Effective treatment of juvenile osteoporosis, which is frequently caused by glucocorticoid (GC) therapy, has not been established due to limited data regarding the efficacy and adverse effects of antiresorptive therapies on the growing skeleton. We previously demonstrated that sialic acid-binding immunoglobulin-like lectin 15 (Siglec-15) targeting therapy, which interferes with osteoclast terminal differentiation in the secondary, but not primary, spongiosa, increased bone mass without adverse effects on skeletal growth, whereas bisphosphonate, a first-line treatment for osteoporosis, increased bone mass but impaired long bone growth in healthy growing rats. In the present study, we investigated the efficacy of anti-Siglec-15 neutralizing antibody (Ab) therapy against GC-induced osteoporosis in a growing rat model. GC decreased bone mass and deteriorated mechanical properties of bone, due to a disproportionate increase in bone resorption. Both anti-Siglec-15 Ab and alendronate (ALN) showed protective effects against GC-induced bone loss by suppressing bone resorption, which was more pronounced with anti-Siglec-15 Ab treatment, possibly due to a reduced negative impact on bone formation. ALN induced histological abnormalities in the growth plate and morphological abnormalities in the long bone metaphysis but did not cause significant growth retardation. Conversely, anti-Siglec-15 Ab did not show any negative impact on the growth plate and preserved normal osteoclast and chondroclast function at the primary spongiosa. Taken together, these results suggest that anti-Siglec-15 targeting therapy could be a safe and efficacious prophylactic therapy for GC-induced osteoporosis in juvenile patients.

中文翻译：

---

Siglec-15靶向治疗可预防糖皮质激素诱导的幼年大鼠生长骨骼骨质疏松症

由于关于抗骨吸收疗法对生长骨骼的疗效和副作用的数据有限，尚未确定有效治疗通常由糖皮质激素 (GC) 治疗引起的青少年骨质疏松症。我们之前证明，唾液酸结合免疫球蛋白样凝集素 15 (Siglec-15) 靶向治疗会干扰继发性而非原发性海绵体中的破骨细胞终末分化，增加骨量而对骨骼生长没有不利影响，而双膦酸盐，骨质疏松症的一线治疗，增加了健康生长大鼠的骨量，但损害了长骨生长。在本研究中，我们在生长的大鼠模型中研究了抗 Siglec-15 中和抗体 (Ab) 治疗对 GC 诱导的骨质疏松症的疗效。由于骨吸收的不成比例增加，GC降低了骨量并恶化了骨的机械性能。抗 Siglec-15 Ab 和阿仑膦酸盐 (ALN) 通过抑制骨吸收显示出对 GC 诱导的骨丢失的保护作用，这在抗 Siglec-15 Ab 治疗中更为明显，可能是由于减少了对骨形成的负面影响。ALN 诱导生长板的组织学异常和长骨干骺端的形态学异常，但没有引起明显的生长迟缓。相反，抗 Siglec-15 Ab 对生长板没有任何负面影响，并且在原发性海绵体中保留了正常的破骨细胞和软骨细胞功能。综合起来，