Skip to content

Advertisement

BMC Musculoskeletal Disorders

What do you think about BMC? Take part in

Open Access

Bone marker reference range study: a comparison of the manufacturer’s reference range and laboratory healthy volunteer results to patients with rheumatoid arthritis

  • Gillian Wheater1Email author,
  • Mohsen Elshahaly2,
  • Stephen P Tuck2, 3,
  • John Drury1 and
  • Jaap M van Laar2, 3
BMC Musculoskeletal Disorders201314(Suppl 1):A3

https://doi.org/10.1186/1471-2474-14-S1-A3

Published: 14 February 2013

Background

Biochemical markers of bone turnover have been used in research for a long time and are now being recognised as helpful tools in the clinical management of bone disease. It is important to establish robust reference values for the interpretation of these markers. In addition to standardising pre-analytical variability it is unclear whether manufacturer’s ranges take into account global differences between subjects and so each laboratory should investigate the transferability of the expected values to its own patient population and if necessary determine its own reference ranges.

Materials and methods

Serum samples from 70 healthy volunteers were analysed for biochemical markers of bone formation (procollagen type I amino-terminal propeptide [P1NP] and osteocalcin [OC]) and bone resorption (beta carboxyterminal cross-linking telopeptide of bone collagen [βCTX] on the Roche Elecsys 2010. The results were compared to the manufacturer’s reference range and to 46 samples from patients with severe refractory rheumatoid arthritis prior to treatment with rituximab.

Results

We found substantial inter-person variability in all of the biomarkers and differences between the manufacturer and healthy control ranges (Table 1).
Table 1

Comparison of bone marker results between manufacturer, healthy controls and rheumatoid arthritis patients

 

Manufacturer

Healthy controls

Rheumatoid arthritis

 

Prec

Postd

Male

Prec

Postd

Male

Prec

Postd

Male

βCTX a

ng/L

299

±274

556

±452

300

±284

192

±196

199

±264

325

±382

139

±184

354

±572

337

±410

P1NP b

µg/L

27.8

15-59

37.1

16-74

No data

31.9

22-58

32.6

18-66

51.5

22-79

30.1

11-50

39.1

12-73

40.5

13-81

OC b

µg/L

23.0

11-43

27.0

15-46

25.0

14-42

14.9

11-26

15.3

10-22

20.2

14-36

12.4

5-21

15.3

6-40

19.6

4-42

a mean ± 2 standard deviations (as reported by manufacturer); b median plus interquartile range (as reported by manufacturer); c pre-menopausal female; d post-menopausal female

Conclusions

These results demonstrate the large between-person variability in serum bone markers and the differences between defined ‘healthy control’ ranges, this can be critical when assessing patients with bone disease. We suggest that it is therefore important for each laboratory to investigate the transferability of the quoted reference range to its own patient population based on equivalent standardised collection conditions, and where necessary determine its own ranges. We recognize that it is often difficult to recruit sufficient healthy volunteers but the widespread availability of automated bone marker assays now means that harmonisation of methods and specific reference ranges may be possible using well-characterised populations in larger cohorts.

Declarations

Acknowledgements

The authors wish to thank staff from the Biochemistry laboratory at the James Cook University Hospital in Middlesbrough, in particular we acknowledge Cheryl Goodrum for analysing the samples.

Authors’ Affiliations

(1)
Biochemistry Department, The James Cook University Hospital
(2)
Musculoskeletal Research Group, Institute of Cellular Medicine, Newcastle University
(3)
Rheumatology Department, The James Cook University Hospital

Copyright

© Wheater et al; licensee BioMed Central Ltd. 2013

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Advertisement