Objectives

Recent studies have shown that modulating inflammation-related lipid signalling after a bone fracture can accelerate healing in animal models. Specifically, decreasing 5-lipoxygenase (5-LO) activity during fracture healing increases cyclooxygenase-2 (COX-2) expression in the fracture callus, accelerates chondrogenesis and decreases healing time. In this study, we test the hypothesis that 5-LO inhibition will increase direct osteogenesis.

When transferring tissue regenerative strategies involving skeletal stem cells to human application, consideration needs to be given to factors that may affect the function of the cells that are transferred. Local anaesthetics are frequently used during surgical procedures, either administered directly into the operative site or infiltrated subcutaneously around the wound. The aim of this study was to investigate the effects of commonly used local anaesthetics on the morphology, function and survival of human adult skeletal stem cells.

Cells from three patients who were undergoing elective hip replacement were harvested and incubated for two hours with 1% lidocaine, 0.5% levobupivacaine or 0.5% bupivacaine hydrochloride solutions. Viability was quantified using WST-1 and DNA assays. Viability and morphology were further characterised using CellTracker Green/Ethidium Homodimer-1 immunocytochemistry and function was assessed by an alkaline phosphatase assay. An additional group was cultured for a further seven days to allow potential recovery of the cells after removal of the local anaesthetic.

A statistically significant and dose dependent reduction in cell viability and number was observed in the cell cultures exposed to all three local anaesthetics at concentrations of 25% and 50%, and this was maintained even following culture for a further seven days.

This study indicates that certain local anaesthetic agents in widespread clinical use are deleterious to skeletal progenitor cells when studied in vitro; this might have relevance in clinical applications.

We attempted to characterise the biological quality and regenerative potential of chondrocytes in osteochondritis dissecans (OCD). Dissected fragments from ten patients with OCD of the knee (mean age 27.8 years (16 to 49)) were harvested at arthroscopy. A sample of cartilage from the intercondylar notch was taken from the same joint and from the notch of ten patients with a traumatic cartilage defect (mean age 31.6 years (19 to 52)). Chondrocytes were extracted and subsequently cultured. Collagen types 1, 2, and 10 mRNA were quantified by polymerase chain reaction. Compared with the notch chondrocytes, cells from the dissecate expressed similar levels of collagen types 1 and 2 mRNA. The level of collagen type 10 message was 50 times lower after cell culture, indicating a loss of hypertrophic cells or genes. The high viability, retained capacity to differentiate and metabolic activity of the extracted cells suggests preservation of the intrinsic repair capability of these dissecates. Molecular analysis indicated a phenotypic modulation of the expanded dissecate chondrocytes towards a normal phenotype. Our findings suggest that cartilage taken from the dissecate can be reasonably used as a cell source for chondrocyte implantation procedures.

This study investigates the use of porous biphasic ceramics as graft extenders in impaction grafting of the femur during revision hip surgery.

Impaction grafting of the femur was performed in four groups of sheep. Group one received pure allograft, group two 50% allograft and 50% BoneSave, group three 50% allograft and 50% BoneSave type 2 and group four 10% allograft and 90% BoneSave as the graft material. Function was assessed using an index of pre- and post-operative peak vertical ground reaction force ratios. Changes in bone mineral density were measured by dual energy X ray absorptiometry (DEXA) scanning. Loosening and subsidence were assessed radiographically and by histological examination of the explanted specimens.

There was no statistically significant difference between the four groups after 18 months of unrestricted functional loading for all outcome measures.

Carbonate-substituted hydroxyapatite (CHA) is more osteoconductive and more resorbable than hydroxyapatite (HA), but the underlying mode of its action is unclear. We hypothesised that increased resorption of the ceramic by osteoclasts might subsequently upregulate osteoblasts by a coupling mechanism, and sought to test this in a large animal model.

Defects were created in both the lateral femoral condyles of 12 adult sheep. Six were implanted with CHA granules bilaterally, and six with HA. Six of the animals in each group received the bisphosphonate zoledronate (0.05 mg/kg), which inhibits the function of osteoclasts, intra-operatively.

After six weeks bony ingrowth was greater in the CHA implants than in HA, but not in the animals given zoledronate. Functional osteoclasts are necessary for the enhanced osteoconduction seen in CHA compared with HA.

We report the incidence of and risk factors for complications after scoliosis surgery in patients with Duchenne muscular dystrophy (DMD) and compare them with those of other neuromuscular conditions.

We identified 110 (64 males, 46 females) consecutive patients with a neuromuscular disorder who underwent correction of the scoliosis at a mean age of 14 years (7 to 19) and had a minimum two-year follow-up. We recorded demographic and peri-operative data, including complications and re-operations.

There were 60 patients with cerebral palsy (54.5%) and 26 with DMD (23.6%). The overall complication rate was 22% (24 patients), the most common of which were deep wound infection (9, 8.1%), gastrointestinal complications (5, 4.5%) and hepatotoxicity (4, 3.6%). The complication rate was higher in patients with DMD (10/26, 38.5%) than in those with other neuromuscular conditions (14/84, 16.7% (p = 0.019). All hepatotoxicity occurred in patients with DMD (p = 0.003), who also had an increased rate of deep wound infection (19% vs 5%) (p = 0.033). In the DMD group, no peri-operative factors were significantly associated with the rate of overall complications or deep wound infection. Increased intra-operative blood loss was associated with hepatotoxicity (p = 0.036).

In our series, correction of a neuromuscular scoliosis had an acceptable rate of complications: patients with DMD had an increased overall rate compared with those with other neuromuscular conditions. These included deep wound infection and hepatotoxicity. Hepatotoxicity was unique to DMD patients, and we recommend peri-operative vigilance after correction of a scoliosis in this group.

Cite this article: Bone Joint J 2014; 96-B:943–9.

Objectives

Our objective in this article is to test the hypothesis that type 2 diabetes mellitus (T2DM) is a factor in the onset and progression of osteoarthritis, and to characterise the quality of the articular cartilage in an appropriate rat model.

We present the results of the surgical correction of lower-limb deformities caused by metabolic bone disease. Our series consisted of 17 patients with a diagnosis of hypophosphataemic rickets and two with renal osteodystrophy; their mean age was 25.6 years (14 to 57). In all, 43 lower-limb segments (27 femora and 16 tibiae) were osteotomised and the deformity corrected using a monolateral external fixator. The segment was then stabilised with locked intramedullary nailing. In addition, six femora in three patients were subsequently lengthened by distraction osteogenesis. The mean follow-up was 60 months (18 to 120). The frontal alignment parameters (the mechanical axis deviation, the lateral distal femoral angle and the medial proximal tibial angle) and the sagittal alignment parameters (the posterior distal femoral angle and the posterior proximal tibial angle) improved post-operatively. The external fixator was removed either at the end of surgery or at the end of the lengthening period, allowing for early mobilisation and weight-bearing. We encountered five problems and four obstacles in the programme of treatment.

The use of intramedullary nails prevented recurrence of deformity and refracture.

Failure of bone repair is a challenging problem in the management of fractures. There is a limited supply of autologous bone grafts for treating nonunions, with associated morbidity after harvesting. There is need for a better source of cells for repair. Mesenchymal stem cells (MSCs) hold promise for healing of bone because of their capacity to differentiate into osteoblasts and their availability from a wide variety of sources. Our review aims to evaluate the available clinical evidence and recent progress in strategies which attempt to use autologous and heterologous MSCs in clinical practice, including genetically-modified MSCs and those grown on scaffolds. We have compared various procedures for isolating and expanding a sufficient number of MSCs for use in a clinical setting.

There are now a number of clinical studies which have shown that implantation of MSCs is an effective, safe and durable method for aiding the repair and regeneration of bone.

Introduction

Osteoarthritis (OA) is a progressively debilitating disease that affects mostly cartilage, with associated changes in the bone. The increasing incidence of OA and an ageing population, coupled with insufficient therapeutic choices, has led to focus on the potential of stem cells as a novel strategy for cartilage repair.

We report our experience using a biodegradable calcium sulphate antibiotic carrier containing tobramycin in the surgical management of patients with chronic osteomyelitis. The patients were reviewed to determine the rate of recurrent infection, the filling of bony defects, and any problems with wound healing. A total of 193 patients (195 cases) with a mean age of 46.1 years (16.1 to 82.0) underwent surgery. According to the Cierny–Mader classification of osteomyelitis there were 12 type I, 1 type II, 144 type III and 38 type IV cases. The mean follow-up was 3.7 years (1.3 to 7.1) with recurrent infection occurring in 18 cases (9.2%) at a mean of 10.3 months post-operatively (1 to 25.0). After further treatment the infection resolved in 191 cases (97.9%). Prolonged wound ooze (longer than two weeks post-operatively) occurred in 30 cases (15.4%) in which there were no recurrent infection. Radiographic assessment at final follow-up showed no filling of the defect with bone in 67 (36.6%), partial filling in 108 (59.0%) and complete filling in eight (4.4%). A fracture occurred in nine (4.6%) of the treated osteomyelitic segments at a mean of 1.9 years (0.4 to 4.9) after operation.

We conclude that Osteoset T is helpful in the management of patients with chronic osteomyelitis, but the filling of the defect in bone is variable. Prolonged wound ooze is usually self-limiting and not associated with recurrent infection.

Cite this article: Bone Joint J 2014; 96-B:829–36

The increasing need for total hip replacement (THR) in an ageing population will inevitably generate a larger number of revision procedures. The difficulties encountered in dealing with the bone deficient acetabulum are amongst the greatest challenges in hip surgery. The failed acetabular component requires reconstruction to restore the hip centre and improve joint biomechanics. Impaction bone grafting is successful in achieving acetabular reconstruction using both cemented and cementless techniques. Bone graft incorporation restores bone stock whilst providing good component stability. We provide a summary of the evidence and current literature regarding impaction bone grafting using both cemented and cementless techniques in revision THR.

Cite this article: Bone Joint J 2013;95-B, Supple A:98–102.

The December 2013 Hip & Pelvis Roundup³⁶⁰ looks at: Enhanced recovery works; Acetabular placement; Exercise better than rest in osteoarthritis patients; if Birmingham hip resurfacing is immune from pseudotumour; HIV and arthroplasty; Labral tears revisited; Prophylactic surgery for FAI; and Ceramics and impaction grafting

Tendinopathy is a debilitating musculoskeletal condition which can cause significant pain and lead to complete rupture of the tendon, which often requires surgical repair. Due in part to the large spectrum of tendon pathologies, these disorders continue to be a clinical challenge. Animal models are often used in this field of research as they offer an attractive framework to examine the cascade of processes that occur throughout both tendon pathology and repair. This review discusses the structural, mechanical, and biological changes that occur throughout tendon pathology in animal models, as well as strategies for the improvement of tendon healing.

Cite this article: Bone Joint Res 2014;3:193–202.

We report the results of the treatment of nine children with an aneurysmal bone cyst of the distal fibula (seven cysts were juxtaphyseal, and two metaphyseal). The mean age of the children was 10 years and 3 months (7 years and 4 months to 12 years and 9 months). All had open physes. All cysts were active and in seven cases substituted and expanded the entire width of the bone (type-2 lesions). The mean longitudinal extension was 5.7 cm (3 to 10). The presenting symptoms were pain, swelling and pathological fracture. Moderate fibular shortening was evident in one patient.

In six patients curettage was performed, using phenol as adjuvant in three. Three with juxtaphyseal lesions underwent resection. A graft from the contralateral fibula (one case) and allografts (two cases) were positioned at the edge of the physis for reconstruction. The mean follow-up was 11.6 years (3.1 to 27.5). There was no recurrence.

At the final follow-up there was no significant difference in the American Orthopaedic Foot and Ankle Society scores (excellent/good in all cases) and in growth disturbance, alignment, stability and bone reconstitution, but in the resection group the number of operations, including removal of hardware, complications (two minor) and time of immobilisation/orthosis, were increased. Movement of the ankle was restricted in one patient.

The potential risks in the management of these lesions include recurrence, physeal injury, instability of the ankle and hardware and graft complications. Although resection is effective it should be reserved for aggressive or recurrent juxtaphyseal lesions.

Impacted bone allograft is often used in revision joint replacement. Hydroxyapatite granules have been suggested as a substitute or to enhance morcellised bone allograft. We hypothesised that adding osteogenic protein-1 to a composite of bone allograft and non-resorbable hydroxyapatite granules (ProOsteon) would improve the incorporation of bone and implant fixation. We also compared the response to using ProOsteon alone against bone allograft used in isolation. We implanted two non-weight-bearing hydroxyapatite-coated implants into each proximal humerus of six dogs, with each implant surrounded by a concentric 3 mm gap. These gaps were randomly allocated to four different procedures in each dog: 1) bone allograft used on its own; 2) ProOsteon used on its own; 3) allograft and ProOsteon used together; or 4) allograft and ProOsteon with the addition of osteogenic protein-1.

After three weeks osteogenic protein-1 increased bone formation and the energy absorption of implants grafted with allograft and ProOsteon. A composite of allograft, ProOsteon and osteogenic protein-1 was comparable, but not superior to, allograft used on its own.

ProOsteon alone cannot be recommended as a substitute for allograft around non-cemented implants, but should be used to extend the volume of the graft, preferably with the addition of a growth factor.

Background

Resveratrol is a polyphenolic compound commonly found in the skins of red grapes. Sirtuin 1 (SIRT1) is a human gene that is activated by resveratrol and has been shown to promote longevity and boost mitochondrial metabolism. We examined the effect of resveratrol on normal and osteoarthritic (OA) human chondrocytes.

Objectives

Nonunion is one of the most troublesome complications to treat in orthopaedics. Former authors believed that atrophic nonunion occurred as a result of lack of mesenchymal stem cells (MSCs). We evaluated the number and viability of MSCs in site of atrophic nonunion compared with those in iliac crest.

The June 2013 Oncology Roundup³⁶⁰ looks at: whether allograft composite is superior to megaprosthesis in massive reconstruction; pain from glomus tumours; thromboembolism and orthopaedic malignancy; bone marrow aspirate and cavity lesions; metastasectomy in osteosarcoma; spinal giant cell tumour; post-atomic strike sarcoma; and superficial sarcomas and post-operative infection rates.