骨质疏松症合并常见老年慢性病管理专家共识

1 制订目的

《“健康中国2030”规划纲要》明确提出重视慢性病共病管理,但目前骨质疏松症合并老年慢性病的诊疗缺乏统一规范,不同科室对共病管理的认知存在差异,基层医疗机构筛查能力不足,部分慢性病合并OP的机制尚未完全阐明,现有指南难以覆盖所有共病场景。基于此,广东省医师协会老年医学科医师分会,广东省医学会骨质疏松学分会,南方十二省骨质疏松联盟组织多学科专家,依据现有循证证据制定本推荐。此推荐的专家组成员包括老年医学科、内分泌科、骨质疏松科、骨科、心血管内科、消化内科、呼吸内科、肿瘤科等多学科专家组成共识工作组;此推荐聚焦OP与心血管疾病、消化系统疾病、炎症性关节病(骨关节炎、类风湿性关节炎)、呼吸系统疾病、肿瘤的共病管理,因糖尿病、慢性肾病已有相关OP共管指南共识,故未纳入本篇推荐;此推荐的内容主要涵盖骨质疏松症与老年慢性病的发病患病情况,危险因素,药物相互作用及管理。此推荐旨在为涉及骨质疏松症合并相关老年慢性病管理的医务人员提供建议,提升临床医师对共病管理的重视程度,促进骨质疏松症多学科协同管理。

2 骨质疏松症(OP)与心血管疾病(CVD)

2.1 “骨-心”共病双向风险关联明确,建议心血管疾病患者开展OP筛查 我国 CVD 患病人数达3.3亿,占死亡人数的40%,是首要致死原因,且与OP存在显著双向风险关联[3]。CVD 患者患OP的风险比无CVD 人群高1.69倍,而OP患者发生心血管事件的风险为非OP 人群的1.2~1.4倍[4]。特定CVD 人群风险更高:一项纳入包括18个队列研究和病例对照研究,总样本为1854441人的荟萃分析显示,缺血性心脏病、中风分别增加髋部骨折风险1.41、2.23倍[5];一项关于心血管疾病(CVD)风险对三年内发生的跌倒率(含急诊)及死亡率的影响的研究显示,心血管疾病与患者急诊跌落的死亡风险密切相关(RR=1.81)[6]。因此,建议CVD 患者将OP筛查纳入常规诊疗,老年、女性、心衰及近期住院患者每6~12个月复查骨密度(BMD)。

2.2 心血管疾病治疗时需充分考虑不同心血管药物的特性,最大限度减少对OP的不良影响 不同 CVD 药物对骨代谢的影响存在显著差异,临床需精准选药,以兼顾“心-骨”健康的相互作用,具体分类及影响见表1。

3 OP与消化系统疾病

3.1 消化系统疾病(炎症性肠病、乳糜泻及慢性肝病)与OP关系明显,建议纳入骨质疏松症高风险筛查体系 OP在消化系统疾病患者中呈高发态势,主要涵盖炎症性肠病(IBD)、乳糜泻(CD)及慢性肝病等。其中,IBD患者普遍存在骨量减少与骨质疏松症[30-31],骨折风险显著高于普通人群[32];乳糜泻患者因肠道黏膜萎缩导致钙吸收障碍,常引发低钙血症,进而促使甲状旁腺激素分泌增加、骨吸收增强,最终升高骨质减少与OP风险[33-35];慢性肝病患者OP患病率更是高达10%~40%,远超普通人群,且肝脏功能恶化会引发蛋白质供应失衡、高氨血症,间接破坏骨骼肌稳态,进一步加剧骨代谢紊乱[36]。

建议筛查情况:美国胃肠病学会建议,IBD患者中既往有脆性骨折史者、65岁女性或>70岁男性、既往/正在使用糖皮质激素者,以及存在其他OP危险因素者,均需强制开展BMD检测[37];慢性肝病患者(尤其肝硬化、肝移植候选者)应作为重点筛查对象,建议每1~2年复查1次BMD,确保早期发现骨量异常并干预。

3.2 以生活方式调整为基础,规范骨健康基础营养补充剂的应用,警惕药物与补充剂的相互作用 生活方式干预是OP预防的首要环节,需结合不同消化

系统疾病特点制定方案:针对IBD患者,规律锻炼、避免吸烟及过量饮酒可直接降低骨折风险[37];慢性肝病患者则需重点规避骨质疏松诱发诱因,尤其是严格戒酒、戒烟,减少酒精与烟草对肝脏及骨骼的双重损害[38]。

钙与维生素D是骨健康的核心营养补充剂,需按需精准补充:IBD患者(特别是长期使用糖皮质激素或已出现低BMD者)需保证充足摄入[37];慢性肝病患者中,胃酸缺乏或胃肠道吸收功能受损者更适合选用枸橼酸钙,以提升吸收效率[38]。需特别注意,钙片需严格规避与特定药物的同服禁忌——与氟喹诺酮类、四环素类、苯妥英类或左甲状腺素同服时,会显著抑制这些药物的吸收,临床需间隔服用,确保用药安全与疗效[38]。

3.3 对于消化系统疾病合并OP的患者,优先选用双膦酸盐,特殊人群可合理替代为其他药物 双膦酸盐是消化系统疾病合并OP患者的一线治疗药物,疗效与安全性均有较充分证据支撑。针对IBD合并OP患者,多项研究证实,双膦酸盐不仅能有效提升椎体与髋部骨密度,还能将椎体骨折风险降低62%(OR = 0.38,95% CI:0.15 ~ 0.96)[39];后续荟萃分析进一步显示,其可使整体骨折风险下降70%(OR = 0.30,95% CI:0.13 ~ 0.69),且不良事件发生率与安慰剂组无显著差异[39]。对于慢性肝病合并OP患者,阿仑膦酸钠表现出明确疗效,可显著改善肝移植患者骨密度并降低骨折发生率[40],对原发性胆汁性胆管炎(PBC)等慢性肝病患者也能发挥骨保护作用,被视为该人群的优选药物[38]。针对骨折高危或无法口服药物的患者,可以使用地舒单抗作为选择,尽管存在罕见药物性肝损伤报道,但因RANKL通路对肝脏无公认不良影响,整体安全性可控[38,41]。需注意,甲状旁腺激素类药物虽能刺激骨形成,但目前缺乏其在慢性肝病患者中的有效性证据,暂不推荐常规使用[38]。

3.4 依据疾病特异性机制制定个体化干预方案,减少继发因素对骨代谢的破坏 不同类型消化系统疾病导致OP的核心机制存在差异,需针对性干预。IBD患者OP的主要诱因是慢性炎症与长期使用糖皮质激素,慢性炎症会通过激活破骨细胞加速骨吸收,而糖皮质激素会进一步加剧骨质疏松失[42],因此临床需优先控制IBD炎症活动度,避免长期大剂量使用糖皮质激素。乳糜泻患者的关键问题是肠道吸收功能异常,需通过无麸质饮食改善肠道黏膜状态。

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纠正维生素D、钙及IGF-1缺乏,缓解吸收不良引发的骨量受损[33,43-44]。慢性肝病患者OP的核心机制是骨重塑失衡,炎症因子(IL-6、IL-1β、TNFα)通过慢性炎症激活破骨细胞,导致骨吸收增加,同时肠道微生物群变化也可能参与骨质疏松失过程[36]。临床需在改善肝功能的基础上,控制炎症反应,避免铁/铜过载对骨骼的额外损害(如病毒性肝炎需重点减少骨吸收,胆汁淤积性肝病改善骨形成)[38]。此外,激素治疗虽能延缓骨质疏松失,但会升高肝细胞癌发生风险,暂不用于慢性肝病合并OP患者;雷洛昔芬因未在肝硬化人群中验证疗效,同样不推荐常规使用[38]。

4 OP与炎症性关节病(骨关节炎/类风湿性关节炎)

4.1 骨关节炎/类风湿性关节炎和OP的共病关联明确,需强化重点人群的骨质疏松症筛查与术前评估 骨关节炎(OA)与OP共病率高且风险关联显著,全球OA患者超3亿例,我国40岁以上人群原发性OA患病率达46.3%,随老龄化共病比例上升[45]。横断面研究证实OP是膝OA独立影响因素(OR=3.56,95% CI: 1.76~7.18),前瞻性队列显示OA患者OP性骨折风险较健康人高50%[45-46]。关节置换术患者骨健康评估关键:人工关节寿命与骨环境相关,60%医生认为骨量影响手术方案,但仅4%术前评估BMD,易致术后假体周围骨密度丢失、翻修风险升高[47],故OA患者需常规筛查OP,拟行关节置换者术前必查BMD。类风湿性关节炎(RA)患者OP患病率达27.6%(95% CI: 23.9~31.3%),显著高于普通人群,早期即出现局部骨质疏松失[48-49]。尤其是接受糖皮质激素治疗,或具有女性、高龄、既往骨折、长病程、绝经后状态等风险因素者,应作为重点人群常规筛查骨质疏松症[50]。

4.2 以共同危险因素管控为核心,实施骨关节炎/类风湿性关节炎合并OP的基础治疗 OA合并OP:除年龄外,性别、慢性炎症、跌倒是共病危险因素,加强肌肉锻炼可减少跌倒风险,既降OP骨折概率,又护OA关节[46];维生素D缺乏与膝关节OA恶化相关,需充足摄入以改善骨代谢与关节健康[51];选择游泳、骑自行车等低强度负重运动,减轻关节负荷延缓OA软骨退变,同时减少OP骨流失[45]。RA合并OP:调整生活方式(规律锻炼、戒烟酒)维持骨健康,RA患者钙吸收能力降低,需保证充足钙摄入[52];抗风湿药(DMARDs)可控制RA进

展,减少全身骨质流失[52]。

4.3 针对病理机制与疾病场景,选用适配的抗OP药物进行治疗 OA合并OP核心机制为炎症介导“骨流失→软骨损坏”循环[45]:维生素D可延缓OA软骨丢失与疼痛[51]:雌激素或SERMs保护软骨下骨,减少绝经后女性骨流失与OA风险[53-54]:双麟酸盐(如阿仑麟酸钠)抑制破骨细胞,减骨吸收与软骨退变[55-56]:特立帕肽调节软骨下骨重塑,阻断循环[57]。OA进展期早期用双麟酸盐改善软骨退化(后期无效)[58],特立帕肽减轻软骨退变[57],降钙素可抗氧化、抗炎、镇痛并保护软骨和骨骼[59];围手术期双麟酸盐(≥6个月)降低THA翻修风险、减少TKA再手术率[51-52],地舒单抗提TKA假体稳定性[60]。

RA合并OP与炎症及糖皮质激素相关,优先选降骨折风险药物:双磷酸盐降低椎体、非椎体及髋部骨折风险,提升RA患者BMD[61-62];特立帕肽降椎体和非椎体骨折率(对髋部无效),治疗后骨形成标志物增加、股骨颈BMD提升[63];地舒单抗增加RA患者腰椎、全髋及股骨颈BMD[64]。长期用糖皮质激素的RA患者优先选双酵酸盐,可应对药物相关骨流失[62]。

5 OP与呼吸系统疾病

5.1 OP与慢性阻塞性肺疾病、哮喘关系较紧密,建议进行相关筛查,长期高剂量使用吸入糖皮质激素(ICS)者为重点监测对象 哮喘是全球高发的炎症性呼吸道疾病,患病人数约3亿,其合并OP的核心机制在于中性粒细胞介导的炎症——TNF-α作为骨生成抑制剂与破骨细胞激活剂,会破坏 RANKL/OPG平衡导致骨吸收增强;IL-6则会抑制成骨细胞分化、显著增加 RANKL 表达,进一步提升破骨细胞活性,最终降低骨密度(BMD) [65-66];慢性阻塞性肺疾病(COPD)患者合并OP的危险因素明确,包括吸烟、体力活动减少、体重过轻、全身炎症、维生素D缺乏、使用糖皮质激素、贫血、低氧血症及高碳酸血症等[67]。

糖皮质激素(包括ICS、全身用糖皮质激素)对骨健康的影响存在剂量及时长差异:常规剂量ICS使用2~3年,无骨折风险增加及BMD丢失的证据;但ICS使用时长>8年或平均日剂量>600 µg/d时,会与骨折风险升高相关[68];全身用糖皮质激素则会通过多重途径损害骨健康,包括增加肾脏钙排泄、减少肠道钙吸收导致钙负平衡,以及降低生

广东医学 2026年4月第47卷第4期

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长激素和性激素生成(分别导致骨形成减少、骨吸收增强),已明确会增加OP及骨折风险[69]。临床中COPD/哮喘合并OP患者,以椎体和前臂/手腕骨折风险最高,需通过早期BMD筛查实现风险预警[68]。

5.2 COPD/哮喘合并OP患者需以“药物风险管控+基础营养补充”为核心干预,参照现有指南开展个体化治疗 药物干预需兼顾呼吸疾病控制与骨健康:ICS虽对长期高剂量使用者存在骨风险,但对COPD患者而言,可通过改善全身炎症状态,减少年度BMD丢失[70],临床需结合患者炎症控制需求与骨风险评估,调整ICS剂量及时长;全身糖皮质激素仅在必要时短期使用,避免长期应用加剧骨代谢紊乱[69]。

基础营养补充是骨健康的重要保障,需常规建议患者摄入充足的维生素D与钙,针对性纠正COPD患者常见的维生素D缺乏问题(该因素为COPD合并OP的明确危险因素),改善钙负平衡以减少骨吸收[67,69]。

目前尚无 COPD/哮喘合并 OP 的专属治疗指南,但对于长期使用激素的患者,临床中可参照2023 版《糖皮质激素性骨质疏松症的诊疗规范》[71]的推荐开展干预,双膦酸盐类药物是目前治疗 GIOP的一线药物,其他药物包括特立帕肽,地舒单抗,雷洛昔芬,降钙素等[68]。

6 OP与肿瘤

6.1 乳腺癌、前列腺癌、胃癌与OP的相关性明确,建议进行OP筛查 乳腺癌与OP关联紧密,绝经后女性接受芳香化酶抑制剂(AI)治疗年骨量丢失2%~3%,绝经前女性用化疗+促性腺激素释放激素(GnRH)激动剂年骨量丢失7%~7.7%,二者联用年骨量丢失达11%,激素三联疗法(化疗+皮质类固醇+雌激素)还会进一步增加骨折风险[72-74]。从机制看,乳腺癌细胞可通过骨转移、定殖增殖直接干扰骨代谢;绝经后女性雌激素补充疗法虽能抗骨吸收、维持骨稳态,但可能促进乳腺癌细胞生长[75];治疗层面,AI通过抑制芳香化酶减少雌激素合成致骨吸收增强,GnRH-a通过抑制性腺轴降低雌激素水平使绝经前女性骨量快速丢失,化疗与类固醇激素则通过抑制成骨细胞活性、增加破骨细胞活性加剧骨流失[72-74]。

前列腺癌患者OP风险显著升高,雄激素剥夺治疗(ADT)是性腺功能减退主因,GnRH激动剂治

疗12个月后,骨密度下降,骨折风险明显升高,双侧睾丸切除术或ADT还会使循环睾酮水平骤降,进一步加剧骨流失[76-77]。其机制在于雌激素对男性骨稳态至关重要,血清雌二醇水平与脊柱BMD正相关、与椎骨骨折风险负相关,ADT(如GnRH-a)不仅降低睾酮,还间接减少雌激素合成,破坏成骨细胞与破骨细胞平衡[77];同时GnRH-a会增加甲状旁腺激素介导的破骨细胞活化,改变骨骼对甲状旁腺激素的敏感性,加速骨吸收,在接受GnRH激动剂治疗的患者,脊柱、髋部和股骨的骨丢失显著[76-77]。

胃癌患者接受胃切除术后OP发生风险显著增加,因胃酸减少破坏肠道钙吸收所需环境。病理机制以吸收障碍为主,胃切除术导致胃酸分泌减少,而胃酸是肠道钙吸收的必要条件,钙吸收不足直接引发钙负平衡,且胃癌患者常伴营养不良,进一步加剧骨量丢失,最终升高OP与骨折风险[78]。

6.2 实施“基础干预+药物治疗”的综合管理策略,兼顾肿瘤控制与骨健康保护 基础干预需从生活方式与营养补充两方面入手:生活方式上,所有患者需开展快走、太极拳等负重运动,增强肌肉质量以降低跌倒风险,同时避免因镇痛药、镇静剂使用导致的平衡障碍,减少椎体、髋部脆性骨折[79-83],接受ADT的前列腺癌患者更需长期坚持负重运动,与药物联用可降低骨折风险[79-83];营养补充方面,需保证充足钙与维生素D摄入,这对胃癌术后(胃酸缺乏)、ADT治疗者尤为关键,可改善钙吸收障碍、减少骨流失。

药物治疗需按肿瘤类型适配选择:对于绝经后乳腺癌患者,联用唑来磷酸可预防AI相关的骨量丢失[84-86]。地舒单抗能够增加AI治疗患者的骨密度,降低与骨质疏松症相关的椎体骨折风险[87-89]。绝经前$GnRH-a+AI$治疗者需联用双膦酸盐/地舒单抗,可以抵消11%的年骨量丢失[72-74];在接受前列腺癌ADT治疗的患者中,使用双膦酸盐(口服/静脉)、地舒单抗可以增加骨密度[90],地舒单抗获FDA批准用于ADT人群,可延长无转移生存期,但需警惕颌骨坏死(ONJ)[91],选择性雌激素受体调节剂(SERMs)托瑞米芬可辅助降骨流失,暂未获批男性OP治疗[92-93];胃癌患者口服双膦酸盐(阿仑膦酸盐、利塞膦酸)可抑制破骨细胞活性,减少术后腰椎、股骨颈骨折[78],胃酸缺乏者需评估药物吸收情况,必要时调整用药方式。

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7此推荐意见的局限性与未来展望

该共识对老年常见的5大类疾病与OP的共病管理进行了分析汇总(总结见表3),但仍存在以下局限性:一是覆盖范围存在局限,聚焦OP与5类老年慢性病,因糖尿病、慢性肾病已有其他指南未纳入,且未涵盖其他常见老年性疾病,同时未针对多重共病、衰弱老年人群制定差异化方案;二是干预阈值缺乏明确界定,对不同慢性病患者OP筛查时机、抗OP治疗随访周期等核心节点无量化标准;三是证据支撑体系尚不完善,部分共病机制(如慢性肝病对骨

代谢的调控路径)未查阅到相关研究内容,部分药物(如甲状旁腺激素类药物在肝病患者中)缺乏安全性有效性证据;四是基层临床适配性不足,未针对基层筛查能力薄弱的现状,设计简化流程或实操工具。

未来可从四方面完善:一是拓展覆盖维度,补充多重共病、衰弱老人的差异化管理方案;二是明确干预阈值,依托高质量研究,量化OP筛查时机、随访周期等标准;三是强化证据支撑,深入研究未明共病机制及药物安全性;四是优化基层支持,设计简易筛查工具并配套医师培训,推动共识落地临床。

编写委员会

组长:刘丰(广州市第一人民医院)

组员:陈柏龄(中山大学附属第一医院),丁悦(中山大学孙逸仙纪念医院),王海彬(广州中医药大学第一附属医院),万雷(广州中医药大学第三附属医院),王晓东(广东药科大学附属第一医院),张金赫(中国人民解放军南部战区总医院),马为(广州市第一人民医院),潘晓华(深圳市宝安区人民医院),陈扬(佛山市第一人民医院),陈劲松(佛山市第一人民医院),梁江声(佛山市顺德区第三人民医院),廖淑金(广州市第一人民医院),高平(广东省人民医院),何文(中山大学附属第一医院),曾欣(汕头大学医学院第一附属医院),杨宇(广东医科大学附属医院),阮云军(南方医科大学南方医院),张艺军(南部战区总医院),梁真(深圳市人民医院),陈龙(南方医科大学深圳医院),银孟卓(广州市第一人民医院),许昕(广州市南沙区中心医院),杜娟(珠海市人

民医院),叶欣(汕头市中心医院),李立新(惠州市第三人民医院),林夏鸿(中山大学附属第七医院),黎佼(广州医科大学附属第二医院),倪晓俊(广州医科大学附属第四医院),宋卫兵(前海人寿广州总医院),苗海锋(东莞市人民医院),陈广湛(顺德市第三人民医院),陈协辉(深圳市龙华区中心医院),杨硕(广州市第十一人民医院),李康宝(广州市第一人民医院),杨崇哲(广州市第一人民医院),李雯曦(广州市第一人民医院)

执笔:刘丰(广州市第一人民医院),廖淑金(广州市第一人民医院)

顾问:邓伟民(前海人寿广州总医院)

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(收稿日期:2025-12-16 编辑:王冰)

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