Implantation of allograft bone is an integral part of revision surgery of the hip. One major concern with its use is the risk of transmission of infective agents. There are a number of methods of processing allograft bone in order to reduce this risk. One method requires washing the tissue using pulsed irrigation immediately before implantation. We report the incidence of deep bacterial infection in 138 patients (144 revision hip arthroplasties) who had undergone implantation of allograft bone. The bone used was fresh-frozen, non-irradiated and pulse-washed with normal saline before implantation. The deep infection rate at a minimum follow-up of one year was 0.7%. This method of processing appears to be associated with a very low risk of allograft-related bacterial infection.

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.

The efficacy of β-tricalcium phosphate (β-TCP) loaded with bone morphogenetic protein-2 (BMP-2)-gene-modified bone-marrow mesenchymal stem cells (BMSCs) was evaluated for the repair of experimentally-induced osteonecrosis of the femoral head in goats.

Bilateral early-stage osteonecrosis was induced in adult goats three weeks after ligation of the lateral and medial circumflex arteries and delivery of liquid nitrogen into the femoral head. After core decompression, porous β-TCP loaded with BMP-2 gene- or β-galactosidase (gal)-gene-transduced BMSCs was implanted into the left and right femoral heads, respectively. At 16 weeks after implantation, there was collapse of the femoral head in the untreated group but not in the BMP-2 or β-gal groups. The femoral heads in the BMP-2 group had a normal density and surface, while those in the β-gal group presented with a low density and an irregular surface. Histologically, new bone and fibrous tissue were formed in the macropores of the β-TCP. Sixteen weeks after implantation, lamellar bone had formed in the BMP-2 group, but there were some empty cavities and residual fibrous tissue in the β-gal group. The new bone volume in the BMP-2 group was significantly higher than that in the β-gal group. The maximum compressive strength and Young’s modulus of the repaired tissue in the BMP-2 group were similar to those of normal bone and significantly higher than those in the β-gal group.

Our findings indicate that porous β-TCP loaded with BMP-2-gene-transduced BMSCs are capable of repairing early-stage, experimentally-induced osteonecrosis of the femoral head and of restoring its mechanical function.

Heterotopic ossification following joint replacement in the lower limb occurs in 3% to 90% of cases. Higher grades of heterotopic ossification can result in significant limitation of function and can negate the benefits of joint replacement. The understanding of the pathophysiology of this condition has improved in recent years. It would appear to be related to a combination of systemic and local factors, including over-expression of bone morphogenetic protein-4. There is currently little evidence to support the routine use of prophylaxis for heterotopic ossification in arthroplasty patients, but prophylaxis is recommended by some for high-risk patients. Radiotherapy given as one dose of 7 Gy to 8 Gy, either pre-operatively (< four hours before) or post-operatively (within 72 hours of surgery), appears to be more effective than indometacin therapy (75 mg daily for six weeks). In cases of prophylaxis against recurrent heterotopic ossification following excision, recent work has suggested that a combination of radiotherapy and indometacin is effective. Advances in our understanding of this condition may permit the development of newer, safer treatment modalities.

The literature on fracture repair has been reviewed. The traditional concepts of delayed and nonunion have been examined in terms of the phased and balanced anabolic and catabolic responses in bone repair. The role of medical manipulation of these inter-related responses in the fracture healing have been considered.

Osteonecrosis of the knee comprises two separate disorders, primary spontaneous osteonecrosis which is often a self-limiting condition and secondary osteonecrosis which is associated with risk factors and a poor prognosis. In a series of 61 knees (38 patients) we analysed secondary osteonecrosis of the knee treated by a new technique using multiple small percutaneous 3 mm drillings.

Total knee replacement was avoided in 59 knees (97%) at a mean follow-up of 3 years (2 to 4). Of the 61 knees, 56 (92%) had a successful clinical outcome, defined as a Knee Society score greater than 80 points. The procedure was successful in all 24 knees with small lesions compared with 32 of 37 knees (86%) with large lesions. All the procedures were performed as day cases and there were no complications. This technique appears to have a low morbidity, relieves symptoms and delays more invasive surgery.

The effect of zoledronic acid on bone ingrowth was examined in an animal model in which porous tantalum implants were placed bilaterally within the ulnae of seven dogs. Zoledronic acid in saline was administered via a single post-operative intravenous injection at a dose of 0.1 mg/kg. The ulnae were harvested six weeks after surgery. Undecalcified transverse histological sections of the implant-bone interfaces were imaged with backscattered scanning electron microscopy and the percentage of available pore space that was filled with new bone was calculated. The mean extent of bone ingrowth was 6.6% for the control implants and 12.2% for the zoledronic acid-treated implants, an absolute difference of 5.6% (95% confidence interval, 1.2 to 10.1) and a relative difference of 85% which was statistically significant. Individual islands of new bone formation within the implant pores were similar in number in both groups but were 69% larger in the zoledronic acid-treated group. The bisphosphonate zoledronic acid should be further investigated for use in accelerating or enhancing the biological fixation of implants to bone.

Critical size defects in ovine tibiae, stabilised with intramedullary interlocking nails, were used to assess whether the addition of carboxymethylcellulose to the standard osteogenic protein-1 (OP-1/BMP-7) implant would affect the implant’s efficacy for bone regeneration. The biomaterial carriers were a ‘putty’ carrier of carboxymethylcellulose and bovine-derived type-I collagen (OPP) or the standard with collagen alone (OPC). These two treatments were also compared to “ungrafted” negative controls. Efficacy of regeneration was determined using radiological, biomechanical and histological evaluations after four months of healing. The defects, filled with OPP and OPC, demonstrated radiodense material spanning the defect after one month of healing, with radiographic evidence of recorticalisation and remodelling by two months. The OPP and OPC treatment groups had equivalent structural and material properties that were significantly greater than those in the ungrafted controls. The structural properties of the OPP- and OPC-treated limbs were equivalent to those of the contralateral untreated limb (p > 0.05), yet material properties were inferior (p < 0.05). Histopathology revealed no residual inflammatory response to the biomaterial carriers or OP-1. The OPP- and OPC-treated animals had 60% to 85% lamellar bone within the defect, and less than 25% of the regenerate was composed of fibrous tissue. The defects in the untreated control animals contained less than 40% lamellar bone and more than 60% was fibrous tissue, creating full cortical thickness defects. In our studies carboxymethylcellulose did not adversely affect the capacity of the standard OP-1 implant for regenerating bone.

Systemic factors are believed to be pivotal for the development of heterotopic ossification in severely-injured patients. In this study, cell cultures of putative target cells (human fibroblastic cells, osteoblastic cells (MG-63), and bone-marrow stromal cells (hBM)) were incubated with serum from ten consecutive polytraumatised patients taken from post-traumatic day 1 to day 21 and with serum from 12 healthy control subjects.

The serum from the polytraumatised patients significantly stimulated the proliferation of fibroblasts, MG-63 and of hBM cells. The activity of alkaline phosphatase in MG-63 and hBM cells was significantly decreased when exposed to the serum of the severely-injured patient. After three weeks in 3D cell cultures, matrix production and osteogenic gene expression of hBM cells were equal in the patient and control groups. However, the serum from the polytraumatised patients significantly decreased apoptosis of hBM cells compared with the control serum (4.3% vs 19.1%, p = 0.031).

Increased proliferation of osteoblastic cells and reduced apoptosis of osteoprogenitors may be responsible for increased osteogenesis in severely-injured patients.

We used a canine intercalary bone defect model to determine the effects of recombinant human osteogenic protein 1 (rhOP-1) on allograft incorporation. The allograft was treated with an implant made up of rhOP-1 and type I collagen or with type I collagen alone.

Radiographic analysis showed an increased volume of periosteal callus in both test groups compared with the control group at weeks 4, 6, 8 and 10. Mechanical testing after 12 weeks revealed increased maximal torque and stiffness in the rhOP-1 treated groups compared with the control group.

These results indicate a benefit from the use of an rhOP-1 implant in the healing of bone allografts. The effect was independent of the position of the implant. There may be a beneficial clinical application for this treatment.