Department of Oncology and Hematology, Hospital of Piacenza, Via Taverna, 49, 29100, Italy.
Head Face Med. 2011 Aug 17;7:16. doi: 10.1186/1746-160X-7-16.
Bisphosphonate - related osteonecrosis of the JAW (BRONJ) is a well known side effect of bisphosphonate therapies in oncologic and non oncologic patients. Since to date no definitive consensus has been reached on the treatment of BRONJ, novel strategies for the prevention, risk reduction and treatment need to be developed. We report a 75 year old woman with stage 3 BRONJ secondary to alendronate and pamidronate treatment of osteoporosis. The patient was unresponsive to recommended treatment of the disease, and her BRONJ was worsening. Since bone marrow stem cells are know as being multipotent and exhibit the potential for differentiation into different cells/tissue lineages, including cartilage, bone and other tissue, we performed autologous bone marrow stem cell transplantation into the BRONJ lesion of the patient.
Under local anesthesia a volume of 75 ml of bone marrow were harvested from the posterior superior iliac crest by aspiration into heparinized siringes. The cell suspension was concentrated, using Ficoll - Hypaque® centrifugation procedures, in a final volume of 6 ml. Before the injection of stem cells into the osteonecrosis, the patient underwent surgical toilet, local anesthesia was done and spongostan was applied as a carrier of stem cells suspension in the bone cavity, then 4 ml of stem cells suspension and 1 ml of patient's activated platelet-rich plasma were injected in the lesion of BRONJ.
A week later the residual spongostan was removed and two weeks later resolution of symptoms was obtained. Then the lesion improved with progressive superficialization of the mucosal layer and CT scan, performed 15 months later, shows improvement also of bone via concentric ossification: so complete healing of BRONJ (stage 0) was obtained in our patient, and 30 months later the patient is well and without signs of BRONJ.
To our knowledge this is the first case of BRONJ successfully treated with autologous stem cells transplantation with a complete response.
双膦酸盐相关性颌骨坏死(BRONJ)是双膦酸盐治疗在肿瘤和非肿瘤患者中的一种已知的副作用。由于迄今为止,对于 BRONJ 的治疗还没有达成明确的共识,因此需要开发新的预防、降低风险和治疗策略。我们报告了一例 75 岁女性患者,因骨质疏松症接受阿仑膦酸钠和帕米膦酸钠治疗而发生 3 期 BRONJ。该患者对推荐的疾病治疗无反应,BRONJ 正在恶化。由于骨髓干细胞具有多能性,并表现出分化为不同细胞/组织谱系的潜力,包括软骨、骨和其他组织,我们对患者的 BRONJ 病变进行了自体骨髓干细胞移植。
在局部麻醉下,通过抽吸肝素化注射器从后上髂嵴中采集 75ml 骨髓。细胞悬浮液通过 Ficoll-Hypaque®离心程序浓缩,最终体积为 6ml。在将干细胞注入骨坏死前,患者接受手术清洗,局部麻醉,将海绵骨作为干细胞悬浮液在骨腔中的载体应用,然后将 4ml 干细胞悬浮液和 1ml 患者激活的富含血小板的血浆注入 BRONJ 病变部位。
一周后去除残留的海绵骨,两周后症状得到缓解。然后,病变随着黏膜层的逐渐浅表化而改善,15 个月后进行 CT 扫描显示,通过同心骨化,骨也得到改善:因此,我们的患者获得了 BRONJ(0 期)的完全愈合,30 个月后患者状况良好,没有 BRONJ 的迹象。
据我们所知,这是首例使用自体干细胞移植成功治疗 BRONJ 的病例,且反应完全。