We examined whether a selective cyclooxygenase-2 (COX-2) inhibitor (celecoxib) was as effective as a non-selective inhibitor (ibuprofen) for the prevention of heterotopic ossification following total hip replacement. A total of 250 patients were randomised to receive celecoxib (200 mg b/d) or ibuprofen (400 mg t.d.s) for ten days after surgery. Anteroposterior radiographs of the pelvis were examined for heterotopic ossification three months after surgery. Of the 250 patients, 240 were available for assessment. Heterotopic ossification was more common in the ibuprofen group (none 40.7% (50), Brooker class I 46.3% (57), classes II and III 13.0% (16)) than in the celecoxib group (none 59.0% (69), Brooker class I 35.9% (42), classes II and III 5.1% (6), p = 0.002). Celecoxib was more effective than ibuprofen in preventing heterotopic bone formation after total hip replacement.

A once-daily dose of rivaroxaban 10 mg, an oral, direct Factor Xa inhibitor, was compared with enoxaparin 40 mg subcutaneously once daily for prevention of venous thromboembolism in three studies of patients undergoing elective hip and knee replacement (RECORD programme).

A pooled analysis of data from these studies (n = 9581) showed that rivaroxaban was more effective than enoxaparin in reducing the incidence of the composite of symptomatic venous thromboembolism and all-cause mortality at two weeks (0.4% vs 0.8%, respectively, odds ratio 0.44; 95% confidence interval 0.23 to 0.79; p = 0.005), and at the end of the planned medication period (0.5% vs 1.3%, respectively; odds ratio 0.38; 95% confidence interval 0.22 to 0.62; p < 0.001). The rate of major bleeding was similar at two weeks (0.2% for both) and at the end of the planned medication period (0.3% vs 0.2%).

Rivaroxaban started six to eight hours after surgery was more effective than enoxaparin started the previous evening in preventing symptomatic venous thromboembolism and all-cause mortality, without increasing major bleeding.

We have evaluated the effect of the short-term administration of low therapeutic doses of modern COX-2 inhibitors on the healing of fractures.

A total of 40 adult male New Zealand rabbits were divided into five groups. A mid-diaphyseal osteotomy of the right ulna was performed and either normal saline, prednisolone, indometacin, meloxicam or rofecoxib was administered for five days. Radiological, biomechanical and histomorphometric evaluation was performed at six weeks.

In the group in which the highly selective anti-COX-2 agent, rofecoxib, was used the incidence of radiologically-incomplete union was similar to that in the control group. All the biomechanical parameters were statistically significantly lower in both the prednisolone and indometacin (p = 0.01) and in the meloxicam (p = 0.04) groups compared with the control group. Only the fracture load values were found to be statistically significantly lower (p = 0.05) in the rofecoxib group. Histomorphometric parameters were adversely affected in all groups with the specimens of the rofecoxib group showing the least negative effect.

Our findings indicated that the short-term administration of low therapeutic doses of a highly selective COX-2 inhibitor had a minor negative effect on bone healing.

In order to clarify the role of cytokines in the remodelling of the grafted tendon for ligament reconstruction we compared the responses to interleukin (IL)-1β, platelet-derived growth factor (PDGF)-BB and transforming growth factor (TGF)-β1 of extrinsic fibroblasts infiltrating the frozen-thawed patellar tendon in rats with that of the normal tendon fibroblasts, in regard to the gene expression of matrix metalloproteinase (MMP)-13, using Northern blot analysis. We also examined, immunohistologically, the local expression of IL-1β, PDGF-BB, and TGF-β1 in fibroblasts infiltrating the frozen-thawed patellar tendon.

Northern blot analysis showed that fibroblasts derived from the patellar tendon six weeks after the freeze-thaw procedure in situ showed less response to IL-1β than normal tendon fibroblasts with respect to MMP-13 mRNA gene expression. The immunohistological findings revealed that IL-1β was over-expressed in extrinsic fibroblasts which infiltrated the patellar tendon two and six weeks after the freeze-thaw procedure in situ, but neither PDGF-BB nor TGF-β1 was over-expressed in these extrinsic fibroblasts. Our findings indicated that IL-1β had a close relationship to matrix remodelling of the grafted tendon for ligament reconstruction, in addition to the commencement of inflammation during the tissue-healing process.

The feasibility of bone transport with bone substitute and the factors which are essential for a successful bone transport are unknown. We studied six groups of 12 Japanese white rabbits. Groups A to D received cylindrical autologous bone segments and groups E and F hydroxyapatite prostheses. The periosteum was preserved in group A so that its segments had a blood supply, cells, proteins and scaffold. Group B had no blood supply. Group C had proteins and scaffold and group D had only scaffold. Group E received hydroxyapatite loaded with recombinant human bone morphogenetic protein-2 and group F had hydroxyapatite alone.

Distraction osteogenesis occurred in groups A to C and E which had osteo-conductive transport segments loaded with osteo-inductive proteins. We conclude that scaffold and proteins are essential for successful bone transport, and that bone substitute can be used to regenerate bone.

We attempted to repair full-thickness defects in the articular cartilage of the trochlear groove of the femur in 30 rabbit knee joints using allogenic cultured chondrocytes embedded in a collagen gel. The repaired tissues were examined at 2, 4, 8, 12 and 24 weeks after operation using histological and histochemical methods. The articular defect filling index measurement was derived from safranin-O stained sections. Apoptotic cellular fractions were derived from analysis of apoptosis in situ using TUNEL staining, and was confirmed using caspase-3 staining along with quantification of the total cellularity. The mean articular defect filling index decreased with time. After 24 weeks it was 0.7 (sd 0.10), which was significantly lower than the measurements obtained earlier (p < 0.01). The highest mean percentage of apoptotic cells were observed at 12 weeks, although the total cellularity decreased with time. Because apoptotic cell death may play a role in delamination after chondrocyte transplantation, anti-apoptotic gene therapy may protect transplanted chondrocytes from apoptosis.

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.

We isolated multilineage mesenchymal progenitor cells from haematomas collected from fracture sites. After the haematoma was manually removed from the fracture site it was cut into strips and cultured. Homogenous fibroblastic adherent cells were obtained. Flow cytometry revealed that the adherent cells were consistently positive for mesenchymal stem-cell-related markers CD29, CD44, CD105 and CD166, and were negative for the haemopoietic markers CD14, CD34, CD45 and CD133 similar to bone-marrow-derived mesenchymal stem cells. In the presence of lineage-specific induction factors the adherent cells could differentiate in vitro into osteogenic, chondrogenic and adipogenic cells.

Our results indicate that haematomas found at a fracture site contain multilineage mesenchymal progenitor cells and play an important role in bone healing. Our findings imply that to enhance healing the haematoma should not be removed from the fracture site during osteosynthesis.

The incidence and long-term outcome of undisplaced fatigue fractures of the femoral neck treated conservatively were examined in Finnish military conscripts between 1970 and 1990.

From 106 cases identified, 66 patients with 70 fractures were followed for a mean of 18.3 years (11 to 32). The original medical records and radiographs were studied and physical and radiological follow-up data analysed for evidence of risk factors for this injury. The development of avascular necrosis and osteoarthritis was determined from the follow-up radiographs and MR scans.

The impact of new military instructions on the management of hip-related pain was assessed following their introduction in 1986. The preventive regimen (1986) improved awareness and increased the detected incidence from 13.2 per 100 000 service-years (1970 to 1986) to 53.2 per 100 000 (1987 to 1990). No patient developed displacement of the fracture or avascular necrosis of the femoral head, or suffered from adverse complications. No differences were found in MRI-measured hip joint spaces at final follow-up. The mean Harris Hip Score was 97 (70 to 100) and the Visual Analogue Scale 5.85 mm (0 to 44).

Non-operative treatment, including avoidance of or reduced weight-bearing, gave favourable short- and long-term outcomes. Undisplaced fatigue fractures of the femoral neck neither predispose to avascular necrosis nor the subsequent development of osteoarthritis of the hip.

We used single-photon emission computed tomography (SPECT) to determine the long-term risk of degenerative change after reconstruction of the anterior cruciate ligament (ACL). Our study population was a prospective series of 31 patients with a mean age at injury of 27.8 years (18 to 47) and a mean follow-up of ten years (9 to 13) after bone-patellar tendon-bone reconstruction of the ACL. The contralateral normal knee was used as a control. All knees were clinically stable with high clinical scores (mean Lysholm score, 93; mean Tegner activity score, 6). Fifteen patients had undergone a partial meniscectomy and ACL reconstruction at or before reconstruction of their ACL.

In the group with an intact meniscus, clinical symptoms of osteoarthritis (OA) were found in only one patient (7%), who was also the only patient with marked isotope uptake on the SPECT scan compatible with OA. In the group which underwent a partial meniscectomy, clinical symptoms of OA were found in two patients (13%), who were among five (31%) with isotope uptake compatible with OA. Only one patient (7%) in this group had evidence of advanced OA on plain radiographs.

The risk of developing OA after ACL reconstruction in this series is very low and lower than published figures for untreated ACL-deficient knees. There is a significant increase (p < 0.05) in degenerative change in patients who had a reconstruction of their ACL and a partial meniscectomy compared with those who had a reconstruction of their ACL alone.

Little is known about the increase in length of tendons in postnatal life or of their response to limb lengthening procedures. A study was carried out in ten young and nine adult rabbits in which the tibia was lengthened by 20% at two rates 0.8 mm/day and 1.6 mm/day.

The tendon of the flexor digitorum longus (FDL) muscle showed a significant increase in length in response to lengthening of the tibia. The young rabbits exhibited a significantly higher increase in length in the FDL tendon compared with the adults. There was no difference in the amount of lengthening of the FDL tendon at the different rates. Of the increase in length which occurred, 77% was in the proximal half of the tendon.

This investigation demonstrated that tendons have the ability to lengthen during limb distraction. This occurred to a greater extent in the young who showed a higher proliferative response, suggesting that there may be less need for formal tendon lengthening in young children.

Treatment strategies for osteoarthritis most commonly involve the removal or replacement of damaged joint tissue. Relatively few treatments attempt to arrest, slow down or reverse the disease process. Such options include peri-articular osteotomy around the hip or knee, and treatment of femoro-acetabular impingement, where early intervention may potentially alter the natural history of the disease. A relatively small proportion of patients with osteoarthritis have a clear predisposing factor that is both suitable for modification and who present early enough for intervention to be deemed worthwhile. This paper reviews recent advances in our understanding of the pathology, imaging and progression of early osteoarthritis.

Articular cartilage repair remains a challenge to surgeons and basic scientists. The field of tissue engineering allows the simultaneous use of material scaffolds, cells and signalling molecules to attempt to modulate the regenerative tissue. This review summarises the research that has been undertaken to date using this approach, with a particular emphasis on those techniques that have been introduced into clinical practice, via in vitro and preclinical studies.

Bone-marrow oedema can occur both in isolation and in association with necrosis of bone, but it has not been shown whether each respond to the same methods of treatment.

We treated 16 patients with isolated oedema and 17, in which it was associated with necrosis of the proximal femur, with the prostacyclin derivative iloprost, which has been shown to be effective in the idiopathic form. The Harris hip score, the range of movement, the extent of the oedema as measured by MRI, pain on a visual analogue scale and patient satisfaction were recorded before and subsequent to treatment.

In both groups, we were able to show a significant improvement (p < 0.001) in these observations during the period of follow-up indicating that iloprost will produce clinical improvement in both circumstances.

In order to assess the efficacy of inspection and accreditation by the Specialist Advisory Committee for higher surgical training in orthopaedic surgery and trauma, seven training regions with 109 hospitals and 433 Specialist Registrars were studied over a period of two years.

There were initial deficiencies in a mean of 14.8% of required standards (10.3% to 19.2%). This improved following completion of the inspection, with a mean residual deficiency in 8.9% (6.5% to 12.7%.) Overall, 84% of standards were checked, 68% of the units improved and training was withdrawn in 4%.

Most units (97%) were deficient on initial assessment. Moderately good rectification was achieved but the process of follow-up and collection of data require improvement. There is an imbalance between the setting of standards and their implementation. Any major revision of the process of accreditation by the new Post-graduate Medical Education and Training Board should recognise the importance of assessment of training by direct inspection on site, of the relationship between service and training, and the advantage of defining mandatory and developmental standards.

The subject of central nervous system damage includes a wide variety of problems, from the slow selective ‘picking off’ of characteristic sub-populations of neurons typical of neurodegenerative diseases, to the wholesale destruction of areas of brain and spinal cord seen in traumatic injury and stroke. Experimental repair strategies are diverse and the type of pathology dictates which approach will be appropriate. Damage may be to grey matter (loss of neurons), white matter (cutting of axons, leaving neurons otherwise intact, at least initially) or both. This review will consider four possible forms of treatment for repair of the human central nervous system.

Despite worldwide clinical use of bio-absorbable devices for internal fixation in orthopaedic surgery, the degradation behaviour and tissue replacement of these implants are not fully understood.

In a long-term experimental study, we have determined the patterns of tissue restoration 36 and 54 months after implantation of polyglycolic acid and poly-laevo-lactic acid screws in the distal femur of the rabbit.

After 36 months in the polyglycolic acid group the specimens showed no remaining polymer and loose connective tissue occupied 80% of the screw track. Tissue restoration remained poor at 54 months, the amounts of trabecular bone and haematopoietic elements being significantly lower than those in the intact control group. The amount of trabecular bone within the screw track at 54 months in the polyglycolic acid group was less than in the empty drill holes (p = 0.04). In the poly-laevo-lactic acid group, polymeric material was present in abundance after 54 months, occupying 60% of the cross-section of the core area of the screw track.

When using absorbable internal fixation implants we should recognise that the degradation of the devices will probably not be accompanied by the restoration of normal trabecular bone.

We reviewed 29 patients who had undergone intercalary resection for malignant tumours. Of these, 14 had received segmental allograft reconstruction and 15 extracorporeally-irradiated autograft.

At a mean follow-up of 71 months (24 to 132), 20 were free from disease, five had died and four were alive with pulmonary metastases. Two patients, one with an allograft and one with an irradiated autograft, had a local recurrence. Reconstruction with extracorporeally-irradiated autograft has a significantly lower rate of nonunion (7% vs 43%, p = 0.031) but an insignificantly higher rate of fracture (20% vs 14%, p = 0.535) than that with segmental allograft. Using the Enneking functional evaluation system, the mean postoperative score for the patients without local recurrence was 87% (80% to 96%) and was similar in both groups.

Extracorporeally-irradiated autograft could be an acceptable alternative for reconstruction after intercalary resection, especially in countries where it is difficult to obtain allografts.