TY - JOUR

T1 - Cancer risk in patients treated with denosumab compared with alendronate

T2 - A population-based cohort study

AU - Yahyavi, Sam Kafai

AU - Holt, Rune

AU - Knudsen, Nadia Krarup

AU - Andreassen, Christine Hjorth

AU - Sejling, Christoffer

AU - Meddis, Alessandra

AU - Kjaer, Susanne K.

AU - Schwarz, Peter

AU - Jensen, Jens Erik Beck

AU - Torp-Pedersen, Christian

AU - Juul, Anders

AU - Selmer, Christian

AU - Blomberg Jensen, Martin

N1 - Publisher Copyright: © 2024

PY - 2024

Y1 - 2024

N2 - Background: Antiresorptive treatment is currently used in millions of patients with osteoporosis and cancer worldwide. Early studies of denosumab suggested a small signal in ovarian cancer incidence and emerging data suggest that denosumab stimulates germ cell proliferation in the gonads. This study aims to determine the association between the use of denosumab and the risk of reproductive cancers compared with the use of alendronate. Research design and methods: Using a cohort study design, we used the Danish nationwide registries to identify a population of subjects ≥50 years of age during 2010–2017 who started denosumab after being on alendronate treatment for at least six months. The cohort was matched 1:2 with patients who had been treated with alendronate alone for at least six months. The risk of reproductive cancers and the risk difference between groups were estimated using the Longitudinal Targeted Maximum Likelihood Estimation (L-TMLE) method. Results: We identified 6054 Danish individuals who underwent treatment with denosumab. These individuals were matched with 12,108 receiving alendronate. The absolute risk of reproductive cancer was 1.05 % (95 % CI 0.75–1.34) after three years for denosumab users and was not different 0.03 % (−0.34–0.39) than for alendronate users. In supplemental analyses, there was no increased risk of non-reproductive cancers associated with the use of denosumab (risk difference of 0.54 % (−0.41–1.19). Analysis comparing denosumab users with the general population gave similar results. Conclusion: There was no difference in the risk of cancer following treatment with denosumab compared to treatment with alendronate assessed after a short follow-up of 3 years.

AB - Background: Antiresorptive treatment is currently used in millions of patients with osteoporosis and cancer worldwide. Early studies of denosumab suggested a small signal in ovarian cancer incidence and emerging data suggest that denosumab stimulates germ cell proliferation in the gonads. This study aims to determine the association between the use of denosumab and the risk of reproductive cancers compared with the use of alendronate. Research design and methods: Using a cohort study design, we used the Danish nationwide registries to identify a population of subjects ≥50 years of age during 2010–2017 who started denosumab after being on alendronate treatment for at least six months. The cohort was matched 1:2 with patients who had been treated with alendronate alone for at least six months. The risk of reproductive cancers and the risk difference between groups were estimated using the Longitudinal Targeted Maximum Likelihood Estimation (L-TMLE) method. Results: We identified 6054 Danish individuals who underwent treatment with denosumab. These individuals were matched with 12,108 receiving alendronate. The absolute risk of reproductive cancer was 1.05 % (95 % CI 0.75–1.34) after three years for denosumab users and was not different 0.03 % (−0.34–0.39) than for alendronate users. In supplemental analyses, there was no increased risk of non-reproductive cancers associated with the use of denosumab (risk difference of 0.54 % (−0.41–1.19). Analysis comparing denosumab users with the general population gave similar results. Conclusion: There was no difference in the risk of cancer following treatment with denosumab compared to treatment with alendronate assessed after a short follow-up of 3 years.

KW - Alendronate

KW - cancer

KW - Denosumab

KW - Osteoporosis

KW - Reproductive cancers

U2 - 10.1016/j.bone.2024.117053

DO - 10.1016/j.bone.2024.117053

M3 - Journal article

C2 - 38395247

AN - SCOPUS:85186398099

VL - 182

JO - Bone

JF - Bone

SN - 8756-3282

M1 - 117053

ER -