In a recent phase 2 superiority clinical trial we demonstrated that a single dose of 60mg of the human monoclonal antibody denosumab inhibits osteolytic lesion activity in patients undergoing revision total hip arthroplasty (THA), demonstrating proof of biological efficacy for this clinical application. Here, we examined the effect that denosumab has on disease biology at the osteolysis tissue level.

Osteolytic tissue taken from the prosthesis-bone lesion interface at revision surgery in patients with osteolysis (n=10 participants that had received a single 60 mg dose of denosumab 8 weeks prior to revision surgery and n=10 that had received placebo) was examined for total genetic message activity and protein levels using whole genome sequencing and mass spectrometry, respectively.

The top five upregulated enriched pathways with denosumab treatment included inflammatory response, myeloid cell activation, myeloid leukocyte migration, neutrophil and granulocyte activation (p<6.26 × 10⁻²⁸). Cell morphogenesis was amongst the most downregulated pathways (p<3.42 ×10⁻²³). Finally, comparison of the trial mRNA and protein data versus mouse single cell RNA sequencing data of the same pathway blockade in mouse tibia showed the same direction of effect, suggesting that giving the drug causes then cells responsible for osteolysis to disperse into a more immature form (128 of 189 genes (z=4.87, P<0.0001) disease and functional pathways at the mRNA level and 10 of 11 (z=2.72, P=0.0065) at the protein level).

In this first-in-man study we identify multiple genes and pathways within periprosthetic osteolysis tissue that are affected by denosumab treatment. The dominant pathways involved upregulation of innate inflammatory signaling and downregulation of cell morphogenesis. We also found enrichment of similar disease and functional pathways at both the mRNA and protein levels versus mRNA pathway enrichment found in mouse osteomorphs. These data provide the first human data of the mechanistic effect of denosumab treatment on inflammatory osteolytic lesion activity after joint replacement that is necessary to support its clinical application.

∗Winner of The Bone & Joint Journal prize∗

Introduction: The HRG 4 coding system was introduced in April 2009 to allow the calculation of tariffs for all surgical procedures. At our institution we felt surgeon input could improve the accuracy of this coding and optimise trust income.

Method: A retrospective audit of one month’s procedures under the care of a single consultant was performed. The hospitals coding and tariff, as performed by coding clerks, was reviewed and the procedures were re-coded by a foot and ankle fellow using the notes and the HRG 4 grouper. A comparison was made between the coding and income generated in the standard fashion and that achieved after optimisation by surgeon input.

Results: The codes of 51 patients were examined. 86% of major foot procedures were correctly coded. However, 56% of ‘minor’ procedures were recoded as ‘intermediate’, many of these involving hallux valgus surgery. 58% of procedures had a different code after surgeon input and 41% generated a different tariff. The total tariff for the coding clerk group was £79,192. The total tariff in the surgeon assessed group was £97,268 - a difference of £18,076. Extrapolated over the year this could represent a potential gain of over £200,000, for a single Consultant in a single Trust.

Conclusion: We believe surgeon involvement in coding is crucial to improve accuracy and to optimise trust income. We will discuss various issues surrounding the new HRG 4 codes and how best to use them in current practice.