Effects of Long-term Denosumab on Bone Histomorphometry and Mineralization in Women With Postmenopausal Osteoporosis.

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Effects of Long-term Denosumab on Bone Histomorphometry and Mineralization in Women With Postmenopausal Osteoporosis.

J Clin Endocrinol Metab. 2018 Apr 16;:

Authors: Dempster DW, Brown JP, Fahrleitner-Pammer A, Kendler D, Rizzo S, Valter I, Wagman RB, Yin X, Yue SV, Boivin G

Abstract
Context: Denosumab is a potent antiresorptive agent that reduces fractures in postmenopausal women with osteoporosis.
Objective: Determine effects of up to 10 years of denosumab on bone histology, bone remodeling, and bone matrix mineralization characteristics.
Design and Setting: International, multicenter, randomized, double-blind trial (FREEDOM) with a long-term open-label extension (Extension).
Patients: Postmenopausal women with osteoporosis (92 women in FREEDOM, 46 in Extension) who provided iliac bone biopsies, including 11 who provided biopsies at multiple time points.
Interventions: FREEDOM subjects were randomized 1:1 to sc denosumab 60 mg or placebo every 6 months for 3 years. Long-term extension subjects continued receiving denosumab, open-label, for 7 additional years.
Outcomes: Bone histology, histomorphometry, and matrix mineralization.
Results: 10-year denosumab biopsies showed normal histology. Bone histomorphometry indicated maintenance of normal bone structure and reduced bone remodeling after 10 years of denosumab, similar to levels after 2/3 and 5 years of denosumab. The degree of mineralization of bone was increased and mineralization heterogeneity was reduced in the denosumab years 2/3 group vs placebo. Changes in these mineralization variables progressed from years 2/3 to year 5 of denosumab, but not thereafter.
Conclusions: Denosumab for 2/3, 5, and 10 years was associated with normal histology, low bone remodeling rate, increased matrix mineralization, and lower mineralization heterogeneity compared with placebo-treated subjects. These variables were unchanged from year 5 to year 10. These data, in combination with the maintenance of low fracture rates for up to 10 years as previously reported with denosumab therapy, suggest that strong, prolonged remodeling inhibition does not impair bone strength.

PMID: 29672714 [PubMed - as supplied by publisher]

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