Retrograde Application of Humerus Fassier-Duval Rod in Osteogenesis Imperfecta: A New Surgical Technique.

BACKGROUND: The aim of this study is to describe the technique of retrograde application of Fassier-Duval (FD) rod for the humerus in patients with osteogenesis imperfecta (OI). This technique was developed to overcome the downsides of the previously used techniques of humerus rodding. METHODS: The study was done at a tertiary care pediatric orthopaedic hospital from April 2014 to August 2021. Skeletally immature patients with OI who underwent retrograde FD rodding were included. This surgery was performed for humeral shaft fractures/bowing limited to the distal half of the bone to ensure appropriate stability of the fixation. Surgical technique of the procedure is described in detail. RESULTS: Six patients with OI, of which 2 (33.3%) had FD rodding bilaterally, were included. The mean age at rodding was 7.6±3.5 (range: 3 to 14) years. The mean duration of postoperative follow-up was 45.5±18.0 (range: 24 to 75) months. All patients had full healing of the fracture/osteotomy, with functional alignment of their humeri. No surgical complications were observed; however, 1 (12.5%) segment only had a traumatic humerus fracture following a fall that was associated with rod migration, occurring 60 months postoperatively. This was treated with a retrograde FD rodding again, with fracture augmentation with plate and screws. CONCLUSIONS: The retrograde FD rodding technique of the humerus in OI patients is relatively simple and preserves the soft tissue surrounding the shoulder joint, with favorable outcomes. Studies with larger sample size and long-term follow-up duration are needed. LEVEL OF EVIDENCE: Level IV-case series.

Osteogenesis Imperfecta-Who Needs Rodding Surgery?

PURPOSE OF REVIEW: The purpose of this review is to precise the indications for intramedullary rodding of long bones in osteogenesis imperfecta, the classic treatment for fractures and deformities in this condition. RECENT FINDINGS: The use of plates and screws alone is not recommended, but its use in conjunction with rodding is becoming more popular as demonstrated in recent literature. The different types of rods are reviewed and their advantages/disadvantages exposed. There is a clear advantage for telescopic rods in terms of incidence of revision surgery but complications are still to be expected. An interdisciplinary approach combining a medical treatment with a surgical correction of deformities as well as a rehabilitation program is the key for success in the treatment of osteogenesis imperfecta children.

Predicting ambulatory function at skeletal maturity in children with moderate to severe osteogenesis imperfecta.

Maximizing ambulation is a key treatment aim in moderate to severe osteogenesis imperfecta (OI). Here we investigated which early clinical characteristics predicted ambulation function at skeletal maturity. We assessed Bleck ambulation scores in 88 individuals with OI at 5 to 6 years of age and again at final height (at 15 to 24 years of age). At 5 to 6 years of age, 33 (38%) children were non-ambulators, 32 (36%) were fully independent ambulators, and 23 (26%) had intermediate ambulation skills. At skeletal maturity, 58% of the study participants had the same mobility level as at first assessment. The ability to ambulate independently at skeletal maturity was predicted by independent ambulation at 5 to 6 years (odds ratio [OR] 22.6, 95% confidence interval [CI] 4.9-105; P < 0.001), height z score at 5 to 6 years (OR 3.1, CI 1.6-6.3; P = 0.001) and weight z score at 5 to 6 years (OR 0.44, CI 0.19-0.99; P = 0.04).Conclusion: Independent ambulation at 5 to 6 years was the main determinant of independent ambulation at skeletal maturity. This highlights the importance of maximizing ambulation in children below 5 years of age. What is Known: •walking ability varies markedly between OI types. The highest level of mobility was found in OI type I, the lowest in OI type III who require mobility aids; intermediate levels were reported for OI type IV. • OI type is a key predictor of ultimate ability to ambulate, whereas the timing of developmental milestones was not associated with walking ability What is New: • overall key predictors of mobility function at skeletal maturity were mobility status and height z-score at 5-6 years of age • Childrenwho were non-ambulators at 5 to 6 years of age had a higher chance of having better mobility at skeletal maturity if they had good upper extremity function, as expressed in the PEDI Self Care Score.

Treatment of Femur Neck Fracture in Children with Osteogenesis Imperfecta: Two Case Reports.

CASE: We present 2 cases of femoral neck fracture (FNF) in patients with osteogenesis imperfecta (OI) with a previously placed intramedullary nail (IMN). Case 1: A 12-year-old girl who sustained a right FNF after spine surgery. Case 2: An 18-year-old boy who sustained a right FNF after IMN of the left side. Both patients underwent our modified surgical technique as described below. Both patients recovered well overall. CONCLUSIONS: FNF in patients with OI poses a significant challenge especially in the presence of an IMN. Here, we describe a surgical technique that provides stable fixation with a less stress riser effect by bypassing the screws and a previously placed nail.

Functional Outcome of Forearm Rodding in Children With Osteogenesis Imperfecta.

BACKGROUND: The impact of corrective forearm surgery on functional ability in children with osteogenesis imperfecta (OI) has not previously been reported. This study addresses this issue. METHODS: A retrospective chart review was conducted on 19 children with OI who underwent 22 corrective forearm procedures between 1996 and 2013. Functional ability was assessed preoperatively and every year postoperatively using the Pediatric Evaluation of Disability Inventory (PEDI). RESULTS: The mean PEDI self-care score increased by 6.8 (P=0.017) and the mean PEDI mobility score increased by 7.2 (P=0.020) at 1-year postsurgery. Functional gains were greater in moderate OI (types IV, V, and VI) than in severe OI (type III). Improved function was maintained in the majority of cases at a mean of 8.9 years postcorrection. CONCLUSIONS: Corrective forearm surgery in children with OI leads to improved functional ability. LEVEL OF EVIDENCE: Level IV.

Functional Outcome of Humeral Rodding in Children With Osteogenesis Imperfecta.

BACKGROUND: The impact of humeral rodding on functional ability in children with osteogenesis imperfecta (OI) has not previously been reported. This article investigates this issue. METHODS: A retrospective chart review was conducted on 35 children with OI who underwent humeral rodding at our institution between 1995 and 2013. Fassier-Duval rods were inserted in 19 cases, K-wires in 13 cases, and Rush rods in 3 cases. Functional ability was assessed preoperatively and every year postoperatively using the self-care and mobility domains of the Pediatric Evaluation of Disability Inventory (PEDI). RESULTS: The mean PEDI self-care score increased by 5.7 (P=0.028) and the mean PEDI mobility score increased by 3.6 (P=0.008) at 1-year postsurgery. Improved function was maintained in the majority of cases at a mean of 7.0 years postcorrection. CONCLUSIONS: Humeral rodding in children with OI leads to significant improvement in functional ability. LEVEL OF EVIDENCE: Level IV.

Fassier-Duval Telescopic System: How I Do It?

The author describes step-by-step the technique for Fassier-Duval rodding of both femurs and tibiae in osteogenesis imperfecta. Preoperative evaluations and planning, postoperative care and place of bisphosphonates as explained. Emphasis is given on the different tricks to avoid intraoperative problems.

Osteogenesis imperfecta.

Skeletal deformity and bone fragility are the hallmarks of the brittle bone dysplasia osteogenesis imperfecta. The diagnosis of osteogenesis imperfecta usually depends on family history and clinical presentation characterized by a fracture (or fractures) during the prenatal period, at birth or in early childhood; genetic tests can confirm diagnosis. Osteogenesis imperfecta is caused by dominant autosomal mutations in the type I collagen coding genes (COL1A1 and COL1A2) in about 85% of individuals, affecting collagen quantity or structure. In the past decade, (mostly) recessive, dominant and X-linked defects in a wide variety of genes encoding proteins involved in type I collagen synthesis, processing, secretion and post-translational modification, as well as in proteins that regulate the differentiation and activity of bone-forming cells have been shown to cause osteogenesis imperfecta. The large number of causative genes has complicated the classic classification of the disease, and although a new genetic classification system is widely used, it is still debated. Phenotypic manifestations in many organs, in addition to bone, are reported, such as abnormalities in the cardiovascular and pulmonary systems, skin fragility, muscle weakness, hearing loss and dentinogenesis imperfecta. Management involves surgical and medical treatment of skeletal abnormalities, and treatment of other complications. More innovative approaches based on gene and cell therapy, and signalling pathway alterations, are under investigation.

Hip Dysplasia in Children With Osteogenesis Imperfecta: Association With Collagen Type I C-Propeptide Mutations.

BACKGROUND: Osteogenesis imperfecta (OI) is a heritable skeletal disorder characterized by bone fragility and short stature that is usually due to mutations in 1 of the 2 genes that code for collagen type I α-chains. The association between hip dysplasia and OI has not been systematically investigated. In this single-center study, we retrospectively reviewed all cases of OI associated with hip dysplasia to describe clinical characteristics and the effect of therapy. METHODS: We reviewed the charts of 687 patients with OI who were seen at the Shriners Hospital for Children in Montreal between 1999 and 2013 to identify patients with a diagnosis of hip dysplasia. Clinical characteristics and the course after therapeutic interventions were extracted from the charts. RESULTS: Hip dysplasia was diagnosed in 8 hips of 5 patients (4 boys, 1 girl; age at diagnosis ranged between 3 wk and 27 mo old). The prevalence of hip dysplasia and OI was therefore 0.87% (per patient). In 4 of the 5 patients (80%), OI was caused by mutations affecting the C-propeptide of collagen type I, which is otherwise rare in OI. Among the 26 patients with C-propeptide mutations followed at our institution, 4 (15%) had hip dysplasia. Pavlik harness treatment was attempted in 2 patients (3 hips) but was not effective in either case and resulted in avascular necrosis of 1 hip. Femoral varus derotational shortening osteotomies using a telescopic rod were performed in all 8 hips along with a closed reduction in 4 hips and an open reduction in 4 hips. Concomitant pelvic osteotomies were performed in 2 hips (1 patient). Surgery resulted in redislocation of 1 hip; all other surgically treated hips remained reduced. CONCLUSIONS: Clinical screening for hip dysplasia is difficult in OI owing to the bowing of the proximal femur and the risk of causing fractures. OI patients with positive C-propeptide mutation should therefore be screened for hip dysplasia by use of ultrasound. Presence of a C-propeptide mutation appears to be a risk factor for hip dysplasia (80%). It appears that Pavlik harness treatment is not useful in children with OI. The usual treatment of children with OI who pull to stand or started walking with femoral deformity is femoral osteotomy and rodding. In case of associated hip dysplasia with a dislocation, open reduction of the hip and a possible concomitant pelvic osteotomy appears to be a valid management option. LEVEL OF EVIDENCE: Level IV.

Diaphyseal Femur Fractures in Osteogenesis Imperfecta: Characteristics and Relationship With Bisphosphonate Treatment.

Several recent case reports have suggested that bisphosphonate treatment in individuals with osteogenesis imperfecta (OI) is causally related to atypical femur fractures. However, it is not known whether atypical femur fractures are actually more frequent in patients who have received bisphosphonates. In the present study, we retrospectively analyzed 166 femur fractures in 119 children with a diagnosis of OI that had not undergone intramedullary rodding procedures. A total of 130 fractures in 90 patients occurred in femurs with preexisting deformities (age at fracture between 1 month and 19.9 years; 43 girls). Because deformities are a typical cause of fracture in OI, deformed femurs were excluded from the analysis of atypical fractures. However, it was noted that in deformed femurs a transverse fracture pattern (one of the criteria of atypical fractures) was associated with a moderate to severe OI phenotype and not related to bisphosphonate treatment. Of the 36 fractures that occurred in nondeformed femurs (30 individuals; age at fracture between 1 month and 17.4 years; 13 girls), 11 (in nine children) occurred during bisphosphonate treatment. Three of these fractures (27%) resembled atypical femur fractures. Among the 25 femur fractures (23 patients) that occurred in the absence of prior bisphosphonate treatment, 8 (22%) resembled atypical femur fractures. Logistic regression analysis showed that bisphosphonate treatment history was not associated with the occurrence of atypical fractures. In contrast, the presence of moderate to severe OI (defined as any OI type other than OI type I) was strongly associated with atypical femur fractures. Thus, we observed an atypical appearance in about a quarter of nondeformed femur fractures that occurred in children with OI. Such atypical femur fractures seemed to be related to the severity of OI rather than to bisphosphonate treatment history. © 2016 American Society for Bone and Mineral Research.

Multidisciplinary Treatment of Severe Osteogenesis Imperfecta: Functional Outcomes at Skeletal Maturity.

OBJECTIVE: To determine the functional outcomes associated with long-term multidisciplinary treatment, intravenous bisphosphonate treatment, orthopedic surgery, and rehabilitation in children with severe osteogenesis imperfecta (OI) (diagnosed clinically as OI types III or IV). DESIGN: Retrospective study where outcomes were measured prospectively. SETTING: Pediatric orthopedic hospital. PARTICIPANTS: Adolescents (N=41; age range, 15-21y) with severe OI (OI type III: n=17; OI type IV: n=24) who had started therapy before the age of 6 years, had received treatment for at least 10 years, and had achieved final height. INTERVENTIONS: Intravenous bisphosphonate treatment, orthopedic surgery, and rehabilitation. MAIN OUTCOME MEASURE: Pediatric Evaluation of Disability Inventory. RESULTS: At the time of the last available follow-up examination, none of the individuals diagnosed with OI type III (most severely affected group) was able to ambulate without ambulation aids, whereas 20 (83%) patients with OI type IV were able to ambulate without ambulation aids. Regarding self-care, we specifically assessed 8 skills that we deemed essential for living independently (grooming; dressing; toileting; bed, chair, toilet, tub, and car transfers). Only 6 (35%) of the youths with OI type III were able to complete all 8 items, whereas 23 (96%) individuals with OI type IV managed to perform all tasks. Teens with OI type III often needed assistance for the transfer to toilet, tub, and car and for personal hygiene and clothing management associated with toileting, usually because of limitations in upper-extremity function. CONCLUSIONS: These observations suggest that further improvements in the functional status of the most severely affected children with OI are contingent on advances in the clinical management of upper-extremity issues.

Intravenous Bisphosphonate Therapy of Young Children With Osteogenesis Imperfecta: Skeletal Findings During Follow Up Throughout the Growing Years.

Cyclical intravenous bisphosphonate therapy is widely used to treat children with osteogenesis imperfecta (OI), but little is known about long-term treatment outcomes. We therefore reviewed 37 children with OI (OI type I, n = 1; OI type III, n = 14; and OI type IV, n = 22) who started intravenous bisphosphonate therapy before 5 years of age (median 2.2 years; range, 0.1 to 4.8 years), and who had a subsequent follow-up period of at least 10 years (median 14.8 years; range, 10.7 to 18.2 years), during which they had received intravenous bisphosphonate treatment (pamidronate or zoledronic acid) for at least 6 years. During the observation period, the mean lumbar spine areal bone mineral density Z-score increased from -6.6 (SD 3.1) to -3.0 (SD 1.8), and weight Z-score increased from -2.3 (SD 1.5) to -1.7 (SD 1.7) (p < 0.001 and p = 0.008). At the time of the last assessment, patients with OI type IV had significantly higher height Z-scores than a control group of patients matched for age, gender, and OI type who had not received bisphosphonates. Patients had a median of six femur fractures (range, 0 to 18) and five tibia fractures (range, 0 to 17) during the follow-up period. At baseline, 35% of vertebra were affected by compression fractures, whereas only 6% of vertebra appeared compressed at the last evaluation (p < 0.001), indicating vertebral reshaping during growth. Spinal fusion surgery was performed in 16 patients (43%). Among the 21 patients who did not have spinal fusion surgery, 13 had scoliosis with a curvature ranging from 10 to 56 degrees. In conclusion, long-term intravenous bisphosphonate therapy was associated with higher Z-scores for lumbar spine areal bone mineral density and vertebral reshaping, but long-bone fracture rates were still high and the majority of patients developed scoliosis.

Homozygosity for frameshift mutations in XYLT2 result in a spondylo-ocular syndrome with bone fragility, cataracts, and hearing defects.

Heparan and chondroitin/dermatan sulfated proteoglycans have a wide range of roles in cellular and tissue homeostasis including growth factor function, morphogen gradient formation, and co-receptor activity. Proteoglycan assembly initiates with a xylose monosaccharide covalently attached by either xylosyltransferase I or II. Three individuals from two families were found that exhibited similar phenotypes. The index case subjects were two brothers, individuals 1 and 2, who presented with osteoporosis, cataracts, sensorineural hearing loss, and mild learning defects. Whole exome sequence analyses showed that both individuals had a homozygous c.692dup mutation (GenBank: NM_022167.3) in the xylosyltransferase II locus (XYLT2) (MIM: 608125), causing reduced XYLT2 mRNA and low circulating xylosyltransferase (XylT) activity. In an unrelated boy (individual 3) from the second family, we noted low serum XylT activity. Sanger sequencing of XYLT2 in this individual revealed a c.520del mutation in exon 2 that resulted in a frameshift and premature stop codon (p.Ala174Profs(∗)35). Fibroblasts from individuals 1 and 2 showed a range of defects including reduced XylT activity, GAG incorporation of (35)SO4, and heparan sulfate proteoglycan assembly. These studies demonstrate that human XylT2 deficiency results in vertebral compression fractures, sensorineural hearing loss, eye defects, and heart defects, a phenotype that is similar to the autosomal-recessive disorder spondylo-ocular syndrome of unknown cause. This phenotype is different from what has been reported in individuals with other linker enzyme deficiencies. These studies illustrate that the cells of the lens, retina, heart muscle, inner ear, and bone are dependent on XylT2 for proteoglycan assembly in humans.

Osteotomy Healing in Children With Osteogenesis Imperfecta Receiving Bisphosphonate Treatment.

A decade ago our group had reported that osteotomy healing was commonly delayed in children with moderate to severe osteogenesis imperfecta (OI) who were treated with intravenous pamidronate infusions. We subsequently maintained a bisphosphonate infusion-free interval of 4 months after osteotomy and changed the surgical approach (use of an osteotome instead of a power saw). In addition, zoledronic acid has become the standard intravenous bisphosphonate for treatment of OI at our institution. In the present study, we compared osteotomy healing before and after these changes were instituted. We evaluated bone healing post-osteotomy on standard radiographs after 261 intramedullary rodding procedures involving osteotomies (139 femur, 112 tibia) in 110 patients (age at surgery 1.2 to 20.4 years). Delayed healing was diagnosed when the osteotomy line was visible 12 months after the event. We observed delayed bone healing after 48 of the 114 osteotomies (42%) performed with the new approach, and in 106 of the 147 osteotomies (72%) using the previous approach (p = 0.001). The odds for delayed osteotomy healing were significantly lower with the new approach even after adjustment for age, sex, height Z-score, weight Z-score, OI type, and bone involved (odds ratio = 0.17; 95% confidence interval 0.16-0.47). Thus, delayed osteotomy healing occurred less frequently in the past 10 years than in the decade before that. It is likely that this improved result is attributable to the implemented changes in both medical and surgical management.

Are Fassier-Duval rods at risk of migration in patients undergoing spine magnetic resonance imaging?

BACKGROUND: The Fassier-Duval (FD) rod is a stainless-steel device widely used to correct bone deformities and reduce the risk of fractures in patients with osteogenesis imperfecta (OI). Since these are telescopic expandable rods, there has been a reluctance to perform magnetic resonance imaging (MRI) in patients with OI secondary to a theoretical risk of migration during the MRI scans. The primary aim of this study was to assess the risk of migration of FD rods in patients who underwent MRI of the spine. The secondary aims are to assess the heating effects and artifact of these implants. METHODS: We retrospectively reviewed our database for all patients with OI who had undergone FD rodding and subsequent MRI evaluation for craniofacial and spinal disorders. Ten patients were eligible to be included in the study. The MRI examination was performed in all patients using a1.5 T magnet. The radiographic images pre-MRI and post-MRI were evaluated and compared to assess whether or not migration of implants had occurred. Patients' charts and MRI logbooks were reviewed to assess the heating effects based on patient-reported events during or immediately after the MRI. In addition, the scans were reviewed to evaluate peri-implant soft tissues to assess for changes that might indicate such effect. Artifact was judged to be present if it interfered with the evaluation of any portion of spinal anatomy of clinical interest. RESULTS: Ten patients underwent 19 FD roddings. The indications for MRI in these patients were basilar invagination, basilar impression, platybasia, and complex scoliosis. None of the implants have shown any migration, heating effect, or artifact. CONCLUSIONS: FD rods are safe and pose no risk of migration, heating effects, or artifact when undergoing an MRI of the spine using a 1.5 T magnet. With the introduction of magnet strengths higher than 1.5 T, further testing should be performed. LEVEL OF EVIDENCE: Level IV.

Topological mapping of BRIL reveals a type II orientation and effects of osteogenesis imperfecta mutations on its cellular destination.

BRIL/IFITM5 is a membrane protein present almost exclusively in osteoblasts, which is believed to adopt a type III (N-out/C-out) topology. Mutations in IFITM5 cause OI type V, but the characteristics of the mutant protein and the mechanism involved are still unknown. The purpose of the current study was to re-assess the topology, localization, and biochemical properties of BRIL and compare it to the OI type V mutant in MC3T3 osteoblasts. Immunofluorescence labeling was performed with antibodies directed against BRIL N- or C-terminus. In intact cells, BRIL labeling was conspicuously detected at the plasma membrane only with the anti-C antibody. Detection of BRIL N-terminus was only possible after cell permeabilization, revealing both plasma membrane and Golgi labeling. Trypsinization of live cells expressing BRIL only cleaved off the C-terminus, confirming that it is a type II protein and that its N-terminus is intracellular. A truncated form of BRIL lacking the last 18 residues did not appear to affect localization, whereas mutation of a single leucine to arginine within the transmembrane segment abolished plasma membrane targeting. BRIL is first targeted to the endoplasmic reticulum as the entry point to the secretory pathway and rapidly traffics to the Golgi via a COPII-dependent pathway. BRIL was found to be palmitoylated and two conserved cysteine residues (C52 and C53) were critical for targeting to the plasma membrane. The OI type V mutant BRIL, having a five residue extension (MALEP) at its N-terminus, presented with exactly the same topological and biochemical characteristics as wild type BRIL. In contrast, the S42 > L mutant BRIL was trapped intracellularly in the Golgi. BRIL proteins and transcripts were equally detected in bone from a patient with OI type V, suggesting that the cause of the disease is a gain of function mediated by a faulty intracellular activity of the mutant BRIL.

Correction of proximal tibial recurvatum using the Ilizarov technique.

BACKGROUND: Genu recurvatum is a debilitating deformity of the knee that can progress during growth and lead to significant deformity if left untreated. Recurvatum can be osseous, ligamentous, or mixed. Osseous genu recurvatum is most often due to asymmetrical growth arrest of the proximal tibial physis affecting primarily the tibial tubercle. Several methods have been described in the literature regarding the correction of this deformity; nevertheless, there is a paucity of knowledge of the correction of proximal tibial recurvatum using the Ilizarov technique. METHODS: A retrospective chart and radiographic review of all patients treated by distraction osteogenesis with angular correction distal to the tibial tubercle using an Ilizarov external fixator was performed. A total of 9 patients were treated during the study period and the average age at the time of surgery was 14.3 years (range, 7-16 y). There were 3 female patients and 6 male patients. Four cases were due to deformity secondary to trauma and the treatment thereof, 2 patients had spondyloepiphyseal dysplasia, and 3 patients had unknown etiology. The angle of recurvatum (RG) and the angle of tilt of the tibial plateau (RT) preoperatively measured 28 degrees (range, 18 to 32 degrees) and 69 degrees (range, 60 to 82 degrees), respectively. At final follow-up, the RG and RT measured 7 degress (range, 4 to 12 degrees) and 93 degrees (range, 86 to 100 degress), respectively. Using the scoring system of Lecuire and colleagues, the overall results were good to excellent at a mean follow-up of 4.4 years. CONCLUSIONS: Correction of osseous proximal tibial recurvatum by the Ilizarov method, allows obtaining an improved sagittal mechanical axis in the lower extremity.

Activities and participation in young adults with osteogenesis imperfecta.

The objective of this cross-sectional study was to compare the activities and participation in the domains of mobility, self-care, domestic life and social functioning in young adults according to osteogenesis imperfecta (OI) type. Fifty-four former OI patients were invited to participate and were sent a structured questionnaire. Twenty-four patients (mean age: 25.0 years, SD: 2.6 years) with OI types I (n=7), III (n=7), IV (n =8) and V (n=2) completed the questionnaire. Participants with OI type I reported full independence, and only few respondents with OI types IV and V reported some limitations in mobility and domestic life activities. Young adults with OI type III had significantly lower activity scores in aspects of mobility and domestic life and lower levels of participation in employment, sporting activities and transportation. Participation in leisure and social interactions were not different across OI types. Young adults with more severe types of osteogenesis imperfecta have greater activity limitations and participation restrictions. Our findings indicate the importance of promoting and facilitating involvement in meaningful activities and roles in young adults with moderate to severe forms of OI.

Fassier-Duval femoral rodding in children with osteogenesis imperfecta receiving bisphosphonates: functional outcomes at one year.

PURPOSE: To examine the functional outcomes of children with osteogenesis imperfecta (OI) following initial Fassier-Duval (FD) rodding to the femur at 1 year, and to determine which factors are associated with change in gross motor function, ambulation, and functional performance. METHODS: Approval from our Institutional Review Board was obtained. A retrospective chart review identified 60 children (28 males, 32 females) with OI who underwent initial FD femoral rodding (101 rods) and who were receiving bisphosphonates. The mean age of the children was 3 years, 11 months at the initial femoral FD rodding. Two had type I OI, 30 type III, 27 type IV, and one type VI. The maximum length of follow-up was 4 years. Telescoping FD rods were used for the femurs, with surgeries performed one leg at a time, with a 1-week interval. The active range of motion (AROM) of the hips and knees in flexion was measured 4-5 weeks post-initial rodding. Outcomes on the Gillette Functional Assessment Questionnaire (FAQ) Ambulation Scale, the Gross Motor Function Measure (GMFM), and the Pediatric Evaluation of Disability Inventory (PEDI) were compared pre-operatively and at 1 year post-surgery using t-tests and multivariate linear regression. RESULTS: Pre-operatively, the mean FAQ score was 2.0, and this increased to 5.8 at 1 year post-surgery. Statistically significant improvements (P ≤ 0.05) were found on the FAQ, crawling, standing, walking and running, and total domains of the GMFM, and PEDI mobility and self-care from baseline to 1 year. The results from the multivariate linear regression indicate that older age (P = 0.0045) and higher weight (P = 0.0164) are significantly associated with lower scores in the self-care domain of the PEDI, and that OI type III compared to type IV is significantly associated (P = 0.0457) with greater improvement on the crawling domain of the GMFM. Higher weight was also associated (P = 0.0289) with lower scores in the standing domain of the GMFM, as well as with the total GMFM score (P = 0.0398). CONCLUSIONS: Our findings indicate that initial FD femoral rodding resulted in benefits in ambulation, gross motor function, self-care, and mobility for children with OI beyond physiological expectations due to developmental growth. FD rodding is a procedure which can improve the overall mobility in children with OI with significant femoral deformities.

Enhancement of difficult nonunion in children with osteogenic protein-1 (OP-1): early experience.

UNLABELLED: Numerous studies have described the use of osteogenic protein-1 (OP-1) in adults, but there are few reports in children. The objectives of this short-term followup cohort study were (1) to examine clinical and radiographic healing of persistent nonunions after OP-1 application in children; and (2) to determine the safety of OP-1 use in this sample. Clinical healing was defined by absence of pain and tenderness at the nonunion site and the ability to fully weight bear on the affected limb. Radiographic healing was determined by bony bridging of the nonunion site in at least one view. Safety was defined as the absence of major adverse events, including allergic reactions, infections, local inflammatory reactions, and heterotopic ossification. OP-1 was used in 19 patients who had an operative procedure for the bridging of persistent nonunions between 1999 and 2007. The mean age was 11.6 years (range, 4.8-20.3 years). Thirteen patients had persistent nonunion after one or more previous surgeries, prior to the initial OP-1 application. A single dose of 3.5 mg of OP-1 mixed with 1 g of Type I bovine collagen was applied to 23 sites of 19 patients. Three patients received additional OP-1 applications. Healing occurred clinically and radiographically in 17 of the 23 sites. Complications included four superficial pin site infections, one deep infection, and two fractures. No major local adverse event related to OP-1 application was noted in our sample. Our findings suggest OP-1 stimulates healing of persistent nonunions without major adverse events in our patient population. LEVEL OF EVIDENCE: Level IV, case series. See the guidelines online for a complete description of levels of evidence.