METABOLIC MEDICINE AND BONE

Metabolic Bone Clinical Service

Clinical Lead: Dr Chadi Rakieh

The metabolic bone service has members of staff working in the laboratory, the bone density unit, the day case unit as well as patient clinics. Staffing is made up of a consultant, speciality doctors, specialist nurses, clinical scientist, metabolic technician, radiographers, DXA technician and HCAs. In 2022 we scanned over 8800 patients and over 1400 patients received intravenous treatment for their bones.

In the laboratory over 1800 patient samples were analysed for the bone resorption marker urinary N-telopeptide crosslink of type I collagen (uNTx), a long-established marker of bone breakdown as part of the clinical service. The marker is used to monitor treatment efficacy, monitor treatment holidays and to determine baseline bone turnover.

Funding from RJAH charitable funds in 2019 allowed us to instal an IDS (Immunodiagnostic Systems Ltd) iSYS speciality automated immunoassay analyser – see Figure 1 & 2. We currently use this to measure the bone formation marker PINP (total procollagen type-1 N-terminal propeptide) in patients attending our outpatient clinics (plasma from a blood sample). Measuring this marker gives us a more complete assessment of bone status in our patients and improves the precision of our clinical decisions including assessing patients on anabolic therapy (parathyroid hormone), whose use is growing in clinical practice. We measured just over 1000 samples for PINP in 2022 and 2750 in total by the end of 2022.

We presented data at the Osteoporosis Online Conference in December 2020 on the use of PINP below the premenopausal reference mean as a useful treatment target for patients on anti-osteoporosis treatment [1]. We showed that 87% of untreated patients with osteoporosis had a PINP level above this target while only 7% of patients treated with IV bisphosphonate were above the treatment target.

With funding from the Orthopaedic Institute, we were able to measure a reference range of pre- and post-menopausal women and of men to compare our local population with that of other groups. We had been using the manufacturer’s reference range to identify patients with high PINP levels but the reference range was much wider than other published reference ranges. We collected data from a total of 62 volunteers – 20 males aged 50-77 years, 21 premenopausal females aged 30-45 years and 21 postmenopausal females aged 50-61 years. Samples were collected in plasma in a non-fasting state. As described in the CSLI guideline C28-A2 a previously established reference range can be validated using 20 results from a new laboratory using the same technique.

The results were compared to the published reference intervals and considered valid if no more than 2 out of the 20 tested values fell outside the original stated reference interval limits.

Due to reduced pre-analytical variation in PINP the differences between the previously published reference intervals and our study population did not result in significant differences in PINP levels. This meant that the reference intervals can effectively be transferred to our population and no further analysis was required. This means we now use a more specific reference ranges for male, pre- and post-menopausal females.

We also presented data on bone microarchitecture in liver cirrhosis at the Osteoporosis Online Conference [2]. We can analyse data from the bone density scans of the lumbar spine to produce a trabecular bone score (TBS) which is an index of microarchitecture and is validated as an independent risk factor for fracture. We were able to show that patients with liver cirrhosis had a lower TBS score than controls matched for age, sex, BMI and lumbar spine bone density. Compromised bone quality may have an important role in the aetiology of metabolic bone disorder associated with chronic liver disease.

Published Abstracts:

1. Powell DE, Evans SF, Rakieh C (2020) Evaluation of treatment target response in real-world clinical service. Therapeutic Advances in Musculoskeletal Disease 12; 7-8.
2. Rakieh C, Silva S, Roberts T, Powell DE, Ho S, Butler R (2020) Trabecular bone score as a risk factor of bone disease in liver cirrhosis. Therapeutic Advances in Musculoskeletal Disease 12; 40-41