Research

***CORTEX: Catching Osteoporosis on Routine computed Tomography as an added EXtra (application pdf with hyperlinks here). This idea was selected from over 600 applications to receive 2014 NHS Innovation funding . It means that we can diagnose and treat osteoporosis in the routine NHS imaging service while still conducting our basic research programme. Our new new team member Polly Barnes is now routinely diagnosing osteoporosis in men and women undergoing clinical CT for other reasons. One in every five high risk patients that she tests turns out to have previously unrecognised osteoporosis in the spine, hip or both sites. Click here for an interesting article in the magazine Science explaining translational research***

Research in the bone group focuses on osteoporotic fragility fractures and osteoarthritis by examining bone structure, shape and biology in health and disease. As part of a team lead by imaging experts Graham Treece and Andrew Gee from the University Engineering department, we developed a way of assessing the 3D structure and shape of cortical bone structure in life called Bone Mapping (BM). We have used BM, histology and microCT to discover that there are defined patches of focal osteoporosis in older people’s femurs that predispose them to hip fracture. Bone mapping measurements from clinical CT predict hip fracture well. Analysing separate clinical trials, we found that teriparatide PTH1-34 and denosumab anti-RANK ligand antibody treatment of osteoporotic women improved bone in patches of the femur at risk of fracture. Older men undertaking high impact exercise (the HIPHOP study) also responded well, with patches of the proximal femur thickening on CT.

Evelyn Trust funding allowed us to purchase the UK’s first high resolution Xtreme CT scanner, and have supported clinical radiology researcher Dr Tom Turmezei to carry forward our shape and image analysis techniques into the field of osteoarthritis. He has published two key papers on the assessment of hip osteoarthritis with novel CT techniques.

Within the Department of Medicine, we represent the Division of Rheumatology and within Cambridge NIHR Biomedical Research Centre we represent the 'Metabolism, Endocrinology and Bone'  theme.

Our HTA licenced laboratory offers a full in-house histomorphometry service for the investigation of bone diseases, under the direction of Dr Linda Skingle. We specialise in hard tissue histomorphometry, embedding samples in LR white resin, applying various stains and then using Surveyor & Bioquant software for quantification purposes. Our long standing collaboration with local experts Objective Imaging has recently lead to our installation of an Oasis glide scanning stage to our Nikon Eclipse E800 microscope.

We have parallel interests in histological and high resolution CT analysis of bone, as well as osteocyte signals and their role in skeletal regulation. We collaborate with scientists from MRC Human Nutrition Research in Cambridge (Dr Kate Ward) and the Wellcome Trust DINAG consortium at Bristol University (Prof. Jon Tobias, Dr Celia Gregson) to study the bone phenotype and genotype of volunteer patients who have very high bone mass. We also collaborate with the AGES-Reykjavik study team (Iceland, Prof. Gunnar Sigurdsson and Fjóla Jóhannesdóttir), Melbourne Dental School (Australia, Prof. John Clement and Mr David Thomas) and Charles University (Czech Republic, Prof. Jan Štepán) on translational research involving novel imaging techniques. Most recently we teamed up with Dr Katherine Brooke-Wavell and the sports scientists at Loughborough University to study the effects of short bursts of hopping exercise on the hip bones of older male volunteers, supported by an Innovation award from the National Osteoporosis Society.

We make use of the Wellcome Trust Clinical Research Facility (WTCRF) for our clinical studies. Our clinical trials research includes an investigator-led  proof of concept study demonstrating that a single dose of intravenous zoledronate prevents bone loss after stroke.

New team member Ilya Burkov MSc Nanomedicine, BEng Medical Engineering, was recently awarded the Adrian J Crisp PhD studentship and will be with us for 3 years. Ilya joined us from Swansea, his MSc involving the study of cellular mediators in osteoarthritis. Information on the studentship is available here . In addition Dr Toni Rikkonen PhD joined us as visiting Research associate for 18 months working on muscle responses to exercise in older adults, supported by the Sybil Eastwood Memorial Trust and Sigrid Juselius Foundation of Finland.

Arthritis Research UK, the Medical Research Council, the Evelyn Trust, the National Osteoporosis Society, Addenbrooke's Charitable Trust and the Cambridge NIHR Biomedical Research Centre support our current research program.

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Selected Publications

Bone Mapping work in Osteoporosis

• Whitmarsh T, Treece GM, Gee AH, Poole KE. JBMR MS#M14080587.R1 Mapping Bone Changes at the Proximal Femoral Cortex of Postmenopausal Women in Response to Alendronate and Teriparatide Alone, Combined or Sequentially. J Bone Miner Res. 2015 in press. http://www.ncbi.nlm.nih.gov/pubmed/25639838
• Poole KE, Treece GM, Gee AH, Brown JP, McClung MR, Wang A, et al. Denosumab rapidly increases cortical bone in key locations of the femur: a 3D bone mapping study in women with osteoporosis. J Bone Miner Res. 2015; 30(1): 46-54.http://www.ncbi.nlm.nih.gov/pubmed/25088963

Sclerostin work

• Gregson CL, Poole KE, McCloskey EV, Duncan EL, Rittweger J, Fraser WD, et al. Elevated circulating sclerostin concentrations in individuals with High Bone Mass, with and without LRP5 mutations. J Clin Endocrinol Metab. 2014: jc20133958. http://www.ncbi.nlm.nih.gov/pubmed/24606091
• Power J, Poole KE, van Bezooijen R, Doube M, Caballero-Alias AM, Lowik C, Papapoulos S, Reeve J, Loveridge N. Sclerostin and the regulation of bone formation: Effects in hip osteoarthritis and femoral neck fracture. J Bone Miner Res 2010; 25:1867-1876. http://www.ncbi.nlm.nih.gov/pubmed/20200987 45 citations (April 2015)
• Poole KE, van Bezooijen RL, Loveridge N, Hamersma H, Papapoulos SE, Lowik CW, Reeve J. Sclerostin is a delayed secreted product of osteocytes that inhibits bone formation. Faseb J 2005; 19:1842-1844. http://www.ncbi.nlm.nih.gov/pubmed/16123173 427 citations (April 2015)

Osteoarthritis imaging work

• Turmezei TD, Lomas DJ, Hopper MA, Poole KE. Severity mapping of the proximal femur: a new method for assessing hip osteoarthritis with computed tomography. Osteoarthritis and cartilage. 2014; 22(10): 1488-98.http://www.ncbi.nlm.nih.gov/pubmed/24631578
• Turmezei TD, Fotiadou A, Lomas DJ, Hopper MA, Poole KE. A new CT grading system for hip osteoarthritis. Osteoarthritis and cartilage 2014; 22(10): 1360-6. http://www.ncbi.nlm.nih.gov/pubmed/24642349

 

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