Introduction

The majority of biochemical markers of bone resorption are based on the measurement of fragments of collagen type I, the fibrillar component which constitutes over 90% of the protein in bone. Other resorption marker assays that are based either on noncollagenous proteins or specific enzyme activities have received more attention since they are available as serum assays and, until recently, most bone resorption markers were those available as urine assays. The aim of this chapter is to give an account of the recent progress in the development of bone markers, with particular emphasis on the biochemical basis for each assay, along with a review of the criteria necessary for properly interpreting the results.

Before 1990, the principal method available clinically for the assessment of bone resorption was urinary hydroxyproline. It was recognized, however, at the time that this method lacked specificity and sensitivity for a number of reasons. In addition to its known release from dietary sources, a major problem with measuring hydroxyproline is the presence of this amino acid in all connective tissues as well as some rapidly metabolized serum components such as C1q. A second major drawback with urinary hydroxyproline was the fact that this assay measures not only the degradation of insoluble tissue collagen but also the release of hydroxyproline from biosynthetic intermediates including degradation of precursors intracellularly, a process which could account for more than 15% of the total collagen synthesized.