Osteosarcoma is the most common primary malignancy of bone. It arises in bone during periods of rapid growth and primarily affects adolescents and young adults. The 5-year survival rate for osteosarcoma is 60%–70%, with no significant improvements in prognosis since the advent of multiagent chemotherapy. Diagnosis, staging, and surgical management of osteosarcoma remain focused on our anatomical understanding of the disease. As our knowledge of the molecular pathogenesis of osteosarcoma expands, potential therapeutic targets are being identified. A comprehensive understanding of these mechanisms is essential if we are to improve the prognosis of patients with osteosarcoma through tumour-targeted therapies. This paper will outline the pathogenic mechanisms of osteosarcoma oncogenesis and progression and will discuss some of the more frontline translational studies performed to date in search of novel, safer, and more targeted drugs for disease management.

The biological roles of PEDF are diverse and multidimensional. As an anti-cancer agent, PEDF has great potential as a focused anti-neoplastic therapy against a variety of tumor types.

With concurrent advances in the fields of molecular biology, pathology and advanced imaging, osteoclast-targeted therapies show great potential for treating conditions in which excess resorption of bone is a key pathological process. Targeting of osteoclast control mechanisms offers the potential of combining 'molecular imaging' with therapeutic intervention and longitudinal monitoring of disease processes.

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Background:Pigment epithelium-derived factor (PEDF) is an endogenous glycoprotein with a potential role as a therapeutic for osteosarcoma. Animal studies have demonstrated the biological effects of PEDF on osteosarcoma; however, these results are difficult to extrapolate for human use due to the chosen study design and drug delivery methods.Methods:In this study we have attempted to replicate the human presentation and treatment of osteosarcoma using a murine orthotopic model of osteosarcoma. The effects of PEDF on osteosarcoma cell lines were evaluated in vitro prior to animal experimentation. Orthotopic tumours were induced by intra-tibial injection of SaOS-2 osteosarcoma cells. Treatment with PEDF was delayed until after the macroscopic appearance of primary tumours. Pigment epithelium-derived factor was administered systemically via an implanted intraperitoneal micro-osmotic pump.Results:In vitro, PEDF inhibited proliferation, induced apoptosis and inhibited cell cycling of osteosarcoma cells. Pigment epithelium-derived factor promoted adhesion to Collagen I and inhibited invasion through Collagen I. In vivo, treatment with PEDF caused a reduction in both primary tumour volume and burden of pulmonary metastases. Systemic administration of PEDF did not cause toxic effects on normal tissues.Conclusion:Systemically delivered PEDF is effective in suppressing the size of primary and secondary tumours in an orthotopic murine model of osteosarcoma.

Hamstring tendon autografts are used for reconstruction of the anterior cruciate ligament. This study tested the hypothesis that a 5-strand hamstring autograft construct is superior in strength to a 4-strand construct. Four-strand and 5-strand tendon grafts constructs were prepared from ovine flexor tendons and then tested in a uniaxial electromechanical load system with suspensory fixation. The 4-strand and 5-strand constructs were pre-conditioned, stress-relaxed and loaded to ultimate failure. Stress-relaxation, stiffness and ultimate load were compared using a one-way ANOVA. There were no statistical differences in stress-relaxation, initial stiffness, secondary stiffness or ultimate load between 4-strand and 5-strand split tendon graft constructs. Inconsistent failure patterns for both 4-strand and 5-strand constructs were observed. The additional strand in the 5-strand construct may be shielded from stress with additional weakness secondary to the use of suspensory fixation. The potential biological benefit of religamentization and bony integration, with more autologous tissue in the intra-articular space and bony tunnels remains unknown.

The non-English-speaking background of a patient is a predictor of less favourable functional outcome after TKA.

First discovered in 1991 as a factor secreted by retinal pigment epithelial cells, the potency of pigment epithelium derived factor (PEDF) as an anti-angiogenic has led to examination of its role in active bone growth, repair and remodelling. In the musculoskeletal system, PEDF expression occurs particularly at sites of active bone formation. Expression has been noted in osteoblasts and to a lesser degree osteoclasts, the major classes of bone cells. In fact, PEDF is capable of inducing differentiation of precursor cells into mature osteoblasts. Expression and localisation are closely linked with that of vascular endothelial growth factor (VEGF). Studies at the epiphyseal plate have revealed that PEDF expression plays a key role in endochondral ossification, and beyond this may account for the epiphyseal plate's innate ability to resist neoplastic cell invasion. Collagen-1, the major protein in bone, is avidly bound by PEDF, implicating an important role played by this protein on PEDF function, possibly through MMP-2 and -9 activity. Surprisingly, the role of PEDF has not been evaluated more widely in bone disorders, so the challenge ahead lies in a more diverse evaluation of PEDF in various osteologic pathologies including osteoarthritis and fracture healing.