Basic bone biology is most simply characterized by two fundamental mechanisms — formation and resorption, which account for the processes of modelling (in early growth and development when skeletal mass is increasing and being shaped) and remodelling, which, when appropriately coordinated, accounts for the healthy maintenance of the skeleton.

Osteoporosis is associated with an uncoupling of this well-coordinated process, resulting in increased resorption, and ultimately lower formation. This increased bone turnover is why markers of both resorption and formation have been investigated and well characterized. Markers of resorption are more clinically relevant, given that the most common therapeutic interventions worldwide for osteoporosis are inhibitors of bone loss, namely the anti-resorptive bisphosphonates.

Data suggests that these resorption markers may be useful as both independent and additive predictors (along with BMD) of fracture risk. In specific populations they help define response to therapy. These markers typically measure, in serum or alternatively urine, the soluble fragments of collagen crosslinks. These are protein components that bind the triple helix together and which are removed during bone resorption (the C or N terminal telopeptides).

Markers of bone formation include enzymes that are secreted by osteoblasts; alkaline phosphatase, and osteocalcin, as well as procollagen peptides (procollagen type-1 N-terminal propeptide [PINP]). While alkaline phosphatase measurement is readily available, it’s not very specific (other AP sources include the liver and GI tract). Osteocalcin measurements are a research tool, a better measure of osteoid formation than bone. They’re also susceptible to wide variations in range due to diet and other factors. The peptide markers are superior but not clinically available, and their role in fracture prediction and therapeutic monitoring have yet to be fully defined.

In Canada, the availability of tests for bone-specific markers may vary between jurisdictions. They can be associated with additional financial charges to the patient, and may be restricted to academic centres with a focus on metabolic bone disease. At present, these tests should only be requested by physicians who specialize in metabolic bone disease, to address specific issues that can’t be characterized by standard investigations such as BMD, routine biochemistry, and radiology.

An useful review of this topic is provided at http://courses.washington.edu/bonephys/opmark.html.