This prospective multicentre study was undertaken to determine whether the timing of the post-operative administration of bisphosphonate affects fracture healing and the rate of complication following an intertrochanteric fracture. Between August 2008 and December 2009, 90 patients with an intertrochanteric fracture who underwent internal fixation were randomised to three groups according to the timing of the commencement of risedronate treatment after surgery: Group A (from one week after surgery), Group B (from one month after surgery), and Group C (from three months after surgery). The radiological time to fracture healing was assessed as the primary endpoint, and the incidence of complications, including excessive displacement or any complication requiring revision surgery, as the secondary endpoint. The mean time to fracture healing post-operatively in groups A, B and C was 10.7 weeks (sd 4.4), 12.9 weeks (sd 6.2) and 12.3 weeks (sd 7.1), respectively (p = 0.420). At 24 weeks after surgery, all fractures had united, except six that had a loss of fixation. Functional outcomes at one year after surgery according to the Koval classification (p = 0.948) and the incidence of complications (p = 0.386) were similar in the three groups.

This study demonstrates that the timing of the post-operative administration of bisphosphonates does not appear to affect the rate of healing of an intertrochanteric fracture or the incidence of complications.

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.

We investigated the eventual diagnosis in patients referred to a tertiary centre with a possible diagnosis of a primary bone malignancy.

We reviewed our database from between 1986 and 2010, during which time 5922 patients referred with a suspicious bone lesion had a confirmed diagnosis. This included bone sarcoma in 2205 patients (37%), benign bone tumour in 1309 (22%), orthopaedic conditions in 992 (17%), metastatic disease in 533 (9%), infection in 289 (5%) and haematological disease in 303 (5%). There was a similar frequency of all diagnoses at different ages except for metastatic disease. Only 0.6% of patients (17 of 2913) under the age of 35 years had metastatic disease compared with 17.1% (516 of 3009) of those over 35 years (p < 0.0001). Of the 17 patients under 35 years with metastatic disease, only four presented with an isolated lesion, had no past history of cancer and were systematically well.

Patients under the age of 35 years should have suitable focal imaging (plain radiography, CT or MRI) and simple systemic studies (blood tests and chest radiography). Reduction of the time to biopsy can be achieved by avoiding an unnecessary investigation for a primary tumour to rule out metastatic disease.

Smoking is known to have an adverse effect on wound healing and musculoskeletal conditions. This case-controlled study looked at whether smoking has a deleterious effect in the outcome of autologous chondrocyte implantation for the treatment of full thickness chondral defects of the knee.

The mean Modified Cincinatti Knee score was statistically significantly lower in smokers (n = 48) than in non-smokers (n = 66) both before and after surgery (p < 0.05). Smokers experienced significantly less improvement in the knee score two years after surgery (p < 0.05). Graft failures were only seen in smokers (p = 0.016). There was a strong negative correlation between the number of cigarettes smoked and the outcome following surgery (Pearson’s correlation coefficient −0.65, p = 0.004).

These results suggest that patients who smoke have worse pre-operative function and obtain less benefit from this procedure than non-smokers. The counselling of patients undergoing autologous chondrocyte implantation should include smoking, not only as a general cardiopulmonary risk but also because poorer results can be expected in smokers following this procedure.

We have previously shown that joint distraction and movement with a hinged external fixation device for 12 weeks was useful for repairing a large articular cartilage defect in a rabbit model. We have now investigated the results after six months and one year. The device was applied to 16 rabbits who underwent resection of the articular cartilage and subchondral bone from the entire tibial plateau. In group A (nine rabbits) the device was applied for six months. In group B (seven rabbits) it was in place for six months, after which it was removed and the animals were allowed to move freely for an additional six months. The cartilage remained sound in all rabbits. The areas of type II collagen-positive staining and repaired soft tissue were larger in group B than in group A. These findings provide evidence of long-term persistence of repaired cartilage with this technique and that weight-bearing has a positive effect on the quality of the cartilage.

Heterotopic ossification occurring after the use of commercially available bone morphogenetic proteins has not been widely reported. We describe four cases of heterotopic ossification in patients treated with either recombinant bone morphogenetic protein 2 or recombinant bone morphogenetic protein 7. We found that while some patients were asymptomatic, heterotopic ossification which had occurred around a joint often required operative excision with good results.

Conventional non-steroidal anti-inflammatory drugs (NSAIDs) and newer specific cyclo-oxygenase-2 (cox-2) inhibitors are commonly used in musculoskeletal trauma and orthopaedic surgery to reduce the inflammatory response and pain. These drugs have been reported to impair bone metabolism. In reconstruction of the anterior cruciate ligament the hamstring tendons are mainly used as the graft of choice, and a prerequisite for good results is healing of the tendons in the bone tunnel. Many of these patients are routinely given NSAIDs or cox-2 inhibitors, although no studies have elucidated the effects of these drugs on tendon healing in the bone tunnel.

In our study 60 female Wistar rats were randomly allocated into three groups of 20. One received parecoxib, one indometacin and one acted as a control. In all the rats the tendo-Achillis was released proximally from the calf muscles. It was then pulled through a drill hole in the distal tibia and sutured anteriorly. The rats were given parecoxib, indometacin or saline intraperitoneally twice daily for seven days. After 14 days the tendon/bone-tunnel interface was subjected to mechanical testing.

Significantly lower maximum pull-out strength (p < 0.001), energy absorption (p < 0.001) and stiffness (p = 0.035) were found in rats given parecoxib and indometacin compared with the control group, most pronounced with parecoxib.

The haematoma occurring at the site of a fracture is known to play an important role in bone healing. We have recently shown the presence of progenitor cells in human fracture haematoma and demonstrated that they have the capacity for multilineage mesenchymal differentiation. There have been many studies which have shown that low-intensity pulsed ultrasound (LIPUS) stimulates the differentiation of a variety of cells, but none has investigated the effects of LIPUS on cells derived from human fracture tissue including human fracture haematoma-derived progenitor cells (HCs). In this in vitro study, we investigated the effects of LIPUS on the osteogenic activity of HCs. Alkaline phosphatase activity, osteocalcin secretion, the expression of osteoblast-related genes and the mineralisation of HCs were shown to be significantly higher when LIPUS had been applied but without a change in the proliferation of the HCs. These findings provide evidence in favour of the use of LIPUS in the treatment of fractures.

Perilesional changes of chronic focal osteochondral defects were assessed in the knees of 23 sheep. An osteochondral defect was created in the main load-bearing region of the medial condyle of the knees in a controlled, standardised manner. The perilesional cartilage was evaluated macroscopically and biopsies were taken at the time of production of the defect (T0), during a second operation one month later (T1), and after killing animals at three (T3; n = 8), four (T4; n = 8), and seven (T7; n = 8) months. All the samples were histologically assessed by the International Cartilage Repair Society grading system and Mankin histological scores. Biopsies were taken from human patients (n = 10) with chronic articular cartilage lesions and compared with the ovine specimens. The ovine perilesional cartilage presented with macroscopic and histological signs of degeneration. At T1 the International Cartilage Repair Society ‘Subchondral Bone’ score decreased from a mean of 3.0 (sd 0) to a mean of 1.9 (sd 0.3) and the ‘Matrix’ score from a mean of 3.0 (sd 0) to a mean of 2.5 (sd 0.5). This progressed further at T3, with the International Cartilage Repair Society ‘Surface’ grading, the ‘Matrix’ grading, ‘Cell Distribution’ and ‘Cell Viability’ grading further decreasing and the Mankin score rising from a mean of 1.3 (sd 1.4) to a mean of 5.1 (sd 1.6). Human biopsies achieved Mankin grading of a mean of 4.2 (sd 1.6) and were comparable with the ovine histology at T1 and T3.

The perilesional cartilage in the animal model became chronic at one month and its histological appearance may be considered comparable with that seen in human osteochondral defects after trauma.

Highly active anti-retroviral therapy has transformed HIV into a chronic disease with a long-term asymptomatic phase. As a result, emphasis is shifting to other effects of the virus, aside from immunosuppression and mortality. We have reviewed the current evidence for an association between HIV infection and poor fracture healing.

The increased prevalence of osteoporosis and fragility fractures in HIV patients is well recognised. The suggestion that this may be purely as a result of highly active anti-retroviral therapy has been largely rejected. Apart from directly impeding cellular function in bone remodelling, HIV infection is known to cause derangement in the levels of those cytokines involved in fracture healing (particularly tumour necrosis factor-α) and appears to impair the blood supply of bone.

Many other factors complicate this issue, including a reduced body mass index, suboptimal nutrition, the effects of anti-retroviral drugs and the avoidance of operative intervention because of high rates of wound infection. However, there are sound molecular and biochemical hypotheses for a direct relationship between HIV infection and impaired fracture healing, and the rewards for further knowledge in this area are extensive in terms of optimised fracture management, reduced patient morbidity and educated resource allocation. Further investigation in this area is overdue.

The use of allograft struts and cerclage wire, possibly augmented by plate fixation, for the treatment of Vancouver type-B1 peri-prosthetic fractures around a total hip replacement has been strongly advocated. We examined our results using plate fixation without allograft struts and compared them with the results of the use of struts alone or when combined with plate fixation. Of 20 consecutive patients with type-B1 fractures treated by open reduction and plate fixation, 19 were available for follow-up. The fractures healed in 18 patients with a mean time to weight-bearing of ten weeks (4 to 19). There were no cases of infection or malunion. Nonunion occurred in one patient and required a second plate fixation to achieve union.

Safe, cost-effective treatment of Vancouver type-B1 fractures can be performed by plate fixation without the addition of cortical struts. This procedure may allow earlier weight-bearing than allograft strut fixation alone.

We have evaluated the effect of the short-term administration of low therapeutic doses of modern COX-2 inhibitors on the healing of fractures.

A total of 40 adult male New Zealand rabbits were divided into five groups. A mid-diaphyseal osteotomy of the right ulna was performed and either normal saline, prednisolone, indometacin, meloxicam or rofecoxib was administered for five days. Radiological, biomechanical and histomorphometric evaluation was performed at six weeks.

In the group in which the highly selective anti-COX-2 agent, rofecoxib, was used the incidence of radiologically-incomplete union was similar to that in the control group. All the biomechanical parameters were statistically significantly lower in both the prednisolone and indometacin (p = 0.01) and in the meloxicam (p = 0.04) groups compared with the control group. Only the fracture load values were found to be statistically significantly lower (p = 0.05) in the rofecoxib group. Histomorphometric parameters were adversely affected in all groups with the specimens of the rofecoxib group showing the least negative effect.

Our findings indicated that the short-term administration of low therapeutic doses of a highly selective COX-2 inhibitor had a minor negative effect on bone healing.

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 retrospectively reviewed 101 consecutive patients with 114 femoral tumours treated by massive bone allograft at our institution between 1986 and 2005. There were 49 females and 52 males with a mean age of 20 years (4 to 74). At a median follow-up of 9.3 years (2 to 19.8), 36 reconstructions (31.5%) had failed. The allograft itself failed in 27 reconstructions (24%).

Mechanical complications such as delayed union, fracture and failure of fixation were studied. The most adverse factor on the outcome was the use of intramedullary nails, followed by post-operative chemotherapy, resection length > 17 cm and age > 18 years at the time of intervention. The simultaneous use of a vascularised fibular graft to protect the allograft from mechanical complications improved the outcome, but the use of intramedullary cementing was not as successful.

In order to improve the strength of the reconstruction and to advance the biology of host–graft integration, we suggest avoiding the use of intramedullary nails and titanium plates, but instead using stainless steel plates, as these gave better results. The use of a supplementary vascularised fibular graft should be strongly considered in adult patients with resection > 17 cm and in those who require post-operative chemotherapy.

A percutaneous supramalleolar osteotomy with multiple drill holes and closed osteoclasis was used to correct rotational deformities of the tibia in patients with cerebral palsy. The technique is described and the results in 247 limbs (160 patients) are reported. The mean age at the time of surgery was 10.7 years (4 to 20). The radiographs were analysed for time to union, loss of correction, and angulation at the site of the osteotomy.

Bone healing was obtained in all patients except one in a mean period of seven weeks (5 to 12). Malunion after loss of reduction at the site of the osteotomy developed in one tibia.

Percutaneous supramalleolar osteotomy of the tibia is a safe and simple surgical procedure.

This paper reviews the current literature concerning the main clinical factors which can impair the healing of fractures and makes recommendations on avoiding or minimising these in order to optimise the outcome for patients. The clinical implications are described.

The literature on fracture repair has been reviewed. The traditional concepts of delayed and nonunion have been examined in terms of the phased and balanced anabolic and catabolic responses in bone repair. The role of medical manipulation of these inter-related responses in the fracture healing have been considered.

In patients with traumatic brain injury and fractures of long bones, it is often clinically observed that the rate of bone healing and extent of callus formation are increased. However, the evidence has been unconvincing and an association between such an injury and enhanced fracture healing remains unclear. We performed a retrospective cohort study of 74 young adult patients with a mean age of 24.2 years (16 to 40) who sustained a femoral shaft fracture (AO/OTA type 32A or 32B) with or without a brain injury. All the fractures were treated with closed intramedullary nailing. The main outcome measures included the time required for bridging callus formation (BCF) and the mean callus thickness (MCT) at the final follow-up. Comparative analyses were made between the 20 patients with a brain injury and the 54 without brain injury. Subgroup comparisons were performed among the patients with a brain injury in terms of the severity of head injury, the types of intracranial haemorrhage and gender. Patients with a brain injury had an earlier appearance of BCF (p < 0.001) and a greater final MCT value (p < 0.001) than those without. There were no significant differences with respect to the time required for BCF and final MCT values in terms of the severity of head injury (p = 0.521 and p = 0.153, respectively), the types of intracranial haemorrhage (p = 0.308 and p = 0.189, respectively) and gender (p = 0.383 and p = 0.662, respectively).

These results confirm that an injury to the brain may be associated with accelerated fracture healing and enhanced callus formation. However, the severity of the injury to the brain, the type of intracranial haemorrhage and gender were not statistically significant factors in predicting the rate of bone healing and extent of final callus formation.

Between 1998 and 2002, 37 neuropathies in 32 patients with a displaced supracondylar fracture of the humerus who were referred to a nerve injury unit were identified. There were 19 boys and 13 girls with a mean age of 7.9 years (3.6 to 11.3). A retrospective review of these injuries was performed. The ulnar nerve was injured in 19, the median nerve in ten and the radial nerve in eight cases. Fourteen neuropathies were noted at the initial presentation and 23 were diagnosed after treatment of the fracture. After referral, exploration of the nerve was planned for 13 patients. Surgery was later cancelled in three because of clinical recovery. Six patients underwent neurolysis alone. Excision of neuroma and nerve grafting were performed in four. At follow-up, 26 patients had an excellent, five a good and one a fair outcome.

Platelet-derived growth factor (PDGF) is known to stimulate osteoblast or osteoprogenitor cell activity. We investigated the effect of locally applied PDGF from poly-d,l-lactide (PDLLA)-coated implants on fracture healing in a rat model. A closed fracture of the right tibia of four-month-old Sprague-Dawley rats (n = 40) was stabilised with implants coated with a biodegradable PDLLA versus implants coated with PDLLA and PDGF. Radiographs were taken throughout the study, and a marker of DNA activity, bromodeoxyuridine (BrdU), was injected before the rats were killed at three, seven and ten days. The radiographs showed consolidation of the callus in the PDGF-treated group compared with the control group at all three time points. In the PDGF-treated group, immunohistochemical staining of BrdU showed that the distribution of proliferating cells in all cellular events was higher after ten days compared with that at three and seven days.

These results indicate that local application of PDGF from biodegradable PDLLA-coated implants significantly accelerates fracture healing in experimental animals. Further development may help fracture healing in the clinical situation.