Objectives

In order to ensure safety of the cell-based therapy for bone regeneration, we examined in vivo biodistribution of locally or systemically transplanted osteoblast-like cells generated from bone marrow (BM) derived mononuclear cells.

The February 2014 Hip & Pelvis Roundup³⁶⁰ looks at: length of stay; cementless metaphyseal fixation; mortality trends in over 400,000 total hip replacements; antibiotics in hip fracture surgery; blood supply to the femoral head after dislocation; resurfacing and THR in metal-on-metal replacement; diabetes and hip replacement; bone remodelling over two decades following hip replacement; and whether bisphosphonates affect acetabular fixation.

Impaction allograft is an established method of securing initial stability of an implant in arthroplasty. Subsequent bone integration can be prolonged, and the volume of allograft may not be maintained. Intermittent administration of parathyroid hormone has an anabolic effect on bone and may therefore improve integration of an implant.

Using a canine implant model we tested the hypothesis that administration of parathyroid hormone may improve osseointegration of implants surrounded by bone graft. In 20 dogs a cylindrical porous-coated titanium alloy implant was inserted into normal cancellous bone in the proximal humerus and surrounded by a circumferential gap of 2.5 mm. Morsellised allograft was impacted around the implant. Half of the animals were given daily injections of human parathyroid hormone (1–34) 5 μg/kg for four weeks and half received control injections. The two groups were compared by mechanical testing and histomorphometry. We observed a significant increase in new bone formation within the bone graft in the parathyroid hormone group. There were no significant differences in the volume of allograft, bone-implant contact or in the mechanical parameters.

These findings suggest that parathyroid hormone improves new bone formation in impacted morsellised allograft around an implant and retains the graft volume without significant resorption. Fixation of the implant was neither improved nor compromised at the final follow-up of four weeks.

Chondral damage to the knee is common and, if left untreated, can proceed to degenerative osteoarthritis. In symptomatic patients established methods of management rely on the formation of fibrocartilage which has poor resistance to shear forces. The formation of hyaline or hyaline-like cartilage may be induced by implanting autologous, cultured chondrocytes into the chondral or osteochondral defect.

Autologous chondrocyte implantation may be used for full-thickness chondral or osteochondral injuries which are painful and debilitating with the aim of replacing damaged cartilage with hyaline or hyaline-like cartilage, leading to improved function. The intermediate and long-term functional and clinical results are promising.

We provide a review of autologous chondrocyte implantation and describe our experience with the technique at our institution with a mean follow-up of 32 months (1 to 9 years).

The procedure is shown to offer statistically significant improvement with advantages over other methods of management of chondral defects.

External fixation of distal tibial fractures is often associated with delayed union. We have investigated whether union can be enhanced by using recombinant bone morphogenetic protein-7 (rhBMP-7).

Osteoinduction with rhBMP-7 and bovine collagen was used in 20 patients with distal tibial fractures which had been treated by external fixation (BMP group). Healing of the fracture was compared with that of 20 matched patients in whom treatment was similar except that rhBMP-7 was not used.

Significantly more fractures had healed by 16 (p = 0.039) and 20 weeks (p = 0.022) in the BMP group compared with the matched group. The mean time to union (p = 0.002), the duration of absence from work (p = 0.018) and the time for which external fixation was required (p = 0.037) were significantly shorter in the BMP group than in the matched group. Secondary intervention due to delayed healing was required in two patients in the BMP group and seven in the matched group.

RhBMP-7 can enhance the union of distal tibial fractures treated by external fixation.

We have undertaken a prospective study in patients with a fracture of the femoral shaft requiring intramedullary nailing to test the hypothesis that the femoral canal could be a potential source of the second hit phenomenon. We determined the local femoral intramedullary and peripheral release of interleukin-6 (IL-6) after fracture and subsequent intramedullary reaming.

In all patients, the fracture caused a significant increase in the local femoral concentrations of IL-6 compared to a femoral control group. The concentration of IL-6 in the local femoral environment was significantly higher than in the patients own matched blood samples from their peripheral circulation. The magnitude of the local femoral release of IL-6 after femoral fracture was independent of the injury severity score and whether the fracture was closed or open.

In patients who underwent intramedullary reaming of the femoral canal a further significant local release of IL-6 was demonstrated, providing evidence that intramedullary reaming can cause a significant local inflammatory reaction.

We undertook a trial on 60 patients with AO 31A2 fractures of the hip who were randomised after stabilisation of the fracture into two equal groups, one of which received post-operative treatment using a non-invasive interactive neurostimulation device and the other with a sham device. All other aspects of their rehabilitation were the same. The treatment was continued for ten days after operation.

Outcome measurements included the use of a visual analogue scale for pain, the brief pain inventory and Ketorolac for post-operative control of pain, and an overall assessment of outcome by the surgeon. There were significantly better results for the patients receiving treatment by active electrical stimulation (repeated measures analysis of variance, p < 0.001). The findings of this pilot trial justify a larger study to determine if these results are more generally applicable.

Orthopaedic surgery is in an exciting transitional period as modern surgical interventions, implants and scientific developments are providing new therapeutic options. As advances in basic science and technology improve our understanding of the pathology and repair of musculoskeletal tissue, traditional operations may be replaced by newer, less invasive procedures which are more appropriately targeted at the underlying pathophysiology. However, evidence-based practice will remain a basic requirement of care. Orthopaedic surgeons can and should remain at the forefront of the development of novel therapeutic interventions and their application. Progression of the potential of bench research into an improved array of orthopaedic treatments in an effective yet safe manner will require the development of a subgroup of specialists with extended training in research to play an important role in bridging the gap between laboratory science and clinical practice. International regulations regarding the introduction of new biological treatments will place an additional burden on the mechanisms of this translational process, and orthopaedic surgeons who are trained in science, surgery and the regulatory environment will be essential. Training and supporting individuals with these skills requires special consideration and discussion by the orthopaedic community.

In this paper we review some traditional approaches to the integration of orthopaedic science and surgery, the therapeutic potential of current regenerative biomedical science for cartilage repair and ways in which we may develop surgeons with the skills required to translate scientific discovery into effective and properly assessed orthopaedic treatments.

A modular femoral head–neck junction has practical advantages in total hip replacement. Taper fretting and corrosion have so far been an infrequent cause of revision. The role of design and manufacturing variables continues to be debated. Over the past decade several changes in technology and clinical practice might result in an increase in clinically significant taper fretting and corrosion. Those factors include an increased usage of large diameter (36 mm) heads, reduced femoral neck and taper dimensions, greater variability in taper assembly with smaller incision surgery, and higher taper stresses due to increased patient weight and/or physical activity. Additional studies are needed to determine the role of taper assembly compared with design, manufacturing and other implant variables.

Cite this article: Bone Joint J 2013;95-B, Supple A:3–6.

The mammalian growth plate is a complex structure which is essential for the elongation of long bones. However, an understanding of how the growth plate functions at the cellular level is lacking. This review, summarises the factors involved in growth-plate regulation, its failure and the consequence of injury. We also describe some of the cellular mechanisms which underpin the increase in volume of the growth-plate chondrocyte which is the major determinant of the rate and extent of bone lengthening. We show how living in situ chondrocytes can be imaged using 2-photon laser scanning microscopy to provide a quantitative analysis of their volume. This approach should give better understanding of the cellular control of bone growth in both healthy and failed growth plates.

The feasibility of bone transport with bone substitute and the factors which are essential for a successful bone transport are unknown. We studied six groups of 12 Japanese white rabbits. Groups A to D received cylindrical autologous bone segments and groups E and F hydroxyapatite prostheses. The periosteum was preserved in group A so that its segments had a blood supply, cells, proteins and scaffold. Group B had no blood supply. Group C had proteins and scaffold and group D had only scaffold. Group E received hydroxyapatite loaded with recombinant human bone morphogenetic protein-2 and group F had hydroxyapatite alone.

Distraction osteogenesis occurred in groups A to C and E which had osteo-conductive transport segments loaded with osteo-inductive proteins. We conclude that scaffold and proteins are essential for successful bone transport, and that bone substitute can be used to regenerate bone.

We describe the management of nonunion combined with limb-length discrepancy following vascularised fibular grafting for the reconstruction of long-bone defects in the lower limb after resection of a tumour in skeletally immature patients. We operated on nine patients with a mean age of 13.1 years (10.5 to 14.5) who presented with a mean limb-length discrepancy of 7 cm (4 to 9) and nonunion at one end of a vascularised fibular graft, which had been performed previously, to reconstruct a bone defect after resection of an osteosarcoma.

Reconstruction was carried out using a ring fixator secured with correction by half pins of any malalignment, compression of the site of nonunion and lengthening through a metaphyseal parafocal osteotomy without bone grafting. The expected limb-length discrepancy at maturity was calculated using the arithmetic method. Solid union and the intended leg length were achieved in all the patients. Excessive scarring and the distorted anatomy from previous surgery in these patients required other procedures to be performed with minimal exposures and dissection in order to avoid further compromise to the vascularity of the graft or damage to neurovascular structures. The methods which we chose were simple and effective in addressing these complex problems.

The aim of this study was to investigate the occurrence of tissue hypoxia and apoptosis at different stages of tendinopathy and tears of the rotator cuff.

We studied tissue from 24 patients with eight graded stages of either impingement (mild, moderate and severe) or tears of the rotator cuff (partial, small, medium, large and massive) and three controls. Biopsies were analysed using three immunohistochemical techniques, namely antibodies against HIF-1α (a transcription factor produced in a hypoxic environment), BNip3 (a HIF-1α regulated pro-apoptotic protein) and TUNEL (detecting DNA fragmentation in apoptosis).

The HIF-1α expression was greatest in mild impingement and in partial, small, medium and large tears. BNip3 expression increased significantly in partial, small, medium and large tears but was reduced in massive tears. Apoptosis was increased in small, medium, large and massive tears but not in partial tears.

These findings reveal evidence of hypoxic damage throughout the spectrum of pathology of the rotator cuff which may contribute to loss of cells by apoptosis. This provides a novel insight into the causes of degeneration of the rotator cuff and highlights possible options for treatment.

We evaluated the possible induction of a systemic immune response to increase anti-tumour activity by the re-implantation of destructive tumour tissue treated by liquid nitrogen in a murine osteosarcoma (LM8) model. The tumours were randomised to treatment by excision alone or by cryotreatment after excision. Tissue from the tumour was frozen in liquid nitrogen, thawed in distilled water and then re-implanted in the same animal. In addition, some mice received an immunological response modifier of OK-432 after treatment. We measured the levels of interferon-gamma and interleukin-12 cytokines and the cytotoxicity activity of splenocytes against murine LM8 osteosarcoma cells. The number of lung and the size of abdominal metastases were also measured.

Re-implantation of tumour tissue after cryotreatment activated immune responses and inhibited metastatic tumour growth. OK-432 synergistically enhanced the anti-tumour effect. Our results suggest that the treatment of malignant bone tumours by reconstruction using autografts containing tumours which have been treated by liquid nitrogen may be of clinical value.

The pathophysiology of intervertebral disc degeneration has been extensively studied. Various factors have been suggested as influencing its aetiology, including mechanical factors, such as compressive loading, shear stress and vibration, as well as ageing, genetic, systemic and toxic factors, which can lead to degeneration of the disc through biochemical reactions. How are these factors linked? What is their individual importance? There is no clear evidence indicating whether ageing in the presence of repetitive injury or repetitive injury in the absence of ageing plays a greater role in the degenerative process. Mechanical factors can trigger biochemical reactions which, in turn, may promote the normal biological changes of ageing, which can also be accelerated by genetic factors. Degradation of the molecular structure of the disc during ageing renders it more susceptible to superimposed mechanical injuries.

This review supports the theory that degeneration of the disc has a complex multifactorial aetiology. Which factors initiate the events in the degenerative cascade is a question that remains unanswered, but most evidence points to an age-related process influenced primarily by mechanical and genetic factors.

Early and accurate prediction of hospital length-of-stay (LOS) in patients undergoing knee replacement is important for economic and operational reasons. Few studies have systematically developed a multivariable model to predict LOS. We performed a retrospective cohort study of 1609 patients aged ≥ 50 years who underwent elective, primary total or unicompartmental knee replacements. Pre-operative candidate predictors included patient demographics, knee function, self-reported measures, surgical factors and discharge plans. In order to develop the model, multivariable regression with bootstrap internal validation was used. The median LOS for the sample was four days (interquartile range 4 to 5). Statistically significant predictors of longer stay included older age, greater number of comorbidities, less knee flexion range of movement, frequent feelings of being down and depressed, greater walking aid support required, total (versus unicompartmental) knee replacement, bilateral surgery, low-volume surgeon, absence of carer at home, and expectation to receive step-down care. For ease of use, these ten variables were used to construct a nomogram-based prediction model which showed adequate predictive accuracy (optimism-corrected R² = 0.32) and calibration. If externally validated, a prediction model using easily and routinely obtained pre-operative measures may be used to predict absolute LOS in patients following knee replacement and help to better manage these patients.

Cite this article: Bone Joint J 2013;95-B:1490–6.

This article provides an overview of the role of genomics in sarcomas and describes how new methods of analysis and comparative screening have provided the potential to progress understanding and treatment of sarcoma. This article reviews genomic techniques, the evolution of the use of genomics in cancer, the current state of genomic analysis, and also provides an overview of the medical, social and economic implications of recent genomic advances.

We present the results of 90 consecutive children with displaced fractures of the forearm treated by elastic stable intramedullary nailing with a mean follow-up of 6.6 months (2.0 to 17.6). Eight (9%) had open fractures and 77 (86%) had sustained a fracture of both bones. The operations were performed by orthopaedic trainees in 78 patients (86%). All fractures healed at a mean of 2.9 months (1.1 to 8.7). There was one case of delayed union of an ulnar fracture. An excellent or good functional outcome was achieved in 76 patients (84%). There was no statistical difference detected when the grade of operating surgeon, age of the patient and the diaphyseal level of the fracture were correlated with the outcome. A limited open reduction was required in 40 fractures (44%).

Complications included seven cases of problematic wounds, two transient palsies of the superficial radial nerve and one case each of malunion and a post-operative compartment syndrome. At final follow-up, all children were pain-free and without limitation of sport and play activities.

Our findings indicate that the functional outcome following paediatric fractures of the forearm treated by elastic stable intramedullary nailing is good, without the need for anatomical restoration of the radial bow.

Sex hormones play important roles in the regulation of the proliferation, maturation and death of chondrocytes in the epiphyseal growth plate. We have investigated the effects of male castration on the cell kinetics of chondrocytes as defined by the numbers of proliferating and dying cells. The growth plates of normal rabbits and animals castrated at eight weeks of age were obtained at 10, 15, 20 and 25 weeks of age.

Our study suggested that castration led to an increase in apoptosis and a decrease in the proliferation of chondrocytes in the growth plate. In addition, the number of chondrocytes in the castrated rabbits was less than that of normal animals of the same age.