The aim of this study was to assess the effect of injecting genetically engineered chondrocytes expressing transforming growth factor beta 1 (TGF-β1) into the knees of patients with osteoarthritis. We assessed the resultant function, pain and quality of life.

A total of 54 patients (20 men, 34 women) who had a mean age of 58 years (50 to 66) were blinded and randomised (1:1) to receive a single injection of the active treatment or a placebo. We assessed post-treatment function, pain severity, physical function, quality of life and the incidence of treatment-associated adverse events. Patients were followed at four, 12 and 24 weeks after injection.

At final follow-up the treatment group had a significantly greater improvement in the mean International Knee Documentation Committee score than the placebo group (16 points; -18 to 49, vs 8 points; -4 to 37, respectively; p = 0.03). The treatment group also had a significantly improved mean visual analogue score at final follow-up (-25; -85 to 34, vs -11 points; -51 to 25, respectively; p = 0.032). Both cohorts showed an improvement in Western Ontario and McMaster Osteoarthritis Index and Knee Injury and Osteoarthritis Outcome Scores, but these differences were not statistically significant. One patient had an anaphylactic reaction to the preservation medium, but recovered within 24 hours. All other adverse events were localised and resolved without further action.

This technique may result in improved clinical outcomes, with the aim of slowing the degenerative process, leading to improvements in pain and function. However, imaging and direct observational studies are needed to verify cartilage regeneration. Nevertheless, this study provided a sufficient basis to proceed to further clinical testing.

Cite this article: Bone Joint J 2015;97-B:924–32.

The incidence of acute and chronic conditions of the tendo Achillis appear to be increasing. Causation is multifactorial but the role of inherited genetic elements and the influence of environmental factors altering gene expression are increasingly being recognised. Certain individuals’ tendons carry specific variations of genetic sequence that may make them more susceptible to injury. Alterations in the structure or relative amounts of the components of tendon and fine control of activity within the extracellular matrix affect the response of the tendon to loading with failure in certain cases.

This review summarises present knowledge of the influence of genetic patterns on the pathology of the tendo Achillis, with a focus on the possible biological mechanisms by which genetic factors are involved in the aetiology of tendon pathology. Finally, we assess potential future developments with both the opportunities and risks that they may carry.

Cite this article: Bone Joint J 2013;95-B:305–13.

The February 2015 Oncology Roundup³⁶⁰ looks at: Achieving global collaboration; A new standard for limb salvage; Inoperable chondrosarcoma and chemotherapy; Soft-tissue sarcoma and adjuvant chemotherapy; Missed diagnoses and malpractice in sarcoma; Radiofrequency and cartilage tumours

Vascularised fibular grafts (VFGs ) are a valuable surgical technique in limb salvage after resection of a tumour. The primary objective of this multicentre study was to assess the risk factors for failure and complications for using a VFG after resection of a tumour.

The study involved 74 consecutive patients (45 men and 29 women with mean age of 23 years (1 to 64) from four tertiary centres for orthopaedic oncology who underwent reconstruction using a VFG after resection of a tumour between 1996 and 2011. There were 52 primary and 22 secondary reconstructions. The mean follow-up was 77 months (10 to 195).

In all, 69 patients (93%) had successful limb salvage; all of these united and 65 (88%) showed hypertrophy of the graft. The mean time to union differed between those involving the upper (28 weeks; 12 to 96) and lower limbs (44 weeks; 12 to 250). Fracture occurred in 11 (15%), and nonunion in 14 (19%) patients.

In 35 patients (47%) at least one complication arose, with a greater proportion in lower limb reconstructions, non-bridging osteosynthesis, and in children. These complications resulted in revision surgery in 26 patients (35%).

VFG is a successful and durable technique for reconstruction of a defect in bone after resection of a tumour, but is accompanied by a significant risk of complications, that often require revision surgery. Union was not markedly influenced by the need for chemo- or radiotherapy, but should not be expected during chemotherapy. Therefore, restricted weight-bearing within this period is advocated.

Cite this article: Bone Joint J 2015;97-B:853–61.

Construction of a functional skeleton is accomplished through co-ordination of the developmental processes of chondrogenesis, osteogenesis, and synovial joint formation. Infants whose movement in utero is reduced or restricted and who subsequently suffer from joint dysplasia (including joint contractures) and thin hypo-mineralised bones, demonstrate that embryonic movement is crucial for appropriate skeletogenesis. This has been confirmed in mouse, chick, and zebrafish animal models, where reduced or eliminated movement consistently yields similar malformations and which provide the possibility of experimentation to uncover the precise disturbances and the mechanisms by which movement impacts molecular regulation. Molecular genetic studies have shown the important roles played by cell communication signalling pathways, namely Wnt, Hedgehog, and transforming growth factor-beta/bone morphogenetic protein. These pathways regulate cell behaviours such as proliferation and differentiation to control maturation of the skeletal elements, and are affected when movement is altered. Cell contacts to the extra-cellular matrix as well as the cytoskeleton offer a means of mechanotransduction which could integrate mechanical cues with genetic regulation. Indeed, expression of cytoskeletal genes has been shown to be affected by immobilisation. In addition to furthering our understanding of a fundamental aspect of cell control and differentiation during development, research in this area is applicable to the engineering of stable skeletal tissues from stem cells, which relies on an understanding of developmental mechanisms including genetic and physical criteria. A deeper understanding of how movement affects skeletogenesis therefore has broader implications for regenerative therapeutics for injury or disease, as well as for optimisation of physical therapy regimes for individuals affected by skeletal abnormalities.

Cite this article: Bone Joint Res 2015;4:105–116

We determined the efficacy of a devitalised autograft (n = 13) and allograft (n = 16) cortical strut bone graft combined with long-stem endoprosthetic reconstruction in the treatment of massive tumours of the lower limb. A total of 29 patients (18 men:11 women, mean age 20.1 years (12 to 45) with a ratio of length of resection to that of the whole prosthesis of > 50% were treated between May 2003 and May 2012. The mean follow-up was 47 months (15 to 132). The stem of the prosthesis was introduced through bone graft struts filled with cement, then cemented into the residual bone. Bone healing was achieved in 23 patients (86%). The mean Musculoskeletal Tumour Society functional score was 85% (57 to 97). The five-year survival rate of the endoprostheses was 81% (95% confidence intervals 67.3 to 92.3). The mean length of devitalised autografts and allografts was 8.6 cm (5 to 15), which increased the ratio of the the length of the stem of the prosthesis to that of the whole length of the prosthesis from a theoretical 35% to an actual 55%.

Cortical strut bone grafting and long-stem endoprosthetic reconstruction is an option for treating massive segmental defects following resection of a tumour in the lower limb. Patients can regain good function with a low incidence of aseptic loosening. The strut graft and the residual bone together serve as a satisfactory bony environment for a revision prosthesis, if required, once union is achieved.

Cite this article: Bone Joint J 2015;97-B:544–9.

The Swansea Morriston Achilles Rupture Treatment (SMART) programme was introduced in 2008. This paper summarises the outcome of this programme. Patients with a rupture of the Achilles tendon treated in our unit follow a comprehensive management protocol that includes a dedicated Achilles clinic, ultrasound examination, the use of functional orthoses, early weight-bearing, an accelerated exercise regime and guidelines for return to work and sport. The choice of conservative or surgical treatment was based on ultrasound findings.

The rate of re-rupture, the outcome using the Achilles Tendon Total Rupture Score (ATRS) and the Achilles Tendon Repair Score, (AS), and the complications were recorded. An elementary cost analysis was also performed.

Between 2008 and 2014 a total of 273 patients presented with an acute rupture 211 of whom were managed conservatively and 62 had surgical repair. There were three re-ruptures (1.1%). There were 215 men and 58 women with a mean age of 46.5 years (20 to 86). Functional outcome was satisfactory. Mean ATRS and AS at four months was 53.0 (sd 14), 64.9 (sd 15) (n = 135), six months 67.8 (sd 16), 73.8 (sd 15) (n = 103) and nine months (72.4; sd 14) 72.3 (sd 13) (n = 43). The programme realised estimated cost savings exceeding £91 000 per annum.

The SMART programme resulted in a low rate of re-rupture, a satisfactory outcome, a reduced rate of surgical intervention and a reduction in healthcare costs.

Cite this article: Bone Joint J 2015; 97-B:510–15.

The February 2015 Trauma Roundup³⁶⁰ looks at: Evaluating the syndesmosis in ankle fractures; Calcaneal fracture management an ongoing problem; Angular stable locking in low tibial fractures did not improve results; Open fractures: do the seconds really count?; Long-term outcomes of tibial fractures; Targeted performance improvements in pelvic fractures

Drug therapy forms an integral part of the management of many orthopaedic conditions. However, many medicines can produce serious adverse reactions if prescribed inappropriately, either alone or in combination with other drugs. Often these hazards are not appreciated. In response to this, the European Union recently issued legislation regarding safety measures which member states must adopt to minimise the risk of errors of medication.

In March 2014 the Medicines and Healthcare products Regulatory Agency and NHS England released a Patient Safety Alert initiative focussed on errors of medication. There have been similar initiatives in the United States under the auspices of The National Coordinating Council for Medication Error and The Joint Commission on the Accreditation of Healthcare Organizations. These initiatives have highlighted the importance of informing and educating clinicians.

Here, we discuss common drug interactions and contra-indications in orthopaedic practice. This is germane to safe and effective clinical care.

Cite this article: Bone Joint J 2015;97-B:434–41.

Louis Pasteur once said that: “Fortune favours the prepared mind.” As one of the great scientists who contributed to the fight against infection, he emphasised the importance of being prepared at all times to recognise infection and deal with it. Despite the many scientific discoveries and technological advances, such as the advent of antibiotics and the use of sterile techniques, infection continues to be a problem that haunts orthopaedic surgeons and inflicts suffering on patients.

The medical community has implemented many practices with the intention of preventing infection and treating it effectively when it occurs. Although high-level evidence may support some of these practices, many are based on little to no scientific foundation. Thus, around the world, there is great variation in practices for the prevention and management of periprosthetic joint infection.

This paper summaries the instigation, conduct and findings of a recent International Consensus Meeting on Surgical Site and Periprosthetic Joint Infection.

Cite this article: Bone Joint J 2013;95-B:1450–2.

We hypothesised that the use of tantalum (Ta) acetabular components in revision total hip arthroplasty (THA) was protective against subsequent failure due to infection. We identified 966 patients (421 men, 545 women and 990 hips) who had undergone revision THA between 2000 and 2013. The mean follow up was 40.2 months (3 months to 13.1 years). The mean age of the men and women was 62.3 years (31 to 90) and 65.1 years (25 to 92), respectively.

Titanium (Ti) acetabular components were used in 536 hips while Ta components were used in 454 hips. In total, 73 (7.3%) hips experienced subsequent acetabular failure. The incidence of failure was lower in the Ta group at 4.4% (20/454) compared with 9.9% (53/536) in the Ti group (p < 0.001, odds ratio 2.38; 95% CI 1.37 to 4.27). Among the 144 hips (64 Ta, 80 Ti) for which revision had been performed because of infection, failure due to a subsequent infection was lower in the Ta group at 3.1% (2/64) compared with 17.5% (14/80) for the Ti group (p = 0.006).

Thus, the use of Ta acetabular components during revision THA was associated with a lower incidence of failure from all causes and Ta components were associated with a lower incidence of subsequent infection when used in patients with periprosthetic joint infection.

Cite this article: Bone Joint J 2015;97-B:45–9.

The December 2013 Oncology Roundup³⁶⁰ looks at: Peri-articular resection fraught with complications; Navigated margins; Skeletal tumours and thromboembolism; Conditional survival in Ewing’s sarcoma; Reverse shoulders and tumour; For how long should we follow up sarcoma patients?; and already metastasised?

The LockDown device (previously called Surgilig) is a braided polyester mesh which is mostly used to reconstruct the dislocated acromioclavicular joint. More than 11 000 have been implanted worldwide. Little is known about the tissue reaction to the device nor to its wear products when implanted in an extra-articular site in humans. This is of importance as an adverse immunological reaction could result in osteolysis or damage to the local tissues, thereby affecting the longevity of the implant.

We analysed the histology of five LockDown implants retrieved from five patients over the last seven years by one of the senior authors. Routine analysis was carried out in all five cases and immunohistochemistry in one.

The LockDown device acts as a scaffold for connective tissue which forms an investing fibrous pseudoligament. The immunological response at the histological level seems favourable with a limited histiocytic and giant cell response to micron-sized wear particles. The connective tissue envelope around the implant is less organised than a native ligament.

Cite this article: Bone Joint J 2015;97-B:83–8.

We have compared three different methods of treating symptomatic non-traumatic tears of the supraspinatus tendon in patients above 55 years of age. A total of 180 shoulders (173 patients) with supraspinatus tendon tears were randomly allocated into one of three groups (each of 60 shoulders); physiotherapy (group 1), acromioplasty and physiotherapy (group 2) and rotator cuff repair, acromioplasty and physiotherapy (group 3). The Constant score was assessed and followed up by an independent observer pre-operatively and at three, six and twelve months after the intervention.

Of these, 167 shoulders were available for assessment at one year (follow-up rate of 92.8%). There were 55 shoulders in group 1 (24 in males and 31 in females, mean age 65 years (55 to 79)), 57 in group 2 (29 male and 28 female, mean age 65 years (55 to 79)) and 55 shoulders in group 3 (26 male and 29 female, mean age 65 years (55 to 81)). There were no between-group differences in the Constant score at final follow-up: 74.1 (sd 14.2), 77.2 (sd 13.0) and 77.9 (sd 12.1) in groups 1, 2 and 3, respectively (p = 0.34). The mean change in the Constant score was 17.0, 17.5, and 19.8, respectively (p = 0.34). These results suggest that at one-year follow-up, operative treatment is no better than conservative treatment with regard to non-traumatic supraspinatus tears, and that conservative treatment should be considered as the primary method of treatment for this condition.

Cite this article: Bone Joint J 2014;96-B:75–81.

The August 2012 Oncology Roundup³⁶⁰ looks at: prolonged symptom duration; peri-operative mortality and above-knee amputation; giant cell tumour of the spine; surgical resection for Ewing’s sarcoma; intercalary allograft reconstruction of the femur for tumour defects; and an induced membrane technique for large bone defects.

The increasing prevalence of osteoporosis in an ageing population has contributed to older patients becoming the fastest-growing group presenting with acetabular fractures. We performed a systematic review of the literature involving a number of databases to identify studies that included the treatment outcome of acetabular fractures in patients aged > 55 years. An initial search identified 61 studies; after exclusion by two independent reviewers, 15 studies were considered to meet the inclusion criteria. All were case series. The mean Coleman score for methodological quality assessment was 37 (25 to 49). There were 415 fractures in 414 patients. Pooled analysis revealed a mean age of 71.8 years (55 to 96) and a mean follow-up of 47.3 months (1 to 210). In seven studies the results of open reduction and internal fixation (ORIF) were presented: this was combined with simultaneous hip replacement (THR) in four, and one study had a mixture of these strategies. The results of percutaneous fixation were presented in two studies, and a single study revealed the results of non-operative treatment.

With fixation of the fracture, the overall mean rate of conversion to THR was 23.1% (0% to 45.5%). The mean rate of non-fatal complications was 39.8% (0% to 64%), and the mean mortality rate was 19.1% (5% to 50%) at a mean of 64 months (95% confidence interval 59.4 to 68.6; range 12 to 143). Further data dealing with the classification of the fracture, the surgical approach used, operative time, blood loss, functional and radiological outcomes were also analysed.

This study highlights that, of the many forms of treatment available for this group of patients, there is a trend to higher complication rates and the need for further surgery compared with the results of the treatment of acetabular fractures in younger patients.

Cite this article: Bone Joint J 2014;96-B:157–63.

The October 2013 Oncology Roundup³⁶⁰ looks at: En bloc resection, irradiation and re-implantation; Metastasis and osteosarcoma; Mobile spine and osteosarcoma; Denosumab miraculous for GCT; Fevers, megaprostheses and sarcomas; PET and prognosis; Canine sarcomas not so different?; Bone cement and giant cell tumours.

The December 2014 Hip & Pelvis Roundup³⁶⁰ looks at: Sports and total hips; topical tranexamic acid and blood conservation in hip replacement; blind spots and biases in hip research; no recurrence in cam lesions at two years; to drain or not to drain?; sonication and diagnosis of implant associated infection; and biomarkers and periprosthetic infection

Giant cell tumours (GCTs) of the small bones of the hands and feet are rare. Small case series have been published but there is no consensus about ideal treatment. We performed a systematic review, initially screening 775 titles, and included 12 papers comprising 91 patients with GCT of the small bones of the hands and feet. The rate of recurrence across these publications was found to be 72% (18 of 25) in those treated with isolated curettage, 13% (2 of 15) in those treated with curettage plus adjuvants, 15% (6 of 41) in those treated by resection and 10% (1 of 10) in those treated by amputation.

We then retrospectively analysed 30 patients treated for GCT of the small bones of the hands and feet between 1987 and 2010 in five specialised centres. The primary treatment was curettage in six, curettage with adjuvants (phenol or liquid nitrogen with or without polymethylmethacrylate (PMMA)) in 18 and resection in six. We evaluated the rate of complications and recurrence as well as the factors that influenced their functional outcome.

At a mean follow-up of 7.9 years (2 to 26) the rate of recurrence was 50% (n = 3) in those patients treated with isolated curettage, 22% (n = 4) in those treated with curettage plus adjuvants and 17% (n = 1) in those treated with resection (p = 0.404). The only complication was pain in one patient, which resolved after surgical removal of remnants of PMMA. We could not identify any individual factors associated with a higher rate of complications or recurrence. The mean post-operative Musculoskeletal Tumor Society scores were slightly higher after intra-lesional treatment including isolated curettage and curettage plus adjuvants (29 (20 to 30)) compared with resection (25 (15 to 30)) (p = 0.091). Repeated curettage with adjuvants eventually resulted in the cure for all patients and is therefore a reasonable treatment for both primary and recurrent GCT of the small bones of the hands and feet.

Cite this article: Bone Joint J 2013;95-B:838–45.

The October 2013 Research Roundup³⁶⁰ looks at: Orthopaedics: a dangerous profession?; Freezing and biomarkers for bone turnover; Herniation or degeneration first?; MARS MRI and metallosis; Programmed cell death in partial thickness cuff tears; Lead glasses for trauma surgery?; Smoking inhibits bone healing; Optimising polyethylene microstructure.