自閉症與髖骨骨折風險增加有關


  【24drs.com】泛自閉症障礙(ASD)孩童與成人之髖骨骨折風險顯著大於無自閉症者,證實了之前的研究懷疑的:ASD和骨密度(BMD)較低有關。
  
  共同作者、波士頓麻州綜合醫院小兒內分泌與神經內分泌、哈佛醫學院小兒科副教授Madhusmita Misra醫師表示,對於骨密度低的ASD病患,應盡一切努力以進行鑑別和治療各個影響因素。
  
  此外,重點在於定期檢測骨密度,特別是患有ASD的年長女性,她們和必須遵守無麩質或無酪蛋白飲食者的骨折風險最高。
  
  這些研究結果發表於美國骨密度與礦物質研究協會(ASBMR)2014年會。
  
  Misra醫師的團隊以前曾發現,患ASD的男孩在青春期前後,脊椎和髖部的BMD顯著低於同齡男孩,在影響骨骼發育的一些因素,如鈣質與維他命D攝取、運動、可體松值等也觀察到重要差異。
  
  這篇新研究首度深入探討自閉症的骨折風險,Misra醫師等人評估了「National Emergency Department Sample 2010」的資料,對象包括18,152名3-22歲ASD孩童與4,215名23-50歲ASD成人;以一年的時間評估這些資料,並和該世代中無ASD的6,311,505名孩童與11,438,194名成人的資料比較。
  
  研究結果顯示,3-22歲者中,患ASD者的髖骨骨折風險是無ASD者的3倍以上([OR],3.33;P < .0001)。
  
  患ASD的女孩中,風險更是遠高於無ASD的女孩(OR,8.1;P = .0005),而且也高於患ASD的男孩(OR,2.0;P = .06);不過,在男孩上肢骨折方面,則是呈相反關聯,ASD男孩的上肢骨折風險低於無ASD的男孩(P < .0001)。
  
  患ASD成人相較於無ASD成人,髖骨骨折勝算比(OR)也呈類似模式(OR,11.7;P < .0001);同樣的,女性的風險(OR,24.8;P < .0001)高於男性(OR,6.8;P < .0001)。
  
  患ASD成年女性的上肢骨折風險也高於沒有ASD的女性(OR,2.27;P = .0038),脊椎骨折也是(OR,10.61;P = .0034),不過,患ASD的成年男性和患ASD的男孩一樣,上肢骨折風險較低,且脊椎骨折風險未增加。
  
  Misra醫師表示,令人驚訝的是,患ASD女孩的髖骨骨折風險、患ASD婦女的髖骨、上肢、脊椎風險較高。
  
  她指出,若未全面評估ASD女性的骨密度以及相關決定因素,很難推論這些女孩和婦女風險比較高的原因;我們希望繼續深入進行這些研究。
  
  作者們分析時並未校正影響骨骼的用藥,因相關資料有限,不過,校正各年齡分組後,研究結果顯著。
  
  在以前的研究中,使用抗抽搐藥物和其他已知會影響骨骼的藥物者都未被納入。
  
  對這鮮為人知的自閉症相關風險而言,這些研究結果相當重要,將會有顯著的潛在影響。
  
  Misra醫師表示,自閉症患者的骨折風險較高,特別是髖骨和脊椎骨折這些與嚴重病症有關的骨折,可能是因為他們表達上有困難、一直久坐、難以配合術後的密集復健。
  
  且因ASD盛行率持續增加,根據2014年的CDC資料為1/68,若其骨折風險增加,意味著會造成健康照護費用增加而使醫療照護體系負擔增加。
  
  根據華盛頓大學骨科與運動醫學助理教授Ronald Y. Kwon博士表示,雖然ASD者的BMD不佳可歸因於各種因素,包括藥物副作用、飲食限制、少運動,最近的研究更注重其神經系統方面的改變。
  
  他表示,過去十年間,有許多研究發現神經會直接調節骨細胞活性。
  
  我們現在知道中樞神經系統的某些區域,例如下視丘和腦幹對於調節骨骼代謝很重要,也引起對其他腦部區域,如大腦皮層,是否也有影響的後續探討。
  
  Kwon博士和華盛頓大學與Baylor大學的研究夥伴已經用動物模式深入探討癲癇、自閉症和其他神經異常的關聯。
  
  Kwon博士等人在ASBMR會議中發表一篇癲癇老鼠的研究時指出,即使將針對腦部而非骨骼的某基因破壞,顯示出的結果是骨骼缺損。
  
  因此,我們相信,用癲癇的基因模式可以有利於鑑別大腦皮質和骨骼的關聯,我們現在用這個模式和其他策略來釐清箇中關聯。
  
  資料來源: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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