The Effect of Altering the Mechanical Loading Environment on the Expression of Bone Regenerating Molecules in Cases of Distraction Osteogenesis

Distraction osteogenesis (DO) is a surgical technique where gradual and controlled separation of two bony fragments following an osteotomy leads to the induction of new bone formation in the distracted gap. DO is used for limb lengthening, correction of bony deformities, and the replacement of bone loss secondary to infection, trauma, and tumors. Although DO gives satisfactory results in most cases, one major drawback of this technique is the prolonged period of time the external fixator has to be kept on until the newly formed bone consolidates thus leading to numerous complications. Numerous attempts at accelerating bone formation during DO have been reported. One specific approach is manipulation of the mechanical environment during DO by applying changes in the standard protocol of distraction. Attempts at changing this mechanical environment led to mixed results. Increasing the rate or applying acute distraction, led to poor bone formation in the distracted zone. On the other hand, the addition of compressive forces (such as weight bearing, alternating distraction with compression or by over-lengthening, and then shortening) has been reported to increase bone formation. It still remains unclear why these alterations may lead to changes in bone formation. While the cellular and molecular changes occurring during the standard DO protocol, specifically increased expression of transforming growth factor-beta 1, platelet-derived growth factor, insulin-like growth factor, basic fibroblast growth factor, vascular endothelial growth factor, and bone morphogenic proteins have been extensively investigated, the literature is sparse on the changes occurring when this protocol is altered. It is the purpose of this article to review the pertinent literature on the changes in the expression of various proteins and molecules as a result of changes in the mechanical loading technique in DO and try to define potential future research directions

Plethora of Traumatic Lesions of Bilateral Knee Extensor Mechanism in Osteogenesis Imperfecta

Introduction: Injuries to the quadriceps extensor mechanism are rare in patients with Osteogenesis Imperfecta (OI). To the best of our knowledge, non-union of the patella in OI, either as an isolated problem or in combination with an acute fracture, has not been previously reported. Case report: We describe how we surgically approached both the fracture and the non-union simultaneously. The surgical technique and steps are described in detail. Post-operative course was uneventful and the outcome was favorable, with full return of function for the patient. Conclusion: A review of various knee extensor mechanism injuries in OI is described as illustrated in a single patient. The unusual simultaneous surgical treatment of a non-union and an acute fracture in the same patella shows that despite the severely compromised bone in this rare bone disease the bone still has a capacity to heal with a functional outcome

Epidemiology, aetiology, interventions and genomics in children with arthrogryposis multiplex congenita: protocol for a multisite registry

IntroductionArthrogryposis multiplex congenita (AMC) is an umbrella term including hundreds of conditions with the common clinical manifestation of multiple congenital contractures. AMC affects 1 in 3000 live births and is caused by lack of movement in utero. To understand the long-term needs of individuals diagnosed with a rare condition, it is essential to know the prevalence, aetiology and functional outcomes in a large sample. The development and implementation of a multicentre registry is critical to gather this data. This registry aims to improve health through genetic and outcomes research, and ultimately identify new therapeutic targets and diagnostics for treating children with AMC.Methods and analysisParticipants for the AMC registry will be recruited from seven orthopaedic hospitals in North America. Enrollment occurs in two phases; Part 1 focuses on epidemiology, aetiology and interventions. For this part, retrospective and cross-sectional data will be collected using a combination of patient-reported outcomes and clinical measures. Part 2 focuses on core subset of the study team, including a geneticist and bioinformatician, identifying causative genes and linking the phenotype to genotype via whole genome sequencing to identify genetic variants and correlating these findings with pedigree, photographs and clinical information. Descriptive analyses on the sample of 400 participants and logistic regression models to evaluate relationships between outcomes will be conducted.Ethics and disseminationEthical approval has been granted from corresponding governing bodies in North America. Dissemination of findings will occur via traditional platforms (conferences, manuscripts) for the scientific community. Other modalities will be employed to ensure that all stakeholders, including youth, families and patient support groups, may be provided with findings derived from the registry. Ensuring the findings are circulated to a maximum amount of interested parties will ensure that the registry can continue to serve as a platform for hypothesis-driven research and further advancement for AMC