METABOLIC MEDICINE AND BONE

In collaboration with Imperial College, London we are conducting a pilot study to assess gut microbiome diversity in 40 postmenopausal women. This study will compare individuals with high central obesity (WHtR >0.6) against those with healthy adiposity, evaluating links between gut microbial composition, bone turnover markers and DXA metrics.

The Rare Bone Disease Clinic, established in 2022–23, now provides access to burosumab for adults with X-linked hypophosphatemia (XLH), a rare, inherited disorder that causes phosphate wasting, leading to soft bones, skeletal deformities and chronic pain. Historically, treatment options for adults were limited, involving cumbersome regimens of phosphate and vitamin D, which were often poorly tolerated and of limited efficacy.

Burosumab is a novel monoclonal antibody therapy that directly targets the underlying molecular cause of XLH by inhibiting FGF23, thereby normalising phosphate levels in the body. Its introduction represents a significant shift in the standard of care, offering patients meaningful improvements in bone mineralisation, pain and mobility.

RJAH is now a registered national treatment centre for XLH and a member of the Rare Bone Disease Network. The initiation of burosumab therapy for our patients, including those with lived experience of both the condition and the healthcare system, marks a new era of patient-centred innovation in metabolic bone care.

TBS (Trabecular Bone Score) provides insight into bone microarchitecture and complements traditional DXA measurements of bone mineral density. As part of a collaborative agreement with Medimaps Group, our centre is undertaking studies to examine TBS in patients with obesity and diabetes, addressing gaps in existing clinical tools. Medimaps have supported the project through provision of two TBS software licenses and data processing tools. This allows enhanced analysis of spinal DXA images to quantify bone texture and microarchitectural degradation.

This initiative ensures that TBS is embedded into clinical care at RJAH and contributes valuable data for ongoing evaluation of fracture risk, particularly in individuals where standard BMD values may underestimate clinical fragility.

With support from the Michael Davie Foundation and the Orthopaedic Institute, we have successfully developed and deployed a secure, research-grade database that integrates clinical data, standard-of-care metrics and research observations. This new infrastructure replaces previous manual and paper-based systems, improving the accuracy and efficiency of data collection across patient pathways.

The database is already supporting a wide range of research projects including drug efficacy studies, frailty scoring, TBS analysis, and metabolic biomarker monitoring. It provides a scalable platform to integrate future data streams such as microbiome profiles and metabolomics, ensuring RJAH remains at the forefront of personalised care in metabolic bone disease.

We have recently installed a new state-of-the-art GE Healthcare DXA Prodigy scanner, significantly enhancing our diagnostic and research capabilities. A second scanner is due to be installed before the end of the year. These scanners allow for high-resolution imaging and full-body composition analysis, including fat mass, lean mass, and visceral adipose tissue distribution.

This upgrade enables:

• Improved throughput and scan quality for clinical care
• Routine collection of body composition data for research into obesity, sarcopenia, and fracture risk
• Integration of whole-body DXA data into ongoing studies, including OsBONE and microbiome/metabolomics projects

With these advanced systems, RJAH is positioned to become a national leader in DXA-based body composition research and continue its contribution to innovation in osteoporosis and metabolic bone health.

We are studying how treatments perform in real-world patients, especially:

• Romosozumab (anabolic agent)
• Teriparatide (anabolic agent)
• Zoledronate (anti-resorptive)

Our aim is to inform personalised prescribing based on comorbidities, age, and risk profiles. We have collected data on over 100 patients at baseline 6 and 12 months for a head-to-head comparison of the effect of these drugs on bone mineral density.  This data will inform future treatment strategies ensuring patients get the right treatment at the right time.

A long-term, ethically approved observational study is underway to explore the impact of:

• Obesity
• Type 2 diabetes
• Sarcopenia
• Frailty

Data is collected using blood, urine, stool samples, CT/MRI imaging, and integrated clinical/research records. The aim is to identify fracture risk markers and inform personalised care.

• Ultra-low freezer (-80°C) for sample storage
• 4 iPads for real-time patient data entry
• Grip power dynamometers for physical assessment

C Rakieh, JH Kuiper, C Mennan, D Powell, S Ho  K Javaid. Central obesity measured by waist to height ratio vs. BMI-derived obesity as predictors of fracture risk: A retrospective cohort study from Oswestry, UK. BRS Edinburgh 2025.

C Rakieh, D Powell, T Roberts, J Cole, S Ho, B Tins & C Mennan. Romosozumab vs. teriparatide: Evaluating early bone mineral density gains at six months in real-world practice from Oswestry, UK. ECTS 2025.

C Rakieh, C Mennan, S Ho, T Roberts, J Cole, B Tins, D Powell^. Romosozumab Improves Bone Microarchitecture Measured By Tissue Thickness-Adjusted Trabecular Bone Score At Six Months: A Real-world Study From Oswestry, Uk. IOF 2025.

C Rakieh, D Powell, C Mennan, B Tins, T Roberts, MK Javaid. The Relationship Between Central Adiposity Measured by Waist to Height Ratio, BMI Obesity, and Recent Osteoporotic Fracture: A Cross-Sectional Study. WCO-IOF-ESCEO Congress 2024, London.

S Sakib Saadi, R Das, A M Ullas, D Powell , E Wilson, I Myrtziou, C Rakieh* and I Kanakis (*joint last author). Impact of Different Anti-Hyperglycaemic Treatments on Bone Turnover Markers and Bone Mineral Density in Type 2 Diabetes Mellitus Patients: A Systematic Review and Meta-Analysis. International Journal of Molecular Sciences, 2024.

A Sagdeo, M Elshehawy, C Rakieh, P Ball, H Morrissey. Severe hypocalcaemia and hypophosphatemia following Denosumab administration in a multi-comorbidity patient. Medicine and Pharmacy Reports, DOI: 10.15386/mpr-2722. 2024.

C Rakieh, T Roberts, J Cole, MK Javaid, B Tins, C Mennan, D Powell. Previous Antiresorptive Therapy and Baseline serum PINP as Indicators of Six-month Bone Mineral Density Response to Romosozumab: Real world Data from a Metabolic Bone Service in England. WCO-IOF-ESCEO Congress 2024, London.

C Rakieh, S Ho, D  Powell, L Maung, T Roberts, C Mennan.
Clinical Frailty is Associated with a Previous Hip, Vertebral, and all Fracture plus Type 2 Diabetes: A Cross Sectional Study of a UK Older Population. ECTS 2024.

D Powell, S Evans, C Rakieh. Bone mineral density response to long-term bisphosphonate treatment and discontinuation in a real-world clinical service. Endoc Pract.2023.