The relationship between length of denosumab treatment for postmenopausal osteoporosis and serum TRAcP5b measured six months after the last injection.
Bone turnover markers
Denosumab
Denosumab discontinuation
Postmenopausal osteoporosis
TRAcP5b
Journal
Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA
ISSN: 1433-2965
Titre abrégé: Osteoporos Int
Pays: England
ID NLM: 9100105
Informations de publication
Date de publication:
02 Oct 2023
02 Oct 2023
Historique:
received:
25
04
2023
accepted:
25
09
2023
medline:
3
10
2023
pubmed:
3
10
2023
entrez:
2
10
2023
Statut:
aheadofprint
Résumé
To test the hypothesis that during treatment with denosumab osteomorphs and precursors recycle to higher number of osteoclasts with time, we measured TRAcP5b in serum taken 6 months after the last injection in postmenopausal women treated for 1-10 years. Serum TRAcP5b values were not related to time of exposure to denosumab. In women with postmenopausal osteoporosis the aetiology of the observed inverse relationship between duration of denosumab (Dmab) therapy and bone loss after its discontinuation is currently unknown. In studies in mice inhibition of RANKL is associated with an increase in osteomorphs and osteoclast precursors that recycle into osteoclasts and may accumulate with time. We hypothesized that longer inhibition of RANKL by Dmab will be followed by the synchronous formation of a larger number of osteoclasts after stopping treatment. To test this hypothesis, we measured serum TRAcP5b, a marker of osteoclast numbers, in postmenopausal women treated with Dmab for different periods of time up to 10 years. TRAcP5b, C-terminal telopeptide of type 1 collagen (CTX) and procollagen type 1 N-terminal propeptide (P1NP) were measured at 6.0 months ± 15 days after last Dmab injection in 59 women who had received Dmab for 4.0 ± 2.3 years (range 1-10 years). Of these, 38 were treatment naïve (group 1) and 21 had received other treatments prior Dmab (group 2). Duration of Dmab treatment was not related to serum TRAcP5b values or to TRAcP5b/CTX ratio either in the whole cohort or in each of the two groups separately. In contrast, serum TRAcP5b values were significantly correlated with serum CTX values (r Our observations indicate that serum TRAcP5b, measured at 6 months after a Dmab injection, is not a useful early marker for time-dependent increased accumulation of osteoclasts in humans and for identification of patients at risk for a higher rebound increase in bone resorption.
Identifiants
pubmed: 37783758
doi: 10.1007/s00198-023-06931-3
pii: 10.1007/s00198-023-06931-3
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2023. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.
Références
Tsourdi E, Zillikens MC, Meier C et al (2020) Fracture risk and management of discontinuation of denosumab therapy: a systematic review and position statement by ECTS. J Clin Endocrinol Metab 26:dgaa756
Solling AS, Tsourdi E, Harslof T, Langdahl BL (2023) Denosumab discontinuation. Curr Osteoporos Rep 21:95–103
doi: 10.1007/s11914-022-00771-6
pubmed: 36564572
Makras P, Appelman-Dijkstra NM, Papapoulos SE, van Wissen S, Winter EM, Polyzos SA, Yavropoulou MP, Anastasilakis AD (2021) The duration of denosumab treatment and the efficacy of zoledronate to preserve bone mineral density after its discontinuation. J Clin Endocrinol Metab 106:e4155–e4162
doi: 10.1210/clinem/dgab321
pubmed: 33978745
Solling AS, Harslof T, Langdahl B (2021) Treatment with zoledronate subsequent to denosumab in osteoporosis: a 2-year randomized study. J Bone Miner Res 36:1245–1254
doi: 10.1002/jbmr.4305
pubmed: 33813753
Ferrari S (2022) Short or long-term osteoporosis therapy with denosumab? J Clin Endocrinol Metab 107:e1760–e1762
doi: 10.1210/clinem/dgab627
pubmed: 34561999
Ferrari S, Langdahl B (2023) Mechanisms underlying the long-term and withdrawal effects of denosumab therapy on bone. Nat Rev Rheumatol 19:307–317
doi: 10.1038/s41584-023-00935-3
pubmed: 37024711
Kim AS, Girgis CM, McDonald MM (2022) Osteoclast recycling and the rebound phenomenon following denosumab discontinuation. Curr Osteoporos Rep 20:505–515
doi: 10.1007/s11914-022-00756-5
pubmed: 36201122
pmcid: 9718877
McDonald MM, Khoo WH, Ng PY et al (2021) Osteoclasts recycle via osteomorphs during RANKL-stimulated bone resorption. Cell 184:1330-1347 e1313
doi: 10.1016/j.cell.2021.02.002
pubmed: 33636130
pmcid: 7938889
Schini M, Vilaca T, Gossiel F, Salam S, Eastell R (2022) Bone turnover markers: basic biology to clinical applications. Endocr Rev 44(3):417–473
doi: 10.1210/endrev/bnac031
pmcid: 10166271
Kim A, Castro-Martinez A, Taylor V, Center J, Girgis C, Croucher P, McDonald MM (2023) Longitudinal changes in bone turnover and osteoclast activity following withdrawal of RANKL inhibition. JBMR Plus 7:368
Bone HG, Bolognese MA, Yuen CK, Kendler DL, Miller PD, Yang YC, Grazette L, San Martin J, Gallagher JC (2011) 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 96:972–980
doi: 10.1210/jc.2010-1502
pubmed: 21289258
Anastasilakis AD, Yavropoulou MP, Makras P, Sakellariou GT, Papadopoulou F, Gerou S, Papapoulos SE (2017) Increased osteoclastogenesis in patients with vertebral fractures following discontinuation of denosumab treatment. Eur J Endocrinol 176:677–683
doi: 10.1530/EJE-16-1027
pubmed: 28283537
Jahn-Rickert K, Wolfel EM, Jobke B, Riedel C, Hellmich M, Werner M, McDonald MM, Busse B (2020) Elevated bone hardness under denosumab treatment, with persisting lower osteocyte viability during discontinuation. Front Endocrinol (Lausanne) 11:250
doi: 10.3389/fendo.2020.00250
pubmed: 32499755
Anastasilakis AD, Papapoulos SE, Polyzos SA, Appelman-Dijkstra NM, Makras P (2019) Zoledronate for the prevention of bone loss in women discontinuing denosumab treatment. a prospective 2-year clinical trial. J Bone Miner Res 34:2220–2228
doi: 10.1002/jbmr.3853
pubmed: 31433518
Fassio A, Adami G, Benini C et al (2019) Changes in Dkk-1, sclerostin, and RANKL serum levels following discontinuation of long-term denosumab treatment in postmenopausal women. Bone 123:191–195
doi: 10.1016/j.bone.2019.03.019
pubmed: 30910600
Solling AS, Harslof T, Jorgensen NR, Langdahl B (2023) Changes in RANKL and TRAcP5b after discontinuation of denosumab suggest RANKL mediated formation of osteoclasts results in the increased bone resorption. Osteoporos Int 34:599–605
doi: 10.1007/s00198-022-06651-0
pubmed: 36543965