Department of Orthopedics, Affiliated Kunshan Hospital of Jiangsu University, Suzhou, China.
Department of Orthopedics, Gusu School, Nanjing Medical University, Suzhou, China.
Front Endocrinol (Lausanne). 2022 Oct 10;13:991913. doi: 10.3389/fendo.2022.991913. eCollection 2022.
To elucidate the independent correlation between vitamin D content and zoledronate (ZOL)-triggered acute-phase response (APR) fever risk in osteoporotic (OP) patients, and to examine the potential threshold for optimal vitamin D concentrations that prevent the occurrence of ZOL-induced fever.
This retrospective investigation was based on a prospectively documented database compiled at the Affiliated Kunshan Hospital of Jiangsu University between January 2015 and March 2022. In total, 2095 OP patients, who received ZOL during hospitalization, were selected for analysis. The primary endpoint was the presence (>37.3°C) or absence (≤37.3°C) of fever, quantified by the maximum body temperature, measured within 3 days of ZOL infusion. The exposure variable was the baseline serum 25-hydroxyvitamin D (25[OH]D) levels.
The OP patients with fever exhibited markedly reduced 25(OH)D content than those without fever. Upon adjusting for age, gender, order of infusion of ZOL, main diagnosis, season of blood collection, year of blood collection, calcitonin usage, and beta-C-terminal telopeptide of type I collagen (β-CTX) levels, a 10 ng/mL rise in serum 25(OH)D content was correlated with a 14% (OR, 0.86; 95% CI, 0.76 to 0.98, -value = 0.0188) decrease in the odds of ZOL-induced fever. In addition, a non-linear relationship was also observed between 25(OH)D levels and fever risk, and the turning point of the adjusted smoothed curve was 35 ng/mL of serum 25(OH)D content.
Herein, we demonstrated the independent negative relationship between serum 25(OH)D content and ZOL-induced fever risk. According to our analysis, 25(OH)D above 35 ng/mL may be more effective in preventing ZOL-induced APR. If this is confirmed, a "vitamin D supplemental period" is warranted prior to ZOL infusion, particularly the first ZOL infusion, to ensure appropriate 25(OH)D levels that protect against ZOL-induced fever.
阐明维生素 D 含量与唑来膦酸（ZOL）引发的骨质疏松症（OP）患者急性期反应（APR）发热风险之间的独立相关性，并探讨预防 ZOL 诱导发热的最佳维生素 D 浓度的潜在阈值。
本回顾性研究基于 2015 年 1 月至 2022 年 3 月在江苏大学附属医院建立的前瞻性文档数据库。共纳入 2095 例住院期间接受 ZOL 治疗的 OP 患者进行分析。主要终点是通过 ZOL 输注后 3 天内测量的最高体温来量化发热（>37.3°C）或不发热（≤37.3°C）的情况。暴露变量为基线血清 25-羟维生素 D（25[OH]D）水平。
发热的 OP 患者的 25（OH）D 含量明显低于无发热患者。在调整年龄、性别、ZOL 输注顺序、主要诊断、采血季节、采血年份、降钙素使用情况和 I 型胶原β-末端肽（β-CTX）水平后，血清 25（OH）D 含量每增加 10ng/ml，ZOL 引起的发热的几率降低 14%（OR，0.86；95%CI，0.76 至 0.98，-值=0.0188）。此外，还观察到 25（OH）D 水平与发热风险之间存在非线性关系，调整后的平滑曲线转折点为血清 25（OH）D 含量 35ng/ml。
本研究证明了血清 25（OH）D 含量与 ZOL 诱导的发热风险之间存在独立的负相关关系。根据我们的分析，血清 25（OH）D 水平高于 35ng/ml 可能更有效地预防 ZOL 引起的 APR。如果这一结果得到证实，在 ZOL 输注前，特别是首次 ZOL 输注前，需要进行“维生素 D 补充期”，以确保适当的 25（OH）D 水平，预防 ZOL 引起的发热。
