Long-term effect of denosumab on bone microarchitecture as assessed by tissue thickness-adjusted trabecular bone score in postmenopausal women with osteoporosis: results from FREEDOM and its open-label extension

Didier Hans; Michele McDermott; Shuang Huang; Min Kim; Enisa Shevroja; Michael McClung

doi:10.1007/s00198-023-06708-8

Long-term effect of denosumab on bone microarchitecture as assessed by tissue thickness-adjusted trabecular bone score in postmenopausal women with osteoporosis: results from FREEDOM and its open-label extension

Osteoporos Int. 2023 Jun;34(6):1075-1084. doi: 10.1007/s00198-023-06708-8. Epub 2023 Mar 2.

Authors

Didier Hans¹, Michele McDermott², Shuang Huang², Min Kim², Enisa Shevroja³, Michael McClung^{4

5}

Affiliations

¹ Interdiciplinary Center of Bone Diseases, Lausanne University Hospital and Lausanne University, Av. Pierre Decker 4, 1011, Lausanne, Switzerland. didier.hans@ascendys.ch.
² Amgen Inc., Thousand Oaks, CA, USA.
³ Interdiciplinary Center of Bone Diseases, Lausanne University Hospital and Lausanne University, Av. Pierre Decker 4, 1011, Lausanne, Switzerland.
⁴ Oregon Osteoporosis Center, Portland, OR, USA.
⁵ Mary MacKillop Institute for Health Research, Australian Catholic University, Melbourne, VIC, Australia.

Abstract

In postmenopausal women with osteoporosis, up to 10 years of denosumab treatment significantly and continuously improved bone microarchitecture assessed by tissue thickness-adjusted trabecular bone score, independently of bone mineral density. Long-term denosumab treatment decreased the number of high fracture-risk patients and shifted more patients to lower fracture-risk categories.

Purpose: To investigate the long-term effect of denosumab on bone microarchitecture assessed by tissue thickness-adjusted trabecular bone score (TBS_TT) in post-hoc subgroup analysis of FREEDOM and open-label extension (OLE).

Methods: Postmenopausal women with lumbar spine (LS) or total hip BMD T-score <-2.5 and ≥-4.0 who completed the FREEDOM DXA substudy and continued in OLE were included. Patients received either denosumab 60 mg subcutaneously every 6 months for 3 years and same-dose open-label denosumab for 7 years (long-term denosumab; n=150) or placebo for 3 years and open-label denosumab for 7 years (crossover denosumab; n=129). BMD and TBS_TT were assessed on LS DXA scans at FREEDOM baseline, month 1, and years 1-6, 8, and 10.

Results: In long-term denosumab group, continued increases from baseline to years 4, 5, 6, 8, and 10 in BMD (11.6%, 13.7%, 15.5%, 18.5%, and 22.4%) and TBS_TT (3.2%, 2.9%, 4.1%, 3.6%, and 4.7%) were observed (all P < 0.0001). Long-term denosumab treatment decreased the proportion of patients at high fracture-risk (according to TBS_TT and BMD T-score) from baseline up to year 10 (93.7 to 40.4%), resulting in increases in the proportions at medium-risk (6.3 to 53.9%) and low-risk (0 to 5.7%) (P < 0.0001). Similar responses were observed in crossover denosumab group. Changes in BMD and TBS_TT were poorly correlated during denosumab treatment.

Conclusion: In postmenopausal women with osteoporosis, up to 10 years of denosumab significantly and continuously improved bone microarchitecture assessed by TBS_TT, independently of BMD, and shifted more patients to lower fracture-risk categories.

Keywords: Bone mineral density (BMD); Denosumab; Osteoporosis; Postmenopausal women; Soft tissue thickness; Trabecular bone score (TBS).

Publication types

Clinical Trial

MeSH terms

Bone Density
Bone Density Conservation Agents* / pharmacology
Bone Density Conservation Agents* / therapeutic use
Cancellous Bone
Denosumab / pharmacology
Denosumab / therapeutic use
Female
Fractures, Bone* / chemically induced
Humans
Lumbar Vertebrae
Osteoporosis* / drug therapy
Osteoporosis, Postmenopausal* / chemically induced
Osteoporosis, Postmenopausal* / drug therapy
Postmenopause

Substances

Bone Density Conservation Agents
Denosumab