尿毒症性サルコペニア

尿毒症性サルコペニアのレビュー論文を紹介します。

Ibrahim H. Fahal. Uraemic sarcopenia: aetiology and implications. Nephrol. Dial. Transplant. (2013) doi: 10.1093/ndt/gft070

尿毒症患者では筋肉量減少を認めやすくなります。この原因はサルコペニアと同様、多くの要因が絡んでいます。尿毒症性サルコペニアを認めると死亡率が高くなるため、筋肉量減少の予防と治療が重要です。尿毒症性サルコペニアという言葉を用いることで腎臓領域で重要性が認識されると思われます。

腎臓領域での筋肉量減少はProtein-Energy Wasting（PEW）という言葉で説明されることが多いと思っていました。尿毒症性サルコペニアという言葉は初めて聞きました。PEWも原因の1つとされています。確かにこの言葉のほうが関心が高まる可能性はあると思います。

尿毒症性サルコペニアはもちろん、加齢以外の原因も含まれる二次性サルコペニアということになります。慢性腎不全では加齢によるサルコペニアより悪液質や低栄養の要素のほうが強いのではと思いますが、広義のサルコペニアの概念を広めるにはよい言葉かもしれません。

Abstract
The term uraemic myopathy has been used loosely to describe the skeletal muscle abnormalities in uraemic patients. However, it does not fully explain the observed abnormalities as recent research has documented a normal skeletal muscle physiology in the presence of reduced muscle force, selective structural changes and significant muscle wasting. Ageing is associated with sarcopenia (muscle wasting) and an increase in the prevalence of chronic kidney disease (CKD), which accelerates the normal physiological muscle wasting. Similar to sarcopenia, muscle wasting in uraemic patients appears to be the hallmark of the disease and its aetiology is multifactorial with hormonal, immunologic and myocellular changes, metabolic acidosis, reduced protein intake and physical inactivity. Uraemic sarcopenia presents a high probability for morbidity and mortality and consequently a high priority for muscle wasting prevention and treatment in these patients. Perhaps, the use of the term ‘uraemic sarcopenia’ would provide recognition by the renal community for this devastating problem. The purpose of this review is to relate the findings of the recent publications that describe abnormalities in uraemic skeletal muscle to the possible pathogenesis of muscle wasting and its consequences in patients with CKD. 

リハ栄養の体系的な知識

日本リハビリテーション栄養研究会では現在、研究会雑誌を出していません。体系的な知識はこのグループ内にあまりストックされていません。そのため、リハ栄養を体系的に学習できる資料を紹介させていただきます。興味のある方はぜひ。

書籍（いずれも医歯薬出版で私が編著です）
①PT・OT・STのための リハビリテーション栄養 栄養ケアがリハを変える
②リハビリテーション栄養ハンドブック
③リハビリテーション栄養ケーススタディ 臨床で成果を出せる30症例
④サルコぺニアの摂食・嚥下障害 リハビリテーション栄養の可能性と実践
①がリハ栄養のWhy、②がWhat、③がHowについての書籍です。下記HPから序文、目次、見本程度は見れます。
http://www.ishiyaku.co.jp/search/search.aspx?N1=131095

雑誌
静脈経腸栄養Vol26(6)：特集「リハビリテーションの栄養管理」下記HPで全文見れます。
https://www.jstage.jst.go.jp/browse/jjspen/26/6/_contents/-char/ja/
リハビリテーション医学48(4)：「リハビリテーションと臨床栄養」下記HPで全文見れます。
https://www.jstage.jst.go.jp/article/jjrmc/48/4/48_4_270/_pdf
MEDICAL REHABILITATION143号（2012年4月号）：特集「リハビリテーション栄養-栄養はリハのバイタルサイン-」目次＋α程度は下記HPで全文見れます。
http://www.zenniti.com/f/b/show/b01/446/zc01/3.html

健常者は骨格筋面積と体表面積が相関

健常者では骨格筋面積と体表面積は相関するという論文を紹介します。

Yoshizumi T, Shirabe K, Nakagawara H, Ikegami T, Harimoto N, Toshima T, Yamashita YI, Ikeda T, Soejima Y, Maehara Y. Skeletal muscle area correlates with body surface area in healthy adults. Hepatol Res. 2013 Mar 29. doi: 10.1111/hepr.12119. [Epub ahead of print]

対象は生体肝移植のドナーの健常者で腹部CTを施行した45人です。骨格筋の横断面積はL3尾側レベルで評価しました。体表面積から骨格筋面積を計算する回帰分析を行いました。また回帰式の妥当性を別の30人の健常者で検討しました。

結果ですが、骨格筋面積は男性155.0 cm² (114.0-203.0)、女性111.7 cm² (89.8-139.3)で男女とも体表面積と有意な相関を認めました男性(p < 0.0001, r² = 0.60)、女性(p < 0.0001, r² = 0.78)。

骨格筋面積の回帰式は男性126.9 × BSA（体表面積） - 66.2、女性125.6 × BSA - 81.1でした。回帰式からの骨格筋面積は、実際の骨格筋面積と有意な相関を認めました男性(p = 0.003, r² = 0.64)、女性(p = 0.0001, r² = 0.70)。

サルコペニアは実際の腹部CTでの骨格筋面積とこの回帰式で体表面積から計算した骨格筋面積との違いで定義できるという結論です。健常者のデータですが、サルコペニアの評価の目安になると思います。次はサルコペニア患者でのデータが欲しいですね。

Abstract

BACKGROUND:

Depletion of skeletal muscle mass (sarcopenia) predicts survival in patients with cancer or liver cirrhosis. Recently, many reports have used computed tomography (CT) to measure muscle area to define sarcopenia. However, the definition of sarcopenia using CT has not been fully determined. The aim of this study was to establish formulae to calculate the standard area of skeletal muscle.

METHODS:

Forty-five healthy adults (24 men and 21 women, age range; 21-66) who wished to donate part of their liver for transplantation underwent CT. Cross sectional areas (cm² ) of skeletal muscle was measured at the caudal end of the third lumbar vertebra. Regression analysis was performed to establish formulae to calculate standard area of skeletal muscle. A validation conducted on 30 other healthy adults was performed to check the accuracy of formulae.

RESULTS:

Men had a median skeletal muscle area of 155.0 cm² (114.0-203.0), compared with 111.7 cm² (89.8-139.3)in women (p < 0.001). Furthermore, skeletal muscle area significantly correlated with body surface area (BSA) in men (p < 0.0001, r² = 0.60) and women (p < 0.0001, r² = 0.78). The formulae to calculate skeletal muscle area were 126.9 × BSA - 66.2 in men and 125.6 × BSA - 81.1 in women. The estimated muscle area significantly correlated with actual muscle area in men (p = 0.003, r² = 0.64) and women (p = 0.0001, r² = 0.70).

CONCLUSIONS:

Sarcopenia can be defined by the difference between measured data and calculated data using our new formulae.

生体肝移植患者の生存とサルコペニア

生体肝移植患者の生存に対するサルコペニアの影響に関する論文を紹介します。

Kaido T, Ogawa K, Fujimoto Y, Ogura Y, Hata K, Ito T, Tomiyama K, Yagi S, Mori A, Uemoto S. Impact of Sarcopenia on Survival in Patients Undergoing Living Donor Liver Transplantation. Am J Transplant. 2013 Apr 19. doi: 10.1111/ajt.12221. [Epub ahead of print]

対象は生体肝移植を行った成人患者124人です。サルコペニアは体成分分析（インピーダンス）で評価しました。結果ですが、術前の骨格筋量の割合は、標準値と比較して中央値92%（67-130%）でした。

骨格筋量が正常もしくは多い群と比較して、骨格筋量が少ない群では有意に生存率が悪かったです。周術期の栄養療法は、骨格筋量が少ない患者の生存率を有意に改善しました。多変量解析では、骨格筋減少は独立した移植後の死亡のリスク因子でした。

生体肝移植患者ですので、加齢によるサルコペニアというよりは疾患と栄養によるサルコペニアや悪液質の影響が大きいと思われます。そのため、周術期の栄養療法で生存率が改善したのではと推測します。腹部CTでのサルコペニア評価でもよいかなと考えます。

Abstract

Skeletal muscle depletion, referred to as sarcopenia, predicts morbidity and mortality in patients undergoing digestive surgery. However, the impact on liver transplantation is unclear. The present study investigated the impact of sarcopenia on patients undergoing living donor liver transplantation (LDLT). Sarcopenia was assessed by a body composition analyzer in 124 adult patients undergoing LDLT between February 2008 and April 2012. The correlation of sarcopenia with other patient factors and the impact of sarcopenia on survival after LDLT were analyzed. The median ratio of preoperative skeletal muscle mass was 92% (range, 67-130%) of the standard mass. Preoperative skeletal muscle mass was significantly correlated with the branched-chain amino acids to tyrosine ratio (r = -0.254, p = 0.005) and body cell mass (r = 0.636, p < 0.001). The overall survival rate in patients with low skeletal muscle mass was significantly lower than in patients with normal/high skeletal muscle mass (p < 0.001). Perioperative nutritional therapy significantly increased overall survival in patients with low skeletal muscle mass (p = 0.009). Multivariate analysis showed that low skeletal muscle mass was an independent risk factor for death after transplantation. In conclusion, sarcopenia was closely involved with posttransplant mortality in patients undergoing LDLT. Perioperative nutritional therapy significantly improved overall survival in patients with sarcopenia.

サルコペニアの新しい栄養戦略

サルコペニアの新しい栄養戦略に関するレビュー論文を紹介します。

R. Calvani, A. Miccheli, F. Landi, M. Bossola, M. Cesari, C. Leeuwenburgh, C.C. Sieber, R. Bernabei, E. Marzetti. CURRENT NUTRITIONAL RECOMMENDATIONS AND NOVEL DIETARY STRATEGIES TO MANAGE SARCOPENIA. J Frailty Aging 2013;2(1):38-53

蛋白質、アミノ酸、ビタミンD、クレアチン、抗酸化物質（これは無効）、栄養摂取のタイミングの後に、新しい栄養戦略ということでHMB、オルニチン、オメガ3脂肪酸、ウルソル酸、硝酸塩、カロリー制限、ジムノミメティクス（運動模倣）、腸内細菌操作が紹介されています。

筋肉量、筋肉合成がどうなるかをパチンコモデル（日本のピンボールと紹介されています）で示している図4が面白いですね。栄養摂取のタイミング、身体活動・運動、腸内細菌操作によって、食事がどう筋蛋白合成につながるかどうかを図にしています。

Abstract
Sarcopenia, the loss of skeletal muscle mass and function that occurs with aging, is associated with increased risk for several adverse health outcomes, including frailty, disability, falls, loss of independent living, and mortality. At present, no pharmacological treatment exists that is able to definitely halt the progression of sarcopenia. Likewise, no pharmacological remedies are yet available to prevent the onset of age-related muscle wasting. The combination of nutritional interventions and physical exercise appears to be the most effective strategy presently available for the management of sarcopenia. The purposes of this review are to summarize the current knowledge on the role of nutrition as a countermeasure for sarcopenia, illustrate the mechanisms of action of relevant dietary agents on the aging muscle, and introduce novel nutritional strategies that may help preserve muscle mass and function into old age. Issues related to the identification of the optimal timing of nutritional interventions in the context of primary and secondary prevention are also discussed. Finally, the prospect of elaborating personalized dietary and physical exercise recommendations through the implementation of integrated, high-throughput analytic approaches is illustrated.

長期人工呼吸器患者の筋力低下と嚥下障害

長期人工呼吸管理患者の筋力低下は咽頭機能障害と症候性誤嚥を予測するという論文を紹介します。

Mirzakhani Hooman, et al. Muscle Weakness Predicts Pharyngeal Dysfunction and Symptomatic Aspiration in Long-term Ventilated Patients. Anesthesiology, doi: 10.1097/ALN.0b013e31829373fe

対象は長期間の人工呼吸管理を要した患者30人です。嚥下機能は嚥下内視鏡で、喉頭蓋谷と梨状窩の残留や侵入・誤嚥を評価しました。筋力低下はMRCスコア（両側の肩外転、肘屈曲、手伸展、股屈曲、膝伸展、足背屈をMMTで評価して合計60点満点）で評価しました。

MRCスコアが48点以下の場合を臨床的に意味のある筋力低下としました。結果ですが、筋力低下は咽頭機能障害（喉頭蓋谷と梨状窩の残留や侵入・誤嚥）の存在を予測しました。ROC曲線のAUCは咽頭残留0.77、侵入・誤嚥0.79、症候性誤嚥0.74でした。

筋力低下のある患者のうち70％で、症候性誤嚥のイベント（誤嚥性肺炎や窒息ということでしょうかね）を認めました。筋力低下があると症候性誤嚥のオッズ比が9.8と約10倍、症候性誤嚥のイベントが多いという結果でした。以上より、四肢MMT評価で症候性誤嚥を予測できる可能性があるという結論です。

長期間の人工呼吸管理を要した患者ですので、反回神経麻痺や感覚障害などの影響も否定できませんが、四肢の筋力が弱いと嚥下筋の筋力も弱いサルコペニアの嚥下障害による要素もあると思います。嚥下筋の筋力評価ができなくても、四肢筋力の評価で嚥下障害を推測できるかもしれません。

Abstract

Background: Prolonged mechanical ventilation is associated with muscle weakness, pharyngeal dysfunction, and symptomatic aspiration. The authors hypothesized that muscle strength measurements can be used to predict pharyngeal dysfunction (endoscopic evaluation-primary hypothesis), as well as symptomatic aspiration occurring during a 3-month follow-up period.

Methods: Thirty long-term ventilated patients admitted in two intensive care units at Massachusetts General Hospital were included. The authors conducted a fiberoptic endoscopic evaluation of swallowing and measured muscle strength using medical research council score within 24 h of each fiberoptic endoscopic evaluation of swallowing. A medical research council score less than 48 was considered clinically meaningful muscle weakness. A retrospective chart review was conducted to identify symptomatic aspiration events.

Results: Muscle weakness predicted pharyngeal dysfunction, defined as either valleculae and pyriform sinus residue scale of more than 1, or penetration aspiration scale of more than 1. Area under the curve of the receiver-operating curves for muscle strength (medical research council score) to predict pharyngeal, valleculae, and pyriform sinus residue scale of more than 1, penetration aspiration scale of more than 1, and symptomatic aspiration were 0.77 (95% CI, 0.63-0.97; P = 0.012), 0.79 (95% CI, 0.56-1; P = 0.02), and 0.74 (95% CI, 0.56-0.93; P = 0.02), respectively. Seventy percent of patients with muscle weakness showed symptomatic aspiration events. Muscle weakness was associated with an almost 10-fold increase in the symptomatic aspiration risk (odds ratio = 9.8; 95% CI, 1.6-60; P = 0.009).

Conclusion: In critically ill patients, muscle weakness is an independent predictor of pharyngeal dysfunction and symptomatic aspiration. Manual muscle strength testing may help identify patients at risk of symptomatic aspiration.

閉経後の骨粗鬆症とサルコペニア

閉経後の骨粗鬆症とサルコペニアの関係をみた論文を紹介します。

Sjöblom Samu, et al. Relationship between postmenopausal osteoporosis and the components of clinical sarcopenia. Maturitas, doi:10.1016/j.maturitas.2013.03.016

対象は590人の閉経後のフィンランド女性です。平均年齢68歳で骨密度と筋肉量はDEXAで評価しています。骨密度で正常、骨質減少、骨粗鬆症、筋肉量で非サルコペニア、前サルコペニア、サルコペニアに分類しました。握力や歩行速度も評価しています。

結果ですがサルコペニアの女性は非サルコペニアの女性と比べて、骨粗鬆症が12.9倍多かったです。握力が下位1/4の女性は上位1/4の女性と比較して、骨粗鬆症が11.7倍多い結果でした。サルコペニアの女性は非サルコペニアの女性と比べて骨折が2.7倍多く、転倒が2.1倍多かったです。

以上より、サルコペニアは骨粗鬆症と強く関連し、握力が最もサルコペニア、骨粗鬆症、転倒、骨折の関連を明らかにする有意な測定項目でした。

握力は栄養指標にも含まれるようになり、サルコペニアの診断基準にも含まれることがあります。在宅でも測定できる項目ですので、リハだけでなく、NST、栄養指導、日常診療でもできるだけ握力は評価しておいたほうがよいですね。

Abstract 

Purpose

The aim of the study was to determine the relationship between the components of clinical sarcopenia and osteoporosis in postmenopausal women.

Methods

A population-based cohort of 590 Finnish postmenopausal women (mean age 67.9; range 65–72) was selected from the Osteoporosis Fracture Prevention (OSTPRE-FPS) study in 2002. Bone mineral density (BMD) and lean tissue mass were assessed by dual X-ray absorptiometry (DXA). The study sample was divided into three categories according to the WHO BMD classification: normal, osteopenia and osteoporosis. The study sample was divided into non-sarcopenic, presarcopenic, sarcopenic and non-classified groups according to quartiles of RSMI i.e. relative skeletal muscle index (appendicular muscle mass (kg)/square of height (m)), hand grip strength (kPa) and walking speed.

Results

In logistic regression analysis sarcopenic women had 12.9 times higher odds of having osteoporosis (p≤0.001, OR=12.9; 95% CI=3.1–53.5) in comparison to non-sarcopenic women. In comparison to women in the highest grip strength quartile, women within the lowest quartile had 11.7 times higher odds of having osteoporosis (p=0.001, OR=11.7; 2.6–53.4). Sarcopenic women had 2.7 times higher odds of having fractures than their non-sarcopenic counterparts (p=0.005, OR=2.732; 1.4–5.5). Sarcopenic women had also 2.1 times higher risk of falls during the preceding 12 months compared to non-sarcopenic women (p=0.021, OR=2.1; 1.1–3.9). Adjustment for age, body mass index (BMI), physical activity and hormone therapy (HT) did not significantly alter these results.

Conclusions

The components of clinical sarcopenia are strongly associated with osteoporosis. Grip strength is the most significant measurement to reveal the association between sarcopenia and osteoporosis, falls and fractures.

サルコペニア肥満と加齢による内分泌適応

サルコペニア肥満と加齢による内分泌適応に関するレビュー論文を紹介します。

Kunihiro Sakuma and Akihiko Yamaguchi. Sarcopenic Obesity and Endocrinal Adaptation with Age. International Journal of Endocrinology Volume 2013 (2013), Article ID 204164

個人的に大変お世話になっている佐久間先生の論文で、下記HPで全文見ることができます。

http://www.hindawi.com/journals/ije/2013/204164/

サルコペニア肥満に対しては多種類の運動（柔軟性トレーニング、有酸素運動、レジスタンストレーニング）と栄養療法（1日エネルギー必要量より200-750kcal少ないエネルギー投与量、高蛋白食1.5g/kgまで）が望ましく、有酸素運動単独はセカンドベストとあります。

サルコペニア肥満の原稿を執筆しなければいけないので、とても参考になります。加齢による内分泌適応のところも後でじっくり読みたいと思います。

Abstract
In normal aging, changes in the body composition occur that result in a shift toward decreased muscle mass and increased fat mass. The loss of muscle mass that occurs with aging is termed sarcopenia and is an important cause of frailty, disability, and loss of independence in older adults. Age-related changes in the body composition as well as the increased prevalence of obesity determine a combination of excess weight and reduced muscle mass or strength, recently defined as sarcopenic obesity. Weight gain increases total/abdominal fat, which, in turn, elicits inflammation and fatty infiltration in muscle. Sarcopenic obesity appears to be linked with the upregulation of TNF-, interleukin (IL)-6, leptin, and myostatin and the downregulation of adiponectin and IL-15. Multiple combined exercise and mild caloric restriction markedly attenuate the symptoms of sarcopenic obesity. Intriguingly, the inhibition of myostatin induced by gene manipulation or neutralizing antibody ameliorates sarcopenic obesity via increased skeletal muscle mass and improved glucose homeostasis. In this review, we describe the possible influence of endocrinal changes with age on sarcopenic obesity.

末期腎不全のサルコペニア

末期腎不全の高齢者におけるサルコペニアの有病割合と関連要因に関する論文を紹介します。

Jwa-Kyung Kim, et al. Prevalence of and factors associated with sarcopenia in elderly patients with end-stage renal disease. Clinical Nutrition, http://dx.doi.org/10.1016/j.clnu.2013.04.002

対象は50歳以上の末期腎不全95人で横断研究です。サルコペニアは筋肉量と筋力で評価しています。結果ですが、平均年齢64歳、半数強が糖尿病を合併していました。サルコペニアは男性で37％、女性で29.3％に認めました。

SGA（栄養スクリーニング）の結果、炎症マーカー、β2マイクログロブリンがサルコペニアの有無と関連していました。また、抑うつと軽度認知障害を認める場合に、サルコペニアが多かったです。末期腎不全ではサルコペニアが多く、これらが関連因子という結論です。

平均年齢64歳ですので高齢者と言えるかどうか微妙なレベルですが、それでも3人に1人はサルコペニア（より正確に言うと腎不全や糖尿病による二次性サルコペニア）を認めるのですね。抑うつと認知障害は低栄養からの二次性サルコペニアに関連しているかもしれません。

Summary

Background & aims

We investigated the prevalence of sarcopenia in elderly patients with end-stage renal disease (ESRD) and its relationship with various markers of nutrition, cognitive function, depressive symptoms, inflammation and β2-microglobulin.

Methods

A cross-sectional study was conducted with 95 patients having ESRD aged over 50 years. Sarcopenia was defined as a decline in both muscle mass and strength.

Results

The mean age was 63.9 ± 10.0 years; 56.8% were men and 52.6% had diabetes. Sarcopenia was highly prevalent in elderly patients with ESRD (37.0% in men and 29.3% in women). Subjective Global Assessment (SGA), inflammatory markers and β2-microglobulin levels were significantly associated with sarcopenia, even after adjustment for age, gender, diabetes, and body mass index. Additionally, patients with depressive symptoms showed a higher risk of sarcopenia relative to those without depressive symptoms (odds ratio, OR = 6.87, 95% confidence interval, CI = 2.06–22.96) and sarcopenia was more likely to be present in patients with mild cognitive dysfunction (OR = 6.35, 95% CI = 1.62–34.96).

Conclusions

Sarcopenia is highly prevalent in elderly patients with ESRD and is closely associated with SGA, inflammatory markers, β2-microglobulin, depression and cognitive dysfunction.

 

Bone Joint Nerveサルコペニア─筋研究の最前線─

Bone Joint Nerveの最新号で、サルコペニア─筋研究の最前線─が特集されています。

http://www.arcmedium.co.jp/bone.html

サルコペニアの特集を組む雑誌も書籍も本当に増えてきましたね。この雑誌では「加齢依存性筋量減少症をサルコペニアという」とありますので、加齢以外の原因による筋肉量減少と、筋力低下や身体機能低下はサルコペニアに含まれていないと思われます。

今後、サルコペニアを診断して治療することが診療報酬に含まれるべきだと私は考えます。そのためには今よりずっと多くのエビデンスが求められますが、サルコペニア（とサルコペニア肥満）の定義と診断基準を明確にしないといけませんね。

腎と骨代謝：サルコペニアと骨代謝

雑誌「腎と骨代謝」の最新号で、サルコペニアと骨代謝が特集されています。

http://www.nmckk.jp/latestThesisList.php?category=KMBD&lang=ja

下記HPで各記事の抄録と最初の頁見本を見ることができます。

http://www.nmckk.jp/pdf.php?mode=magsample&category=KMBD&vol=26&no=2

腎よりも骨代謝との関連に重きをおいた内容になっています。欲をいえば腎不全によるPEWと悪液質、サルコペニアに関する記事もあれば嬉しかったですね。見本頁を見るだけでも参考になります。

目次
1筋細胞分化の分子メカニズムMolecular mechanism of skeletal muscle differentiation

内藤 昌志 Masashi Naito

2サルコペニア発症のメカニズムCellular and molecular mechanisms underlying sarcopenia

宮崎 剛 Tsuyoshi Miyazaki

3メカニカルストレスと筋Relation between mechanical stress and muscle

宇都宮 健郎 Kenro Utsunomiya

4サルコペニアの診断Diagnosis of sarcopenia

原田 敦 Atsushi Harada

5骨粗鬆症の疫学とサルコペニアEpidemiology of osteoporosis and sarcopenia

村木 重之 Shigeyuki Muraki

6サルコペニアと栄養Nutrition and sarcopenia

葛谷 雅文 Masafumi Kuzuya

7骨粗鬆症治療とサルコペニアTreatment for osteoporosis and sarcopenia

小川 純人 Sumito Ogawa

8無重力と骨量減少・サルコペニアOsteopenia and sarcopenia in weightlessness

大島 博 Hiroshi Ohshima

認知症高齢者に対する経口栄養補助食：メタ解析

認知症高齢者に対する経口栄養補助食（ONS）の系統的レビューとメタ解析の論文を紹介します。

Victoria J. Allen, Lisa Methven, Margot A. Gosney. Use of nutritional complete supplements in older adults with dementia: systematic review and meta-analysis of clinical outcomes. Clinical Nutrition, http://dx.doi.org/10.1016/j.clnu.2013.03.015

結果ですが、認知症高齢者に対する経口栄養補助食（ONS）投与で、平均6.5カ月後のフォローで、体重増加（3.54kg）、BMI増加（0.92）、認知機能改善（MMSEで1.6点、ただし症例数少ない）が得られました。これより認知症へのONS投与は有用という結論です。

認知症の体重増加にONSが有用ということは以前の系統的レビューでも言われていましたが、今回は認知機能改善まで出ました。ただ、この解釈には十分な注意が必要だと思います。生命予後改善までは得られていませんので、今後のさらなる研究も必要かと思います。

Abstract

Background

& Aims: Malnutrition is prevalent in people diagnosed with dementia however ensuring adequate oral intake within this group is often problematic. It is important to determine whether providing nutritionally complete oral nutritional supplements (ONS) drinks is an effective way of improving clinical outcomes for older people with dementia. This paper systematically reviewed clinical, wellbeing and nutritional outcomes in people with long-term cognitive impairment.

Methods

The CINAHL, Medline and EMBASE databases were searched from their inception until January 2012. Reference lists of the included papers, foreign language papers and review articles obtained were manually searched.

Results

Twelve articles were included in the review containing 1076 people in the supplement groups (intervention) and 748 people in the control groups. Meta-analysis shows there was a significant improvement in weight (p=<0 .0001="" 6.5="" and="" at="" body="" cognition="" compared="" control="" follow="" given="" group.="" index="" mass="" month="" p="" supplements="" the="" to="" up="" were="" when="">

Conclusions

Providing ONS drinks has a positive effect on weight gain and cognition at follow up in older people with dementia. Additional research is required in both comparing nutritional supplements to vitamin/mineral tablets and high protein/calorie shots and clinical outcomes relevant to people with dementia.

悪液質に対する酢酸メゲステロール：コクラン

悪液質に対する酢酸メゲステロールのコクランレビューを紹介します。

Ruiz Garcia V, López-Briz E, Carbonell Sanchis R, Gonzalvez Perales JL, Bort-Marti S. Megestrol acetate for treatment of anorexia-cachexia syndrome. Cochrane Database Syst Rev. 2013 Mar 28;3:CD004310. doi: 10.1002/14651858.CD004310.pub3.

前回2005年のバージョンからアップデートされたものです。結果ですが、エイズやがんによる悪液質に対する酢酸メゲステロール投与で、プラセボと比較すると食欲増進や体重増加が得られました。一方、他の薬との比較では有意な改善は認めませんでした。

投与量に関しては量が多いほうが体重増加が多いです。QOLはプラセボとの比較では改善しましたが、他の薬との比較では有意差を認めませんでした。酢酸メゲステロールの副作用として、浮腫、血栓塞栓症、死亡が有意に増加しました。

以上より、エイズやがんによる悪液質に対する酢酸メゲステロール投与で、食欲改善とわずかな体重増加を認めるという結論です。ただし、緩和ケアを受けている患者であっても、リスクについて十分に伝えることが必要です。

コクランレビューで有効というのは意味がありますが、体重増加の一因は浮腫かもしれません。また死亡が有意に増加するようでは、食欲改善や体重増加より問題が大きいです。日本では使用できない薬剤ですが、使用できたとしても適応は少ない気がします。

Abstract

BACKGROUND:

This is an updated version of a previously published review in The Cochrane Library (2005, Issue 2) on 'Megestrol acetate for the treatment of anorexia-cachexia syndrome'. Megestrol acetate (MA) is currently used to improve appetite and to increase weight in cancer-associated anorexia. In 1993, MA was approved by the US Food and Drug Administration for the treatment of anorexia, cachexia or unexplained weight loss in patients with AIDS. The mechanism by which MA increases appetite is unknown and its effectiveness for anorexia and cachexia in neoplastic and AIDS (acquired immunodeficiency syndrome) patients is under investigation.

OBJECTIVES:

To evaluate the efficacy, effectiveness and safety of MA in palliating anorexia-cachexia syndrome in patients with cancer, AIDS and other underlying pathologies.

SEARCH METHODS:

We sought studies through an extensive search of electronic databases, journals, reference lists, contact with investigators and other search strategies outlined in the methods. The most recent search for this update was carried out in May 2012.

SELECTION CRITERIA:

Studies were included in the review if they assessed MA compared to placebo or other drug treatments in randomised controlled trials of patients with a clinical diagnosis of anorexia-cachexia syndrome related to cancer, AIDS or any other underlying pathology.

DATA COLLECTION AND ANALYSIS:

Two independent review authors conducted data extraction and evaluated methodological quality. We performed quantitative analyses using appetite and quality of life as a dichotomous variable, and analysed weight gain as continuous and dichotomous variables.

MAIN RESULTS:

We included 35 trials in this update, the same number but not the same trials as in the previous version of the review. The trials comprised 3963 patients for effectiveness and 3180 for safety. Sixteen trials compared MA at different doses with placebo, seven trials compared different doses of MA with other drug treatments and 10 trials compared different doses of MA. Meta-analysis showed a benefit of MA compared with placebo, particularly with regard to appetite improvement and weight gain in cancer, AIDS and other underlying conditions, and lack of benefit in the same patients when MA was compared to other drugs. There was insufficient information to define the optimal dose of MA, but higher doses were more related to weight improvement than lower doses. Quality of life improvement in patients was seen only when comparing MA versus placebo but not other drugs in both subcategories: cancer and AIDS. Oedema, thromboembolic phenomena and deaths were more frequent in the patients treated with MA. More than 40 side effects were studied.

AUTHORS' CONCLUSIONS:

This review shows that MA improves appetite and is associated with slight weight gain in cancer, AIDS and in patients with other underlying pathology. Despite the fact that these patients are receiving palliative care they should be informed of the risks involved in taking MA.

大腿骨近位部骨折術後の嚥下障害

大腿骨近位部骨折術後の高齢者の嚥下障害を前向きコホートで調査した論文を紹介します。

Amanda Louise Love, Petrea Louise Cornwell, and Sarah Lilian Whitehouse. Oropharyngeal dysphagia in an elderly post-operative hip fracture population: a prospective cohort study. Age Ageing (2013) doi: 10.1093/ageing/aft037 First published online: March 26, 2013

181人の大腿骨近位部骨折術後の高齢者（平均年齢83歳）のうち、61人（34％）に嚥下障害を認めました。多変量解析では、骨折前からの神経疾患や呼吸器疾患の合併、術後せん妄、年齢、入院前の生活場所が介護施設の場合、嚥下障害が多かったです。

以上より、大腿骨近位部骨折術後の高齢者に嚥下障害を認めることは多く、嚥下障害の早期発見が二次的合併症の予防や入院期間の短縮に重要という結論です。

大腿骨近位部骨折術後に嚥下障害や誤嚥性肺炎を認めるのは、臨床ではよくありますよね。私はサルコペニア、低栄養（骨折、手術の侵襲を含め）の要素が大きいと感じていますが、この研究ではそもそもサルコペニアや栄養状態を評価していませんので、今後の研究課題ですね。

ちなみに日本では、大腿骨近位部骨折術後の嚥下障害について、以下の論文があります。

高齢者大腿骨近位部骨折後の誤嚥性肺炎と嚥下機能評価に基づいた食事摂取方法(原著論文)
Author：田積 匡平(岡崎市民病院 リハビリテーション室), 鳥居 行雄
Source：Hip Joint(0389-3634)38巻Suppl. Page287-290(2012.08)
Abstract：過去1年間に大腿骨近位部骨折で入院加療した60歳以上の患者199例を対象として、骨折後の肺炎発症状況と嚥下機能に関する調査を行い、食事開始前の嚥下機能評価の有用性を検討した。1年間の入院中肺炎発症率と誤嚥性肺炎の占める割合、誤嚥性肺炎発症患者の肺炎発症状況、ST介入時の評価と経過を後方視的に調査した結果、入院中に199例中12例が肺炎を発症し(肺炎発症率6%)、その66.7%(8例)が誤嚥性肺炎であったが、誤嚥性肺炎発症患者の中にはSTの評価後も食形態の調整などで経口摂取を継続できた患者が存在した。大腿骨近位部骨折においても食事開始前に適切な嚥下機能評価を行い、栄養摂取方法を調整することで誤嚥性肺炎の発症を予防できる可能性が示された。

Abstract

Background: normal ageing processes impact on oropharyngeal swallowing function placing older adults at risk of developing oropharyngeal dysphagia (OD). Anecdotal clinical experience has observed that older patients recovering from hip fracture surgery commonly develop OD post-operatively.

Objective: to document the presence of OD following hip fracture surgery, and the factors associated with OD.

Methods: one hundred and eighty-one patients with a mean age of 83 years (range: 65–103) admitted to a specialised orthogeriatric unit were assessed for OD post-surgery for hip fracture. Pre-admission, intra-operative and post-operative factors were examined to determine their relationship with the presence of OD.

Results: OD was found to be present post-operatively in 34% (n = 61) of the current population. Multivariate logistic regression analyses revealed the presence of pre-existing neurological and respiratory medical co-morbidities, presence of post-operative delirium, age and living in a residential aged care facility prior to hospital admission to be associated with the post-operative OD.

Conclusion: these results highlight that OD is present in a large number of the older hip fracture population. Early identification of OD has important implications for the provision of timely dysphagia management that may prevent secondary complications and potentially reduce the hospital length of stay.