Archives of physical medicine and rehabilitation, Jan 30, 2015
to determine the functional outcomes associated with long term multidisciplinary treatment; intra... more to determine the functional outcomes associated with long term multidisciplinary treatment; intravenous bisphosphonate treatment, orthopedic surgery and rehabilitation in children with severe osteogenesis imperfecta (OI) (diagnosed clinically as OI type III or IV). retrospective study where outcomes were measured prospectively SETTING: pediatric orthopedic hospital PARTICIPANTS: 41 adolescents (age 15 to 21 years), with severe OI (OI type III, N = 17; OI type IV, N = 24) who had started therapy before the age of 6 years and had received treatment for at least 10 years and had achieved final height. intravenous bisphosphonate treatment, orthopedic surgery and rehabilitation MAIN OUTCOME MEASURE: Pediatric Evaluation of Disability Inventory (PEDI) RESULTS: At the time of the last available follow-up examination none of the individuals diagnosed with OI type III (the most severely affected group) was able to ambulate without ambulation aids, whereas 20 (83%) patients with OI type IV we...
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, Jan 8, 2015
Cyclical intravenous bisphosphonate therapy is widely used to treat children with osteogenesis im... more Cyclical intravenous bisphosphonate therapy is widely used to treat children with osteogenesis imperfecta (OI), but little is known about long-term treatment outcomes. We therefore reviewed 37 children with OI (OI type I, N = 1; OI type III, N = 14; OI type IV, N = 22) who started intravenous bisphosphonate therapy before 5 years of age (median 2.2 years; range 0.1 to 4.8 years), and who had a subsequent follow up period of at least 10 years (median 14.8 years; range 10.7 to 18.2 years), during which they had received intravenous bisphosphonate treatment (pamidronate or zoledronic acid) for at least 6 years. During the observation period, the mean lumbar spine areal bone mineral density z-score increased from -6.6 (SD 3.1) to -3.0 (SD 1.8), and weight z-score increased from -2.3 (SD 1.5) to -1.7 (SD 1.7) (P < 0.001 and P = 0.008). At the time of the last assessment, patients with OI type IV had significantly higher height z-scores than a control group of patients matched for age,...
Heparan and chondroitin/dermatan sulfated proteoglycans have a wide range of roles in cellular an... more Heparan and chondroitin/dermatan sulfated proteoglycans have a wide range of roles in cellular and tissue homeostasis including growth factor function, morphogen gradient formation, and co-receptor activity. Proteoglycan assembly initiates with a xylose monosaccharide covalently attached by either xylosyltransferase I or II. Three individuals from two families were found that exhibited similar phenotypes. The index case subjects were two brothers, individuals 1 and 2, who presented with osteoporosis, cataracts, sensorineural hearing loss, and mild learning defects. Whole exome sequence analyses showed that both individuals had a homozygous c.692dup mutation (GenBank: NM_022167.3) in the xylosyltransferase II locus (XYLT2) (MIM: 608125), causing reduced XYLT2 mRNA and low circulating xylosyltransferase (XylT) activity. In an unrelated boy (individual 3) from the second family, we noted low serum XylT activity. Sanger sequencing of XYLT2 in this individual revealed a c.520del mutation...
Osteogenesis Imperfecta (OI) is characterized by bone fragility. At least seven discrete types ha... more Osteogenesis Imperfecta (OI) is characterized by bone fragility. At least seven discrete types have been described ranging from mild disease to a lethal form. In a large number of cases, mutations in one of the two genes encoding type I collagen have been found. In forms recently described (types V, VI, VII), such mutations have been excluded. In two other forms, (Bruck, and osteoporosis - pseudoglioma syndromes) defects in other proteins have been characterized. In OI, bone fragility stems from: decreased bone mass, disturbed organization of bone tissue, and altered bone geometry (size and shape). Histologic studies have shown that increased bone turnover is the rule in OI bone. This justifies using bisphosphonates in order to reduce osteoclast mediated bone resorption. Initial results are encouraging. Cyclical intravenous pamidronate administration reduces bone pain and fracture incidence, and increases bone density and level of ambulation, with minimal side effects. Effects on bone include increase in size of vertebral bodies and thickening of cortical bone. These results allow for more efficacious corrective surgery using intramedullary rodding of the long bones and paravertegral instrumentation. Specific occupational and physiotherapy programs are integral parts of the treatment protocol. This multidisciplinary approach will prevail until strategies aiming at the correction of the basic defect(s) will have come to fruition.
The charts and radiographs of 159 children with osteogenesis imperfecta (OI) were retrospectively... more The charts and radiographs of 159 children with osteogenesis imperfecta (OI) were retrospectively reviewed to measure the severity of upper limb deformities and to evaluate the functional outcome using the Pediatric Evaluation of Disability Inventory (PEDI). The patients were classified according to the Sillence classification modified by Glorieux: 51 type 1, 33 type 3, 54 type 4, and 21 5ype 5. Fifty-nine patients (37.1%) had deformities of their upper limbs. Children with type 3 OI had the highest incidence and the most severe deformities. The humerus was the most commonly involved bone, followed by the ulna and radius. Upper limb deformities were classified into four groups according to the severity of the maximum deformity angle. The mean self-care scores of PEDI were significantly low only in the group with severe deformities, but mobility scores were dramatically decreased in both the moderate and severe deformity groups. Therefore, upper limb deformities in children with OI do not represent only a cosmetic problem, but may also significantly impair functional activities of daily living.
Distraction through the physis (chondrodiatasis) is a controversial technique with unpredictable ... more Distraction through the physis (chondrodiatasis) is a controversial technique with unpredictable results. However, it has been used in the past for the lengthening and correction of angular deformities of long bones. We report the case of an 11-year-old patient with spondyloepimetaphyseal dysplasia (SEMD) who presented with a severe recurvatum deformity of the left proximal tibia secondary to collapse of the tibial plateau into a large metaphyseal cystic lesion. Using the chondrodiatasis technique with a percutaneously applied Ilizarov circular frame, we were able to correct this deformity. Surprisingly, healing and ossification of the metaphyseal lesion was simultaneously observed at the end of the treatment, a finding which, to the best of our knowledge, has not been previously reported.
Osteochondrodysplasias are a heterogeneous group of genetic skeletal dysplasias. Patients with th... more Osteochondrodysplasias are a heterogeneous group of genetic skeletal dysplasias. Patients with these diseases commonly develop an early degenerative arthritis or osteoarthritis. Occasional observations of inflammatory arthritis have been made in this population but such observations are based on clinical grounds alone without confirmatory imaging studies. Four patients followed up in a paediatric rheumatology clinic with three different skeletal dysplasias, who had both clinical and radiological evidence of an inflammatory arthritis and coexistent degenerative arthritis, are described.
A decade ago our group had reported that osteotomy healing was commonly delayed in children with ... more A decade ago our group had reported that osteotomy healing was commonly delayed in children with moderate to severe osteogenesis imperfecta (OI) who were treated with intravenous pamidronate infusions. We subsequently maintained a bisphosphonate infusion-free interval of four months following osteotomy and changed the surgical approach (use of an osteotome instead of a power saw). In addition, zoledronic acid has become the standard intravenous bisphosphonate for treatment of OI at our institution. In the present study, we compared osteotomy healing before and after these changes were instituted. We evaluated bone healing post-osteotomy on standard radiographs after 261 intramedullary rodding procedures involving osteotomies (139 femur, 112 tibia) in 110 patients (age at surgery 1.2 to 20.4 years). Delayed healing was diagnosed when the osteotomy line was visible 12 months after the event. We observed delayed bone healing after 48 of the 114 osteotomies (42%) performed with the new approach, and in 106 of the 147 osteotomies (72%) using the previous approach (P = 0.001). The odds for delayed osteotomy healing were significantly lower with the new approach even after adjustment for age, gender, height z-score, weight z-score, OI type and bone involved (odds ratio, 0.17; 95% confidence interval, 0.16-0.47). Thus, delayed osteotomy healing occurred less frequently in the past ten years than in the decade before that. It is likely that this improved result is due to the implemented changes in both medical and surgical management. This article is protected by copyright. All rights reserved.
Archives of physical medicine and rehabilitation, Jan 30, 2015
to determine the functional outcomes associated with long term multidisciplinary treatment; intra... more to determine the functional outcomes associated with long term multidisciplinary treatment; intravenous bisphosphonate treatment, orthopedic surgery and rehabilitation in children with severe osteogenesis imperfecta (OI) (diagnosed clinically as OI type III or IV). retrospective study where outcomes were measured prospectively SETTING: pediatric orthopedic hospital PARTICIPANTS: 41 adolescents (age 15 to 21 years), with severe OI (OI type III, N = 17; OI type IV, N = 24) who had started therapy before the age of 6 years and had received treatment for at least 10 years and had achieved final height. intravenous bisphosphonate treatment, orthopedic surgery and rehabilitation MAIN OUTCOME MEASURE: Pediatric Evaluation of Disability Inventory (PEDI) RESULTS: At the time of the last available follow-up examination none of the individuals diagnosed with OI type III (the most severely affected group) was able to ambulate without ambulation aids, whereas 20 (83%) patients with OI type IV we...
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, Jan 8, 2015
Cyclical intravenous bisphosphonate therapy is widely used to treat children with osteogenesis im... more Cyclical intravenous bisphosphonate therapy is widely used to treat children with osteogenesis imperfecta (OI), but little is known about long-term treatment outcomes. We therefore reviewed 37 children with OI (OI type I, N = 1; OI type III, N = 14; OI type IV, N = 22) who started intravenous bisphosphonate therapy before 5 years of age (median 2.2 years; range 0.1 to 4.8 years), and who had a subsequent follow up period of at least 10 years (median 14.8 years; range 10.7 to 18.2 years), during which they had received intravenous bisphosphonate treatment (pamidronate or zoledronic acid) for at least 6 years. During the observation period, the mean lumbar spine areal bone mineral density z-score increased from -6.6 (SD 3.1) to -3.0 (SD 1.8), and weight z-score increased from -2.3 (SD 1.5) to -1.7 (SD 1.7) (P < 0.001 and P = 0.008). At the time of the last assessment, patients with OI type IV had significantly higher height z-scores than a control group of patients matched for age,...
Heparan and chondroitin/dermatan sulfated proteoglycans have a wide range of roles in cellular an... more Heparan and chondroitin/dermatan sulfated proteoglycans have a wide range of roles in cellular and tissue homeostasis including growth factor function, morphogen gradient formation, and co-receptor activity. Proteoglycan assembly initiates with a xylose monosaccharide covalently attached by either xylosyltransferase I or II. Three individuals from two families were found that exhibited similar phenotypes. The index case subjects were two brothers, individuals 1 and 2, who presented with osteoporosis, cataracts, sensorineural hearing loss, and mild learning defects. Whole exome sequence analyses showed that both individuals had a homozygous c.692dup mutation (GenBank: NM_022167.3) in the xylosyltransferase II locus (XYLT2) (MIM: 608125), causing reduced XYLT2 mRNA and low circulating xylosyltransferase (XylT) activity. In an unrelated boy (individual 3) from the second family, we noted low serum XylT activity. Sanger sequencing of XYLT2 in this individual revealed a c.520del mutation...
Osteogenesis Imperfecta (OI) is characterized by bone fragility. At least seven discrete types ha... more Osteogenesis Imperfecta (OI) is characterized by bone fragility. At least seven discrete types have been described ranging from mild disease to a lethal form. In a large number of cases, mutations in one of the two genes encoding type I collagen have been found. In forms recently described (types V, VI, VII), such mutations have been excluded. In two other forms, (Bruck, and osteoporosis - pseudoglioma syndromes) defects in other proteins have been characterized. In OI, bone fragility stems from: decreased bone mass, disturbed organization of bone tissue, and altered bone geometry (size and shape). Histologic studies have shown that increased bone turnover is the rule in OI bone. This justifies using bisphosphonates in order to reduce osteoclast mediated bone resorption. Initial results are encouraging. Cyclical intravenous pamidronate administration reduces bone pain and fracture incidence, and increases bone density and level of ambulation, with minimal side effects. Effects on bone include increase in size of vertebral bodies and thickening of cortical bone. These results allow for more efficacious corrective surgery using intramedullary rodding of the long bones and paravertegral instrumentation. Specific occupational and physiotherapy programs are integral parts of the treatment protocol. This multidisciplinary approach will prevail until strategies aiming at the correction of the basic defect(s) will have come to fruition.
The charts and radiographs of 159 children with osteogenesis imperfecta (OI) were retrospectively... more The charts and radiographs of 159 children with osteogenesis imperfecta (OI) were retrospectively reviewed to measure the severity of upper limb deformities and to evaluate the functional outcome using the Pediatric Evaluation of Disability Inventory (PEDI). The patients were classified according to the Sillence classification modified by Glorieux: 51 type 1, 33 type 3, 54 type 4, and 21 5ype 5. Fifty-nine patients (37.1%) had deformities of their upper limbs. Children with type 3 OI had the highest incidence and the most severe deformities. The humerus was the most commonly involved bone, followed by the ulna and radius. Upper limb deformities were classified into four groups according to the severity of the maximum deformity angle. The mean self-care scores of PEDI were significantly low only in the group with severe deformities, but mobility scores were dramatically decreased in both the moderate and severe deformity groups. Therefore, upper limb deformities in children with OI do not represent only a cosmetic problem, but may also significantly impair functional activities of daily living.
Distraction through the physis (chondrodiatasis) is a controversial technique with unpredictable ... more Distraction through the physis (chondrodiatasis) is a controversial technique with unpredictable results. However, it has been used in the past for the lengthening and correction of angular deformities of long bones. We report the case of an 11-year-old patient with spondyloepimetaphyseal dysplasia (SEMD) who presented with a severe recurvatum deformity of the left proximal tibia secondary to collapse of the tibial plateau into a large metaphyseal cystic lesion. Using the chondrodiatasis technique with a percutaneously applied Ilizarov circular frame, we were able to correct this deformity. Surprisingly, healing and ossification of the metaphyseal lesion was simultaneously observed at the end of the treatment, a finding which, to the best of our knowledge, has not been previously reported.
Osteochondrodysplasias are a heterogeneous group of genetic skeletal dysplasias. Patients with th... more Osteochondrodysplasias are a heterogeneous group of genetic skeletal dysplasias. Patients with these diseases commonly develop an early degenerative arthritis or osteoarthritis. Occasional observations of inflammatory arthritis have been made in this population but such observations are based on clinical grounds alone without confirmatory imaging studies. Four patients followed up in a paediatric rheumatology clinic with three different skeletal dysplasias, who had both clinical and radiological evidence of an inflammatory arthritis and coexistent degenerative arthritis, are described.
A decade ago our group had reported that osteotomy healing was commonly delayed in children with ... more A decade ago our group had reported that osteotomy healing was commonly delayed in children with moderate to severe osteogenesis imperfecta (OI) who were treated with intravenous pamidronate infusions. We subsequently maintained a bisphosphonate infusion-free interval of four months following osteotomy and changed the surgical approach (use of an osteotome instead of a power saw). In addition, zoledronic acid has become the standard intravenous bisphosphonate for treatment of OI at our institution. In the present study, we compared osteotomy healing before and after these changes were instituted. We evaluated bone healing post-osteotomy on standard radiographs after 261 intramedullary rodding procedures involving osteotomies (139 femur, 112 tibia) in 110 patients (age at surgery 1.2 to 20.4 years). Delayed healing was diagnosed when the osteotomy line was visible 12 months after the event. We observed delayed bone healing after 48 of the 114 osteotomies (42%) performed with the new approach, and in 106 of the 147 osteotomies (72%) using the previous approach (P = 0.001). The odds for delayed osteotomy healing were significantly lower with the new approach even after adjustment for age, gender, height z-score, weight z-score, OI type and bone involved (odds ratio, 0.17; 95% confidence interval, 0.16-0.47). Thus, delayed osteotomy healing occurred less frequently in the past ten years than in the decade before that. It is likely that this improved result is due to the implemented changes in both medical and surgical management. This article is protected by copyright. All rights reserved.
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