We investigated the use of hypoxia-inducible factor (HIF) proteins as prognostic markers in chondrosarcoma and the relationship of HIF to the biological characteristics of cartilage tumours. The expression of HIF-1α, HIF-2α, proliferating cell nuclear antigen (PCNA) and microvessel density (MVD) were measured immunohistochemically in 29 specimens of cartilage tumour.

There was no HIF-1α and HIF-2α staining in any of the nine benign cartilage tumours. In 20 specimens of chondrosarcoma, the rate of HIF-1α and HIF-2α expression was 40% and 25%, respectively. The tumour size (≥ 8 cm), histological grade (grade 2 and grade 3) surgical margin (marginal and intralesional) and HIF-1α expression (positive) correlated significantly with a shorter disease-free survival. There was a significant association between HIF-1α and the MVD and a strong trend towards a correlation between HIF-1α and the PCNA index or histological grade.

Our findings suggest that HIF-1α protein may be a useful objective marker in the assessment of the prognosis in chondrosarcoma, since it plays an important role in tumour angiogenesis and cell proliferation.

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.

Stems improve the mechanical stability of tibial components in total knee replacement (TKR), but come at a cost of stress shielding along their length. Their advantages include resistance to shear, reduced tibial lift-off and increased stability by reducing micromotion. Longer stems may have disadvantages including stress shielding along the length of the stem with associated reduction in bone density and a theoretical risk of subsidence and loosening, peri-prosthetic fracture and end-of-stem pain. These features make long stems unattractive in the primary TKR setting, but often desirable in revision surgery with bone loss and instability. In the revision scenario, stems are beneficial in order to convey structural stability to the construct and protect the reconstruction of bony defects. Cemented and uncemented long stemmed implants have different roles depending on the nature of the bone loss involved.

This review discusses the biomechanics of the design of tibial components and stems to inform the selection of the component and the technique of implantation.

We have evaluated the effect of vacuum aspiration of the iliac wing on the osseointegration of cement into the acetabulum. We entered a total of 40 patients undergoing primary total hip arthroplasty into two consecutive study groups. Group 1 underwent acetabular cement pressurisation for 60 seconds before insertion of the acetabular component. Group 2 had the same pressurisation with simultaneous vacuum suction of the ilium using an iliac-wing aspirator. Standard post-operative radiographs were reviewed blindly to assess the penetration of cement into the iliac wing. Penetration was significantly greater in the group with aspiration of the iliac wing.

Ciprofloxacin hydrochloride-loaded microspheres were prepared by a spray-drying method using pectin and chitosan. The effects of different polymers and drug ratios were investigated.

The most appropriate carriers were selected by in vitro testing. A rat methicillin-resistant Staphylococcus aureus osteomyelitis model was used to evaluate the effects of the loaded microspheres.

The drug was released rapidly from the pectin carrier but this was more sustained in the chitosan formulation.

Chitosan microspheres loaded with ciprofloxacin hydrochloride were more effective for the treatment of osteomyelitis than equivalent intramuscular antibiotics.

In an interdisciplinary project involving electronic engineers and clinicians, a telemetric system was developed to measure the bending load in a titanium internal femoral fixator. As this was a new device, the main question posed was: what clinically relevant information could be drawn from its application? As a first clinical investigation, 27 patients (24 men, three women) with a mean age of 38.4 years (19 to 66) with femoral nonunions were treated using the system. The mean duration of the nonunion was 15.4 months (5 to 69). The elasticity of the plate-callus system was measured telemetrically until union. Conventional radiographs and a CT scan at 12 weeks were performed routinely, and healing was staged according to the CT scans. All nonunions healed at a mean of 21.5 weeks (13 to 37). Well before any radiological signs of healing could be detected, a substantial decrease in elasticity was recorded. The relative elasticity decreased to 50% at a mean of 7.8 weeks (3.5 to 13) and to 10% at a mean of 19.3 weeks (4.5 to 37). At 12 weeks the mean relative elasticity was 28.1% (0% to 56%). The relative elasticity was significantly different between the different healing stages as determined by the CT scans.

Incorporating load measuring electronics into implants is a promising option for the assessment of bone healing. Future application might lead to a reduction in the need for exposure to ionising radiation to monitor fracture healing.

The aims of this study were to examine the repeatability of measurements of bone mineral density (BMD) around a cemented polyethylene Charnley acetabular component using dual-energy x-ray absorptiometry and to determine the longitudinal pattern of change in BMD during the first 24 months after surgery.

The precision of measurements of BMD in 19 subjects ranged from 7.7% to 10.8% between regions, using a four-region-of-interest model. A longitudinal study of 27 patients demonstrated a transient decrease in net pelvic BMD during the first 12 months, which recovered to baseline at 24 months. The BMD in the region medial to the dome of the component reduced by between 7% and 10% during the first three months, but recovered to approximately baseline values by two years.

Changes in BMD in the pelvis around cemented acetabular components may be measured using dual-energy x-ray absorptiometry. Bone loss after insertion of a cemented Charnley acetabular component is small, transient and occurs mainly at the medial wall of the acetabulum. After two years, bone mass returns to baseline values, with a pattern suggesting a uniform transmission of load to the acetabulum.

We compared the clinical and radiological outcomes of two cementless femoral stems in the treatment of patients with a Garden III or IV fracture of the femoral neck. A total of 70 patients (70 hips) in each group were enrolled into a prospective randomised study. One group received a short anatomical cementless stem and the other received a conventional cementless stem. Their mean age was 74.9 years (50 to 94) and 76.0 years (55 to 96), respectively (p = 0.328). The mean follow-up was 4.1 years (2 to 5) and 4.8 years (2 to 6), respectively. Perfusion lung scans and high resolution chest CTs were performed to detect pulmonary microemboli.

At final follow-up there were no statistically significant differences between the short anatomical and the conventional stems with regard to the mean Harris hip score (85.7 (66 to 100) versus 86.5 (55 to 100); p = 0.791), the mean Western Ontario and McMaster Universities Osteoarthritis Index (17 (6 to 34) versus 16 (5 to 35); p = 0.13) or the mean University of California, Los Angeles activity score (5 (3 to 6) versus 4 (3 to 6); p = 0.032). No patient with a short stem had thigh pain, but 11 patients (16%) with a conventional stem had thigh pain. No patients with a short stem had symptomatic pulmonary microemboli, but 11 patients with a conventional stem had pulmonary microemboli (symptomatic in three patients and asymptomatic in eight patients). One hip (1.4%) in the short stem group and eight (11.4%) in the conventional group had an intra-operative undisplaced fracture of the calcar. No component was revised for aseptic loosening in either group. One acetabular component in the short stem group and two acetabular components in the conventional stem group were revised for recurrent dislocation.

Our study demonstrated that despite the poor bone quality in these elderly patients with a fracture of the femoral neck, osseo-integration was obtained in all hips in both groups. However, the incidence of thigh pain, pulmonary microemboli and peri-prosthetic fracture was significantly higher in the conventional stem group than in the short stem group.

The Capital Hip implant was a Charnley-based system which included a flanged and a roundback stem, both of which were available in stainless steel and titanium. The system was withdrawn from the market because of its inferior performance. However, all four of the designs did not produce poor rates of survival. Using a simulated-based, finite-element analysis, we have analysed the Capital Hip system. Our aim was to investigate whether our simulation was able to detect differences which could account for the varying survival between the Capital Hip designs, thereby further validating the simulation.

We created finite-element models of reconstructions with the flanged and roundback Capital Hips. A loading history was applied representing normal walking and stair-climbing, while we monitored the formation of fatigue cracks in the cement.

Corresponding to the clinical findings, our simulation was able to detect the negative effects of the titanium material and the flanged design in the Capital Hip system. Although improvements could be made by including the effect of the roughness of the surface of the stem, our study increased the value of the model as a predictive tool for determining failure of an implant.

This study explored the relationship between the initial stability of the femoral component and penetration of cement into the graft bed following impaction allografting.

Impaction allografting was carried out in human cadaveric femurs. In one group the cement was pressurised conventionally but in the other it was not pressurised. Migration and micromotion of the implant were measured under simulated walking loads. The specimens were then cross-sectioned and penetration of the cement measured.

Around the distal half of the implant we found approximately 70% and 40% of contact of the cement with the endosteum in the pressure and no-pressure groups, respectively. The distal migration/micromotion, and valgus/varus migration were significantly higher in the no-pressure group than in that subjected to pressure. These motion components correlated negatively with the mean area of cement and its contact with the endosteum.

The presence of cement at the endosteum appears to play an important role in the initial stability of the implant following impaction allografting.

We investigated the effect of stimulation with a pulsed electromagnetic field on the osseointegration of hydroxyapatite in cortical bone in rabbits. Implants were inserted into femoral cortical bone and were stimulated for six hours per day for three weeks.

Electromagnetic stimulation improved osseointegration of hydroxyapatite compared with animals which did not receive this treatment in terms of direct contact with the bone, the maturity of the bone and mechanical fixation. The highest values of maximum push-out force (F_max) and ultimate shear strength (σ_u) were observed in the treated group and differed significantly from those of the control group at three weeks (F_max; p < 0.0001; σ_u, p < 0.0005).

Traditional techniques for the insertion of femoral stems in arthroplasty of the hip in osteopetrosis carry a considerable risk of penetration of the femoral cortex and intra-operative fractures, due to obliteration of the intramedullary cavity and greatly increased stiffness and brittleness of the bone. In order to reduce the risk of such complications we manufactured a customised stem and a computer-based guiding device for the preparation of a cavity within the proximal femur. This system was used successfully in three hips in two patients. We describe the system and the operative technique.

We retrospectively studied 14 patients with proximal and diaphyseal tumours and disappearing bone (Gorham’s) disease of the humerus treated with wide resection and reconstruction using an allograft-resurfacing composite (ARC). There were ten women and four men, with a mean age of 35 years (8 to 69). At a mean follow-up of 25 months (10 to 89), two patients had a fracture of the allograft. In one of these it was revised with a similar ARC and in the other with an intercalary prosthesis. A further patient had an infection and a fracture of the allograft that was revised with a megaprosthesis. In all patients with an ARC, healing of the ARC-host bone interface was observed. One patient had failure of the locking mechanism of the total elbow replacement. The mean post-operative Musculoskeletal Tumor Society score for the upper extremity was 77% (46.7% to 86.7%), which represents good and excellent results; one patient had a poor result (46.7%).

In the short term ARC effectively relieves pain and restores shoulder function in patients with wide resection of the proximal humerus. Fracture and infection remain significant complications.

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

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

We studied the effects of hyperbaric oxygen (HBO) and zoledronic acid (ZA) on posterior lumbar fusion using a validated animal model. A total of 40 New Zealand white rabbits underwent posterior lumbar fusion at L5–6 with autogenous iliac bone grafting. They were divided randomly into four groups as follows: group 1, control; group 2, HBO (2.4 atm for two hours daily); group 3, local ZA (20 μg of ZA mixed with bone graft); and group 4, combined HBO and local ZA. All the animals were killed six weeks after surgery and the fusion segments were subjected to radiological analysis, manual palpation, biomechanical testing and histological examination.

Five rabbits died within two weeks of operation. Thus, 35 rabbits (eight in group 1 and nine in groups 2, 3 and 4) completed the study. The rates of fusion in groups 3 and 4 (p = 0.015) were higher than in group 1 (p < 0.001) in terms of radiological analysis and in group 4 was higher than in group 1 with regard to manual palpation (p = 0.015). We found a statistically significant difference in the biomechanical analysis between groups 1 and 4 (p = 0.024). Histological examination also showed a statistically significant difference between groups 1 and 4 (p = 0.036).

Our results suggest that local ZA combined with HBO may improve the success rate in posterior lumbar spinal fusion.

The scarcity of mesenchymal stem cells (MSCs) in iliac crest bone marrow aspirate (ICBMA), and the expense and time in culturing cells, has led to the search for alternative harvest sites. The reamer-irrigation-aspirator (RIA) provides continuous irrigation and suction during reaming of long bones. The aspirated contents pass via a filter, trapping bony fragments, before moving into a ‘waste’ bag from which MSCs have been previously isolated. We examined the liquid and solid phases, performed a novel digestion of the solid phase, and made a comparative assessment in terms of number, phenotype and differentiation capacity with matched ICBMA.

The solid fraction from the filtrate was digested for 60 minutes at 37°C with collagenase. Enumeration was performed via the colony-forming unit fibroblast (CFU-F) assay. Passage (P2) cells were differentiated towards osteogenic, adipogenic and chondrogenic lineages, and their phenotypes assessed using flow cytometry (CD33, CD34, CD45, CD73, CD90, and CD105).

MSCs from the RIA phases were able to differentiate at least as well as those from ICBMA, and all fractions had phenotypes consistent with other established sources. The median number of colonies for the three groups was: ICBMA = 8.5 (2 to 86), RIA-liquid = 19.5 (4 to 90), RIA-solid = 109 (67 to 200) per 200 μl. The mean total yield of cells for the three groups was: ICBMA = 920 (0 to 4275), RIA-liquid = 114 983 (16 500 to 477 750), RIA-solid = 12 785 (7210 to 28 475).

The RIA filtrate contains large numbers of MSCs that could potentially be extracted without enzymatic digestion and used for bone repair without prior cell expansion.

There have been comparatively few studies of the incidence of osteolysis and the survival of hybrid and cementless total hip replacements (THRs) in patients younger than 50 years of age. We prospectively reviewed 78 patients (109 hips) with a hybrid THR having a mean age of 43.4 years (21 to 50) and 79 patients (110 hips) with a cementless THR with a mean age of 46.8 years (21 to 49). The patients were evaluated clinically using the Harris hip score, the Western Ontario and McMaster Universities (WOMAC) osteoarthritis score and the University of California, Los Angeles (UCLA) activity score. Radiographs and CT scans were assessed for loosening and osteolysis. The mean follow-up was for 18.4 years (16 to 19) in both groups.

The mean post-operative Harris hip scores (91 points versus 90 points), the mean WOMAC scores (11 points versus 13 points) and UCLA activity scores (6.9 points versus 7.1 points) were similar in both groups. The revision rates of the acetabular component (13% versus 16%) and the femoral component (3% versus 4%), and the survival of the acetabular component (87% versus 84%) and the femoral component (97% versus 96%) were similar in both groups.

Although the long-term fixation of the acetabular metallic shell and the cemented and cementless femoral components was outstanding, wear and peri-acetabular osteolysis constitute the major challenges of THR in young patients.

Between November 1997 and December 2000 we performed 27 total hip replacements in 22 patients with high congenital dislocation of the hip using porous tantalum monoblock acetabular components implanted in the true acetabular bed. Clinical and radiological evaluation was performed at regular intervals for a mean of 10.2 years (8.5 to 12). The mean Harris Hip Score improved from 48.3 (15 to 65) pre-operatively to 89.5 (56 to 100) at the final follow-up. The mean Oxford Hip Score was 49.5 (35 to 59) pre-operatively and decreased to 21.2 (12 to 48) at one year and 15.2 (10 to 28) at final follow-up. Migration of the acetabular component was assessed with the EBRA software system. There was a mean migration of 0.68 mm (0.49 to 0.8) in the first year and a mean 0.89 mm (0.6 to 0.98) in the second year, after excluding one initial excessive migration. No revision was necessary for any reason, no acetabular component became loose, and no radiolucent lines were observed at the final follow-up.

The porous tantalum monoblock acetabular component is an implant offering adequate initial stability in conjunction with a modulus of elasticity and porosity close to that of cancellous bone. It favours bone ingrowth, leading to good mid-term results.