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.Osteogenesis imperfecta is a disease that shows a large variation in phenotype, ranging from very mild bone fragility (type I) through intermediate severity (types IV and III) to the most severe lethal form (type II). This clinical classification into four major subgroups was designed by Sillence in 1979^1,2 and describes most cases. Recent modifications encompass additional, even less common, forms of the disease. In most cases, there are mutations in the COLIA1 or COLIA2 genes localised to chromosomes 17 and 7, respectively. This leads either to a reduced production of normal collagen type I or to the synthesis of collagen type I with abnormal structure and function. In general, the genotype is an unreliable predictor of phenotype and severity, and no new classification based on the different mutations has yet been devised.Intravenous disodium pamidronate (APD) treatment of children with osteogenesis imperfecta has been used since 1991, and we presented the first case at the Fifth International Conference on Osteogenesis Imperfecta in 1993. The rationale for bisphosphonate treatment in osteogenesis imperfecta is that the complex function of bisphosphonate, with a predominantly inhibitory effect on osteoclasts, might lead to a net effect of increased bone mass, especially as growing children with osteogenesis imperfecta have thin bone with few trabeculae, thin cortices and high remodelling rates.^3,4,5,6,7 We have previously published long‐term results in 3 adolescents and 28 children aged 0.6–18 years.^8,9 The few reports of bisphosphonate treatment of infants with osteogenesis imperfecta are mainly, a mix of toddlers and infants, few under the age of 15 months.^{9,10,11,12,13,14,15,16} Here we present very promising results of APD treatment in a group of 11 infants with severe but not lethal forms of osteogenesis imperfecta.     

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 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.     

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.     

Bone densitometry in pediatric patients treated with pamidronate

Background: Increasing numbers of children are being treated with the bisphosphonate pamidronate for low bone mineral density, particularly children with increased risk of fractures caused by bone disorders or low/non-weight bearing. Objective: To determine the effect of intravenous pamidronate on the bone mineral density of children with osteogenesis imperfecta and spastic quadriplegic cerebral palsy. Materials and methods: Charts of 38 children with osteogenesis imperfecta (n=20) and spastic quadriplegic cerebral palsy (n=18) treated with pamidronate were retrospectively reviewed. Patients were selected for treatment because of prior fracture and/or abnormally low bone mineral density. All received intravenous pamidronate at two-month to eight-month intervals and were periodically examined using dual energy X-ray absorptiometry. Results: All patients had abnormally low bone mineral density prior to treatment. Lumbar spine bone mineral density and z-scores showed serial improvement in 31 of 32 patients. Spine bone mineral density increased 78±38.1% in OI and 47.4±39.0% in children with cerebral palsy. The area of greatest lateral distal femur bone mineral density improvement was in the metaphysis adjacent to the growth plate, with a 96±87.8% improvement in the osteogenesis imperfecta group and 65.7±55.2% improvement in the cerebral palsy group. Increases in bone mineral density exceeded that expected for age-specific growth. This was demonstrated by improvement in both spine and femur z-scores for both groups. No children with spastic quadriplegic cerebral palsy experienced fractures after the first week of treatment, whereas patients with osteogenesis imperfecta continued to have fractures but at a decreased rate. Conclusions: Intravenous pamidronate given at 3- to 4-month intervals proved to be effective in increasing bone mineral density in patients with osteogenesis imperfecta and spastic quadriplegic cerebral palsy. The greatest gains in bone mineral density were observed in the children with osteogenesis imperfecta, but they did continue to fracture, albeit at a decreased rate. Children with cerebral palsy gained bone mineral density and did not continue to fracture.     

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.     

Low-dose intravenous pamidronate treatment in osteogenesis imperfecta

Different therapy models have been tried in order to decrease bone resorption in osteogenesis imperfecta. Bisphosphonates are a group of drugs that mainly suppress osteoclast-mediated bone resorption, thus reducing bone turnover. We assessed the effects of low-dose bisphosphonate treatment in children with osteogenesis imperfecta. Sixteen osteogenesis imperfecta patients (12 female, 4 male) with severe deformities were treated with cyclic (3-4 mg/kg/year) intravenous infusions of bisphosphonate (Aredia-Novartis) therapy for a period ranging from 0.6 to 4.7 years (mean 2.50 +/- 1.09 years). Bone mineral density increased from 0.304 +/- 0.146 g/cm2 to 0.362 +/- 0.142 g/cm2 in the first year and to 0.421 +/- 0.146 g/cm2 in the second year. A clinical response was shown with a reduction in fracture rate and improvement in mobilization scores. Fracture rates decreased from a median of 4/year (0-30/year) before treatment to 0/year (0-5/year) during treatment. Ambulation improved in 10 children and remained unchanged in three. Two of the children were fully functional before therapy and one was below two years of age. No adverse effects were seen with pamidronate infusions of 7-10 mg/kg/year (monthly) or with 4 cycles/year 3-4 mg/kg/year. Low-dose cyclical pamidronate infusions markedly increased bone density and decreased bone fracture rate and should be considered as a part of a multi-disciplinary treatment.     

Experience with bisphosphonates in osteogenesis imperfecta

Until recently, medical management of osteogenesis imperfecta, a genetic disorder of reduced bone mass and frequent fractures, was elusive, and treatment was focused on maximizing mobility and function. The introduction of bisphosphonates for the treatment of osteogenesis imperfecta 14 years ago changed this paradigm. Cyclic intravenous pamidronate therapy leads to an increase in bone density and a decrease in fracture rate in patients with osteogenesis imperfecta. Pamidronate therapy has a positive impact on functional parameters including improved energy, decreased bone pain, and increased ambulation. Histomorphometric studies have shown that the reduced osteoclast activity results in gains in cortical thickness and trabecular bone volume. Potential negative effects may include prolonged time to heal after osteotomies and a decrease in the rate of bone remodeling. Overall, it seems clear that the benefits of pamidronate therapy outweigh its potential risks in moderate-to-severe osteogenesis imperfecta, and pamidronate therapy has become the standard of care for patients with this condition. Questions remain regarding when treatment should be stopped and the need for pamidronate therapy in patients with mild osteogenesis imperfecta.     

Wirbelkörperkompressionen bei Osteogenesis imperfecta

Background

Some studies show a positive effect of i.v. pamidronate therapy on reconstruction of vertebral deformities in children with osteogenesis imperfecta. This analysis aimed to evaluate the effect of i.v. neridronate therapy.

Patients and methods

To evaluate changes in vertebrae, a retrospective analysis included 12 children aged 0.1–14.6 years (mean age 6.6 years at the start of therapy) with moderate and severe types of osteogenesis imperfecta. We used quantitative vertebral morphometry to assess the anterior, posterior, and middle heights of lumbar vertebrae L1–L4 at the start of therapy and after 1.1±0.2 years. Based on these measurements, concavity indices for lumbar vertebrae were calculated.

Results

The i.v. treatment with neridronate led to a significant increase in lumbar vertebral heights (except for anterior and middle heights of L4, p=0.091/p=0.068). The mean improvements were 19.3% in anterior height, 22.9% in middle height, and 18.4% in posterior height. The concavity indices showed improvements in vertebral morphometry at vertebrae L1 (p=0.132) and L2 (p=0.034).

Conclusion

During the first year of i.v. neridronate therapy, reconstitution of lumbar vertebrae L1–L4 was seen in children with moderate and severe types of osteogenesis imperfecta.     

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.     

Osteogenesis imperfecta with joint contractures: Bruck syndrome

We describe an Egyptian boy with osteogenesis imperfecta who was born with thumb contractures and bilateral antecubital pterygia. He was seen at 16 months of age with femur and tibial fractures, thoracic vertebral compression fractures, scoliosis and Wormian bones. The findings are consistent with a diagnosis of Bruck syndrome. Received: 6 June 1997 Accepted: 17 July 1997     

Efficacy of low dose schedule pamidronate infusion in children with osteogenesis imperfecta

BACKGROUND: Osteogenesis imperfecta (OI) is a rare condition in which bones are abnormally brittle with frequent fractures. A variety of therapeutic agents has been used with low efficacy. In this study, we present three patients treated for 4 years with i.v. pamidronate. PATIENTS AND METHODS: Three prepubertal patients, aged 9 (M), 9 (F) and 11 (F) years old, with OI, were treated with 30-60 mg i.v. pamidronate every 6 months over four years. Determinations were made of plasma 1,25-dihydroxycholecalciferol, 25-hydroxycholecalciferol, insulin-like growth factor-I (IGF-I) and its transport protein (IGFBP3), osteocalcin, total alkaline phosphatase and its osseous fraction, and parathormone (PTH) at baseline and after every pamidronate infusion, Densitometry and X-ray of the vertebral column were performed at the same intervals. RESULTS: Significant reductions of number of bone fractures and pain were observed in all patients, despite lack of any modification in biochemical parameters. Lumbar X-ray and densitometry showed a striking improvement by the end of the treatment period. CONCLUSION: Pamidronate seems to be useful in the treatment of patients with osteogenesis imperfecta.     

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.     

Osteogenesis imperfecta: a new, early therapeutic approach with biphosphonates. A case report]

Management of type III osteogenesis imperfecta (O.I.) (brittle bone disease) is primarily supportive; early introduction of cyclic intravenous pamidronate administration in children younger than 2 years of age is an innovative and promising therapeutic approach. CASE REPORT: We present the case of a 6-month-old infant, whose preliminary data have already been partly published, with severe type III O.I. referred because of aching and crumbling from multiple fractures. Cyclic intravenous disodic pamidronate administration improved the clinical status (fracture incidence, pain, growth curve) and biological status (bone density, osseous alkaline phosphatases, urinary desoxypiridoline excretion), allowing a remarkable recovery. CONCLUSION: Biphosphonates are a new and innovative therapeutic agent in O.I. Clinical safety, easy administration, and overall efficacy are likely to extend their use in severe type III O.I. from the very first months of life, the time of best efficacy.     

Effect of intravenous pamidronate therapy on functional abilities and level of ambulation in children with osteogenesis imperfecta

OBJECTIVE: To evaluate the functional abilities and the level of ambulation during pamidronate therapy in children with moderate to severe osteogenesis imperfecta. STUDY DESIGN: Functional abilities, ambulation, and grip force were assessed in 59 patients (mean age, 6.1 years; range, 0.5-15.7 years; 30 girls) during 3 years of pamidronate treatment. Functional skills (mobility and self-care) were both assessed by using the Pediatric Evaluation of Disability Inventory. Ambulation level was assessed by using the modified Bleck score. For 48 patients, results after 3 years of pamidronate treatment could be matched to those of patients with similar age and disease severity who had not received pamidronate. RESULTS: Mobility and self-care scores increased during the study period (+43% and +30%, respectively). The average ambulation score changed from 0.8 to 1.9. Maximal isometric grip force increased by 63%. Mobility and ambulation scores and grip force measures were significantly higher than in patients who had not received pamidronate. The difference in self-care scores did not reach significance. CONCLUSION: This study suggests that cyclical pamidronate treatment improves mobility, ambulation level, and muscle force in children with moderate to severe osteogenesis imperfecta.     

Muscle weakness as presenting symptom of osteogenesis imperfecta

A young boy presented with severe muscle weakness of his legs at the age of 2 years. Muscle morphology and computer tomography imaging findings were compatible with a metabolic myopathy. Additional investigation showed an osteopenic skeleton and signs of healing fractures. A skin biopsy showed an abnormal electrophoresis pattern of collagen, consistent with a variant of osteogenesis imperfecta. The patient improved with intravenous treatment with pamidronate.     

Two doses of pamidronate in infants with osteogenesis imperfecta.

INTRODUCTION: Current regimens of intravenous pamidronate for infants and children with osteogenesis imperfecta (OI) typically deliver 3-12 mg/kg/year of drug. We wished to ascertain the effect of pamidronate at 6 or 12 mg/kg/year on skeletal health in infants with OI. METHODS: We recruited 12 infants over a period of 4 years. Infants received either 6 or 12 mg/kg/year of pamidronate. Bone outcomes were assessed by skeletal surveys and DXA bone density measurements at baseline and at 12 months. RESULTS: Bone mass increased in both groups. Infants receiving 12 as opposed to 6 mg/kg/year pamidronate had increased spine bone density after adjusting for covariates at study entry (p = 0.04). Crush fractures improved or remained unchanged in all but one infant. Biochemical markers of bone turnover fell but remained within or above the normal range for age. Metaphyseal remodelling was not impaired. CONCLUSIONS: Pamidronate dose in infants may influence lumbar spine bone acquisition. Pamidronate improved vertebral size after prior crush fracturing and did not over-suppress bone turnover.     

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.     

Cyclic pamidronate infusion improves bone mineralisation and reduces fracture incidence in osteogenesis imperfecta

A prospective open study was performed to determine the efficacy and safety of pamidronate in improving bone mineralisation and reducing fracture incidence in osteogenesis imperfecta (OI). Intravenous pamidronate was administered at 1.5 mg/kg bi-monthly to six children with OI, over 12-23 months. The number of fractures decreased from median of 3 (range 1-12) to 0 fractures/year (range 0-4) (P<0.05). After 12 months of treatment, there was significant improvement in areal bone mineral density (BMD) z-scores of the lumbar spine from median of -2.40 (range -3.20 to -1.67) to -1.90 (range -2.38 to -0.91) (P<0.05) and in the volumetric BMD which increased from median of 0.095 to 0.146 g/cm3 (P<0.05). Urine N-telopeptide levels (bone resorption marker) decreased from a median of 461.5 bone collagen equivalent/creatinine (BCE/Cr) (range 129-721 BCE/Cr) to 223.5 BCE/Cr (range 107-312 BCE/Cr) (P<0.05) and serum alkaline phosphatase (ALP) (bone formation marker) from a median of 230.0 U/l (range 148-305 U/l) to 133.5 U/l (range 79-233 U/l) (P<0.05), reflecting reduced bone turnover. This may represent a net reduction in bone resorption and provides a biochemical explanation for the increase in bone mineralisation. Height standard deviation scores were not affected and there were no significant adverse effects. CONCLUSION: 1 year cyclical pamidronate is effective and safe in improving bone mineralisation and reducing fracture incidence in osteogenesis imperfecta.     

Intravenous pamidronate in juvenile osteoporosis.

AIMS: To investigate the use of the aminobisphosphonate, disodium pamidronate, in children with vertebral osteoporosis. METHODS: Five children (aged 10-15 years) with vertebral osteoporosis who developed compression fractures in the thoracic and/or lumbar spine as a consequence of five different conditions, received treatment with intravenous disodium pamidronate in doses ranging from 0.5 to 12 mg/kg/y. RESULTS: Each child had rapid pain relief following the first treatment, followed by large increments in lumbar spine bone density over one year; the change in bone density standard deviation score ranged from 0.5 to 2.5 with percentage increments of 26% to 54%. CONCLUSION: Intravenous pamidronate appears to be a useful therapeutic option in childhood osteoporosis, but its use in children must still be regarded as experimental and therefore closely monitored.