van de Laarschot Denise M, Zillikens M Carola
Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands.
Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands.
Bone. 2016 Oct;91:148-51. doi: 10.1016/j.bone.2016.07.022. Epub 2016 Jul 29.
Long-term use of bisphosphonates has raised concerns about the association with Atypical Femur Fractures (AFFs) that have been reported mainly in postmenopausal women. We report a case of an 18-year-old patient with juvenile osteoporosis based on X-linked osteoporosis due to a PLS3 mutation who developed a low trauma femoral fracture after seven years of intravenous and two years of oral bisphosphonate use, fulfilling the revised ASBMR diagnostic criteria of an AFF. The occurrence of AFFs has not been described previously in children or adolescents. The underlying monogenetic bone disease in our case strengthens the possibility of a genetic predisposition at least in some cases of AFF. We cannot exclude that a transverse fracture of the tibia that also occurred after a minor trauma at age 16 might be part of the same spectrum of atypical fractures related to the use of bisphosphonates. In retrospect our patient experienced prodromal pain prior to both the tibia and the femur fracture. Case reports of atypical fractures in children with a monogenetic bone disease such as Osteogenesis Imperfecta (OI) or juvenile osteoporosis are important to consider in the discussion about optimal duration of bisphosphonate therapy in growing children. In conclusion, this case report 1) highlights that AFFs also occur in adolescents treated with bisphosphonates during childhood and pain in weight-bearing bones can point towards this diagnosis 2) supports other reports suggesting that low trauma fractures of other long bones besides the femur may be related to long-term use of bisphosphonates 3) strengthens the concept of an underlying genetic predisposition in some cases of AFF, now for the first time reported in X-linked osteoporosis due to a mutation in PLS3 and 4) should be considered in decisions about the duration of bisphosphonate therapy in children with congenital bone disorders.
长期使用双膦酸盐引发了人们对其与非典型股骨骨折（AFFs）相关性的担忧，此类骨折主要在绝经后女性中被报道。我们报告了一例18岁患有青少年骨质疏松症的患者，其病因是由于PLS3基因突变导致的X连锁骨质疏松症，在静脉注射双膦酸盐7年及口服双膦酸盐2年后发生了低创伤性股骨骨折，符合修订后的美国骨矿研究学会（ASBMR）AFF诊断标准。此前尚未有儿童或青少年发生AFFs的报道。我们病例中的潜在单基因骨病强化了至少在某些AFF病例中存在遗传易感性的可能性。我们不能排除16岁时在一次轻微创伤后发生的胫骨横行骨折可能是与双膦酸盐使用相关的同一类非典型骨折谱的一部分。回顾来看，我们的患者在胫骨和股骨骨折之前都经历了前驱疼痛。在讨论生长中的儿童双膦酸盐治疗的最佳疗程时，患有诸如成骨不全（OI）或青少年骨质疏松症等单基因骨病的儿童非典型骨折的病例报告很重要。总之，本病例报告1）强调AFFs也发生在儿童期接受双膦酸盐治疗的青少年中，负重骨疼痛可能指向这一诊断；2）支持其他报告，表明除股骨外其他长骨的低创伤骨折可能与双膦酸盐的长期使用有关；3）强化了在某些AFF病例中存在潜在遗传易感性的概念，这是首次在因PLS3基因突变导致的X连锁骨质疏松症中报道；4）在决定先天性骨病儿童双膦酸盐治疗疗程时应予以考虑。
