Department of Psychiatry, University of Iowa Carver College of Medicine, Psychiatry Research, 2-209 MEB, 500 Newton Rd, Iowa City, IA 52242, USA.
J Clin Psychiatry. 2010 Mar;71(3):338-47. doi: 10.4088/JCP.08m04595gre.
The aim of the present study was to investigate the effect of risperidone-induced hyperprolactinemia on trabecular bone mineral density (BMD) in children and adolescents.
Medically healthy 7- to 17-year-old males chronically treated, in a naturalistic setting, with risperidone were recruited for this cross-sectional study through child psychiatry outpatient clinics between November 2005 and June 2007. Anthropometric measurements and laboratory testing were conducted. The clinical diagnoses were based on chart review, and developmental and treatment history was obtained from the medical record. Volumetric BMD of the ultradistal radius was measured using peripheral quantitative computed tomography, and areal BMD of the lumbar spine was estimated using dual-energy x-ray absorptiometry.
Hyperprolactinemia was present in 49% of 83 boys (n = 41) treated with risperidone for a mean of 2.9 years. Serum testosterone concentration increased with pubertal status but was not affected by hyperprolactinemia. As expected, bone mineral content and BMD increased with sexual maturity. After adjusting for the stage of sexual development and height and BMI z scores, serum prolactin was negatively associated with trabecular volumetric BMD at the ultradistal radius (P < .03). Controlling for relevant covariates, we also found treatment with selective serotonin reuptake inhibitors (SSRIs) to be associated with lower trabecular BMD at the radius (P = .03) and BMD z score at the lumbar spine (P < .05). These findings became more marked when the analysis was restricted to non-Hispanic white patients. Of 13 documented fractures, 3 occurred after risperidone and SSRIs were started, and none occurred in patients with hyperprolactinemia.
This is the first study to link risperidone-induced hyperprolactinemia and SSRI treatment to lower BMD in children and adolescents. Future research should evaluate the longitudinal course of this adverse event to determine its temporal stability and whether a higher fracture rate ensues.
本研究旨在探讨利培酮诱导的高催乳素血症对儿童和青少年的小梁骨骨密度（BMD）的影响。
本横断面研究招募了 2005 年 11 月至 2007 年 6 月期间在儿童精神病学门诊接受利培酮长期治疗的 7 至 17 岁男性。通过体格检查和实验室检测进行了相关指标的测量。临床诊断基于图表回顾，发育和治疗史则从病历中获得。使用外周定量计算机断层扫描测量桡骨远端容积 BMD，使用双能 X 线吸收法估计腰椎的面积 BMD。
在接受利培酮治疗的 83 名男孩中（n = 41），有 49%（41/83）存在高催乳素血症，平均治疗时间为 2.9 年。血清睾酮浓度随青春期进展而增加，但不受高催乳素血症影响。正如预期的那样，骨矿物质含量和 BMD 随性成熟而增加。在校正性发育阶段、身高和 BMI z 评分后，血清催乳素与桡骨远端小梁体积 BMD 呈负相关（P<.03）。控制相关协变量后，我们还发现选择性 5-羟色胺再摄取抑制剂（SSRIs）治疗与桡骨小梁 BMD 降低（P=0.03）和腰椎 BMD z 评分降低（P<.05）相关。当分析仅限于非西班牙裔白人患者时，这些发现更为明显。在 13 例有记录的骨折中，有 3 例发生在开始使用利培酮和 SSRIs 之后，而无一例发生在催乳素升高的患者中。
这是第一项将利培酮诱导的高催乳素血症和 SSRI 治疗与儿童和青少年 BMD 降低联系起来的研究。未来的研究应评估该不良事件的纵向病程，以确定其时间稳定性，以及是否会出现更高的骨折率。
