Department of Medical Research, 251 Hellenic Air Force & VA General Hospital, 3 Kanellopoulou st, 11525, Athens, Greece.
Department of Endocrinology and Diabetes, 251 Hellenic Air Force & VA General Hospital, Athens, Greece.
Osteoporos Int. 2024 Feb;35(2):365-370. doi: 10.1007/s00198-023-06931-3. Epub 2023 Oct 2.
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 = 0.619; p < 0.001), but not with serum P1NP values or BMD at all skeletal sites.
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.
在绝经后骨质疏松症女性中，观察到 denosumab（Dmab）治疗时间与停药后骨丢失之间呈反比关系，其病因目前尚不清楚。在小鼠研究中，RANKL 抑制与破骨细胞前体和成骨细胞形态的增加有关，这些细胞会在破骨细胞中循环，并随着时间的推移而积累。我们假设，Dmab 对 RANKL 的更长时间抑制将导致停药后同步形成更多的破骨细胞。为了验证这一假设，我们测量了接受 Dmab 治疗不同时间（最长 10 年）的绝经后女性的血清 TRAcP5b，这是一种破骨细胞数量的标志物。
在 59 名接受 Dmab 治疗 4.0±2.3 年（1-10 年）的女性中，在最后一次 Dmab 注射后 6.0±15 天测量了 TRAcP5b、Ⅰ型胶原 C 端肽（CTX）和Ⅰ型前胶原 N 端前肽（P1NP）。其中 38 例为治疗初治患者（组 1），21 例在接受 Dmab 治疗前接受了其他治疗（组 2）。
Dmab 治疗时间与整个队列或两组中血清 TRAcP5b 值或 TRAcP5b/CTX 比值均无相关性。相反，血清 TRAcP5b 值与血清 CTX 值显著相关（r=0.619；p<0.001），但与血清 P1NP 值或所有骨骼部位的 BMD 均无关。
我们的观察结果表明，在 Dmab 注射后 6 个月测量的血清 TRAcP5b 不是一种有用的早期标志物，不能用于预测人类破骨细胞随时间积累增加，也不能用于识别骨吸收反弹增加风险较高的患者。
