Bone Abstracts (2013) 1 PP435 | DOI: 10.1530/boneabs.1.PP435

Denosumab's dynamic CTX profile is maintained over 6 years of treatment: first 3 years of the FREEDOM extension study

C Roux1, MR McClung2, N Franchimont3, S Adami4, PR Ebeling5, IR Reid6, H Resch7, G Weryha8, N Daizadeh3, A Wang3, RB Wagman3 & R Eastell9

1Paris Descartes University, Paris, France; 2Oregon Osteoporosis Center, Protland, Oregon, USA; 3Amgen, Inc., Thousand Oaks, California, USA; 4University of Verona, Verona, Italy; 5University of Melbourne, Melbourne, Victoria, Australia; 6University of Auckland, Auckland, New Zealand; 7St Vincent Hospital, University of Vienna, Vienna, Austria; 8Hôpitaux de Brabois, CHU de Nancy, Vandoeuvre, France; 9University of Sheffield, Sheffield, UK.

Denosumab (DMAb) has a unique profile of bone resorption inhibition: CTX decreases rapidly by 3 days and inhibition is released at the end of the 6-month dosing interval, when DMAb serum levels decrease (McClung NEJM 2006). The dynamic CTX inhibition profile is not curtailed by continued treatment. In the 3-year FREEDOM study, CTX values at 6 months were influenced by baseline CTX values and days since the 1st injection (Eastell JBMR 2011). With 3 additional years of data in the FREEDOM extension study, we explored whether CTX inhibition follows the same profile, and whether the relationship persists between CTX levels with pre-treatment CTX values and by the days since last injection. In the ongoing FREEDOM extension, subjects receive 60 mg DMAb every 6 months and daily supplemental calcium/vitamin D. The dynamic profile of CTX was evaluated in 50 subjects from the long-term group (3 years DMAb in FREEDOM, 3 years in extension) who had CTX measurements (in fasting serum samples by ELISA; Nordic Bioscience) at 10 days and 6 months following the 1st DMAb dose in the extension. Whether pre-treatment CTX values and time since last injection continued to predict CTX values over time was determined in 79 subjects in the long-term group who had CTX measurements available at FREEDOM and extension baseline and year 6. A Tobit-style model was used to account for censoring due to the quantifiable limit at year 6 and to evaluate its relationship with days since the last injection, and the FREEDOM and extension baseline CTX values. CTX values were decreased by 10 days after the 1st DMAb dose in the extension, with a median reduction of 91%; by 6 months after DMAb administration, CTX values were reduced by 77% (n=50). Median reduction in CTX at the end of the dosing interval at year 6 was 57% (n=79). CTX values at year 6 were significantly correlated with CTX values at FREEDOM baseline (P<0.01), time since the last DMAb dose at year 5.5 (P<0.0001), and CTX values at the extension study baseline (after 3 years of DMAb in FREEDOM, P<0.0001). In conclusion, long-term DMAb treatment is associated with a dynamic profile of CTX reduction. Pre-treatment CTX values and time since the last DMAb injection continue to be significant predictors of CTX values at year 6.