Effect of Denosumab on the Change of Osteoclast Precursors Compared to Zoledronate Treatment in Postmenopausal Women with Osteoporosis
2
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Background: A rapid increase in bone turnover and bone loss has been observed in response to the discontinuation of denosumab. It led to an acute increase in the fracture risk, similar to that observed in the untreated patients. We aimed to investigate the effect of denosumab on osteoclast (OC) precursor cells compared to that of zoledronate. Methods: The study compared the effects of denosumab (60 mg/24-week) and zoledronate (5 mg/48-week) over 48 weeks in postmenopausal women with osteoporosis. From patients’ peripheral mononuclear cells, CD14+/CD11b+/vitronectin receptor (VNR)- and CD14+/CD11b+/VNR+ cells were isolated using fluorescent-activated cell sorting, representing early and late OC precursors, respectively. The primary endpoint was the changes in OC precursors after 48 weeks of treatment. Results: Among the 23 patients, 11 were assigned to the denosumab group and 12 to the zoledronate group (mean age, 69 years). After 48 weeks, the changes in OC precursors were similar between and within the groups. Serum C-terminal telopeptide of type I collagen levels were inversely correlated with OC precursor levels after denosumab treatment (r=-0.72, P<0.001). Lumbar spine, femur neck, and total hip bone mineral density (BMD) increased in both groups. Lumbar spine BMD increased more significantly in the denosumab group than in the zoledronate group. Conclusions: Denosumab and zoledronate treatments induced similar changes in OC precursors. During denosumab treatment, old age and suppressed bone turnover were associated with increased OC precursor cell populations. Further validation studies with prospective designs are required.
Abstract
Background: A rapid increase in bone turnover and bone loss has been observed in response to the discontinuation of denosumab. It led to an acute increase in the fracture risk, similar to that observed in the untreated patients. We aimed to investigate the effect of denosumab on osteoclast (OC) precursor cells compared to that of zoledronate. Methods: The study compared the effects of denosumab (60 mg/24-week) and zoledronate (5 mg/48-week) over 48 weeks in postmenopausal women with osteoporosis. From patients’ peripheral mononuclear cells, CD14+/CD11b+/vitronectin receptor (VNR)- and CD14+/CD11b+/VNR+ cells were isolated using fluorescent-activated cell sorting, representing early and late OC precursors, respectively. The primary endpoint was the changes in OC precursors after 48 weeks of treatment. Results: Among the 23 patients, 11 were assigned to the denosumab group and 12 to the zoledronate group (mean age, 69 years). After 48 weeks, the changes in OC precursors were similar between and within the groups. Serum C-terminal telopeptide of type I collagen levels were inversely correlated with OC precursor levels after denosumab treatment (r=-0.72, P<0.001). Lumbar spine, femur neck, and total hip bone mineral density (BMD) increased in both groups. Lumbar spine BMD increased more significantly in the denosumab group than in the zoledronate group. Conclusions: Denosumab and zoledronate treatments induced similar changes in OC precursors. During denosumab treatment, old age and suppressed bone turnover were associated with increased OC precursor cell populations. Further validation studies with prospective designs are required.
참고문헌 (30)
- Cummings SR, "Denosumab for prevention of fractures in postmenopausal women with osteoporosis", N Engl J Med, 361, pp.756~765 (2009)[DOI]
- Bone HG, "10 years of denosumab treatment in postmenopausal women with osteoporosis : results from the phase 3 randomised FREEDOM trial and open-label extension", Lancet Diabetes Endocrinol, 5, pp.513~523 (2017)[DOI]
- Brown JP, "Discontinuation of denosumab and associated fracture incidence : analysis from the Fracture Reduction Evaluation of Denosumab in Osteoporosis Every 6 Months(FREEDOM)trial", J Bone Miner Res, 28, pp.746~752 (2013)[DOI]
- Bone HG, "Effects of denosumab treatment and discontinuation on bone mineral density and bone turnover markers in postmenopausal women with low bone mass", J Clin Endocrinol Metab, 96, pp.972~980 (2011)[DOI]
- Tsourdi E, "Discontinuation of denosumab therapy for osteoporosis : A systematic review and position statement by ECTS", Bone, 105, pp.11~17 (2017)[DOI]
- McClung MR, "Observations following discontinuation of long-term denosumab therapy", Osteoporos Int, 28, pp.1723~1732 (2017)[DOI]
- Miller PD, "Effect of denosumab on bone density and turnover in postmenopausal women with low bone mass after long-term continued, discontinued, and restarting of therapy: a randomized blinded phase 2 clinical trial", Bone, 43, pp.222~229 (2008)[DOI]
- Iranikhah M, "Effects of denosumab after treatment discontinuation : A review of the literature", Consult Pharm, 33, pp.142~151 (2018)[DOI]
- Deodati A, "Mechanisms of acute hypercalcemia in pediatric patients following the interruption of Denosumab", J Endocrinol Invest, 45, pp.159~166 (2022)[DOI]
- Fontalis A, "The effect of denosumab treatment on osteoclast precursor cells in postmenopausal osteoporosis", Bone Rep, 13, pp.100457~ (2020)[DOI]
- McDonald MM, "Osteoclasts recycle via osteomorphs during RANKL-stimulated bone resorption", Cell, 184, pp.1330~1347 (2021)[DOI]
- Cornish J, "Bone-bound bisphosphonate inhibits growth of adjacent non-bone cells", Bone, 49, pp.710~716 (2011)[DOI]
- Eslami B, "Reduced osteoclastogenesis and RANKL expression in marrow from women taking alendronate", Calcif Tissue Int, 88, pp.272~280 (2011)[DOI]
- Takahashi N, "Regulatory mechanism of osteoclastogenesis by RANKL and Wnt signals", Front Biosci(Landmark Ed), 16, pp.21~30 (2011)[DOI]
- Wada A, "A new osteoclastogenesis pathway induced by cancer cells targeting osteoclast precursor cells", Biochem Biophys Res Commun, 509, pp.108~113 (2019)[DOI]
- Dalbeth N, "No reduction in circulating preosteoclasts 18 months after treatment with zoledronate : analysis from a randomized placebo controlled trial", Calcif Tissue Int, 92, pp.1~5 (2013)[DOI]
- Gossiel F, "The effect of bisphosphonate treatment on osteoclast precursor cells in postmenopausal osteoporosis : The TRIO study", Bone, 92, pp.94~99 (2016)[DOI]
- D'Amelio P, "Alendronate reduces osteoclast precursors in osteoporosis", Osteoporos Int, 21, pp.1741~1750 (2010)[DOI]
- D’Amelio P, "Risedronate reduces osteoclast precursors and cytokine production in postmenopausal osteoporotic women", J Bone Miner Res, 23, pp.373~379 (2008)[DOI]
- Møller AMJ, "Aging and menopause reprogram osteoclast precursors for aggressive bone resorption", Bone Res, 8, pp.27~ (2020)[DOI]
- Jevon M, "Gender-and age-related differences in osteoclast formation from circulating precursors", J Endocrinol, 172, pp.673~681 (2002)[DOI]
- Chung PL, "Effect of age on regulation of human osteoclast differentiation", J Cell Biochem, 115, pp.1412~1419 (2014)[DOI]
- Popp AW, "Bone mineral density changes after 1 year of denosumab discontinuation in postmenopausal women with long-term denosumab treatment for osteoporosis", Calcif Tissue Int, 103, pp.50~54 (2018)[DOI]
- Gonzalez-Rodriguez E, "Clinical features of 35 patients with 172 spontaneous vertebral fractures after denosumab discontinuation: a single center observational study", American Society for Bone and Mineral Research, ~ (2018)
- Massey HM, "Human osteoclasts derive from CD14-positive monocytes", Br J Haematol, 106, pp.167~170 (1999)[DOI]
- Pickl WF, "Molecular and functional characteristics of dendritic cells generated from highly purified CD14+ peripheral blood monocytes", J Immunol, 157, pp.3850~3859 (1996)
- Athanasou NA, "Immunophenotypic differences between osteoclasts and macrophage polykaryons : immunohistological distinction and implications for osteoclast ontogeny and function", J Clin Pathol, 43, pp.997~1003 (1990)[DOI]
- Lader CS, "Generation of human osteoclasts in stromal cell-free and stromal cell-rich cultures : differences in osteoclast CD11c", CD18 integrin expression, 2001, pp.112, 430~437
- Anderson DM, "A homologue of the TNF receptor and its ligand enhance T-cell growth and dendritic-cell function", Nature, 390, pp.175~179 (1997)[DOI]
- Lakkakorpi PT, "Kinetics of the osteoclast cytoskeleton during the resorption cycle in vitro", J Bone Miner Res, 6, pp.817~826 (1991)[DOI]