Objectives

Venous thromboembolism (VTE) is a major potential complication following orthopaedic surgery. Subcutaneously administered enoxaparin has been used as the benchmark to reduce the incidence of VTE. However, concerns have been raised regarding the long-term administration of enoxaparin and its possible negative effects on bone healing and bone density with an increase of the risk of osteoporotic fractures. New oral anticoagulants such as rivaroxaban have recently been introduced, however, there is a lack of information regarding how these drugs affect bone metabolism and post-operative bone healing.

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.

Pigmented villonodular synovitis (PVNS) is a rare benign disease of the synovium of joints and tendon sheaths, which may be locally aggressive. We present 18 patients with diffuse-type PVNS of the foot and ankle followed for a mean of 5.1 years (2 to 11.8). There were seven men and 11 women, with a mean age of 42 years (18 to 73). A total of 13 patients underwent open or arthroscopic synovectomy, without post-operative radiotherapy. One had surgery at the referring unit before presentation with residual tibiotalar PVNS. The four patients who were managed non-operatively remain symptomatically controlled and under clinical and radiological surveillance. At final follow-up the mean Musculoskeletal Tumour Society score was 93.8% (95% confidence interval (CI) 85 to 100), the mean Toronto Extremity Salvage Score was 92 (95% CI 82 to 100) and the mean American Academy of Orthopaedic Surgeons foot and ankle score was 89 (95% CI 79 to 100). The lesion in the patient with residual PVNS resolved radiologically without further intervention six years after surgery. Targeted synovectomy without adjuvant radiotherapy can result in excellent outcomes, without recurrence. Asymptomatic patients can be successfully managed non-operatively. This is the first series to report clinical outcome scores for patients with diffuse-type PVNS of the foot and ankle.

Cite this article: Bone Joint J 2013;95-B:384–90.

The June 2014 Research Roundup³⁶⁰ looks at:Intraoperative irrigation a balance of toxicities; Ibandronate effective in bone marrow oedema; Risk stratification in damage control surgery; Osteoblast like cells potentially safe; Better wear and antibacterial?; Assessing outcomes in hip fracture.

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.

Systemic factors are believed to be pivotal for the development of heterotopic ossification in severely-injured patients. In this study, cell cultures of putative target cells (human fibroblastic cells, osteoblastic cells (MG-63), and bone-marrow stromal cells (hBM)) were incubated with serum from ten consecutive polytraumatised patients taken from post-traumatic day 1 to day 21 and with serum from 12 healthy control subjects.

The serum from the polytraumatised patients significantly stimulated the proliferation of fibroblasts, MG-63 and of hBM cells. The activity of alkaline phosphatase in MG-63 and hBM cells was significantly decreased when exposed to the serum of the severely-injured patient. After three weeks in 3D cell cultures, matrix production and osteogenic gene expression of hBM cells were equal in the patient and control groups. However, the serum from the polytraumatised patients significantly decreased apoptosis of hBM cells compared with the control serum (4.3% vs 19.1%, p = 0.031).

Increased proliferation of osteoblastic cells and reduced apoptosis of osteoprogenitors may be responsible for increased osteogenesis in severely-injured patients.

Peri-prosthetic osteolysis and subsequent aseptic loosening is the most common reason for revising total hip replacements. Wear particles originating from the prosthetic components interact with multiple cell types in the peri-prosthetic region resulting in an inflammatory process that ultimately leads to peri-prosthetic bone loss. These cells include macrophages, osteoclasts, osteoblasts and fibroblasts. The majority of research in peri-prosthetic osteolysis has concentrated on the role played by osteoclasts and macrophages. The purpose of this review is to assess the role of the osteoblast in peri-prosthetic osteolysis.

In peri-prosthetic osteolysis, wear particles may affect osteoblasts and contribute to the osteolytic process by two mechanisms. First, particles and metallic ions have been shown to inhibit the osteoblast in terms of its ability to secrete mineralised bone matrix, by reducing calcium deposition, alkaline phosphatase activity and its ability to proliferate. Secondly, particles and metallic ions have been shown to stimulate osteoblasts to produce pro inflammatory mediators in vitro. In vivo, these mediators have the potential to attract pro-inflammatory cells to the peri-prosthetic area and stimulate osteoclasts to absorb bone. Further research is needed to fully define the role of the osteoblast in peri-prosthetic osteolysis and to explore its potential role as a therapeutic target in this condition.

Cite this article: Bone Joint J 2013;95-B:1021–5.

Osteochondral lesions (OCLs) occur in up to 70% of sprains and fractures involving the ankle. Atraumatic aetiologies have also been described. Techniques such as microfracture, and replacement strategies such as autologous osteochondral transplantation, or autologous chondrocyte implantation are the major forms of surgical treatment. Current literature suggests that microfracture is indicated for lesions up to 15 mm in diameter, with replacement strategies indicated for larger or cystic lesions. Short- and medium-term results have been reported, where concerns over potential deterioration of fibrocartilage leads to a need for long-term evaluation.

Biological augmentation may also be used in the treatment of OCLs, as they potentially enhance the biological environment for a natural healing response. Further research is required to establish the critical size of defect, beyond which replacement strategies should be used, as well as the most appropriate use of biological augmentation. This paper reviews the current evidence for surgical management and use of biological adjuncts for treatment of osteochondral lesions of the talus.

Cite this article: Bone Joint J 2014;96-B:164–71.

Primary giant-cell tumour of soft tissue arising in the ligamentum teres has not been previously described. We report a case of such a tumour in a 46-year-old woman. The lesion was only detected at the time of hip arthroscopy despite pre-operative MRI being performed. It was successfully excised arthroscopically with resolution of the symptoms.

The scarcity of mesenchymal stem cells (MSCs) in iliac crest bone marrow aspirate (ICBMA), and the expense and time in culturing cells, has led to the search for alternative harvest sites. The reamer-irrigation-aspirator (RIA) provides continuous irrigation and suction during reaming of long bones. The aspirated contents pass via a filter, trapping bony fragments, before moving into a ‘waste’ bag from which MSCs have been previously isolated. We examined the liquid and solid phases, performed a novel digestion of the solid phase, and made a comparative assessment in terms of number, phenotype and differentiation capacity with matched ICBMA.

The solid fraction from the filtrate was digested for 60 minutes at 37°C with collagenase. Enumeration was performed via the colony-forming unit fibroblast (CFU-F) assay. Passage (P2) cells were differentiated towards osteogenic, adipogenic and chondrogenic lineages, and their phenotypes assessed using flow cytometry (CD33, CD34, CD45, CD73, CD90, and CD105).

MSCs from the RIA phases were able to differentiate at least as well as those from ICBMA, and all fractions had phenotypes consistent with other established sources. The median number of colonies for the three groups was: ICBMA = 8.5 (2 to 86), RIA-liquid = 19.5 (4 to 90), RIA-solid = 109 (67 to 200) per 200 μl. The mean total yield of cells for the three groups was: ICBMA = 920 (0 to 4275), RIA-liquid = 114 983 (16 500 to 477 750), RIA-solid = 12 785 (7210 to 28 475).

The RIA filtrate contains large numbers of MSCs that could potentially be extracted without enzymatic digestion and used for bone repair without prior cell expansion.

The nervous system is known to be involved in inflammation and repair. We aimed to determine the effect of physical activity on the healing of a muscle injury and to examine the pattern of innervation. Using a drop-ball technique, a contusion was produced in the gastrocnemius in 20 rats. In ten the limb was immobilised in a plaster cast and the remaining ten had mobilisation on a running wheel. The muscle and the corresponding dorsal-root ganglia were studied by histological and immunohistochemical methods.

In the mobilisation group, there was a significant reduction in lymphocytes (p = 0.016), macrophages (p = 0.008) and myotubules (p = 0.008) between three and 21 days. The formation of myotubules and the density of nerve fibres was significantly higher (both p = 0.016) compared with those in the immobilisation group at three days, while the density of CGRP-positive fibres was significantly lower (p = 0.016) after 21 days.

Mobilisation after contusional injury to the muscle resulted in early and increased formation of myotubules, early nerve regeneration and progressive reduction in inflammation, suggesting that it promoted a better healing response.

Invasive group A streptococcus (iGAS) is the most common cause of monomicrobial necrotising fasciitis. Necrotising infections of the extremities may present directly to orthopaedic surgeons or by reference from another admitting specialty. Recent epidemiological data from the Health Protection Agency suggest an increasing incidence of iGAS infection in England. Almost 40% of those affected had no predisposing illnesses or risk factors, and the proportion of children presenting with infections has risen. These observations have prompted the Chief Medical Officer for the Central Alerting System in England to write to general practitioners and hospitals, highlighting the need for clinical vigilance, early diagnosis and rapid initiation of treatment in suspected cases.

The purpose of this annotation is to summarise the recent epidemiological trends, describe the presenting features and outline the current investigations and treatment of this rare but life-threatening condition.

Giant-cell tumour of the synovium is known to affect the fingers or toes of adults. It has seldom been described in the spine and rarely in the thoracic vertebrae or in a child. The lesions of giant-cell tumour of the synovium have a classical radiological appearance, but require a high index of suspicion for correct recognition. Unlike giant-cell tumour of the synovium at other well-known sites, spinal lesions lack the characteristic papillary architecture, thereby raising other diagnostic possibilities. We describe a giant-cell tumour of the synovium of the left facet joint of a thoracic vertebra in a nine-year-old girl. The tumour was treated successfully by surgical excision.

Successful healing of a nine-year tibial nonunion resistant to six previous surgical procedures was achieved by tissue engineering. We used autologous bone marrow stromal cells (BMSCs) expanded to 5 × 10⁶ cells after three weeks’ tissue culture. Calcium sulphate (CaSO₄) in pellet form was combined with these cells at operation. The nonunion was clinically and radiologically healed two months after implantation.

This is the description of on healing of a long-standing tibial nonunion by tissue engineering. The successful combination of BMSCs and CaSO₄ has not to our knowledge been reported in a clinical setting.

Four patients who developed malignant synovial tumours are described; one with chondromatosis developed a synovial chondrosarcoma and three with pigmented villonodular synovitis developed malignant change. The relevant literature is discussed.

The management of osteonecrosis of the femoral head ranges from symptomatic therapy to total hip replacement. Conservative treatment is effective only in small, early-stage lesions. Free vascularised fibular grafting has provided more consistently successful results than any other joint-preserving method. It supports the collapsing subchondral plate by primary callus formation, reduces intra-osseous pressure, removes and replaces the necrotic segment, and adds viable cortical bone graft plus fresh cancellous graft, which has osseoinductive and osseoconductive potential. Factors predisposing to success are the aetiology, stage and size of the lesion. Furthermore, it is a hip-salvaging procedure in early pre-collapse stages, and a time-buying one when the femoral head has collapsed.

Multiple drilling is reported to be an effective treatment for osteonecrosis of the head of femur, but its effect on intra-osseous pressure has not been described. We undertook multiple drilling and recorded the intra-osseous pressure in 75 osteonecrotic hips in 60 patients with a mean age of 42 years (19 to 67). At a mean follow-up of 37.1 months (24 to 60), 42 hips (56%) had a clinically successful outcome. The procedure was effective in reducing the mean intra-osseous pressure from 57 mmHg (SD 22) to 16 mmHg (SD 9). Hips with a successful outcome had a mean pressure of 26 mmHg (SD 19). It was less effective in preventing progression of osteonecrosis in hips with considerable involvement and in those with a high intra-osseous pressure in the intertrochanteric region (mean 45 mmHg (SD 25)). This study is not able to answer whether a return of the intra-osseous pressure to normal levels is required for satisfactory healing.

Despite worldwide clinical use of bio-absorbable devices for internal fixation in orthopaedic surgery, the degradation behaviour and tissue replacement of these implants are not fully understood.

In a long-term experimental study, we have determined the patterns of tissue restoration 36 and 54 months after implantation of polyglycolic acid and poly-laevo-lactic acid screws in the distal femur of the rabbit.

After 36 months in the polyglycolic acid group the specimens showed no remaining polymer and loose connective tissue occupied 80% of the screw track. Tissue restoration remained poor at 54 months, the amounts of trabecular bone and haematopoietic elements being significantly lower than those in the intact control group. The amount of trabecular bone within the screw track at 54 months in the polyglycolic acid group was less than in the empty drill holes (p = 0.04). In the poly-laevo-lactic acid group, polymeric material was present in abundance after 54 months, occupying 60% of the cross-section of the core area of the screw track.

When using absorbable internal fixation implants we should recognise that the degradation of the devices will probably not be accompanied by the restoration of normal trabecular bone.

We produced large full-thickness articular cartilage defects in 33 rabbits in order to evaluate the effect of joint distraction and autologous culture-expanded bone-marrow-derived mesenchymal cell transplantation (ACBMT) at 12 weeks. After fixing the knee on a hinged external fixator, we resected the entire surface of the tibial plateau. We studied three groups: 1) with and without joint distraction; 2) with joint distraction and collagen gel, and 3) with joint distraction and ACBMT and collagen gel.

The histological scores were significantly higher in the groups with ACBMT collagen gel (p < 0.05). The area of regenerated soft tissue was smaller in the group allowed to bear weight (p < 0.05). These findings suggest that the repair of large defects of cartilage can be enhanced by joint distraction, collagen gel and ACBMT.