Hans Pruijs

Skeletal effects and functional outcome with olpadronate in children with osteogenesis imperfecta: a 2-year randomised placebo-controlled study

BACKGROUND Non-randomised studies have suggested beneficial effects of bisphosphonates in osteogenesis imperfecta. We assessed the effects of oral olpadronate in children with this disorder in a randomised double-blind placebo-controlled trial. METHODS 34 children recruited from the Dutch national centre for osteogenesis imperfecta were randomly assigned olpadronate (10 mg/m2 daily; n=16) or placebo (n=18) for 2 years. All children also received calcium and vitamin D supplements. Primary endpoints were incident fractures of long bones and changes in bone mineral content (BMC), bone mineral density (BMD), and functional outcome. Anthropometry, vertebral height, and urinary markers of bone resorption were also studied. Analyses were by intention to treat. FINDINGS Fracture follow-up was complete for all the children, including two who withdrew from the study (one from each group). Olpadronate treatment was associated with a 31% reduction in relative risk of fracture of long bones (hazard ratio 0.69 [95% CI 0.52-0.91], p=0.01). The olpadronate group showed significantly greater increases than the placebo group in spinal BMC (difference between groups 2.24 g/year [0.20-4.29], p=0.03) and spinal BMD (difference between groups 0.054 g/cm2 per year [0.012-0.096], p=0.01). There were no detectable effects on functional outcome, anthropometrics, or vertebral height and no differences between the groups in changes in urinary markers of bone resorption. INTERPRETATION Oral treatment with olpadronate at a daily dose of 10 mg/m2 results in a reduction of fracture risk of long bones in children with osteogenesis imperfecta. However, the issue of whether bisphosphonates will alter the natural course of osteogenesis imperfecta remains unresolved, and further studies are needed.

Osteogenesis imperfecta in childhood: treatment strategies.

Osteogenesis imperfecta (OI) is a skeletal disorder of remarkable clinical variability characterized by bone fragility, osteopenia, variable degrees of short stature, and progressive skeletal deformities. Additional clinical manifestations such as blue sclerae, dentinogenesis imperfecta, joint laxity, and maturity onset deafness are described in the literature. OI occurs in about 1 in 20,000 births and is caused by quantitative and qualitative defects in the synthesis of collagen I. Depending on the severity of the disease, a large impact on motor development, range of joint motion, muscle strength, and functional ability may occur. Treatment strategies should primarily focus on the improvement of functional ability and the adoption of compensatory strategies, rather than merely improving range of joint motion and muscle strength. Surgical treatment of the extremities may be indicated to stabilize the long bones to optimize functional ability and walking capacity. Surgical treatment of the spine may be indicated in patients with progressive spinal deformity and in those with symptomatic basilar impression.

Spinal complications in osteogenesis imperfecta: 47 patients 1-16 years of age

We examined in a cross-sectional study, 47 children (mean age 7.7 (1-16) years) with osteogenesis imperfecta (OI) to find the prevalence of spinal deformities and to correlate these observations with anthropometry. The associations between dentinogenesis imperfecta, joint hypermobility and spinal deformities were also studied. Disproportion in stature in OI type I and type IV was mainly caused by spinal involvement, as evidenced by a greater decrease in body height than in leg length. In OI type I, the decrease in sitting height was mainly caused by platyspondyly, whereas in OI types III and IV, it was also caused by progressive scoliosis and kyphosis. Scoliosis was present in 22 children, and pathological kyphosis in 18, mainly in the severe OI types. Basilar impression was observed in 10 children, mainly in type III. Children with dentinogenesis imperfecta seemed to be prone to develop scoliosis, pathological kyphosis and basilar impression. Children with generalized joint hypermobility were less prone to develop scoliosis and basilar impression. Our observations may contribute to a better understanding of the risk factors for progressive spinal deformities in OI.

Intramedullary rodding in type III osteogenesis imperfecta. Effects on neuromotor development in 10 children.

We studied retrospectively gross motor development and the impact of intramedullary rodding in 10 children with type III osteogenesis imperfecta (OI). There was a pronounced delay in motor development and the order in achieving gross motor milestones differed from the normal developmental sequence. Static milestones developed at an earlier stage than dynamic milestones. Intramedullary rodding of the lower extremities prior to the age of 3.5 years enhanced neuromotor development, especially regarding the milestones supported standing, rolling from prone to supine and crawling with abdomen on the floor. The different sequence in achieving gross motor milestones should have implications for future rehabilitation programs and for orthopedic surgery.

Results of Pavlik harness treatment in children with dislocated hips between the age of six and twenty-four months.

Background We retrospectively studied the outcome of Pavlik harness treatment in late-diagnosed hip dislocation in infants between 6 and 24 months of age (Graf type 3 and 4 or dislocated hips on radiographs) treated in our hospital between 1984 and 2004. The Pavlik harness was progressively applied to improve both flexion and abduction of the dislocated hip. In case of persistent adduction contracture, an abduction splint was added temporarily to improve the abduction. Methods We included 24 patients (26 hips) between 6 and 24 months of age who presented with a dislocated hip and primarily treated by Pavlik harness in our hospital between 1984 and 2004. The mean age at diagnosis was 9 months (range 6 to 23 mo). The average follow-up was 6 years 6 months (2 to 12 y). Ultrasound images and radiographs were assessed at the time of diagnosis, one year after reposition and at last follow-up. Results Twelve of the twenty-six hips (46%) were successfully reduced with Pavlik harness after an average treatment of 14 weeks (4 to 28 wk). One patient (9%) needed a secondary procedure 1 year 9 months after reposition because of residual dysplasia (Pelvis osteotomy). Seventeen of the 26 hips were primary diagnosed by Ultrasound according to the Graf classification. Ten had a Graf type 3 hip and 7 hips were classified as Graf type 4. The success rate was 60% for the type 3 hips and 0% for the type 4 hips. (P=0.035). None of the hips that were reduced with the Pavlik harness developed an avascular necrosis (AVN). Of the hips that failed the Pavlik harness treatment, three hips showed signs of AVN, 1 after closed reposition and 2 after open reposition. Conclusion The use of a Pavlik harness in the late-diagnosed hip dislocation type Graf 3 can be a successful treatment option in the older infant. We have noticed few complications in these patients maybe due to progressive and gentle increase of abduction and flexion, with or without temporary use of an abduction splint. The treatment should be abandoned if the hips are not reduced after 6 weeks. None of the Graf 4 hips could be reduced successfully by Pavlik harness. This was significantly different from the success rate for the Graf type 3 hips. Level of Evidence Therapeutic study, clinical case series: Level IV.

Complications of the Bailey-Dubow elongating nail in osteogenesis imperfecta: 34 children with 110 nails.

The Bailey-Dubow nail, inserted in the femur or tibia of 34 children with osteogenesis imperfecta (OI), was studied retrospectively. Comparing the various groups of OI, no significant difference was found. Location of the nail (tibia or femur) did not influence the complication rate significantly. The reoperation rate was 29%, a rate comparable to that reported in earlier studies. The part of the nail located around the knee had a significantly higher migration rate (P = 0.005 at obturator ends and P = 0.007 at sleeve ends). Migration of the nail was the reason to reoperate in 50% of the patients. Better anchoring of the T-piece will substantially decrease the complication rate. In consideration of the different functional capacities of the OI population, the complications are likely related more to the hardware than to the patient.

Urological Problems After Surgical Treatment of Scoliosis in Children with Myelomeningocele

PURPOSE We assessed urological problems and complications after scoliosis surgery in children with myelomeningocele. MATERIALS AND METHODS A total of 16 children with myelodysplasia underwent surgery for scoliosis using different surgical techniques and instrumentation systems. Mean patient age at operation as 11 years and mean postoperative followup was 3 years. All patients had urological assessment before and after surgery, including urodynamics. RESULTS Urological problems after surgical correction of scoliosis developed in 6 patients (38%). Three girls had difficulty performing clean intermittent self-catheterization postoperatively because of altered body posture, a genital pressure sore and a plaster body cast, respectively. In 4 patients, including 1 girl with problems performing clean intermittent self-catheterization, lower urinary tract function was altered, leading to upper urinary tract deterioration in 1 and worsening of urinary incontinence in 3. CONCLUSIONS Children with myelomeningocele have a high incidence of urological complications after surgical treatment of scoliosis. Anticipation of the problems and a thorough postoperative urological evaluation, including urodynamics, can reduce morbidity and facilitate appropriate treatment.

Transinguinal sonographic determination of the position of the femoral head after reposition and follow-up in a spica cast.

BackgroundTransinguinal sonography can be used to demonstrate the position of the femoral head after reduction of a dislocated hip.ObjectiveTo determine whether transinguinal sonography can replace radiography and CT in the follow-up after reduction of a hip dislocation?Materials and methodsThirty-three children with 39 dislocated hips were followed up with sonography after reduction and immobilization in a spica cast. In cases of an abnormal position a CT scan was advised. A pelvic radiograph at the end of treatment served as an indicator that no dislocations were missed during the previous sonographic examinations.ResultsThe repositioned hips were examined on 138 occasions. Twenty-four examinations were abnormal and CT scanning was performed on 11 occasions. In four children additional CT was done because a recurrent dislocation was suspected or because sonography was difficult to perform. No dislocations were demonstrated. In five children a recurrent dislocation was suspected, on one or more occasions. In all but one child a CT scan was performed that confirmed the dislocation.ConclusionTransinguinal sonography is well-suited to demonstrate a normal position of the femoral head in a spica cast. Transinguinal sonography decreases the number of radiographs and CT scans and reduces the exposure to ionizing radiation.

The Interaction Between Sillence Type and BMD in Osteogenesis Imperfecta

Clinical studies with bisphosphonates in children with osteogenesis imperfecta (OI) show an increase in BMD and a decrease in fracture rate. Bone strength in children with OI is not only influenced by changes in BMD but also by changes in collagen I structure of the organic bone matrix. Therefore, we studied the interaction between these two factors in a cross-sectional, single center study including 54 children. We assumed that vertebral deformities in OI represent an unbalance between load and bone strength. Body weight was considered to be a well quantifiable load on vertebral bodies. BMD served as a marker, representing the amount of bone tissue available for vertebral load bearing, and the Sillence classification, either type I or III/IV, as a marker representing the quality of the organic bone matrix. Independent associations were observed between the prevalence of vertebral deformities and (1) Sillence type (OR: 5.7, 95%Cl:1.2–26.8), (2) BMD (OR: 0.003, 95%Cl: 0–0.25) and (3) body weight (OR: 1.15, 95%Cl: 1.05–1.25). Regarding the anthropometrical differences among the different types of OI, the BMD/body weight ratio was introduced to evaluate the BMD in relation to body size. Prevalent vertebral deformities were associated with low BMD/body weight ratios (OR: 0.04, 95%Cl: 0.008–0.2) in OI type I, but no association was found in type III/IV. It was concluded that BMD and Sillence type have independent relationships with vertebral deformities. The BMD/body weight ratio correlates with vertebral deformities in children with OI type I. Its meaning in types III/IV needs further research with larger samples because of the relatively high prevalence of vertebral deformities in this group.