Article(id=1256183443956838401, tenantId=1146029695717560320, journalId=1255847919539208197, issueId=1256183358493679805, articleNumber=null, orderNo=null, doi=10.13193/j.issn.1673-7717.2025.12.047, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=null, receivedDateStr=null, revisedDate=null, revisedDateStr=null, acceptedDate=null, acceptedDateStr=null, onlineDate=1777427071798, onlineDateStr=2026-04-29, pubDate=1765296000000, pubDateStr=2025-12-10, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1777427071798, onlineIssueDateStr=2026-04-29, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1777427071798, creator=13701087609, updateTime=1777427071798, updator=13701087609, issue=Issue{id=1256183358493679805, tenantId=1146029695717560320, journalId=1255847919539208197, year='2025', volume='43', issue='12', pageStart='1', pageEnd='258', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=1, specialIssue=null, createTime=1777427051344, creator=13701087609, updateTime=1777427760067, updator=13701087609, preIssue=null, nextIssue=null, ext={EN=IssueExt(id=1256186331126969089, tenantId=1146029695717560320, journalId=1255847919539208197, issueId=1256183358493679805, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1256186331126969090, tenantId=1146029695717560320, journalId=1255847919539208197, issueId=1256183358493679805, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null}, startPage=253, endPage=258, ext={EN=ArticleExt(id=1256183447534579771, articleId=1256183443956838401, tenantId=1146029695717560320, journalId=1255847919539208197, language=EN, title=Expert Consensus on Integrated Traditional Chinese and Western Medicine Diagnosis and Treatment of Multiple Myeloma Bone Disease in Guangdong-Hong Kong-Macao Greater Bay Area, columnId=1256183446796382258, journalTitle=Chinese Archives of Traditional Chinese Medicine, columnName=Expert Consensus and Guidelines, runingTitle=null, highlight=null, articleAbstract=

Multiplemyeloma(MM)is one of the most common malignant tumors of the hematologic system,with multiple myeloma bone disease(MBD)as a hematological complication.MBD is prominently characterized by pathological fractures,osteoporosis and osteolytic lesions,all of which severely impact patients'quality of life and survival rates.The primary mechanisms of MBD involve bone destruction and impaired osteogenesis,especially the abnormal activation of the receptor activator of nuclear factor kappa B(RANK)/ligand of RANK(RANK-L)/osteoprotegerin(OPG)system,along with an imbalance in the regulation of osteoclast and osteoblast function by pro-inflammatory cytokines in the bone marrow microenvironment.In recent years,substantial progress has been achieved in MBD treatment through integrated traditional Chinese and Western therapeutic strategies.This combined approach harnesses multiple therapeutic advantages to alleviate bone pain,enhance bone strength and reduce the risk of complications.To standardize this integrated diagnosis and treatment protocol,an expert team has developed a consensus based on evidence-based medicine and regional resources in traditional Chinese and Western medicine within the Lingnan area.This consensus aims to provide guidance for clinical practice and improve patients'quality of life and prognosis.

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多发性骨髓瘤(multiplemyeloma,MM)是血液系统常见的恶性肿瘤之一,其中骨病(multiplemyeloma bone disease,MBD)是其典型的并发症,以病理性骨折、骨质疏松症、溶骨性病变等表现显著,严重影响患者的生活质量和生存期。MBD的发生机制主要涉及骨破坏与成骨障碍,特别是RANK/RANK-L/OPG系统的异常激活,以及骨髓微环境中促炎细胞因子对破骨和成骨细胞功能的调控失衡。近年来,随着中西医结合治疗策略的不断发展,MBD的治疗取得了显著成效。中西医结合方法能够发挥多重治疗优势,改善骨痛症状,增强骨强度,并减少并发症风险。为规范中西医结合诊疗,专家团队基于循证医学证据,整合岭南地区中西医资源,达成MBD中西医结合诊疗专家共识,旨在为临床实践提供指导,提升患者生活质量和预后。

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蓝海(1980-),男,广东梅州人,主任医师,博士研究生导师,博士,研究方向:多发性骨髓瘤中西结合诊治的基础与临床。E-mail:
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杨宏光(1971-),男,湖南通道人,副主任医师,硕士,研究方向:中西医结合血液病临床。

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杨宏光(1971-),男,湖南通道人,副主任医师,硕士,研究方向:中西医结合血液病临床。

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杨宏光(1971-),男,湖南通道人,副主任医师,硕士,研究方向:中西医结合血液病临床。

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种类用法剂量给药时间肾功能不全患者用法用量调整
帕米膦酸静脉90 mg/月持续至少4 hCrCI<30 mL/min或SCr>265.2μ mol/L(3 mg/dl)时输注时间需延长至4~6 h
唑来膦酸静脉4 mg/月持续至少15 min①CrCI 50~60 mL/min:3.5 mg/月;②CrCI 40~50 mL/min:3.3mg/月;③CrCI 30~40 mL/min:3mg/月;④CrCI<30 mL/min:禁用
因卡膦酸静脉10 mg/月静脉滴注2~4 h>65岁推荐5 mg/次
), ArticleFig(id=1256183483727229398, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1256183443956838401, language=CN, label=表1, caption=

常用双膦酸盐推荐用法

, figureFileSmall=null, figureFileBig=null, tableContent=
种类用法剂量给药时间肾功能不全患者用法用量调整
帕米膦酸静脉90 mg/月持续至少4 hCrCI<30 mL/min或SCr>265.2μ mol/L(3 mg/dl)时输注时间需延长至4~6 h
唑来膦酸静脉4 mg/月持续至少15 min①CrCI 50~60 mL/min:3.5 mg/月;②CrCI 40~50 mL/min:3.3mg/月;③CrCI 30~40 mL/min:3mg/月;④CrCI<30 mL/min:禁用
因卡膦酸静脉10 mg/月静脉滴注2~4 h>65岁推荐5 mg/次
), ArticleFig(id=1256183484620616156, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1256183443956838401, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=
药物唑来膦酸/因卡膦酸地舒单抗帕米膦酸
适应证首选,无论影像学检查是否存在MBD影像学证实存在MBD,伴肾功能不全时首选仅在首选药物不可及或存在禁忌证时
给药方式静脉皮下静脉
疗程<VGPR,每月1次;<VGPR,每月1次;≥VGPR,每月1次用够12个月后改为每3个月或每6个月或每年1次,或者停药;出现生化复发/进展则重新启用。每月1次,持续用药;每月1次,持续用药如果停药,则在末次给药后至少6个月应用1次唑来膦酸;或每6个月应用1次地舒单抗临床医师根据患者的因素及疾病相关的因素来决定
管理每月监测内生肌酐清除率、电解质、尿蛋白;口腔健康状况:基线,以后每年1次,或出现症状时;补充钙剂及维生素D;做好患者教育
), ArticleFig(id=1256183484930994659, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1256183443956838401, language=CN, label=表2, caption=

抗MBD药物的选择

, figureFileSmall=null, figureFileBig=null, tableContent=
药物唑来膦酸/因卡膦酸地舒单抗帕米膦酸
适应证首选,无论影像学检查是否存在MBD影像学证实存在MBD,伴肾功能不全时首选仅在首选药物不可及或存在禁忌证时
给药方式静脉皮下静脉
疗程<VGPR,每月1次;<VGPR,每月1次;≥VGPR,每月1次用够12个月后改为每3个月或每6个月或每年1次,或者停药;出现生化复发/进展则重新启用。每月1次,持续用药;每月1次,持续用药如果停药,则在末次给药后至少6个月应用1次唑来膦酸;或每6个月应用1次地舒单抗临床医师根据患者的因素及疾病相关的因素来决定
管理每月监测内生肌酐清除率、电解质、尿蛋白;口腔健康状况:基线,以后每年1次,或出现症状时;补充钙剂及维生素D;做好患者教育
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粤港澳大湾区多发性骨髓瘤骨病中西医诊疗专家共识
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国家中医区域血液病诊疗中心华南分中心 , 杨宏光 1 , 陈群群 1 , 蓝海 2
中华中医药学刊 | 专家共识指南 2025,43(12): 253-258
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中华中医药学刊 | 专家共识指南 2025, 43(12): 253-258
粤港澳大湾区多发性骨髓瘤骨病中西医诊疗专家共识
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国家中医区域血液病诊疗中心华南分中心, 杨宏光1, 陈群群1, 蓝海2
作者信息
  • 1.广州中医药大学第三附属医院,广东 广州 510240
  • 2.广州中医药大学顺德医院,广东 顺德 538300
  • 杨宏光(1971-),男,湖南通道人,副主任医师,硕士,研究方向:中西医结合血液病临床。

通讯作者:

蓝海(1980-),男,广东梅州人,主任医师,博士研究生导师,博士,研究方向:多发性骨髓瘤中西结合诊治的基础与临床。E-mail:
Expert Consensus on Integrated Traditional Chinese and Western Medicine Diagnosis and Treatment of Multiple Myeloma Bone Disease in Guangdong-Hong Kong-Macao Greater Bay Area
National Traditional Chinese Medicine Regional Hematology Diagnosis and Treatment Center South China Branch, Hongguang YANG1, Qunqun CHEN1, Hai LAN2
Affiliations
  • 1.Third Affiliated Hospital of Guangzhou University of Chinese Medicine,Guangzhou 510240,Guangdong,China
  • 2.Shunde Hospital of Guangzhou University of Chinese Medicine,Shunde 538300,Guangzhou,China
出版时间: 2025-12-10 doi: 10.13193/j.issn.1673-7717.2025.12.047
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多发性骨髓瘤(multiplemyeloma,MM)是血液系统常见的恶性肿瘤之一,其中骨病(multiplemyeloma bone disease,MBD)是其典型的并发症,以病理性骨折、骨质疏松症、溶骨性病变等表现显著,严重影响患者的生活质量和生存期。MBD的发生机制主要涉及骨破坏与成骨障碍,特别是RANK/RANK-L/OPG系统的异常激活,以及骨髓微环境中促炎细胞因子对破骨和成骨细胞功能的调控失衡。近年来,随着中西医结合治疗策略的不断发展,MBD的治疗取得了显著成效。中西医结合方法能够发挥多重治疗优势,改善骨痛症状,增强骨强度,并减少并发症风险。为规范中西医结合诊疗,专家团队基于循证医学证据,整合岭南地区中西医资源,达成MBD中西医结合诊疗专家共识,旨在为临床实践提供指导,提升患者生活质量和预后。

多发性骨髓瘤  /  骨病  /  中西医结合  /  专家共识

Multiplemyeloma(MM)is one of the most common malignant tumors of the hematologic system,with multiple myeloma bone disease(MBD)as a hematological complication.MBD is prominently characterized by pathological fractures,osteoporosis and osteolytic lesions,all of which severely impact patients'quality of life and survival rates.The primary mechanisms of MBD involve bone destruction and impaired osteogenesis,especially the abnormal activation of the receptor activator of nuclear factor kappa B(RANK)/ligand of RANK(RANK-L)/osteoprotegerin(OPG)system,along with an imbalance in the regulation of osteoclast and osteoblast function by pro-inflammatory cytokines in the bone marrow microenvironment.In recent years,substantial progress has been achieved in MBD treatment through integrated traditional Chinese and Western therapeutic strategies.This combined approach harnesses multiple therapeutic advantages to alleviate bone pain,enhance bone strength and reduce the risk of complications.To standardize this integrated diagnosis and treatment protocol,an expert team has developed a consensus based on evidence-based medicine and regional resources in traditional Chinese and Western medicine within the Lingnan area.This consensus aims to provide guidance for clinical practice and improve patients'quality of life and prognosis.

multiple myeloma  /  bone disease  /  integrated traditional Chinese and Western medicine  /  expert consensus
国家中医区域血液病诊疗中心华南分中心, 杨宏光, 陈群群, 蓝海. 粤港澳大湾区多发性骨髓瘤骨病中西医诊疗专家共识. 中华中医药学刊, 2025 , 43 (12) : 253 -258 . DOI: 10.13193/j.issn.1673-7717.2025.12.047
National Traditional Chinese Medicine Regional Hematology Diagnosis and Treatment Center South China Branch, Hongguang YANG, Qunqun CHEN, Hai LAN. Expert Consensus on Integrated Traditional Chinese and Western Medicine Diagnosis and Treatment of Multiple Myeloma Bone Disease in Guangdong-Hong Kong-Macao Greater Bay Area[J]. Chinese Archives of Traditional Chinese Medicine, 2025 , 43 (12) : 253 -258 . DOI: 10.13193/j.issn.1673-7717.2025.12.047
多发性骨髓瘤(multiplemyeloma,MM)是发病率居第二位的血液系统肿瘤,占血液系统恶性肿瘤的10% ~15%[1]。骨痛是MM常见的临床症状之一,大约2/3的MM患者因骨痛就诊,80%的患者X线片显示骨骼异常包括骨折、弥漫性骨质疏松症、溶骨性改变或上述几种病变同时存在[2]。多发性骨髓瘤骨病(multiple myeloma bone disease,MBD)是指由于骨髓瘤溶骨破坏导致的病理性骨折、脊髓与神经根压迫症、骨质疏松症、高钙血症以及骨痛等一系列临床并发症的总称,在骨髓瘤患者中的发生率高达80% 以上[3]。MBD发病的机制主要是破骨和成骨的失衡造成的,一方面是核因子κB受体激活剂(RANK)及其配体(RANK-L)和护骨素(OPG)系统对破骨细胞通路的激活导致骨破坏和骨形成失衡导致MBD,另一方面骨髓微环境中可溶性分子(包括细胞因子、胞外体和代谢产物)通过介导破骨细胞活化和成骨细胞失活诱导发生MBD[4-5]。患者发生骨相关事件(skeletal- related events,SRE)包括病理性骨折、脊髓压迫等的风险极高,脊柱骨、颅骨、肋骨骨病发病率高于四肢长骨,严重影响MM患者的生活质量和生存[6]。近年来,随着中西医治疗药物的不断研发和治疗手段的改进,MBD的预后得到很大地改善。目前,国内多数中医医院对于MBD的治疗均采用中西医结合疗法,而该病的中西医结合专家诊疗共识尚属空白。鉴于此,为了更好地规范中西医结合临床诊疗行为,使MBD患者得到更好的临床疗效和生存期,笔者组织岭南地区的粤港澳大湾区内各中医、西医三级甲等医院血液病专家讨论、达成此共识,以便更好地指导中西医结合临床实践,提高患者生活质量,延长生存期。
MM是一种起病隐匿、逐渐进展的浆细胞恶性肿瘤。其主要特征为异常浆细胞在骨髓中大量增殖,进而引发一系列骨骼系统病变,即MBD。骨痛、病理性骨折、溶骨性损伤及骨质疏松症等为MBD的核心表现,严重影响患者的生活质量和长期生存[7]。根据流行病学调查,约80%的MM患者会在疾病进展过程中发生骨病,其中骨痛为最常见的临床首发症状[8]。西医对MBD的诊疗主要包括抗骨吸收药物(如双膦酸盐和地诺单抗)、放疗、手术干预等,以减轻骨痛、预防病理性骨折和SRE,并延缓病情进展[9]。然而,由于MBD的发病机制涉及破骨细胞活化与成骨细胞抑制的复杂交互作用,以及多种细胞因子的调控,现有治疗方法仍难以完全阻止骨病的进展[10]。同时,患者的治疗依从性差异较大,部分药物可能带来不良反应,如双膦酸盐引起的颌骨坏死等问题[11]。因此,加强对MBD的早期诊断和多学科联合治疗,推进新型治疗药物的研发和应用,成为亟待解决的问题。
在中医理论体系中,尚无直接对应“多发性骨髓瘤骨病”之病名,但根据其骨痛、骨质疏松症、病理性骨折等临床表现,可归属于中医“骨痹”“骨痿”“肾虚”等病证范畴[12]。中医认为,MBD的发生与“肾虚”密切相关,肾主骨、生髓,骨髓瘤的溶骨性破坏在一定程度上反映了肾精亏虚、骨髓空虚等病理变化[13]。因此,中医治疗MBD主要从补肾益髓、活血通络、健脾祛湿等方面入手,以减轻骨痛、增强骨骼强度、提升患者的整体抗病能力。近年来,中医药在缓解MBD症状、减轻西药不良反应方面的作用逐渐得到认可[14]。然而,目前中医对MBD的辨证标准、方药选择及疗效评价等方面仍存在主观性大、标准化不足等问题,这在一定程度上限制了其疗效的推广和评价。亟需通过高质量的临床研究来提升中医药治疗MBD的循证证据级别,进一步优化中西医结合治疗方案,以期为MBD患者提供更好的疗效。
(1)MBD的诊断主要基于影像学的评估,常用的评估手段有X线、低剂量CT、MRI及PET-CT。
(2)影像学对MBD分为0~4级:0级为无骨质疏松症及溶骨性损害;1级为严重的弥漫性骨质疏松症;2级为一个解剖学部位的一个或多个溶骨性损害;3级为多个解剖学部位的多个溶骨性损害;4级为严重溶骨性损害并发病理性骨折[15]
(3)X线与CT检查是目前显示骨质疏松症与骨质破坏最常用、最经济的方法,CT对1、2级分级骨病分辨率优于X线,而对于3、4级骨病则两者相同。X线片空间分辨率高,整体观察效果较好,对于头颅、四肢长骨的MBD仍可作为首选检查;CT密度分辨率高,对组织重叠较多的部位和较小的骨质破坏病灶及软组织肿块显示明显优于X线,是MBD的选择性影像学检查方法[16]
(4)MRI对可疑溶骨病变或骨质疏松症部位的骨髓浸润的判断上具有重要的诊断意义;但是MRI主要反映的是MM的骨髓浸润,并不是直接发现骨质破坏[17]
(5)PET/CT可有效地检查出MBD的活动,以高灵敏度和高特异性揭示骨髓受累情况,其价值更在于对疾病治疗的缓解程度与进展情况的评估与监测,以及对髓外病变的判断[18]
(1)骨吸收标志物的检测:抗酒石酸酸性磷酸酶(由破骨细胞产生和分泌)、尿中羟脯氨酸(骨胶原代谢产物)、尿脱氧吡啶酚和吡啶酚(骨胶原降解产物),以及I型胶原C末端肽(S-CTX)等。
(2)骨形成标志物的检测:血清碱性磷酸酶、骨源性碱性磷酸酶、骨钙素、I型原胶原前肽等。
MBD的诊断主要依据影像学检查,是活动性MM全面诊断的重要组成部分。MRI是评价骨髓浸润程度的金标准,也是排除脊柱压缩性骨折的首选手段。凡是考虑诊断为活动性MM患者均应进行影像学检查。同时对于无靶器官损害的患者,MRI检查出现≥1处以上且超过5 mm的局灶性骨质破坏也是需要启动治疗的指征:
(1)普通X线平片:对颅骨、四肢长骨进行普通X线摄片检查。
(2)CT检查:肋骨病变常用CT检查,包括全身低剂量CT,已广泛用于X片检测不敏感及高度可疑骨病的模糊区域的检查。
(3)核磁共振成像(MRI):适用于颈椎、胸椎、腰椎、骨盆病变及脊髓压迫等检查。
(4)18 F-氟脱氧葡萄糖正电子发射断层扫描-CT(18 FDG PET-CT):有助于了解是否有髓外浆细胞瘤及微小残留病(MRD)检测。
MBD需与常见骨质破坏的疾病如骨淋巴瘤、骨转移瘤相鉴别。三者均好发于富含红骨髓的部位,均可合并有软组织肿块;病理性骨折发生率为MM>骨转移瘤>骨淋巴瘤;PET/CT代谢程度为骨淋巴瘤>骨转移瘤大于MM。影像学上,MM以溶骨型骨质破坏为主,多为虫蚀样、穿凿样,边界清晰,骨轮廓呈“破而不烂”,可见典型“微脑征”;骨淋巴瘤以溶骨及骨髓浸润型为主,典型表现为轻微骨质破坏伴较大软组织肿块,部分可见“融冰征”;骨转移瘤表现多样化,溶骨性骨质破坏约占74.0%,呈“局灶性”表现多见,成骨性改变约占26.0%[21-22]
MBD治疗的目标包括:①缓解疼痛,降低血钙,改善生活质量;②治疗和预防SRE;③控制肿瘤进展,延长生存期。原发病的规范化整体治疗是MBD治疗的基石。通过有效的抗骨髓瘤治疗,可以阻断或延缓MM的病理进程,避免骨质破坏的进一步加重,起到治疗骨病的作用。MBD的治疗[23-25]包括抗骨髓瘤药物、骨靶向药物治疗、局部放疗、手术治疗以及镇痛等措施,抗骨髓瘤药物治疗不列入本共识中。
除非脊柱骨折的急性期,一般不建议患者绝对卧床,否则更容易发生钙丢失,应鼓励患者进行适当的活动,如步行和游泳等,但应避免剧烈运动或对抗性运动。有脊柱病变的患者应使用加有软垫的硬板床。
骨靶向药物使用原则:
(1)所有接受MM治疗的患者均应给予双膦酸盐或地舒单抗;
(2)强烈建议进行牙科基线检查;
(3)使用双膦酸盐治疗时,应该监测肾功能障碍和颌骨骨坏死情况;
(4)骨靶向治疗(双膦酸盐和/或地舒单抗)宜持续长达2年;
(5)给药的频率(每月1次还是每3个月1次)取决于患者的个体情况和治疗反应;
(6)治疗2年以上时,应根据临床判断。
(1)适应证:所有接受抗骨髓瘤治疗的MM患者,无论影像学检查是否存溶骨性病变,均应使用双膦酸盐。对于骨髓瘤相关的高钙血症,唑来膦酸优于帕米膦酸。对于MGUS、SMM、孤立性浆细胞瘤患者,仅在伴有明显骨质疏松症的情况下推荐双膦酸盐。对于临床诊断为活动性MM,即使影像学没有骨病也建议使用双膦酸盐。
(2)常用双膦酸盐的选择及推荐用法:第一代双膦酸盐以氯膦酸为代表(基本淘汰),第二代是含氮的双膦酸盐,以帕米膦酸、阿仑膦酸钠为代表,第三代是含氮杂环结构的双膦酸盐以唑来膦酸、因卡膦酸为代表。唑来膦酸/因卡膦酸由于其特有的含氮杂环结构,在用药方法和疗效上均有优势。需要注意的是,无论是诊断时还是在治疗过程中都需要根据患者的肾功能调整双膦酸盐的剂量。
(3)治疗疗程:从MM初始治疗即开始使用双膦酸盐,每月1次,总疗程持续2年以上。如果12个月后获得≥非常好的部分缓解(VGPR)的疗效,可以减少给药频率为每2~3个月1次,或者根据骨病严重程度适当延长给药间隔。停用双膦酸前需全面评估发生骨折的风险。当疾病出现生化复发后,需要重新开始双膦酸治疗以降低新的SRE风险。
(4)双膦酸盐的安全应用:①常见不良反应:包括感冒样症状、胃肠道症状(主要是口服制剂)、低钙血症、颌骨坏死、贫血、肾功能损伤、皮疹、药物热等。其中下颌骨坏死(ONJ)和肾脏损害尤其应重视。②双膦酸盐治疗血钙水平正常后均应补充钙片及维生素D:MM患者的具体剂量参照健康老年人推荐的钙摄入量:51~70岁的男性1000 mg/d,50岁以上女性及70岁以上男性1200 mg/d,最大剂量2000 mg/d。维生素D:51~70岁600 IU/d,70岁以上800 IU/d,最大剂量4000 IU/d。③伴有肾功能不全的患者补钙需密切监测肾功能:双膦酸盐可能诱发急性肾衰竭,因此用药过程中每月监测内生肌酐清除率、电解质、尿白蛋白,并相应作出剂量调整。
(1)适应证:具有MBD证据的MM。地舒单抗对于SRE的预防效果与唑来膦酸相似,但肾毒性发生率更低,在密切监测下,即使内生肌酐清除率低于30 mL/min,仍可应用地舒单抗,因此在肾功能损伤的MM患者中更为推荐。对于SMM、MGUS或孤立性浆细胞瘤,仅在患者同时存在骨质疏松症时推荐应用地舒单抗(60 mg皮下注射,每6个月1次)。
(2)给药方式及安全使用:①使用剂量:地舒单抗120mg皮下注射,每月1次,持续至给药后2年。②注意事项:当给药超过24个月,且MM疗效达到≥VGPR时,可以考虑降低给药频次甚至停药,建议最后一次地舒单抗给药后至少每6个月应用1次静脉双膦酸盐以预防潜在的反弹效应。③补充钙剂和维生素D:接受地舒单抗治疗的患者,尤其是伴有肾功能损害的患者,均需要补充钙片及维生素D;血钙高的患者在血钙水平降至正常后开始补充,并定期监测血清钙、维生素D、磷及镁的水平。
对于化疗和双膦酸盐治疗后仍无法缓解的顽固性疼痛、椎体不稳、即将发生的病理性骨折和脊髓压迫,可采用局部放疗,可以有效迅速缓解骨病和软组织病变的疼痛,并有可能促进骨折愈合。推荐剂量为8~10 Gy/次。
骨髓瘤外科治疗的目的不是根治疾病,而应以缓解症状、提高生存质量为重点,强化多学科协作,通过手术早期干预治疗潜在的或已经发生的病理性骨折、解除脊髓与神经根压迫,缓解疼痛,重建骨连续性及脊柱、骨盆等重要结构的稳定性,为患者后续的治疗创造条件。
(1)外科手术指征:①四肢长骨病理性骨折或存在潜在病理性骨折风险;②脊柱病变压迫脊髓与神经根致神经功能损害进行性加重;③脊柱压缩骨折和(或)脊柱不稳;④药物和(或)放疗无法缓解的严重骨痛,且对应部位存在明确骨破坏。
(2)禁忌证:①全身状况差,不能耐受手术者;②心、肺、肾、肝功能衰竭不能控制者;③凝血功能严重障碍不能纠正者;④合并严重感染不能控制者;⑤接受外科治疗前,应由血液科医师进行严格的评估。
(3)手术时机:①短时间内迅速进展的截瘫;②无法实现有效外固定的长骨病理性骨折。
对于骨内孤立性浆细胞瘤患者,建议对相关区域先进行放射治疗。如果病变引起结构不稳定或神经损害,可以进行手术。对于骨外浆细胞瘤,主要的治疗是放射治疗,若临床需要可对受累区域进行手术治疗。
MBD患者通常会出现不同程度的骨痛,严重疼痛时给予镇痛药物治疗,应遵循WHO镇痛药物三阶梯原则规范化使用镇痛药,对服用药物种类、用法和剂量等应详细记录和疼痛评估,镇痛需求的减少往往意味着治疗有效。
中医临床多依据MBD临床表现,将其归属于“骨痹”“腰痛”“虚劳”“骨蚀”的范畴,以骨痛为主要表现者称之为“骨痹”,以骨质破坏为主要表现者称之为“骨蚀”。2009年11月中国中西医结合学会和中华中医药学会组织血液病专家就常见血液病中医病名进行专题讨论并达成共识,确定MM的中医病名为“骨髓瘤”[26]。本病发病内因素体禀赋薄弱,或脏腑功能失调,后天失于调养,精血亏损,脏腑气血阴阳亏虚;外因六邪之毒侵袭,留滞经络筋骨关节,久致气滞、痰浊、血瘀。病位在肺、脾、肾三脏,基本病机为脏腑正气虚弱,外感毒邪,导致瘀血痰浊的聚集成瘤,而肾虚血瘀贯穿疾病始终[27-28]。中医认识MM是在辨病与辨证相结合的基础上,按照本病证候及其演变特点的不同属性,通过证候、病机、治法、方剂及药物治疗一体化不断揭示出疾病的疗效机制[29]。中医认为MBD是MM初起及全病程主要表现,总属本虚标实之证,初以邪毒为主,正气充足,后则肾虚而筋骨失荣,邪毒进而独盛,其本质概为肾虚血瘀毒蕴,治疗以益肾益气、活血解毒为基本治则[30-32]
MBD以骨痛和骨破坏为主要证候,是正虚邪侵,深传骨髓,病邪痹阻经络关节筋骨所致,其病机总体可概括为“虚”“痰”“瘀”“毒”四字。因患者多为先天不足或各种后天因素导致五脏虚损,内外毒邪侵袭脏腑,流注骨髓,损伤正气,肺脾肾失于通调水道,日久则痰瘀毒邪内生,脉络痹阻,肾精耗损,筋骨失养。其病骨损主要责之肾精亏虚、痰瘀毒结,骨痛责之气机失于升降出入,病位主要责之于肾与骨髓,又与肝、脾、肺密切相关[33-36]
MBD中医病机总属本虚标实之证,治疗大法为扶正虚而祛邪毒,扶正当扶肾精之虚,祛邪首当活血兼以解毒[37-39]。临床具体运用当中西医结合,分期分阶段,辨证论治,如化疗期间患者毒邪症状表现明显,邪气盛,此时治疗以足量足疗程“大毒”之西药攻伐为主,中医治应以健脾益肾为主[40-42];化疗后为巩固治疗阶段,此期为大剂攻伐过后,正气亏虚,本虚为主,中医当治疗以健脾益气,补肾滋阴;化疗后缓解期为维持治疗阶段,此期患者无攻伐之西药,中医治疗以“瘥”后防复为主,攻补兼施,治以调畅气机、健脾滋肾,消积解毒[43-51]
MBD的临床论治以骨痛的有无为依据,痛者以经络筋骨关节痹阻为主,骨破坏者以五脏精血亏虚为主。因MM的中医辨证论治在中西诊疗专家共识已有详述,故本共识仅对这两种临床特征作分型论治。
(1)痰瘀毒结证
主症:腰背脊骨或胸胁疼痛。
兼症:痰核肿大,癥瘕痞块,或咳嗽多痰,或口干便结。
舌脉:舌黯红可有瘀斑瘀点,苔黄或白腻,脉弦滑或数。
治法:涤痰祛瘀止痛,解毒散结。
方药:涤痰汤合身痛逐瘀汤加减:法半夏10 g,茯苓10 g,陈皮10 g,海藻10 g,黄药子10 g,当归10 g,川芎6 g,桃仁10 g,牡丹皮10 g,赤芍10 g,乌药10 g,白花蛇舌草15 g,鳖甲10 g,蛇六谷15 g。
加减法:痰核明显加白芥子10 g,山慈菇10 g;癥瘕痞块加莪术10 g,三棱10 g,炮山甲10 g;邪毒蕴结加全蝎10 g,水蛭10 g,蜂房10 g;咳喘痰多加麻黄6 g,葶苈子10 g,瓜蒌皮10 g,杏仁10 g;热毒盛加蛇莓30 g,重楼10 g,石见穿30 g。
(2)肺脾肾虚证
主症:腰痛难以屈伸,腰膝酸软,神疲乏力,头晕耳鸣。
兼症:偏阳虚者多面色白,畏风寒,脘腹时胀满,纳差,便溏,夜尿多;偏阴虚者多消瘦,失眠多梦,烦躁易怒,五心烦热,尿赤便干。
舌脉:舌质淡边有齿印或舌瘦而红,苔白或少苔无苔,脉沉细或细数。
治法:健脾益气,补肾填精。
方药:参苓白术散和左归丸加减:党参15 g,黄芪15 g,熟附子10 g,桂枝10 g,熟地黄15 g,山茱萸15 g,枸杞子10 g,淫羊藿10 g,杜仲15 g,仙茅10 g,巴戟天10 g,山药15 g,茯神15 g,陈皮10 g,白术10 g,薏苡仁15 g,鹿角胶6 g,阿胶6 g,麦芽15 g,炙甘草6 g。
加减法水肿明显加茯苓15 g,车前子15 g;畏寒明显加肉苁蓉15 g,锁阳15;阴虚明显者加女贞子15 g,旱莲草15 g;失眠多梦加酸枣仁15 g,夜交藤15 g;心悸心慌加龙骨15 g,牡蛎15 g。
中医特色治疗为广州中医药大学第三附属医院骨伤治疗特色项目,作为华南区中医血液病诊疗中心治疗该病的特色疗法,经与会专家讨论达成共识。
(1)药物罐疗法
①评估患者病情、既往史、意识、活动能力、有无感觉迟钝或障碍,患者体质及实施拔罐处的皮肤有无破损和伤口、对疼痛的耐受程度、心理状况、有无药物过敏史。
②以竹罐为工具,经药液蒸煮后,利用高热排除罐内空气,造成负压,使罐吸拔于皮肤上,或是将一定量的药液放入玻璃罐(抽气罐)内,运用闪火法(抽气法)使罐内形成负压,从而使罐吸拔于皮肤上,从而达到平衡阴阳,扶正祛邪,调节功能,调整气血,疏通经络,增强体质的作用。
(2)中药外敷法(祛瘀消肿止痛膏)
①评估患者病情,体质及实施部位的皮肤有无破损和伤口、有无药物过敏史。
②将祛瘀消肿止痛膏敷于患处或穴位上,使药物从毛孔深入腠理,行气血、营阴阳、通经络,从而达到活血化瘀、清热拔毒、消肿止痛,改善周围组织营养的作用。
(3)艾灸床
①评估患者病情、查看皮肤情况、询问大小便、对热的耐受能力,查看舌苔脉象,告知其注意事项,询问过敏史、疾病史及禁忌证等。
②将做好的艾饼置于艾灸盘里,点燃艾饼,将艾灸盘置于艾灸床下方固定位置,扶患者仰卧于艾灸床上,治疗过程密切听取患者的反馈,根据患者的温度感觉调整艾灸盘的高度。
③治疗完毕后告知患者注意事项。
(4)温阳罐
①评估患者病情、查看皮肤情况、对热的耐受能力,查看舌苔脉象,告知其注意事项,有无内脏出血史,询问过敏史、疾病史及禁忌证等。
②手法推拿对痛点及经脉进行按压推揉以达到疏通经脉,减轻疼痛,改善功能。
③放置艾灸垫,酒精燃烧形成负压,温阳罐吸附皮肤,达到行气活血,祛风散寒,消肿止痛,放置艾饼,添加酒精助其燃烧,留罐15~20 min,进行温阳灸,达到温经通络,温补阳气,防治疾病。
④告知患者治疗后注意事项。
中医疗效评价可参照国家中医药管理局发布的《中医内科病证诊断疗效标准》中的痹证及《中药新药临床研究指导原则》对多发性骨髓瘤患者的主要症状要素进行证候积分,治疗前后作评分分级,分级下降至少一级为有效,分级无下降为无效。也可以把治疗前后的证候积分按尼莫地平法计算疗效。
共识发起人:杨宏光(广州中医药大学第三附属医院)、蓝海(广州中医药大学顺德医院)
共识起草人:杨宏光(广州中医药大学第三附属医院)、范婷婷(广州中医药大学第三附属医院)、宋振杰(广州中医药大学第三附属医院)
西医专家组成员(按姓氏汉语拼音顺序排序):
夏忠军、王华(中山大学肿瘤防治中心),钟立业(暨南大学附属华侨医院),曾辉(广东省人民医院),李勇华(南部战区总医院),周红升(南方医科大学南方医院),许昕、周薇(广州市第一人民医院)、刘丹(广州医科大学一附院),程淑琴(广州市番禺区中心医院),郭子文(中山市人民医院),陈荣袢(江门市中心医院),李小亮(珠海市人民医院),周继豪(深圳市人民医院),原超(广州中医药大学第三附属医院),赵莹(佛山市第一人民医院),张复华(华南理工大学第六附属医院),郑彦铭(澳门科技大学医院)
中医专家组成员(按姓氏汉语拼音顺序排序):
代喜平(广东省中医院),戴媺(广州医科大学附属中医医院),方灿途(中山市中医院),郭添胜(番禺中医院),蓝海(广州中医药大学顺德医院),李宜真(广州中西结合医院),李宏良(佛山市中医院),吴远斌(广东省中医院),吴建伟(五邑中医院),谢莹、周华(广东省中医院),王春明(澳门大学中华医药学院),杨宏光(广州中医药大学第三附属医院),张庆文、陈群群(广州中医药大学第三附属医院),方剑锋(香港浸会大学)
主审:陈志雄(广州中医药大学第一附属医院),于天启(广州中医药大学第三附属医院)
  • 国家科技部、广东省政府省部共建国家重点实验室项目(SZGZZ20240001)
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2025年第43卷第12期
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doi: 10.13193/j.issn.1673-7717.2025.12.047
  • 首发时间:2026-04-29
  • 出版时间:2025-12-10
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国家科技部、广东省政府省部共建国家重点实验室项目(SZGZZ20240001)
作者信息
    1.广州中医药大学第三附属医院,广东 广州 510240
    2.广州中医药大学顺德医院,广东 顺德 538300

通讯作者:

蓝海(1980-),男,广东梅州人,主任医师,博士研究生导师,博士,研究方向:多发性骨髓瘤中西结合诊治的基础与临床。E-mail:
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2种不同金属材料的力学参数

Family
属数
Number of
genus
种数
Number of
species
占总种数比例
Percentage of
total species (%)

Genus
种数
Number of
species
占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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