We evaluated the efficacy of Escherichia coli-derived recombinant human bone morphogenetic protein-2 (E-BMP-2) in a mini-pig model of spinal anterior interbody fusion. A total of 14 male mini-pigs underwent three-level anterior lumbar interbody fusion using polyether etherketone (PEEK) cages containing porous hydroxyapatite (HA). Four groups of cages were prepared: 1) control (n = 10 segments); 2) 50 μg E-BMP-2 (n = 9); 3) 200 μg E-BMP-2 (n = 10); and 4) 800 μg E-BMP-2 (n = 9). At eight weeks after surgery the mini-pigs were killed and the specimens were evaluated by gross inspection and manual palpation, radiological evaluation including plain radiographs and micro-CT scans, and histological analysis. Rates of fusion within PEEK cages and overall union rates were calculated, and bone formation outside vertebrae was evaluated. One animal died post-operatively and was excluded, and one section was lost and also excluded, leaving 38 sites for assessment. This rate of fusion within cages was 30.0% (three of ten) in the control group, 44.4% (four of nine) in the 50 μg E-BMP-2 group, 60.0% (six of ten) in the 200 μg E-BMP-2 group, and 77.8% (seven of nine) in the 800 μg E-BMP-2 group. Fusion rate was significantly increased by the addition of E-BMP-2 and with increasing E-BMP-2 dose (p = 0.046). In a mini-pig spinal anterior interbody fusion model using porous HA as a carrier, the implantation of E-BMP-2-loaded PEEK cages improved the fusion rate compared with PEEK cages alone, an effect that was significantly increased with increasing E-BMP-2 dosage.

Cite this article: Bone Joint J 2013;95-B:217–23.

Objectives

Osteochondral injuries, if not treated adequately, often lead to severe osteoarthritis. Possible treatment options include refixation of the fragment or replacement therapies such as Pridie drilling, microfracture or osteochondral grafts, all of which have certain disadvantages. Only refixation of the fragment can produce a smooth and resilient joint surface. The aim of this study was the evaluation of an ultrasound-activated bioresorbable pin for the refixation of osteochondral fragments under physiological conditions.

The October 2012 Oncology Roundup³⁶⁰ looks at: the causes of primary bone tumours; adjuvant chemotherapy in the longer term; vascularised fibular grafts to salvage massive femoral allografts; a new look at old risks; reconstruction with excised irradiated bone; predicting chemosensitivity in osteosarcoma ; and chemotherapy, osteoporosis and the risk of fracture.

Implantation of autologous chondrocytes and matrix autologous chondrocytes are techniques of cartilage repair used in the young adult knee which require harvesting of healthy cartilage and which may cause iatrogenic damage to the joint. This study explores alternative sources of autologous cells.

Chondrocytes obtained from autologous bone-marrow-derived cells and those from the damaged cartilage within the lesion itself are shown to be viable alternatives to harvest-derived cells. A sufficient number and quality of cells were obtained by the new techniques and may be suitable for autologous chondrocyte and matrix autologous chondrocyte implantation.

We describe the results of cemented total hip replacement in 23 patients (23 hips) with active tuberculous arthritis of the hip with a mean follow-up of 4.7 years (4 to 7). In two patients the diagnosis was proved by pre-operative biopsy, whereas all others were diagnosed on a clinicoradiological basis with confirmation obtained by histopathological examination and polymerase chain reaction of tissue samples taken at the time of surgery. All patients received chemotherapy for at least three months before surgery and treatment was continued for a total of 18 months. Post-operative dislocation occurred in one patient and was managed successfully by closed reduction. No reactivation of the infection or loosening of the implant was recorded and function of the hip improved in all patients.

Total hip replacement in the presence of active tuberculous arthritis of the hip is a safe procedure when pre-operative chemotherapy is commenced and continued for an extended period after operation.

The October 2012 Knee Roundup³⁶⁰ looks at: autologous chondrocytes and chondromalacia patellae; drilling the femoral tunnel at ACL reconstruction; whether we repair the radially torn lateral meniscus; factors associated with patellofemoral pain; mechanoreceptors and the allografted ACL; whether high tibial osteotomy can delay the need for knee replacement; return to sport after ACL reconstruction; tissue-engineered cartilage; and the benefits of yoga.

We report the effects of local administration of osteogenic protein-1 on the biomechanical properties of the overstretched anterior cruciate ligament in an animal model. An injury in the anterior cruciate ligament was created in 45 rabbits. They were divided into three equal groups. In group 1, no treatment was applied, in group II, phosphate-buffered saline was applied around the injured ligament, and in group III, 12.5 μg of osteogenic protein-1 mixed with phosphate-buffered saline was applied around the injured ligament. A control group of 15 rabbits was assembled from randomly-selected injured knees from among the first three groups. Each rabbit was killed at 12 weeks.

The maximum load and stiffness of the anterior cruciate ligament was found to be significantly greater in group III than either group 1 (p = 0.002, p = 0.014) or group II (p = 0.032, p = 0.025). The tensile strength and the tangent modulus of fascicles from the ligament were also significantly greater in group III than either group I (p = 0.002, p = 0.0174) or II (p = 0.005, p = 0.022).

The application of osteogenic protein-1 enhanced the healing in the injured anterior cruciate ligament, but compared with the control group the treated ligament remained lengthened. The administration of osteogenic protein-1 may have a therapeutic role in treating the overstretched anterior cruciate ligament.

Post-natal vasculogenesis, the process by which vascular committed bone marrow stem cells or endothelial precursor cells migrate, differentiate and incorporate into the nacent endothelium and thereby contribute to physiological and pathological neurovascularisation, has stimulated much interest. Its contribution to neovascularisation of tumours, wound healing and revascularisation associated with ischaemia of skeletal and cardiac muscles is well established. We evaluated the responses of endothelial precursor cells in bone marrow to musculoskeletal trauma in mice.

Bone marrow from six C57 Black 6 mice subjected to a standardised, closed fracture of the femur, was analysed for the combined expression of cell-surface markers stem cell antigen 1 (sca-1⁺) and stem cell factor receptor, CD117 (c-kit⁺) in order to identify the endothelial precursor cell population. Immunomagnetically-enriched sca-1⁺ mononuclear cell (MNC^sca-1+) populations were then cultured and examined for functional vascular endothelial differentiation. Bone marrow MNC^{sca-1+,c-kit+} counts increased almost twofold within 48 hours of the event, compared with baseline levels, before decreasing by 72 hours.

Sca-1⁺ mononuclear cell populations in culture from samples of bone marrow at 48 hours bound together Ulex Europus-1, and incorporated fluorescent 1,1′-dioctadecyl- 3,3,3,’3′-tetramethylindocarbocyanine perchlorate-labelled acetylated low-density lipoprotein intracellularily, both characteristics of mature endothelium.

Our findings suggest that a systemic provascular response of bone marrow is initiated by musculoskeletal trauma. Its therapeutic manipulation may have implications for the potential enhancement of neovascularisation and the healing of fractures.

Metal-on-metal total hip replacement has been targeted at younger patients with anticipated long-term survival, but the effect of the production of metal ions is a concern because of their possible toxicity to cells. We have reviewed the results of the use of the Ultima hybrid metal-on-metal total hip replacement, with a cemented polished tapered femoral component with a 28 mm diameter and a cobalt-chrome (CoCr) modular head, articulating with a 28 mm CoCr acetabular bearing surface secured in a titanium alloy uncemented shell.

Between 1997 and 2004, 545 patients with 652 affected hips underwent replacement using this system. Up to 31 January 2008, 90 (13.8%) hips in 82 patients had been revised. Pain was the sole reason for revision in 44 hips (48.9%) of which 35 had normal plain radiographs. Peri-prosthetic fractures occurred in 17 hips (18.9%) with early dislocation in three (3.3%) and late dislocation in 16 (17.8%). Infection was found in nine hips (10.0%).

At operation, a range of changes was noted including cavities containing cloudy fluid under pressure, necrotic soft tissues with avulsed tendons and denuded osteonecrotic upper femora. Corrosion was frequently observed on the retrieved cemented part of the femoral component. Typically, the peri-operative findings confirmed those found on pre-operative metal artefact reduction sequence MRI and histological examination showed severe necrosis.

Metal artefact reduction sequence MRI proved to be useful when investigating these patients with pain in the absence of adverse plain radiological features.

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.

We compared the quality of debridement of chondral lesions performed by four arthroscopic (SH, shaver; CU, curette; SHCU, shaver and curette; BP, bipolar electrodes) and one open technique (OPEN, scalpel and curette) which are used prior to autologous chondrocyte implantation (ACI). The ex vivo simulation of all five techniques was carried out on six juvenile equine stifle joints. The OPEN, SH and SHCU techniques were tested on knees harvested from six adult human cadavers.

The most vertical walls with the least adjacent damage to cartilage were obtained with the OPEN technique. The CU and SHCU methods gave inferior, but still acceptable results whereas the SH technique alone resulted in a crater-like defect and the BP method undermined the cartilage wall. The subchondral bone was severely violated in all the equine samples which might have been peculiar to this model. The predominant depth of the debridement in the adult human samples was at the level of the calcified cartilage. Some minor penetrations of the subchondral end-plate were induced regardless of the instrumentation used.

Our study suggests that not all routine arthroscopic instruments are suitable for the preparation of a defect for ACI. We have shown that the preferred debridement technique is either open or arthroscopically-assisted manual curettage. The use of juvenile equine stifles was not appropriate for the study of the cartilage-subchondral bone interface.

The August 2012 Research Roundup³⁶⁰ looks at: PRP and chondrogenic differentiation; basic fibroblast growth factor; whether glucosamine works; randomised trials; ossification of the ligamentum flavum; treadmill running; inhibiting BMP antagonists; and whether NSAIDs delay union after all.

We report on two cases of infective spondylodiscitis caused by Gemella haemolysans in otherwise healthy patients. This organism has only rarely been identified as a cause of bone and joint infection, with only two previous reports of infective spondylodiscitis.

We describe the clinical features, investigations and treatment options.

We have developed a CT-based navigation system using infrared light-emitting diode markers and an optical camera. We used this system to perform cementless total hip replacement using a ceramic-on-ceramic bearing couple in 53 patients (60 hips) between 1998 and 2001. We reviewed 52 patients (59 hips) at a mean of six years (5 to 8) postoperatively. The mid-term results of total hip replacement using navigation were compared with those of 91 patients (111 hips) who underwent this procedure using the same implants, during the same period, without navigation. There were no significant differences in age, gender, diagnosis, height, weight, body mass index, or pre-operative clinical score between the two groups. The operation time was significantly longer where navigation was used, but there was no significant difference in blood loss or navigation-related complications. With navigation, the acetabular components were placed within the safe zone defined by Lewinnek, while without, 31 of the 111 components were placed outside this zone. There was no significant difference in the Merle d’Aubigne and Postel hip score at the final follow-up. However, hips treated without navigation had a higher rate of dislocation. Revision was performed in two cases undertaken without navigation, one for aseptic acetabular loosening and one for fracture of a ceramic liner, both of which showed evidence of neck impingement on the liner. A further five cases undertaken without navigation showed erosion of the posterior aspect of the neck of the femoral component on the lateral radiographs. These seven impingement-related mechanical problems correlated with malorientation of the acetabular component. There were no such mechanical problems in the navigated group.

We conclude that CT-based navigation increased the precision of orientation of the acetabular component and control of limb length in total hip replacement, without navigation-related complications. It also reduced the rate of dislocation and mechanical problems related to impingement.

This study was designed to test the hypothesis that the sensory innervation of bone might play an important role in sensing and responding to low-intensity pulsed ultrasound and explain its effect in promoting fracture healing. In 112 rats a standardised mid-shaft tibial fracture was created, supported with an intramedullary needle and divided into four groups of 28. These either had a sciatic neurectomy or a patellar tendon resection as control, and received the ultrasound or not as a sham treatment. Fracture union, callus mineralisation and remodelling were assessed using plain radiography, peripheral quantitative computed tomography and histomorphology.

Daily ultrasound treatment significantly increased the rate of union and the volumetric bone mineral density in the fracture callus in the neurally intact rats (p = 0.025), but this stimulating effect was absent in the rats with sciatic neurectomy. Histomorphology demonstrated faster maturation of the callus in the group treated with ultrasound when compared with the control group. The results supported the hypothesis that intact innervation plays an important role in allowing low-intensity pulsed ultrasound to promote fracture healing.

The establishment of a suitable animal model of repair of the rotator cuff is difficult since the presence of a true rotator cuff anatomically appears to be restricted almost exclusively to advanced primates. Our observational study describes the healing process after repair of the cuff in a primate model. Lesions were prepared and repaired in eight ‘middle-aged’ baboons. Two each were killed at four, eight, 12 and 15 weeks post-operatively. The bone-tendon repair zones were assessed macroscopically and histologically.

Healing of the baboon supraspinatus involved a sequence of stages resulting in the reestablishment of the bone-tendon junction. It was not uniform and occurred more rapidly at the sites of suture fixation than between them. Four weeks after repair the bone-tendon healing was immature. Whereas macroscopically the repair appeared to be healed at eight weeks, the Sharpey fibres holding the repair together did not appear in any considerable number before 12 weeks. By 15 weeks, the bone-tendon junction was almost, but not quite mature.

Our results support the use of a post-operative rehabilitation programme in man which protects the surgical repair for at least 12 to 15 weeks in order to allow maturation of tendon-to-bone healing.

We performed a systematic review of the optimal management of septic arthritis in children as recommended in the current English literature using MEDLINE, EMBASE, CINAHL, the Cochrane Library and reference lists of retrieved articles without date restrictions up to 31 January 2009. From 2236 citations, 227 relevant full-text articles were screened in detail; 154 papers fulfilled the inclusion criteria, from which conclusions were drawn on the management of infected joints in children.

Our review showed that no single investigation, including joint aspiration, is sufficiently reliable to diagnose conclusively joint infection. The roles of aspiration, arthrotomy and arthroscopy in treatment are not clear cut, and the ideal duration of antibiotic therapy is not yet fully defined. These issues are discussed. Further large-scale, multi-centre studies are needed to delineate the optimal management of paediatric septic arthritis.

In developmental dysplasia of the hip, a deficient acetabulum may be augmented by placing local autogenous iliac osseous graft, or the ilium itself, over the head of the femur with the expectation that the added bone will function as a bearing surface. We analysed this bone obtained en bloc during subsequent surgery which was performed for degenerative osteoarthritis in three patients at 6, 25 and 30 years after the initial augmentation procedure. In each patient, the augmentation comprised of red cancellous bone covered on its articulating surface by a distinct layer of white tissue. Microscopy of this tissue showed parallel rows of spindle-shaped cells lying between linearly arranged collagen bundles typical of joint capsule. Biochemical analysis showed type I collagen, the principal collagen of joint capsule and bone, with no significant quantity of type II collagen, the principal collagen of cartilage. While the added bone produced by acetabular augmentation was durable, histological and biochemical analyses suggested that it had not undergone cartilage metaplasia. The augmented acetabulum articulates with the head of the femur by means of an interposed hip joint capsule.

The April 2012 Research Roundup³⁶⁰ looks at who is capable of being an arthroscopist, bupivacaine, triamcinolone and chondrotoxicity, reducing scarring in injured skeletal muscle, horny Goat Weed and the repair of osseous defects, platelet-derived growth factor and fracture healing, the importance of the reserve zone in a child’s growth plate, coping with advanced arthritis, hydroxyapatite and platelet-rich plasma for bone defects, and calcium phosphate and bone regeneration

This review summarises the opinions and conclusions reached from a symposium on infected total knee replacement (TKR) held at the British Association of Surgery of the Knee (BASK) annual meeting in 2011. The National Joint Registry for England and Wales reported 5082 revision TKRs in 2010, of which 1157 (23%) were caused by infection. The diagnosis of infection beyond the acute post-operative stage relies on the identification of the causative organism by aspiration and analysis of material obtained at arthroscopy. Ideal treatment then involves a two-stage surgical procedure with extensive debridement and washout, followed by antibiotics. An articulating or non-articulating drug-eluting cement spacer is used prior to implantation of the revision prosthesis, guided by the serum level of inflammatory markers. The use of a single-stage revision is gaining popularity and we would advocate its use in certain patients where the causative organism is known, no sinuses are present, the patient is not immunocompromised, and there is no radiological evidence of component loosening or osteitis.

It is our opinion that single-stage revision produces high-quality reproducible results and will soon achieve the same widespread acceptance as it does in infected hip arthroplasty.