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Meningiomas with bone invasion: Differential diagnosis with fibrous dysplasia
262
Abstracts
conditions (5 mM Ca), the effect of Al on the NO synthesis either on EC or VSMC was sustained (160% stimulus above control in EC; 48% of inhibition respect to control values in VSMC, p b 0.02). The calcium channel antagonist nifedipine did not modify the bisphosphonate action. However, in CaV conditions, Ral loses its ability to regulate NO synthesis in both cell types. These results suggest that, although both drugs exert a positive effect on vascular homeostasis under physiological conditions, in an unfavorable environment Ral vascular actions were impaired meanwhile Al effects were sustained.
doi:10.1016/j.bone.2014.03.033
Streptococcus mutans growth inhibition by bisphosphonates V.Montangero, E. Roldan, L. Canigia Maimonides University German Hospital, Argentina This study evaluated the in vitro antibacterial activity of three bisphosphonates (olpadronate, pamidronate and etidronate) at two different possible clinical concentrations (1.5% and 3%) against two representative oral pathogens: Streptococcus mutans and Actinobacillus actinomycetemcomitans. The inhibitory capacity of these bisphosphonates was measured by the diffusion method. The inhibition zones surrounding the six resulting bisphosphonates solutions were equal (6.0 ± 0.0 mm) against S. mutans but were different against A. actinomycetemcomitans, showing olpadronate 3% and 1.5% solutions the greatest diameters (19.5 ± 0.7 mm and 15.5 ± 0.7 mm, respectively). The antibacterial action of bisphosphonates was also measured, defining bactericidal activity as a ≥3 log10 CFU/mL decrease and bacteriostatic activity as a ≤2 log10 CFU/mL decrease in the colony count measured at 0, 8 and 24 h after incubation. All six bisphosphonate solutions showed bactericidal activity against A. actinomycetemcomitans after 8 and 24 h of incubation, but only bacteriostatic activity against S. mutans after 24 h of incubation. Therefore, olpadronate, pamidronate and etidronate can inhibit S. mutans growth and development, at concentrations similar to those found in the oral cavity after their administration at clinical oral doses. Hence, it is possible to speculate with a transient antibacterial effect of these bisphosphonates in this localization.
doi:10.1016/j.bone.2014.03.034
Effect of strontium ranelate on bone mass. Follow-up to 3 years L.R. Bruna, A.M. Galichb, L. Maffeic, V. Premrouc, E. Vegad, H. Salernid, M.A. Sarlif, P. Costanzoe, P. Reye, M.S. Larroudég, M.S. Moggiah, M.L. Brancei, A. Sánchezj a Laboratorio de Biología Ósea. Facultad de Ciencias Médicas. UNRosario, Argentina b Servicio de Endocrinología del Hospital Italiano de Buenos Aires, Argentina c Consultorios Asociados de Endocrinología Dra. Laura Maffei. Buenos Aires, Argentina d CESAN, Buenos Aires. Instituto de la Mujer, Campana, Argentina e Consultorios de Investigación Clínica Endocrinológica y del Metabolismo Óseo (CICEMO), Argentina f Instituto de Investigaciones Metabólicas Dr. Zanchetta, Argentina g Hospital César Milstein. Buenos Aires, Argentina h Centro Tiempo. Buenos Aires, Argentina i Centro de Reumatología. Rosario, Argentina j Centro de Endocrinología. Rosario, Argentina Strontium ranelate (SrR) is an effective treatment for osteoporosis. The aim of this study was to evaluate the effect of SrR on bone mineral density (BMD) after 3 years of treatment. In addition, we examined the effect of SrR in patients previously treated with bisphosphonates (BP-prior) compared with patients who received SrR as first drug (BP-naive). This retrospective study included 441 postmenopausal women treated with2 SrR (2 g/day) for at least 1 year, 108 for 2 years and 55 for 3 years. The BMD (g/cm ) was measured by DXA on a GE Lunar Prodigy. Data are expressed as mean ± SEM, and analyzed using the Mann–Whitney test or the Wilcoxon test. Significantly increased in BMD at the lumbar spine (LS), femoral neck (FN) and total hip (TH) was observed at 1, 2 and 3 year of treatment from baseline. 1 year: LS: 3.7 ± 0.2%, FN: 2.3 ± 0.3%, TH: 1.6 ± 0.2%. 2 y: LS: 7.4 ± 0.8%, FN: 4.4 ± 0.6%, TH: 4.8 ± 0.6%. 3 y: LS: 10.3 ± 0.9%, FN: 5.4 ± 0.8%, TH: 6.1& ± 1.0%. BMD was also analyzed in BP-prior (n = 350) and BP-naive (n = 87). The change (%) in BMD after 1 year of treatment with SrR was higher in the BF-naïve: CL: BF-naïve = 4.58 ± 0.62% BFprior = 3.45 ± 0.28% (p = 0.078). CF: BF-naïve = 2.79 ± 0.56% BF-prior = 2.13 ± 0.29% (p = 0.161). CT: BF-naïve = 3.01 ± 0.55% BF-prior = 1.22 ± 0.27% (p = 0.0006). The change (%) after 2 years of treatment showed no difference. In conclusion, treatment with SrR increased BMD and markers of bone formation and decreased bone resorption
markers in the entire group with better response in patients BF-naïve to 1 year of treatment, suggesting that the SrR could be considered as one first-line drug.
doi:10.1016/j.bone.2014.03.035
The VDR is required for α1,25(oh)2-vitamin d3-regulation of the cellular cycle in skeletal muscle cells A.P. Irazoqui, R.L. Boland, C.G. Buitrago Departamento de Biología, Bioquímica y Farmacia, Universidad Nacional del Sur, Bahía Blanca, Argentina We previously reported that the VDR participates in non-transcriptional events triggered by 1,25(OH)2-vitamin D3 [1,25D] in skeletal muscle cells. Furthermore, in separate studies we demonstrated that 1,25D promotes muscle cell proliferation and differentiation, but we did not study in depth the hormone actions on these processes. In this work we present data indicating that the VDR also plays a role in the mechanism by which 1,25D stimulates myogenesis. To investigate VDR involvement in hormone regulation of muscle cell cycle, we significantly reduced its expression by infection of C2C12 murine myoblasts with lentiviral particles containing the pLKO.1 plasmid encoding a shRNA against mouse VDR. The vitamin D receptor was knocked down (80%) in these cells [C2C12 (−VDR)]. Cell cycle studies by flow cytometry using propidium iodide staining evidenced that hormone treatment induced an S-phase peak followed by an arrest in G0/G1 phase, events which were dependent on VDR expression. Investigation of changes in cellular cycle regulating proteins by immunoblotting showed that 1,25D augments cyclin D3 protein levels while cyclin D1 was not modified during G0/G1 arrest of cells. The up-regulation of cyclin D3 by 1,25D was abolished in C2C12 (−VDR). We detected in parallel a 1,25D-dependent acute increase in myogenin expression, implying that the G0/G1 arrest was a pro-differentiating event. In agreement with these observations, the hormone increased the cyclin inhibitors p21Waf1/Cip1 and p27Kip1 in C2C12 wild type cells. The results indicate that the VDR is involved in the control of the cellular cycle by 1,25D in skeletal muscle cells, sustaining the operation of a VDRdependent mechanism in hormone modulation of myogenesis.
doi:10.1016/j.bone.2014.03.036
Effect of cadmium on endochondral ossification in growing animals J. Rodríguez, P.M. Mandalunis Department of Histology and Embryology, School of Dentistry, University of Buenos Aires, Argentina The heavy metal Cadmium (Cd) has gained importance due to its presence in fertilizers and electronic and tobacco industry wastes. There are no experimental studies on the effect of Cd on endochondral ossification in the literature. Thus, the objective of the present study was to evaluate the effect of Cd on endochondral ossification in growing experimental animals. Materials and methods: Fourteen male Wistar rats aged 45 days (65 ± 10 g) were assigned to one of two groups: Cadmium group (Cd), treated with subcutaneous CdCl2 (0.5 mg/kg, Sigma) 5 times a week, for 3 months; and the Control group (C), injected with vehicle only, for the same length of time. Following euthanasia, the tibiae were resected and processed to obtain histological sections, which were stained with H&E. The following histomorphometric parameters were determined on digital microphotographs: subchondral bone volume (BV/TV%), trabecular thickness (Tb.Th) (mm), number of trabeculae (Tb.N) (/mm), space between trabeculae (Tb.Sp) (mm), total thickness of the growth plate cartilage (GPC.Th) (μm), and yellow bone marrow volume (YBM/TV%). The obtained data were analyzed using Student's t test; statistical significance was set at a value of p b 0.05. Results: BV/TV(%): C 14.71 ± 5.28, Cd 9.35 ± 3.07 p b 0.05; (Tb.Th) (mm): C 0.071 ± 0.006, Cd 0.077 ± 0.004 NS; (Tb.N) (/mm): C 2.07 ± 0.76, Cd 1.31 ± 0.26, p b 0.05; (Tb.Sp) (mm): C 0.47 ± 0.19, Cd 0.71 ± 0.17, p b 0.05; GPCTh (μm): C 307 ±34, Cd: 305 ± 27 NS; YBM/TV (%): C 17.81 ± 6.21, Cd 27.64 ± 9.16, p b 0.05. Conclusion: The obtained results indicate that Cd affects trabecular bone tissue formed by endochondral ossification. The increase in yellow bone marrow suggests that Cd may inhibit differentiation of mesenchymal cells and osteoblasts, favoring differentiation into adipocytes, and/or increase bone resorption.
doi:10.1016/j.bone.2014.03.037
Meningiomas with bone invasion: Differential diagnosis with fibrous dysplasia A.M. Galich, M. Buttazzoni Sector: Metabolic Osteopathies, Endocrinology Service Metabolism and Nuclear Medicine, Italian Hospital from Bs.As, Argentina
Abstracts Introduction: Meningioma (MG) is an intracranial benign tumor. It originated in meningothelial cells and it's more common in adults than in children. The sphenoorbital MG represents 9% of all intracranial MG. In general this one produces hyperostosis of the underlying bone and/or dilatation of the maxillary sinus. Bone invasion is not very common. In angiography, they are very vascularized tumors and in the RMN with contrast, there is hyper intensity; this does not happen in the fibrous dysplasia (DF). We describe two clinical cases diagnosed in our hospital. Case 1: a woman aged 62 (RM) treated with hypothyroidism and insulin resistance since 2004. We detected upper right orbital protrusion, increase of eyelid opening and edema of upper eyelid. She had sporadic blurred vision and lagophtalm. In the skull radiography (RxC) we could see bone sclerosis of right orbit proptosis in the right eye without diplopia and lower arciforme scotoma in the right eye. TC showed changes in the bone morphology of the right orbit (temporal and frontal sphenoid) with deviation of extrinsic muscles, displacement of optic nerve and proptosis. We could detect increase of catchment in right fronto-temporal and sphenoid shell, compatible with DF. There was deterioration of CVC in right eye. The lab study of bone and mineral metabolism (MOyM) was normal. Ibandronate (3 mg) was given to the patient and periocular
263
edema improved. Surgical resection with titanium mesh was done. Case 2: a woman aged 55 (BN) with presumptive diagnosis of skull DF. She had right ocular discomfort, occipital headache without visual disturbances. She had edema and right proptosis RxC. TC Skull: image with increase of bone density, in ground glass, in greater wing of right sphenoid. Bone scintigraphy: increase of catchment in right orbit with extention fronto-temporal. RNM: injury that intensifies with contrast, decrease of orbitary space without injuries in NO. Lab studies: MOyM was normal .She was indicated Ibandronate 3 mg IV with improvement of periocular edema. Bone biopsy: infiltration with MG. She was given surgical treatment with exeresis of tumor. Conclusion: The MG with bone invasion is a rare pathology and it is difficult to differentiate of DF and the biopsy of injury was confirmatory. The surgical resection is the chosen treatment. We think that osteocondensantes bone injuries in face and skull suggesting DF should be biopsied even more when RNM shows backing with contrast.
doi:10.1016/j.bone.2014.03.038
Abstracts
conditions (5 mM Ca), the effect of Al on the NO synthesis either on EC or VSMC was sustained (160% stimulus above control in EC; 48% of inhibition respect to control values in VSMC, p b 0.02). The calcium channel antagonist nifedipine did not modify the bisphosphonate action. However, in CaV conditions, Ral loses its ability to regulate NO synthesis in both cell types. These results suggest that, although both drugs exert a positive effect on vascular homeostasis under physiological conditions, in an unfavorable environment Ral vascular actions were impaired meanwhile Al effects were sustained.
doi:10.1016/j.bone.2014.03.033
Streptococcus mutans growth inhibition by bisphosphonates V.Montangero, E. Roldan, L. Canigia Maimonides University German Hospital, Argentina This study evaluated the in vitro antibacterial activity of three bisphosphonates (olpadronate, pamidronate and etidronate) at two different possible clinical concentrations (1.5% and 3%) against two representative oral pathogens: Streptococcus mutans and Actinobacillus actinomycetemcomitans. The inhibitory capacity of these bisphosphonates was measured by the diffusion method. The inhibition zones surrounding the six resulting bisphosphonates solutions were equal (6.0 ± 0.0 mm) against S. mutans but were different against A. actinomycetemcomitans, showing olpadronate 3% and 1.5% solutions the greatest diameters (19.5 ± 0.7 mm and 15.5 ± 0.7 mm, respectively). The antibacterial action of bisphosphonates was also measured, defining bactericidal activity as a ≥3 log10 CFU/mL decrease and bacteriostatic activity as a ≤2 log10 CFU/mL decrease in the colony count measured at 0, 8 and 24 h after incubation. All six bisphosphonate solutions showed bactericidal activity against A. actinomycetemcomitans after 8 and 24 h of incubation, but only bacteriostatic activity against S. mutans after 24 h of incubation. Therefore, olpadronate, pamidronate and etidronate can inhibit S. mutans growth and development, at concentrations similar to those found in the oral cavity after their administration at clinical oral doses. Hence, it is possible to speculate with a transient antibacterial effect of these bisphosphonates in this localization.
doi:10.1016/j.bone.2014.03.034
Effect of strontium ranelate on bone mass. Follow-up to 3 years L.R. Bruna, A.M. Galichb, L. Maffeic, V. Premrouc, E. Vegad, H. Salernid, M.A. Sarlif, P. Costanzoe, P. Reye, M.S. Larroudég, M.S. Moggiah, M.L. Brancei, A. Sánchezj a Laboratorio de Biología Ósea. Facultad de Ciencias Médicas. UNRosario, Argentina b Servicio de Endocrinología del Hospital Italiano de Buenos Aires, Argentina c Consultorios Asociados de Endocrinología Dra. Laura Maffei. Buenos Aires, Argentina d CESAN, Buenos Aires. Instituto de la Mujer, Campana, Argentina e Consultorios de Investigación Clínica Endocrinológica y del Metabolismo Óseo (CICEMO), Argentina f Instituto de Investigaciones Metabólicas Dr. Zanchetta, Argentina g Hospital César Milstein. Buenos Aires, Argentina h Centro Tiempo. Buenos Aires, Argentina i Centro de Reumatología. Rosario, Argentina j Centro de Endocrinología. Rosario, Argentina Strontium ranelate (SrR) is an effective treatment for osteoporosis. The aim of this study was to evaluate the effect of SrR on bone mineral density (BMD) after 3 years of treatment. In addition, we examined the effect of SrR in patients previously treated with bisphosphonates (BP-prior) compared with patients who received SrR as first drug (BP-naive). This retrospective study included 441 postmenopausal women treated with2 SrR (2 g/day) for at least 1 year, 108 for 2 years and 55 for 3 years. The BMD (g/cm ) was measured by DXA on a GE Lunar Prodigy. Data are expressed as mean ± SEM, and analyzed using the Mann–Whitney test or the Wilcoxon test. Significantly increased in BMD at the lumbar spine (LS), femoral neck (FN) and total hip (TH) was observed at 1, 2 and 3 year of treatment from baseline. 1 year: LS: 3.7 ± 0.2%, FN: 2.3 ± 0.3%, TH: 1.6 ± 0.2%. 2 y: LS: 7.4 ± 0.8%, FN: 4.4 ± 0.6%, TH: 4.8 ± 0.6%. 3 y: LS: 10.3 ± 0.9%, FN: 5.4 ± 0.8%, TH: 6.1& ± 1.0%. BMD was also analyzed in BP-prior (n = 350) and BP-naive (n = 87). The change (%) in BMD after 1 year of treatment with SrR was higher in the BF-naïve: CL: BF-naïve = 4.58 ± 0.62% BFprior = 3.45 ± 0.28% (p = 0.078). CF: BF-naïve = 2.79 ± 0.56% BF-prior = 2.13 ± 0.29% (p = 0.161). CT: BF-naïve = 3.01 ± 0.55% BF-prior = 1.22 ± 0.27% (p = 0.0006). The change (%) after 2 years of treatment showed no difference. In conclusion, treatment with SrR increased BMD and markers of bone formation and decreased bone resorption
markers in the entire group with better response in patients BF-naïve to 1 year of treatment, suggesting that the SrR could be considered as one first-line drug.
doi:10.1016/j.bone.2014.03.035
The VDR is required for α1,25(oh)2-vitamin d3-regulation of the cellular cycle in skeletal muscle cells A.P. Irazoqui, R.L. Boland, C.G. Buitrago Departamento de Biología, Bioquímica y Farmacia, Universidad Nacional del Sur, Bahía Blanca, Argentina We previously reported that the VDR participates in non-transcriptional events triggered by 1,25(OH)2-vitamin D3 [1,25D] in skeletal muscle cells. Furthermore, in separate studies we demonstrated that 1,25D promotes muscle cell proliferation and differentiation, but we did not study in depth the hormone actions on these processes. In this work we present data indicating that the VDR also plays a role in the mechanism by which 1,25D stimulates myogenesis. To investigate VDR involvement in hormone regulation of muscle cell cycle, we significantly reduced its expression by infection of C2C12 murine myoblasts with lentiviral particles containing the pLKO.1 plasmid encoding a shRNA against mouse VDR. The vitamin D receptor was knocked down (80%) in these cells [C2C12 (−VDR)]. Cell cycle studies by flow cytometry using propidium iodide staining evidenced that hormone treatment induced an S-phase peak followed by an arrest in G0/G1 phase, events which were dependent on VDR expression. Investigation of changes in cellular cycle regulating proteins by immunoblotting showed that 1,25D augments cyclin D3 protein levels while cyclin D1 was not modified during G0/G1 arrest of cells. The up-regulation of cyclin D3 by 1,25D was abolished in C2C12 (−VDR). We detected in parallel a 1,25D-dependent acute increase in myogenin expression, implying that the G0/G1 arrest was a pro-differentiating event. In agreement with these observations, the hormone increased the cyclin inhibitors p21Waf1/Cip1 and p27Kip1 in C2C12 wild type cells. The results indicate that the VDR is involved in the control of the cellular cycle by 1,25D in skeletal muscle cells, sustaining the operation of a VDRdependent mechanism in hormone modulation of myogenesis.
doi:10.1016/j.bone.2014.03.036
Effect of cadmium on endochondral ossification in growing animals J. Rodríguez, P.M. Mandalunis Department of Histology and Embryology, School of Dentistry, University of Buenos Aires, Argentina The heavy metal Cadmium (Cd) has gained importance due to its presence in fertilizers and electronic and tobacco industry wastes. There are no experimental studies on the effect of Cd on endochondral ossification in the literature. Thus, the objective of the present study was to evaluate the effect of Cd on endochondral ossification in growing experimental animals. Materials and methods: Fourteen male Wistar rats aged 45 days (65 ± 10 g) were assigned to one of two groups: Cadmium group (Cd), treated with subcutaneous CdCl2 (0.5 mg/kg, Sigma) 5 times a week, for 3 months; and the Control group (C), injected with vehicle only, for the same length of time. Following euthanasia, the tibiae were resected and processed to obtain histological sections, which were stained with H&E. The following histomorphometric parameters were determined on digital microphotographs: subchondral bone volume (BV/TV%), trabecular thickness (Tb.Th) (mm), number of trabeculae (Tb.N) (/mm), space between trabeculae (Tb.Sp) (mm), total thickness of the growth plate cartilage (GPC.Th) (μm), and yellow bone marrow volume (YBM/TV%). The obtained data were analyzed using Student's t test; statistical significance was set at a value of p b 0.05. Results: BV/TV(%): C 14.71 ± 5.28, Cd 9.35 ± 3.07 p b 0.05; (Tb.Th) (mm): C 0.071 ± 0.006, Cd 0.077 ± 0.004 NS; (Tb.N) (/mm): C 2.07 ± 0.76, Cd 1.31 ± 0.26, p b 0.05; (Tb.Sp) (mm): C 0.47 ± 0.19, Cd 0.71 ± 0.17, p b 0.05; GPCTh (μm): C 307 ±34, Cd: 305 ± 27 NS; YBM/TV (%): C 17.81 ± 6.21, Cd 27.64 ± 9.16, p b 0.05. Conclusion: The obtained results indicate that Cd affects trabecular bone tissue formed by endochondral ossification. The increase in yellow bone marrow suggests that Cd may inhibit differentiation of mesenchymal cells and osteoblasts, favoring differentiation into adipocytes, and/or increase bone resorption.
doi:10.1016/j.bone.2014.03.037
Meningiomas with bone invasion: Differential diagnosis with fibrous dysplasia A.M. Galich, M. Buttazzoni Sector: Metabolic Osteopathies, Endocrinology Service Metabolism and Nuclear Medicine, Italian Hospital from Bs.As, Argentina
Abstracts Introduction: Meningioma (MG) is an intracranial benign tumor. It originated in meningothelial cells and it's more common in adults than in children. The sphenoorbital MG represents 9% of all intracranial MG. In general this one produces hyperostosis of the underlying bone and/or dilatation of the maxillary sinus. Bone invasion is not very common. In angiography, they are very vascularized tumors and in the RMN with contrast, there is hyper intensity; this does not happen in the fibrous dysplasia (DF). We describe two clinical cases diagnosed in our hospital. Case 1: a woman aged 62 (RM) treated with hypothyroidism and insulin resistance since 2004. We detected upper right orbital protrusion, increase of eyelid opening and edema of upper eyelid. She had sporadic blurred vision and lagophtalm. In the skull radiography (RxC) we could see bone sclerosis of right orbit proptosis in the right eye without diplopia and lower arciforme scotoma in the right eye. TC showed changes in the bone morphology of the right orbit (temporal and frontal sphenoid) with deviation of extrinsic muscles, displacement of optic nerve and proptosis. We could detect increase of catchment in right fronto-temporal and sphenoid shell, compatible with DF. There was deterioration of CVC in right eye. The lab study of bone and mineral metabolism (MOyM) was normal. Ibandronate (3 mg) was given to the patient and periocular
263
edema improved. Surgical resection with titanium mesh was done. Case 2: a woman aged 55 (BN) with presumptive diagnosis of skull DF. She had right ocular discomfort, occipital headache without visual disturbances. She had edema and right proptosis RxC. TC Skull: image with increase of bone density, in ground glass, in greater wing of right sphenoid. Bone scintigraphy: increase of catchment in right orbit with extention fronto-temporal. RNM: injury that intensifies with contrast, decrease of orbitary space without injuries in NO. Lab studies: MOyM was normal .She was indicated Ibandronate 3 mg IV with improvement of periocular edema. Bone biopsy: infiltration with MG. She was given surgical treatment with exeresis of tumor. Conclusion: The MG with bone invasion is a rare pathology and it is difficult to differentiate of DF and the biopsy of injury was confirmatory. The surgical resection is the chosen treatment. We think that osteocondensantes bone injuries in face and skull suggesting DF should be biopsied even more when RNM shows backing with contrast.
doi:10.1016/j.bone.2014.03.038