Hotchkiss Charlotte E, Latendresse John, Ferguson Sherry A
The Bionetics Corporation, 2Toxicologic Pathology Associates, National Center for Toxicological Research (NCTR), Jefferson, Arkansas, USA.
Comp Med. 2006 Dec;56(6):502-11.
13-cis-retinoic acid (13-cis-RA, isotretinoin) is used to treat severe recalcitrant acne. Other retinoids have adverse effects on bone. Recent studies of human patients treated with 13-cis-RA have had varying results, perhaps because of variability among patients and the lack of control groups. The effects of retinoids have been studied in rodents, but little information is available regarding the effects of clinically relevant retinoid doses as evaluated by use of bone densitometric techniques. We treated rats for 15 or 20 wk with 13-cis-RA, all-trans-RA, or soybean oil (control) by gavage. We used dual-energy X-ray absorptiometry, histomorphometry, and histologic evaluation to evaluate effects on bone. Spontaneous long bone fractures occurred in some rats treated with 15 mg/kg all-trans-RA daily. Bone mineral density, bone mineral content, bone diameter, and cortical thickness of the femur were reduced in rats treated daily with 10 or 15 mg/kg all-trans-RA or 30 mg/kg 13-cis-RA. The lumbar spine was not affected. Although the effects of 13-cis-RA were not as dramatic as those of all-trans-RA, further study of the effects of 13-cis-RA on long bones is warranted.
13 - 顺式维甲酸（13 - cis - RA，异维甲酸）用于治疗重度难治性痤疮。其他维甲酸类药物对骨骼有不良影响。近期对接受13 - 顺式维甲酸治疗的人类患者的研究结果各异，这可能是由于患者个体差异以及缺乏对照组所致。维甲酸类药物对啮齿动物的影响已得到研究，但关于通过骨密度测量技术评估的临床相关维甲酸剂量的影响，目前可用信息较少。我们通过灌胃法用13 - 顺式维甲酸、全反式维甲酸或大豆油（对照）对大鼠进行15或20周的治疗。我们使用双能X线吸收法、组织形态计量学和组织学评估来评估对骨骼的影响。一些每天接受15 mg/kg全反式维甲酸治疗的大鼠发生了自发性长骨骨折。每天接受10或15 mg/kg全反式维甲酸或30 mg/kg 13 - 顺式维甲酸治疗的大鼠，其股骨的骨密度、骨矿物质含量、骨直径和皮质厚度均降低。腰椎未受影响。尽管13 - 顺式维甲酸的影响不如全反式维甲酸显著，但仍有必要进一步研究13 - 顺式维甲酸对长骨的影响。
