This article presents a unified clinical theory that links established facts about the physiology of bone and homeostasis, with those involved in the healing of fractures and the development of nonunion. The key to this theory is the concept that the tissue that forms in and around a fracture should be considered a specific functional entity. This ‘bone-healing unit’ produces a physiological response to its biological and mechanical environment, which leads to the normal healing of bone. This tissue responds to mechanical forces and functions according to Wolff’s law, Perren’s strain theory and Frost’s concept of the “mechanostat”. In response to the local mechanical environment, the bone-healing unit normally changes with time, producing different tissues that can tolerate various levels of strain. The normal result is the formation of bone that bridges the fracture – healing by callus. Nonunion occurs when the bone-healing unit fails either due to mechanical or biological problems or a combination of both. In clinical practice, the majority of nonunions are due to mechanical problems with instability, resulting in too much strain at the fracture site. In most nonunions, there is an intact bone-healing unit. We suggest that this maintains its biological potential to heal, but fails to function due to the mechanical conditions. The theory predicts the healing pattern of multifragmentary fractures and the observed morphological characteristics of different nonunions. It suggests that the majority of nonunions will heal if the correct mechanical environment is produced by surgery, without the need for biological adjuncts such as autologous bone graft.

Cite this article: Bone Joint J 2016;98-B:884–91.

Osteochondritis Dissecans (OCD) is a condition for which the aetiology remains unknown. It affects subchondral bone and secondarily its overlying cartilage and is mostly found in the knee. It can occur in adults, but is generally identified when growth remains, when it is referred to as juvenile OCD. As the condition progresses, the affected subchondral bone separates from adjacent healthy bone, and can lead to demarcation and separation of its associated articular cartilage. Any symptoms which arise relate to the stage of the disease. Early disease without separation of the lesion results in pain. Separation of the lesion leads to mechanical symptoms and swelling and, in advanced cases, the formation of loose bodies.

Early identification of OCD is essential as untreated OCD can lead to the premature degeneration of the joint, whereas appropriate treatment can halt the disease process and lead to healing. Establishing the stability of the lesion is a key part of providing the correct treatment. Stable lesions, particularly in juvenile patients, have greater propensity to heal with non-surgical treatment, whereas unstable or displaced lesions usually require surgical management.

This article discusses the aetiology, clinical presentation and prognosis of OCD in the knee. It presents an algorithm for treatment, which aims to promote healing of native hyaline cartilage and to ensure joint congruity.

Take home message: Although there is no clear consensus as to the best treatment of OCD, every attempt should be made to retain the osteochondral fragment when possible as, with a careful surgical technique, there is potential for healing even in chronic lesions

Cite this article: Bone Joint J 2016;98-B:723–9.

Methods

Between 2005 and 2012, 50 patients (23 female, 27 male) with nonunion of the humeral shaft were included in this retrospective study. The mean age was 51.3 years (14 to 88). The patients had a mean of 1.5 prior operations (sd 1.2;1 to 8).

All patients were assessed according to a specific risk score in order to devise an optimal and individual therapy plan consistent with the Diamond Concept. In 32 cases (64%), a change in the osteosynthesis to an angular stable locking compression plate was performed. According to the individual risk an additional bone graft and/or bone morphogenetic protein-7 (BMP-7) were applied.

The continual cycle of bone formation and resorption is carried out by osteoblasts, osteocytes, and osteoclasts under the direction of the bone-signaling pathway. In certain situations the host cycle of bone repair is insufficient and requires the assistance of bone grafts and their substitutes. The fundamental properties of a bone graft are osteoconduction, osteoinduction, osteogenesis, and structural support. Options for bone grafting include autogenous and allograft bone and the various isolated or combined substitutes of calcium sulphate, calcium phosphate, tricalcium phosphate, and coralline hydroxyapatite. Not all bone grafts will have the same properties. As a result, understanding the requirements of the clinical situation and specific properties of the various types of bone grafts is necessary to identify the ideal graft. We present a review of the bone repair process and properties of bone grafts and their substitutes to help guide the clinician in the decision making process.

Cite this article: Bone Joint J 2016;98-B(1 Suppl A):6–9.

Large osteochondral lesions (OCLs) of the shoulder of the talus cannot always be treated by traditional osteochondral autograft techniques because of their size, articular geometry and loss of an articular buttress. We hypothesised that they could be treated by transplantation of a vascularised corticoperiosteal graft from the ipsilateral medial femoral condyle.

Between 2004 and 2011, we carried out a prospective study of a consecutive series of 14 patients (five women, nine men; mean age 34.8 years, 20 to 54) who were treated for an OCL with a vascularised bone graft. Clinical outcome was assessed using a visual analogue scale (VAS) for pain and the American Orthopaedic Foot and Ankle Society (AOFAS) hindfoot score. Radiological follow-up used plain radiographs and CT scans to assess graft incorporation and joint deterioration.

At a mean follow-up of 4.1 years (2 to 7), the mean VAS for pain had decreased from 5.8 (5 to 8) to 1.8 (0 to 4) (p = 0.001) and the mean AOFAS hindfoot score had increased from 65 (41 to 70) to 81 (54 to 92) (p = 0.003). Radiologically, the talar contour had been successfully reconstructed with stable incorporation of the vascularised corticoperiosteal graft in all patients. Joint degeneration was only seen in one ankle.

Treatment of a large OCL of the shoulder of the talus with a vascularised corticoperiosteal graft taken from the medial condyle of the femur was found to be a safe, reliable method of restoring the contour of the talus in the early to mid-term.

Cite this article: Bone Joint J 2015;97-B:1242–9.

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.

Currently, there is no animal model in which to evaluate the underlying physiological processes leading to the heterotopic ossification (HO) which forms in most combat-related and blast wounds. We sought to reproduce the ossification that forms under these circumstances in a rat by emulating patterns of injury seen in patients with severe injuries resulting from blasts. We investigated whether exposure to blast overpressure increased the prevalence of HO after transfemoral amputation performed within the zone of injury. We exposed rats to a blast overpressure alone (BOP-CTL), crush injury and femoral fracture followed by amputation through the zone of injury (AMP-CTL) or a combination of these (BOP-AMP). The presence of HO was evaluated using radiographs, micro-CT and histology. HO developed in none of nine BOP-CTL, six of nine AMP-CTL, and in all 20 BOP-AMP rats. Exposure to blast overpressure increased the prevalence of HO.

This model may thus be used to elucidate cellular and molecular pathways of HO, the effect of varying intensities of blast overpressure, and to evaluate new means of prophylaxis and treatment of heterotopic ossification.

Cite this article: Bone Joint J 2015;97-B:572–6

Impaction bone grafting for the reconstitution of bone stock in revision hip surgery has been used for nearly 30 years. Between 1995 and 2001 we used this technique in acetabular reconstruction, in combination with a cemented component, in 304 hips in 292 patients revised for aseptic loosening. The only additional supports used were stainless steel meshes placed against the medial wall or laterally around the acetabular rim to contain the graft. All Paprosky grades of defect were included. Clinical and radiographic outcomes were collected in surviving patients at a minimum of ten years after the index operation. Mean follow-up was 12.4 years (sd 1.5) (10.0 to 16.0). Kaplan–Meier survival with revision for aseptic loosening as the endpoint was 85.9% (95% CI 81.0 to 90.8) at 13.5 years. Clinical scores for pain relief remained satisfactory, and there was no difference in clinical scores between cups that appeared stable and those that appeared radiologically loose.

Cite this article: Bone Joint J 2014;96-B:188–94.

We welcome letters to the Editor concerning articles that have recently been published. Such letters will be subject to the usual stages of selection and editing; where appropriate the authors of the original article will be offered the opportunity to reply.

Matrix metalloproteinases (MMPs), responsible for extracellular matrix remodelling and angiogenesis, might play a major role in the response of the growth plate to detrimental loads that lead to overuse injuries in young athletes. In order to test this hypothesis, human growth plate chondrocytes were subjected to mechanical forces equal to either physiological loads, near detrimental or detrimental loads for two hours. In addition, these cells were exposed to physiological loads for up to 24 hours. Changes in the expression of MMPs -2, -3 and -13 were investigated.

We found that expression of MMPs in cultured human growth plate chondrocytes increases in a linear manner with increased duration and intensity of loading. We also showed for the first time that physiological loads have the same effect on growth plate chondrocytes over a long period of time as detrimental loads applied for a short period.

These findings confirm the involvement of MMPs in overuse injuries in children. We suggest that training programmes for immature athletes should be reconsidered in order to avoid detrimental stresses and over-expression of MMPs in the growth plate, and especially to avoid physiological loads becoming detrimental.

Cite this article: Bone Joint J 2013;95-B:568–73.

In this paper, we consider wound healing after total knee arthroplasty.

Disruption of the extensor mechanism in total knee arthroplasty may occur by tubercle avulsion, patellar or quadriceps tendon rupture, or patella fracture, and whether occurring intra-operatively or post-operatively can be difficult to manage and is associated with a significant rate of failure and associated complications. This surgery is frequently performed in compromised tissues, and repairs must frequently be protected with cerclage wiring and/or augmentation with local tendon (semi-tendinosis, gracilis) which may also be used to treat soft-tissue loss in the face of chronic disruption. Quadriceps rupture may be treated with conservative therapy if the patient retains active extension. Component loosening or loss of active extension of 20° or greater are clear indications for surgical treatment of patellar fracture. Acute patellar tendon disruption may be treated by primary repair. Chronic extensor failure is often complicated by tissue loss and retraction can be treated with medial gastrocnemius flaps, achilles tendon allografts, and complete extensor mechanism allografts. Attention to fixing the graft in full extension is mandatory to prevent severe extensor lag as the graft stretches out over time.

The femoral head receives its blood supply primarily from the medial femoral circumflex artery, with its deep branch being the most important.

In a previous study, we performed classical anatomical dissections of 16 hips. We have extended our investigation with a radiological study, in which we aimed to visualise the arteries supplying the femoral head in healthy individuals. We analysed 55 CT angiographic images of the hip.

Using 64-row CT angiography, we identified three main arteries supplying the femoral head: the deep branch of the medial femoral circumflex artery and the posterior inferior nutrient artery originating from the medial femoral circumflex artery, and the piriformis branch of the inferior gluteal artery. CT angiography is a good method for visualisation of the arteries supplying the femoral head. The current radiological studies will provide information for further investigation of vascularity after traumatic dislocation of the hip, using CT angiography.

We present a series of 35 patients (19 men and 16 women) with a mean age of 64 years (36.7 to 75.9), who underwent total hip replacement using the ESKA dual-modular short stem with metal on-polyethylene bearing surfaces. This implant has a modular neck section in addition to the modular head. Of these patients, three presented with increasing post-operative pain due to pseudotumour formation that resulted from corrosion at the modular neck-stem junction. These patients underwent further surgery and aseptic lymphocytic vaculitis associated lesions were demonstrated on histological analysis.

Retrieval analysis of two modular necks showed corrosion at the neck-stem taper. Blood cobalt and chromium levels were measured at a mean of nine months (3 to 28) following surgery. These were compared with the levels in seven control patients (three men and four women) with a mean age of 53.4 years (32.1 to 64.1), who had an identical prosthesis and articulation but with a prosthesis that had no modularity at neck-stem junction. The mean blood levels of cobalt in the study group were raised at 50.75 nmol/l (5 to 145) compared with 5.6 nmol/l (2 to 13) in control patients.

Corrosion at neck-stem tapers has been identified as an important source of metal ion release and pseudotumour formation requiring revision surgery. Finite element modelling of the dual modular stem demonstrated high stresses at the modular stem-neck junction. Dual modular cobalt-chrome hip prostheses should be used with caution due to these concerns.

We performed a series of 16 anatomical dissections on Caucasian cadaver material to determine the surgical anatomy of the medial femoral circumflex artery (MFCA) and its anastomoses. These confirmed that the femoral head receives its blood supply primarily from the MFCA via a group of posterior superior nutrient arteries and the posterior inferior nutrient artery. In terms of anastomoses that may also contribute to the blood supply, the anastomosis with the inferior gluteal artery, via the piriformis branch, is the most important. These dissections provide a base of knowledge for further radiological studies on the vascularity of the normal femoral head and its vascularity after dislocation of the hip.

Failure of bone repair is a challenging problem in the management of fractures. There is a limited supply of autologous bone grafts for treating nonunions, with associated morbidity after harvesting. There is need for a better source of cells for repair. Mesenchymal stem cells (MSCs) hold promise for healing of bone because of their capacity to differentiate into osteoblasts and their availability from a wide variety of sources. Our review aims to evaluate the available clinical evidence and recent progress in strategies which attempt to use autologous and heterologous MSCs in clinical practice, including genetically-modified MSCs and those grown on scaffolds. We have compared various procedures for isolating and expanding a sufficient number of MSCs for use in a clinical setting.

There are now a number of clinical studies which have shown that implantation of MSCs is an effective, safe and durable method for aiding the repair and regeneration of bone.

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.

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 describe a retrospective review of 38 cases of reconstruction following resection of the metaphysiodiaphysis of the lower limb for malignant bone tumours using free vascularised fibular grafts. The mean follow-up was for 7.6 years (0.4 to 18.4). The mean Musculoskeletal Tumor Society score was 27.2 (20 to 30). The score was significantly higher when the graft was carried out in a one-stage procedure after resection of the tumour rather than in two stages. Bony union was achieved in 89% of the cases. The overall mean time to union was 1.7 years (0.2 to 10.3).

Free vascularised fibular transfer is a major operation with frequent, but preventable, complications which allows salvage of the limb with satisfactory functional results.

We present the results of 13 patients who suffered severe injuries to the lower leg. Five sustained a traumatic amputation and eight a Gustilo-Anderson type IIIC open fracture. All were treated with debridement, acute shortening and stabilisation of the fracture and vascular reconstruction. Further treatment involved restoration of tibial length by callus distraction through the distal or proximal metaphysis, which was commenced soon after the soft tissues had healed (n = 8) or delayed until union of the fracture (n = 5).

All patients were male with a mean age of 28.4 years (17 to 44), and had sustained injury to the leg only. Chen grade II functional status was achieved in all patients. Although the number of patients treated with each strategy was limited, there was no obvious disadvantage in the early lengthening programme, which was completed more quickly.