自闭症与髋骨骨折风险增加有关


  【24drs.com】泛自闭症障碍(ASD)孩童与成人之髋骨骨折风险显著大于无自闭症者,证实了之前的研究怀疑的:ASD和骨密度(BMD)较低有关。
  
  共同作者、波士顿麻州综合医院小儿内分泌与神经内分泌、哈佛医学院小儿科副教授Madhusmita Misra医师表示,对于骨密度低的ASD病患,应尽一切努力以进行监别和治疗各个影响因素。
  
  此外,重点在于定期检测骨密度,特别是患有ASD的年长女性,她们和必须遵守无麸质或无酪蛋白饮食者的骨折风险最高。
  
  这些研究结果发表于美国骨密度与矿物质研究协会(ASBMR)2014年会。
  
  Misra医师的团队以前曾发现,患ASD的男孩在青春期前后,脊椎和髋部的BMD显著低于同龄男孩,在影响骨骼发育的一些因素,如钙质与维他命D摄取、运动、可体松值等也观察到重要差异。
  
  这篇新研究首度深入探讨自闭症的骨折风险,Misra医师等人评估了「National Emergency Department Sample 2010」的资料,对象包括18,152名3-22岁ASD孩童与4,215名23-50岁ASD成人;以一年的时间评估这些资料,并和该世代中无ASD的6,311,505名孩童与11,438,194名成人的资料比较。
  
  研究结果显示,3-22岁者中,患ASD者的髋骨骨折风险是无ASD者的3倍以上([OR],3.33;P < .0001)。
  
  患ASD的女孩中,风险更是远高于无ASD的女孩(OR,8.1;P = .0005),而且也高于患ASD的男孩(OR,2.0;P = .06);不过,在男孩上肢骨折方面,则是呈相反关联,ASD男孩的上肢骨折风险低于无ASD的男孩(P < .0001)。
  
  患ASD成人相较于无ASD成人,髋骨骨折胜算比(OR)也呈类似模式(OR,11.7;P < .0001);同样的,女性的风险(OR,24.8;P < .0001)高于男性(OR,6.8;P < .0001)。
  
  患ASD成年女性的上肢骨折风险也高于没有ASD的女性(OR,2.27;P = .0038),脊椎骨折也是(OR,10.61;P = .0034),不过,患ASD的成年男性和患ASD的男孩一样,上肢骨折风险较低,且脊椎骨折风险未增加。
  
  Misra医师表示,令人惊讶的是,患ASD女孩的髋骨骨折风险、患ASD妇女的髋骨、上肢、脊椎风险较高。
  
  她指出,若未全面评估ASD女性的骨密度以及相关决定因素,很难推论这些女孩和妇女风险比较高的原因;我们希望继续深入进行这些研究。
  
  作者们分析时并未校正影响骨骼的用药,因相关资料有限,不过,校正各年龄分组后,研究结果显著。
  
  在以前的研究中,使用抗抽搐药物和其它已知会影响骨骼的药物者都未被纳入。
  
  对这鲜为人知的自闭症相关风险而言,这些研究结果相当重要,将会有显著的潜在影响。
  
  Misra医师表示,自闭症患者的骨折风险较高,特别是髋骨和脊椎骨折这些与严重病症有关的骨折,可能是因为他们表达上有困难、一直久坐、难以配合术后的密集复健。
  
  且因ASD盛行率持续增加,根据2014年的CDC资料为1/68,若其骨折风险增加,意味著会造成健康照护费用增加而使医疗照护体系负担增加。
  
  根据华盛顿大学骨科与运动医学助理教授Ronald Y. Kwon博士表示,虽然ASD者的BMD不佳可归因于各种因素,包括药物副作用、饮食限制、少运动,最近的研究更注重其神经系统方面的改变。
  
  他表示,过去十年间,有许多研究发现神经会直接调节骨细胞活性。
  
  我们现在知道中枢神经系统的某些区域,例如下视丘和脑干对于调节骨骼代谢很重要,也引起对其它脑部区域,如大脑皮层,是否也有影响的后续探讨。
  
  Kwon博士和华盛顿大学与Baylor大学的研究伙伴已经用动物模式深入探讨癫痫、自闭症和其它神经异常的关联。
  
  Kwon博士等人在ASBMR会议中发表一篇癫痫老鼠的研究时指出,即使将针对脑部而非骨骼的某基因破坏,显示出的结果是骨骼缺损。
  
  因此,我们相信,用癫痫的基因模式可以有利于监别大脑皮质和骨骼的关联,我们现在用这个模式和其它策略来厘清个中关联。
  
  资料来源:http://www.24drs.com/professional/list/content.asp?x_idno=7122&x_classno=0&x_chkdelpoint=Y
  

Autism Linked to Increased Hip Fracture Risk

By Nancy A. Melville
Medscape Medical News

HOUSTON ─ Children and adults with autism spectrum disorder (ASD) show a significantly higher risk for hip fracture than do those without autism, confirming suspicions raised by previous research showing a link between ASD and lower bone mineral density (BMD).

"In patients with ASD who have low bone density, every effort should be made to identify and treat contributing factors," coauthor Madhusmita Misra, MD, MPH, an associate professor of pediatrics at Harvard Medical School and the Pediatric Endocrine and Neuroendocrine Units at Massachusetts General Hospital in Boston, told Medscape Medical News.

"In addition, it may be important to monitor bone density at regular intervals, particularly in older women with ASD, who appear to be at the highest risk for fracture, and those on specialized diets, such as the gluten-free and casein-free diet."

The findings were presented here at American Society for Bone and Mineral Research (ASBMR) 2014.

Growing Evidence Base

Dr Misra's team has previously shown that peripubertal boys with ASD have markedly lower BMD at the spine and hip than typically developing boys of the same age, and important differences were also observed in factors known to affect bone accrual, including calcium and vitamin D intake, physical activity, and cortisol levels.

The new study is the first to take the research a step further and assess fracture risk in autism. For the study, Dr Misra and her colleagues evaluated data from the National Emergency Department Sample 2010 on 18,152 children aged 3 to 22 years with ASD and 4215 adults aged 23 to 50 years with ASD.

The data were evaluated during the course of a year and were compared with data on 6,311,505 children and 11,438,194 adults without ASD in the sample.

The findings showed that the risk for hip fracture in the 3- to 22-year-old population was more than 3 times higher among those with ASD than among individuals without ASD (odds ratio [OR], 3.33; P < .0001).

Among girls with ASD, the risk was notably higher than for girls without ASD (OR, 8.1; P = .0005) and somewhat higher than for boys with ASD (OR, 2.0; P = .06).

A reverse association was seen, however, in terms of upper extremity fractures in boys ─ boys with ASD had a significantly lower risk for upper extremity fractures than boys without ASD (P < .0001).

Adults with ASD similarly showed an increased OR of hip fracture compared with those without the disorder (OR, 11.7; P < .0001); likewise, the risk among women was higher (OR, 24.8; P < .0001) than for men (OR, 6.8; P < .0001).

Adult women with ASD also had a higher risk for upper extremity fractures than did those without ASD (OR, 2.27; P = .0038), as well as for spine fractures (OR, 10.61; P = .0034). However, adult men with ASD, as seen in boys with ASD, had a lower risk for upper extremity fractures and no increase in the risk for spine fractures.

"It was a surprise to find the higher odds ratio for hip fracture in girls, and for hip, forearm, and spine fracture in women with ASD," Dr Misra said.

"It is difficult to speculate on the reason for this higher odds ratio in girls and women without a systematic evaluation of bone density and its determinants in females with ASD," she added. "We hope to conduct these studies going forward."

The authors did not control for medications that could affect bone, owing to limitations in the data that were available. However, the findings were significant after adjusting for age groups.

Patients receiving antiseizure medications and other medications known to affect bone were excluded in the previous study.

The findings are important in shedding light on a lesser-known health risk associated with autism, which can have significant potential implications.

"A higher risk for fracture, particularly for fractures associated with significant morbidity, such as hip and spine fracture, is concerning in this population, given difficulties expressing pain, sitting still, and cooperating with the intense rehabilitative therapies after surgery," Dr Misra said.

"And because ASD is increasing in prevalence ─ 1 in 68, based on the CDC 2014 data ─ a higher risk of fracture could lead to significant healthcare costs and thus further burden our healthcare system."

Brain, Bone Link

Although the BMD deficits seen with ASD have been attributed to various factors, including adverse effects of medications, dietary restrictions, and decreased exercise, recent research has focused more on changes in the nervous system, according to Ronald Y. Kwon, PhD, an assistant professor of orthopedics and sports medicine at the University of Washington in Seattle.

"Over the last decade, a large body of studies has accumulated demonstrating the potential for nerves to directly regulate bone cell activity," he told Medscape Medical News.

"We now know that certain regions of the central nervous system, such as the hypothalamus and brain stem, are important for regulating bone metabolism, bringing forth the question of whether other regions of the brain, such as the cerebral cortex, may also be involved."

Dr Kwon and colleagues at the University of Washington and Baylor University have delved into that association in research involving animal models of epilepsy, autism, and other neurologic disorders.

A study involving mice with epilepsy, presented by Dr Kwon and his colleagues at the ASBMR meeting, in fact showed skeletal deficits even when the gene knocked out is targeted primarily to the brain instead of the bone.

"Thus, we believe that the use of genetic models of epilepsy may be a powerful approach for identifying links between the cerebral cortex and bone, and we are now using this and other strategies to determine how this crosstalk occurs," Dr Kwon said.

Dr Misra and Dr Kwon report no relevant financial relationships.

American Society of Bone and Mineral Research (ASBMR) 2014. Abstract 1098. Presented September 13, 2014.

    
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