Introduction

The biochemical markers of bone metabolism are substances that can be measured in a body fluid – typically serum or urine – and which are derived as a result of bone formation or bone resorption and thus act as indices of the activity of the bone remodelling process. Several markers of bone formation have been introduced in recent years, and it has become quite evident that they do not necessarily behave similarly under the different physiological and pathological situations that affect bone turnover.

Each marker of bone formation reflects one of the three different phases of bone formation: matrix synthesis, matrix maturation or mineralization (Table 10.1). The carboxy- and aminoterminal propeptides of type I procollagen (PICP and PINP, respectively) are liberated during the first phase. The second phase is reflected by bone-specific alkaline phosphatase (BAP) and the third by osteocalcin (OC). Since the organic matrix of bone is mostly type I collagen, the best biochemical marker of new bone formation should be the one that is able to estimate reliably the rate of synthesis of type I collagen.

Knock-out experiments and human genetic diseases

Knock-out experiments have elucidated the role of proteins as markers of bone formation. Since type I collagen is essential for life, it is not possible to generate knock-out mice with a total lack of type I collagen. However, mice missing the α2-chain of type I collagen are available. These animals produce a variant form of type I collagen, called α1-homotrimer collagen [1].