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-dihydroxycholecalciferol 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.     

Biochemical bone markers in the assessment and pamidronate treatment of children and adolescents with osteogenesis imperfecta

Aim: To assess the role of biochemical bone markers in classification of children with osteogenesis imperfecta (OI), their possible association with vertebral compression fractures in milder forms of OI and their role in monitoring of intravenous pamidronate (APD) treatment. Methods: Serum total alkaline phosphatase (ALP), bone ALP isoforms (in a subgroup), osteocalcin, type I procollagen carboxy‐terminal propeptide, carboxy‐terminal telopeptide of type I collagen, and urine deoxypyridinoline (DPD) were measured in a cross‐sectional study of 130 untreated individuals, 0.25–20.9 years (median 6.7), with OI types I, III and IV. Of those, sixty‐nine were also assessed longitudinally during monthly APD treatment. Bone mineral density (BMD) was measured by dual‐energy X‐ray absorptiometry. Results: Significant differences in bone markers, however not sufficient for individual clinical use, were found in the larger untreated group but not between subgroups with or without vertebral compressions. All bone markers decreased during treatment for 1.0–12.5 years, but with different relative amounts. Changes were not correlated to the improvement in BMD, mobility or pain. Conclusion: Bone markers are, despite significant differences, not useful for the classification of OI type in the individual child and are not associated with vertebral compressions. Serum ALP and urinary DPD are sensitive in monitoring bisphosphonate treatment.     

Osteogenesis imperfecta: anthropometric, skeletal and mineral metabolic effects of long-term intravenous pamidronate therapy

BACKGROUND: Administration of bisphosphonates represents a beneficial therapy in children and adolescents with severe osteogenesis imperfecta (OI) because it significantly reduces the annual rate of bone fractures. AIM: To evaluate the anthropometric, skeletal and mineral metabolic effects of long-term intravenous pamidronate therapy in OI. METHODS: Ten patients, aged 5 mo to 25 y, with OI received cyclical intravenous pamidronate. The yearly dose of pamidronate was approximately 9 mg/kg/d at all ages. Duration of treatment varied from a minimum of 2 y to a maximum of 5 y. Growth, bone mass and mineral metabolic parameters were studied at baseline and repeated every year thereafter. Bone mass was assessed by calculation of bone mineral apparent density (L2-L4 BMAD). This represents the first study on the changes in size-adjusted measures of bone mass observed with such therapy. RESULTS: While on therapy, all children and adolescents grew normally but did not experience any manifest catch-up growth. A significant decrease in the incidence of bone fractures was observed. In seven patients with severe forms, L2-L4 BMAD increased by 80% after the first 2 y of therapy but tended to stabilize or even decrease over the following years despite maintenance of therapy. A significant inverse correlation could be established between urinary Ca excretion and L2-L4 BMAD (r = -0.30, p < 0.05). CONCLUSION: Our results confirm that cyclical pamidronate infusions reduce the incidence of bone fractures and allow normal growth. The improvement in bone mass initially observed after the first 2 y of therapy is not always sustained over the following years despite maintenance of therapy.     

Cyclic pamidronate therapy in children with osteogenesis imperfecta: results of treatment and follow-up after discontinuation

BACKGROUND: Cyclic intravenous pamidronate treatment is widely used for symptomatic therapy of osteogenesis imperfecta (OI). However, data after discontinuation are very limited. AIM: The results of cyclical pamidronate treatment in 14 patients with moderate/severe OI and follow up of six of them after discontinuation are presented to assess the effects of pamidronate and its discontinuation. PATIENTS AND METHODS: Pamidronate was administered at a dosage of 0.5 mg/kg for 3 successive days every 2 months in 14 patients with OI aged 5.10 +/- 3.68 years. Treatment was stopped in six patients after a duration of 16.33 +/- 4.63 months, due to stable bone mineral density (BMD) values and/or no fracture in the last 6 months, or due to family demand. The main outcome measures were areal BMD (aBMD) of the lumbar spine, biochemical markers of bone metabolism, fracture rate, and clinical evaluation. RESULTS: Areal BMD and aBMD z-scores showed significant improvement during the treatment period. Both serum and bone-specific alkaline phosphatase values were significantly decreased. Fracture rate reduced significantly from 3.5 +/- 1.01 to 0.83 +/- 0.77 fractures/year. Bone pain, which was severe in five patients, disappeared just after the first cycle, and the activity and mobility of patients increased. aBMD and aBMD z-scores were decreased 1.5 years after discontinuation, although not statistically significant. Annual fracture rate increased significantly. Bone pain recurred in four patients. Pamidronate treatment was reinstituted in five of these patients at the end of 1.5 years. CONCLUSION: Cyclical pamidronate treatment is very effective in children with moderate/severe OI. This treatment should be started early enough before the occurrence of irreversible deformities and must be given for a longer time during the growth period.     

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.     

Levetiracetam in children,adolescents and young adults with intractable epilepsy: Efficacy,tolerability and effect on electroencephalogram – A pilot study

Levetiracetam has been authorized for use in Israel as an add-on therapy for intractable epilepsy since May 2006. The aim of the present study was to document its effectiveness for this indication in children, adolescents, and young adults. The medical files of 78 patients aged 0.5–39 years (mean, 14.2 years) treated at our center for intractable epilepsy were reviewed. All received levetiracetam as add-on therapy following a failure to respond to at least 3 anti-epileptic drugs. Fifty-two patients (67%) had partial epilepsy and the remainder had primary generalized epilepsy. The epilepsy was symptomatic in 57%, cryptogenic in 27%, and idiopathic in 15%. Average age at first seizure was 4.1 years. In 45% of patients, the number of seizures was reduced by half with levetiracetam treatment; 11.5% of the cohort achieved complete remission. There was a statistically significant correlation between clinical seizure control and improvement in the electroencephalography findings (p = 0.0012). The drug was well tolerated, with a retention rate of 69% after one year. The most common adverse effects were irritability and impulsiveness, in 26.9% of patients. Severe behavioral side effects (psychosis, confusion) were experienced by 6.4%. In conclusion, levetiracetam is an effective and tolerable add-on agent for use in most epileptic children, adolescents, and young adults who fail to respond to at least 3 antiepileptic drugs and should be the treatment of choice in this setting. Despite the relatively high rate of behavioral side effects in this study, the retention rate at one year was high.     

Alendronate treatment in children with osteogenesis imperfecta

BACKGROUND: Recent studies reported beneficial effect of cyclical intravenous administration of pamidronate in children and adolescents with osteogenesis imperfecta (OI). However, this treatment requires frequent hospital admissions and is relatively expensive. Alendronate is an oral bisphosphonate effectively used in adults with osteoporosis. Experience with alendronate treatment in children with OI is limited. AIMS: To report our experience with alendronate in children with OI. METHODS: 12 children with OI (7 with type I, 4 with type III and 1 with type IV; 7 boys, 5 girls) aged 1.8 to 15.4 years (7.9+/-; 4.4 yrs) were included in this retrospective study. The patients were treated with alendronate in a dose of 5-10 mg/day along with calcium (500 mg/day) and vitamin D (400-1000 IU/day) supplements for 19.8+/-11.3 months (range: 7-46 months). Serum calcium (Ca), phosphorus (P), alkaline phosphatase (ALP), osteocalcin (OC), pyrilinks-D and urinary Ca/Cr ratio were studied 3 monthly and bone mineral density (BMD) by DXA on 6-12 monthly basis. RESULTS: Fracture rate of the patients significantly decreased after treatment (1.2+/-1.5 vs. 0.16+/-0.32 per year, P<0.05). Treatment improved bone density in each individual case. Z-scores of lumbar DXA (L2-L4) significantly increased during treatment (-4.60+/-1.30 vs - 2.47+/-1.52, P< 0.05). Urinary pyrilinks-D decreased with treatment (90.8+/-136.3 vs. 35.1+/-29.9, P< 0.05). Serum Ca, P, ALP, OC and urinary Ca/Cr did not change significantly during treatment. CONCLUSION: We conclude that alendronate is effective, safe and practical alternative to intravenous bisphosphonates in treatment of children with OI.     

Pamidronate treatment of less severe forms of osteogenesis imperfecta in children

BACKGROUND: Bisphosphonate therapy improves bone quality in children with severe osteogenesis imperfecta (OI). Children with milder phenotypes also have prepubertal fractures, bone pain and reduced bone mass, predisposing them to adult osteoporosis. OBJECTIVE: To evaluate treatment effects of pamidronate in children with mild phenotypes of OI. METHODS: Open label, 2-year observational study of 18 patients, using pamidronate, with clinical, biochemical and radiological monitoring. RESULTS: Over 2 years, bone pain decreased from 16 to 1 patient and disturbed sleep from 12 children to 0. Independent mobility improved from 10 to 17 children. Fracture incidence decreased from 1.6 to 0.5 fractures/child/year. Surgical interventions decreased from a mean 1.3 procedures/patient to 0 in the second year of treatment. Growth velocity remained stable at a mean 4.8 cm/year. Mean lumbar vertebral bone mineral density improved by 40.8%, from 0.375 to 0.528 g/cm2 (p <0.0001), z-score from -3.77 to -2.44 (p <0.0001). Mean vertebral height improved by 17.3%, from 15.6 to 18.38 mm (p = 0.07); plasma alkaline phosphatase decreased from 222 to 169 U/l (p = 0.0009) and urinary deoxypyridinoline crosslinks decreased from 26.7 to 21.8 nmol/mmol creatinine (p = 0.21). Two children with vitamin D insufficiency were concurrently treated. A significant association (r = -0.6, p = 0.008) was shown between age at start of treatment and percentage change in BMD after 2 years. CONCLUSIONS: Pamidronate treatment improves bone quality in children with mild types of OI. It ameliorates clinical symptoms, improves mobility, reduces fracture frequency and thus improves quality of life and in future is likely to reduce the severity and consequences of adult osteoporosis by improved peak bone mass in these children.     

Pamidronate treatment of osteogenesis imperfecta--lack of correlation between clinical severity, age at onset of treatment, predicted collagen mutation and treatment response

Severe forms of osteogenesis imperfecta (OI) are characterised by osteoporosis with multiple fractures, deformity, progressive loss of mobility and chronic bone pain. Bisphosphonates, as osteoclast inhibitors, reduce bone turnover and improve osteoporosis. OBJECTIVE: To investigate the effect of pamidronate treatment of severe OI in children, and find any correlation between clinical severity, age at start of treatment, type of predicted collagen mutation and treatment response. DESIGN: Open, observational trial. PATIENTS: A two-year study of pamidronate treatment was undertaken in a cohort of 18 children, (1.4-14.5 years) with OI types III and IV. INTERVENTIONS: Disodium pamidronate, 1 mg/kg/day for 3 days every 4 months, by i.v. infusion with measurement of bone turnover, bone density, vertebral morphology and skin biopsies to assess collagen mutation. RESULTS: Eleven children have completed 2 years of treatment and three more have completed 20 months. Sustained cessation of bone pain, improved mobility and decreased fracture rate were seen in all patients. Bone turnover decreased slightly but was not statistically significant. Bone mineral density (BMD) of lumbar spine increased by a mean of 124.7 +/- 75.7% over 2 years (Z score mean -5.08 +/- 1.27, to -3.30 +/- 1.71, p <0.001); the greatest change in BMD was seen in the most severely affected patients: 138 +/- 50.6% (severe), 62.47 +/- 22.9% (mild). There was a mean increase in vertebral height at L4 of 68.5% and in vertebral area of 85.4%. The majority of patients had slow electrophoretic migration of type I collagen alpha chains or reduced secretion of type I collagen, indicative of structural, helix-breaking mutations. There was no correlation between phenotypic severity, age at start of treatment and treatment response (r2 = 0.14) CONCLUSIONS: Pamidronate treatment of severe forms of OI is an effective therapeutic modality to increase bone density, decrease fracture rate, increase mobility and improve quality of life, irrespective of the severity of the mutation or clinical phenotype. It has a good short-term safety profile.     

Oral bisphosphonate treatment for osteogenesis imperfecta--an Indian perspective

BACKGROUND: Various treatments for the management of osteogenesis imperfecta (OI) have been tried, of which bisphosphonates seem to have the maximum benefit in reducing fracture rate and improving bone density. This study investigated the value of oral alendronate for treating OI in Indian children. METHODS: Between 2002 and 2005, 11 patients with OI were referred for bisphosphonate therapy. The various types of OI were classified using the Sillence criteria. All patients underwent baseline biochemistry, radiographic studies and bone mineral density (BMD) measurements before commencing therapy. Patients were commenced on oral alendronate (0.5 mg/kg/day) and followed up for a period ranging from 1 month to 2 years. A retrospective analysis of pre- and post-treatment changes in fracture rate and bone density was undertaken using the paired sample t-test. RESULTS: One patient lost to follow-up was excluded from the study and three completed only 2 months of therapy. Pre-treatment fracture rate per year before treatment ranged from 0.5 to 6 with a mean (SD) of 2.95 (1.57) and median of 2.5. The post-treatment fracture rate was 1.1 (0.59)/year (p=0.02). Seven children underwent BMD analysis while on treatment and all had a rise in BMD, of which the change in lumbar spine BMD was statistically significant (p=0.001), and lumbar (p=0.005) and femoral neck t-score (p=0.04) showed a significant change. No significant change was seen in serum biochemistry except for disappearance ofhypercalciuria (p=0.04). No child had an adverse reaction to alendronate. CONCLUSION: After a median of 9.5 months of treatment, oral alendronate is associated with a lower fracture rate, improvement in BMD and a decrease in hypercalciuria.     

Efficacy and safety of lamotrigine monotherapy in children and adolescents with epilepsy

Lamotrigine (LTG) has shown to confer broad-spectrum, well-tolerated control of epilepsy. Monotherapy is preferable over polytherapy because of better compliance, fewer adverse events, less interactions, lower teratogenicity and lower cost. The aim of this study is to evaluate the efficacy and safety of LTG monotherapy on seizure control in a cohort of children and adolescents with epilepsy.We retrospectively reviewed the records of children and adolescents treated with LTG monotherapy at our institution between 2001 and 2006. Data collected included demographics, seizure type, etiology of seizures, age at onset of seizures and at initiation of LTG treatment, number of antiepileptic drugs (AEDs) prior to LTG, dose of LTG, length of follow-up, treatment response, and adverse events.Seventy-two children and adolescents were identified (mean age 12.1 years); 37.5% had mental retardation. Age at onset of epilepsy was 5.7 years (0–16). Twenty three percent had symptomatic focal epilepsy, 15.5% idiopathic focal epilepsy, 19.4% symptomatic generalized epilepsy and 41.6% idiopathic generalized epilepsy. LTG was used as first-line monotherapy in 26.4% of patients and as a second-line monotherapy in 73.6%. Age at initiation of LTG therapy was 10 years (2.8–19). Mean number of AEDs tried prior to LTG was 1.3 (0–6). Mean dose of LTG was 5.5 mg/kg/day (1.1–13.7). Mean follow-up period was 33 months (3 weeks to 11.5 years).The degree of seizure reduction was as follows: seizure free in 42%, 75–90% reduction in 17.4%, 50–74% in 11.6%, 25–49% in 10%. Sixteen percent had no change in seizure control and 3% became worse. The most common adverse event was rash (6.9%). Six (8.3%) patients discontinued LTG because of the adverse events. No patient had Stevens–Johnson syndrome.In conclusion, LTG was effective and well-tolerated as monotherapy in children and adolescents for both focal and generalized epilepsies.     

Treatment of osteogenesis imperfecta with the bisphosphonate olpadronate (dimethylaminohydroxypropylidene bisphosphonate)

Osteoporosis is an important feature of osteogenesis imperfecta (OI). So far, no effective medical treatment is available. We treated three boys with severe OI type III and vertebral deformities for 5–7 years with continuous oral administration of the bisphosphonate, olpadronate. Treatment resulted in a decreased number of bone fractures, an increased calcification of the long bones and an amelioration of vertebral shape. No side-effects were encountered. Conclusion These preliminary but long-term obser- vations suggest that the bisphosphonate olpadronate may be a useful treatment for patients with OI and vertebral fractures. Bisphosphonates may be promi- sing drugs for children with OI. Received: 20 November 1996 / Accepted: 25 February 1997     

Recurrence risk after withdrawal of antiepileptic drugs in children with epilepsy: A prospective study

AimTo study recurrence risk after withdrawal of antiepileptic drugs in children with epilepsy.MethodsAll children younger than 14 with two or more unprovoked seizures 24 h apart who were seen at our Hospital between 1994 and 2004 were included consecutively and prospectively followed. Patients previously examined in other centres were excluded. All patients who entered a remission were proposed to stop medication and were followed.ResultsThree hundred and fifty three children with two or more unprovoked seizures were attended. A total of 238 entered a remission period and were proposed to stop medication, 216 accept. Mean seizure-free time before medication withdrawal was 2.2 years. Kaplan-Meier estimate of recurrence risk was 23% at 2 years (95% CI: 17–29) and 28% at 5 years (95% CI: 22–34). A remote symptomatic etiology, various seizure types and a history of prior febrile seizures or prior neonatal seizures were associated with a significant increase in recurrence risk in univariable and multivariable analyses using Cox proportional hazards model. Recurrence risk at 2 years was 17% (95% CI: 11–23) for idiopathic/cryptogenic epilepsies and 41% (85% CI: 28–54) for remote symptomatic epilepsies. Recurrence risks at 2 years by epileptic syndrome were West syndrome (0%), benign rolandic epilepsy (10%), epilepsy without unequivocal partial or generalized seizures (11%), benign infantile seizures (13%), absence epilepsy (16%), cryptogenic partial epilepsies (20%), symptomatic partial epilepsies (45%), symptomatic generalized epilepsies (54%).ConclusionsRecurrence risk after withdrawal of antiepileptic treatment in children is low. Etiology and syndromic diagnosis are the main predictive factors.     

Symptomatic rickets in adolescence

AIM—To describe 21 cases of symptomatic rickets in adolescents.METHODS—The setting was a primary and secondary care hospital in Saudi Arabia providing medical care to Saudi Arab company employees and their families. Cases of symptomatic rickets diagnosed between January 1996 and December 1997 in adolescents aged 10 to 15 years were assessed with respect to clinical presentation, biochemical and radiological evaluation, dietary assessment, and estimation of sun exposure.RESULTS—Symptomatic rickets developed in 21 adolescents (20 females), with a prevalence rate of 68 per 100 000 children years. Presentation included carpopedal spasms (n = 12), diffuse limb pains (n = 6), lower limbs deformities (n = 2), and generalised weakness (n = 1). Biochemical findings included hypocalcaemia (n = 19), hypophosphoraemia (n = 9), raised serum alkaline phosphatase (n = 21) and parathormone (n = 7), and reduced 25-hydroxyvitamin D concentrations (n = 7). Radiological studies were suggestive of rickets in only eight children. All children had an inadequate dietary calcium and vitamin D intake. All but one had less than 60 minutes sun exposure per day.CONCLUSION—Even in sunny climates, adolescents, especially females, can be at risk of rickets. Hypocalcaemic tetany and limb pains were the most common presenting symptoms. Radiological evidence was not present in every case.     

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). METHODS: In a prospective observational study, monthly intravenous pamidronate infusions were given to 43 children (aged 4 months-16 years) with different severity and form of OI. Outcome measures included the Pediatric Evaluation of Disability Inventory (PEDI), a score of well-being, registration of days with pain and bone density measured by using dual energy X-ray absorptiometry (DXA). Data were collected before and after the first year of treatment. RESULTS: Self-care and mobility measured by PEDI increased significantly in both the Functional Skill scale and in the Caregiver Assistance scale. The youngest children improved more than the older ones according to the PEDI. The days with skeletal pain were reduced and both well-being and bone density increased. CONCLUSIONS: Intravenous treatment with bisphosphonates influenced health status, according to the International Classification of Functioning, Disability and Health (ICF). This group of 43 children experienced beneficial effects on everyday activities, skeletal pain, well-being and bone density.     

Quantitative ultrasonometry of the calcaneus in children with osteogenesis imperfecta

Aims: Osteogenesis imperfecta (OI) is characterised by low bone density and increased bone fragility. The aim was to evaluate calcaneal quantitative ultrasonometry (QUS) parameters in children with OI and to look for relationship with the number of prevalent fractures. Methods: Eighteen children (12 boys and six girls; mean age 9.8 ± 3.5 years) with OI (type I, n= 15; type IV, n= 3; mean fracture prevalence 3.7 per patient) had the velocity of sound (VOS) and broadband ultrasound attenuation (BUA) measured on both heels with a Cuba Clinical (McCue Ultrasonics, Winchester, UK) dry ultrasound portable device. Both BUA and VOS were expressed as either age‐dependent or height‐related values. The obtained values of VOS and BUA were correlated to number of prevalent fractures. Results: The patients were of short stature (Z‐score –1.73 ± 1.20 SD; P < 0.001). Both age‐related BUA and VOS were low in comparison to reference values (P < 0.0001), same as height‐adjusted BUA and VOS (P < 0.0001). We found no correlations between number of prevalent fractures and BUA or VOS (age‐related or height‐adjusted) (r= 0.02, r= 0.017, r=–0.13, r= 0.015, respectively). Conclusions: Children with OI have low QUS parameters with no relationship to number of prevalent fractures.     

Management of osteogenesis imperfecta

Osteogenesis imperfecta (OI) is in most cases a congenital disease of collagen type I with a remarkable variation in phenotype, ranging from severe forms that result in perinatal death to very mild forms. In general, the genotype is an unreliable predictor of phenotype and severity and no classification based on the different mutations has yet been devised. Symptoms are common in the ligaments, sclerae and teeth. Hearing can be affected, sometimes leading to deafness. There is also an increased disposition for bruises and haematoma and insufficiency of the valves of the heart. Over 800 mutations have been reported. Since each person/family with OI has their own unique mutation the management of these children must be individualized. These children benefit from the competence of a multidisciplinary team. Amino-bisphosphonates have proven effective in treating children and adolescents with OI of severe form and milder forms with vertebral compressions. These accumulate in bone and reduce remodelling rate, and residual levels are measurable after many years. Until long-term safety data are available, treatment should be reserved for those for whom the benefits clearly outweigh the risks.