Kindmark A, Rollman O, Mallmin H, Petrén-Mallmin M, Ljunghall S, Melhus H
Department of Internal Medicine, University Hospital, Uppsala, Sweden.
Acta Derm Venereol. 1998 Jul;78(4):266-9. doi: 10.1080/000155598441837.
Although dietary vitamin A is required for normal growth and development, long-term or high-dose administration of vitamin A derivatives (retinoids) may produce a variety of skeletal side-effects in man. In this study we investigated the early effects of oral isotretinoin therapy on bone turnover and calcium homeostasis in eleven consecutive patients with nodulocystic acne. The effects on bone metabolism were correlated to radiological and bone mineral density measurements following drug therapy for six months. Markers of bone turnover, i.e. serum osteocalcin, the carboxyterminal propeptide of type I collagen, bone specific alkaline phosphatase, the carboxyterminal telopeptide of type I collagen, and urine levels of calcium and hydroxyproline decreased significantly within five days of treatment (p < 0.05). There was also a statistically significant decrease in serum calcium, with a minimum on day five, and a marked increase in serum parathyroid hormone (p < 0.05). With continued treatment, however, the abnormal levels of these markers returned to baseline values within 14 days. No significant roentgenological changes or effects on bone mineral density were found in response to the drug. The observed inhibitory effects of isotretinoin on bone turnover, despite elevated parathyroid hormone levels, indicates that the drug exerts a direct effect on bone tissue.
尽管正常生长发育需要膳食维生素A，但长期或大剂量给予维生素A衍生物（维甲酸）可能会在人体产生多种骨骼方面的副作用。在本研究中，我们调查了连续11例结节囊肿性痤疮患者口服异维A酸治疗对骨转换和钙稳态的早期影响。将对骨代谢的影响与药物治疗6个月后的放射学和骨密度测量结果相关联。治疗5天内，骨转换标志物，即血清骨钙素、I型胶原羧基末端前肽、骨特异性碱性磷酸酶、I型胶原羧基末端端肽以及尿钙和羟脯氨酸水平显著下降（p < 0.05）。血清钙也有统计学意义的下降，在第5天降至最低，而血清甲状旁腺激素显著升高（p < 0.05）。然而，随着治疗的持续，这些标志物的异常水平在14天内恢复到基线值。未发现药物治疗引起明显的放射学变化或对骨密度有影响。尽管甲状旁腺激素水平升高，但观察到异维A酸对骨转换有抑制作用，这表明该药物对骨组织有直接作用。
