戈谢病(GD)患者进行性骨受累,临床表现为衰弱性骨痛,骨结构改变,骨髓浸润(BMI),锥形瓶(EM)畸形,和骨质疏松症。大多数GD患者表示疼痛,尽管有这种治疗类型,但疼痛仍持续存在。GD的疼痛被描述为慢性深穿透性疼痛;然而,有时,患者经历严重的急性疼痛。骨痛的来源主要被争论为继发于骨病理学或神经性或炎症起源的伤害性疼痛。骨细胞构成协调骨重建的分泌分子的重要来源。骨细胞标志物,硬化蛋白(SOST)和Dickkopf-1(DKK-1),使经典的Wnt信号通路失活并导致骨形成抑制。因此,循环硬化蛋白和DKK-1是骨骼异常的潜在生物标志物.本研究旨在评估GD患者硬化蛋白和DKK-1的循环水平及其与临床骨病理参数的相关性:疼痛,骨矿物质密度(BMD),和EM畸形。根据骨骼表现的存在和严重程度,将39例GD患者分为队列。通过酶联免疫吸附测定定量血清硬化蛋白和DKK-1的水平。在患有疼痛的GD患者中测量到最高水平的硬化蛋白,BMI,和EM畸形。多参数分析表明,95%的GD患者有疼痛,BMI,EM畸形的硬化蛋白水平升高。大多数硬化蛋白升高的患者也有骨质减少或骨质疏松症。此外,循环硬化蛋白水平随年龄增加,与同年龄组的健康对照组相比,GD患者的硬化素水平升高。Pearson线性相关分析显示,健康对照组和骨密度正常的GD患者血清DKK-1与硬化蛋白呈正相关。然而,骨量减少或骨质疏松的GD患者硬化蛋白和DKK-1之间的平衡减弱。总之,骨细胞标记,硬化蛋白,当升高时,与骨痛有关,BMI,GD患者的EM烧瓶畸形。硬化蛋白/DKK-1比率的改变与骨矿物质密度的降低相关。这些数据证实了Wnt信号通路在GD相关骨病中起作用。硬化蛋白和骨痛可以作为生物标志物来评估BMI和EM烧瓶畸形高风险患者。
Patients with Gaucher disease (GD) have progressive bone involvement that clinically presents with debilitating bone pain, structural bone changes, bone marrow infiltration (BMI), Erlenmeyer (EM) flask deformity, and osteoporosis. Pain is referred by the majority of GD patients and continues to persist despite the type of therapy. The pain in GD is described as chronic deep penetrating pain; however, sometimes, patients experience severe acute pain. The source of bone pain is mainly debated as nociceptive pain secondary to bone pathology or neuropathic or inflammatory origins. Osteocytes constitute a significant source of secreted molecules that coordinate bone remodeling. Osteocyte markers, sclerostin (SOST) and Dickkopf-1 (DKK-1), inactivate the canonical Wnt signaling pathway and lead to the inhibition of bone formation. Thus, circulated sclerostin and DKK-1 are potential biomarkers of skeletal abnormalities. This study aimed to assess the circulating levels of sclerostin and DKK-1 in patients with GD and their correlation with clinical bone pathology parameters: pain, bone mineral density (BMD), and EM deformity. Thirty-nine patients with GD were classified into cohorts based on the presence and severity of bone manifestations. The serum levels of sclerostin and DKK-1 were quantified by enzyme-linked immunosorbent assays. The highest level of sclerostin was measured in GD patients with pain, BMI, and EM deformity. The multiparameter analysis demonstrated that 95% of GD patients with pain, BMI, and EM deformity had increased levels of sclerostin. The majority of patients with elevated sclerostin also have osteopenia or osteoporosis. Moreover, circulating sclerostin level increase with age, and GD patients have elevated sclerostin levels when compared with healthy control from the same age group. Pearson\'s linear correlation analysis showed a positive correlation between serum DKK-1 and sclerostin in healthy controls and GD patients with normal bone mineral density. However, the balance between sclerostin and DKK-1 waned in GD patients with osteopenia or osteoporosis. In conclusion, the osteocyte marker, sclerostin, when elevated, is associated with bone pain, BMI, and EM flask deformity in GD patients. The altered sclerostin/DKK-1 ratio correlates with the reduction of bone mineral density. These data confirm that the Wnt signaling pathway plays a role in GD-associated bone disease. Sclerostin and bone pain could be used as biomarkers to assess patients with a high risk of BMI and EM flask deformities.