Le Minh V, Sim Felix, Varatharajah Kapilan, Goh Asher, Yates Christopher J
Department of Diabetes and Endocrinology, Royal Melbourne Hospital, Melbourne, VIC 3050, Australia.
Department of Oral and Maxillofacial Surgery, Royal Melbourne Hospital, Melbourne, VIC 3050, Australia.
JBMR Plus. 2024 Dec 13;9(2):ziae164. doi: 10.1093/jbmrpl/ziae164. eCollection 2025 Feb.
Cherubism is a rare autosomal dominant skeletal dysplasia, affecting the maxilla and/or mandible. The condition typically has childhood onset, followed by progression until puberty, with subsequent regression. Cherubism lesions share histological features with giant cell tumor of bone, where high-dose monthly denosumab is an effective medical treatment. Therefore, high-dose denosumab has also been trialed in children with cherubism with positive outcomes. However, the role of denosumab in adult cherubism, particularly a lower dose and frequency, has not been established. We present the case of a 60-year-old man with cherubism, reviewed for a new 39 × 21 mm left mandibular lesion. The patient had multiple surgeries up to the age of 30 for tumors in the right maxilla and mandible. Given the impact of further surgery on his appearance and quality of life, the patient was referred to Endocrinology for consideration of medical therapy. His bone turnover markers were slightly elevated with normal calcium, phosphate, 25-OH vitamin D, and parathyroid hormone levels. A bone density scan showed lumbar spine osteopenia. He was commenced on 60 mg denosumab 6-monthly with excellent clinical and radiological responses over the next 30 months. The most recent CT mandible showed a sustained reduction in the lesion size, measuring 36 × 18 mm, with osteoid formation and improvement in cortical thinning. Surgery is no longer indicated. No adverse effects from denosumab were reported in the patient. This is the first study to report the efficacy and safety of a low-dose denosumab regimen in the management of cherubism. This treatment approach was able to prevent major surgery and minimize denosumab-related adverse effects. While the optimal treatment duration remains unclear, the patient will continue with 60 mg denosumab 6-monthly in the short-term given the favorable response. In summary, a low-dose denosumab regimen should be considered for patients with cherubism, particularly those with contraindications or preferences to avoid surgery.
cherubism是一种罕见的常染色体显性遗传性骨骼发育不良，影响上颌骨和/或下颌骨。该病通常在儿童期发病，随后进展至青春期，之后病情会逐渐缓解。 cherubism病变与骨巨细胞瘤具有共同的组织学特征，高剂量每月一次的地诺单抗是一种有效的药物治疗方法。因此，高剂量地诺单抗也已在患有cherubism的儿童中进行试验，并取得了积极的结果。然而，地诺单抗在成人cherubism中的作用，特别是较低剂量和频率的作用，尚未得到证实。我们报告了一例60岁患有cherubism的男性病例，对其新出现的左侧下颌骨39×21mm病变进行了检查。该患者在30岁之前因右上颌骨和下颌骨的肿瘤接受了多次手术。考虑到进一步手术对其外貌和生活质量的影响，该患者被转诊至内分泌科考虑药物治疗。他的骨转换标志物略有升高，而钙、磷、25-羟维生素D和甲状旁腺激素水平正常。骨密度扫描显示腰椎骨质减少。他开始每6个月注射60mg地诺单抗，在接下来的30个月里，临床和影像学反应良好。最近的下颌骨CT显示病变大小持续缩小，为36×18mm，有类骨质形成，皮质变薄情况有所改善。不再需要手术治疗。该患者未报告地诺单抗的不良反应。这是第一项报告低剂量地诺单抗方案治疗cherubism的疗效和安全性的研究。这种治疗方法能够避免大手术，并将地诺单抗相关的不良反应降至最低。虽然最佳治疗持续时间尚不清楚，但鉴于反应良好，该患者短期内将继续每6个月注射60mg地诺单抗。总之，对于患有cherubism的患者，特别是那些有手术禁忌证或倾向于避免手术的患者，应考虑采用低剂量地诺单抗方案。
