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.

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.

Using a dynamic biomechanical model of malunion of the shoulder, we have determined the change in deltoid force required for abduction with various combinations of superior and posterior displacement of fractures of the greater tuberosity of the humerus. We tested eight fresh human cadaver shoulders in a dynamic shoulder-testing apparatus during cycles of glenohumeral abduction from 0° to 90°. The greater tuberosities were osteotomised and stabilised to represent malunion with combinations of superior and posterior displacements of 1 cm and less. The peak force was measured for each displacement in each specimen and statistically compared with values of no displacement using a repeated-measures analysis of variance.

The abduction force was significantly increased by 16% (p = 0.006) and 27% (p = 0.0001) by superior displacements of 0.5 cm and 1 cm, respectively, while combined superior and posterior displacement of 1 cm gave an increase in force of 29% (p = 0.001). While treatment criteria for acceptable residual displacement of the greater tuberosity are widely used, there is little information on the direct biomechanical effects of displacement on shoulder mechanics. Although the results of conservative treatment are influenced by a number of factors, including associated injuries, rehabilitation and the pre-existing function of the shoulder, our data suggest that small amounts of residual displacement may alter the balance of forces required to elevate the arm at the glenohumeral joint.

In impaction grafting of contained bone defects after revision joint arthroplasty the graft behaves as a friable aggregate and its resistance to complex forces depends on grading, normal load and compaction. Bone mills in current use produce a distribution of particle sizes more uniform than is desirable for maximising resistance to shear stresses.

We have performed experiments in vitro using morsellised allograft bone from the femoral head which have shown that its mechanical properties improve with increasing normal load and with increasing shear strains (strain hardening). The mechanical strength also increases with increasing compaction energy, and with the addition of bioglass particles to make good the deficiency in small and very small fragments. Donor femoral heads may be milled while frozen without affecting the profile of the particle size. Osteoporotic femoral heads provide a similar grading of sizes, although fewer particles are obtained from each specimen. Our findings have implications for current practice and for the future development of materials and techniques.