The June 2012 Research Roundup³⁶⁰ looks at: platelet-rich plasma; ageing, bone and mesenchymal stem cells; cytokines and the herniated intervertebral disc; ulcerative colitis, Crohn’s disease and anti-inflammatories; the effect of NSAIDs on bone healing; osteoporosis of the fractured hip; herbal medicine and recovery after acute muscle injury; and ultrasound and the time to fracture union.

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

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.

Free vascularised fibular grafting has been reported to be successful for adult patients with osteonecrosis of the femoral head (ONFH). However, its benefit in teenage patients with post-traumatic ONFH has not been determined. We evaluated the effectiveness of free vascularised fibular grafting in the treatment of this condition in children and adolescents. We retrospectively analysed 28 hips in 28 patients in whom an osteonecrotic femoral head had been treated with free vascularised fibular grafting between 2002 and 2008. Their mean age was 16.3 years (13 to 19). The stage of the disease at time of surgery, and results of treatment including pre- and post-operative Harris hip scores, were studied. We defined clinical failure as conversion to total hip replacement. All patients were followed up for a mean of four years (2 to 7). The mean Harris hip score improved from 60.4 (37 to 84) pre-operatively to 94.2 (87 to 100) at final follow-up. At the latest follow-up we found improved or unchanged radiographs in all four initially stage II hips and in 23 of 24 stage III or IV hips. Only one hip (stage V) deteriorated. No patient underwent total hip replacement.

Free vascularised fibular grafting is indicated for the treatment of post-traumatic ONFH in teenage patients.

We report the results of intramedullary leg lengthening conducted between 2002 and 2009 using the Intramedullary Skeletal Kinetic Distractor in 69 unilateral lengthenings involving 58 femora and 11 tibiae. We identified difficulties that occurred during the treatment and assessed whether they were specifically due to the implant or independent of it. Paley’s classification for evaluating problems, obstacles and complications with external fixators was adopted, and implant-specific difficulties were continuously noted. There were seven failures requiring premature removal of the device, in four due to nail breakage and three for other reasons, and five unsuccessful outcomes after completion of the lengthening. In all, 116 difficulties were noted in 45 patients, with only 24 having problem-free courses. In addition to the difficulties arising from the use of external fixators, there were almost the same number again of implant-specific difficulties.

Nevertheless, successful femoral lengthening was achieved in 52 of the 58 patients (90%). However, successful tibial lengthening was only achieved in five of 11 patients (45%).

We prospectively evaluated the long-term outcome of 158 consecutive patients who underwent revision total hip replacement using uncemented computer-assisted design-computer-assisted manufacture femoral components. There were 97 men and 61 women. Their mean age was 63.1 years (34.6 to 85.9). The mean follow-up was 10.8 years (10 to 12).

The mean Oxford, Harris and Western Ontario and McMaster hip scores improved from 41.1, 44.2 and 52.4 pre-operatively to 18.2, 89.3 and 12.3, respectively (p < 0.0001, for each). Six patients required further surgery. The overall survival of the femoral component was 97% (95% confidence interval 94.5 to 99.7). These results are comparable to those of previously published reports for revision total hip replacement using either cemented or uncemented components.

Bacterial infection in orthopaedic surgery can be devastating, and is associated with significant morbidity and poor functional outcomes, which may be improved if high concentrations of antibiotics can be delivered locally over a prolonged period of time. The two most widely used methods of doing this involve antibiotic-loaded polymethylmethacrylate or collagen fleece. The former is not biodegradable and is a surface upon which secondary bacterial infection may occur. Consequently, it has to be removed once treatment has finished. The latter has been used successfully as an adjunct to systemic antibiotics, but cannot effect a sustained release that would allow it to be used on its own, thereby avoiding systemic toxicity.

This review explores the newer biodegradable carrier systems which are currently in the experimental phase of development and which may prove to be more effective in the treatment of osteomyelitis.

Revision surgery of the hip was performed on 114 hips using an extensively porous-coated femoral component. Of these, 95 hips (94 patients) had a mean follow-up of 10.2 years (5 to 17). No cortical struts were used and the cortical index and the femoral cortical width were measured at different levels.

There were two revisions for aseptic loosening. Survivorship at 12 years for all causes of failure was 96.9% (95% confidence interval 93.5 to 100) in the best-case scenario. Fibrous or unstable fixation was associated with major bone defects. The cortical index (p = 0.045) and the lateral cortical thickness (p = 0.008) decreased at the proximal level over time while the medial cortex increased (p = 0.001) at the proximal and distal levels. An increase in the proximal medial cortex was found in patients with an extended transtrochanteric osteotomy (p = 0.026) and in those with components shorter than 25 cm (p = 0.008).

The use of the extensively porous-coated femoral component can provide a solution for difficult cases in revision surgery. Radiological bony ingrowth is common. Although without clinical relevance at the end of follow-up, the thickness of the medial femoral cortex often increased while that of the lateral cortex decreased. In cases in which a shorter component was used and in those undertaken using an extended trochanteric osteotomy, there was a greater increase in thickness of the femoral cortex over time.

We describe the treatment by subperiosteal resection of an aneurysmal bone cyst in the distal fibula in eight patients and highlight the role of the periosteum in the regeneration of bone defects. The mean age of the patients was 13.5 years (12 to 17). Seven had an open growth plate. The mean size of the resected specimen was 5.12 cm (3.5 to 8.0). None of the patients received instillation of bone marrow, autogenous bone graft, allograft or any synthetic bone substitutes. All had complete regeneration of the bone defect within three to nine months, with no joint instability or recurrence. The mean length of follow-up was 11.5 years (2 to 18). At the final follow-up there was no difference in the range of movement, alignment or stability of the ankle when compared with the opposite side. The periosteum played a major role in the complete filling of the bone defects and avoided the morbidity of other techniques

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.

Extensive limb lengthening may be indicated in achondroplastic patients who wish to achieve a height within the normal range for their population. However, increasing the magnitude of lengthening is associated with further complications particularly adjacent joint stiffness and fractures. We studied the relationship between the magnitude of femoral lengthening and callus pattern, adjacent joint stiffness and fracture of the regenerate bone in 40 femoral lengthenings in 20 achondroplastic patients. They were divided into two groups; group A had lengthening of less than 50% and group B of more than 50% of their initial femoral length. The patterns of radiological callus formation were classified according to shape, type and features. The incidence of callus features, knee stiffness and regenerate bone fracture were analysed in the two groups. Group B was associated with an increased incidence of concave, lateral and central callus shapes, adjacent joint and stiffness and fracture. Statistically, the incidence of stiffness in adjacent joints and regenerate bone fracture was significantly associated with the magnitude of lengthening. We suggest that careful radiological assessment of the patterns of callus formation is a useful method for the evaluation and monitoring of regenerate bone

We present the results of ankle fusion using the Ilizarov technique for bone loss around the ankle in 20 patients. All except one had sustained post-traumatic bone loss. Infection was present in 17. The mean age was 33.1 years (7 to 71). The mean size of the defect was 3.98 cm (1.5 to 12) and associated limb shortening before the index procedure varied from 1 cm to 5 cm. The mean time in the external fixator was 335 days (42 to 870). Tibiotalar fusion was performed in 19 patients and tibiocalcaneal fusion in one. Associated problems included diabetes in one patient, pelvic and urethral injury in one, visual injury in one patient and ipsilateral tibial fracture in five. At the final mean follow-up of 51.55 months (24 to 121) fusion had been achieved in 19 of 20 patients. A total of 16 patients were able to return to work. The results were graded as good in 11 patients, fair in six and poor in three. The mean external fixation index was 8.8 days/mm (0 to 30). One patient with diabetes developed severe infection which required early removal of the fixator. Refractures occurred in three patients, two of which were at the site of fusion and one at a previous tibial shaft fracture site. Equinus deformity of the ankle fusion occurred after a further fracture in one patient. There were two patients with residual forefoot equinus, and one developed late valgus at the fusion site. Poor consolidation of the regenerated bone in two patients was treated by bone grafting in one and by bone and fibular strut grafting in the other. Residual soft-tissue infection was still present in two patients

We studied the safety of external fixation during post-operative chemotherapy in 28 patients who had undergone distraction osteogenesis (17, group A) or vascularised fibular grafting (11, group B) after resection of a tumour. Four cycles of multi-agent post-operative chemotherapy were administered over a mean period of 14 weeks (6 to 27). The mean duration of external fixation for all patients was 350 days (91 to 828). In total 204 wires and 240 half pins were used.

During the period of post-operative chemotherapy, 14 patients (11 in group A, 3 in group B) developed wire- and pin-track infection. A total of ten wires (4.9%) and 11 half pins (4.6%) became infected. Seven of the ten infected wires were in periarticular locations.

External fixation during post-operative chemotherapy was used safely and successfully for fixation of a vascularised fibular graft and distraction osteogenesis in 27 of 28 patients. Post-operative chemotherapy for malignant bone tumours did not adversely affect the ability to achieve union or cause hypertrophy of the vascularised fibular graft and had a minimal effect on distraction osteogenesis. Only one patient developed osteomyelitis which required further surgery.

We report our experience of the use of callus distraction with a monolateral fixator for the treatment of acquired radial club-hand deformity after osteomyelitis. Between 1994 and 2004, 13 patients with a mean age of eight years (4 to 15) were treated by callus distraction with a monolateral fixator after a preliminary period of at least four weeks in a corrective short-arm cast.

All patients achieved bony union and were satisfied with the functional and cosmetic outcome. There were no major complications, but three patients required cancellous bone grafting at the docking site for delayed union. Local treatment and oral antibiotics were required for pin-site infection in six patients. There were no deep infection or recurrence of osteomyelitis.

We describe a 13-year-old boy with atrophic tibial pseudarthrosis associated with neurofibromatosis who had undergone nine unsuccessful operations. Eventually, union was obtained by the use of bone morphogenetic protein 7 in conjunction with intramedullary stabilisation and autologous bone graft.

Platelet-rich plasma is a new inductive therapy which is being increasingly used for the treatment of the complications of bone healing, such as infection and nonunion. The activator for platelet-rich plasma is a mixture of thrombin and calcium chloride which produces a platelet-rich gel.

We analysed the antibacterial effect of platelet-rich gel in vitro by using the platelet-rich plasma samples of 20 volunteers. In vitro laboratory susceptibility to platelet-rich gel was determined by the Kirby-Bauer disc-diffusion method. Baseline antimicrobial activity was assessed by measuring the zones of inhibition on agar plates coated with selected bacterial strains.

Zones of inhibition produced by platelet-rich gel ranged between 6 mm and 24 mm (mean 9.83 mm) in diameter. Platelet-rich gel inhibited the growth of Staphylococcus aureus and was also active against Escherichia coli. There was no activity against Klebsiella pneumoniae, Enterococcus faecalis, and Pseudomonas aeruginosa. Moreover, platelet-rich gel seemed to induce the in vitro growth of Ps. aeruginosa, suggesting that it may cause an exacerbation of infections with this organism. We believe that a combination of the inductive and antimicrobial properties of platelet-rich gel can improve the treatment of infected delayed healing and nonunion.

Failure of fixation is a common problem in the treatment of osteoporotic fractures around the hip. The reinforcement of bone stock or of fixation of the implant may be a solution. Our study assesses the existing evidence for the use of bone substitutes in the management of these fractures in osteoporotic patients. Relevant publications were retrieved through Medline research and further scrutinised. Of 411 studies identified, 22 met the inclusion criteria, comprising 12 experimental and ten clinical reports. The clinical studies were evaluated with regard to their level of evidence. Only four were prospective and randomised.

Polymethylmethacrylate and calcium-phosphate cements increased the primary stability of the implant-bone construct in all experimental and clinical studies, although there was considerable variation in the design of the studies. In randomised, controlled studies, augmentation of intracapsular fractures of the neck of the femur with calcium-phosphate cement was associated with poor long-term results. There was a lack of data on the long-term outcome for trochanteric fractures. Because there were only a few, randomised, controlled studies, there is currently poor evidence for the use of bone cement in the treatment of fractures of the hip.

The Ilizarov method for leg lengthening was used for cosmetic reasons in 54 patients with constitutional short stature. A mean lengthening of 7 cm with a low rate of complications produced an excellent or good outcome in all the patients, including improvement in psychological disturbances related to short stature. Those who undergo the procedure must be highly motivated, fully informed and understand the technique and possible complications. We suggest that the Ilizarov method for cosmetic limb lengthening is a technique without major complications. However, it requires careful follow-up, and the involvement of orthopaedic surgeons who are familiar with use of the circular frame and are experienced in limb lengthening and correction of deformity for pathological conditions.

Although mechanical stabilisation has been a hallmark of orthopaedic surgical management, orthobiologics are now playing an increasing role. Platelet-rich plasma (PRP) is a volume of plasma fraction of autologous blood having platelet concentrations above baseline. The platelet α granules are rich in growth factors that play an essential role in tissue healing, such as transforming growth factor-β, vascular endothelial growth factor, and platelet-derived growth factor. PRP is used in various surgical fields to enhance bone and soft-tissue healing by placing supraphysiological concentrations of autologous platelets at the site of tissue damage. The easily obtainable PRP and its possible beneficial outcome hold promise for new regenerative treatment approaches.

The aim of this literature review was to describe the bioactivities of PRP, to elucidate the different techniques for PRP preparation, to review animal and human studies, to evaluate the evidence regarding the use of PRP in trauma and orthopaedic surgery, to clarify risks, and to provide guidance for future research.