Effects of Long-Term Denosumab on Bone Histomorphometry and Mineralization in Women With Postmenopausal Osteoporosis
| Autor: | Xiang Yin, Astrid Fahrleitner-Pammer, Jacques P. Brown, Sébastien Rizzo, Rachel B. Wagman, Susan V Yue, Georges Boivin, Ivo Valter, David W. Dempster, David L. Kendler |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Time Factors Endocrinology Diabetes and Metabolism Clinical Biochemistry Osteoporosis Urology 030209 endocrinology & metabolism Placebo Biochemistry Mineralization (biology) Drug Administration Schedule Bone remodeling law.invention 03 medical and health sciences Calcification Physiologic 0302 clinical medicine Endocrinology Double-Blind Method Randomized controlled trial law Internal medicine medicine Humans Osteoporosis Postmenopausal Aged Bone Density Conservation Agents business.industry Biochemistry (medical) Middle Aged medicine.disease Treatment Outcome 030104 developmental biology Denosumab Female Bone Remodeling business Calcification medicine.drug |
| Zdroj: | The Journal of Clinical Endocrinology & Metabolism. 103:2498-2509 |
| ISSN: | 1945-7197 0021-972X |
| DOI: | 10.1210/jc.2017-02669 |
| Popis: | 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, remodeling, and matrix mineralization characteristics. Design and Setting International, multicenter, randomized, double-blind trial [Fracture Reduction Evaluation of Denosumab in Osteoporosis Every 6 Months (FREEDOM)] with a long-term open-label 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 subcutaneous 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, matrix mineralization. Results Ten-year denosumab biopsies showed normal histology. Bone histomorphometry indicated normal bone structure and reduced bone remodeling after 10 years of denosumab, similar to levels after 2 and/or 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. 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. |
| Databáze: | OpenAIRE |
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