Long-term denosumab treatment significantly improves bone microarchitecture as assessed by tissue thickness-adjusted trabecular bone score (TBSTT) independent of bone mass density (BMD) in postmenopausal women with osteoporosis. These study findings were published in Osteoporosis International.
Researchers retroactively examined participants from the previously completed FREEDOM study and its open-label extension (OLE) study. The FREEDOM study was a double-blind, randomized, placebo-controlled study of 7808 postmenopausal women with BMD T-scores between -4.0 and -2.5 at the lumbar spine or total hip. Participants were randomly assigned to receive either denosumab 60 mg or placebo every 6 months for 3 years.
Those who did not miss more than 1 dose of the study medications were then eligible for the OLE study in which they received denosumab 60 mg subcutaneously every 6 months for 7 years. Participants were excluded from the retroactive analysis if they had a body mass index (BMI) above 38 kg/m2 or less than 15 kg/m2, as this was out of the range of a manufacturer-recommended BMI for accurate measurement using TBSTT.
A total of 279 participants who completed the FREEDOM study and were included in the OLE study comprised the final analysis. Of these, 150 had received denosumab therapy for 10 years, and 129 had received placebo for the first 3 years before transitioning to 7 years of denosumab therapy. There were significant increases in the patients’ lumbar spine BMDs from baseline in the FREEDOM trial at years 4, 5, 6, 8, and 10 (mean increase, 11.6%, 13.7%, 15.5%, 18.5%, and 22.4%, respectively; P <.0001). There were also significant increases in TBSTT at the lumbar spine at years 4, 5, 6, 8, and 10 (3.2%, 2.9%, 4.1%, 3.6%, and 4.7%, respectively; P <.0001).
Participants’ risk for osteoporotic fracture was assessed based on TBSTT and BMD T-scores. In the long-term denosumab group, the percentage of participants in the high-risk fracture category decreased significantly from 93.7% to 40.4% at year 10, and the low-risk and medium-risk fracture groups grew from 6.3% to 53.9% and 0% to 5.7%, respectively (P <.0001). Significant decreases in fracture risk were also found in the crossover group that received placebo for 3 years and denosumab for 7 years.
Limitations of the study include the lack of a placebo group in the long-term denosumab therapy group and the lack of overall generalizability.
The researchers conclude, “up to 10 years of denosumab treatment significantly and continuously improved TBSTT and bone microarchitecture in postmenopausal women with osteoporosis.”
Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
This article originally appeared on Endocrinology Advisor
Hans D, McDermott M, Huang S, Kim M, Shevroja E, McClung M. 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. Published online March 2, 2023. doi:10.1007/s00198-023-06708-8