Research advances in the pathogenesis and clinical drug treatment of osteoporosis

Chen Changjun, Wang Qiuru, Zhao Xin, Ma Qingwei, Zhang Lei, Pan Xin, Kang Pengde

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Journal of Chongqing Medical University ›› 2024, Vol. 49 ›› Issue (10) : 1031-1038. DOI: 10.13406/j.cnki.cyxb.003571
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Research advances in the pathogenesis and clinical drug treatment of osteoporosis

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Abstract

Osteoporosis is a systemic metabolic bone disease,which can cause decreased bone density,bone microstructure destruction,and decreased bone strength,thus increasing the risk of fracture. With the aging of China’s population,an increasing number of patients are suffering from osteoporosis. This condition and its related complications continue to affect patients’ daily activities and reduce their quality of life. In recent years,global researchers have conducted increasingly in-depth research on this disease,leading to progress in its pathogenesis and clinical diagnosis and treatment. Literature search revealed that chronic liver and kidney dysfunction,alcohol consumption,and endocrine dysfunction can affect the development of osteoporosis by influencing bone metabolism. The Wnt signaling pathway,bone growth factor related signaling pathway,and RANKL/RANK/OPG signaling pathway are the key signaling pathways affecting the development of osteoporosis. Moreover,bisphosphonates and denosumab are commonly used drugs in the clinical treatment of osteoporosis. For individuals at high risk of osteoporotic fractures,bone-forming agents such as teriparatide and romosozumab can be considered. A rational sequence of drug therapy can help enhance the effectiveness of osteoporosis treatment. In this article,we will review the above advances to raise the awareness of clinicians and society about this disease,and help clinicians make better treatment decisions.

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osteoporosis / pathogenesis / clinical drug treatment / research advances / review

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Chen Changjun , Wang Qiuru , Zhao Xin , et al . Research advances in the pathogenesis and clinical drug treatment of osteoporosis. Journal of Chongqing Medical University. 2024, 49(10): 1031-1038 https://doi.org/10.13406/j.cnki.cyxb.003571

References

1
Chen CJ Alqwbani M Zhao J,et al. Effects of teriparatide versus salmon calcitonin therapy for the treatment of osteoporosis in Asia:a meta-analysis of randomized controlled trials[J]. Endocr Metab Immune Disord Drug Targets202121(5):932-942.
2
Tatangelo G Watts J Lim K,et al. The cost of osteoporosis,osteopenia,and associated fractures in Australia in 2017[J]. J Bone Miner Res201934(4):616-625.
3
Gao YG Chen N Fu ZD,et al. Progress of Wnt signaling pathway in osteoporosis[J]. Biomolecules202313(3):483.
4
Alejandro P Constantinescu F. A review of osteoporosis in the older adult:an update[J]. Rheum Dis Clin North Am201844(3):437-451.
5
Vilaca T Eastell R Schini M. Osteoporosis in men[J]. Lancet Diabetes Endocrinol202210(4):273-283.
6
Mendoza FA Le Roux M Ahmed I. Primary osteoporosis in men:an unmet medical need[J]. Fertil Steril2019112(5):791-798.
7
Wang TT He HC Liu SX,et al. Autophagy:a promising target for age-related osteoporosis[J]. Curr Drug Targets201920(3):354-365.
8
Jaghsi S Hammoud T Haddad S. Relation between circulating vitamin K1 and osteoporosis in the lumbar spine in Syrian post-menopausal women[J]. Open Rheumatol J201812:1-9.
9
陈长军. 特立帕肽与鲑鱼降钙素治疗亚洲人群骨质疏松症的疗效对比-meta分析[D]. 济南:山东大学,2019.
Chen CJ. Comparison and-meta-analysis of the efficacy of teripartite and salmon calcitonin in the treatment of osteoporosis in Asian population[D]. Jinan:Shandong University,2019.
10
陈长军,赵 鑫,陈李毅乐,等. 外泌体在骨代谢及骨、关节疾病诊治中的研究进展[J]. 重庆医科大学学报202146(5):610-617.
Chen CJ Zhao X Chen LYL,et al. Progress of exosomes in bone metabolism,and diagnosis and treatment of bone and joint diseases[J]. J Chongqing Med Univ202146(5):610-617.
11
Huo SC Tang XZ Chen WJ,et al. Epigenetic regulations of cellular senescence in osteoporosis[J]. Ageing Res Rev202499:102235.
12
Wu D Cline-Smith A Shashkova E,et al. T-cell mediated inflammation in postmenopausal osteoporosis[J]. Front Immunol202112:687551.
13
Chen CJ Zhao X Luo Y,et al. Imbalanced T-cell subsets may facilitate the occurrence of osteonecrosis of the femoral head[J]. J Inflamm Res202215:4159-4169.
14
Uda Y Azab E Sun NY,et al. Osteocyte mechanobiology[J]. Curr Osteoporos Rep201715(4):318-325.
15
Cheng CH Chen LR Chen KH. Osteoporosis due to hormone imbalance:an overview of the effects of estrogen deficiency and glucocorticoid overuse on bone turnover[J]. Int J Mol Sci202223(3):1376.
16
Zhang L Zheng YL Wang R,et al. Exercise for osteoporosis:a literature review of pathology and mechanism[J]. Front Immunol202213:1005665.
17
Guañabens N Parés A. Osteoporosis in chronic liver disease[J]. Liver Int201838(5):776-785.
18
Bezerra de Carvalho KS Vasco RFV Custodio MR,et al. Chronic kidney disease is associated with low BMD at the hip but not at the spine[J]. Osteoporos Int201930(5):1015-1023.
19
González-Reimers E Martín-González C de la Vega-Prieto MJ,et al. Serum sclerostin in alcoholics:a pilot study[J]. Alcohol Alcohol201348(3):278-282.
20
Godos J Giampieri F Chisari E,et al. Alcohol consumption,bone mineral density,and risk of osteoporotic fractures:a dose-response meta-analysis[J]. Int J Environ Res Public Health202219(3):1515.
21
Neglia C Argentiero A Chitano G,et al. Diabetes and obesity as independent risk factors for osteoporosis:updated results from the ROIS/EMEROS registry in a population of five thousand post-menopausal women living in a region characterized by heavy environmental pressure[J]. Int J Environ Res Public Health201613(11):1067.
22
Williams GR Bassett JHD. Thyroid diseases and bone health[J]. J Endocrinol Invest201841(1):99-109.
23
Wu B Fu ZY Wang XY,et al. A narrative review of diabetic bone disease:Characteristics,pathogenesis,and treatment[J]. Front Endocrinol202213:1052592.
24
Martiniakova M Biro R Penzes N,et al. Links among obesity,type 2 diabetes mellitus,and osteoporosis:bone as a target[J]. Int J Mol Sci202425(9):4827.
25
Lian XL Zhang YP Li X,et al. Exploration on the relationship between the elderly osteoporosis and cardiovascular disease risk factors[J]. Eur Rev Med Pharmacol Sci201721(19):4386-4390.
26
Hoes JN Bultink IE Lems WF. Management of osteoporosis in rheumatoid arthritis patients[J]. Expert Opin Pharmacother201516(4):559-571.
27
Hill QA Grainger JD Thachil J,et al. The prevention of glucocorticoid-induced osteoporosis in patients with immune thrombocytopenia receiving steroids:a British Society for Hematology Good Practice Paper[J]. Br J Haematol2019185(3):410-417.
28
Adami G Saag KG. Glucocorticoid-induced osteoporosis:2019 concise clinical review[J]. Osteoporos Int201930(6):1145-1156.
29
Edens C Robinson AB. Systemic lupus erythematosus,bone health,and osteoporosis[J]. Curr Opin Endocrinol Diabetes Obes201522(6):422-431.
30
Al-Kushi AG Azzeh FS Header EA,et al. Effect of vitamin D and calcium supplementation in patients with systemic lupus erythematosus[J]. Saudi J Med Med Sci20186(3):137-142.
31
Myneni VD Mezey E. Immunomodulatory effect of vitamin K2:Implications for bone health[J]. Oral Dis201824(1/2):67-71.
32
Villa JKD MAN Diaz Pizziolo VR,et al. Effect of vitamin K in bone metabolism and vascular calcification:a review of mechanisms of action and evidences[J]. Crit Rev Food Sci Nutr201757(18):3959-3970.
33
Hardcastle SA Yahya F Bhalla AK. Pregnancy-associated osteoporosis:a UK case series and literature review[J]. Osteoporos Int201930(5):939-948.
34
Houschyar KS Tapking C Borrelli MR,et al. Wnt pathway in bone repair and regeneration - what do we know so far[J]. Front Cell Dev Biol20186:170.
35
Bengoa-Vergniory N Kypta RM. Canonical and noncanonical Wnt signaling in neural stem/progenitor cells[J]. Cell Mol Life Sci201572(21):4157-4172.
36
Yu J Chia J Canning CA,et al. WLS retrograde transport to the endoplasmic reticulum during Wnt secretion[J]. Dev Cell201429(3):277-291.
37
Meffre D Grenier J Bernard S,et al. Wnt and lithium:a common destiny in the therapy of nervous system pathologies?[J]. Cell Mol Life Sci201471(7):1123-1148.
38
Chen CJ Fu L Luo Y,et al. Engineered exosome-functionalized extracellular matrix-mimicking hydrogel for promoting bone repair in glucocorticoid-induced osteonecrosis of the femoral head[J]. ACS Appl Mater Interfaces202315(24):28891-28906.
39
Jiang HW Zhang ZK Yu YY,et al. Drug discovery of DKK1 inhibitors[J]. Front Pharmacol202213:847387.
40
Chen GQ Deng CX Li YP. TGF-β and BMP signaling in osteoblast differentiation and bone formation[J]. Int J Biol Sci20128(2):272-288.
41
Kang MG Lee S Seo JP,et al. Cell-permeable bone morphogenetic protein 2 facilitates bone regeneration by promoting osteogenesis[J]. Mater Today Bio202425:100983.
42
Fromigué O Modrowski D Marie PJ. Growth factors and bone formation in osteoporosis:roles for fibroblast growth factor and transforming growth factor beta[J]. Curr Pharm Des200410(21):2593-2603.
43
Fei YR Gronowicz G Hurley MM. Fibroblast growth factor-2,bone homeostasis and fracture repair[J]. Curr Pharm Des201319(19):3354-3363.
44
Celik E Guzel S Abali R,et al. The relationship between fibroblast growth factor 23 and osteoporosis in postmenopausal women[J]. Minerva Med2013104(5):497-504.
45
Abdulrahman SJ Abdulhadi MA Turki Jalil A,et al. Conjugated linoleic acid and glucosamine supplements may prevent bone loss in aging by regulating the RANKL/RANK/OPG pathway[J]. Mol Biol Rep202350(12):10579-10588.
46
Yasuda H. Discovery of the RANKL/RANK/OPG system[J]. J Bone Miner Metab202139(1):2-11.
47
Xian YS Gao YJ Su YJ,et al. Cichoric acid targets RANKL to inhibit osteoclastogenesis and prevent ovariectomy-induced bone loss[J]. Phytother Res202438(4):1971-1989.
48
Ni XM Wu B Li S,et al. Equol exerts a protective effect on postmenopausal osteoporosis by upregulating OPG/RANKL pathway[J]. Phytomedicine2023108:154509.
49
中华医学会骨质疏松和骨矿盐疾病分会. 原发性骨质疏松症诊疗指南(2022) [J].中国全科医学202326(14):1671-1691.
Chinese Society of Osteoporosis and Bone Mineral Research. Guidelines for the Diagnosis and Treatment of Primary Osteoporosis(2022) [J]. Chinese General Practice,202326(14):1671-1691.
50
中华医学会骨科学分会. 骨质疏松性骨折诊疗指南(2022年版)[J]. 中华骨科杂志202242(22):1473-1491.
Chinese Orthopaedic Association. Guidelines for the diagnosis and treatment of osteoporotic fractures(2022 edition)[J]. Chinese Journal of Orthopaedics202242(22):1473-1491.
51
Ebeling PR Nguyen HH Aleksova J,et al. Secondary osteoporosis[J]. Endocr Rev202243(2):240-313.
52
Drake MT Clarke BL Khosla S. Bisphosphonates:mechanism of action and role in clinical practice[J]. Mayo Clin Proc200883(9):1032-1045.
53
Tzschentke TM. Pharmacology of bisphosphonates in pain[J]. Br J Pharmacol2021178(9):1973-1994.
54
Himelstein AL Foster JC Khatcheressian JL,et al. Effect of longer-interval vs standard dosing of zoledronic acid on skeletal events in patients with bone metastases:a randomized clinical trial[J]. JAMA2017317(1):48-58.
55
Ayers C Kansagara D Lazur B,et al. Effectiveness and safety of treatments to prevent fractures in people with low bone mass or primary osteoporosis:a living systematic review and network meta-analysis for the American college of physicians[J]. Ann Intern Med2023176(2):182-195.
56
Chandran T Venkatachalam I. Efficacy and safety of denosumab compared to bisphosphonates in improving bone strength in postmenopausal osteoporosis:a systematic review[J]. Singapore Med J201960(7):364-378.
57
Saag KG Pannacciulli N Geusens P,et al. Denosumab versus risedronate in glucocorticoid-induced osteoporosis:final results of a twenty-four-month randomized,double-blind,double-dummy trial[J]. Arthritis Rheumatol201971(7):1174-1184.
58
Qaseem A Hicks LA Etxeandia-Ikobaltzeta I,et al. Pharmacologic treatment of primary osteoporosis or low bone mass to prevent fractures in adults:a living clinical guideline from the American college of physicians[J]. Ann Intern Med2023176(2):224-238.
59
Salamanna F Borsari V Contartese D,et al. Link between estrogen deficiency osteoporosis and susceptibility to bone metastases:a way towards precision medicine in cancer patients[J]. Breast201841:42-50.
60
MacKnight JM. Osteopenia and osteoporosis in female athletes[J]. Clin Sports Med201736(4):687-702.
61
Patel HK Bihani T. Selective estrogen receptor modulators (SERMs) and selective estrogen receptor degraders(SERDs) in cancer treatment[J]. Pharmacol Ther2018186:1-24.
62
Mirkin S Pickar JH. Selective estrogen receptor modulators (SERMs):a review of clinical data[J]. Maturitas201580(1):52-57.
63
Park SB Kim CH Hong M,et al. Effect of a selective estrogen receptor modulator on bone formation in osteoporotic spine fusion using an ovariectomized rat model[J]. Spine J201616(1):72-81.
64
Kishida K Furukawa M Nakashima M,et al. Selective estrogen receptor modulators and deep venous thrombosis after an emergent operation in senior women[J]. JA Clin Rep20239(1):73.
65
Naot D Musson DS Cornish J. The activity of peptides of the calcitonin family in bone[J]. Physiol Rev201999(1):781-805.
66
Henriksen K Byrjalsen I Andersen JR,et al. A randomized,double-blind,multicenter,placebo-controlled study to evaluate the efficacy and safety of oral salmon calcitonin in the treatment of osteoporosis in postmenopausal women taking calcium and vitamin D[J]. Bone201691:122-129.
67
Terashima Y Takebayashi T Jimbo S,et al. Analgesic effects of calcitonin on radicular pain in male rats[J]. J Pain Res201912:223-230.
68
Gou Y Tian FM Kong QF,et al. Salmon calcitonin attenuates degenerative changes in cartilage and subchondral bone in lumbar facet joint in an experimental rat model[J]. Med Sci Monit201824:2849-2857.
69
Kilinc E Dagistan Y Kukner A,et al. Salmon calcitonin ameliorates migraine pain through modulation of CGRP release and dural mast cell degranulation in rats[J]. Clin Exp Pharmacol Physiol201845(6):536-546.
70
Karponis A Rizou S Pallis D,et al. Analgesic effect of nasal salmon calcitonin during the early post-fracture period of the distal radius fracture[J]. J Musculoskelet Neuronal Interact201515(2):186-189.
71
Shi ZJ Zhou HX Pan B,et al. Effectiveness of teriparatide on fracture healing:a systematic review and meta-analysis[J]. PLoS One201611(12):e0168691.
72
Ikeda T Kaji H Tamura Y,et al. Once-weekly teriparatide reduces serum sclerostin levels in postmenopausal women with osteoprosis[J]. J Orthop Sci201924(3):532-538.
73
Tang YT Xia H Kang L,et al. Effects of intermittent parathyroid hormone 1-34 administration on circulating mesenchymal stem cells in postmenopausal osteoporotic women[J]. Med Sci Monit201925:259-268.
74
Raef H Al-Bugami M Balharith S,et al. Updated recommendations for the diagnosis and management of osteoporosis:a local perspective[J]. Ann Saudi Med201131(2):111-128.
75
Singh S Dutta S Khasbage S,et al. A systematic review and meta-analysis of efficacy and safety of Romosozumab in postmenopausal osteoporosis[J]. Osteoporos Int202233(1):1-12.
76
Kobayakawa T Miyazaki A Saito M,et al. Denosumab versus romosozumab for postmenopausal osteoporosis treatment[J]. Sci Rep202111(1):11801.
77
Park D Kim SE Shin HK,et al. Comparison of the efficacy of romosozumab and teriparatide for the management of osteoporotic vertebral compression fractures[J]. Neurospine202320(4):1217-1223.
78
Miyauchi A Hamaya E Shimauchi J,et al. Effectiveness of romosozumab in patients with osteoporosis at high fracture risk:a Japanese real-world study[J]. J Bone Miner Metab202442(1):77-89.
79
Cao G Hu SQ Ning Y,et al. Traditional Chinese medicine in osteoporosis:from pathogenesis to potential activity[J]. Front Pharmacol202415:1370900.
80
Du JZ Wang YC Wu CL,et al. Targeting bone homeostasis regulation:potential of traditional Chinese medicine flavonoids in the treatment of osteoporosis[J]. Front Pharmacol202415:1361864.
81
史晓林,刘康. 老年性骨质疏松症中西医结合诊疗指南[EB/OL] .(2024-04-09) [2024-04-30].
Shi XL Liu K. Guideline for diagnosis and treatment of senile osteoporosis with the integrated traditional Chinese and western medicine[EB/OL] .(2024-04-09) [2024-04-30].
82
Cheng BR Wu RY Gao QY,et al. Chinese proprietary medicine xianling gubao capsule for osteoporosis:a systematic review and meta-analysis of randomized clinical trials[J]. Front Endocrinol202213:870277.
83
Fu YS Wang WG Zhao MH,et al. Efficacy of the Chinese herbal medicine Jintiange capsules in the postoperative treatment of osteoporotic vertebral compression fractures:a systematic review and meta-analysis[J]. Front Med202310:1289818.
84
Ayers C Kansagara D Lazur B,et al. Effectiveness and safety of treatments to prevent fractures in people with low bone mass or primary osteoporosis:a living systematic review and network meta-analysis for the American college of physicians[J]. Ann Intern Med2023176(2):182-195.
85
Sauhta R Makkar D Siwach PS. The sequential therapy in osteoporosis[J]. Indian J Orthop202357(Suppl 1):S150-S162.
86
Leder BZ Tsai JN Uihlein AV,et al. Denosumab and teriparatide transitions in postmenopausal osteoporosis(the DATA-Switch study):extension of a randomised controlled trial[J]. Lancet2015386(9999):1147-1155.
87
Kamanda-Kosseh M Shiau S Agarwal S,et al. Bisphosphonates maintain BMD after sequential teriparatide and denosumab in premenopausal women with idiopathic osteoporosis[J]. J Clin Endocrinol Metab2024:dgae240.
88
Kobayakawa T Miyazaki A Takahashi J,et al. Verification of efficacy and safety of ibandronate or denosumab for postmenopausal osteoporosis after 12-month treatment with romosozumab as sequential therapy:the prospective VICTOR study[J]. Bone2022162:116480.
89
Cosman F Kendler DL Langdahl BL,et al. Romosozumab and antiresorptive treatment:the importance of treatment sequence[J]. Osteoporos Int202233(6):1243-1256.
90
Miller PD Pannacciulli N Brown JP,et al. Denosumab or zoledronic acid in postmenopausal women with osteoporosis previously treated with oral bisphosphonates[J]. J Clin Endocrinol Metab2016101(8):3163-3170.
91
陈长军,赵 鑫,罗月,等. 外泌体的优化策略及在促进骨修复再生中的应用研究进展[J]. 中华骨科杂志202343(24):1688-1694.
Chen CJ Zhao X Luo Y,et al. Enhancing bone regeneration:advances and innovations in exosome engineering[J]. Chin J Orthop202343(24):1688-1694.

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