Of mice and men: divergent risks of teriparatide-induced osteosarcoma
Of mice and men: divergent risks of teriparatide-induced osteosarcoma
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DOI：
10.1007/s00198-009-1004-0
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发表时间：
2010-06-01
影响因子：
4
通讯作者：
Ludwig, J. A.
中科院分区：
文献类型：
--
作者：
Subbiah, V.;Madsen, V. S.;Ludwig, J. A.
自2002年12月获得美国食品和药物管理局（FDA）批准以来，特立哌酮（重组1-34 PTH; ForteoA（R））已被超过43万名患者安全使用。然而，在FDA批准之前，人们担心特立帕妥可能会增加患者患骨肉瘤的风险，因为在最高测试剂量水平下接受这种药物治疗的大鼠中，近45%的大鼠患上了这种侵袭性的骨癌。为了平衡临床试验所证明的特立帕肽的益处与特立帕肽诱导人骨肉瘤的理论风险，FDA要求对这种潜在副作用进行“黑匣子”警告，并要求公司赞助上市后监测计划。作为该监测计划的参与机构，我们报告了第二个潜在的特立帕肽诱导的骨肉瘤患者，在这种情况下，伴有盆腔放射史。考虑到特立帕肽药物的理论风险和已知的诱导骨肉瘤的放射风险，我们提出了一个问题，即teriparterine是否会放大辐射的风险，诱导我们患者的骨肉瘤，并试图确定哪个因素在他的疾病的发展中起主导作用。我们分析了临床前大鼠数据，人类使用特立帕肽的临床经验，和我们病人的临床病史，以评估人类的风险teriparbidine和辐射暴露。第一例疑似骨肉瘤报告后，在2005年12月，不到一年后，我们遇到了第二个可能的特立帕肽诱导的骨肉瘤。临床前动物数据的审查表明，当按照生产商的建议使用时，特立帕鲁肽可安全用于人体。考虑到肉瘤在辐射范围内的位置以及诊断前对teriparbazole的有限暴露，teriparbazole不太可能在该患者骨肉瘤的出现中发挥主要作用。然而，我们不能排除特立哌酮放大放射治疗的致癌作用而诱发骨肉瘤的可能性。在超过43万例接受特立哌酮治疗严重骨质疏松症的患者中，我们报告了第二例发生骨肉瘤的患者。尽管特立帕替尼可减少某些患者人群中的骨关节炎相关骨折，但在使用前应考虑重要的禁忌症，如既往放射暴露。
Since approval by the U.S. Food and Drug Administration (FDA) in December 2002, teriparatide (recombinant 1-34 PTH; ForteoA (R)) has been safely used by more than 430,000 patients. Prior to FDA approval, however, there was concern that teriparatide might increase the risk for patients to develop osteosarcoma, as almost 45% of the rats treated with this drug at the highest-tested dose level developed this aggressive form of bone cancer. Balancing the proven benefits of teriparatide shown by clinical trials with the theoretical risk for teriparatide-induced human osteosarcoma, the FDA mandated both a 'black-box' warning of this potential side-effect and a company-sponsored postmarketing surveillance program. As a participating institute of that surveillance program, we report upon the second person with potential teriparatide-induced osteosarcoma, in this case, complicated by a history of pelvic radiation.Given the theoretic risk of the drug teriparatide and the known risk of radiation in inducing osteosarcoma, we raise the issue of whether teriparatide magnified the risk of radiation-induced osteosarcoma in our patient and try to determine which factor played the predominant role in the development of his disease.We analyzed preclinical rat data, human clinical experience with teriparatide, and our patient's clinical history to assess the human risk of teriparatide and radiation exposure.After the first case of suspected osteosarcoma was reported in December 2005, we encountered a second possible teriparatide-induced osteosarcoma less than a year later. Review of the preclinical animal data would suggest that teriparatide is safe for human use when used as recommended by the manufacturer. Given the location of the sarcoma within the field of radiation and the limited exposure to teriparatide before diagnosis, it is unlikely that teriparatide played the predominant role in the emergence of this patient's osteosarcoma. We cannot, however, exclude the possibility that teriparatide magnified the carcinogenic effect of radiation therapy to induce the osteosarcoma.Of more than 430,000 persons who have received teriparatide for treatment of severe osteoporosis, we report the second patient to develop osteosarcoma. Although teriparatide reduces osteoporosis-related fractures in select patient populations, important contraindications, such as prior radiation exposure, should be considered before use.