid-associated osteonecrosis lesion X.-L. Wanga, G. Zhanga, X.-H. Xiea, K.-M. Leea, G. Lia, X.-O. Wangb, X.-S. Yaoc, Y. Lengd, K.-S. Leunga, L. Qina a Musculoskeletal Research Laboratory, Department of Orthopaedics and Traumatology, the Chinese University of Hong Kong, Shatin, N.T., Hong Kong b Department of Mechanical Engineering, Centre of Laser Rapid Forming, Tsinghua University, Beijing, China c Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy, Jinan University, Guangzhou, China d Department of Physics and the Institute of Nano Science and Technology, The Hong Kong University of Science and Technology, Kowloon, Hong Kong Introduction: Tissue engineering strategy for repairing steroidassociated osteonecrosis lesion requires both qualified platform and
S105
factor for osteogenesis. Our pilot study showed that PLGA/TCP (poly lactic-co-glycolic acid and tricalcium phosphate) was a promising porous scaffold biomaterial with needed mechanical strength for orthopaedics applications. On the other hand, bone strengthening herb-derived small molecule Icaritin with stable chemical property (compared to BMP) demonstrated osteoinductive potential, evidenced by the finding in our recently finished muscle pouch model. Taken together, the investigators produced PLGA/TCP composite material with incorporation of Icaritin before employing it for repairing steroid-associated osteonecrosis lesion. However, the release behaviour of Icaritin from PLGA/TCP/Icaritin composite scaffold remained unclear. The aim of the study was to address the question. Methods: Approximately 25 mg of scaffold at three different Icaritin concentrations (7 × 10− 4 M, 7 × 10− 5 M, 7 × 10− 6 M) was added to a test tube with 5 ml phosphate buffered saline (PBS, pH 7.4) inside, respectively. The resultant mixture was placed in an orbital shaker bath at 37 °C, 120 rpm. One millilitre of sample mixture was extracted at specific time intervals from each test tube within 60 days, and an equal volume of fresh buffer was for supplement. HPLC was used to test the concentration of Icaritin inside the PBS solutions at 270 nm. Results: During the 60 days examined, the first phase was described as an initial burst lasting about 5 days, which was attributed to the diffusion of Icaritin from the PLGA/TCP scaffold. Following the initial phase, there was a slow and constant Icaritin release due to the erosion of the PLGA/TCP scaffold. The behaviour of both the release amount and release rate showed dose-dependent pattern. Conclusion: Icaritin could be controlled and sustained release from the PLGA/TCP/Icaritin scaffold, which is essential to facilitate achieving the tissue engineering strategy for repairing steroidassociated osteonecrosis lesion. doi:10.1016/j.bone.2009.04.176
PF-31 A randomised trial investigating an exercise programme to prevent reduction of bone mineral density and impairment of motor performance during treatment for childhood acute lymphoblastic leukaemia M.L. te Winkela, A. Hartmana, R.D. van Beeka, S.M.P.F. de Muinck Keizer-Schramaa, H.C.G. Kemperb, W. Hopc, M.M. van den HeuvelEibrinka, R. Pietersa a Erasmus MC-Sophia Children's Hospital, Rotterdam, Netherlands b EMGO Institute VU University Medical Center, Amsterdam, Netherlands c Erasmus MC, Rotterdam, Netherlands Reduced bone mineral density (BMD), altered body composition, impaired motor performance and passive ankle dorsiflexion are side effects of acute lymphoblastic leukaemia (ALL) treatment. We performed a randomised study investigating whether an exercise programme could prevent these side effects. At diagnosis, 51 ALL patients (median age: 5.4 years) were randomised into a group receiving a two-year exercise programme (including twice-daily highintensity weight-bearing activities) or a control group receiving standard care. BMD of total body (BMDTB), lumbar spine (BMDLS) and body composition were measured using dual energy X-ray absorptiometry. Motor performance was measured with Bayley Scales of Infant Development/Movement-ABC, and passive ankle dorsiflexion with a goniometer. The investigator was blinded to the randomisation. Repeated measurements analysis (ANOVA) was used. Body fat increased equally during treatment in both the intervention and control group (Δfat: 1.04 SDS vs. 1.56 SDS, p = 0.25). One year after