Obtain normal reference data for bone markers in human blood
Research type
Research Study
Full title
Collection of blood to obtain normal reference data to aid measurement of markers of bone formation and resorption in the clinical service.
IRAS ID
275462
Contact name
S F Evans
Contact email
Sponsor organisation
RJAH Orthopaedic Hospital NHS Foundation Trust
Duration of Study in the UK
0 years, 11 months, 31 days
Research summary
Summary of Research
The Metabolic Bone department is a clinical department of the Robert Jones and Agnes Hunt Orthopaedic Hospital (RJAH). Our patients have a range of metabolic bone disorders, however the majority have osteoporosis. Osteoporosis is a condition where the bones becomes fragile and can break easily. It is commonly linked to post-menopausal women; however men and younger women can be affected. The department has recently acquired a machine which measures two markers of bone turnover, one reflecting bone formation and the other bone breakdown. It is recommended that both these are measured to monitor how patients respond to treatment for osteoporosis. In order to know how our patients compare with the local healthy population we need to collect local reference data from healthy women, both pre- and post-menopausal, and men. These participants will need to be of a certain age and there will be a set of exclusion criteria. The study will be advertised locally and anyone who expresses an interest and fulfills the criteria will be sent an information sheet. Those then wanting to take part will be given an appointment at the RJAH. They will be seen by a nurse and asked to sign a consent form. The nurse will then take a sample of blood (approx. 4ml). The participant will then be free to leave. The blood sample will then be taken to the laboratory to be processed. The participant’s details will be recorded into a secure sample database. Each sample will be given an individual specimen ID. The blood samples will be spun in a centrifuge and the plasma removed and aliquoted into a clean tube, labelled with the specimen number and frozen. The remaining material will be destroyed. The study should last approximately 12 months.Summary of Results
The metabolic bone health laboratory at the Robert Jones & Agnes Hunt Orthopaedic Hospital NHS Foundation Trust recently obtained an automated machine (iSYS) to measure the bone formation marker PINP (amino-terminal propeptide of type I procollagen). We use this marker to help monitor patients on treatment for osteoporosis in our metabolic clinics.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. Each volunteer completed a health questionnaire and subjects were excluded if taking contraceptives, HRT, steroids or any drug known to affect bone metabolism. Subjects with known bone disease, a current or previous diagnosis of cancer or who had fractured in the last 6 months were also excluded from the study.
Analysis Method: 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 new results should be checked for outliers which should be removed, and new samples collected if required to ensure a comparison of at least 20 results. These results should be compared to the original reference interval and considered valid if at least 18 of the 20 tested values fall within the original stated reference interval limits.
Results: The data was skewed but outlier analysis indicated that there was only one outlier in the premenopausal group. This result was excluded from the analysis and no further samples were collected as we still had 20 samples in this group for analysis.
Our reference ranges in all three groups -pre-menopausal, post-menopausal, and males were compatible with published data so we are able to use these.Discussion:
Due to reduced pre-analytical variation in PINP, the differences between the previously published reference intervals and our study population does not result in significant differences in PINP levels. This means that the results can effectively and confidently be transferred to our population and no further analysis is required.Reference:
Clinical and Laboratory Standards Institute. How to define and determine reference intervals in the clinical laboratory: approved guideline – second edition. CLSI document C28-A2. Wayne, PA, USA: CLSI 2000.REC name
South West - Cornwall & Plymouth Research Ethics Committee
REC reference
20/SW/0075
Date of REC Opinion
5 May 2020
REC opinion
Favourable Opinion