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Purpose: Denosumab discontinuation (DD) is associated with serum C-terminal X-linked telopeptides (sCTX) increase, bone mineral density (BMD) loss and vertebral fractures (VFs) risk increase. We compared clinical characteristics of women losing or not lumbar spine (LS) BMD one-year after DD, and their sCTX values at different time-points., Methods: We included women from the ReoLaus cohort having received ≥2 denosumab 60 mg injections, with three BMD measurements on the same device (before (DXA1), at the end of denosumab treatment (DXA2), and one-year after (DXA3)) and sCTX measured at different time-points. Losers (LS DXA3-DXA2 > 2.8 %) and stable groups were compared., Results: 63 postmenopausal women were included (mean age 64.2 ± 9.1 years, 7.9 ± 2.7 denosumab injections). 19 months after last denosumab injection, 65 % had lost LS BMD. Losers were younger, had lower BMD and higher sCTX before denosumab, received more injections and gained more BMD under denosumab, and had higher sCTX after DD. Same proportion of patients received bisphosphonates in both groups, but 11 (all in losers group) received ≥1 zoledronate infusion. Three women developed VFs in the losers group (none in the stable). Mean sCTX at 10 and 19 months were 590 ± 372 versus 221 ± 101, and 598 ± 324 versus 293 ± 157 ng/l, respectively (premenopausal range < 573 ng/l, p < 0.01 for both). LS BMD loss and sCTX levels measured at 10 and 19 months were correlated (r 2  = 0.29, p = 0.01, and r 2  = 0.16, p < 0.005)., Conclusion: Maintenance of BMD gained with denosumab is associated with sCTX in the low premenopausal range after DD. Whether this could be achieved by regular sCTX monitoring and adjustment of bisphosphonates doses or frequency administration needs to be confirmed by further studies., Competing Interests: Declaration of competing interest All authors state that they have no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: To compare bone quality using the trabecular bone score (TBS) and bone microarchitecture in the distal tibia using high-resolution peripheral quantitative computed tomography (HR-pQCT) in ankylosing spondylitis (AS) patients and healthy controls (HC)., Methods: Areal bone mineral density (aBMD) and TBS (TBS iNsight software) were evaluated using DXA (Hologic, QDR 4500); while volumetric bone mineral density (vBMD) and bone microarchitecture were analyzed in the distal tibia using HR-pQCT (Scanco) in 73 male patients with AS and 52 age-matched HC., Results: AS patients were a mean 41.6 ± 7.9 years old and had a mean disease duration of 16.4 ± 8.6 y, with a mean mSASSS 25.6 ± 16.4. No difference was observed in lumbar spine aBMD in AS patients and HC (p = 0.112), but total hip BMD (p = 0.011) and TBS (p < 0.001) were lower in AS patients. In the distal tibia, reduced trabecular volumetric density [Tb.vBMD (p < 0.006)] and structural alterations - trabecular thickness (Tb.Th), p = 0.044 and trabecular separation (Tb.Sp), p = 0.039 - were observed in AS patients relative to controls. Further analysis comparing TBS < 1.310 and TBS ≥ 1.310 in AS patients revealed a higher mean body mass index [BMI] (p = 0.010), lower tibia cortical vBMD [Ct.vBMD] (p = 0.007), lower tibia cortical thickness [Ct.Th]: (p = 0.048) in the former group. On logistic regression analysis, BMI (OR = 1.27; 95%IC = 1.08-1.50, p = 0.005), (VF 4.65; 1.13-19.1, p = 0.033) and tibial Ct.vBMD (0.98; 0.97-1.00, p = 0.007) were associated with a lower TBS (<1.310)., Conclusions: The present study demonstrates that TBS and HR-pQCT imaging are important technologies evaluating bone impairment in AS patients. Moreover, in these patients vertebral fractures were associated with lower TBS., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: The optimal duration of osteoporosis treatment is controversial. As opposed to bisphosphonates, denosumab does not incorporate into bone matrix and bone turnover is not suppressed after its cessation. Recent reports imply that denosumab discontinuation may lead to an increased risk of multiple vertebral fractures., Methods: The European Calcified Tissue Society (ECTS) formed a working group to perform a systematic review of existing literature on the effects of stopping denosumab and provide advice on management., Results: Data from phase 2 and 3 clinical trials underscore a rapid decrease of bone mineral density (BMD) and a steep increase in bone turnover markers (BTMs) after discontinuation of denosumab. Clinical case series report multiple vertebral fractures after discontinuation of denosumab and a renewed analysis of FREEDOM and FREEDOM Extension Trial suggests, albeit does not prove, that the risk of multiple vertebral fractures may be increased when denosumab is stopped due to a rebound increase in bone resorption., Conclusion: There appears to be an increased risk of multiple vertebral fractures after discontinuation of denosumab although strong evidence for such an effect and for measures to prevent the occurring bone loss is lacking. Clinicians and patients should be aware of this potential risk. Based on available data, a re-evaluation should be performed after 5years of denosumab treatment. Patients considered at high fracture risk should either continue denosumab therapy for up to 10years or be switched to an alternative treatment. For patients at low risk, a decision to discontinue denosumab could be made after 5years, but bisphosphonate therapy should be considered to reduce or prevent the rebound increase in bone turnover. However, since the optimal bisphosphonate regimen post-denosumab is currently unknown continuation of denosumab can also be considered until results from ongoing trials become available. Based on current data, denosumab should not be stopped without considering alternative treatment in order to prevent rapid BMD loss and a potential rebound in vertebral fracture risk., (Copyright © 2017 Elsevier Inc. All rights reserved.)