Objectives

Recent studies have shown that modulating inflammation-related lipid signalling after a bone fracture can accelerate healing in animal models. Specifically, decreasing 5-lipoxygenase (5-LO) activity during fracture healing increases cyclooxygenase-2 (COX-2) expression in the fracture callus, accelerates chondrogenesis and decreases healing time. In this study, we test the hypothesis that 5-LO inhibition will increase direct osteogenesis.

Recently, the use of metal-on-metal articulations in total hip arthroplasty (THA) has led to an increase in adverse events owing to local soft-tissue reactions from metal ions and wear debris. While the majority of these implants perform well, it has been increasingly recognised that a small proportion of patients may develop complications secondary to systemic cobalt toxicity when these implants fail. However, distinguishing true toxicity from benign elevations in cobalt ion levels can be challenging.

The purpose of this two part series is to review the use of cobalt alloys in THA and to highlight the following related topics of interest: mechanisms of cobalt ion release and their measurement, definitions of pathological cobalt ion levels, and the pathophysiology, risk factors and treatment of cobalt toxicity. Historically, these metal-on-metal arthroplasties are composed of a chromium-cobalt articulation.

The release of cobalt is due to the mechanical and oxidative stresses placed on the prosthetic joint. It exerts its pathological effects through direct cellular toxicity.

This manuscript will highlight the pathophysiology of cobalt toxicity in patients with metal-on-metal hip arthroplasties.

Take home message: Patients with new or evolving hip symptoms with a prior history of THA warrant orthopaedic surgical evaluation. Increased awareness of the range of systemic symptoms associated with cobalt toxicity, coupled with prompt orthopaedic intervention, may forestall the development of further complications.

Cite this article: Bone Joint J 2016;98-B:6–13.

The June 2012 Trauma Roundup³⁶⁰ looks at: nerve injuries of warfare; the medical complications of earthquakes; the measuring of tissue pressures in compartment syndrome; the risk of plunging through the bone when drilling; bony nonunion and negative pressure therapy; surgery for the posteriorly dislocated hip; whether to use the sliding screw or intramedullary nail for the trochanteric fracture; antegrade interlocking nailing for the distal femoral fracture; and gunshot wounds to the pancreas.

Objectives

Healing in cancellous metaphyseal bone might be different from midshaft fracture healing due to different access to mesenchymal stem cells, and because metaphyseal bone often heals without a cartilaginous phase. Inflammation plays an important role in the healing of a shaft fracture, but if metaphyseal injury is different, it is important to clarify if the role of inflammation is also different. The biology of fracture healing is also influenced by the degree of mechanical stability. It is unclear if inflammation interacts with stability-related factors.

Objectives

An experimental rabbit model was used to test the null hypothesis, that there is no difference in new bone formation around uncoated titanium discs compared with coated titanium discs when implanted into the muscles of rabbits.

The number of arthroplasties being undertaken is expected to grow year on year, and periprosthetic joint infections will be an increasing socioeconomic burden. The challenge to prevent and eradicate these infections has resulted in the emergence of several new strategies, which are discussed in this review.

Cite this article: Bone Joint J 2015;97-B:1162–9.

The ability of mesenchymal stem cells (MSCs) to differentiate in vitro into chondrocytes, osteocytes and myocytes holds great promise for tissue engineering. Skeletal defects are emerging as key targets for treatment using MSCs due to the high responsiveness of bone to interventions in animal models. Interest in MSCs has further expanded in recognition of their ability to release growth factors and to adjust immune responses.

Despite their increasing application in clinical trials, the origin and role of MSCs in the development, repair and regeneration of organs have remained unclear. Until recently, MSCs could only be isolated in a process that requires culture in a laboratory; these cells were being used for tissue engineering without understanding their native location and function. MSCs isolated in this indirect way have been used in clinical trials and remain the reference standard cellular substrate for musculoskeletal engineering. The therapeutic use of autologous MSCs is currently limited by the need for ex vivo expansion and by heterogeneity within MSC preparations. The recent discovery that the walls of blood vessels harbour native precursors of MSCs has led to their prospective identification and isolation. MSCs may therefore now be purified from dispensable tissues such as lipo-aspirate and returned for clinical use in sufficient quantity, negating the requirement for ex vivo expansion and a second surgical procedure.

In this annotation we provide an update on the recent developments in the understanding of the identity of MSCs within tissues and outline how this may affect their use in orthopaedic surgery in the future.

Cite this article: Bone Joint J 2014;96-B:291–8.

Biochemical markers of bone-turnover have long been used to complement the radiological assessment of patients with metabolic bone disease. Their implementation in daily clinical practice has been helpful in the understanding of the pathogenesis of osteoporosis, the selection of the optimal dose and the understanding of the progression of the onset and resolution of treatment. Since they are derived from both cortical and trabecular bone, they reflect the metabolic activity of the entire skeleton rather than that of individual cells or the process of mineralisation.

Quantitative changes in skeletal-turnover can be assessed easily and non-invasively by the measurement of bone-turnover markers. They are commonly subdivided into three categories; 1) bone-resorption markers, 2) osteoclast regulatory proteins and 3) bone-formation markers. Because of the rapidly accumulating new knowledge of bone matrix biochemistry, attempts have been made to use them in the interpretation and characterisation of various stages of the healing of fractures. Early knowledge of the individual progress of a fracture could help to avoid delayed or nonunion by enabling modification of the host’s biological response.

The levels of bone-turnover markers vary throughout the course of fracture repair with their rates of change being dependent on the size of the fracture and the time that it will take to heal. However, their short-term biological variability, the relatively low bone specificity exerted, given that the production and destruction of collagen is not limited to bone, as well as the influence of the host’s metabolism on their concentration, produce considerable intra- and inter-individual variability in their interpretation. Despite this, the possible role of bone-turnover markers in the assessment of progression to union, the risks of delayed or nonunion and the impact of innovations to accelerate fracture healing must not be ignored.

In this paper we propose a new classification of neurogenic peri-articular heterotopic ossification (HO) of the hip based on three-dimensional (3D) CT, with the aim of improving pre-operative planning for its excision.

A total of 55 patients (73 hips) with clinically significant HO after either traumatic brain or spinal cord injury were assessed by 3D-CT scanning, and the results compared with the intra-operative findings.

At operation, the gross pathological anatomy of the HO as identified by 3D-CT imaging was confirmed as affecting the peri-articular hip muscles to a greater or lesser extent. We identified seven patterns of involvement: four basic (anterior, medial, posterior and lateral) and three mixed (anteromedial, posterolateral and circumferential). Excellent intra- and inter-observer agreement, with kappa values > 0.8, confirmed the reproducibility of the classification system.

We describe the different surgical approaches used to excise the HO which were guided by the 3D-CT findings. Resection was always successful.

3D-CT imaging, complemented in some cases by angiography, allows the surgeon to define the 3D anatomy of the HO accurately and to plan its surgical excision with precision.

Cite this article: Bone Joint J 2015; 97-B:899–904.

Several bisphosphonates are now available for the treatment of osteoporosis. Porous hydroxyapatite/collagen (HA/Col) composite is an osteoconductive bone substitute which is resorbed by osteoclasts. The effects of the bisphosphonate alendronate on the formation of bone in porous HA/Col and its resorption by osteoclasts were evaluated using a rabbit model. Porous HA/Col cylinders measuring 6 mm in diameter and 8 mm in length, with a pore size of 100 μm to 500 μm and 95% porosity, were inserted into a defect produced in the lateral femoral condyles of 72 rabbits. The rabbits were divided into four groups based on the protocol of alendronate administration: the control group did not receive any alendronate, the pre group had alendronate treatment for three weeks prior to the implantation of the HA/Col, the post group had alendronate treatment following implantation until euthanasia, and the pre+post group had continuous alendronate treatment from three weeks prior to surgery until euthanasia. All rabbits were injected intravenously with either saline or alendronate (7.5 μg/kg) once a week. Each group had 18 rabbits, six in each group being killed at three, six and 12 weeks post-operatively. Alendronate administration suppressed the resorption of the implants. Additionally, the mineral densities of newly formed bone in the alendronate-treated groups were lower than those in the control group at 12 weeks post-operatively. Interestingly, the number of osteoclasts attached to the implant correlated with the extent of bone formation at three weeks.

In conclusion, the systemic administration of alendronate in our rabbit model at a dose-for-weight equivalent to the clinical dose used in the treatment of osteoporosis in Japan affected the mineral density and remodelling of bone tissue in implanted porous HA/Col composites.

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.

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 August 2013 Research Roundup³⁶⁰ looks at: passive smoking and bone substitutes; platelet-rich plasma and osteogenesis; plantar fasciitis and platelet-rich plasma: a match made in heaven?; MRSA decolonisation decreases infection rates; gums, bisphosphonates and orthopaedics; PRAISE and partner violence; blunt impact and post-traumatic OA; and IDEAL research and implants

We have examined the deterioration of implant fixation after withdrawal of parathyroid hormone (PTH) in rats. First, the pull-out force for stainless-steel screws in the proximal tibia was measured at different times after withdrawal. The stimulatory effect of PTH on fixation was lost after 16 days. We then studied whether bisphosphonates could block this withdrawal effect. Mechanical and histomorphometric measurements were conducted for five weeks after implantation. Subcutaneous injections were given daily. Specimens treated with either PTH or saline during the first two weeks showed no difference in the mechanical or histological results (pull-out force 76 N vs 81 N; bone volume density 19% vs 20%). Treatment with PTH for two weeks followed by pamidronate almost doubled the pull-out force (152 N; p < 0.001) and the bone volume density (37%; ANOVA, p < 0.001). Pamidronate alone did not have this effect (89 N and 25%, respectively). Thus, the deterioration can be blocked by bisphosphonates. The clinical implications are discussed.

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.

This multicentre prospective clinical trial aimed to determine whether early administration of alendronate (ALN) delays fracture healing after surgical treatment of fractures of the distal radius. The study population comprised 80 patients (four men and 76 women) with a mean age of 70 years (52 to 86) with acute fragility fractures of the distal radius requiring open reduction and internal fixation with a volar locking plate and screws. Two groups of 40 patients each were randomly allocated either to receive once weekly oral ALN administration (35 mg) within a few days after surgery and continued for six months, or oral ALN administration delayed until four months after surgery. Postero-anterior and lateral radiographs of the affected wrist were taken monthly for six months after surgery. No differences between groups was observed with regard to gender (p = 1.0), age (p = 0.916), fracture classification (p = 0.274) or bone mineral density measured at the spine (p = 0.714). The radiographs were assessed by three independent assessors. There were no significant differences in the mean time to complete cortical bridging observed between the ALN group (3.5 months (se 0.16)) and the no-ALN group (3.1 months (se 0.15)) (p = 0.068). All the fractures healed in the both groups by the last follow-up. Improvement of the Quick-Disabilities of the Arm, Shoulder and Hand (QuickDASH) score, grip strength, wrist range of movement, and tenderness over the fracture site did not differ between the groups over the six-month period. Based on our results, early administration of ALN after surgery for distal radius fracture did not appear to delay fracture healing times either radiologically or clinically.

Cite this article: Bone Joint J 2013;95-B:1544–50.

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.

Objectives

The major problem with repair of an articular cartilage injury is the extensive difference in the structure and function of regenerated, compared with normal cartilage. Our work investigates the feasibility of repairing articular osteochondral defects in the canine knee joint using a composite lamellar scaffold of nano-ß-tricalcium phosphate (ß-TCP)/collagen (col) I and II with bone marrow stromal stem cells (BMSCs) and assesses its biological compatibility.

Florid reactive periostitis is a pronounced periosteal reaction, usually affecting the hands and feet, for which there is no obvious cause. It is rare in children and in long bones. We report an unusual case of florid reactive periostitis in a ten-year-old girl that involved both bones of the forearm. The lesion resolved over a period of one year, leaving a residual exostosis. She developed a physeal bar in the distal ulna in the region of the lesion at one-year follow-up. This was thought to be a complication of the biopsy procedure and was treated by resection and proximal ulnar lengthening.