Abstract：
BACKGROUND: Increased RANKL expression is observed in the bone tissue of fibrous dysplasia of bone/McCune-Albright syndrome (FD/MAS). In one animal model of FD/MAS, the inhibition of RANKL reduced tumor volume. A beneficial effect of denosumab on pain in patients refractory to bisphosphonates has been reported, but without systematic quantification of pain improvement. This work describes the clinical experience of our group on the efficacy on pain of denosumab treatment, along with safety, in FD/MAS patients refractory to bisphosphonates.
METHODS: We have conducted a retrospective multicenter study in 6 academic rheumatology centers in France. We have collected patients and FD/MAS characteristics, duration of prior exposure to bisphosphonates, denosumab treatment modalities (dosage - administration regimen - number of courses); evolution of pain evaluated by Visual Analogic Scale (VAS).
RESULTS: 13 patients were included (10 women and 3 men) 45 years on average, 5 MAS, 4 monostotic and 4 polyostotic forms. The average duration post-diagnosis of FD/MAS was 25 years and the mean duration of prior exposure to bisphosphonates was 4.7 years. Pain could be analyzed in 7 patients, showing a significant improvement from a mean VAS of 7.8 to 2.9 (-4.9 points, p = 0.003). In one patient with fronto-orbital FD/MAS, a 30 % decrease in lesional volume, assessed by MRI, was observed within 6 months of treatment, that was sustained over the following 12 months. Treatment regimens were heterogeneous. No hypercalcemia was observed after treatment cessation and the clinical tolerance was good.
CONCLUSIONS: This study suggests that denosumab reduces pain in patients with DF/MAS refractory to bisphosphonates, and quantifies this improvement for the first time in a multicenter study. In our cohort, no patients who discontinued denosumab developed hypercalcemia and clinical tolerance was overall good. This study also provides encouraging data regarding lesion volume control. Further controlled studies are required to determine the place and modalities of the denosumab treatment of FD/MAS.
CONCLUSIONS: Denosumab significantly decreased pain in FD/MAS refractory to bisphosphonate. This study paves the way for a randomized clinical trial to validate and standardize the prescription of denosumab in FD/MAS.
METHODS: We have conducted a retrospective multicenter study in 6 academic rheumatology centers in France. We have collected patients and FD/MAS characteristics, duration of prior exposure to bisphosphonates, denosumab treatment modalities (dosage - administration regimen - number of courses); evolution of pain evaluated by Visual Analogic Scale (VAS).
RESULTS: 13 patients were included (10 women and 3 men) 45 years on average, 5 MAS, 4 monostotic and 4 polyostotic forms. The average duration post-diagnosis of FD/MAS was 25 years and the mean duration of prior exposure to bisphosphonates was 4.7 years. Pain could be analyzed in 7 patients, showing a significant improvement from a mean VAS of 7.8 to 2.9 (-4.9 points, p = 0.003). In one patient with fronto-orbital FD/MAS, a 30 % decrease in lesional volume, assessed by MRI, was observed within 6 months of treatment, that was sustained over the following 12 months. Treatment regimens were heterogeneous. No hypercalcemia was observed after treatment cessation and the clinical tolerance was good.
CONCLUSIONS: This study suggests that denosumab reduces pain in patients with DF/MAS refractory to bisphosphonates, and quantifies this improvement for the first time in a multicenter study. In our cohort, no patients who discontinued denosumab developed hypercalcemia and clinical tolerance was overall good. This study also provides encouraging data regarding lesion volume control. Further controlled studies are required to determine the place and modalities of the denosumab treatment of FD/MAS.
CONCLUSIONS: Denosumab significantly decreased pain in FD/MAS refractory to bisphosphonate. This study paves the way for a randomized clinical trial to validate and standardize the prescription of denosumab in FD/MAS.
摘要：
背景：在骨/McCune-Albright综合征（FD/MAS）的纤维发育不良的骨组织中观察到RANKL表达增加。在一种FD/MAS动物模型中，RANKL的抑制减小了肿瘤体积。已经报道了denosumab对双膦酸盐难治性患者疼痛的有益效果，但没有系统地量化疼痛的改善。这项工作描述了我们小组对denosumab治疗疼痛疗效的临床经验，还有安全,双膦酸盐难治性FD/MAS患者。
方法：我们在法国6个风湿病学术中心进行了一项多中心回顾性研究。我们收集了患者和FD/MAS特征，先前接触双膦酸盐的持续时间，denosumab治疗方式（剂量-给药方案-疗程数）；通过视觉类比量表（VAS）评估疼痛的演变。
结果：包括13例患者（10例女性和3例男性），平均45年，5MAS,4个单核和4个多核形式。FD/MAS诊断后的平均持续时间为25年，先前暴露于双膦酸盐的平均持续时间为4.7年。可以分析7例患者的疼痛，显示出比7.8至2.9的平均VAS有显著改善(-4.9分，p=0.003)。在一名前眶FD/MAS患者中，病灶体积减少30%,通过MRI评估，在治疗后6个月内观察到，在接下来的12个月中持续了下来。治疗方案是异质的。治疗停止后未观察到高钙血症，临床耐受性良好。
结论：这项研究表明，denosumab可以减轻双膦酸盐难治性DF/MAS患者的疼痛，并在多中心研究中首次量化了这种改善。在我们的队列中，停用地诺塞马的患者没有出现高钙血症,临床耐受性总体良好.这项研究还提供了有关病变体积控制的令人鼓舞的数据。需要进一步的对照研究来确定denosumab治疗FD/MAS的位置和方式。
结论：Denosumab可显著减轻双膦酸盐难治性FD/MAS的疼痛。这项研究为随机临床试验铺平了道路，以验证和标准化FD/MAS中denosumab的处方。
方法：我们在法国6个风湿病学术中心进行了一项多中心回顾性研究。我们收集了患者和FD/MAS特征，先前接触双膦酸盐的持续时间，denosumab治疗方式（剂量-给药方案-疗程数）；通过视觉类比量表（VAS）评估疼痛的演变。
结果：包括13例患者（10例女性和3例男性），平均45年，5MAS,4个单核和4个多核形式。FD/MAS诊断后的平均持续时间为25年，先前暴露于双膦酸盐的平均持续时间为4.7年。可以分析7例患者的疼痛，显示出比7.8至2.9的平均VAS有显著改善(-4.9分，p=0.003)。在一名前眶FD/MAS患者中，病灶体积减少30%,通过MRI评估，在治疗后6个月内观察到，在接下来的12个月中持续了下来。治疗方案是异质的。治疗停止后未观察到高钙血症，临床耐受性良好。
结论：这项研究表明，denosumab可以减轻双膦酸盐难治性DF/MAS患者的疼痛，并在多中心研究中首次量化了这种改善。在我们的队列中，停用地诺塞马的患者没有出现高钙血症,临床耐受性总体良好.这项研究还提供了有关病变体积控制的令人鼓舞的数据。需要进一步的对照研究来确定denosumab治疗FD/MAS的位置和方式。
结论：Denosumab可显著减轻双膦酸盐难治性FD/MAS的疼痛。这项研究为随机临床试验铺平了道路，以验证和标准化FD/MAS中denosumab的处方。
