Background: A randomised, blinded study evaluated the effect of treatment with blosozumab, a humanised monoclonal antibody targeted against sclerostin, on BMD and bone turnover markers (BTMs) in postmenopausal women with low BMD. The objectives of these analyses are to determine the 1) relationship between change in BTMs (PINP, BALP, OC, and CTX) at 2, 4, and 12 weeks and change in BMD after 1 year of treatment; 2) BTM and time point most strongly associated with 1-year change in spine, hip, and total body BMD; 3) proportion of patients responding to treatment based on change in BTMs.
Method: Multiple regression models with applied forward selection identified the strongest association between change in BTM and change in spine, hip, and total body BMD after 1 year of treatment. Least significant change (LSC) in BTM was determined from within subject variability of repeated measures to define proportion of responders.
Results: A strong association was observed between early change in BTMs reflecting bone formation and BMD increases with 1-year of blosozumab treatment. In a model considering treatment effect and BTMs reflecting bone formation, changes in PINP at 2 and 4 weeks were significantly correlated with changes in spine (p<.01) and hip BMD (p<.02) at 1 year. When treatment and PINP increases are considered, CTX decrease at 2 weeks was also significantly correlated with change in hip (p=.04) but not spine BMD. In the highest dose group, PINP at 4 weeks was correlated (p<.01) with BMD at 52 weeks (spine r=.51, hip r=.56, whole body r=.62). The LSC from post-baseline PINP measurements in the placebo group was 10 ng/mL; response rates were >95% with Q2W dosing, 52% with Q4W dosing, and 8% with placebo.
Conclusion: We conclude change in PINP by 4 weeks of treatment with blosozumab identifies later BMD response at 1 year of treatment.
Disclosure: Dr Richard Eastell-consultant and grant funding, Eli Lilly and Company; Dr Alan Chiang, Dr John Krege, Dr Fernando Marin and Dr Bruce Mitlak are employees and shareholders of Eli Lilly and Company. This work was sponsored by Eli Lilly and Company.