1、充分发挥护理在降低骨相关事件中的作用,Chen MinDirector for Department of oncology nurse , Central Hospital,FuLing,ChongQing Cityl,骨相关事件类型Types of Skeletal-Related Events,病理性骨折,SREs,外科干预,需要放疗,高钙血症,脊髓压迫,骨转移流行病学：问题严重性Bone Metastases Epidemiology: Scope of the Problem,美国每年影响 400,000个人 1Greater than any other site of tumor
2、 metastasis,1. Coleman RE, et al. Cancer Treat Rev. 2010;36:615-620. 2. Kyle RA, et al. Mayo Clin Proc. 2003;78:21-33. 3. Coleman RE. Oncologist. 2004;9(suppl 4):14-27. 4. Palumbo A, et al. Blood. 2004;104:3052-3057. 5. Smith W, et al. Semin Oncol. 2004;31(2 suppl 4):11-15. 6. Lipton A. J Support On
3、col. 2004;2:205-213. 7. Tu SM, et al. Cancer Treat Res. 2004;118:23-46.,骨转移：详情Bone Metastasis: Details,转移常常发生于中轴骨骼红骨髓位点循环量大,流速低骨基质促进肿瘤细胞侵入肿瘤细胞产生粘附分子有助肿瘤细胞附着,骨转移发生的病理生理学Pathophysiology of the Development of Bone Metastases,骨重塑过程：终身持续1，两种细胞的活性是由骨微环境中的激素和生长因子调节1,1. Roodman GD. N Engl J Med. 2004;350:16
4、55-1664. 2. Kodama H, et al. J Exp Med. 1991;173:1291-1294. 3. Lacey DL, et al. Cell. 1998;93:165-176. 4. Simonet WS, et al. Cell. 1997;89:309-319.,覆盖作用Frosts Contribution,破骨细胞重吸收,新骨形成,Hattner R, et al. Nature. 1965:206:489-490.,异常骨重塑导致骨质疏松Abnormal Bone Remodeling Leads to Osteoporosis,Osteoporosis,
5、破骨组织再吸收,成骨细胞的新骨形成,胜于,骨,RANK,RANKL配体,骨再吸收,破骨细胞,骨肿瘤细胞,生长因子 (TGF-, IGFs, FGFs, PDGFs, BMPs),细胞因子和生长因子(IL-6, IL-8, IL-1, PGE-2, TNF-, CSF-1, PTHrP),Adapted from Roodman GD. N Engl J Med. 2004;350:1655-1664.,RANKL,RANKL,对肿瘤的直接效应?,成骨细胞,RANK 配体是骨组织破坏“恶性循环”的关键介导子Ligand Is a Key Mediator in the “Vicious Cycl
6、e” of Bone Destruction,骨转移的类型Types of Bone Metastasis,骨转移的类型Types of Bone Metastasis,溶骨性转移,成骨性转移,Lipton A. J Support Oncol. 2004;2:205-220.,肿瘤导致的溶骨性破坏,骨转移的后果Morbidity From Bone Metastases,临床评估确定骨健康Clinical Evaluation to Assess Bone Health Health,体格检查应该全面，不能只局限于骨骼系统实验室检查应全面而系统,Saylor PJ, et al. Prost
7、ate Cancer Prostatic Dis. 2010;13:20-27.Gralow JR, et al. J Natl Compr Canc Netw. 2009;7(suppl 3):S1-S32.,骨相关事件风险Risk of Skeletal-Related Events,骨相关事件发生率年骨折发生率为 20% 到30%未经双磷类药物治疗者平均每3-6月发生一次明显的骨并发症,骨并发症,脊髓压迫,骨外科,高血钙HCM,骨折,骨放疗,0,10,20,30,40,50,患者 (%),其他前列腺癌骨髓瘤乳腺癌,Reproduced and adapted with permissio
8、n from the American Association for Cancer Research. Coleman RE. Clin Cancer Res. 2006;12:6243s-6249s.,骨转移主要治疗选择Primary Treatment Options for Bone Metastases,双膦酸盐的作用机制,抑制破骨细胞形成分化成熟和活性，促进其凋亡,骨吸收过程中局部释放,成骨细胞和破骨细胞活动时浓度增加,调制成骨细胞和破骨细胞之间信号传递,骨修正剂Bone-Modifying Agents,双磷酸盐NF-kB(RANK) 活化因子配体抑制因子 Denosomab,I
9、II 期研究:芳香酶抑制剂治疗早期乳腺癌期间加用戴诺单抗的疗效,在美国和加拿大进行多中心、随机 、双盲、安慰剂对照研究,接受芳香酶抑制剂治疗的ER+的乳腺癌患者(N = 252),Ellis GK, et al. J Clin Oncol. 2008;26:4875-4882.,Denosumab 60 mg SC q6m x 4 (n = 127),Placebo SC q6m x 4 (n = 125),Ellis GK, et al. J Clin Oncol. 2008:26:4875-4882. Reprinted with permission. 2008 American Soc
10、iety of Clinical Oncology. All rights reserved.,*P .0001 vs placebo.,Change ( 95% CI) From Baseline in L-Spine BMD (%),8,6,4,2,0,-2,7,5,3,1,-1,-3,*,*,*,*,*,1,3,6,12,24,5.5% differenceat Mo 12,Denosumab (n = 123),Placebo (n = 122),7.6% differenceat Mo 24,Mos,Effect of Denosumab on Lumbar Spine Bone M
11、ineral Density,Denosumab package insert.,治疗效果： Denosumab Treatment Effect: Denosumab,2011指南更新内容 2011 Updates to Clinical Practice Guidelines,1. Van Poznak C, et al. J Clin Oncol. 29:1221-1227. 2. NCCN. Clinical practice guidelines in oncology: breast cancer. v.2.2011. 3. NCCN. Clinical practice guid
12、elines in oncology: prostate cancer. v.1.2011.,小结(Summary),尸解分析提示：肿瘤致死的患者70%具有骨转移 最常见于乳腺癌、前列腺癌、肾癌和肺癌治疗骨转移是近16年发展起来的，主要是为了降低 SREs,护理思考Putting It All Together:Overall Nursing Considerations,肿瘤护理是患者治疗有效的关键Oncology Nurses Are Central to Effective Patient Management,患者教育：骨健康Patient Education: Bone Health
13、,肿瘤转移所致的骨痛Causes of Bone Pain in Metastatic Cancer,疼痛病因骨肿瘤、骨折 炎症介质骨内压增加疼痛类型间断的，慢性的，爆发性，偶然性,评估定位（Location）定性（性质Quality ）相关的症状Associated symptoms时间Time强度Intensity/持续时间duration,Faiman B. Cleve Clin J Med. 2010;77:273-278.Siemionow K, et al. Cleve Clin J Med. 2008;75:557-566.,0,10,Least to Worst,0,轻 to
14、重,10,WHO的三阶梯药物治疗World Health Organization Medical Management,1 级轻度疼痛 (1-4),2级中度疼痛(5-7),3级 重度疼痛 (8-10),吗啡二氢吗啡酮美沙酮芬太尼羟考酮辅助剂,阿司匹林/可待因阿司匹林/羟考酮曲马多辅助剂,阿司匹林扑热息痛NSAIDs 辅助剂,Christo PJ, et al. Ann NY Acad Sci. 2008;1138:278-298.Adapted from WHOs pain ladder. Available at: http:/www.who.int/cancer/palliative/p
15、ainladder/en/.,骨健康：精心计划Bone Health: Care Plan,确定部位和骨折病因 X-ray, CT scan, or MRI骨扫描Bone scan, 骨测定bone survey (MM)疼痛控制 药物治疗:阿片制剂(opiates)有否放化疗指征?病变位点, 疾病进展范围、疼痛范围和程度双磷酸盐或 denosumab治疗的时间,死亡率增加,脊柱压缩性骨折级联Vertebral Compression Fracture Cascade,肿瘤患者钙补充Calcium Supplementation in Cancer,双磷酸盐和RANKL抑制剂可致低血钙骨重建必
16、须物质美国骨质疏松协会推荐50岁: 每天总量1200mg钙和800-1000IU维生素D摄入检查血钙和维生素D水平骨密度基线评估和风险度监测蛋白、咖啡，质子泵抑制剂饮食含钙,柠檬酸钙,双膦酸盐和Denosumab,对骨转移患者有效专科护理（Specific nursing）要关注双磷酸盐和denosumab的应用指征和使用观察,双磷酸盐和Denosumab的副反应Bisphosphonates and Novel Agents: Adverse Effects,双磷酸盐相关的肾脏毒性Bisphosphonate-Associated Renal Toxicity,包括水肿、尿频、血尿、肾功能衰
17、竭Cr升高范围从无症状到透析依赖唑来磷酸的剂量要根据Cr清除率确定,Zoledronic acid package insert. 2011. Kyle et al, J Clin Oncol. 2007;25:2464-2472. Tanvetyanon T, et al. Ann Oncol. 2006;17:897-907.,双磷酸相关肾脏毒性Bisphosphonate-Associated Renal Toxicity,停药指征：Cr清除率 30 mL/min Cr值从正常上升 0.5mg/dL Cr从异常基线上升 1.0mg/dL 等到Cr降到基线值10%以内才能再次用药,Kyle
18、 RA, et al. J Clin Oncol. 2007;25:2464-2472.,双磷酸盐和戴诺单抗：骨坏死Bisphosphonates and Denosumab: Osteonecrosis,2004 国际网络调查显示 唑来磷酸的发生率是10%,帕米磷酸二钠的发生率是4% 颌骨坏死可能与应用双磷酸盐的持续时间相关当牙齿或颌骨出现疼痛或骨外露，要高度怀疑颌骨坏死,Aapro M, et al. Oncologist. 2010;15:1147-1158. Durie BG, et al. N Engl J Med. 2005;353:99-102. Zervas K, et al.
19、 Br J Haematol. 2006;134:620-623.,防止牙坏死的指南Guidelines for the Prevention of ONJ,在接受任何双磷酸盐治疗前患者应该进行全面的牙齿评估和适当牙齿预防,Aapro M, et al. Oncologist. 2010;15:1147-1158. Kyle RA, et al. J Clin Oncol. 2007;25:2464-2472. Khan AA, et al. J Rheumatol. 2008;35:1391-1397.,护士能提供优化的结果,SREs能发生在任何时候，因此，护士必须保持警觉！,Thanks for your attention!,So，we must try our best,
