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.

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.

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.

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.

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.