Eva Åström

Beneficial effect of long term intravenous bisphosphonate treatment of osteogenesis imperfecta

Aim: To find an effective symptomatic treatment for osteogenesis imperfecta (OI). Methods: In a prospective observational study disodium pamidronate (APD) was given as monthly intravenous infusions to 28 children and adolescents (aged 0.6–18 years) with severe OI or a milder form of the disease, but with spinal compression fractures. Results: During treatment for 2–9 years, dual energy x ray absorptiometry measurements of the total body and of the lumbar spine showed a gradual increase in bone density. All bone metabolism variables in serum (alkaline phosphatase, osteocalcin, procollagen 1 C-terminal peptide, collagen 1 teleopeptide) and urine (deoxypyridinoline) indicated that there was a decrease in bone turnover. All patients experienced beneficial effects and the younger patients reported a major improvement in wellbeing, pain, and mobility without significant side effects. Vertebral remodelling was also seen. Conclusions: APD seems to be an efficient symptomatic treatment for children and adolescents with OI.

Beneficial effect of bisphosphonate during five years of treatment of severe osteogenesis imperfecta

We report results of 2–5 y treatment with intravenous disodium pamidronate (APD) in three girls with severe osteogenesis imperfecta (OI). Treatment was given as monthly infusions. Additional oral 1,25‐dihydroxy‐cholecalciferol was given to compensate for a transient decrease in serum calcium levels. During treatment, DEXA measurements showed a gradual increase in bone density in all patients. All parameters analysed in serum (ALP, osteocalcin, PICP, ICTP) and in urine (deoxypyridinoline and pyridinoline) showed a decreased bone turnover. The two younger patients reported a major improvement in well‐being, pain and activities of daily life. The effect on the older patient was less pronounced. No negative side effects in clinical or laboratory variables were observed. This study indicates that APD is of value in the symptomatic treatment of children with severe OI.

No osteonecrosis in jaws of young patients with osteogenesis imperfecta treated with bisphosphonates.

BACKGROUND Recent reports of osteonecrosis of the jaw (ONJ) after dental surgery in patients treated with second- and third-generation nitrogen-containing bisphosphonates instigated this retrospective study. As treatment with bisphosphonates in patients with osteogenesis imperfecta (OI) has become an important symptomatic therapy, especially for severe forms of the disease, we found it important to investigate whether healing after surgical exposure of jaw bone was influenced by the bisphosponate treatment in our group of children, adolescents and young adults with OI. SUBJECTS AND METHODS Disodiumpamidronate was given as monthly intravenous infusion to 64 patients with OI aged 3 months to 20.9 years at the start of treatment (mean 8.1, median 7.7). During 0.5-12.5 years of treatment (mean 4.5, median 4.0), a total individual dose of 140-4020 mg/m(2) disodiumpamidronate was given (mean 1623 and median 1460). Ten patients continued with oral alendronate and two with zoledronic acid therapy. In 22 of these patients, 38 dental surgery procedures were performed at the age of 3.4-31.9 years (mean 12.2, median 12.3) after 0.03-7.9 years of treatment (mean 3.6, median 3.4). RESULTS Despite long-term intravenous monthly disodiumpamidronate treatment, none of the 64 patients had any clinical signs of ONJ. CONCLUSIONS The risk of ONJ in these patients must be considered so low that the patients with indications for treatment should be treated and get the chance to experience the well-documented beneficial effect for children with severe OI.

Intravenous pamidronate treatment of infants with severe osteogenesis imperfecta

Objective: Children with the severe forms of osteogenesis imperfecta have in several studies been treated with intravenous pamidronate, but there are only few reports of the effect of early treatment. Aim: To evaluate the effect of treatment started in infancy. Methods: In a prospective observational study, with a historic control group, intravenous disodium pamidronate (APD) was given as monthly infusions to 11 children with osteogenesis imperfecta aged 3–13 (median 3.6) months, who had severe osteogenesis imperfecta with congenital bowing of the femora and vertebral compression fractures. Results: During treatment of children aged between 3 and 6 (median 4.5) years, dual-energy x ray absorptiometry measurements of the lumbar spine showed a gradual increase in bone density. Bone metabolism parameters in serum (alkaline phosphatase, osteocalcin, procollagen 1 carboxy-terminal peptide, collagen 1 teleopeptide) and in urine (deoxypyridinoline) indicated a decrease in bone turnover. An improvement of mobility was seen and at the latest recording, at the age of 3.3–6.5 (median 4.8) years, the children could all walk. Vertebral remodelling was seen, with increased vertebral height, and no child developed scoliosis, kyphosis or basilar impression. All children required femoral intramedullar rods for fractures, and five needed tibial rodding for extreme curvatures that prevented functional standing and walking. No adverse effects were seen on growth, fracture healing or blood chemistry. Conclusions: APD is an efficient symptomatic treatment for infants with severe osteogenesis imperfecta, but additional orthopaedic surgery is often needed. Early treatment may prevent scoliosis and basilar impression. Long-term follow-up is important.

Does loss of spasticity matter? A 10-year follow-up after selective dorsal rhizotomy in cerebral palsy.

Aim  The aim of this study was to evaluate the long‐term effects of selective dorsal rhizotomy (SDR) in children with cerebral palsy (CP).

Genetic epidemiology, prevalence, and genotype–phenotype correlations in the Swedish population with osteogenesis imperfecta

Osteogenesis imperfecta (OI) is a rare hereditary bone fragility disorder, caused by collagen I mutations in 90% of cases. There are no comprehensive genotype–phenotype studies on >100 families outside North America, and no population-based studies determining the genetic epidemiology of OI. Here, detailed clinical phenotypes were recorded, and the COL1A1 and COL1A2 genes were analyzed in 164 Swedish OI families (223 individuals). Averages for bone mineral density (BMD), height and yearly fracture rate were calculated and related to OI and mutation type. N-terminal helical mutations in both the α1- and α2-chains were associated with the absence of dentinogenesis imperfecta (P<0.0001 vs 0.0049), while only those in the α1-chain were associated with blue sclera (P=0.0110). Comparing glycine with serine substitutions, α1-alterations were associated with more severe phenotype (P=0.0031). Individuals with type I OI caused by qualitative vs quantitative mutations were shorter (P<0.0001), but did not differ considering fractures or BMD. The children in this cohort were estimated to represent >95% of the complete Swedish pediatric OI population. The prevalence of OI types I, III, and IV was 5.16, 0.89, and 1.35/100 000, respectively (7.40/100 000 overall), corresponding to what has been estimated but not unequivocally proven in any population. Collagen I mutation analysis was performed in the family of 97% of known cases, with causative mutations found in 87%. Qualitative mutations caused 32% of OI type I. The data reported here may be helpful to predict phenotype, and describes for the first time the genetic epidemiology in >95% of an entire OI population.

Effect of intravenous pamidronate therapy on everyday activities in children with osteogenesis imperfecta

Aim: To evaluate the effect of intravenous pamidronate therapy on everyday activities, well‐being, skeletal pain and bone density in children with osteogenesis imperfecta (OI).

Intravenous Pamidronate Treatment Improves Growth in Prepubertal Osteogenesis Imperfecta Patients

Background/Aims: Pamidronate is widely used to treat pediatric patients with osteogenesis imperfecta (OI). We aimed at delineating the effects of monthly pamidronate therapy on the growth of different body segments in prepubertal OI patients. Methods: The study included 14 prepubertal patients (12 boys, 2 girls) with mild forms of OI (type I and IV). The mean age at treatment start was 7:8 years:months (3:7–11:0). Pamidronate was given as monthly intravenous infusions. The patients were measured 1 year before, at treatment start and 1 and 2 years after treatment start. Results: Height standard deviation score (SDS) and sitting height SDS significantly increased (p < 0.05) during the first year of treatment when compared to the pre-treatment year. No further improvement was detected during the second year of treatment. However, when plotted on disease-specific growth charts (untreated patients with the same OI types), height gain was significant during the first (p < 0.001) and second (p < 0.05) years of treatment. All patients increased their bone mineral density throughout the follow-up. Conclusion: Monthly pamidronate improves the growth of prepubertal patients with mild OI, where the most prominent growth stimulation is seen in the upper body segment.