Endocrine Abstracts

Background: Bone turnover markers (BTM) are potential measures for understanding the effect of antiresorptive medications upon osteoclast activity. As a dynamic marker of therapy effect, they could complement or replace DXA-BMD. The translation of population data on BTM changes with therapy to the individual patient is less established. Post-hoc trial data suggests a reduction in BTM of 40% may represent a target for defining appropriate response to therapy.

Aim: We modeled the clinical application of this target threshold in an individual patient setting where assay measurement uncertainty and biological variation are included.

Methods: Using C-telo-peptide (CTX), we constructed hypothetical scenarios of CTX measurement pre and post bisphosphonate therapy. Using typical CTX assay characteristics (analytical CV 5.0%) and published intra-individual CTX data for post-menopausal women (CVi 18.0%), we calculated the level of post-therapy CTX that must be seen on single repeat measure in order to be 95% confident that the observed result was ≥40% lower from baseline. Sensitivity analyses considered greater and lesser variations in the combined sources of variation.

Results: The one-tailed 95% reference change value for any detectable therapeutic decrease in CTX was 22% at the mid-point reference interval. However, to have 95% confidence of having achieved a reduction ≥ 40%, an observed CTX decrease of 56% is required. Even larger decreases are needed for scenarios of greater analytical or intra-individual variation.

Conclusions: Although population data may suggest a CTX decrease of 40% is commensurate with adequate therapeutic response to anti-resorptives, the application to an individual patient where measurement and natural variation are present is problematic. CTX decreases much greater than 40% are required in order to be certain of having achieved a 40% decrease. It is uncertain whether this is a legitimate change to be expected in most individual patients and therefore clinical application of this threshold is uncertain.