Bone markers are useful tools for the management of bone diseases, because they provide information that is different but complementary to bone mineral density (BMD) measurement. Problems in the measurement and interpretation of bone marker values are still hampering the optimal utility of this clinical tool. Most of these difficulties originate from problems related to the handling and control of analytical and biological variability of bone marker measurements. These sources of variability can be substantial and need to be controlled. In this context, certain applications of bone marker testing may have different requirements for the handling and control of these sources of variability. Finally, certain bone markers or bone marker tests may require special considerations, such as analyte stability. This document addresses these issues and provides information related to applications of bone marker measurements.

Biochemical bone marker tests are increasingly used in the management of metabolic bone diseases. They provide valuable information when performed in research centers dealing with osteoporosis and bone metabolism under well-controlled conditions and experienced personnel. However, their use in general, less specialized institutions in treating individual patients appears to be difficult, and has hampered the broad use of bone markers as a clinical tool. This situation is partially due to the lack of guidance on managing and controlling biological variation and appropriate preanalytical specimen handling. Guidance is also needed for applying and using findings from clinical trials and epidemiological studies for data interpretation. 

Bone markers exhibit substantial short-term and long-term fluctuations related to time of day, phase of the menstrual cycle, season of the year, diet, exercise, and other factors known to alter bone remodeling. These biological factors produce significant within-subject and between-subject variability in markers, in addition to assay imprecision and method bias. To minimize this variability, preanalytical, analytical, and postanalytical factors need to be considered and testing procedures harmonized. 

This document will guide laboratorians and clinicians in selecting and using bone markers for assessing and monitoring metabolic bone diseases. Guidance is provided on managing and controlling biological variation, appropriate preanalytical sample handling, postanalytical reporting of results, and applying findings from clinical trials and epidemiological studies for data interpretation. 

The document will be useful to both laboratorians and healthcare providers involved in the care of patients with bone diseases, as well as to individuals and organizations involved in developing and conducting clinical studies. In addition, this document is a starting point for discussions about further harmonization of bone marker testing. 

Although efforts have been undertaken to use markers of bone metabolism in the management of related diseases such as cancer or arthritis, such applications are not considered in this document, nor does this guideline provide information about the management of the disease with regard to medications and other forms of patient care. Such clinical guidelines need to be developed separately by the appropriate organizations. This guideline focuses on the following bone markers: 

Formation Markers 

• Osteocalcin 

• Total and bone alkaline phosphatase 

• Type I collagen propeptides Resorption Markers 

• Pyridinoline and deoxypyridinoline 

• Type I collagen telopeptidesa 

• Tartrate resistant acid phosphatase isoform 5b