Summary

Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome caused by tumoral overproduction of FGF-23. Due to local recurrence, we describe the long-term efficacy and safety profile of burosumab, an anti-FGF-23 monoclonal antibody, in a TIO patient after three unsuccessfully surgical attempts.

Introduction

TIO is a rare paraneoplastic syndrome caused by tumoral overproduction of fibroblast growth factor 23 (FGF23), resulting in hyperphospaturia, hypophosphatemia, and osteomalacia. Surgery is the only definitive treatment, but tumor can locally recur, even after years from primary surgery. Furthermore, some tumors cannot be removed by surgery due to their location.

Methods

We describe the case of a 54-year-old woman affected by recurrent TIO who, after three unsuccessful surgical attempts of tumor removal, was treated with burosumab, an anti-FGF-23 monoclonal antibody.

Results

The patient was referred to our Bone Unit after experiencing several fractures in different sites, both traumatic and non-traumatic. At the time of first evaluation, at the age of 46, serum-phosphate (SP) was 1.2 mg/dL (reference range (RR) 2.5–4.5), 24-h urinary phosphate was 842 mg (RR 400–1000), and intact-FGF-23 was 117 pg/mL (RR 25–45). Imaging showed a metabolic pre-sacral lesion that firstly underwent to exploratory laparotomy. Then, patient underwent to surgical excision of tumor. After 18 months of well-being, tumor relapsed and even the subsequent surgery was not able to completely remove it. Since 2015, patient was maintained in phosphorus supplements and 1,25(OH)₂vitamin D₃, but SP levels never normalized. In September 2019, she was started on burosumab, initially at the dose of 0.3 mg/kg/month, progressively increased to the current 0.8 mg/kg/month, with great improvement of pain, physical performance, and normalization of SP levels. Burosumab was temporary and cautionary discontinued for COVID-19 pneumonia, with a worsening of SP. After restart of burosumab, biochemistry returned to normal.

Conclusions

To our knowledge, this is the first European patient affected by TIO treated with burosumab for more than 2 years. Burosumab is a promising therapy in the medical treatment of TIO refractory or not eligible for definitive surgery, with good efficacy and safety profile.

中文翻译：

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长期使用burosumab治疗肿瘤诱导的骨软化症

概括

肿瘤诱导的骨软化症 (TIO) 是一种罕见的副肿瘤综合征，由 FGF-23 的肿瘤过度产生引起。由于局部复发，我们描述了 burosumab（一种抗 FGF-23 单克隆抗体）在 TIO 患者中在三次手术尝试失败后的长期疗效和安全性。

介绍

TIO 是一种罕见的副肿瘤综合征，由成纤维细胞生长因子 23 (FGF23) 的肿瘤过度产生，导致高磷尿、低磷血症和骨软化症。手术是唯一确定的治疗方法，但即使初次手术后数年，肿瘤也可能局部复发。此外，一些肿瘤由于其位置而无法通过手术切除。

方法

我们描述了一名 54 岁女性受复发性 TIO 影响的病例，该女性在 3 次肿瘤切除手术尝试失败后，接受了抗 FGF-23 单克隆抗体 burosumab 治疗。

结果

患者在不同部位经历了几次骨折（包括创伤性和非创伤性）后被转诊到我们的骨科。在第一次评估时，46 岁时，血清磷酸盐 (SP) 为 1.2 mg/dL（参考范围 (RR) 2.5-4.5），24 小时尿磷酸盐为 842 mg（RR 400-1000），完整的 FGF-23 为 117 pg/mL (RR 25–45)。影像学显示一个代谢性的骶前病变，首先进行了剖腹探查。然后，患者接受了手术切除肿瘤。经过18个月的健康，肿瘤复发了，甚至随后的手术也无法将其完全切除。自 2015 年以来，患者一直服用磷补充剂和 1,25(OH) ₂维生素 D ₃，但 SP 水平从未归一化。2019 年 9 月，她开始使用 burosumab，最初的剂量为 0.3 mg/kg/月，逐渐增加到目前的 0.8 mg/kg/月，疼痛、身体机能和 SP 水平正常化有很大改善。由于 SP 恶化， Burosumab 是暂时性的，并因 COVID-19 肺炎而被警告停用。重新启动burosumab后，生化恢复正常。

结论

据我们所知，这是欧洲首位接受 burosumab 治疗超过 2 年的 TIO 患者。Burosumab 是治疗 TIO 难治性或不适合根治性手术的一种很有前景的疗法，具有良好的疗效和安全性。