[摘要]"隨著老齡化加劇,與身體成分和衰老相關(guān)的疾病,如骨質(zhì)疏松、肌肉減少癥、肥胖等疾病日益增多,而老年人“三病共存”時(shí)則導(dǎo)致活動能力下降和不良后果,包括進(jìn)行性殘疾和死亡率、住院率增加。骨量-肌量減少性肥胖綜合征的概念于2014年首次提出,目前關(guān)于骨量-肌量減少性肥胖綜合征的診斷標(biāo)準(zhǔn)及影響因素仍處于探索研究階段。本文就骨量-肌量減少性肥胖綜合征與老年慢性疾病的關(guān)系及其治療進(jìn)行綜述,旨在為老年患者預(yù)防及治療骨量-肌量減少性肥胖綜合征提供參考意見,提高老年患者的生活質(zhì)量。
[關(guān)鍵詞]"老年患者;骨質(zhì)疏松;肌肉減少癥;肥胖;骨量-肌量減少性肥胖綜合征
[中圖分類號]"R592""""""[文獻(xiàn)標(biāo)識碼]"A""""""[DOI]"10.3969/j.issn.1673-9701.2025.06.031
2014年由Ormsbee[1]等首次提出骨量-肌量減少性肥胖綜合征(osteosarcopenic"obesity"syndrome,OSO)的概念。此病是指骨骼健康受損(骨質(zhì)減少/骨質(zhì)疏松癥)、肌肉質(zhì)量或力量下降(肌肉減少癥)和脂肪沉積增加(肥胖癥)[2]。一項(xiàng)關(guān)于OSO全球患病率的研究表明全球中老年人OSO患病率8%,女性患病率9%;男性患病率5%,老年人(≥60歲)OSO患病率13%[3]。一項(xiàng)土耳其社區(qū)老年人OSO患病率研究表明OSO"在總?cè)丝谥械幕疾÷蕿?0.7%;女性和男性分別為11%和9.8%[2]。導(dǎo)致OSO發(fā)生的發(fā)病機(jī)制相互交織,錯(cuò)綜復(fù)雜,可能與慢性炎癥、持續(xù)存在超重/肥胖、不良生活方式及某些慢性疾病如癌癥、糖尿病、維生素D缺乏等密切相關(guān)[3]。不僅如此,肌纖維細(xì)胞在處于運(yùn)動狀態(tài)時(shí)表達(dá)并釋放3000多種細(xì)胞因子和多肽分子,稱為“肌因子”,作用于骨骼肌本身,是介導(dǎo)肌肉、肝臟、骨骼和其他器官之間的通路,并可通過內(nèi)分泌機(jī)制參與調(diào)節(jié)骨骼、肝臟、心臟和其他器官的代謝活動,而當(dāng)疾病發(fā)生及體力活動減少時(shí),“肌因子”也相應(yīng)減少[4]。
韓國一項(xiàng)研究表明年齡增長、女性、非華裔種族及酗酒是OSO的危險(xiǎn)因素[5]。同時(shí)雌激素缺乏有利于促炎細(xì)胞因子的釋放,特別是腫瘤壞死因子,導(dǎo)致破骨細(xì)胞前體的產(chǎn)生和骨吸收[6];另外,血尿酸水平與促炎細(xì)胞因子水平呈正相關(guān),故血尿酸異??稍黾覱SO的發(fā)生率[7]。
1""OSO與相關(guān)疾病的關(guān)系
1.1""OSO與血脂異常的關(guān)系
Xu等[8]研究表明在骨質(zhì)疏松患者中,高密度脂蛋白膽固醇、載脂蛋白A和脂蛋白水平呈正相關(guān),而與血清中的維生素D濃度和甘油三酯水平呈負(fù)相關(guān)。血脂在骨骼、肌肉和身體脂肪中發(fā)生異常的可能機(jī)制:①低密度脂蛋白膽固醇增高可抑制骨髓基質(zhì)細(xì)胞向成骨細(xì)胞的分化,可能導(dǎo)致骨量減少[9];②肌質(zhì)流失加速骨骼肌群對胰島素的抵抗作用,導(dǎo)致動脈粥樣硬化性血脂異常,肌糖原減少;③脂肪量的增加可升高白細(xì)胞介素6和腫瘤壞死因子等炎癥細(xì)胞因子的水平,誘導(dǎo)胰島素抵抗和甘油三酯浸潤到肌肉中,影響血脂代謝[10]。一項(xiàng)不同民族之間OSO與血脂之間的研究表明,OSO患者患血脂異常主要在年長組,是年輕組的2倍[11]。所以長期血脂異常,可加重肌糖原的流失及炎癥因子的發(fā)生,這一系列異常變化導(dǎo)致OSO的發(fā)生,控制血脂,成為預(yù)防OSO必要途徑之一。
1.2""OSO與體力活動及心臟代謝疾病的關(guān)系
缺乏體力活動是慢性疾病增多的獨(dú)立危險(xiǎn)因素[12]。韓國一項(xiàng)研究表明隨著體力活動的升高,骨質(zhì)疏松癥、肌肉減少癥、肥胖癥和肌肉減少性肥胖的患病率下降。與低體力活動相比,中等體力活動以上可有效降低體質(zhì)量、體脂百分比,同時(shí)增加四肢骨骼肌質(zhì)量及高密度脂蛋白膽固醇水平。此外已知的研究表明體力活動越高,心臟代謝疾病、骨質(zhì)疏松癥、肌少癥、肥胖癥和肌肉減少性肥胖的患病率越低。Alipouri等[13]研究顯示較高的體力活動可使骨質(zhì)疏松的患病率下降,而較低的體力活動可隨著血液中維生素D含量的增加而下降。故增強(qiáng)老年人體力活動和增加血液中維生素D含量,可有效降低OSO與心臟代謝疾病的患病率。
1.3""OSO與糖尿病的關(guān)系
2型糖尿?。╠iabetes"mellitus"type"2,T2DM)患者隨著年齡增長,也易出現(xiàn)OSO。OSO在T2DM患者中的發(fā)病率高,可歸因于:①與肌肉減少癥相關(guān)的胰島素敏感度受損,T2DM患者骨骼肌中胰島素的合成及代謝逐漸喪失,可造成蛋白質(zhì)的降解增加,從而引起肌肉質(zhì)量降低,肌肉力量下降[14]。②慢性高血糖也可促使骨骼肌中糖基化終產(chǎn)物(advanced"glycation"end"products,AGEs)在晚期的累積,而AGEs與握力、腿部伸展力量和步態(tài)速度的降低有關(guān)[15]。Zhang等[16]研究發(fā)現(xiàn)AGEs與肌肉減少癥的發(fā)生之間存在顯著關(guān)聯(lián)。其中,骨質(zhì)疏松癥在其中發(fā)揮中介作用,增加骨質(zhì)疏松發(fā)生概率。③馮娜等[17]研究表明老年T2DM患者發(fā)生骨質(zhì)疏松與性別、年齡、血壓、總膽固醇及血清Toll樣受體4(Toll-like"receptors-4,TLR-4)水平升高、體質(zhì)量指數(shù)降低密切相關(guān)。由此可見,糖尿病與肌肉減少癥相輔相成,長期糖尿病也可增加骨質(zhì)疏松的風(fēng)險(xiǎn),有效控制血糖,有助于OSO的預(yù)防。
1.4""OSO與骨折的關(guān)系
研究表明年齡≥65歲患有骨肌肉減少癥老年男性患者的骨折風(fēng)險(xiǎn)較大[18];加拿大一項(xiàng)老齡化縱向研究發(fā)現(xiàn)與骨質(zhì)減少/骨質(zhì)疏松癥男性相比,骨質(zhì)疏松癥男性的骨折風(fēng)險(xiǎn)更大[19];Scott等[20]報(bào)道與骨密度正常但未患肌肉減少癥的男性相比,患有肌肉減少癥的社區(qū)男性跌倒和骨折的可能性增加。生長激素/胰島素樣生長因子-1對調(diào)節(jié)骨骼和肌肉質(zhì)量的代謝至關(guān)重要,其水平的降低可增加骨質(zhì)疏松癥和肌肉減少癥的患病率[21];同時(shí)長期體力活動下降、久坐行為增多,可導(dǎo)致身體虛弱的發(fā)生。多方面的研究均表明OSO與骨折之間存在正相關(guān),特別是老年男性;可通過提高老年人的生活質(zhì)量,多進(jìn)行體力活動,減少久坐行為減少OSO的發(fā)生。
1.5""OSO與慢性阻塞性肺疾病的關(guān)系
研究顯示當(dāng)呼吸系統(tǒng)受損時(shí),老年人的體力活動減少,導(dǎo)致肌肉力量下降,加重肺功能下降[22];另外,脂肪組織在肺功能中起著核心作用,當(dāng)肥胖發(fā)生時(shí),尤其是向心性肥胖,與肺功能較差獨(dú)立相關(guān);呼吸功能下降和向心性肥胖可能與阻塞性改變的限制性模式有關(guān)[23]。韓國一項(xiàng)針對gt;50歲老年人的研究表明患有OSO人群具有更大的肺功能不良風(fēng)險(xiǎn)[24];表明OSO和異常身體成分可能是導(dǎo)致肺功能不良的惡化因素,故早期識別及預(yù)防,有利于改善老年患者的肺功能。
2""OSO的治療
目前關(guān)于OSO的治療暫無特效藥及手術(shù)治療的研究。老年患者多有多病共存,針對老年OSO患者,有氧運(yùn)動、抗阻運(yùn)動及飲食營養(yǎng)均可作為預(yù)防和治療的策略。
2.1""低體力活動在OSO治療中的影響
運(yùn)動可很好地激活肌因子。針對老年人的綜合鍛煉計(jì)劃應(yīng)包括有氧運(yùn)動、力量、柔韌性和平衡訓(xùn)練,這對維持身體組成和健康老齡化至關(guān)重要,有助于降低跌倒風(fēng)險(xiǎn)、提高功能能力并改善老年人的生活質(zhì)量、預(yù)防或治療OSO,并可能為治療代謝性疾病提供新的見解和潛在的醫(yī)學(xué)策略。
2.1.1""太極拳運(yùn)動""太極拳運(yùn)動強(qiáng)度低、簡單且可行性強(qiáng),在家中就可輕松進(jìn)行,對老年人群,特別是絕經(jīng)婦女的骨骼健康有益。一項(xiàng)對105名久坐的中國老年女性的研究顯示,每天打太極拳、跳舞或散步40min,太極拳組女性的骨密度在12個(gè)月后顯著提高[25];另一項(xiàng)針對定期練習(xí)太極拳或久坐不動的絕經(jīng)后女性的橫斷面研究顯示練習(xí)太極拳的女性脊柱、大轉(zhuǎn)子和股骨近端的骨密度顯著較高[26]。以上研究表明,定期練習(xí)太極拳可維持骨量,但太極拳對肌肉質(zhì)量的影響尚未得到廣泛研究。另一項(xiàng)研究將肥胖女性隨機(jī)分為兩組,一組為對照組,一組為太極拳運(yùn)動組,兩組女性同時(shí)接受低熱量飲食。結(jié)果顯示太極拳運(yùn)動組女性數(shù)周后脂肪量顯著減少[27]。
2.1.2""瑜伽運(yùn)動""一項(xiàng)比較瑜伽專業(yè)人群和非專業(yè)人群的研究表明,專業(yè)人群的心率和血清白細(xì)胞介素6較低[28];另一項(xiàng)針對絕經(jīng)期女性的研究表明,練習(xí)瑜伽的時(shí)間與骨骼特異性堿性磷酸酶(骨形成標(biāo)志物)之間存在顯著直接關(guān)系[28]。瑜伽的類型較多,且均包括呼吸和平衡訓(xùn)練、冥想肌力量訓(xùn)練[26]。一項(xiàng)研究表明在8周內(nèi)進(jìn)行24次瑜伽課程后,年輕人的硬拉力量及下背部、腿筋和肩部柔韌性均有所提高[29]??梢婅べた赡芫哂懈纳乒趋澜】档臐摿?,可為未來OSO治療發(fā)展及預(yù)防提供新方向。
2.1.3""普拉提運(yùn)動""目前還無研究調(diào)查普拉提對骨骼健康的影響。在一項(xiàng)關(guān)于社區(qū)老年人進(jìn)行5周普拉提訓(xùn)練的研究中,對那些在干預(yù)結(jié)束后繼續(xù)練習(xí)普拉提的人(12個(gè)月隨訪),腿部力量得以維持[30];另有研究表明每周進(jìn)行一次普拉提鍛煉,持續(xù)8周,可顯著提高步行速度和其他幾項(xiàng)步態(tài)參數(shù),從而全面改善跌倒風(fēng)險(xiǎn)指數(shù)。功能和力量的改善是骨質(zhì)疏松癥、肌肉減少癥和肥胖癥的重要臨床終點(diǎn),老年人群建議做動作簡單且危險(xiǎn)性低的動作。
2.2""營養(yǎng)在OSO治療中的作用
2.2.1""蛋白質(zhì)的攝入""蛋白質(zhì)攝入量與骨骼健康之間的關(guān)系主要集中在較高的蛋白質(zhì)攝入量與尿鈣流失有關(guān),從而影響骨礦物質(zhì)狀態(tài)。研究顯示蛋白質(zhì)攝入量較高者3年內(nèi)肌肉量損失最多減少40%,這表明通過食物補(bǔ)充或增加膳食蛋白質(zhì)攝入量是減少老年人肌肉量損失營養(yǎng)計(jì)劃的第一步[31]。然而,對老年人的高蛋白飲食需注意腎功能。較高的蛋白質(zhì)攝入量與認(rèn)知優(yōu)勢有關(guān),尤其是色氨酸,但隨著年齡的增長,色氨酸可能無法有效通過血-腦脊液屏障而影響認(rèn)知功能[32];因此腎功能受損患者需根據(jù)慢性腎病分期評估所需攝入的蛋白質(zhì)和能量。在所有認(rèn)知指標(biāo)中,只有反應(yīng)時(shí)間隨著蛋白質(zhì)補(bǔ)充而顯著改善。這表明蛋白質(zhì)補(bǔ)充是有益的,因?yàn)榉磻?yīng)時(shí)間可能是影響步速等功能指標(biāo)的重要組成部分,故建議老年人多食用肉類、蛋類、豆類及豆制品、奶制品、堅(jiān)果類等高蛋白質(zhì)食物,提高骨質(zhì)狀態(tài)。
2.2.2""維生素的攝入""水果有抗氧化及抗炎特性。研究表明50~64歲女性水果攝入量增加可顯著降低OSO的發(fā)病率,同時(shí)攝入富含維生素C和鉀的水果可能有助于降低OSO相關(guān)身體成分異常的風(fēng)險(xiǎn),包括低骨量、低肌肉量和肥胖[33]。維生素C在膠原蛋白合成中發(fā)揮作用,可參與膠原蛋白生物合成,促進(jìn)骨骼肌重塑。研究表明鉀離子與肥胖及骨質(zhì)疏松之間存在關(guān)聯(lián)[34]。因此老年人日常生活中可食用富含鉀、維生素C的水果,有利于預(yù)防OSO的發(fā)生。
3"小結(jié)與展望
目前OSO的發(fā)病機(jī)制尚未完全明確,未來的管理路徑可集中在預(yù)防和治療上,側(cè)重于生物學(xué)途徑及診斷方法的改進(jìn),如用早期檢測的生物標(biāo)志物為OSO患者提供較好的治療方法,并建立預(yù)測OSO治療反應(yīng)的敏感措施。
利益沖突:所有作者均聲明不存在利益沖突。
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(修回日期:2025–02–12)