ECTS2013 Poster Presentations Osteoporosis: treatment (64 abstracts)
Factors influencing levels of bone resorption during denosumab dosing
Richard Eastell 1 , Ethel Siris 2 , Christian Roux 3 , Dennis M. Black 4 , Nathalie Franchimont 5 , Graham Jang 5 , Nadia Daizadeh 5 , Rachel B. Wagman 5 & Matt Austin 5
1University of Sheffield, Sheffield, UK, 2Columbia University Medical Center, New York, NY, USA, 3Paris Descartes University, Paris, France, 4University of California, San Francisco, San Francisco, CA, USA, 5Amgen Inc., Thousand Oaks, CA, USA.
Denosumab treatment is associated with low fracture incidence, sustained BMD increases, and reduced sCTX. The decrease in median sCTX is at the quantifiable limit (0.049 ng/ml) one month post-dose, remains low, and attenuates at the end of the 6-month dosing interval. Using 7 years of data from the FREEDOM study and its extension, we characterized changes in sCTX over time and the influencing factors. In the bone turnover marker and pharmacokinetic substudies, serum was collected after an overnight fast and prior to denosumab dosing. Post-dose sCTX values within 7 months of denosumab dosing were included. sCTX values obtained after a subject experienced an on-study fracture or received bone-active medication were excluded. A mixed model was constructed using a cubic polynomial to estimate the attenuation of sCTX while allowing for individual subject fluctuation in the rate of attenuation. sCTX values below the quantifiable limit were assigned half the limit (0.0245 ng/ml). With each denosumab dose, there was a rapid decrease in sCTX that was not influenced by duration of denosumab exposure or other factors. Mean sCTX begins to increase after ~5 months in the first year, reaching 0.11 ng/ml at the end of the 6-month dosing interval. In the third and subsequent years, mean sCTX begins to increase after ~4 months reaching 0.18 ng/ml 6 months post-dose. The increase was greater in subjects with higher baseline sCTX, P1NP, body weight, spine BMD, and older age. We conclude that up to 7 years of denosumab administration consistently resulted in post-dose sCTX reduction, with increasing attenuation at the end of the dosing interval during the first 3 years of treatment This attenuation did not increase further with subsequent denosumab treatment, and was affected by several baseline subject characteristics. Understanding sCTX dynamics while receiving denosumab may help understand the sustained BMD increases over time.
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Bone Abstracts
ISSN 2052-1219 (online)
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