We report the outcome of 84 nonunions involving long bones which were treated with rhBMP-7, in 84 patients (60 men: 24 women) with a mean age 46 years (18 to 81) between 2003 and 2011. The patients had undergone a mean of three previous operations (one to 11) for nonunion which had been present for a mean of 17 months (4 months to 20 years). The nonunions involved the lower limb in 71 patients and the remainder involved the upper limb. A total of 30 nonunions were septic. Treatment was considered successful when the nonunion healed without additional procedures. The relationship between successful union and the time to union was investigated and various factors including age and gender, the nature of the nonunion (location, size, type, chronicity, previous procedures, infection, the condition of the soft tissues) and type of index procedure (revision of fixation, type of graft, amount of rhBMP-7) were analysed. The improvement of the patients’ quality of life was estimated using the Short Form (SF) 12 score.

A total of 68 nonunions (80.9%) healed with no need for further procedures at a mean of 5.4 months (3 to 10) post-operatively. Multivariate logistic regression analysis of the factors affecting union suggested that only infection significantly affected the rate of union (p = 0.004).Time to union was only affected by the number of previous failed procedures (p = 0.006). An improvement of 79% and 32.2% in SF-12 physical and mental score, respectively, was noted within the first post-operative year.

Rh-BMP-7 combined with bone grafts, enabled healing of the nonunion and improved quality of life in about 80% of patients. Aseptic nonunions were much more likely to unite than septic ones. The number of previous failed operations significantly delayed the time to union.

Cite this article: Bone Joint J 2015;97-B:997–1003.

Aims

To compare the structural durability of hydroxyapatite-tricalcium phosphate (HATCP) to autologous iliac crest bone graft in calcaneal lengthening osteotomy (CLO) for pes planovalgus in childhood.

MicroRNAs (miRNAs ) are small non-coding RNAs that regulate gene expression. We hypothesised that the functions of certain miRNAs and changes to their patterns of expression may be crucial in the pathogenesis of nonunion. Healing fractures and atrophic nonunions produced by periosteal cauterisation were created in the femora of 94 rats, with 1:1 group allocation. At post-fracture days three, seven, ten, 14, 21 and 28, miRNAs were extracted from the newly generated tissue at the fracture site. Microarray and real-time polymerase chain reaction (PCR) analyses of day 14 samples revealed that five miRNAs, miR-31a-3p, miR-31a-5p, miR-146a-5p, miR-146b-5p and miR-223-3p, were highly upregulated in nonunion. Real-time PCR analysis further revealed that, in nonunion, the expression levels of all five of these miRNAs peaked on day 14 and declined thereafter.

Our results suggest that miR-31a-3p, miR-31a-5p, miR-146a-5p, miR-146b-5p and miR-223-3p may play an important role in the development of nonunion. These findings add to the understanding of the molecular mechanism for nonunion formation and may lead to the development of novel therapeutic strategies for its treatment.

Cite this article: Bone Joint J 2015; 97-B:1144–51.

Objectives

To elucidate the effects of age on the expression levels of the receptor activator of the nuclear factor-κB ligand (RANKL) and osteoclasts in the periodontal ligament during orthodontic mechanical loading and post-orthodontic retention.

Aims

Heterotopic ossification (HO) occurs after arthroplasty, especially total hip arthroplasty. In this study we describe the incidence, evolution, morphology and clinical consequences of HO following reverse shoulder arthroplasty.

Implant-associated infection is a major source of morbidity in orthopaedic surgery. There has been extensive research into the development of materials that prevent biofilm formation, and hence, reduce the risk of infection. Silver nanoparticle technology is receiving much interest in the field of orthopaedics for its antimicrobial properties, and the results of studies to date are encouraging. Antimicrobial effects have been seen when silver nanoparticles are used in trauma implants, tumour prostheses, bone cement, and also when combined with hydroxyapatite coatings. Although there are promising results with in vitro and in vivo studies, the number of clinical studies remains small. Future studies will be required to explore further the possible side effects associated with silver nanoparticles, to ensure their use in an effective and biocompatible manner. Here we present a review of the current literature relating to the production of nanosilver for medical use, and its orthopaedic applications.

Cite this article: Bone Joint J 2015; 97-B:582–9.

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.

As the number of younger and more active patients treated with total knee arthroplasty (TKA) continues to increase, consideration of better fixation as a means of improving implant longevity is required. Cemented TKA remains the reference standard with the largest body of evidence and the longest follow-up to support its use. However, cementless TKA, may offer the opportunity of a more bone-sparing procedure with long lasting biological fixation to the bone. We undertook a review of the literature examining advances of cementless TKA and the reported results.

Cite this article: Bone Joint J 2016;98-B:867–73.

The osteoinductive properties of demineralised bone matrix have been demonstrated in animal studies. However, its therapeutic efficacy has yet to be proven in humans. The clinical properties of AlloMatrix, an injectable calcium-based demineralised bone matrix allograft, were studied in a prospective randomised study of 50 patients with an isolated unstable distal radial fracture treated by reduction and Kirschner (K-) wire fixation. A total of 24 patients were randomised to the graft group (13 men and 11 women, mean age 42.3 years (20 to 62)) and 26 to the no graft group (8 men and 18 women, mean age 45.0 years (17 to 69)).

At one, three, six and nine weeks, and six and 12 months post-operatively, patients underwent radiological evaluation, assessments for range of movement, grip and pinch strength, and also completed the Disabilities of Arm, Shoulder and Hand questionnaire. At one and six weeks and one year post-operatively, bone mineral density evaluations of both wrists were performed.

No significant difference in wrist function and speed of recovery, rate of union, complications or bone mineral density was found between the two groups. The operating time was significantly higher in the graft group (p = 0.004). Radiologically, the reduction parameters remained similar in the two groups and all AlloMatrix extraosseous leakages disappeared after nine weeks.

This prospective randomised controlled trial did not demonstrate a beneficial effect of AlloMatrix demineralised bone matrix in the treatment of this category of distal radial fractures treated by K-wire fixation.

Cite this article: Bone Joint J 2013;95-B:1514–20.

Medial open-wedge high tibial osteotomy has been gaining popularity in recent years, but adequate supporting material is required in the osteotomy gap for early weight-bearing and rapid union. The purpose of this study was to investigate whether the implantation of a polycaprolactone-tricalcium phosphate composite scaffold wedge would enhance healing of the osteotomy in a micro pig model. We carried out open-wedge high tibial osteotomies in 12 micro pigs aged from 12 to 16 months. A scaffold wedge was inserted into six of the osteotomies while the other six were left open. Bone healing was evaluated after three and six months using plain radiographs, CT scans, measurement of the bone mineral density and histological examination.

Complete bone union was obtained at six months in both groups. There was no collapse at the osteotomy site, loss of correction or failure of fixation in either group. Staining with haematoxylin and eosin demonstrated that there was infiltration of new bone tissue into the macropores and along the periphery of the implanted scaffold in the scaffold group. The CT scans and measurement of the bone mineral density showed that at six months specimens in the scaffold group had a higher bone mineral density than in the control group, although the implantation of the polycaprolactone-tricalcium phosphate composite scaffold wedge did not enhance healing of the osteotomy.

We analysed the effects of commonly used medications on human osteoblastic cell activity in vitro, specifically proliferation and tissue mineralisation. A list of medications was retrieved from the records of patients aged > 65 years filed in the database of the largest health maintenance organisation in our country (> two million members). Proliferation and mineralisation assays were performed on the following drugs: rosuvastatin (statin), metformin (antidiabetic), metoprolol (β-blocker), citalopram (selective serotonin reuptake inhibitor [SSRI]), and omeprazole (proton pump inhibitor (PPI)). All tested drugs significantly stimulated DNA synthesis to varying degrees, with rosuvastatin 5 µg/ml being the most effective among them (mean 225% (sd 20)), compared with metformin 10 µg/ml (185% (sd 10)), metoprolol 0.25 µg/ml (190% (sd 20)), citalopram 0.05 µg/ml (150% (sd 10)) and omeprazole 0.001 µg/ml (145% (sd 5)). Metformin and metoprolol (to a small extent) and rosuvastatin (to a much higher extent) inhibited cell mineralisation (85% (sd 5)). Our results indicate the need to evaluate the medications prescribed to patients in terms of their potential action on osteoblasts. Appropriate evaluation and prophylactic treatment (when necessary) might lower the incidence and costs associated with potential medication-induced osteoporosis.

Cite this article: Bone Joint J 2013;95-B:1575–80.

Aims

The aims of this study were to describe the course of non-operatively managed, bilateral Perthes’ disease, and to determine specific prognostic factors for the radiographic and clinical outcome.

Aims

This retrospective cohort study compared the results of vascularised and non-vascularised anterior sliding tibial grafts for the treatment of osteoarthritis (OA)of the ankle secondary to osteonecrosis of the talus.

Fracture repair occurs by two broad mechanisms: direct healing, and indirect healing with callus formation. The effects of bisphosphonates on fracture repair have been assessed only in models of indirect fracture healing.

A rodent model of rigid compression plate fixation of a standardised tibial osteotomy was used. Ten skeletally mature Sprague–Dawley rats received daily subcutaneous injections of 1 µg/kg ibandronate (IBAN) and ten control rats received saline (control). Three weeks later a tibial osteotomy was rigidly fixed with compression plating. Six weeks later the animals were killed. Fracture repair was assessed with mechanical testing, radiographs and histology.

The mean stress at failure in a four-point bending test was significantly lower in the IBAN group compared with controls (8.69 Nmm^-2 (sd 7.63) vs 24.65 Nmm^-2 (sd 6.15); p = 0.017). On contact radiographs of the extricated tibiae the mean bone density assessment at the osteotomy site was lower in the IBAN group than in controls (3.7 mmAl (sd 0.75) vs 4.6 mmAl (sd 0.57); p = 0.01). In addition, histological analysis revealed progression to fracture union in the controls but impaired fracture healing in the IBAN group, with predominantly cartilage-like and undifferentiated mesenchymal tissue (p = 0.007).

Bisphosphonate treatment in a therapeutic dose, as used for risk reduction in fragility fractures, had an inhibitory effect on direct fracture healing. We propose that bisphosphonate therapy not be commenced until after the fracture has united if the fracture has been rigidly fixed and is undergoing direct osteonal healing.

Cite this article: Bone Joint J 2013;95-B:1263–8.

Objectives

Effects of insulin-like growth factor 1 (IGF1), fibroblast growth factor 2 (FGF2) and bone morphogenetic protein 2 (BMP2) on the expression of genes involved in the proliferation and differentiation of osteoblasts in culture were analysed. The best sequence of growth factor addition that induces expansion of cells before their differentiation was sought.

We evaluated the maturation of grafted bone in cases of successful fusion after a one- or two-level posterior lumbar interbody fusion (PLIF) using interbody carbon cages. We carried out a five-year prospective longitudinal radiological evaluation of patients using plain radiographs and CT scans. One year after surgery, 117 patients with an early successful fusion were selected for inclusion in the study. Radiological evaluation of interbody bone fusion was graded on a 4-point scale. The mean grades of all radiological and CT assessments increased in the five years after surgery, and differences compared to the previous time interval were statistically significant for three or four years after surgery. Because the grafted bone continues to mature for three years after surgery, the success of a fusion should not be assessed until at least three years have elapsed. There were no significant differences in the longitudinal patterns of grafted bone maturity between iliac bone and local bone. However, iliac bone grafting may remodel faster than local bone.

Aims

The aims of this study were to evaluate the clinical and radiological outcomes of instrumented posterolateral fusion (PLF) performed in patients with rheumatoid arthritis (RA).

The purpose of this study was to compare clinical outcomes of total knee arthroplasty (TKA) after manipulation under anaesthesia (MUA) for post-operative stiffness with a matched cohort of TKA patients who did not requre MUA.

In total 72 patients (mean age 59.8 years, 42 to 83) who underwent MUA following TKA were identified from our prospective database and compared with a matched cohort of patients who had undergone TKA without subsequent MUA. Patients were evaluated for range of movement (ROM) and clinical outcome scores (Western Ontario and McMaster Universities Arthritis Index, Short-Form Health Survey, and Knee Society Clinical Rating System) at a mean follow-up of 36.4 months (12 to 120). MUA took place at a mean of nine weeks (5 to 18) after TKA. In patients who required MUA, mean flexion deformity improved from 10° (0° to 25°) to 4.4° (0° to 15°) (p < 0.001), and mean range of flexion improved from 79.8° (65° to 95°) to 116° (80° to 130°) (p < 0.001). There were no statistically significant differences in ROM or functional outcome scores at three months, one year, or two years between those who required MUA and those who did not. There were no complications associated with manipulation.

At most recent follow-up, patients requiring MUA achieved equivalent ROM and clinical outcome scores when compared with a matched control group. While other studies have focused on ROM after manipulation, the current study adds to current literature by supplementing this with functional outcome scores.

Cite this article: Bone Joint J 2015;97-B:1640–4.

Objectives

Small animal models of fracture repair primarily investigate indirect fracture healing via external callus formation. We present the first described rat model of direct fracture healing.