Bone loss after denosumab discontinuation is prevented by alendronate and zoledronic acid but not risedronate: a retrospective study

• Published in: Osteoporosis international 2023-03, Vol.34 (3), p.573-584
• Main Authors: Tutaworn, Teerapat, Nieves, Jeri W., Wang, Zhaorui, Levin, Justin E., Yoo, Jae E., Lane, Joseph M.
• Format: Article
• Language: English
• Subjects: Alendronate; Alendronic acid; Bisphosphonates; Bone Density; Bone Density Conservation Agents - adverse effects; Bone Diseases, Metabolic - drug therapy; Bone loss; Bone mineral density; Denosumab - adverse effects; Diphosphonates - therapeutic use; Endocrinology; Female; Fractures; Hip; Humans; Lumbar Vertebrae; Medicine; Medicine & Public Health; Monoclonal antibodies; Original; Original Article; Orthopedics; Osteoporosis; Osteoporosis, Postmenopausal - chemically induced; Osteoporosis, Postmenopausal - drug therapy; Osteoporosis, Postmenopausal - prevention & control; Retrospective Studies; Rheumatology; Risedronic Acid; Risk factors; Spinal Fractures - drug therapy; Spine (lumbar); Vertebrae; Zoledronic Acid
• ISSN: 0937-941X; 1433-2965
• DOI: 10.1007/s00198-022-06648-9

Summary A retrospective study of 121 patients who stopped denosumab (Dmab) then received no treatment (NT), risedronate (RIS), alendronate (ALN), or zoledronic acid (ZOL). Bone density (spine and hip) during and after Dmab discontinuation was measured. Treatment with ALN or ZOL, not NT and RIS, mitigated BMD loss after Dmab discontinuation. Introduction Denosumab (Dmab) discontinuation is associated with bone loss and multiple vertebral fractures. The purpose was to compare bone mineral density (BMD) change in patients following Dmab discontinuation with no subsequent treatment (NT) and three bisphosphonate (BP) treatments: risedronate (RIS), alendronate (ALN), and zoledronic acid (ZOL). Methods In a review of 121 patients aged 71.2 ± 8.1 years, discontinuing Dmab (mean 5.4 doses), 33 received NT and 88 received BP (22 RIS; 34 ALN; 32 ZOL). BMD change after 1 year was compared between groups at the lumbar spine (LS), femoral neck (FN), and total hip (TH). Risk factors for bone loss after Dmab discontinuation were compared between groups and incidence of vertebral fractures was determined. Results Following Dmab discontinuation, LS mean change (g/cm 2 ; 95% CI) was for NT: − 0.041 (− 0.062 to − 0.021); RIS: − 0.035 (− 0.052 to − 0.017); ALN: − 0.005 (− 0.020 to 0.009); and ZOL: − 0.009 (− 0.025 to 0.008). Differences in LS were found between NT and ALN ( p =  0.015), and NT and ZOL ( p= 0.037), but not between NT and RIS. The only significant difference in TH was found between NT and ZOL ( p 0.034) with no group differences in FN. BMD gains during Dmab treatment were associated with BMD loss after Dmab discontinuation. In a subset, discontinuation after Dmab treatment (> 5 doses) followed by ALN ( n  = 22) and ZOL ( n  = 11) showed no difference in BMD. Five of 7 vertebral fractures occurred after Dmab discontinuation in NT. Conclusion Subsequent treatment with ALN or ZOL but not NT and RIS mitigates BMD loss after Dmab discontinuation.