绝经后骨质疏松症的预防和药物联合序贯治疗

doi:10.3969/j.issn.2095-4344.2338

中国组织工程研究 ›› 2020, Vol. 24 ›› Issue (33): 5385-5390.doi: 10.3969/j.issn.2095-4344.2338

• 骨与关节综述 bone and joint review • 上一篇下一篇

绝经后骨质疏松症的预防和药物联合序贯治疗

孙国平1，罗选翔2，潘彬2

¹南京市高淳人民医院，江苏省南京市 211300；²徐州医科大学，江苏省徐州市 221000

收稿日期:2020-02-25 修回日期:2020-02-29 接受日期:2020-03-21 出版日期:2020-11-28 发布日期:2020-10-14
通讯作者: 罗选翔，医师，徐州医科大学，江苏省徐州市 221000
作者简介:孙国平，男，1981年生，江苏省南京市人，汉族，2004年江苏大学药学院毕业，副主任药师，主要从事临床药学等方面的研究。
基金资助:
国家自然科学基金资助项目(81801213)

Prevention and sequential therapies combined with drugs for postmenopausal osteoporosis

Sun Guoping1, Luo Xuanxiang2, Pan Bin2

1Nanjing Gaochun People’s Hospital, Nanjing 211300, Jiangsu Province, China; 2Xuzhou Medical University, Xuzhou 221000, Jiangsu Province, China

Received:2020-02-25 Revised:2020-02-29 Accepted:2020-03-21 Online:2020-11-28 Published:2020-10-14
Contact: Luo Xuanxiang, Physician, Xuzhou Medical University, Xuzhou 221000, Jiangsu Province, China
About author:Sun Guoping, Associate chief pharmacist, Nanjing Gaochun People’s Hospital, Nanjing 211300, Jiangsu Province, China
Supported by:
the National Natural Science Foundation of China, No. 81801213

摘要/Abstract

摘要：

文题释义：

绝经后骨质疏松症：绝经后妇女由于雌激素和维生素D缺乏导致骨吸收增加、骨量减少、骨皮质变薄和骨小梁断裂，是一种慢性进行性疾病。

药物联合序贯治疗：是一种治疗方法的选择，旨在增加疗效、减低毒副反应、提高患者的顺应性。

背景：绝经期后的妇女由于雌激素水平下降导致骨吸收迅速增加，造成骨吸收和形成之间的不平衡，增加了骨质疏松和相关部位骨折的风险。然而，目前的临床防治并不足以抑制长期的骨丢失和不断增加的骨折风险。近年来，针对绝经后骨质疏松症及时有效的预防和抗骨质疏松药物序贯联合治疗已成为必然趋势。

目的：就绝经后骨质疏松症的预防和抗骨质疏松药物治疗的相关文献进行总结，介绍绝经后骨质疏松症的临床预防措施和常见的抗骨质疏松药物联合序贯治疗进展。

方法：作者于2020年1月应用计算机检索2009年1月至2019年12月中国期刊全文数据库CNKI、万方和PubMed数据库的相关文章，中文检索词“绝经后骨质疏松症，预防，药物，治疗”；英文检索词“Postmenopausal osteoporosis，prevention，drug therapy，medication”，根据纳入标准及排除标准摘选41篇文章进行分析讨论。

结果与结论：①绝经后妇女要及时进行骨密度测试，通过改变饮食结构和生活方式进行预防，以降低骨折风险；②与单一药物相比，联合序贯疗法可以更有效地治疗绝经后骨质疏松症，对绝经后骨质疏松症的治疗具有深远的意义。

ORCID: 0000-0002-1731-9443(孙国平)

中国组织工程研究杂志出版内容重点：人工关节；骨植入物；脊柱；骨折；内固定；数字化骨科；组织工程

关键词: 骨, 绝经后, 骨质疏松症, 骨折, 预防, 药物

Abstract:

BACKGROUND: In postmenopausal women, a rapid increase in bone resorption due to decreased estrogen levels leads to an imbalance between bone resorption and bone formation, increasing the risk of osteoporosis and associated fractures. However, current clinical interventions are not sufficient to inhibit long-term bone loss

and increased risk of fracture. In recent years, it has become an inevitable trend to treat postmenopausal osteoporosis with timely and effective prevention and sequential combination of anti-osteoporosis drugs.

OBJECTIVE: To summarize the literature on the prevention of postmenopausal osteoporosis and the anti-osteoporosis drug therapy, and introduce the progress of the clinical preventive measures and the common anti-osteoporosis drug combination sequential treatment of postmenopausal osteoporosis.

METHODS: The author retrieved the relevant articles in CNKI, Wanfang and PubMed databases from January 2009 to December 2019 in January 2020. The search words were “postmenopausal osteoporosis, prevention, drug therapy, medication” in Chinese and English respectively. Finally, 41 articles were selected according to inclusion and exclusion criteria for analysis and discussion.

RESULTS AND CONCLUSION: (1) Postmenopausal women should receive the test of bone mineral density and osteoporosis was prevented by changes in diet and lifestyle to reduce the risk of fractures. (2) Compared with single drugs, combination with sequential therapies can be more effective in the treatment of postmenopausal osteoporosis, which has far-reaching significance for the treatment of postmenopausal osteoporosis.

Key words: bone, postmenopausal, osteoporosis, fracture, prevention, drugs

中图分类号:

孙国平, 罗选翔, 潘彬. 绝经后骨质疏松症的预防和药物联合序贯治疗[J]. 中国组织工程研究, 2020, 24(33): 5385-5390.

Sun Guoping, Luo Xuanxiang, Pan Bin. Prevention and sequential therapies combined with drugs for postmenopausal osteoporosis[J]. Chinese Journal of Tissue Engineering Research, 2020, 24(33): 5385-5390.

图/表（结果） 2

参考文献

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[23] BEAUDOIN C, JEAN S, BESSETTE L, et al. Denosumab compared to other treatments to prevent or treat osteoporosis in individuals at risk of fracture: a systematic review and meta-analysis. Osteoporos Int. 2016; 27(9): 2835-2844.

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[25] LI X, OMINSKY MS, WARMINGTON KS, et al. Sclerostin antibody treatment increases bone formation, bone mass, and bone strength in a rat model of postmenopausal osteoporosis. J Bone Miner Res. 2009;24(4):578-588.

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[27] BLACK DM, REID IR, CAULEY JA, et al. The effect of 6 versus 9 years of zoledronic acid treatment in osteoporosis: a randomized second extension to the HORIZON-Pivotal Fracture Trial (PFT). J Bone Miner Res. 2015;30(5):934-944.

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[35] MUSCHITZ C, KOCIJAN R, FAHRLEITNE-PAMMER A, et al. Overlapping and continued alendronate or raloxifene administration in patients on teriparatide: effects on areal and volumetric bone mineral density the CONFORS study. J Bone Miner Res. 2014;29(8):1777-1785.

[36] MCCLUNG MR, BROWN JP, DIEZ-PEREZ A, et al. Effects of 24 months of treatment with romosozumab followed by 12 months of denosumab or placebo in postmenopausal women with low bone mineral density: a randomized, double-blind, phase 2, parallel group study. J Bone Miner Res. 2018;33(8): 1397-1406.

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引言

骨是一种新陈代谢活跃的组织，骨形成和骨吸收的过程是连续的。在正常情况下，成骨细胞和破骨细胞的偶联作用确保骨组织不断更新，维持正常的骨骼结构^[1]。此外，由骨细胞介导的骨重建能够使骨结构和骨强度适应身体负荷情况^[2]。如果在生长过程中未能获得最佳的骨量和强度，或者骨吸收和骨形成之间失衡，都可能导致骨质疏松症的发生^[3]。骨质疏松症是一种以低骨密度和骨微结构恶化为特征的退行性骨病，随着世界范围内预期寿命的延长，骨质疏松症的患病率正在急剧上升，已经成为世界范围内一个日益严重的健康和经济问题^[4]，会导致骨量和骨强度的降低，增加骨折风险，其最常见的累及部位是椎体、髋部和前臂。全世界有2亿妇女患有骨质疏松症，50岁以上的妇女中就有1/3患有骨质疏松性骨折，这是由于女性进入绝经期后，雌激素水平下降导致骨吸收迅速增加，骨吸收和形成之间的不平衡导致骨丢失，增加了骨质疏松和相关部位骨折的风险^[5]。骨质疏松性骨折给患者、家人和社会带来了相当大的负担，髋部骨折的患者失去日常活动能力，需要长期护理、死亡率高^[6]；脊柱骨折会导致疼痛、身高下降、胸椎后凸畸形和行动不便；骨折会增加患者对他人的依赖，并可能导致抑郁、焦虑和自尊的改变^[7]。

从临床角度来看，骨质疏松症是一种无声的疾病，通常在患者发生第一次骨折后才会被诊断出来^[8]。因此，在这种情况下，治疗的首要目的是防止其他部位再次骨折。对于医务工作者来说，还需要对低骨密度的绝经期妇女进行早期诊断，并随后进行预防或治疗，以降低骨折风险。在当今世界，通过改变生活方式和及时行骨质疏松药物治疗来预防骨折是具有成本效益的，可以提高绝经后妇女的生活质量，并减轻与骨质疏松症相关的医疗费用负担^[9]。在此次综述中，总结了预防绝经后骨质疏松症的方案，并讨论了抗骨质疏松药物联合序贯治疗的进展。

中国组织工程研究杂志出版内容重点：人工关节；骨植入物；脊柱；骨折；内固定；数字化骨科；组织工程

材料方法

讨论

当人体骨骼出现损伤时，会吸引破骨细胞启动骨吸收过程，这一过程需要3-5周，成骨细胞随后在骨形成中的作用可能需要3-5个月^[39]。骨重建过程的持续时间在骨小梁和骨皮质之间是不同的，且重建的启动、维持和完成的信号传递过程仍在深入研究中，尚未被完全阐明^[40]。绝经后妇女由于雌激素缺乏，骨吸收增加，患骨质疏松症的风险明显提高，需要及时行骨质疏松筛查，并通过摄入足够的钙和维生素D，避免吸烟和过量饮酒，同时合理进行物理锻炼，以有效预防骨质疏松症的发生。

绝经后骨折疏松症药物联合序贯治疗的结果在一定程度上反映了治疗骨质疏松症的挑战。特定抗吸收药物的特立帕肽联合地诺单抗以及双膦酸盐类药物分别进行治疗后，绝经后骨质疏松症取得了理想的效果，而与雷洛昔芬行联合序贯治疗后，效果并不理想；此外，地诺单抗作为人源性抗核因子受体激活剂的单克隆抗体，与Romosozumab进行序贯治疗后有效改善了绝经后骨质疏松症患者的骨密度，而与唑来膦酸的序贯治疗在提升患者骨密度方面效果并不显著。并且联合序贯疗法的试验研究时间较短，治疗后骨密度的变化需要几个月到几年的时间才能达到最大效果^[41]，因此现有的临床试验还不能看到治疗的全部效果。目前，随着对骨代谢过程认知的不断发展以及抗骨质疏松症药物的研究和开发，新型抗骨质疏松症药物相继进入临床一线，需要针对不同患者疾病发展的进展程度和个体差异，合理进行抗骨质疏松药物的联合用药和序贯治疗，有效治疗绝经后骨质疏松症的同时，减少因长期服用单一药物而产生的不良反应。

中国组织工程研究杂志出版内容重点：人工关节；骨植入物；脊柱；骨折；内固定；数字化骨科；组织工程

绝经后骨质疏松症的预防和药物联合序贯治疗

Prevention and sequential therapies combined with drugs for postmenopausal osteoporosis

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