Disclosures: Boivin reports receiving research grants paid to his institution from Amgen, Biom’up, Hoffmann-La Roche, Eli Lilly, MSD, NIH, Noraker, Procter & Gamble, and Servier; and serving as a consultant and receiving travel grants for Amgen, MSD and Servier. Please see the study for all other authors’ relevant financial disclosures.
Postmenopausal women assigned denosumab have increases in mineral to matrix ratio at the cortical and cancellous bone at 2 to 3 years, but changes were not observed beyond 5 years, according to study findings.
In an analysis of data from the FREEDOM trial, denosumab therapy (Prolia, Amgen) was associated with lower mineral carbonation and a higher mineral to matrix ratio, mineral maturity and crystallinity at 2 to 3 years compared with placebo, with improvements continuing up to 5 years. However, bone mineral metrics were mostly unchanged at 10 years compared with 5 years for adults using denosumab.
“Short- and long-term data on the effects of denosumab on matrix mineralization are of particular interest considering denosumab’s rapid and strong antiresorptive effects throughout the skeleton, including in the cancellous and cortical compartments,” Georges Boivin, PhDemeritus director of research in the National Institute of Health and Medical Research at the University of Lyon in France, and colleagues wrote in a study published in the Journal of Bone and Mineral Research. “The FREEDOM trial and its extension provide a unique opportunity to assess the degree to which human bone matrix can have higher degree of mineralization and lower mineralization heterogeneity as a result of denosumab treatment. Furthermore, it allows one to assess the contribution of bone quality to the clinical outcomes.”
Researchers collected bone matrix quality data from the FREEDOM and FREEDOM extension trials, in which postmenopausal women aged 60 to 90 years were randomly assigned to 60 mg denosumab or placebo every 6 months for 3 years. The extension trial followed up with participants at 5 and 10 years. The analysis included 42 participants from FREEDOM receiving denosumab and 30 from the placebo group. There were 28 participants from the FREEDOM extension 5-year follow-up included in the analysis and 21 from the 10-year follow-up.
In the FREEDOM trial analysis, mineral to matrix bone ratio at both the cortical and cancellous compartments was higher in the denosumab group compared with placebo. Microhardness was higher in those assigned denosumab compared with placebo in the cortical bone only.
Women in the 5-year follow-up group had a higher mineral to matrix ratio in both the cortical and cancellous bone at 5 years compared with 2 to 3 years. The mineral to matrix ratio in both compartments was unchanged at 10 years compared with 5 years. Mineral maturity and crystallinity were also higher at 5 years compared with 2 to 3 years, with no mineral maturity and crystallinity changes observed at 10 years, except for mineral maturity in the cancellous bone, which was higher at 10 years compared with 5 years , the researchers reported.
Mineral carbonation was lower in both the cortical and cancellous bone at 5 years compared with 2 to 3 years, with no further changes at 10 years. Collagen maturity was higher in the cancellous bone at 5 years, with no further difference at 10 years. Microhardness was lower at 5 years compared with 2 to 3 years in both the cortical and cancellous bone, but no further changes were observed at 10 years, according to the study.
“These data support a transition of mineral to more mature crystals and the completeness of secondary mineralization within 5 years of denosumab treatment,” the researchers wrote. “The lower microhardness at years 5 and 10 is likely the result of maturation of the organic matrix in a persistently low state of bone remodeling over 5 and 10 years.”