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.     

Effects of 3 years of intravenous pamidronate treatment on bone markers and bone mineral density in a patient with osteoporosis-pseudoglioma syndrome (OPPG)

We present a 21 year-old woman with osteoporosis-pseudoglioma syndrome (OPPG) suffering from bone pain and frequent long bone fractures (approximately 1 or 2 fractures/year) who was treated with i.v. pamidronate for 3 years. OPPG is a rare autosomal recessive disorder characterized by severe widespread osteoporosis leading to pathological fractures and congenital or early onset blindness. Bone mineral density (BMD) (g/cm2) was determined at lumbar spine and femur neck by dual energy X-ray absorptiometry. BMD studies were also performed in her parents and 18 year-old brother who were phenotypically normal. Within 2 months of the first pamidronate treatment the patient reported considerable decrease in bone pain and improved mobility. During the treatment period no important side effects and no recurrent bone fracture were reported. There were substantial increases in BMD, T score and z-score at both lumbar spine and femoral neck during therapy. Baseline lumbar spine BMD increased from 0.416 to 0.489 g/cm2 and femoral neck BMD increased from 0.455 to 0.532 g/cm2 after 3 years. Although her parents and brother did not have any history of fracture, BMD measurements revealed that her parents were osteopenic and her brother was osteoporotic. We demonstrated that pamidronate therapy seems to be safe and beneficial in both spinal and peripheral skeleton osteoporosis in patients with OPPG. Moreover, the present study clearly indicates that bone density studies and LRPS gene screening for mutations should be performed in phenotypically normal family members of patients with OPPG.     

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.     

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.     

Recent progress in diagnosis and treatment of osteogenesis imperfecta

Osteogenesis imperfecta (OI) is an inheritable disorder characterized by bone fragility with various symptoms of connective tissue disorders. OI is commonly classified by Sillence's classification into four types according to the clinical features. The cardinal symptom is pathologic fracture, which is often recognized before birth, is frequent during infancy and childhood, then decreases at puberty. Bone mineral density is markedly decreased in OI, especially of the lumbar spine. Bone deformities are frequently observed in the long bones of the extremities, and spinal deformities and compression fractures are also common. Growth retardation is extremely severe, especially in type III. Calcitonin has been the most common therapy for OI. Recently, bisphosphonates have been found to be potent drugs that increase bone mass in OI patients. To prevent further fracture or bone deformity, appropriate orthopedic managements, including intramedullary rodding, are critically important. Growth hormone is effective in stimulating bone growth during childhood. The pathogenesis of OI is quantitative or qualitative abnormalities of type I collagen. The clinical features of each type usually correspond to the type of mutation. Several possibilities for gene therapy have been proposed.     

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.     

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.     

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.     

Alendronate treatment for infants with osteogenesis imperfecta: demonstration of efficacy in a mouse model

Recent non-placebo-controlled studies of the bisphosphonate pamidronate have shown it to be effective in reducing fractures and improving bone density in infants and children with osteogenesis imperfecta (OI). To evaluate the effects of bisphosphonate treatment in a controlled study, the oim/oim mouse model of OI was studied. Nursing infant mouse pups (approximately 2 wk old) with moderate to severe OI (oim/oim mouse) and age- and background-matched control mice (+/+) were treated either with the third-generation bisphosphonate alendronate (ALN), or with saline. Fracture risk, bone quality, and growth were evaluated over a 12-wk treatment period. ALN at a dose of 0.03 mg/kg/d or saline was administered via s.c. injection to infant oim/oim and wild-type (+/+) mice from 2 to 14 wk of age (n = 20 per subgroup). The average number of fractures sustained by the ALN-treated oim/oim mice was reduced significantly compared with the untreated oim/oim mice (0.7 +/- 0.7 fractures/mouse versus 2.0 +/- 0.2 fractures/mouse). Bone density increased significantly in the femur and the spine with treatment (2.0 +/- 0.5 versus 1.2 +/- 0.5 in femur and 2.1 +/- 0.5 versus1.6 +/- 0.5 in spine). Histologic evaluation revealed the percentage of metaphyseal tibial bone increased significantly with treatment in both +/+ and oim/oim mice. Mechanical testing revealed an increase in structural stiffness for both treated +/+ and oim/oim mice compared with untreated animals. None of the material properties examined were significantly altered with treatment, nor was spinal curvature affected. Weight gain and long bone growth were comparable in the treated and untreated oim/oim mice. In wild-type mice, femur lengths were significantly shorter in the treated mice compared with untreated counterparts. This animal study demonstrates that treatment of OI in mice as early as 2 wk of age with ALN appears to be effective in reducing fractures and increasing bone properties. Based on the data from this study, ALN therapy in infants with OI should prove to be effective.     

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: 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.     

Management of lower limb deformities in children with osteogenesis imperfecta

Osteogenesis imperfecta (OI) often leads to severe lower limb (LL) deformities due to recurrent fractures that significantly hamper ambulation. We describe our management experience of correction of LL deformities in four children with OI. Medical management consisted of peri and postoperative pamidronate therapy, calcium supplementation and rehabilitative care. Deformities were corrected with multiple osteotomies and intramedullary fixation by titanium elastic nails. At a mean follow-up of 30 months, all children have significantly reduced fracture incidence and have no evidence of recurrence of deformities with improved ambulatory status. We emphasize the importance of combined medical and surgical therapy for these patients.     

Developmental outcomes in persistent pulmonary hypertension treated with nitric oxide therapy

Background:  The aim of the present study was to assess 3 year auditory and neurodevelopmental outcomes of persistent pulmonary hypertension of the newborn (PPHN) before and after introducing inhaled nitric oxide (i-NO) therapy, and to detect the clinical factors affecting poor outcome.
Methods:  A retrospective historical cohort study of 26 survivors with PPHN with oxygenation index (OI) ≥25 (13 infants without i-NO therapy, control group; 13 with i-NO therapy, i-NO group) was performed. Auditory brainstem response (ABR) at 6 and 12 months and neurodevelopmental outcomes at 3 years of age were evaluated.
Results:  ABR abnormalities at 6 months were observed in one infant in the i-NO group and six in the control group ( P  = 0.04). At 1 year, one infant in the i-NO group and two of six infants in the control group still had ABR abnormality. In the i-NO group, two children had abnormal neurodevelopmental outcomes, as compared with five children in the control group at 3 year follow up. Two children in the control group and no children in the i-NO group had hearing loss at 3 years of age. Hypocapnea ( P  = 0.04) and elevated creatine phosphokinase ( P  = 0.04) were found to be most predictive for neurodevelopmental abnormality.
Conclusion:  Avoidance of excessive hypocapnea via introduction of i-NO therapy might reduce both ABR and neurodevelopmental abnormalities.     

Biomechanical analysis of arm fracture in obese boys

Objective:   To determine the role of the biomechanical factors of force of impact, bone strength, fall height and surface stiffness on the risk of forearm fracture in obese children compared to non-obese children.
Methodology:   Anthropometric and dual-energy X-ray absorptiometry bone density data from 50 boys (25 obese pair-matched with 25 non-obese subjects) aged 4−17 years were entered into a rheological-stochastic simulation model of arm impact.
Results:   Obese children were shown to be at 1.7 times greater risk of fracture compared to non-obese children. Lower fall heights and softer impact surfaces were found not to reduce the relative risk of fracture between obese and non-obese children.
Conclusions:   Environmental modifications are unlikely to lower the risk of arm fracture in obese children to the same levels experienced by non-obese children. The best option available for obese children to reduce fracture risk is to take steps to attain a healthy bodyweight.     

Incidence of sterile cerebrospinal fluid pleocytosis in infants with urinary tract infection

Aim:   To determine the incidence of sterile cerebrospinal fluid (CSF) pleocytosis in infants ≤6 months old with urinary tract infection (UTI).
Methods:   Retrospective study of children admitted to a tertiary children's hospital in 2006 and 2007 with UTI who also had a lumbar puncture performed. All urine specimens were tested for anti-microbial activity.
Results:   Twelve (11.3%) of 106 infants with UTI had concurrent CSF pleocytosis. None of these patients had anti-microbial activity in the urine, showing that they had not received prior antibiotics. None of the 15 neonates (≤28 days old) with UTI and lumbar puncture had CSF pleocytosis. Antibiotics were stopped after a maximum of 10 days.
Conclusion:   Our results are compatible with published reports on the proportion of infants with UTI who have concurrent sterile CSF pleocytosis. We were able to exclude previous antibiotic therapy by measuring urinary anti-microbial activity. Our work supports the hypothesis that CSF pleocytosis in UTI is inflammatory and not because of infection of the central nervous system.     

Osteoporosis pseudoglioma syndrome: treatment of spinal osteoporosis with intravenous bisphosphonates

OBJECTIVES: To determine whether intravenous bisphosphonate treatment is helpful for children with osteoporosis pseudoglioma syndrome who have severe osteoporosis. METHODS: Three children (ages 9 to 11 years) with osteoporosis pseudoglioma syndrome who had multiple vertebral collapse were treated over a 2-year period with intermittent intravenous bisphosphonate infusions (pamidronate in 2, clodronate in 1). The responses to therapy were assessed with clinical and radiographic evaluation and bone densitometry of the spine. RESULTS: All 3 subjects reported early reductions in bone pain and improved mobility. Radiographs showed dense new bone in the vertebral end plates and remodeling of the vertebral bodies. Areal bone mineral density at the lumbar spine (age-appropriate SD score) improved from a mean of -4.5 before treatment to -2.8 after 2 years (P <.05). No new fractures occurred, and side effects were minimal. Growth and pubertal development proceeded normally. CONCLUSIONS: Intravenous bisphosphonate therapy appears safe and beneficial in patients with this condition and may prevent progressive vertebral deformity.     

Acquisition of bone mass in normal individuals and in patients with growth hormone deficiency

Children and adolescents with growth hormone (GH) deficiency (GHD) have reduced bone turnover and bone mass in comparison with normal individuals. GH replacement therapy stimulates bone turnover and improves bone mass during childhood and adolescence. At final height, patients with GHD treated with GH have normal mean values of bone mass, but some patients have reduced lumbar BMD (Z score <1) with an increased susceptibility to fractures. Children and adolescents with GHD have approximately a fourfold decreased fracture frequency during treatment in comparison with controls. The changes of bone mass during the transition to adulthood in patients with GHD who discontinued GH treatment after final height are not defined. An increase of lumbar BMD after final height has been reported until 2 years after discontinuation of GH treatment; this could be the result of a spontaneous progression towards peak bone mass or of a persisting effect of GH treatment on bone mass accumulation. GH has an important role in the accrual of bone mass during childhood and adolescence, but the impact of GHD on bone mass during the transiton to adulthood is unknown.     

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.     

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.