Osteogenesis Imperfecta (OI) is a heritable bone disorder characterized by bone fragility and often caused by mutations in the Type I collagen-encoding genes COL1A1 and COL1A2. The pathophysiology of OI, particularly at the cellular level, is still not well understood. This contributes to the lack of a cure for this disorder as well as an effective preventive or management options of its complications. In the bone environment, mesenchymal stem cells (MSCs) and osteoblasts (Ob) exert their function, at least partially, through the secretion of extracellular vesicles (EV). EV is a heterogeneous group of nanosized membrane-enclosed vesicles that carry/transfer a cargo of proteins, lipid and nucleic acids from the secreting cell to its target cells. Our objective is to characterize EVs secreted by human control (HC)- and OI-MSCs and their derived Obs, with focus on their protein content. We hypothesize that there will be differences in the protein content of EVs secreted by OI-Obs compared to HC-Ob, which may indicate a deviation from healthy Ob behavior and, thus, a role in OI pathophysiology.

MSCs were harvested from the adipose tissue of four COL1A1-OI and two HC patients. They were proliferated in an EV-depleted media, then induced to differentiate to extracellular matrix (ECM)-producing osteoblasts, which then gets mineralized. EVs secreted by MSCs (MSC-EV) and Obs (Ob-EV) were then purified and concentrated.

Using liquid chromatography- tandem mass spectrometry, proteomic analysis of the EV groups was done. A total of 384 unique proteins were identified in all EVs, 373 were found in Vesiclepedia indicating a good enrichment of our samples with EV proteins. 67 proteins of the total 384 were exclusively or significantly upregulated (p-value < 0 .05) in OI-Ob-EV and 28 proteins in the HC-Ob-EVs, relative to each other. These two groups of differentially expressed proteins were compared by Gene Ontology (GO) analysis of their cellular compartment, molecular functions and biological processes. We observed that there were differences in the cellular origin of EV-proteins, which may indicate heterogeneity of the isolated EVs. Molecular function and biological process analyses of the HC-Ob-EV proteins showed, as expected, predominantly calcium-related activities such as extracellular matrix (ECM) mineralization. OI-Ob-EV proteins were still predominantly exhibiting ECM organization and formation functions. Annexins A1,2,4,5 and 6 were differentially and significantly upregulated by the HC-Ob-EVs. Fibronectin (FN), Fibulin-1 and −2, and Laminins (α4 & γ1), which are amongst the early non-collagenous proteins to form the ECM, were differentially and significantly upregulated in the OI-Ob-EVs.

We concluded that the persistent expression of Fibronectin (FN), Fibulin-1 and −2, and Laminins in OI-Ob-EVs might indicate the presence of an immature ECM that the OI-Obs are trying to organize. ECM mineralization is largely dependent on the presence of an organized mature ECM, and this being compromised in OI bone environment, may be a contributor to the bone fragility seen in these patients. Annexins, which are calcium-binders that are vital for ECM mineralization, were significantly downregulated in the OI-Ob-EVs and this may be a further contributor to ECM mineralization impairment and bone fragility.

The use of intramedullary implants in Osteogenesis Imperfecta (OI) patients to treat and prevent fractures, non-unions and limb deformities has been well established. To serve this purpose different implants are available from non-telescoping rods such as Rush rods and Kirschner wires, to telescoping rods such as the Dubow-Bailey rod, the Sheffield rod and the Fassier-Duval (FD) rod (Pega Medical, Laval, Quebec, Canada). The purpose of this study is to report on the long-term results of the femoral Fassier-Duval rod.

A retrospective chart review of all patients with OI who underwent a femoral intramedullary Fassier-Duval rodding between 2002 and 2017 and followed for an average of 12 years at the Shriner's Hospital, Montreal, Quebec, Canada was performed.

A total of 81 patients underwent femoral FD rodding between 2002 and 2017. Twenty-seven children undergoing 83 procedures had completed a minimum 10-year follow up with complete charts and these were included here. The average follow up time was 12 years (10–15 years). Fifty procedures were initial rodding surgeries and 30 (36.1%) were revision surgeries. A total of 69 complications were reported in the medical record and confirmed on x-ray. The 3 most common complications were a bent rod 24 (34.8%), femur fracture 16 (23.2%) and loss of telescoping in 12 (17.4%) of patients. The 3 most common cause of revision were femur fracture 16 (53.3%), broken rod 5 (16.7%) and coxa vara in 3 (10%) of patients. The average time from initial surgery to the first revision was 5.9 years.

Long term performance of femoral FD rodding shows that despite improved functioning with these rods, certain complications are to be expected, most commonly a risk of femoral fracture requiring revision surgery.

Objectives

Bone fracture healing is regulated by a series of complex physicochemical and biochemical processes. One of these processes is bone mineralization, which is vital for normal bone development. Phosphatase, orphan 1 (PHOSPHO1), a skeletal tissue-specific phosphatase, has been shown to be involved in the mineralization of the extracellular matrix and to maintain the structural integrity of bone. In this study, we examined how PHOSPHO1 deficiency might affect the healing and quality of fracture callus in mice.

Purpose

Introduction: The Dega osteotomy is a versatile procedure that is widely used to treat neuromuscular hip dysplasia. There is a paucity of English-language literature on its use in acetabular dysplasia seen in developmental dysplasia of the hip (DDH).

Purpose

Pediatric orthopaedic surgeons encounter referrals from primary care practitioners and pediatricians that are benign in nature or within accepted limitations for physiological musculoskeletal variance. These referrals are believed to be secondary to insufficient pediatric musculoskeletal expertise and consume already limited pediatric orthopaedic resources. To date, our annual CME course dedicated to pediatric musculoskeletal medicine is the only one of its kind in Canada. It includes didactic teaching as well as a clinic of unnecessary referrals in which participants examine patients and receive feedback from consultants. The purpose of this study was to evaluate the impact of a pediatric musculoskeletal CME course on the quality of local outpatient referrals over a four year period.

We reviewed retrospectively 22 patients (23 limb segments) with fibular hemimelia treated by amputation or limb lengthening to evaluate these methods of treatment. There were 12 boys and 10 girls, all with associated anomalies in the lower limbs. Twelve patients (13 limb segments) had early amputation and prosthetic fitting and ten had tibial lengthening using the Ilizarov technique.

At the latest follow-up, the twelve patients who had amputation were functioning well and had few complications. The ten patients who had lengthening had suffered numerous complications, and all had needed either further corrective surgery or to wear braces or shoe-raises. Two of the ten lengthened limbs required late amputation for poor function or cosmesis. There were fewer hospital admissions, clinic visits, and periods of absence from school in the amputation group.

Our findings suggest that amputation is a more effective method of management than limb-lengthening in severe fibular hemimelia. The Ilizarov method is an attractive alternative for selected patients, but its exact role is not yet established. One problem is that families often have unrealistic expectations of the surgical and prosthetic technology available and may refuse amputation when this has been recommended.