Understanding the effects of bisphosphonates on bone mineral chemistry and atypical femoral fracture in East London

Osteoporosis causes fragile bones and painful fractures in millions of people worldwide. Bisphosphonate drugs are widely prescribed to reduce fracture risk, but some patients who take them long-term develop catastrophic atypical femoral fractures (AFFs). These breaks are disproportionately common in women of Asian backgrounds. This disparity is directly relevant in diverse regions such as East London where large numbers of patients from these communities receive long-term bisphosphonate treatment.

We believe AFFs occur because bisphosphonates alter bone mineral chemistry at the molecular scale. Our preliminary research in patients with a rare condition in which the body accumulates a molecule chemically similar to bisphosphonates showed, using solid-state nuclear magnetic resonance (SSNMR) spectroscopy and electron microscopy, that this changes how bone mineral forms, generating an abnormally crystalline, brittle structure. This project will test whether bisphosphonate drugs cause the same changes in patients.

You will study bone tissue from diverse AFF patients, developing expertise in state-of-the-art physical sciences technologies including SSNMR, electron microscopy and small-angle X-ray scattering (SAXS). You will also use synthetic bone mineral and cell culture systems to investigate how bisphosphonates alter mineral chemistry and its interaction with the collagen matrix. This is an interdisciplinary project and you will collaborate with clinicians, biologists, chemists and physicists, acquiring a broad and highly distinctive skillset.

Year 1: Optimise the synthetic bone mineral model with a range of bisphosphonate drugs and characterise their effects on early mineral phase formation by SSNMR, electron microscopy and SAXS.

Year 2: Generate isotopically labelled osteoblast cell culture samples to investigate bisphosphonate-induced changes in bone mineral–collagen intermolecular interactions by SSNMR.

Year 3: Characterise bone mineral molecular structure in AFF patient samples using SSNMR, electron microscopy and SAXS.

Year 4: Perform subgroup analyses correlating bone mineral structure with bisphosphonate treatment status and ethnic background across the patient cohort.