Bone turnover markers have “potential” to provide clinically useful information in the treatment of osteoporosis but their utility continues to be hampered by problems including an inconsistent association with fracture risk and wide variations in assays.

International experts, including Professor Howard Morris from the University of Adelaide and Dr Sam Vasikaran from the Fiona Stanley Hospital in Perth, reviewed the current status of bone turnover markers (BTMs) on behalf of the International Osteoporosis Foundation and the International Federation of Clinical Chemistry and Laboratory Medicine.

An earlier review by the same group, published in 2011, concluded there was not enough evidence to include BTMs in clinical practice. However, they suggested that standardised assays of PINP and CTX should be used in observational and interventional studies as markers of bone formation and resorption, respectively.

The updated review confirmed that associations between BTM concentrations and fracture risk are, at best, modest. Relevant studies had many limitations, including the use of many different markers, differences in the assays used, inconsistencies in the expression of risk, and inconsistent predictive values.

There was more positive news for the use of BTMs in monitoring responses to osteoporosis treatment. In clinical trials, changes in BTMs in the first year of treatment explained about half the reduction in fracture risk – an effect at least as great as the change in bone mineral density.

“The finding of significant positive associations between the reduction in BTM and the reduction in fracture risk support the use of BTM in monitoring treatment,” the review concluded.

Patients with chronic kidney disease are at increased risk of osteoporosis and fractures. CTX is recommended as the bone resorption biomarker for clinical studies in this group, and there is increasing interest in alternatives such as TRAP-5B, fibroblast growth factor 23 and sclerostin, an inhibitor of the wnt pathway that reduces bone formation.

“With a new anti-sclerostin agent becoming available, interest in this analyte will likely grow but robust analytical methods are required to provide true measurements suitable for clinical interpretation,” the reviewers said.

Another challenge is the development of appropriate reference intervals that can be used in healthy premenopausal women aged 30-45, when BTM levels are at their lowest. While markedly elevated levels occur in metabolic bone diseases, it would be helpful to establish ‘normal’ levels more accurately, both for assessment of risk in younger women and to establish a target for anti-resorptive treatment.