Observational studyJournal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research2025
The effects of denosumab on osteoclast precursors in postmenopausal women: a possible explanation for the overshoot phenomenon after discontinuation.
Observational study in Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed.
- Real-world rebound pattern of serum collagen type I C-telopeptide after denosumab discontinuation and zoledronate rescue in postmenopausal osteoporosis and cancer treatment-induced bone loss.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2026Article
- In silico exploration of osteoclast precursor inhibition for preventing rapid bone loss after denosumab discontinuation.NPJ systems biology and applications · 2026Article
- Non-metastatic breast cancer patients discontinuing aromatase inhibitor on denosumab: what next?Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2026Review
- Evaluation of Osteonecrosis Risk Using Serum C-Terminal Cross-Linked Telopeptide of Type 1 Collagen (CTX-1) Levels in Osteoporotic Patients: Effects of Drug Holidays and Risk Factors.The Eurasian journal of medicine · 2026Article
- Osteoporosis After Menopause and After Drug Therapy: The Molecular Mechanism of Bone Loss and Its Treatment.International journal of molecular sciences · 2026Review
- Comparison of the effects of denosumab and alendronate on fracture risk and bone metabolism in postmenopausal rheumatoid arthritis patients treated with oral glucocorticoids: A propensity score-matched retrospective cohort study.Therapeutic advances in musculoskeletal disease · 2026Article
- Mechanisms and management strategies for exacerbated bone loss following denosumab discontinuation.Frontiers in aging · 2026Review
- Transient increase in skeletal-related events after discontinuation of high-dose denosumab in cancer patients.Journal of bone oncology · 2025Article
- Expert Perspective: How, When, and Why to Potentially Stop Antiresorptive Drugs in Osteoporosis.Arthritis & rheumatology (Hoboken, N.J.) · 2025Review
- Mechanisms to explain the overshoot in bone remodeling markers after denosumab discontinuation: are we there yet?Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2025Article
- Digital twin simulations with a micro-multiphysics agent-based model reveal key drivers of bone loss after denosumab discontinuation.Frontiers in bioengineering and biotechnology · 2025Article
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Abstract
Upon denosumab discontinuation, an observed overshoot phenomenon in bone turnover may occur, potentially leading to a reduction in bone mineral density and the occurrence of vertebral fractures. Several theories have been proposed to explain this phenomenon, one of which is that osteoclast precursors might be accumulating during treatment. Our aim was to study the effects of denosumab on osteoclast precursors in postmenopausal women. This cross-sectional observational study included 30 postmenopausal women with osteopenia or osteoporosis, divided into 2 groups: 15 treated with denosumab (mean duration 4 years, range 6 months-9 years) and 15 treatment-naïve controls. Peripheral blood mononuclear cells were isolated from whole blood and were stained for CD14, MCSFR, CD11b, and TNFRII. Osteoclast precursors (CD14+/MCSFR+, CD14+/CD11b + OR CD14+/TNFRII+) were identified with fluorescent activated cell sorting. The proportion of osteoclasts was determined by calculating their percentage of the total cell population in each whole blood sample. To confirm the expected suppression of bone turnover in the subjects treated with denosumab, we measured serum PINP, CTX, and TRACP5b. Denosumab-treated patients exhibited a significantly higher count of CD14+/CD11b + osteoclast precursors compared with controls (median 4% vs 0.75%, p=.011). There was no correlation with the duration of treatment. Bone turnover markers were significantly lower in the group treated with denosumab than controls. Our findings indicate an increase in osteoclast precursors, which could explain the overshoot phenomenon observed after discontinuing denosumab.
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