Effect of the Sharrard procedure on hip instability in children with Down syndrome: a retrospective study.

PURPOSE: The aim of this study was to retrospectively analyze the effect of the Sharrard procedure on hip instability in children with Down syndrome (DS), as measured by the migration index. METHODS: In total, 17 children (21 hips) were included from six hospitals in the Netherlands between 2003 and 2019. The primary outcome, hip instability, was assessed with the Reimers' migration index on preoperative and postoperative plain anteroposterior pelvic radiographs. The mean age at surgery was 8.1 years, the majority of children were male (64.7%) and the mean follow-up time was 7.3 years. RESULTS: The mean preoperative migration index was 46% (sd 23.5) and the mean postoperative migration index was 37% (sd 28.4). The mean Delta migration index (the difference in pre-operative migration index and most recent post-operative migration index) showed an improvement of 9.3% (sd 22.7). An improvement in migration index was observed in 52%, no change in 29% and deterioration in 19% of hips. No (re)dislocations occurred in 91% of the hips. No major complications were observed during the follow-up period. CONCLUSION: Early intervention is warranted in children with DS showing hip instability or hip migration, in order to succeed with less complex procedures. The Sharrard procedure should be considered in children with DS showing hip instability or hip migration, since it aims to rebalance the muscles of the hip joint, is less complex than bony procedures of the femur and acetabulum, surgery time is often shorter, there are fewer major complications and the rehabilitation period is shorter. LEVEL OF EVIDENCE: IV - retrospective case series.

Satisfaction and pain levels after proximal femoral valgus osteotomy according to Schanz in patients with cerebral palsy and hip dislocation.

Outcome after Schanz osteotomy in the treatment of chronic hip dislocation in children with cerebral palsy was evaluated. Medical charts and questionnaires were used to assess pain, functional outcome and satisfaction. A total of 24 children, with a mean age of 13.8 years (± 8.9), were included in the study, out of which 11 were classified with Gross Motor Function Classification System (GMFCS) level IV and 13 with GMFCS level V. Current pain was comparable to patients without chronic hip dislocation, and satisfaction was intermediate. Functional outcome improved in several domains. Longer postoperative time was associated with improved pain and satisfaction. The Schanz osteotomy allowed improvement in pain levels; however, it did not completely meet caregiver's expectation and has high reoperation rates.

Spinal cord transection before scoliosis correction in myelomeningocele may improve bladder function.

AIMS: In patients with myelomeningocele (MMC) and coexistent scoliosis, a spinal cord transection (SC-transection) is sometimes performed before scoliosis correction to prevent traction on the myelum after stretching the spinal column. Performing a SC-transection may have positive effects on bladder function, especially in case of refractory detrusor-sphincter dyssynergia. This study investigates the effects of SC-transection on lower and upper urinary tract outcomes. METHODS: All children with MMC who underwent scoliosis correction (1989-2009) were retrospectively reviewed. Cases were defined as those who underwent a SC-transection before scoliosis correction, whereas the control group comprised children who had a scoliosis correction alone. Urodynamic and clinical outcomes were examined. RESULTS: A total of 7 cases and 13 controls were identified. Postoperatively, compared to the control group, cases had relatively more often improvement of compliance (improvement in 6/7 vs. 9/13) and bladder capacity (improvement in 6/7 vs. 8/13). No effect of SC-transection was found on incontinence severity, clean intermittent catheterization frequency, use of antimuscarinic drugs, or signs of renal damage on ultrasound. CONCLUSIONS: SC-transection before scoliosis correction in children with MMC without lower extremity function, may improve bladder function with respect to bladder compliance and bladder capacity. Changes in symptoms or renal ultrasound were not found. No harmful effects of SC-transection were found, indicating that this procedure can be performed safely with respect to bladder function in these patients. Whether or not SC-transection should be recommended during scoliosis correction in patients with MMC to improve bladder function requires further study.

PLS3 mutations in X-linked osteoporosis with fractures.

Plastin 3 (PLS3), a protein involved in the formation of filamentous actin (F-actin) bundles, appears to be important in human bone health, on the basis of pathogenic variants in PLS3 in five families with X-linked osteoporosis and osteoporotic fractures that we report here. The bone-regulatory properties of PLS3 were supported by in vivo analyses in zebrafish. Furthermore, in an additional five families (described in less detail) referred for diagnosis or ruling out of osteogenesis imperfecta type I, a rare variant (rs140121121) in PLS3 was found. This variant was also associated with a risk of fracture among elderly heterozygous women that was two times as high as that among noncarriers, which indicates that genetic variation in PLS3 is a novel etiologic factor involved in common, multi-factorial osteoporosis.

Bone mineral density in developing children with osteogenesis imperfecta: a longitudinal study with 9 years of follow-up.

BACKGROUND AND PURPOSE: Osteogenesis imperfecta (OI) is a heritable disorder of connective tissue caused by a defect in collagen type I synthesis. For bone, this includes fragility, low bone mass, and progressive skeletal deformities, which can result in various degrees of short stature. The purpose of this study was to investigate development of bone mineral density in children with OI. PATIENTS AND METHODS: Development of lumbar bone mineral density was studied retrospectively in a cohort of 74 children with OI. Mean age was 16.3 years (SD 4.3). In 52 children, repeated measurements were available. Mean age at the start of measurement was 8.8 years (SD 4.1), and mean follow-up was 9 years (SD 2.7). A longitudinal data analysis was performed. In the total cohort (74 children), a cross-sectional analysis was performed with the latest-measured BMD. Age at the latest BMD measurement was almost equal for girls and boys: 17.4 and 17.7 years respectively. RESULT: Mean annual increase in BMD in the 52 children was 0.038 g/cm(2)/year (SD 0.024). Annual increase in BMD was statistically significantly higher in girls, in both the unadjusted and adjusted analysis. In cross-sectional analysis, in the whole cohort the latest-measured lumbar BMD was significantly higher in girls, in the children with OI of type I, in walkers, and in those who were older, in both unadjusted and adjusted analysis. INTERPRETATION: During 9 years of follow-up, there appeared to be an increase in bone mineral density, which was most pronounced in girls. One possible explanation might be a later growth spurt and older age at peak bone mass in boys.

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

BACKGROUND: Transinguinal sonography can be used to demonstrate the position of the femoral head after reduction of a dislocated hip. OBJECTIVE: To determine whether transinguinal sonography can replace radiography and CT in the follow-up after reduction of a hip dislocation? MATERIALS AND METHODS: Thirty-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. RESULTS: The 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. CONCLUSION: Transinguinal 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.

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.

Prevalence of vertebral pars defects (spondylolysis) in a population with osteogenesis imperfecta.

STUDY DESIGN: We performed a retrospective study of spinal roentgenograms of a large cohort of patients suffering from osteogenesis imperfecta. OBJECTIVE: To determine the prevalence of vertebral pars defects (spondylolysis) in patients with osteogenesis imperfecta. SUMMARY OF BACKGROUND DATA: Patients suffering from osteogenesis imperfecta are known to be prone to pathologic fractures. Pathologic fractures due to microtraumas, repetitive activities, and posture acting together on a congenitally weakened pars interarticularis may lead to vertebral pars defects. The prevalence of vertebral pars defects in patients with osteogenesis imperfecta has never been studied before to our knowledge. METHODS: We performed a retrospective study of posterior-anterior and lateral, standing, roentgenograms of the spine of patients with osteogenesis imperfecta for the occurrence of vertebral pars interarticularis defects. RESULTS: The patients (5.3%) in our series showed vertebral pars defects, this is not significantly different from the prevalence of vertebral pars defects in the general population. CONCLUSION: 5.3% of the patients with osteogenesis imperfecta showed vertebral pars defects, this does not differ significantly from the occurrence in the general population.

Physical training in children with osteogenesis imperfecta.

OBJECTIVE: To study the effects of a physical training program on exercise capacity, muscle force, and subjective fatigue levels in patients with mild to moderate forms of osteogenesis imperfecta (OI). STUDY DESIGN: Thirty-four children with OI type I or IV were randomly assigned to either a 12-week graded exercise program or care as usual for 3 months. Exercise capacity and muscle force were studied; subjective fatigue, perceived competence, and health-related quality of life were secondary outcomes. All outcomes were measured at baseline (T = 0), after intervention (T = 1), and after 6 and 9 months (T = 2 and T = 3, respectively). RESULTS: After intervention (T = 1), peak oxygen consumption (VO2peak), relative VO2peak (VO2peak/kg), maximal working capacity (Wmax), and muscle force were significantly improved (17%, 18%, 10%, and 12%, respectively) compared with control values. Subjective fatigue decreased borderline statistically significantly. Follow-up at T = 2 showed a significant decrease of the improvements measured at T = 1 of VO2peak, but VO2peak/kg, Wmax, and subjective fatigue showed no significant difference. At T = 3, we found a further decrease of the gained improvements. CONCLUSION: A supervised training program can improve aerobic capacity and muscle force and reduces levels of subjective fatigue in children with OI type I and IV in a safe and effective manner.

Quality of life in children with osteogenesis imperfecta treated with oral bisphosphonates (Olpadronate): a 2-year randomized placebo-controlled trial.

UNLABELLED: In this double-blind randomised placebo-controlled trial it was investigated during a two-year follow-up whether oral bisphosphonates (Olpadronate 10 mg/m2/day) influence quality of life in children with osteogenesis imperfecta (OI). Thirty-four children with OI (classified according to Sillence criteria), aged 3 to 18 years of age, with a restricted level of ambulation were included. Randomisation was performed using a list of computer generated random numbers to allocate patients to receive Olpadronate or placebo. Quality of life was measured using self-perception profile for children (SPPC) and health-utility index (HUI). Differences between baseline measurements and measurements at two years follow-up were analysed within the Olpadronate and placebo group using a student's t-test. Differences in HUI and SPPC regression coefficients were analysed by random-effects repeated measures analysis (SAS, Proc Mixed, version 8.2), adjusted for age, gender and type of OI. Within the Olpadronate group there was a significant decrease in pain utility; however, difference in six months' regression coefficients between the placebo and Olpadronate group were not significant. Within the placebo group there was a significant increase in scholastic competence and behavioural conduct. The item behavioural conduct showed a steeper annual regression coefficient favourable for the placebo group. In the other SPPC items none of the annual regression coefficients showed a significant difference between the Olpadronate and the placebo group. CONCLUSION: We found only slight differences in quality of life in favour of the bisphosphonate group. A small but not significant decrease in pain was detected in the bisphosphonate group.

Spinal decompensation in neuromuscular disease.

STUDY DESIGN: In this retrospective radiography study, we analyzed curve shape and direction in scoliosis secondary to neuromuscular disease. OBJECTIVE: To determine if in different types of neuromuscular scoliosis a predominant curve pattern can be found and if similarities with idiopathic scoliosis exist. SUMMARY OF BACKGROUND DATA: To the authors' knowledge, systematic analysis of curve patterns in patients with neuromuscular scoliosis has not been performed in a group of this size and composition. METHODS: Spinal full-length radiographs of 198 patients with neuromuscular scoliosis were analyzed for curve shape and direction. Patients were divided into 4 groups consisting of Duchenne muscular dystrophy, cerebral palsy, spinal muscular atrophy, and spina bifida. RESULTS: The results of this study show a predominance of right-sided thoracic and thoracolumbar curves, and left-sided lumbar curves, which differed significantly from an equal right-left distribution. Apical levels were respectively at T8, T12/L1 disc, and L2. CONCLUSION: In neuromuscular scoliosis, curve patterns and apical levels are similar to what is seen in the most prevalent types of adolescent idiopathic scoliosis.

Cardiopulmonary fitness and muscle strength in patients with osteogenesis imperfecta type I.

OBJECTIVE: To evaluate cardiopulmonary function, muscle strength, and cardiopulmonary fitness (VO 2 peak) in patients with osteogenesis imperfecta (OI). STUDY DESIGN: In 17 patients with OI type I (mean age 13.3 +/- 3.9 years) cardiopulmonary function was assessed at rest using spirometry, plethysmography, electrocardiography, and echocardiography. Exercise capacity was measured using a maximal exercise test on a bicycle ergometer and an expired gas analysis system. Muscle strength in shoulder abductors, hip flexors, ankle dorsal flexor, and grip strength were measured. All results were compared with reference values. RESULTS: Cardiopulmonary function at rest was within normal ranges, but when it was compared with normal height for age and sex, vital capacities were reduced. Mean absolute and relative VO 2 peak were respectively -1.17 (+/- 0.67) and -1.41 (+/- 1.52) standard deviations lower compared with reference values ( P < .01). Muscle strength also was significantly reduced in patients with OI, ranging from -1.24 +/- 1.40 to -2.88 +/- 2.67 standard deviations lower compared with reference values. CONCLUSIONS: In patients with OI type I, no pulmonary or cardiac abnormalities at rest were found. The exercise tolerance and muscle strength were significantly reduced in patients with OI, which might account for their increased levels of fatigue during activities of daily living.

Osteogenesis imperfecta in childhood: impairment and disability. A prospective study with 4-year follow-up.

OBJECTIVES: To study (1). changes in anthropometrics, joint range of motion (ROM), muscle strength, functional ability, caregiver assistance, and level of ambulation in children with osteogenesis imperfecta (OI) and (2). the prediction of clinical characteristics at the level of ambulation at follow-up and the prediction of clinical characteristics on progression or regression at the level of ambulation over time. DESIGN: Prospective study with follow-up of 4 years. SETTING: A children's hospital that serves a nationwide center for treatment and research in children with OI in the Netherlands. PARTICIPANTS: At follow-up, 49 children (24 boys, 25 girls; mean age +/- standard deviation, 11.3+/-3.8y; range, 5.2-19.4y) participated. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Anthropometry, joint ROM, muscle strength, fracture frequency, intramedullary rodding, level of ambulation, functional ability, and caregiver assistance. RESULTS: In type I OI, total joint ROM decreased significantly over time, especially in the lower extremities, with a significant decrease in generalized joint hypermobility according to Bulbena (median start, 7.5; interquartile range [IQR], 4-9; median end, 6; IQR, 2-7; P<.001). In types III and IV, a severe decrease in total joint ROM was present without significant changes over time. No significant changes in total muscle strength (upper or lower extremities) in the different types of OI were measured at follow-up. In OI type I, a significant increase in self-care (P=.003) and social function (P=.008) was measured; in type III, a significant increase in self-care (P=.003), mobility (P=.004), and social function (P=.005) was measured, with a significant decrease in parental assistance in self-care (P=.02) and mobility (P=.005). In type IV, a significant increase was observed in the self-care (P=.01) and social function domains (P=.02). Type of OI (regression coefficient=-1.0; 95% confidence interval [CI], -1.64 to -0.47) and total muscle strength were the only significant predictors for level of ambulation (regression coefficient=.01; 95% CI,.17-.32). Body weight was significantly lower in the group that progressed in level of ambulation (P=.03), whereas children with a decline in level of ambulation had significantly higher body weight (P=.05). CONCLUSIONS: Ours is the first study with a long-term follow-up that provides information concerning the natural course of developmental outcome parameters of OI in childhood. Joint ROM and muscle strength did not change significantly over time, possibly because of the biomechanical skeletal properties of the different OI types. Functional ability improved significantly over time, but, especially in types III and IV, did not reach normative values, possibly because of a plateau phase in functional ability. Knowledge of the natural course of the disease is essential to interpret the results from intervention studies.

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.

Identification of PLOD2 as telopeptide lysyl hydroxylase, an important enzyme in fibrosis.

The hallmark of fibrotic processes is an excessive accumulation of collagen. The deposited collagen shows an increase in pyridinoline cross-links, which are derived from hydroxylated lysine residues within the telopeptides. This change in cross-linking is related to irreversible accumulation of collagen in fibrotic tissues. The increase in pyridinoline cross-links is likely to be the result of increased activity of the enzyme responsible for the hydroxylation of the telopeptides (telopeptide lysyl hydroxylase, or TLH). Although the existence of TLH has been postulated, the gene encoding TLH has not been identified. By analyzing the genetic defect of Bruck syndrome, which is characterized by a pyridinoline deficiency in bone collagen, we found two missense mutations in exon 17 of PLOD2, thereby identifying PLOD2 as a putative TLH gene. Subsequently, we investigated fibroblasts derived from fibrotic skin of systemic sclerosis (SSc) patients and found that PLOD2 mRNA is highly increased indeed. Furthermore, increased pyridinoline cross-link levels were found in the matrix deposited by SSc fibroblasts, demonstrating a clear link between mRNA levels of the putative TLH gene (PLOD2) and the hydroxylation of lysine residues within the telopeptides. These data underscore the significance of PLOD2 in fibrotic processes.

Scoliosis in children with osteogenesis imperfecta: influence of severity of disease and age of reaching motor milestones.

We studied the relationship between the age of reaching motor milestones, especially anti-gravity activities, and the age of development of pathological spinal curvatures in children with osteogenesis imperfecta (OI). We hypothesized that earlier achievement of anti-gravity motor milestones predicts a later development of pathological spinal curvatures. Ninety-six children participated in this retrospective study. The severity of the disease was classified according to Sillence into types I-IV. Spinal radiography was performed annually and spinal deformities were measured according to the Cobb angle. Scoliosis was defined as a Cobb angle exceeding 9 degrees. Pathological thoracic kyphosis was defined as a Cobb angle exceeding 40 degrees. The parents were asked to report the age at which the child achieved motor milestones, and data were checked against health care records. Thirty-seven of 96 children (39%) developed a scoliosis of more than 9 degrees. Nine of 96 children (9%) developed a pathological kyphosis. The age of developing scoliosis was significantly lower than the age of development of the pathological kyphosis (P=0.01). Bone mineral density was measured by dual energy X-ray absorptiometry (DEXA) in 53 children, 28 of whom developed scoliosis, and 25 of whom did not. The mean DEXA Z-score of the 28 children with scoliosis was significantly lower than that of the 25 children without (-5.2, SD 1.3 vs -3.2, SD 1.9; P-value <0.001). Children with OI type IV, but particularly OI type III, reached motor milestones much later than children with OI type I. The motor milestone "supported sitting" showed a significant inverse association with time of the first presence of scoliosis with a Cobb angle greater than 9 degrees (linear regression coefficient: -1.3, 95% confidence interval: -2.6 to -0.03). The age of achieving the motor milestones "lifting the head to 45 degrees in prone position", "rolling", and "supported-" and "unsupported standing" were not significantly associated with age of the first presence of scoliosis with a Cobb angle greater than 9 degrees. However, the directions of associations suggest that here, too, there is a tendency for later development of scoliosis in those who reach milestones at earlier ages. Multivariable analyses showed that the motor milestone "sitting with support" was significantly associated with age of first achieving scoliosis, independent of gender and type of OI (linear regression coefficient: -0.9, 95% confidence interval: -1.3 to -0.5). We conclude that in children with OI, the age of anti-gravity motor milestones was associated with the age of development of pathological spinal curvatures. Earlier achievement of the motor milestone "supported sitting" predicted significantly a later development of pathological spinal curvatures, independent of gender and type of OI.

Ultrasound in the management of the position of the femoral head during treatment in a spica cast after reduction of hip dislocation in developmental dysplasia of the hip.

In this prospective study of 18 hips we compared the efficacy of ultrasound with CT in determining the position of the femoral head in a spica cast after closed or open reduction in children with developmental dysplasia of the hip. Ultrasound was performed through the perineal opening of the cast. With a transinguinal approach, the superior ramus of the pubis, the acetabulum, the femoral head and the femoral neck can be depicted in one plane. The CT and ultrasound images were blinded and reviewed by two of the authors. Ultrasound was inconclusive in the first two reductions since the perineal opening was too small to see all the landmarks in one plane. In the following 16 reductions the landmarks were well defined and interpretation of the CT and ultrasound was similar. The perineal opening in the spica cast should be made in such a way that the ultrasound probe can be positioned in the groin so that the landmarks can be shown in one plane.