The Use of Bone Turnover Markers in Monitoring Osteoporosis Treatment in Clinical Practice

Osteoporosis is a skeletal disease of compromised bone strength resulting in fragile bones at greater risk of fracture. Clinical trials of bisphosphonate and denosumab treatments show fracture reduction, but with secondary end points of suppression of bone turnover markers (BTM). Markers of bone formation, procollagen I N-extension peptide (PINP) and osteocalcin (OC) suppress after 3 months of anti-resorptives, because of the coupled bone turnover cycle. I explored the utility in monitoring osteoporosis treatment with a biological target of BTM named the threshold level, defined as the geometric mean of a healthy premenopausal reference interval. Using a single-centre, cross-sectional study I examined the use of the threshold of PINP and OC by two commonly used assays (IDS iSYS and Roche Cobas e411) in an unselected mixed-gender clinical sample on oral or parenteral anti-resorptives. Comparison was made with the performance in controlled subjects of a RCT in which least significant change (LSC) was also analysed as a biological target. In practically all analyses the two assays of each BTM were equivalent in performance owing to almost perfect method agreement. The sensitivity of the BTM at threshold to detect apparent response to oral bisphosphonates, was lower in the Clinical cohort than in the Trial cohort, with a low specificity in the Clinical cohort also impacting on the significant difference in the AUC in ROC analysis. The sensitivity improved in the cohorts on IV zoledronate and SC denosumab, owing mainly to unquestionable adherence, but with a subset of individuals that did not supress. Impacting on the sensitivity were recent fracture history and renal impairment, in which the assays differed in behaviour. The specificity remained low in the parenteral cohorts likely because of the previous anti-resorptive use as well as calcium supplementation and glucocorticoid prescription. The impact of this on change in BMD was inconclusive.