osteoporosis

 osteomalacia and rickets

 Paget’s disease.

Bone metabolism

Bone is constantly being broken down and reformed in the process of bone remodelling (Fig 38.1). The clinician looking after patients with bone disease will certainly need to know to what extent bone is being broken down, and, indeed, if new bone is being made. Biochemical markers of bone resorption and bone formation can be useful in assessing the extent of disease, as well as monitoring treatment.

Hydroxyproline, from the breakdown of collagen, can be used to monitor bone resorption. However, urinary hydroxyproline is markedly influenced by dietary gelatin. Better markers of resorption are required. One candidate would seem to be another collagen degradation product: the fragments of the molecule containing the pyridinium cross-links. Deoxypyridinoline is one such cross-link that is specific for bone, and not metabolized or influenced by diet.

The activity of the enzyme alkaline phosphatase has traditionally been used as an indicator of bone turnover. The osteoblasts that lay down the collagen framework and the mineral matrix of bone have high activity of this enzyme. Increased osteoblastic activity is indicated by an elevated alkaline phosphatase activity in a serum specimen. Indeed, children who have active bone growth compared with adults have higher ‘normal’ alkaline phosphatase activity in serum. However, alkaline phosphatase is also produced by the cells lining the bile canaliculi and is a marker for cholestasis. The bone isoenzyme of alkaline phosphatase may be measured, but there is need for a more specific and more sensitive marker.

Osteocalcin meets some of these requirements. It is synthesized by osteoblasts and is an important non-collagenous constituent of bone. Not all of the osteocalcin that an osteoblast makes is incorporated into the bone matrix. Some is released into plasma, and provides a sensitive indicator of osteoblast activity. The test is available in specialized laboratories.

Common bone disorders