Radiological assessment of the cement mantle is used routinely to determine the outcome of total hip replacement. We performed a simulated replacement arthroplasty on cadaver femora and took standard postoperative radiographs. The femora were then sectioned into 7 mm slices starting at the calcar, and high-resolution faxitron radiographs were taken of these sections. Analysis of the faxitron images showed that defects in the cement mantle were observed up to 100 times more frequently than on the standard films. We therefore encourage the search for a better technique in assessing the cement mantle

Objectives. The aim of the current study was to assess whether calcaneal broadband ultrasound attenuation (BUA) can predict whole body and regional dual-energy x-ray absorptiometry (DXA)-derived bone mass in healthy, Australian children and adolescents at different stages of maturity. Methods. A total of 389 boys and girls across a wide age range (four to 18 years) volunteered to participate. The estimated age of peak height velocity (APHV) was used to classify children into pre-, peri-, and post-APHV groups. BUA was measured at the non-dominant heel with quantitative ultrasonometry (QUS) (Lunar Achilles Insight, GE), while bone mineral density (BMD) and bone mineral content (BMC) were examined at the femoral neck, lumbar spine and whole body (DXA, XR-800, Norland). Associations between BUA and DXA-derived measures were examined with Pearson correlations and linear regression. Participants were additionally ranked in quartiles for QUS and DXA measures in order to determine agreement in rankings. Results. For the whole sample, BUA predicted 29% of the study population variance in whole body BMC and BMD, 23% to 24% of the study population variance in lumbar spine BMC and BMD, and 21% to 24% of the variance in femoral neck BMC and BMD (p < 0.001). BUA predictions were strongest for the most mature participants (pre-APHV R. 2. = 0.03 to 0.19; peri-APHV R. 2. = 0.05 to 0.17; post-APHV R. 2. = 0.18 to 0.28) and marginally stronger for girls (R. 2. = 0.25-0.32, p < 0.001) than for boys (R. 2. = 0.21-0.27, p < 0.001). Agreement in quartile rankings between QUS and DXA measures of bone mass was generally poor (27.3% to 38.2%). Conclusion. Calcaneal BUA has a weak to moderate relationship with DXA measurements of bone mass in children, and has a tendency to misclassify children on the basis of quartile rankings. Cite this article: B. K. Weeks, R. Hirsch, R. C. Nogueira, B. R. Beck. Is calcaneal broadband ultrasound attenuation a valid index of dual-energy x-ray absorptiometry-derived bone mass in children? Bone Joint Res 2016;5:538–543. DOI: 10.1302/2046-3758.511.BJR-2016-0116.R1

Objectives. The objective of this study was to investigate the therapeutic effect of peripheral blood mononuclear cells (PBMNCs) treated with quality and quantity control culture (QQ-culture) to expand and fortify angiogenic cells on the acceleration of fracture healing. Methods. Human PBMNCs were cultured for seven days with the QQ-culture method using a serum-free medium containing five specific cytokines and growth factors. The QQ-cultured PBMNCs (QQMNCs) obtained were counted and characterised by flow cytometry and real-time polymerase chain reaction (RT-PCR). Angiogenic and osteo-inductive potentials were evaluated using tube formation assays and co-culture with mesenchymal stem cells with osteo-inductive medium in vitro. In order to evaluate the therapeutic potential of QQMNCs, cells were transplanted into an immunodeficient rat femur nonunion model. The rats were randomised into three groups: control; PBMNCs; and QQMNCs. The fracture healing was evaluated radiographically and histologically. Results. The total number of PBMNCs was decreased after QQ-culture, however, the number of CD34+ and CD206+ cells were found to have increased as assessed by flow cytometry analysis. In addition, gene expression of angiogenic factors was upregulated in QQMNCs. In the animal model, the rate of bone union was higher in the QQMNC group than in the other groups. Radiographic scores and bone volume were significantly associated with the enhancement of angiogenesis in the QQMNC group. Conclusion. We have demonstrated that QQMNCs have superior potential to accelerate fracture healing compared with PBMNCs. The QQMNCs could be a promising option for fracture nonunion. Cite this article: K. Mifuji, M. Ishikawa, N. Kamei, R. Tanaka, K. Arita, H. Mizuno, T. Asahara, N. Adachi, M. Ochi. Angiogenic conditioning of peripheral blood mononuclear cells promotes fracture healing. Bone Joint Res 2017;6: 489–498. DOI: 10.1302/2046-3758.68.BJR-2016-0338.R1

Objectives. The cytotoxicity induced by cobalt ions (Co. 2+. ) and cobalt nanoparticles (Co-NPs) which released following the insertion of a total hip prosthesis, has been reported. However, little is known about the underlying mechanisms. In this study, we investigate the toxic effect of Co. 2+. and Co-NPs on liver cells, and explain further the potential mechanisms. Methods. Co-NPs were characterised for size, shape, elemental analysis, and hydrodynamic diameter, and were assessed by Transmission Electron Microscope, Scanning Electron Microscope, Energy Dispersive X-ray Spectroscopy and Dynamic Light Scattering. BRL-3A cells were used in this study. Cytotoxicity was evaluated by MTT and lactate dehydrogenase release assay. In order to clarify the potential mechanisms, reactive oxygen species, Bax/Bcl-2 mRNA expression, IL-8 mRNA expression and DNA damage were assessed on BRL-3A cells after Co. 2+. or Co-NPs treatment. Results. Results showed cytotoxic effects of Co. 2+. and Co-NPs were dependent upon time and dosage, and the cytotoxicity of Co-NPs was greater than that of Co. 2+. In addition, Co-NPs elicited a significant (p < 0.05) reduction in cell viability with a concomitant increase in lactic dehydrogenase release, reactive oxygen species generation, IL-8 mRNA expression, Bax/Bcl-2 mRNA expression and DNA damage after 24 hours of exposure. Conclusion. Co-NPs induced greater cytotoxicity and genotoxicity in BRL-3A cells than Co. 2+. Cell membrane damage, oxidative stress, immune inflammation and DNA damage may play an important role in the effects of Co-NPs on liver cells. Cite this article: Y. K. Liu, X. X. Deng, H.L. Yang. Cytotoxicity and genotoxicity in liver cells induced by cobalt nanoparticles and ions. Bone Joint Res 2016;5:461–469. DOI: 10.1302/2046-3758.510.BJR-2016-0016.R1

Objectives. To explore the therapeutic potential of combining bone marrow-derived mesenchymal stem cells (BM-MSCs) and hydroxyapatite (HA) granules to treat nonunion of the long bone. Methods. Ten patients with an atrophic nonunion of a long bone fracture were selectively divided into two groups. Five subjects in the treatment group were treated with the combination of 15 million autologous BM-MSCs, 5g/cm. 3. (HA) granules and internal fixation. Control subjects were treated with iliac crest autograft, 5g/cm. 3. HA granules and internal fixation. The outcomes measured were post-operative pain (visual analogue scale), level of functionality (LEFS and DASH), and radiograph assessment. Results. Post-operative pain evaluation showed no significant differences between the two groups. The treatment group demonstrated faster initial radiographic and functional improvements. Statistically significant differences in functional scores were present during the first (p = 0.002), second (p = 0.005) and third (p = 0.01) month. Both groups achieved similar outcomes by the end of one-year follow-up. No immunologic or neoplastic side effects were reported. Conclusions. All cases of nonunion of a long bone presented in this study were successfully treated using autologous BM-MSCs. The combination of autologous BM-MSCs and HA granules is a safe method for treating nonunion. Patients treated with BM-MSCs had faster initial radiographic and functional improvements. By the end of 12 months, both groups had similar outcomes. Cite this article: H.D. Ismail, P. Phedy, E. Kholinne, Y. P. Djaja, Y. Kusnadi, M. Merlina, N. D. Yulisa. Mesenchymal stem cell implantation in atrophic nonunion of the long bones: A translational study. Bone Joint Res 2016;5:287–293. DOI: 10.1302/2046-3758.57.2000587

Studies on the migration of an implant may be the only way of monitoring the early performance of metal-on-metal prostheses. The Ein Bild Roentgen Analyse - femoral component analysis (EBRA-FCA) method was adapted to measure migration of the femoral component in a metal-on-metal surface arthroplasty of the hip using standard antero-posterior radiographs. In order to determine the accuracy and precision of this method a prosthesis was implanted into cadaver bones. Eleven series of radiographs were used to perform a zero-migration study. After adjustment of the femoral component to simulate migration of 3 mm the radiographs were repeated. All were measured independently by three different observers. The accuracy of the method was found to be ± 1.6 mm for the x-direction and ± 2 mm for the y-direction (95% percentile). The method was validated using 28 hips with a minimum follow-up of 3.5 years after arthroplasty. Seventeen were sound, but 11 had failed because of loosening of the femoral component. The normal (control) group had a different pattern of migration compared with that of the loose group. At 29.2 months, the control group showed a mean migration of 1.62 mm and 1.05 mm compared with 4.39 mm and 4.05 mm in the failed group, for the centre of the head and the tip of the stem, respectively (p = 0.001). In the failed group, the mean time to migration greater than 2 mm was earlier than the onset of clinical symptoms or radiological evidence of failure, 19.1 versus 32.2 months (p = 0.001) and 24.8 months (p = 0.012), respectively. EBRA-FCA is a reliable and valid tool for measuring migration of the femoral component after surface arthroplasty and can be used to predict early failure of the implant. It may be of value in determining the long-term performance of surface arthroplasty

Objectives. There is increasing application of bone morphogenetic proteins (BMPs) owing to their role in promoting fracture healing and bone fusion. However, an optimal delivery system has yet to be identified. The aims of this study were to synthesise bioactive BMP-2, combine it with a novel α-tricalcium phosphate/poly(D,L-lactide-co-glycolide) (α-TCP/PLGA) nanocomposite and study its release from the composite. Methods. BMP-2 was synthesised using an Escherichia coli expression system and purified. In vitro bioactivity was confirmed using C2C12 cells and an alkaline phosphatase assay. The modified solution-evaporation method . was used to fabricate α-TCP/PLGA nanocomposite and this was characterised using X-ray diffraction and scanning electron microscopy. Functionalisation of α-TCP/PLGA nanocomposite by adsorption of BMP-2 was performed and release of BMP-2 was characterised using an enzyme-linked immunosorbent assay (ELISA). Results. Alkaline phosphatase activity of C2C12 cells was increased by the presence of all BMP-2/nanocomposite discs compared with the presence of a blank disc (p = 0.0022), and increased with increasing incubation concentrations of BMP-2, showing successful adsorption and bioactivity of BMP-2. A burst release profile was observed for BMP-2 from the nanocomposite. . Conclusions. Functionalisation of α-TCP/PLGA with BMP-2 produced osteoinduction and was dose-dependent. This material therefore has potential application as an osteoinductive agent in regenerative medicine

The aim of this study was to establish a classification system for the acromioclavicular joint using cadaveric dissection and radiological analyses of both reformatted computed tomographic scans and conventional radiographs centred on the joint. This classification should be useful for planning arthroscopic procedures or introducing a needle and in prospective studies of biomechanical stresses across the joint which may be associated with the development of joint pathology. We have demonstrated three main three-dimensional morphological groups namely flat, oblique and curved, on both cadaveric examination and radiological assessment. These groups were recognised in both the coronal and axial planes and were independent of age

In order to evaluate the relationship between acetabular and proximal femoral alignment in the initiation and evolution of osteoarthritis of the dysplastic hip, the acetabular and femoral angles were calculated geometrically from radiographs of 62 patients with pre-arthrosis and early osteoarthritis. The sum of the lateral opening angle of the acetabulum and the neck-shaft angle was defined as the lateral instability index (LII), and the sum of the anterior opening angle of the acetabulum and the anteversion angle of the femoral neck as the anterior instability index (AII). These two indices were compared in dysplastic and unaffected hips. A total of 22 unilateral hips with pre-arthrosis were followed for at least 15 years to determine whether the two indices were associated with the progression of osteoarthritis. The LII of the affected hips (197.4 (. sd. 6.0)) was significantly greater than that of the unaffected hips (1830 (. sd. 6.9)). A follow-up study of 22 hips with pre-arthrosis showed that only the LII was associated with progression of the disease, and an LII of 196 was the threshold value for this progression

Aims

Second-generation metal-on-metal (MoM) articulations in total hip arthroplasty (THA) were introduced in order to reduce wear-related complications. The current study reports on the serum cobalt levels and the clinical outcome at a minimum of 20 years following THA with a MoM (Metasul) or a ceramic-on-polyethylene (CoP) bearing.

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 have investigated the anatomy of the proximal part of the ulna to assess its influence on the use of plates in the management of fractures at this site. We examined 54 specimens from cadavers. The mean varus angulation in the proximal third was 17.5° (11° to 23°) and the mean anterior deviation 4.5° (1° to 14°). These variations must be considered when applying plates to the dorsal surface of the ulna for Monteggia-type fractures. A pre-operative radiograph of the contralateral elbow may also be of value

The operative treatment of fractures of the proximal humerus can be complicated by poor bone quality. Our aim was to evaluate a new method which allows prediction of the bone quality of the proximal humerus from radiographs. Anteroposterior radiographs were taken of 19 human cadaver humeri. The cortical thickness was measured at two levels of the proximal humeral diaphysis. The bone mineral density (BMD) was determined for the humeral head (HH), the surgical neck (SN), the greater tuberosity (GT) and lesser tuberosity (LT) using dual-energy x-ray absorptiometry. The mean cortical thickness was 4.4 ± 1.0 mm. Specimens aged 70 years or less had a significantly higher cortical thickness than those aged over 70 years. A significant positive correlation was found between cortical thickness and the BMD for each region of interest. The cortical thickness of the proximal diaphysis is a reliable predictor of the bone quality of the proximal humerus

Our aim was to determine whether tantalum markers improved the accuracy and/or precision of methods for the measurement of migration in total hip replacement based on conventional measurements without mathematical correction of the data, and with Ein Bild Roentgen Analyse – Femoral Component Analysis (EBRA-FCA) which allows a computerised correction. Three observers independently analysed 13 series of roentgen-stereophotogrammetric-analysis (RSA)-compatible radiographs (88). Data were obtained from conventional measurements, EBRA-FCA and the RSA method and all the results were compared with the RSA data. Radiological evaluation was also used to quantify in how many radiographs the intraosseous position of the bone markers had been simulated. The results showed that tantalum markers improve reliability whereas they do not affect accuracy for conventional measurements and for EBRA-FCA. Because of the danger of third-body wear their implantation should be avoided unless they are an integral part of the method

In this prospective, randomised study, we have compared the wear rate of cemented, acetabular polyethylene cups articulating with either a 22 mm or a 32 mm cobalt-chromium head. We evaluated 89 patients who had a total of 484 radiographs. The mean follow-up period was 71.4 months (SD 29.1). All the radiographs were digitised and electronically measured. The linear wear rate was significantly higher during the first two years and decreased after this period to a constant value. We suggest that this is partly due to a ‘run-in’ process caused by irregularities between surfaces of the cup and head and an initial plastic deformation of the polyethylene. The mean volumetric wear was 120.3 mm. 3. /year for the 32 mm head, which was significantly higher than the 41.5 mm. 3. /year for the 22 mm heads. The mean linear wear rate was not significantly different. We were, however, unable to find radiological signs of osteolysis in the patients who had higher wear rates

This study investigates the use of porous biphasic ceramics as graft extenders in impaction grafting of the femur during revision hip surgery. Impaction grafting of the femur was performed in four groups of sheep. Group one received pure allograft, group two 50% allograft and 50% BoneSave, group three 50% allograft and 50% BoneSave type 2 and group four 10% allograft and 90% BoneSave as the graft material. Function was assessed using an index of pre- and post-operative peak vertical ground reaction force ratios. Changes in bone mineral density were measured by dual energy X ray absorptiometry (DEXA) scanning. Loosening and subsidence were assessed radiographically and by histological examination of the explanted specimens. There was no statistically significant difference between the four groups after 18 months of unrestricted functional loading for all outcome measures

We assessed carpal collapse by measuring the capitate-radius (CR) distance on standard plain radiographs. This new method required validation of diagnostic accuracy, so we compared it with the method of Nattrass et al. 1. known as revised carpal height (RCH). We studied wrist radiographs from 16 normal subjects and 11 patients with unilateral Kienböck’s disease. We found that there was a significant difference in the left/right CR index between the normal wrists and those with Kienböck’s disease (p < 0.001). The use of left/right RCH index showed no significant difference (p = 0.30). Diagnostic accuracy was shown to be higher for the CR index using ROC curves. We then assessed 40 normal wrists and found the mean CR index to be 0.999 ± 0.034, and suggest that values less than 0.92 are abnormal. The CR index can be used for diagnosis in unilateral carpal collapse, and for monitoring progress where the condition is bilateral

Acetabular dysplasia was produced in 24 immature white rabbits. A rotational acetabular osteotomy was then carried out and radiological and histological studies of the articular cartilage were made. In the hips which did not undergo osteotomy, radiographs at 26 weeks showed that residual subluxation remained and arthritic changes such as narrowing of the joint space or dislocation were still seen. However, in the operated group there was a remarkable increase in cover, but arthritic changes were not observed. After 24 weeks, the Mankin grading score in the operated group was significantly lower than that in the non-operated group. The latter hips showed an irregular surface of the cartilage, exfoliation and proliferation of synovial tissue. In those undergoing osteotomy, primary cloning of chondrocytes or hypercellularity was seen and at 24 weeks after operation and metaplasia of the cartilage in the fibrous tissue was observed in the boundary between the medial area of the acetabulum and the acetabular fossa

There are many methods for analysing wear volume in failed polyethylene acetabular components. We compared a radiological technique with three recognised ex vivo methods of measurement. We tested 18 ultra-high-molecular-weight polyethylene acetabular components revised for wear and aseptic loosening, of which 13 had pre-revision radiographs, from which the wear volume was calculated based upon the linear wear. We used a shadowgraph technique on silicone casts of all of the retrievals and a coordinate measuring method on the components directly. For these techniques, the wear vector was calculated for each component and the wear volume extrapolated using mathematical equations. The volumetric wear was also measured directly using a fluid-displacement method. The results of each technique were compared. The series had high wear volumes (mean 1385 mm. 3. ; 730 to 1850) and high wear rates (mean 205 mm. 3. /year; 92 to 363). There were wide variations in the measurements of wear volume between the radiological and the other techniques. Radiograph-derived wear volume correlated poorly with that of the fluid-displacement method, co-ordinate measuring method and shadowgraph methods, becoming less accurate as the wear increased. The mean overestimation in radiological wear volume was 47.7% of the fluid-displacement method wear volume. Fluid-displacement method, coordinate measuring method and shadowgraph determinations of wear volume were all better than that of the radiograph-derived linear measurements since they took into account the direction of wear. However, only radiological techniques can be used in vivo and remain useful for monitoring linear wear in the clinical setting. Interpretation of radiological measurements of acetabular wear must be done judiciously in the clinical setting. In vitro laboratory techniques, in particular the fluid-displacement method, remain the most accurate and reliable methods of assessing the wear of acetabular polyethylene

The long-term biological effects of wear debris are unknown. We have investigated whether there is any evidence of cumulative mutagenic damage in peripheral blood lymphocytes of patients undergoing revision arthroplasty of predominantly metal-on-plastic total hip replacements compared with those at primary arthroplasty. There was a threefold increase in aneuploidy and a twofold increase in chromosomal translocations which could not be explained by the confounding variables of smoking, gender, age and diagnostic radiographs. In the patients with TiVaAl prostheses there was a fivefold increase in aneuploidy but no increase in chromosomal translocations. By contrast, in patients with cobalt-chrome prostheses there was a 2.5-fold increase in aneuploidy and a 3.5-fold increase in chromosomal translocations. In six patients with stainless-steel prostheses there was no increase in either aneuploidy or chromosomal translocations. Our results suggest that future epidemiological studies of the putative long-term risks of joint replacement should take into account the type of alloy used in the prosthesis

We have examined 26 retrieved, failed titanium-alloy femoral stems. The clinical details, radiological appearances and the histology of the surrounding soft tissues in each patient were also investigated. The stems were predominantly of the flanged design and had a characteristic pattern of wear. A review of the radiographs showed a series of changes, progressive with time. The first was lateral debonding with subsidence of the stem. This was followed by calcar resorption and fragmentation or fracture of the cement. Finally, osteolysis was seen, starting with a radiolucency at the cement-bone interface and progressing to endosteal cavitation. Three histological appearances were noted: granulomatous, necrobiotic and necrotic. We suggest that an unknown factor, possibly related to the design of the stem, caused it to move early. After this, micromovement at the cement-stem interface led to the generation of particulate debris and fracture of the cement. A soft-tissue reaction to the debris resulted in osteolysis and failure of fixation of the prostheses

We studied the reliability of the Singh classification of trabecular bone structure in the proximal femur as a measure of osteoporosis, using kappa statistics. Radiographs of fractures of the femoral neck or trochanteric region in 80 consecutive patients were assessed by six observers. The interobserver variation was large; only three of 72 radiographs were given the same classification by all six observers and the kappa values ranged from 0.15 to 0.54. The intraobserver variation showed substantial strength of agreement; kappa values ranged from 0.63 to 0.88. In 77 patients dual-energy X-ray absorptiometry was used to measure bone mineral density. The results were compared with those of the Singh classification: we found no correlation

Recent studies of the fibroblast growth factor receptor 3 (FGFR3) gene have established that achondroplasia and hypochondroplasia are allelic disorders of different mutations. To determine whether the genotype could be distinguished on the basis of the phenotype, we analysed height, arm span, and skeletal radiographs from 23 patients with achondroplasia and the G380R mutation of FGFR3 and eight with hypochondroplasia and the N540K mutation. Both conditions share the classical pathological features of micromelic short stature, reduced or unchanged interpedicular distances in the lumbar spine, disproportionately long fibulae, and squared and shortened pelvic ilia. These were significantly more severe in the G380R patients than in the N540K patients. Our findings have shown a firm statistical correlation between the genotype and the phenotype, although there were a few exceptional cases in which there was phenotypic overlap between the two conditions

We used fresh small-fragment osteochondral allografts to reconstruct post-traumatic osteochondral defects in 126 knees of 123 patients with a mean age of 35 years. At a mean follow-up of 7.5 years (2 to 20), 108 knees were rated as successful (85%) and 18 had failed (15%). The factors related to failure included age over 50 years (p = 0.008), bipolar defects (p < 0.05), malaligned knees with overstressing of the grafts, and workers’ compensation cases (p < 0.04). Collapse of the graft by more than 3 mm and of the joint space of more than 50% were seen more frequently in radiographs of failed grafts. Our encouraging clinical results for fresh small-fragment osteochondral allografts show that they are indicated for unipolar post-traumatic osteochondral defects of the knee in young active patients

We compared wear particles from two different designs of total hip arthroplasty with polycrystalline alumina-ceramic bearings of different production periods (group 1, before ISO 6474: group 2, according to ISO 6474). The neocapsules and interfacial connective tissue membranes were retrieved after mean implantation times of 131 months and 38 months, respectively. Specimen blocks were freed from embedding media, either methylmethacrylate or paraffin and digested in concentrated nitric acid. Particles were then counted and their sizes and composition determined by SEM and energy-dispersive x-ray analysis (EDXA). The mean numbers and sizes of most alumina wear particles did not differ for both production periods, but the larger sizes of particle in group 1 point to more severe surface destruction. The increased metal wear in group 2 was apparently due to alumina-induced abrasion of the stems. In this study the concentrations of particles in the periprosthetic tissues were 2 to 22 times lower than those observed previously with polyethylene and alumina/polyethylene wear couples

We examined the radiographs from a prospective clinical study of fixation by pedicle screws and those from an experimental study in a sheep model. In the clinical study, instruments were removed from 21 patients after implantation for 11 to 16 months and the extraction torques of the screws were recorded. A structured protocol was used for the radiological examinations. In the experimental study, loaded pedicle screw instrumentations were implanted in the sheep for six or 12 weeks. After radiological examination the pull-out resistance and the histological characteristics were studied. In the clinical study, all screws with radiolucent zones had a significantly reduced mean extraction torque compared with screws without radiolucent zones (16 ± 10 Ncm v 403 ± 220 Ncm; p < 0.0001). In the experimental study the mean maximum pull-out resistance for the screws with radiolucent zones was significantly lower than for those with no radiolucency (243 ± 156 N v 2214 ± 578 N; p = 0.0006) and the mean bone-to-screw contact was reduced for screws with zones compared with those without zones (8 ± 9% v 55 ± 29%; p = 0.0002). Our findings showed that all screws with radiolucent zones had low extraction torques or low pull-out resistance. A radiolucent zone is a good indicator of loosening of a pedicle screw

Abundant implant-derived biomaterial wear particles are generated in aseptic loosening and are deposited in periprosthetic tissues in which they are phagocytosed by mononuclear and multinucleated macrophage-like cells. It has been stated that the multinucleated cells which contain wear particles are not bone-resorbing osteoclasts. To investigate the validity of this claim we isolated human osteoclasts from giant-cell tumours of bone and rat osteoclasts from long bones. These were cultured on glass coverslips and on cortical bone slices in the presence of particles of latex, PMMA and titanium. Osteoclast phagocytosis of these particle types was shown by light microscopy, energy-dispersive X-ray analysis and SEM. Giant cells containing phagocytosed particles were seen to be associated with the formation of resorption lacunae. Osteoclasts containing particles were also calcitonin-receptor-positive and showed an inhibitory response to calcitonin. Our findings demonstrate that osteoclasts are capable of phagocytosing particles of a wide range of size, including particles of polymeric and metallic bio-materials found in periprosthetic tissues, and that after particle phagocytosis, they remain fully functional, hormone-responsive, bone-resorbing cells

We analysed synovial fluid from 88 hips, 38 with osteoarthritis and 12 with well-functioning and 38 with loose hip prostheses. The levels of TNF-α, IL-1ß (71 hips) and IL-6 (45 hips) were measured using the ELISA technique. Joints with well-functioning or loose prostheses had significantly increased levels of TNF-α compared with those with osteoarthritis. Hips with aseptic loosening also had higher levels of IL-1ß but not of IL-6 compared with those without an implant. The levels of TNF-α and IL-1ß did not differ between hips with stable and loose prostheses. Higher levels of TNF-α were found in hips with bone resorption of type II and type III (Gustilo-Pasternak) compared with those with type-I loosening. The level of cytokines in joint fluid was not influenced by the time in situ of the implants or the age, gender or area of the osteolysis as measured on conventional radiographs. Our findings support the theory that macrophages in the joint capsule increase the production of TNF-α at an early phase probably because of particle load and in the absence of clinical loosening. Since TNF-α has an important role in the osteolytic process, the interfaces should be protected from penetration of joint fluid

The direction of wear in the acetabular socket has implications for the amount of debris that is generated during movement, for the magnitude of eccentric loading and for the incidence of impingement of the neck. We observed the direction of penetration with respect to a global co-ordinate system in 84 acetabular components retrieved at reoperation. The mean direction of wear relative to the open face of the sockets was found to be 37° with a range from 0° to 87°. For those values determined using the inclination of the socket on the prerevision radiograph, the mean direction of penetration in the coronal plane had a lateral, rather than a medial, component. The mean angle was 84° (SD 17°) with respect to the horizontal. The angle of penetration was found to correlate significantly with the depth, in that the lateral component became larger as the wear progressed. There was also a significant correlation between the rate of penetration and the direction of wear. Despite the theoretical advantage of penetration in the superolateral direction, i.e., along the margin of the socket, in reducing the probability of impingement of the neck, no significant correlation was seen between the angle of penetration and the period of use in vivo. This may suggest that impingement of the femoral neck on the rim of the socket may not be the dominant factor in loosening of the socket but can still be important in a few cases

We revised 24 consecutive hips with loosening of the femoral stem using impaction allograft and a cemented stem with an unpolished proximal surface. Repeated radiostereometric examinations for up to two years showed a slow rate of subsidence with a mean of 0.32 mm (−2.0 to +0.31). Fifteen cases followed for a further year showed the same mean subsidence after three years, indicating stabilisation. A tendency to retroversion of the stems was noted between the operation and the last follow-up. Retroversion was also recorded when displacement of the stem was studied in ten of the patients after two years. Repeated determination of bone mineral density showed an initial loss after six months, followed by recovery to the postoperative level at two years. Defects in the cement mantle and malalignment of the stem were often noted on postoperative radiographs, but did not correlate with the degrees of migration or displacement. After one year, increasing frequency of trabecular remodelling or resorption of the graft was observed in the greater trochanter and distal to the tip of the stem. Cortical repair was noted distally and medially (Gruen regions 3, 5 and 6). Migration of the stems was the lowest reported to date, which we attribute to the improved grafting technique and to the hardness of the graft

We analysed revised Mathys isoelastic polyacetal femoral stems with stainless-steel heads and polyethylene acetabular cups from eight patients in order to differentiate various types of particle of wear debris. Loosening of isoelastic femoral stems is associated with the formation of polyacetal wear particles as well as those of polyethylene and metal. All three types of particle were isolated simultaneously by tissue digestion followed by sucrose gradient centrifugation. Polyacetal particles were either elongated, ranging from 10 to 150 μm in size, or shred-like and up to 100 μm in size. Polyethylene particles were elongated or granules, and were typically submicron or micronsized. Polyacetal and polyethylene polymer particles were differentiated by the presence of BaSO. 4. , which is added as a radiopaque agent to polyacetal but not to polyethylene. This was easily detectable by back-scattered SEM analysis and verified by energy dispersive x-ray analysis. Two types of foreign-body giant cell (FBGC) were recognised in the histological specimens. Extremely large FBGCs with irregular polygonal particles showing an uneven, spotty birefringence in polarised light were ascribed to polyacetal debris. Smaller FBGCs with slender elongated particles shining uniformly brightly in polarisation were related to polyethylene. Mononucleated histiocytes containing both types of particle were also present. Our findings offer a better understanding of the processes involved in the loosening of polyacetal stems and indicate why the idea of ‘isoelasticity’ proved to be unsuccessful in clinical practice

Proponents of the biological theory of aseptic loosening have in recent years tended to concentrate on the production and distribution of particulate ultra-high-molecular-weight polyethylene (UHMWPE) debris around the potential joint space. However, mechanical loading of cemented implants with the differing elastic moduli of metal stems, polymethylmethacrylate (PMMA) cement and bone can result in relative micromotion, implying the potential for production of metal and PMMA particles from the stem-cement interface by fretting wear. In order to investigate the production and biological reactivity of debris from this interface, PMMA and metal particulate debris was produced by sliding wear of PMMA pins containing barium sulphate and zirconium dioxide against a Vaquasheened stainless steel counterface. This debris was characterised by SEM, energy-dispersive analysis by X-ray (EDAX) and image analysis, then added to cell cultures of a human monocytic cell line, U937, and stimulation of pro-osteolytic cytokines measured by ELISA. Large quantities of PMMA cement debris were generated by the sliding wear of PMMA pins against Vaquasheened stainless steel plates in the method developed for this study. Both cements stimulated the release of pro-osteolytic TNFα from the U937 monocytic cell line, in a dose-dependent fashion. There was a trend towards greater TNFα release with Palacos cement than CMW cement at the same dose. Palacos particles also caused significant release of IL-6, another pro-osteolytic cytokine, while CMW did not. The particulate cement debris produced did not stimulate the release of GM-CSF or IL1β from the U937 cells. These results may explain the cytokine pathway responsible for bone resorption caused by particulate PMMA debris. Radio-opaque additives are of value in surgical practice and clinical studies to quantify the relevance of these in vitro findings are required before the use of cement containing radio-opacifier is constrained

Two acetabula which contained large bone allografts introduced at revision arthroplasty were obtained at post-mortem. The allografts had been placed in superior defects to support cementless acetabular components, and both hips were functioning well at the time of death. Clinical radiographs demonstrated apparent healing of graft to host bone, no graft collapse and stability of the acetabular components. Microscopic examination of sections through these specimens showed that the bulk allografts were encapsulated in fibrous tissue. Vascularity was increased at the host-graft interface, but there was limited evidence of bone union between the graft and the host. In the few areas where union had occurred, revascularisation extended no more than 2 mm beyond the graft-host interface. Within the body of the graft, the acellular matrix of trabecular bone maintained structural integrity up to 48 months after surgery. In areas where the allograft was adjacent to an implant, there was fibrous tissue orientated parallel to the implant surface. The acetabulum which contained a porous-coated component showed evidence of bone growth into the porous surface where it was in contact with viable host bone. No ingrowth occurred in areas where the porous coating was in contact with the graft. Although the grafts were functioning well, allograft revascularisation and remodelling were minimal, and the radiological appearance of healing did not correlate with histological findings

Aternatives to autogenous bone graft for spinal fusion have been investigated for many years. It has been shown that osteoconductive materials alone do not give a rate of fusion which is comparable to that of autogenous bone graft. We analysed the effectiveness of porous ceramic loaded with cultured mesenchymal stem cells as a new graft material for spinal fusion in an animal model. Posterolateral fusion was carried out at the L4/L5 level in 40 White New Zealand rabbits using one of the following graft materials: porous ceramic granules plus cultured mesenchymal stem cells (group I); ceramic granules plus fresh autogenous bone marrow (group II); ceramic granules alone (group III); and autogenous bone graft (group IV). The animals were killed eight weeks after surgery and the spines were evaluated radiographically, by a manual palpation test and by histological analysis. The rate of fusion was significantly higher in group I compared with group III and higher, but not significantly, in group I compared with groups II and IV. In group I histological analysis showed newly formed bone in contact with the implanted granules and highly cellular bone marrow between the newly formed trabecular bone. In group II, thin trabeculae of newly formed bone were present in the peripheral portion of the fusion mass. In group III, there was a reduced mount of newly formed bone and abundant fibrous tissue. In group IV, there were thin trabeculae of newly formed bone close to the decorticated transverse processes and dead trabecular bone in the central portion of the fusion mass. In vitro cultured mesenchymal stem cells may be loaded into porous ceramic to make a graft material for spinal fusion which appears to be more effective than porous ceramic alone. Further studies are needed to investigate the medium- to long-term results of this procedure, its feasibility in the clinical setting and the most appropriate carrier for mesenchymal stem cells

We have examined whether primary human muscle-derived cells can be used in ex vivo gene therapy to deliver BMP-2 and to produce bone in vivo. Two in vitro experiments and one in vivo experiment were used to determine the osteocompetence and BMP-2 secretion capacity of cells isolated from human skeletal muscle. We isolated five different populations of primary muscle cells from human skeletal muscle in three patients. In the first in vitro experiment, production of alkaline phosphatase by the cells in response to stimulation by rhBMP-2 was measured and used as an indicator of cellular osteocompetence. In the second, secretion of BMP-2 was measured after the cell populations had been transduced by an adenovirus encoding for BMP-2. In the in vivo experiment, the cells were cotransduced with a retrovirus encoding for a nuclear localised β-galactosidase gene and an adenovirus encoding for BMP-2. The cotransduced cells were then injected into the hind limbs of severe combined immune-deficient (SCID) mice and analysed radiographically and histologically. The nuclear localised β-galactosidase gene allowed identification of the injected cells in histological specimens. In the first in vitro experiment, the five different cell populations all responded to in vitro stimulation of rhBMP-2 by producing higher levels of alkaline phosphatase when compared with non-stimulated cells. In the second, the five different cell populations were all successfully transduced by an adenovirus to express and secrete BMP-2. The cells secreted between 444 and 2551 ng of BMP-2 over three days. In the in vivo experiment, injection of the transduced cells into the hind-limb musculature of SCID mice resulted in the formation of ectopic bone at 1, 2, 3 and 4 weeks after injection. Retroviral labelling of the cell nuclei showed labelled human muscle-derived cells occupying locations of osteoblasts in the ectopic bone, further supporting their osteocompetence. Cells from human skeletal muscle, because of their availability to orthopaedic surgeons, their osteocompetence, and their ability to express BMP-2 after genetic engineering, are an attractive cell population for use in BMP-2 gene therapy approaches

Objectives

Osteoporosis is a chronic disease. The aim of this study was to identify key genes in osteoporosis.

Objectives

The objectives of this study were: 1) to examine osteophyte formation, subchondral bone advance, and bone marrow lesions (BMLs) in osteoarthritis (OA)-prone Hartley guinea pigs; and 2) to assess the disease-modifying activity of an orally administered phosphocitrate ‘analogue’, Carolinas Molecule-01 (CM-01).

Objectives

The treatment of osteoporotic fractures is a major challenge, and the enhancement of healing is critical as a major goal in modern fracture management. Most osteoporotic fractures occur at the metaphyseal bone region but few models exist and the healing is still poorly understood. A systematic review was conducted to identify and analyse the appropriateness of current osteoporotic metaphyseal fracture animal models.

Objectives

Intramedullary fixation is considered the most stable treatment for pertrochanteric fractures of the proximal femur and cut-out is one of the most frequent mechanical complications. In order to determine the role of clinical variables and radiological parameters in predicting the risk of this complication, we analysed the data pertaining to a group of patients recruited over the course of six years.

Objectives

This study looked to analyse the expression levels of microRNA-140-3p and microRNA-140-5p in synovial fluid, and their correlations to the severity of disease regarding knee osteoarthritis (OA).

Objectives

The patient-rated wrist evaluation (PRWE) and the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire are patient-reported outcome measures (PROMs) used for clinical and research purposes. Methodological high-quality clinimetric studies that determine the measurement properties of these PROMs when used in patients with a distal radial fracture are lacking. This study aimed to validate the PRWE and DASH in Dutch patients with a displaced distal radial fracture (DRF).

Objectives

Bisphosphonates (BP) are the first-line treatment for preventing fragility fractures. However, concern regarding their efficacy is growing because bisphosphonate is associated with over-suppression of remodelling and accumulation of microcracks. While dual-energy X-ray absorptiometry (DXA) scanning may show a gain in bone density, the impact of this class of drug on mechanical properties remains unclear. We therefore sought to quantify the mechanical strength of bone treated with BP (oral alendronate), and correlate data with the microarchitecture and density of microcracks in comparison with untreated controls.

Objectives

We have previously investigated an association between the genome copy number variation (CNV) and acetabular dysplasia (AD). Hip osteoarthritis is associated with a genetic polymorphism in the aspartic acid repeat in the N-terminal region of the asporin (ASPN) gene; therefore, the present study aimed to investigate whether the CNV of ASPN is involved in the pathogenesis of AD.

Objectives

This systematic review aimed to assess the in vivo and clinical effect of strontium (Sr)-enriched biomaterials in bone formation and/or remodelling.

Objectives

Osteoporosis has become an increasing concern for older people as it may potentially lead to osteoporotic fractures. This study is designed to assess the efficacy and safety of ten therapies for post-menopausal women using network meta-analysis.

Objectives

Microindentation has the potential to measure the stiffness of an individual patient’s bone. Bone stiffness plays a crucial role in the press-fit stability of orthopaedic implants. Arming surgeons with accurate bone stiffness information may reduce surgical complications including periprosthetic fractures. The question addressed with this systematic review is whether microindentation can accurately measure cortical bone stiffness.

Objectives

Ultraviolet (UV) light-mediated photofunctionalisation is known to improve osseointegration of pure titanium (Ti). However, histological examination of titanium alloy (Ti6Al4V), which is frequently applied in orthopaedic and dental surgery, has not yet been performed. This study examined the osseointegration of photofunctionalised Ti6Al4V implants.

Objectives

To compare the therapeutic potential of tissue-engineered constructs (TECs) combining mesenchymal stem cells (MSCs) and coral granules from either Acropora or Porites to repair large bone defects.

Objectives

We investigated the effects on fracture healing of two up-regulators of inducible nitric oxide synthase (iNOS) in a rat model of an open femoral osteotomy: tadalafil, a phosphodiesterase inhibitor, and the recently reported nutraceutical, COMB-4 (consisting of L-citrulline, Paullinia cupana, ginger and muira puama), given orally for either 14 or 42 days.

Objectives

We have observed clinical cases where bone is formed in the overlaying muscle covering surgically created bone defects treated with a hydroxyapatite/calcium sulphate biomaterial. Our objective was to investigate the osteoinductive potential of the biomaterial and to determine if growth factors secreted from local bone cells induce osteoblastic differentiation of muscle cells.

Objectives

Ubiquitin E3 ligase-mediated protein degradation regulates osteoblast function. Itch, an E3 ligase, affects numerous cell functions by regulating ubiquitination and proteasomal degradation of related proteins. However, the Itch-related cellular and molecular mechanisms by which osteoblast differentiation and function are elevated during bone fracture repair are as yet unknown.

Objectives

Mechanical wear and corrosion at the head-stem junction of total hip arthroplasties (THAs) (trunnionosis) have been implicated in their early revision, most commonly in metal-on-metal (MOM) hips. We can isolate the role of the head-stem junction as the predominant source of metal release by investigating non-MOM hips; this can help to identify clinically significant volumes of material loss and corrosion from these surfaces.

Objectives

To assess the structure and extracellular matrix molecule expression of osteogenic cell sheets created via culture in medium with both dexamethasone (Dex) and ascorbic acid phosphate (AscP) compared either Dex or AscP alone.

Objectives

This study aims to evaluate if micro-CT can work as a method for the 3D assessment and analysis of cancellous bone by comparing micro-CT with undecalcified histological sections in OVX rats.

Objectives

The purpose of this study was to compare the results and complications of tibial lengthening over an intramedullary nail with treatment using the traditional Ilizarov method.

Objectives

There are various pin-in-plaster methods for treating fractures of the distal radius. The purpose of this study is to introduce a modified technique of ‘pin in plaster’.

Objectives

“Virtual fracture clinics” have been reported as a safe and effective alternative to the traditional fracture clinic. Robust protocols are used to identify cases that do not require further review, with the remainder triaged to the most appropriate subspecialist at the optimum time for review. The objective of this study was to perform a “top-down” analysis of the cost effectiveness of this virtual fracture clinic pathway.

Rebound growth after hemiepiphysiodesis may be a normal event, but little is known about its causes, incidence or factors related to its intensity. The aim of this study was to evaluate rebound growth under controlled experimental conditions.

A total of 22 six-week-old rabbits underwent a medial proximal tibial hemiepiphysiodesis using a two-hole plate and screws. Temporal growth plate arrest was maintained for three weeks, and animals were killed at intervals ranging between three days and three weeks after removal of the device. The radiological angulation of the proximal tibia was studied at weekly intervals during and after hemiepiphysiodesis. A histological study of the retrieved proximal physis of the tibia was performed.

The mean angulation achieved at three weeks was 34.7° (standard deviation (sd) 3.4), and this remained unchanged for the study period of up to two weeks. By three weeks after removal of the implant the mean angulation had dropped to 28.2° (sd 1.8) (p < 0.001). Histologically, widening of the medial side was noted during the first two weeks. By three weeks this widening had substantially disappeared and the normal columnar structure was virtually re-established.

In our rabbit model, rebound was an event of variable incidence and intensity and, when present, did not appear immediately after restoration of growth, but took some time to appear.

Cite this article: Bone Joint J 2015;97-B:862–8.

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.

Objectives

Lengthening osteotomies of the calcaneus in children are in general grafted with bone from the iliac crest. Artificial bone grafts have been introduced, however, their structural and clinical durability has not been documented. Radiostereometric analysis (RSA) is a very accurate and precise method for measurements of rigid body movements including the evaluation of joint implant and fracture stability, however, RSA has not previously been used in clinical studies of calcaneal osteotomies. We assessed the precision of RSA as a measurement tool in a lateral calcaneal lengthening osteotomy (LCLO).

Objectives

The aim of this experimental study on New Zealand’s white rabbits was to investigate the transplantation of autogenous growth plate cells in order to treat the injured growth plate. They were assessed in terms of measurements of radiological tibial varus and histological characteristics.

Objectives

Excessive acetabular coverage is the most common cause of pincer-type femoroacetabular impingement. To date, an association between acetabular over-coverage and genetic variations has not been studied. In this study we investigated the association between single nucleotide polymorphisms (SNPs) of paralogous Homeobox (HOX)9 genes and acetabular coverage in Japanese individuals to identify a possible genetic variation associated with acetabular over-coverage.

Objectives

This study tests the biomechanical properties of adjacent locked plate constructs in a femur model using Sawbones. Previous studies have described biomechanical behaviour related to inter-device distances. We hypothesise that a smaller lateral inter-plate distance will result in a biomechanically stronger construct, and that addition of an anterior plate will increase the overall strength of the construct.

The treatment of chronic osteomyelitis often includes surgical debridement and filling the resultant void with antibiotic-loaded polymethylmethacrylate cement, bone grafts or bone substitutes. Recently, the use of bioactive glass to treat bone defects in infections has been reported in a limited series of patients. However, no direct comparison between this biomaterial and antibiotic-loaded bone substitute has been performed.

In this retrospective study, we compared the safety and efficacy of surgical debridement and local application of the bioactive glass S53P4 in a series of 27 patients affected by chronic osteomyelitis of the long bones (Group A) with two other series, treated respectively with an antibiotic-loaded hydroxyapatite and calcium sulphate compound (Group B; n = 27) or a mixture of tricalcium phosphate and an antibiotic-loaded demineralised bone matrix (Group C; n = 22). Systemic antibiotics were also used in all groups.

After comparable periods of follow-up, the control of infection was similar in the three groups. In particular, 25 out of 27 (92.6%) patients of Group A, 24 out of 27 (88.9%) in Group B and 19 out of 22 (86.3%) in Group C showed no infection recurrence at means of 21.8 (12 to 36), 22.1 (12 to 36) and 21.5 (12 to 36) months follow-up, respectively, while Group A showed a reduced wound complication rate.

Our results show that patients treated with a bioactive glass without local antibiotics achieved similar eradication of infection and less drainage than those treated with two different antibiotic-loaded calcium-based bone substitutes.

Cite this article: Bone Joint J 2014; 96-B:845–50.

Introduction

Osteoarthritis (OA) is a progressively debilitating disease that affects mostly cartilage, with associated changes in the bone. The increasing incidence of OA and an ageing population, coupled with insufficient therapeutic choices, has led to focus on the potential of stem cells as a novel strategy for cartilage repair.

Malpositioning of the trochanteric entry point during the introduction of an intramedullary nail may cause iatrogenic fracture or malreduction. Although the optimal point of insertion in the coronal plane has been well described, positioning in the sagittal plane is poorly defined.

The paired femora from 374 cadavers were placed both in the anatomical position and in internal rotation to neutralise femoral anteversion. A marker was placed at the apparent apex of the greater trochanter, and the lateral and anterior offsets from the axis of the femoral shaft were measured on anteroposterior and lateral photographs. Greater trochanteric morphology and trochanteric overhang were graded.

The mean anterior offset of the apex of the trochanter relative to the axis of the femoral shaft was 5.1 mm (sd 4.0) and 4.6 mm (sd 4.2) for the anatomical and neutralised positions, respectively. The mean lateral offset of the apex was 7.1 mm (sd 4.6) and 6.4 mm (sd 4.6), respectively.

Placement of the entry position at the apex of the greater trochanter in the anteroposterior view does not reliably centre an intramedullary nail in the sagittal plane. Based on our findings, the site of insertion should be about 5 mm posterior to the apex of the trochanter to allow for its anterior offset.

Cite this article: Bone Joint J 2014;96-B:1274–81.

Objectives

To review the systemic impact of smoking on bone healing as evidenced within the orthopaedic literature.

Objectives

An experimental piglet model induces avascular necrosis (AVN) and deformation of the femoral head but its secondary effects on the developing acetabulum have not been studied. The aim of this study was to assess the development of secondary acetabular deformation following femoral head ischemia.

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.

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.

Objectives

To assess the sensitivity and specificity of self-reported osteoporosis compared with dual energy X-ray absorptiometry (DXA) defined osteoporosis, and to describe medication use among participants with the condition.

Osteoarthritis (OA) is an important cause of pain, disability and economic loss in humans, and is similarly important in the horse. Recent knowledge on post-traumatic OA has suggested opportunities for early intervention, but it is difficult to identify the appropriate time of these interventions. The horse provides two useful mechanisms to answer these questions: 1) extensive experience with clinical OA in horses; and 2) use of a consistently predictable model of OA that can help study early pathobiological events, define targets for therapeutic intervention and then test these putative therapies. This paper summarises the syndromes of clinical OA in horses including pathogenesis, diagnosis and treatment, and details controlled studies of various treatment options using an equine model of clinical OA.

This review is aimed at clinicians appraising preclinical trauma studies and researchers investigating compromised bone healing or novel treatments for fractures. It categorises the clinical scenarios of poor healing of fractures and attempts to match them with the appropriate animal models in the literature.

We performed an extensive literature search of animal models of long bone fracture repair/nonunion and grouped the resulting studies according to the clinical scenario they were attempting to reflect; we then scrutinised them for their reliability and accuracy in reproducing that clinical scenario.

Models for normal fracture repair (primary and secondary), delayed union, nonunion (atrophic and hypertrophic), segmental defects and fractures at risk of impaired healing were identified. Their accuracy in reflecting the clinical scenario ranged greatly and the reliability of reproducing the scenario ranged from 100% to 40%.

It is vital to know the limitations and success of each model when considering its application.

The success of long-term transcutaneous implants depends on dermal attachment to prevent downgrowth of the epithelium and infection. Hydroxyapatite (HA) coatings and fibronectin (Fn) have independently been shown to regulate fibroblast activity and improve attachment. In an attempt to enhance this phenomenon we adsorbed Fn onto HA-coated substrates. Our study was designed to test the hypothesis that adsorption of Fn onto HA produces a surface that will increase the attachment of dermal fibroblasts better than HA alone or titanium alloy controls.

Iodinated Fn was used to investigate the durability of the protein coating and a bioassay using human dermal fibroblasts was performed to assess the effects of the coating on cell attachment. Cell attachment data were compared with those for HA alone and titanium alloy controls at one, four and 24 hours. Protein attachment peaked within one hour of incubation and the maximum binding efficiency was achieved with an initial droplet of 1000 ng. We showed that after 24 hours one-fifth of the initial Fn coating remained on the substrates, and this resulted in a significant, three-, four-, and sevenfold increase in dermal fibroblast attachment strength compared to uncoated controls at one, four and 24 hours, respectively.

Objectives

This study aims to assess the correlation of CT-based structural rigidity analysis with mechanically determined axial rigidity in normal and metabolically diseased rat bone.

The purposes of this study were to define the range of laxity of the interosseous ligaments in cadaveric wrists and to determine whether this correlated with age, the morphology of the lunate, the scapholunate (SL) gap or the SL angle. We evaluated 83 fresh-frozen cadaveric wrists and recorded the SL gap and SL angle. Standard arthroscopy of the wrist was then performed and the grades of laxity of the scapholunate interosseous ligament (SLIL) and the lunotriquetral interosseous ligament (LTIL) and the morphology of the lunate were recorded. Arthroscopic evaluation of the SLIL revealed four (5%) grade I specimens, 28 (34%) grade II, 40 (48%) grade III and 11 (13%) grade IV. Evaluation of the LTIL showed 17 (20%) grade I specimens, 40 (48%) grade II, 28 (30%) grade III and one (1%) grade IV.

On both bivariate and multivariate analysis, the grade of both the SLIL and LTIL increased with age, but decreased with female gender. The grades of SLIL or LTIL did not correlate with the morphology of the lunate, the SL gap or the SL angle. The physiological range of laxity at the SL and lunotriquetral joints is wider than originally described. The intercarpal ligaments demonstrate an age-related progression of laxity of the SL and lunotriquetral joints. There is no correlation between the grades of laxity of the SLIL or LTIL and the morphology of the lunate, the SL gap or the SL grade. Based on our results, we believe that the Geissler classification has a role in describing intercarpal laxity, but if used alone it cannot adequately diagnose pathological instability.

We suggest a modified classification with a mechanism that may distinguish physiological laxity from pathological instability.

Although success has been achieved with implantation of bone marrow mesenchymal stem cells (bMSCs) in degenerative discs, its full potential may not be achieved if the harsh environment of the degenerative disc remains. Axial distraction has been shown to increase hydration and nutrition. Combining both therapies may have a synergistic effect in reversing degenerative disc disease. In order to evaluate the effect of bMSC implantation, axial distraction and combination therapy in stimulating regeneration and retarding degeneration in degenerative discs, we first induced disc degeneration by axial loading in a rabbit model.

The rabbits in the intervention groups performed better with respect to disc height, morphological grading, histological scoring and average dead cell count. The groups with distraction performed better than those without on all criteria except the average dead cell count.

Our findings suggest that bMSC implantation and distraction stimulate regenerative changes in degenerative discs in a rabbit model.

We used a biodegradable mesh to convert an acetabular defect into a contained defect in six patients at total hip replacement. Their mean age was 61 years (46 to 69). The mean follow-up was 32 months (19 to 50). Before clinical use, the strength retention and hydrolytic in vitro degradation properties of the implants were studied in the laboratory over a two-year period. A successful clinical outcome was determined by the radiological findings and the Harris hip score.

All the patients had a satisfactory outcome and no mechanical failures or other complications were observed. No protrusion of any of the impacted grafts was observed beyond the mesh. According to our preliminary laboratory and clinical results the biodegradable mesh is suitable for augmenting uncontained acetabular defects in which the primary stability of the implanted acetabular component is provided by the host bone. In the case of defects of the acetabular floor this new application provides a safe method of preventing graft material from protruding excessively into the pelvis and the mesh seems to tolerate bone-impaction grafting in selected patients with primary and revision total hip replacement.

Platelet-leucocyte gel (PLG), a new biotechnological blood product, has hitherto been used primarily to treat chronic ulcers and to promote soft-tissue and bone regeneration in a wide range of medical fields. In this study, the antimicrobial efficacy of PLG against Staphylococcus aureus (ATCC 25923) was investigated in a rabbit model of osteomyelitis. Autologous PLG was injected into the tibial canal after inoculation with Staph. aureus. The prophylactic efficacy of PLG was evaluated by microbiological, radiological and histological examination. Animal groups included a treatment group that received systemic cefazolin and a control group that received no treatment.

Treatment with PLG or cefazolin significantly reduced radiological and histological severity scores compared to the control group. This result was confirmed by a significant reduction in the infection rate and the number of viable bacteria. Although not comparable to cefazolin, PLG exhibited antimicrobial efficacy in vivo and therefore represents a novel strategy to prevent bone infection in humans.

In a rabbit model we investigated the efficacy of a silk fibroin/hydroxyapatite (SF/HA) composite on the repair of a segmental bone defect. Four types of porous SF/HA composites (SF/HA-1, SF/HA-2, SF/HA-3, SF/HA-4) with different material ratios, pore sizes, porosity and additives were implanted subcutaneously into Sprague-Dawley rats to observe biodegradation. SF/HA-3, which had characteristics more suitable for a bone substitite based on strength and resorption was selected as a scaffold and co-cultured with rabbit bone-marrow stromal cells (BMSCs). A segmental bone defect was created in the rabbit radius. The animals were randomised into group 1 (SF/HA-3 combined with BMSCs implanted into the bone defect), group 2 (SF/HA implanted alone) and group 3 (nothing implanted). They were killed at four, eight and 12 weeks for visual, radiological and histological study.

The bone defects had complete union for group 1 and partial union in group 2, 12 weeks after operation. There was no formation of new bone in group 3. We conclude that SF/HA-3 combined with BMSCs supports bone healing and offers potential as a bone-graft substitute.

We have developed an animal model to examine the formation of heterotopic ossification using standardised muscular damage and implantation of a beta-tricalcium phosphate block into a hip capsulotomy wound in Wistar rats. The aim was to investigate how cells originating from drilled femoral canals and damaged muscles influence the formation of heterotopic bone. The femoral canal was either drilled or left untouched and a tricalcium phosphate block, immersed either in saline or a rhBMP-2 solution, was implanted. These implants were removed at three and 21 days after the operation and examined histologically, histomorphometrically and immunohistochemically.

Bone formation was seen in all implants in rhBMP-2-immersed, whereas in those immersed in saline the process was minimal, irrespective of drilling of the femoral canals. Bone mineralisation was somewhat greater in the absence of drilling with a mean mineralised volume to mean total volume of 18.2% (sd 4.5) versus 12.7% (sd 2.9, p < 0.019), respectively.

Our findings suggest that osteoinductive signalling is an early event in the formation of ectopic bone. If applicable to man the results indicate that careful tissue handling is more important than the prevention of the dissemination of bone cells in order to avoid heterotopic ossification.

We evaluated the histological changes before and after fixation in ten knees of ten patients with osteochondritis dissecans who had undergone fixation of the unstable lesions. There were seven males and three females with a mean age of 15 years (11 to 22). The procedure was performed either using bio-absorbable pins only or in combination with an autologous osteochondral plug. A needle biopsy was done at the time of fixation and at the time of a second-look arthroscopy at a mean of 7.8 months (6 to 9) after surgery.

The biopsy specimens at the second-look arthroscopy showed significant improvement in the histological grading score compared with the pre-fixation scores (p < 0.01). In the specimens at the second-look arthroscopy, the extracellular matrix was stained more densely than at the time of fixation, especially in the middle to deep layers of the articular cartilage.

Our findings show that articular cartilage regenerates after fixation of an unstable lesion in osteochondritis dissecans.

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.

Soaking bone grafts in a bisphosphonate solution before implantation can prevent their resorption and increase the local bone density in rats and humans. However, recent studies suggest that pre-treatment of allografts with bisphosphonate can prevent bone ingrowth into impaction grafts. We tested the hypothesis that excessive amounts of bisphosphonate would also cause a negative response in less dense grafts. We used a model where non-impacted metaphyseal bone grafts were randomised into three groups with either no bisphosphonate, alendronate followed by rinsing, and alendronate without subsequent rinsing, and inserted into bone chambers in rats. The specimens were evaluated histologically at one week, and by histomorphometry and radiology at four weeks. At four weeks, both bisphosphonate groups showed an increase in the total bone content, increased newly formed bone, and higher radiodensity than the controls. In spite of being implanted in a chamber with a limited opportunity to diffuse, even an excessive amount of bisphosphonate improved the outcome. We suggest that the negative results seen by others could be due to the combination of densely compacted bone and a bisphosphonate.

We suggest that bisphosphonates are likely to have a negative influence where resorption is a prerequisite to create space for new bone ingrowth.

We used interconnected porous calcium hydroxyapatite ceramic to bridge a rabbit ulnar defect. Two weeks after inducing the defect we percutaneously injected rabbit bone marrow-derived mesenchymal stromal cells labelled with ferumoxide. The contribution of an external magnetic targeting system to attract these cells into the ceramic and their effect on subsequent bone formation were evaluated.

This technique significantly facilitated the infiltration of ferumoxide-labelled cells into ceramic and significantly contributed to the enhancement of bone formation even in the chronic phase. As such, it is potentially of clinical use to treat fractures, bone defects, delayed union and nonunion.

We evaluated two reconstruction techniques for a simulated posterolateral corner injury on ten pairs of cadaver knees. Specimens were mounted at 30° and 90° of knee flexion to record external rotation and varus movement. Instability was created by transversely sectioning the lateral collateral ligament at its midpoint and the popliteus tendon was released at the lateral femoral condyle. The left knee was randomly assigned for reconstruction using either a combined or fibula-based treatment with the right knee receiving the other. After sectioning, laxity increased in all the specimens. Each technique restored external rotatory and varus stability at both flexion angles to levels similar to the intact condition. For the fibula-based reconstruction method, varus laxity at 30° of knee flexion did not differ from the intact state, but was significantly less than after the combined method.

Both the fibula-based and combined posterolateral reconstruction techniques are equally effective in restoring stability following the simulated injury.

We implanted titanium and carbon fibre-reinforced plastic (CFRP) femoral prostheses of the same dimensions into five prosthetic femora. An abductor jig was attached and a 1 kN load applied. This was repeated with five control femora. Digital image correlation was used to give a detailed two-dimensional strain map of the medial cortex of the proximal femur. Both implants caused stress shielding around the calcar. Distally, the titanium implant showed stress shielding, whereas the CFRP prosthesis did not produce a strain pattern which was statistically different from the controls. There was a reduction in strain beyond the tip of both the implants.

This investigation indicates that use of the CFRP stem should avoid stress shielding in total hip replacement.

Carbonate-substituted hydroxyapatite (CHA) is more osteoconductive and more resorbable than hydroxyapatite (HA), but the underlying mode of its action is unclear. We hypothesised that increased resorption of the ceramic by osteoclasts might subsequently upregulate osteoblasts by a coupling mechanism, and sought to test this in a large animal model.

Defects were created in both the lateral femoral condyles of 12 adult sheep. Six were implanted with CHA granules bilaterally, and six with HA. Six of the animals in each group received the bisphosphonate zoledronate (0.05 mg/kg), which inhibits the function of osteoclasts, intra-operatively.

After six weeks bony ingrowth was greater in the CHA implants than in HA, but not in the animals given zoledronate. Functional osteoclasts are necessary for the enhanced osteoconduction seen in CHA compared with HA.

A total of 20 pairs of fresh-frozen cadaver femurs were assigned to four alignment groups consisting of relative varus (10° and 20°) and relative valgus (10° and 20°), 75 composite femurs of two neck geometries were also used. In both the cadaver and the composite femurs, placing the component in 20° of valgus resulted in a significant increase in load to failure. Placing the component in 10° of valgus had no appreciable effect on increasing the load to failure except in the composite femurs with varus native femoral necks. Specimens in 10° of varus were significantly weaker than the neutrally-aligned specimens.

The results suggest that retention of the intact proximal femoral strength occurs at an implant angulation of ≥ 142°. However, the benefit of extreme valgus alignment may be outweighed in clinical practice by the risk of superior femoral neck notching, which was avoided in this study.

A cadaver study using six pairs of lower limbs was conducted to investigate the accuracy of computer navigation and standard instrumentation for the placement of the Birmingham Hip Resurfacing femoral component. The aim was to place all the femoral components with a stem-shaft angle of 135°.

The mean stem-shaft angle obtained in the standard instrumentation group was 127.7° (120° to 132°), compared with 133.3° (131° to 139°) in the computer navigation group (p = 0.03). The scatter obtained with computer-assisted navigation was approximately half that found using the conventional jig.

Computer navigation was more accurate and more consistent in its placement of the femoral component than standard instrumentation. We suggest that image-free computer-assisted navigation may have an application in aligning the femoral component during hip resurfacing.

A cavovarus foot deformity was simulated in cadaver specimens by inserting metallic wedges of 15° and 30° dorsally into the first tarsometatarsal joint. Sensors in the ankle joint recorded static tibiotalar pressure distribution at physiological load.

The peak pressure increased significantly from neutral alignment to the 30° cavus deformity, and the centre of force migrated medially. The anterior migration of the centre of force was significant for both the 15° (repeated measures analysis of variance (ANOVA), p = 0.021) and the 30° (repeated measures ANOVA, p = 0.007) cavus deformity. Differences in ligament laxity did not influence the peak pressure.

These findings support the hypothesis that the cavovarus foot deformity causes an increase in anteromedial ankle joint pressure leading to anteromedial arthrosis in the long term, even in the absence of lateral hindfoot instability.

The aim of our study was to investigate the effect of platelet-rich plasma on the proliferation and differentiation of rat bone-marrow cells and to determine an optimal platelet concentration in plasma for osseous tissue engineering. Rat bone-marrow cells embedded in different concentrations of platelet-rich plasma gel were cultured for six days. Their potential for proliferation and osteogenic differentiation was analysed. Using a rat limb-lengthening model, the cultured rat bone-marrow cells with platelet-rich plasma of variable concentrations were transplanted into the distraction gap and the quality of the regenerate bone was evaluated radiologically.

Cellular proliferation was enhanced in all the platelet-rich plasma groups in a dose-dependent manner. Although no significant differences in the production and mRNA expression of alkaline phosphatase were detected among these groups, mature bone regenerates were more prevalent in the group with the highest concentration of platelets.

Our results indicate that a high platelet concentration in the platelet-rich plasma in combination with osteoblastic cells could accelerate the formation of new bone during limb-lengthening procedures.

External fixation of distal tibial fractures is often associated with delayed union. We have investigated whether union can be enhanced by using recombinant bone morphogenetic protein-7 (rhBMP-7).

Osteoinduction with rhBMP-7 and bovine collagen was used in 20 patients with distal tibial fractures which had been treated by external fixation (BMP group). Healing of the fracture was compared with that of 20 matched patients in whom treatment was similar except that rhBMP-7 was not used.

Significantly more fractures had healed by 16 (p = 0.039) and 20 weeks (p = 0.022) in the BMP group compared with the matched group. The mean time to union (p = 0.002), the duration of absence from work (p = 0.018) and the time for which external fixation was required (p = 0.037) were significantly shorter in the BMP group than in the matched group. Secondary intervention due to delayed healing was required in two patients in the BMP group and seven in the matched group.

RhBMP-7 can enhance the union of distal tibial fractures treated by external fixation.

Nanometre-sized particles of ultra-high molecular weight polyethylene have been identified in the lubricants retrieved from hip simulators. Tissue samples were taken from seven failed Charnley total hip replacements, digested using strong alkali and analysed using high-resolution field emission gun-scanning electron microscopy to determine whether nanometre-sized particles of polyethylene debris were generated in vivo. A randomised method of analysis was used to quantify and characterise all the polyethylene particles isolated.

We isolated nanometre-sized particles from the retrieved tissue samples. The smallest identified was 30 nm and the majority were in the 0.1 μm to 0.99 μm size range. Particles in the 1.0 μm to 9.99 μm size range represented the highest proportion of the wear volume of the tissue samples, with 35% to 98% of the total wear volume comprised of particles of this size. The number of nanometre-sized particles isolated from the tissues accounted for only a small proportion of the total wear volume. Further work is required to assess the biological response to nanometre-sized polyethylene particles.

An experimental sheep model was used for impaction allografting of 12 hemiarthroplasty femoral components placed into two equal-sized groups. In group 1, a 50:50 mixture of ApaPore hydroxyapatite bone-graft substitute and allograft was used. In group 2, ApaPore and allograft were mixed in a 90:10 ratio. Both groups were killed at six months. Ground reaction force results demonstrated no significant differences (p > 0.05) between the two groups at 8, 16 and 24 weeks post-operatively, and all animals remained active. The mean bone turnover rates were significantly greater in group 1, at 0.00206 mm/day, compared to group 2 at 0.0013 mm/day (p < 0.05). The results for the area of new bone formation demonstrated no significant differences (p > 0.05) between the two groups. No significant differences were found between the two groups in thickness of the cement mantle (p > 0.05) and percentage ApaPore-bone contact (p > 0.05).

The results of this animal study demonstrated that a mixture of ApaPore allograft in a 90:10 ratio was comparable to using a 50:50 mixture.