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Francis H. Glorieux - One of the best experts on this subject based on the ideXlab platform.
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Case Report Maternal and Fetal Outcome After Long-Term Pamidronate Treatment Before Conception: A Report of Two Cases
2020Co-Authors: Craig Fj Munns, Frank Rauch, Leanne Ward, Francis H. GlorieuxAbstract:ABSTRACT: The pregnancies of two women with osteogenesis imperfecta who received intravenous Pamidronate before conception are reported. The mothers suffered no ill effects. One baby had transient asymptomatic hypocalcemia and one had bilateral talipes equinovarus. This report documents the pregnancy outcomes of two women with osteogenesis imperfecta (OI), types I and IV, who received intravenous Pamidronate as part of an observational trial before conception. Pamidronate was not administered after conception. Other than hyperemesis in one woman, the pregnancies and deliveries were uneventful. Both babies inherited OI from their mothers. The baby with OI type IV also had bilateral talipes equinovarus. Biochemical evaluation of the mothers and babies at 24 h and/or 2 weeks postpartum was normal, apart from one baby with asymptomatic hypocalcemia at 24 h of age that had resolved when next measured on day 11 of life. No biochemistry was available on the second child until 13 days of age. Neither baby had skeletal modeling abnormalities consistent with in utero Pamidronate exposure. The lumbar spine (L 1 -L 4 ) areal BMD and anterior to posterior height ratios of lumbar vertebral bodies of both women remained constant during pregnancy. Both the mothers and babies remain well and free of fracture 14 and 16 months postpartum
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Respiratory distress with Pamidronate treatment in infants with severe osteogenesis imperfecta
2020Co-Authors: Craig F. Munns, Richard J. Mier, Frank Rauch, Francis H. GlorieuxAbstract:Abstract This report aims to describe the adverse respiratory events associated with the first Pamidronate cycle in four infants with severe osteogenesis imperfecta (OI) who were less than 2 years of age. Fifty-nine infants with severe OI were commenced on cyclical intravenous Pamidronate therapy in an observation trial. Routine observations were measured during each infusion cycle. During the first treatment cycle, four infants (7%) with preexisting respiratory compromise developed respiratory distress. The respiratory distress was successfully managed with bronchodilator therapy. Two of the infants required intensive care admission. There was no recurrence of respiratory distress with subsequent Pamidronate infusion cycles. In infants with severe OI and preexisting respiratory compromise, the first Pamidronate infusion cycle may be associated with an acute deterioration of respiratory function. The etiology is unclear but may involve cytokine release and/or hemodynamic compromise from fluid administration during the first infusion cycle. Close monitoring throughout the first treatment cycle is of paramount importance. D 2004 Elsevier Inc. All rights reserved
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Osteogenesis Imperfecta Types I, III, and IV: Effect of Pamidronate Therapy on Bone and Mineral Metabolism
2020Co-Authors: Frank Rauch, Horacio Plotkin, Rose Travers, And Leonid Zeitlin, Francis H. GlorieuxAbstract:Cyclical iv therapy with Pamidronate improves the clinical course in children and adolescents with osteogenesis imperfecta (OI). In this study we evaluated the effect of this therapy on bone and mineral metabolism in 165 patients with OI types I, III, and IV (age, 2 wk to 17.9 yr; 86 girls and 79 boys). All patients received iv Pamidronate infusions on 3 successive days, administered at age-dependent intervals of 2-4 months. During the 3 d of the first infusion cycle, serum concentrations of ionized calcium dropped by 0.14 ؎ 0.008 mmol (mean ؎ SE; P < 0.001), and serum PTH levels transiently almost doubled (P < 0.001). At the same time, urinary excretion of the bone resorption marker type I collagen N-telopeptide related to creatinine (uNTX/uCr) decreased by 61-73% (P < 0.001). Two to 4 months later, ionized calcium had returned to pretreatment levels, and uNTX/uCr remained 30 -35% lower than at baseline (P < 0.001). During 4 yr of Pamidronate therapy (n ؍ 40 patients), ionized calcium levels remained stable, but PTH levels increased by about 30% (P < 0.01). uNTX/uCr, expressed as a percentage of the age-and sex-specific mean value in healthy children, decreased from 132 ؎ 13% (mean ؎ SE) at baseline to 49 ؎ 3% after 4 yr of therapy (P < 0.001). In conclusion, serum calcium levels can decrease considerably during and after Pamidronate infusions, requiring close monitoring especially at the first infusion cycle. In long-term therapy, bone turnover is suppressed to levels lower than those in healthy children. Despite the severity of the skeletal findings, there are only subtle abnormalities in routine parameters of bone and mineral metabolism. Serum levels of Ca, inorganic phosphorus (Pi), PTH, and vitamin D metabolites are usually within the reference range (2). However, the activity of cancellous bone remodeling is elevated, as shown by iliac bone histomorphometry (3). Urinary markers of bone resorption are commonly increased (4) and so is the urinary excretion of calcium (uCa) over urinary creatinine (uCr) (4 -6). We and others have previously shown that cyclical iv therapy with the bisphosphonate Pamidronate has a beneficial effect in children and adolescents with severe OI (7-9). Lumbar spine areal bone mineral density and metacarpal cortical width increased, fracture rates decreased, and mobility improved. Markers of bone metabolism decreased during Pamidronate therapy. These studies provided useful information on the biochemical effects of Pamidronate therapy in children with OI, but detailed reports are lacking. This is an important gap in the safety profile of this treatment modality. In the present study we therefore evaluated bone and mineral metabolism in a large group of pediatric OI patients who received Pamidronate therapy
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long bone changes after Pamidronate discontinuation in children and adolescents with osteogenesis imperfecta
Bone, 2007Co-Authors: Frank Rauch, Sylvie Cornibert, Moira S Cheung, Francis H. GlorieuxAbstract:Cyclical intravenous Pamidronate is a widely used symptomatic therapy in moderate to severe osteogenesis imperfecta (OI). The effects of treatment discontinuation on long bone development have not been characterized. In this observational study we used peripheral quantitative computed tomography to assess the radius at the distal metaphysis and at the diaphysis in 23 young OI patients (11 female) who had received Pamidronate for at least 3 years. Measurements were performed twice, at the time of treatment discontinuation (when the age of the patients ranged from 5.9 to 21.3 years) and at an average of 1.9 years (range 1.5 to 2.4 years) later. At the time of Pamidronate discontinuation, all but one of the patients who were below 15 years of age (n=14) had a positive age- and sex-specific z-score for bone mineral content (BMC) at the metaphysis, resulting in a mean z-score of +2.0 (SD=1.0) for this subgroup. In contrast, patients aged 15 years or older (n=9) had an average metaphyseal BMC z-score of �1.5 (SD=1.5). After Pamidronate discontinuation, metaphyseal BMC z-score decreased by an average of 2.4 (SD=2.0) in the whole group. The change in BMC z-score was growth-dependent, as BMC z-scores decreased by about 2 or more in all patients in whom distal radius growth plates were open when Pamidronate was discontinued. In contrast, none of the 11 patients with closed distal radius growth plates experienced a decrease in metaphyseal BMC z-score by more than 2. At the diaphysis, the average BMC z-score was low at the time of the last Pamidronate infusion [z-score �1.7 (SD=1.4)]. After Pamidronate discontinuation, the average diaphyseal BMC z-score decreased by only 0.3 (SD=0.4). In summary,thisstudyshowsthattheeffectofPamidronatediscontinuationismuchlargerattheradialmetaphysisthanatthediaphysisandisdependent on growth. Metaphyseal bone tissue added by longitudinal growth after treatment discontinuation has a lower density than tissue created during treatment. It is possible that this produces zones of localized bone fragility after Pamidronate treatment is stopped in growing children.
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osteogenesis imperfecta type vi in childhood and adolescence effects of cyclical intravenous Pamidronate treatment
Bone, 2007Co-Authors: Christof Land, Frank Rauch, Rose Travers, Francis H. GlorieuxAbstract:Cyclical intravenous treatment with Pamidronate is of clinical benefit in children with moderate to severe osteogenesis imperfecta (OI) types I, III and IV, but there is no information on the effects of this treatment on the newly described OI type VI. Here, we report on the results of 3 years of Pamidronate treatment in 10 children and adolescents with OI type VI (age range 0.8 to 14.5 years, three girls). Treatment effects were compared to those of 10 patients with OI types I, III, and IV, who were matched for age and disease severity (based on height and lumbar spine areal bone mineral density). During Pamidronate therapy, lumbar spine areal bone mineral density z scores increased and lumbar spine vertebral bodies improved in shape. Iliac bone histomorphometry showed a tendency to higher cortical thickness (+53%, P=0.06) but the mineralization defect, a characteristic feature of OI type VI, did not change during Pamidronate treatment. Annualized fracture incidence decreased from 3.1 per year before treatment to 1.4 fractures per year during treatment (P<0.05). Regarding mobility, the Pediatric Evaluation of Disability Inventory gross motor score increased by 42% during Pamidronate treatment (P<0.005). Significant improvements were also found for age-related z scores of maximal isometric grip force. In comparison to the OI control group, the fracture incidence was higher and the gross motor scores were lower in OI type VI, both before and after Pamidronate treatment (P<0.05 for each parameter). No differences were found between the groups for changes in densitometric measures and cortical thickness during Pamidronate treatment. Our results suggest that 3 years of intravenous Pamidronate therapy led to improvements in bone mineral mass, gross motor function, muscle force and fracture incidence in patients with OI type VI. However, the gains in mobility scores and reductions in fracture incidence during Pamidronate treatment are less than in other OI types.
Frank Rauch - One of the best experts on this subject based on the ideXlab platform.
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Case Report Maternal and Fetal Outcome After Long-Term Pamidronate Treatment Before Conception: A Report of Two Cases
2020Co-Authors: Craig Fj Munns, Frank Rauch, Leanne Ward, Francis H. GlorieuxAbstract:ABSTRACT: The pregnancies of two women with osteogenesis imperfecta who received intravenous Pamidronate before conception are reported. The mothers suffered no ill effects. One baby had transient asymptomatic hypocalcemia and one had bilateral talipes equinovarus. This report documents the pregnancy outcomes of two women with osteogenesis imperfecta (OI), types I and IV, who received intravenous Pamidronate as part of an observational trial before conception. Pamidronate was not administered after conception. Other than hyperemesis in one woman, the pregnancies and deliveries were uneventful. Both babies inherited OI from their mothers. The baby with OI type IV also had bilateral talipes equinovarus. Biochemical evaluation of the mothers and babies at 24 h and/or 2 weeks postpartum was normal, apart from one baby with asymptomatic hypocalcemia at 24 h of age that had resolved when next measured on day 11 of life. No biochemistry was available on the second child until 13 days of age. Neither baby had skeletal modeling abnormalities consistent with in utero Pamidronate exposure. The lumbar spine (L 1 -L 4 ) areal BMD and anterior to posterior height ratios of lumbar vertebral bodies of both women remained constant during pregnancy. Both the mothers and babies remain well and free of fracture 14 and 16 months postpartum
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Osteogenesis Imperfecta Types I, III, and IV: Effect of Pamidronate Therapy on Bone and Mineral Metabolism
2020Co-Authors: Frank Rauch, Horacio Plotkin, Rose Travers, And Leonid Zeitlin, Francis H. GlorieuxAbstract:Cyclical iv therapy with Pamidronate improves the clinical course in children and adolescents with osteogenesis imperfecta (OI). In this study we evaluated the effect of this therapy on bone and mineral metabolism in 165 patients with OI types I, III, and IV (age, 2 wk to 17.9 yr; 86 girls and 79 boys). All patients received iv Pamidronate infusions on 3 successive days, administered at age-dependent intervals of 2-4 months. During the 3 d of the first infusion cycle, serum concentrations of ionized calcium dropped by 0.14 ؎ 0.008 mmol (mean ؎ SE; P < 0.001), and serum PTH levels transiently almost doubled (P < 0.001). At the same time, urinary excretion of the bone resorption marker type I collagen N-telopeptide related to creatinine (uNTX/uCr) decreased by 61-73% (P < 0.001). Two to 4 months later, ionized calcium had returned to pretreatment levels, and uNTX/uCr remained 30 -35% lower than at baseline (P < 0.001). During 4 yr of Pamidronate therapy (n ؍ 40 patients), ionized calcium levels remained stable, but PTH levels increased by about 30% (P < 0.01). uNTX/uCr, expressed as a percentage of the age-and sex-specific mean value in healthy children, decreased from 132 ؎ 13% (mean ؎ SE) at baseline to 49 ؎ 3% after 4 yr of therapy (P < 0.001). In conclusion, serum calcium levels can decrease considerably during and after Pamidronate infusions, requiring close monitoring especially at the first infusion cycle. In long-term therapy, bone turnover is suppressed to levels lower than those in healthy children. Despite the severity of the skeletal findings, there are only subtle abnormalities in routine parameters of bone and mineral metabolism. Serum levels of Ca, inorganic phosphorus (Pi), PTH, and vitamin D metabolites are usually within the reference range (2). However, the activity of cancellous bone remodeling is elevated, as shown by iliac bone histomorphometry (3). Urinary markers of bone resorption are commonly increased (4) and so is the urinary excretion of calcium (uCa) over urinary creatinine (uCr) (4 -6). We and others have previously shown that cyclical iv therapy with the bisphosphonate Pamidronate has a beneficial effect in children and adolescents with severe OI (7-9). Lumbar spine areal bone mineral density and metacarpal cortical width increased, fracture rates decreased, and mobility improved. Markers of bone metabolism decreased during Pamidronate therapy. These studies provided useful information on the biochemical effects of Pamidronate therapy in children with OI, but detailed reports are lacking. This is an important gap in the safety profile of this treatment modality. In the present study we therefore evaluated bone and mineral metabolism in a large group of pediatric OI patients who received Pamidronate therapy
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Respiratory distress with Pamidronate treatment in infants with severe osteogenesis imperfecta
2020Co-Authors: Craig F. Munns, Richard J. Mier, Frank Rauch, Francis H. GlorieuxAbstract:Abstract This report aims to describe the adverse respiratory events associated with the first Pamidronate cycle in four infants with severe osteogenesis imperfecta (OI) who were less than 2 years of age. Fifty-nine infants with severe OI were commenced on cyclical intravenous Pamidronate therapy in an observation trial. Routine observations were measured during each infusion cycle. During the first treatment cycle, four infants (7%) with preexisting respiratory compromise developed respiratory distress. The respiratory distress was successfully managed with bronchodilator therapy. Two of the infants required intensive care admission. There was no recurrence of respiratory distress with subsequent Pamidronate infusion cycles. In infants with severe OI and preexisting respiratory compromise, the first Pamidronate infusion cycle may be associated with an acute deterioration of respiratory function. The etiology is unclear but may involve cytokine release and/or hemodynamic compromise from fluid administration during the first infusion cycle. Close monitoring throughout the first treatment cycle is of paramount importance. D 2004 Elsevier Inc. All rights reserved
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long bone changes after Pamidronate discontinuation in children and adolescents with osteogenesis imperfecta
Bone, 2007Co-Authors: Frank Rauch, Sylvie Cornibert, Moira S Cheung, Francis H. GlorieuxAbstract:Cyclical intravenous Pamidronate is a widely used symptomatic therapy in moderate to severe osteogenesis imperfecta (OI). The effects of treatment discontinuation on long bone development have not been characterized. In this observational study we used peripheral quantitative computed tomography to assess the radius at the distal metaphysis and at the diaphysis in 23 young OI patients (11 female) who had received Pamidronate for at least 3 years. Measurements were performed twice, at the time of treatment discontinuation (when the age of the patients ranged from 5.9 to 21.3 years) and at an average of 1.9 years (range 1.5 to 2.4 years) later. At the time of Pamidronate discontinuation, all but one of the patients who were below 15 years of age (n=14) had a positive age- and sex-specific z-score for bone mineral content (BMC) at the metaphysis, resulting in a mean z-score of +2.0 (SD=1.0) for this subgroup. In contrast, patients aged 15 years or older (n=9) had an average metaphyseal BMC z-score of �1.5 (SD=1.5). After Pamidronate discontinuation, metaphyseal BMC z-score decreased by an average of 2.4 (SD=2.0) in the whole group. The change in BMC z-score was growth-dependent, as BMC z-scores decreased by about 2 or more in all patients in whom distal radius growth plates were open when Pamidronate was discontinued. In contrast, none of the 11 patients with closed distal radius growth plates experienced a decrease in metaphyseal BMC z-score by more than 2. At the diaphysis, the average BMC z-score was low at the time of the last Pamidronate infusion [z-score �1.7 (SD=1.4)]. After Pamidronate discontinuation, the average diaphyseal BMC z-score decreased by only 0.3 (SD=0.4). In summary,thisstudyshowsthattheeffectofPamidronatediscontinuationismuchlargerattheradialmetaphysisthanatthediaphysisandisdependent on growth. Metaphyseal bone tissue added by longitudinal growth after treatment discontinuation has a lower density than tissue created during treatment. It is possible that this produces zones of localized bone fragility after Pamidronate treatment is stopped in growing children.
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osteogenesis imperfecta type vi in childhood and adolescence effects of cyclical intravenous Pamidronate treatment
Bone, 2007Co-Authors: Christof Land, Frank Rauch, Rose Travers, Francis H. GlorieuxAbstract:Cyclical intravenous treatment with Pamidronate is of clinical benefit in children with moderate to severe osteogenesis imperfecta (OI) types I, III and IV, but there is no information on the effects of this treatment on the newly described OI type VI. Here, we report on the results of 3 years of Pamidronate treatment in 10 children and adolescents with OI type VI (age range 0.8 to 14.5 years, three girls). Treatment effects were compared to those of 10 patients with OI types I, III, and IV, who were matched for age and disease severity (based on height and lumbar spine areal bone mineral density). During Pamidronate therapy, lumbar spine areal bone mineral density z scores increased and lumbar spine vertebral bodies improved in shape. Iliac bone histomorphometry showed a tendency to higher cortical thickness (+53%, P=0.06) but the mineralization defect, a characteristic feature of OI type VI, did not change during Pamidronate treatment. Annualized fracture incidence decreased from 3.1 per year before treatment to 1.4 fractures per year during treatment (P<0.05). Regarding mobility, the Pediatric Evaluation of Disability Inventory gross motor score increased by 42% during Pamidronate treatment (P<0.005). Significant improvements were also found for age-related z scores of maximal isometric grip force. In comparison to the OI control group, the fracture incidence was higher and the gross motor scores were lower in OI type VI, both before and after Pamidronate treatment (P<0.05 for each parameter). No differences were found between the groups for changes in densitometric measures and cortical thickness during Pamidronate treatment. Our results suggest that 3 years of intravenous Pamidronate therapy led to improvements in bone mineral mass, gross motor function, muscle force and fracture incidence in patients with OI type VI. However, the gains in mobility scores and reductions in fracture incidence during Pamidronate treatment are less than in other OI types.
Horacio Plotkin - One of the best experts on this subject based on the ideXlab platform.
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COMPARABLE BIOAVAILABILITY OF TWO ESOPHAGO-GASTRIC PROTECTIVE FORMULATIONS CONTAINING Pamidronate A CROSS-OVER TRIAL IN HEALTHY YOUNG ADULTS
2020Co-Authors: Emilio J A Roldan, Oscar Quattrocchi, Jose Zanchetta, Horacio Plotkin, Graciela Araujo, Enrique PiccinniAbstract:Abstract The net absorbable amount of Pamidronate (APD), according to AUC values assessed in blood, in the customary dose interval of 24 hours, was found to be similar in 8 healthy young volunteers, who received single doses of 3 capsules of 100 mg APD (AUC 0-24 = 510.3 ± 91.5 µg/Lxh -1 ) and 2 tablets of 150 mg (AUC 0-24 = 580.5 ± 117.6 µg/Lxh -1 ; p= 0.58) in the fasting state. Both formulations present acid-resistant coatings, designed to protect the mucosa of the upper digestive system from contact with insoluble particles of the bisphosphonates. T max values were different, and C max values presented a wide inter-individual variation, so that both formulations were not strictly bioequivalent. However, these latter factors were of minor clinical importance given the kinetic features of the bisphosphonates. In conclusion, both formulations afforded comparable bioavailability; that is to say that they can provide a sufficient amount of APD within the studied dose interval, so as to cause similar clinical effects. Key words: Pamidronate bioavailability, oral bisphosphonates Resumen Biodisponibilidad comparable de dos formulaciones gastroprotectoras que contienen pamidronato. Un estudio cruzado en voluntarios sanos. Las cantidades netas absorbidas de pamidronato (APD), de acuerdo con el área bajo la curva de concentraciones sanguíneas, calculadas en el intervalo de dosis habitual de 24 horas, fueron en promedio similares en 8 voluntarios sanos; quienes en ayuno recibieron dosis únicas de 3 cápsulas de 100 mg APD (AUC 0-24 = 510.3 ± 91.5 µg/Lxh -1 ) y 2 comprimidos de 150 mg (AUC 0-24 = 580.5 ± 117.6 µg/Lxh -1 ; p= 0.58). Ambas formulaciones presentan cubiertas resistentes al medio ácido, diseñadas para proteger las mucosas del sistema digestivo superior del contacto e irritación proveniente de las partículas insolubles del bisfosfonato. Los valores de T max fueron diferentes y los de C max presentaron una amplia variación interindividual, por lo que ambas formulaciones no fueron estrictamente bioequivalentes. De todos modos, estas últimas variables son de una importancia clínica menor teniendo en cuenta las características cinéticas especiales de los bisfosfonatos. En conclusión, ambas formulaciones ofrecen una biodisponibilidad comparable; es decir, pueden proveer suficientes cantidades de APD durante el intervalo de dosis como para promover efectos clínicos similares. Palabras clave: biodisponibilidad del pamidronato, bisfosfonatos orale
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Osteogenesis Imperfecta Types I, III, and IV: Effect of Pamidronate Therapy on Bone and Mineral Metabolism
2020Co-Authors: Frank Rauch, Horacio Plotkin, Rose Travers, And Leonid Zeitlin, Francis H. GlorieuxAbstract:Cyclical iv therapy with Pamidronate improves the clinical course in children and adolescents with osteogenesis imperfecta (OI). In this study we evaluated the effect of this therapy on bone and mineral metabolism in 165 patients with OI types I, III, and IV (age, 2 wk to 17.9 yr; 86 girls and 79 boys). All patients received iv Pamidronate infusions on 3 successive days, administered at age-dependent intervals of 2-4 months. During the 3 d of the first infusion cycle, serum concentrations of ionized calcium dropped by 0.14 ؎ 0.008 mmol (mean ؎ SE; P < 0.001), and serum PTH levels transiently almost doubled (P < 0.001). At the same time, urinary excretion of the bone resorption marker type I collagen N-telopeptide related to creatinine (uNTX/uCr) decreased by 61-73% (P < 0.001). Two to 4 months later, ionized calcium had returned to pretreatment levels, and uNTX/uCr remained 30 -35% lower than at baseline (P < 0.001). During 4 yr of Pamidronate therapy (n ؍ 40 patients), ionized calcium levels remained stable, but PTH levels increased by about 30% (P < 0.01). uNTX/uCr, expressed as a percentage of the age-and sex-specific mean value in healthy children, decreased from 132 ؎ 13% (mean ؎ SE) at baseline to 49 ؎ 3% after 4 yr of therapy (P < 0.001). In conclusion, serum calcium levels can decrease considerably during and after Pamidronate infusions, requiring close monitoring especially at the first infusion cycle. In long-term therapy, bone turnover is suppressed to levels lower than those in healthy children. Despite the severity of the skeletal findings, there are only subtle abnormalities in routine parameters of bone and mineral metabolism. Serum levels of Ca, inorganic phosphorus (Pi), PTH, and vitamin D metabolites are usually within the reference range (2). However, the activity of cancellous bone remodeling is elevated, as shown by iliac bone histomorphometry (3). Urinary markers of bone resorption are commonly increased (4) and so is the urinary excretion of calcium (uCa) over urinary creatinine (uCr) (4 -6). We and others have previously shown that cyclical iv therapy with the bisphosphonate Pamidronate has a beneficial effect in children and adolescents with severe OI (7-9). Lumbar spine areal bone mineral density and metacarpal cortical width increased, fracture rates decreased, and mobility improved. Markers of bone metabolism decreased during Pamidronate therapy. These studies provided useful information on the biochemical effects of Pamidronate therapy in children with OI, but detailed reports are lacking. This is an important gap in the safety profile of this treatment modality. In the present study we therefore evaluated bone and mineral metabolism in a large group of pediatric OI patients who received Pamidronate therapy
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low doses of Pamidronate to treat osteopenia in children with severe cerebral palsy a pilot study
Developmental Medicine & Child Neurology, 2006Co-Authors: Horacio Plotkin, Susan Coughlin, Rose M Kreikemeier, Kathryn Heldt, Matias Bruzoni, Gary LernerAbstract:The aim of this study was to test the efficacy of low doses of Pamidronate in increasing bone mineral density (BMD) in non-ambulatory children and adolescents with cerebral palsy (CP). Twenty-three non-ambulatory children and adolescents (12 females, 11 males; mean age 10y [SD 5y], range 4y 1 mo-17 y 11 mo) with severe spastic quadriplegic CP and low BMD were recruited from a multidisciplinary clinic. Severity of CP was graded at Level IV (n=10) and Level V (n=13) using the Gross Motor Function Classification System. Patients received intravenous Pamidronate (4.12 mg/kg/y, maximum 45 mg/d) every 4 months. Lumbar spine and femoral neck BMD were measured at baseline and after 4 and 12 months. Twelve months after the first dose of Pamidronate there was a significant increase in lumbar spine and femoral neck BMD (p<0.01 for both sites) and z scores compared with baseline values (p<0.01 for both sites). Mean BMD z scores increased 1.6 points for femoral neck and 1.9 points for lumbar spine after 12 months of Pamidronate treatment. Serum intact parathyroid hormone increased significantly and cross-linked N-teleopeptide of type I collagen decreased significantly at 12 months. No significant side effect was noted. Low doses of Pamidronate are well tolerated and significantly increase BMD in non-ambulatory children and adolescents with CP.
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effect of Pamidronate treatment in children with polyostotic fibrous dysplasia of bone
The Journal of Clinical Endocrinology and Metabolism, 2003Co-Authors: Horacio Plotkin, Craig F. Munns, Frank Rauch, Rose Travers, Leonid Zeitlin, Francis H. GlorieuxAbstract:Intravenous infusions with the bisphosphonate compound Pamidronate decrease bone pain and reportedly can lead to refilling of dysplastic lesions in adults with fibrous dysplasia (FD) of bone. Here we describe the effects of this treatment approach in 18 children and adolescents (age at start of therapy, 6.2-17.5 yr; eight girls) with polyostotic FD, who received Pamidronate for 1.2-9.1 yr (median, 3.8 yr). Treatment cycles with Pamidronate (1-1.5 mg/kg.d on 3 consecutive days) were given every 4 months. Levels of serum alkaline phosphatase and urinary collagen type I N-telopeptide were elevated at baseline and decreased continuously during the first 3 yr of therapy. There was no radiographic evidence of filling of lytic lesions or thickening of the bone cortex surrounding the lesions in any patient. Histomorphometric results in dysplastic bone tissue of patients receiving Pamidronate (n = 7; time of therapy, 1.4-4.8 yr) were similar to those of patients without medical therapy (n = 9). No serious side effects were noted. In conclusion, Pamidronate therapy appears to be safe in children and adolescents with polyostotic FD. However, we found no clear evidence that Pamidronate has an effect on dysplastic lesions in such patients.
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height and weight development during four years of therapy with cyclical intravenous Pamidronate in children and adolescents with osteogenesis imperfecta types i iii and iv
Pediatrics, 2003Co-Authors: Leonid Zeitlin, Frank Rauch, Horacio Plotkin, Francis H. GlorieuxAbstract:Objectives. Treatment with Pamidronate improves the clinical course in children with osteogene- sis imperfecta (OI), but theoretically might affect longi- tudinal growth. In this study we analyzed growth during cyclical intravenous Pamidronate treatment in children and adolescents (age .04 -15.6 years at baseline) with moderate to severe forms of OI types I, III, and IV. Methods. The effect of 1 year of Pamidronate treat- ment on height and weight was analyzed in 116 patients (OI-I, N 29; OI-III, N 42; OI-IV, N 45). The results of 4 years of therapy were evaluated in 41 children (OI-I, N 12; OI-III, N 14; OI-IV, N 15). Results. Baseline height was low for age in all OI types. After 1 year of Pamidronate therapy, height z scores had increased significantly in OI-III (by 0.3 0.8, mean standard deviation; P.04) and did not change in OI-I and OI-IV. Weight z scores increased signifi- cantly in OI-I (by 0.2 0.4, P.01). After 4 years of Pamidronate therapy, mean height z scores increased significantly in OI-IV (by 0.41 0.71, P.04), whereas nonsignificant trends to increase were found for OI-I and OI-III. When height was expressed as a percentage of the result expected for untreated patients with the same OI type, long-term Pamidronate therapy was associated with a significant height gain in all 3 OI types (P < .001). Eight patients who reached final height after 3.0 1.0 years of treatment were taller on average than expected for un- treated patients (P.04). Conclusions. Four years of cyclical intravenous pam- idronate treatment led to a significant height gain in moderately to severely affected OI patients. Pediatrics 2003;111:1030 -1036; bisphosphonates, child and adoles- cent, growth, osteogenesis imperfecta, Pamidronate.
Leonid Zeitlin - One of the best experts on this subject based on the ideXlab platform.
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the effect of cyclical intravenous Pamidronate in children and adolescents with osteogenesis imperfecta type v
Bone, 2006Co-Authors: Leonid Zeitlin, Frank Rauch, Craig Munns, Rose Travers, Francis H. GlorieuxAbstract:Intravenous treatment with Pamidronate is beneficial in children and adolescents with moderate to severe forms of osteogenesis imperfecta (OI) types I, III and IV, but there is little information on the effects of this treatment on the newly described OI type V. Here, we describe the results of 2 years of Pamidronate treatment in 11 children and adolescents with OI type V (age at start of therapy 1.8 to 15.0 years; 6 girls). Pamidronate was given in intravenous cycles at a cumulative yearly dose of 9 mg/kg. The first infusion cycle was associated with fever and mild hypocalcemia in most patients, but no other short-term side effects were noted. Two years of Pamidronate treatment led to a decrease in the urinary excretion of N-terminal telopeptide of type I collagen to 50% of baseline levels. Both the size and volumetric bone mineral density of lumbar vertebrae increased compared to age- and sex-matched reference data (P < 0.05 in both cases). Histomorphometry of transiliac bone samples showed an average increase of 86% in cortical thickness (N = 7; P = 0.005). No significant changes with treatment were observed in the age-related z scores of isometric maximal grip force and height. Fracture incidence decreased from 1.5 fractures per year before treatment to 0.5 fractures per year during the fist 2 years of treatment. Ambulation status improved in four patients and remained unchanged in the others. In conclusion, the intravenous Pamidronate therapy has a similar effect in OI type V as it has in the other OI types.
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delayed osteotomy but not fracture healing in pediatric osteogenesis imperfecta patients receiving Pamidronate
Journal of Bone and Mineral Research, 2004Co-Authors: Craig F. Munns, Frank Rauch, Leonid Zeitlin, Francois Fassier, Francis H. GlorieuxAbstract:This study evaluated factors influencing fracture (n 197) and osteotomy (n 200) healing in children with moderate to severe OI. Pamidronate treatment was associated with delayed healing after osteotomy, but not after fracture. The data suggest that both Pamidronate and mechanical factors influence bone healing in this cohort. Introduction: Intravenous Pamidronate is widely used to treat children with moderate to severe osteogenesis imperfecta (OI). However, the effect of this treatment on bone healing is not well characterized. We therefore retrospectively analyzed the healing of lower limb fractures and osteotomies in children with moderate to severe OI, both before and after the start of Pamidronate treatment. Materials and Methods: Bone healing was evaluated on standard radiographs after 197 lower limb fractures (132 femur and 65 tibia) in 82 patients (age at fracture, 0.0 -19.9 years) and 200 intramedullary rodding procedures in 79 patients (age at surgery, 1.2-19.8 years). Delayed healing was diagnosed when a fracture or osteotomy line was at least partially visible 12 months after the event. Results: Delayed fracture healing was observed more frequently during than before Pamidronate treatment. However, the effect of Pamidronate was no longer significant when age differences were taken into account (odds ratio (OR), 1.76; 95% CI, 0.61-5.10). Better mobility status was a strong independent predictor of delayed healing after fractures that occurred during Pamidronate treatment. After osteotomies, delayed healing was more frequent when Pamidronate had been started before surgery (OR, 7.29; 95% CI, 2.62-20.3), and this effect persisted after adjustment for multiple confounders. During Pamidronate treatment, older age (OR per year of age, 1.25; 95% CI, 1.06 -1.47) and osteotomy of the tibia (OR, 3.51; 95% CI, 1.57-7.82) were independent predictors of delayed healing. Conclusions: This study suggests that Pamidronate therapy is associated with delayed healing of osteotomy sites after intramedullary rodding procedures. Better mobility status, but not Pamidronate treatment, seems to be predictive of delayed healing after fractures. J Bone Miner Res 2004;19:1779-1786. Published online on August 23, 2004; doi: 10.1359/JBMR.040814
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effect of Pamidronate treatment in children with polyostotic fibrous dysplasia of bone
The Journal of Clinical Endocrinology and Metabolism, 2003Co-Authors: Horacio Plotkin, Craig F. Munns, Frank Rauch, Rose Travers, Leonid Zeitlin, Francis H. GlorieuxAbstract:Intravenous infusions with the bisphosphonate compound Pamidronate decrease bone pain and reportedly can lead to refilling of dysplastic lesions in adults with fibrous dysplasia (FD) of bone. Here we describe the effects of this treatment approach in 18 children and adolescents (age at start of therapy, 6.2-17.5 yr; eight girls) with polyostotic FD, who received Pamidronate for 1.2-9.1 yr (median, 3.8 yr). Treatment cycles with Pamidronate (1-1.5 mg/kg.d on 3 consecutive days) were given every 4 months. Levels of serum alkaline phosphatase and urinary collagen type I N-telopeptide were elevated at baseline and decreased continuously during the first 3 yr of therapy. There was no radiographic evidence of filling of lytic lesions or thickening of the bone cortex surrounding the lesions in any patient. Histomorphometric results in dysplastic bone tissue of patients receiving Pamidronate (n = 7; time of therapy, 1.4-4.8 yr) were similar to those of patients without medical therapy (n = 9). No serious side effects were noted. In conclusion, Pamidronate therapy appears to be safe in children and adolescents with polyostotic FD. However, we found no clear evidence that Pamidronate has an effect on dysplastic lesions in such patients.
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height and weight development during four years of therapy with cyclical intravenous Pamidronate in children and adolescents with osteogenesis imperfecta types i iii and iv
Pediatrics, 2003Co-Authors: Leonid Zeitlin, Frank Rauch, Horacio Plotkin, Francis H. GlorieuxAbstract:Objectives. Treatment with Pamidronate improves the clinical course in children with osteogene- sis imperfecta (OI), but theoretically might affect longi- tudinal growth. In this study we analyzed growth during cyclical intravenous Pamidronate treatment in children and adolescents (age .04 -15.6 years at baseline) with moderate to severe forms of OI types I, III, and IV. Methods. The effect of 1 year of Pamidronate treat- ment on height and weight was analyzed in 116 patients (OI-I, N 29; OI-III, N 42; OI-IV, N 45). The results of 4 years of therapy were evaluated in 41 children (OI-I, N 12; OI-III, N 14; OI-IV, N 15). Results. Baseline height was low for age in all OI types. After 1 year of Pamidronate therapy, height z scores had increased significantly in OI-III (by 0.3 0.8, mean standard deviation; P.04) and did not change in OI-I and OI-IV. Weight z scores increased signifi- cantly in OI-I (by 0.2 0.4, P.01). After 4 years of Pamidronate therapy, mean height z scores increased significantly in OI-IV (by 0.41 0.71, P.04), whereas nonsignificant trends to increase were found for OI-I and OI-III. When height was expressed as a percentage of the result expected for untreated patients with the same OI type, long-term Pamidronate therapy was associated with a significant height gain in all 3 OI types (P < .001). Eight patients who reached final height after 3.0 1.0 years of treatment were taller on average than expected for un- treated patients (P.04). Conclusions. Four years of cyclical intravenous pam- idronate treatment led to a significant height gain in moderately to severely affected OI patients. Pediatrics 2003;111:1030 -1036; bisphosphonates, child and adoles- cent, growth, osteogenesis imperfecta, Pamidronate.
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bone mass size and density in children and adolescents with osteogenesis imperfecta effect of intravenous Pamidronate therapy
Journal of Bone and Mineral Research, 2003Co-Authors: Frank Rauch, Horacio Plotkin, Leonid Zeitlin, Francis H. GlorieuxAbstract:Cyclical intravenous therapy with Pamidronate improves the clinical course in children and adolescents with osteogenesis imperfecta (OI). In this study, we evaluated the effect of this therapy on lumbar spine bone mass (bone mineral content [BMC]), size (bone volume [BV]), and density (volumetric bone mineral density [vBMD]). Results from 56 patients (age, 0.2–15.9 years; 25 girls) on long-term Pamidronate treatment were compared with those of 167 patients who had not received Pamidronate before densitometry. In all patients who received Pamidronate, BMC, BV, and vBMD increased above levels expected for untreated patients (p < 0.001 in each case). After 4 years of treatment, BMC, BV, and vBMD were 154%, 44%, and 65% higher, respectively, in treated than in untreated patients who were matched for age and OI type. A multiple regression model showed that baseline BMC was negatively associated with the increase in BMC. In conclusion, the bone mass increase in pediatric OI patients receiving Pamidronate is caused by increases in both bone size and density. Patients with larger deficits in bone mass at baseline have a more marked bone mass gain during therapy.
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zoledronic acid reduces skeletal related events in patients with osteolytic metastases a double blind randomized dose response study
Cancer, 2001Co-Authors: James R Berenson, Allan Lipton, Lee S Rosen, Anthony Howell, Robert E Coleman, Lester Porter, Walter Morley, Robert Dreicer, Steven A Kuross, John J SeamanAbstract:BACKGROUND This study evaluated the dose–response relation for zoledronic acid, a new generation high potency bisphosphonate, given as a 5-minute infusion in patients with malignant osteolytic disease. METHODS Two-hundred eighty patients with osteolytic lesions due to metastatic breast carcinoma or multiple myeloma were randomized to double-blind treatment with either 0.4, 2.0, or 4.0 mg of zoledronic acid or 90 mg Pamidronate. The primary efficacy endpoint was the proportion of patients receiving radiation to bone. Other skeletal-related events, bone mineral density (BMD), bone markers, Eastern Cooperative Oncology Group performance status, pain and analgesic scores, and safety also were evaluated. RESULTS Zoledronic acid at doses of 2.0 and 4.0 mg and Pamidronate at a dose of 90 mg each significantly reduced the need for radiation therapy to bone (P < 0.05) in contrast with 0.4 mg zoledronic acid, which did not. Skeletal-related events of any kind, pathologic fractures, and hypercalcemia also occurred less frequently in patients treated with 2.0 or 4.0 mg zoledronic acid or Pamidronate than with 0.4 mg zoledronic acid. Increases in lumbar spine BMD (6.2–9.6%) and decreases in the bone resorption marker N-telopeptide (range, −37.1 to −60.8%) were observed for all treatment groups. Skeletal pain, fatigue, nausea, vomiting, and headache were the most commonly reported adverse events. Adverse events were similar in nature and frequency with zoledronic acid and Pamidronate. CONCLUSIONS A 5-minute infusion of 2.0–4.0 mg zoledronic acid was at least as effective as a 2-hour 90-mg Pamidronate infusion in treatment of osteolytic metastases. A 0.4-mg dose of zoledronic acid was significantly less effective. Both zoledronic acid and Pamidronate were well tolerated. Cancer 2001;91:1191–200. © 2001 American Cancer Society.
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zoledronic acid is superior to Pamidronate in the treatment of hypercalcemia of malignancy a pooled analysis of two randomized controlled clinical trials
Journal of Clinical Oncology, 2001Co-Authors: Pierre Major, Jeanjacques Body, A Lortholary, E Abdi, Gordon B Mills, H D Menssen, F Yunus, R Bell, E Quebefehling, John J SeamanAbstract:PURPOSE: Two identical, concurrent, parallel, multicenter, randomized, double-blind, double-dummy trials were conducted to compare the efficacy and safety of zoledronic acid and Pamidronate for treating hypercalcemia of malignancy (HCM). PATIENTS AND METHODS: Patients with moderate to severe HCM (corrected serum calcium [CSC] ≥ 3.00 mmol/L [12.0 mg/dL]) were treated with a single dose of zoledronic acid (4 or 8 mg) via 5-minute infusion or Pamidronate (90 mg) via 2-hour infusion. A protocol-specified pooled analysis of the two parallel trials was performed. Clinical end points included rate of complete response by day 10, response duration, and time to relapse. RESULTS: Two hundred eighty-seven patients were randomized and evaluated for safety; 275 were evaluated for efficacy. Both doses of zoledronic acid were superior to Pamidronate in the treatment of HCM. The complete response rates by day 10 were 88.4% (P = .002), 86.7% (P = .015), and 69.7% for zoledronic acid 4 mg and 8 mg and Pamidronate 90 mg, re...
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Pamidronate prevents skeletal complications and is effective palliative treatment in women with breast carcinoma and osteolytic bone metastases long term follow up of two randomized placebo controlled trials
Cancer, 2000Co-Authors: Allan Lipton, Richard L Theriault, Gabriel N Hortobagyi, J F Simeone, Robert Knight, Kathleen Mellars, Dirk J Reitsma, Maika Heffernan, John J SeamanAbstract:BACKGROUND Pamidronate therapy previously has been shown to reduce skeletal complications effectively for up to 12 months in breast carcinoma patients with bone metastases. The current study data provide further follow-up results regarding the effects of long term (up to 24 months) Pamidronate treatment in women with breast carcinoma and osteolytic metastases. METHODS Follow-up results from two prospective, multicenter, randomized, double-blind, placebo-controlled intervention trials conducted at academic and community oncology centers were combined to provide a large data set with which to evaluate the long term efficacy and safety of Pamidronate therapy. Seven hundred fifty-four women with Stage IV breast carcinoma and osteolytic metastases were randomized to the 2 treatment arms of the trial. Three patients were excluded from the intent-to-treat population for the analysis. A total of 751 evaluable patients were randomized to receive either a 90-mg intravenous Pamidronate infusion (367 patients) or a placebo infusion (384 patients) every 3–4 weeks. The primary outcome measures were skeletal morbidity rate (events/year), proportion of patients developing a skeletal complication, and time to first skeletal complication. RESULTS Of the 367 women receiving Pamidronate, 115 (31.3%) completed the trial and 81 (22.1%) discontinued the study due to adverse events. Of the 384 women who received placebo, 100 (26.0%) completed the study and 76 (19.8%) discontinued the study due to adverse events. The skeletal morbidity rate was 2.4 in the Pamidronate group and 3.7 in the placebo group (P < 0.001). In the Pamidronate group, 186 of the 367 patients (51%) had skeletal complications compared with 246 of the 384 patients in the placebo group (64%) (P < 0.001). The median time to first skeletal complication was 12.7 months in the Pamidronate group and 7 months in the placebo group (P < 0.001). Six patients treated with Pamidronate discontinued treatment due to drug-related adverse events. Pain and analgesic scores were significantly worse in the placebo group compared with those patients in the Pamidronate group. CONCLUSIONS In the current study, monthly infusions of 90 mg of Pamidronate as a supplement to antineoplastic therapy were found to be well tolerated and superior to antineoplastic therapy alone in preventing skeletal complications and palliating symptoms for at least 24 months in breast carcinoma patients with osteolytic bone metastases. Cancer 2000;88:1082–90. © 2000 American Cancer Society.
