Karl Lindberg - Institutionen för kliniska vetenskaper, Lund

Title: Improved bone-healing through biomodulation using bioactive molecules: Preclinical and clinical studies

Main supervisor: Magnus Tägil

Reviewers: Pär Swärd, Neserin Ali, Emanuel Larsson

Abstract

Background

Failed bone healing remains a challenge in hand surgery. However, the overall burden of non-union in small-joint arthrodesis of the hand is poorly defined due to limited scientific investigation. Successful bone healing requires reliable fixation of the osteosynthesis material. Preclinical work from our group has shown that biomodulation with bisphosphonates and hydroxyapatite have the potential to enhance bone regeneration and improve implant anchorage. Clinical translation of these findings is warranted.

Research questions

• What are the non-union rates, complication patterns, and potential risk factors following elective small-joint arthrodesis in the hand?
• Can local biomodulation using a calcium sulphate/hydroxyapatite (CaS/HA) carrier combined with zoledronic acid (ZA) and/or recombinant human bone morphogenetic protein-2 (rhBMP-2) improve metaphyseal bone healing and screw fixation in a rat model?
• Does systemic administration of a ZA improve screw fixation in the same metaphyseal fracture model?
• Can ZA-enhanced screw fixation be safely applied in distal interphalangeal (DIP) joint arthrodesis in humans, and does it show signs of improved anchorage and fusion?

Preliminary results

A retrospective cohort of 366 small-joint arthrodesis showed a non-union rate of 5.5%, few major complications, and no clear patient- or surgery-related risk factors for non-union. Hardware-related symptoms were common.

In a preclinical study, local biomodulation using CaS/HA with ZA and/or rhBMP-2 markedly increased peri-implant bone and improved mechanical screw fixation in a rat metaphyseal fracture model.

In a second preclinical study, systemic ZA increased peri-implant bone and enhanced intramedullary screw anchorage.

Together, these findings support translation to a pilot clinical study of ZA-augmented DIP arthrodesis.

Significance

This project combines retrospective clinical data, preclinical studies, and an upcoming pilot trial to address a clinically relevant problem: improving bone healing through augmented implant/screw anchorage. Successful translation of these findings may  enable  more  reliable  arthrodesis  and  osteosynthesis techniques, reduce reoperation rates, and provide a foundation for future adequately powered clinical trials.

Studies and manuscripts

• Retrospective study on union rates, complications, and risk factors in small-joint arthrodesis: manuscript completed and ready for submission.
• Two preclinical studies on ZA-based biomodulation of screw fixation: experimental work completed; manuscripts in preparation.
• Clinical pilot study of ZA-augmented DIP arthrodesis: preparation ongoing.