Makras Polyzois, Yavropoulou Maria P, Anastasilakis Athanasios D, Papatheodorou Athanasios, Papapoulos Socrates E
Department of Medical Research, 251 Hellenic Air Force & VA General Hospital, 3 Kanellopoulou Str, Athens, Greece.
Department of Medical Research, LCH Adult Clinic, 251 Hellenic Air Force & VA General Hospital, 3 Kanellopoulou Str, 11525, Athens, Greece.
Osteoporos Int. 2025 May 26. doi: 10.1007/s00198-025-07538-6.
Denosumab (Dmab) discontinuation in osteoporosis leads to overshoot (rebound) of bone turnover, but its cause remains largely unclear. In a prospective trial, Dmab-treated Langerhans cell histiocytosis (LCH) patients showed no overshoot of bone turnover markers despite high short-term dosing. Findings suggest that total Dmab dose does not drive the overshoot of bone turnover markers.
In patients with osteoporosis, the length of treatment with denosumab (Dmab) is an important risk factor for the overshoot (rebound) of bone turnover markers following its discontinuation. Whether this is due to the higher total Dmab dose given and/or the severity of the disease is unknown. To address this question, long-term follow-up of changes in bone metabolism after stopping Dmab with doses higher than those used in osteoporosis is essential.
In a prospective, single-arm, open label, phase 2b clinical trial, ten adult patients with Langerhans cell histiocytosis (LCH), eight with bone lesions (four single, four multiple) and two without, were treated with Dmab sc injections 120 mg/2 months for 6 months (total 480 mg) and were followed for 24 months after the last injection.
Treatment reduced bone turnover markers to about 10% of pretreatment values, which increased after treatment arrest to a peak that did not exceed pretreatment levels; mean (± SD) peak serum CTX 0.522 ± 0.366 ng/mL and P1NP 72.2 ± 35.9 ng/mL were not significantly different from baseline (p = 0.11 and 0.65, respectively). Moreover, pretreatment and peak serum CTX values were significantly correlated (r = 0.818, p = 0.007). No vertebral fractures, bone loss, or hypercalcemia were observed.
Dmab withdrawal in patients with LCH was not followed by an overshoot of bone turnover markers or bone loss despite the administration in 6 months of a total dose equal to that given in osteoporosis for 4 years. Total Dmab dose is, thus, not an important determinant of the bone turnover overshoot after treatment withdrawal.
骨质疏松症患者停用狄诺塞麦（Dmab）会导致骨转换过度（反弹），但其原因仍不清楚。在一项前瞻性试验中，接受Dmab治疗的朗格汉斯细胞组织细胞增多症（LCH）患者尽管短期高剂量给药，但骨转换标志物并未出现过度升高。研究结果表明，Dmab总剂量并非导致骨转换标志物过度升高的原因。
在骨质疏松症患者中，狄诺塞麦（Dmab）治疗时间是停药后骨转换标志物过度升高（反弹）的重要危险因素。这是由于给予的Dmab总剂量较高和/或疾病严重程度所致尚不清楚。为解决这个问题，对高于骨质疏松症治疗剂量的Dmab停药后骨代谢变化进行长期随访至关重要。
在一项前瞻性、单臂、开放标签的2b期临床试验中，10例成年朗格汉斯细胞组织细胞增多症（LCH）患者，其中8例有骨病变（4例单发，4例多发），2例无骨病变，接受皮下注射Dmab 120mg/2个月，共6个月（总剂量480mg），最后一次注射后随访24个月。
治疗使骨转换标志物降至治疗前值的约10%，停药后升高至峰值，但未超过治疗前水平；血清CTX均值（±标准差）峰值0.522±0.366ng/mL和P1NP 72.2±35.9ng/mL与基线无显著差异（分别为p = 0.11和0.65）。此外，治疗前和血清CTX峰值显著相关（r = 0.818，p = 0.007）。未观察到椎体骨折、骨质流失或高钙血症。
LCH患者停用Dmab后，尽管6个月内给予的总剂量与骨质疏松症4年的给药量相当，但并未出现骨转换标志物过度升高或骨质流失。因此，Dmab总剂量并非停药后骨转换过度的重要决定因素。
