Abstract
Background: Bone health relies on the equilibrium between resorption and new bone generation. Postmenopausal osteoporosis depends on estrogen deficiency which favorite bone resorption and elevated risk of fractures. Moreover, osteoporosis is characterized by a high release of proinflammatory cytokines suggesting the role of the immune system in the pathogenesis of this complex disease (immunoporosis).
Aims: To review the pathophysiology of osteoporosis from an endocrinological and immunological viewpoint and treatments with a specific focus on nutraceuticals.
Methods: PubMed/MEDLINE, Scopus, Google Scholar, and institutional web site were searched. Original articles and reviews were screened and selected by September 2022.
Results: The activation of the Gut Microbiota-Bone Axis contributes to bone health by releasing several metabolites, including short-chain fatty acids (SCFAs), that facilitate bone mineralization directly and indirectly by the induction of T regulatory cells, triggering anti-inflammatory pathways.
Conclusion: Treatments of postmenopausal osteoporosis are based on lifestyle changes, calcium and vitamin D supplementation, and anti-resorptive and anabolic agents, such as bisphosphonates, Denosumab, Teriparatide, Romosozumab. However, phytoestrogens, polyphenols, probiotics, and polyunsaturated fatty acids may improve bone health by several mechanisms, including anti-inflammatory properties. Specific clinical trials are needed to assess the efficacy/effectiveness of the possible anti-osteoporotic activity of natural products as add on to background treatment.
Keywords: Estrogen, immunity, natural products, osteoblasts, osteoclasts, osteoporosis.
[http://dx.doi.org/10.1080/03008207.2017.1290085] [PMID: 28324674]
[http://dx.doi.org/10.1177/0004563218759371] [PMID: 29368538]
[http://dx.doi.org/10.3389/fimmu.2019.01408] [PMID: 31275328]
[http://dx.doi.org/10.1007/s00774-020-01175-1] [PMID: 33389131]
[http://dx.doi.org/10.1007/s11914-021-00708-5] [PMID: 34757588]
[http://dx.doi.org/10.1111/j.0105-2896.2005.00334.x] [PMID: 16313351]
[http://dx.doi.org/10.1038/nrrheum.2017.213] [PMID: 29323344]
[http://dx.doi.org/10.1007/s00774-020-01162-6] [PMID: 33079279]
[http://dx.doi.org/10.1016/S0140-6736(10)62349-5] [PMID: 21450337]
[http://dx.doi.org/10.1177/1759720X16670154] [PMID: 28255336]
[http://dx.doi.org/10.3389/fimmu.2021.687037] [PMID: 34421899]
[PMID: 20890027]
[http://dx.doi.org/10.1007/s00018-013-1317-1] [PMID: 23516016]
[http://dx.doi.org/10.1002/jbmr.5650110802] [PMID: 8854239]
[http://dx.doi.org/10.1002/jbmr.5650090614] [PMID: 8079663]
[http://dx.doi.org/10.1016/j.semcdb.2021.05.014] [PMID: 34024716]
[http://dx.doi.org/10.1002/jbmr.5650110307] [PMID: 8852944]
[http://dx.doi.org/10.1073/pnas.86.7.2398] [PMID: 2522659]
[http://dx.doi.org/10.1359/jbmr.1998.13.10.1577] [PMID: 9783546]
[http://dx.doi.org/10.1371/journal.pone.0235174] [PMID: 32574226]
[http://dx.doi.org/10.1007/s00198-009-1018-7] [PMID: 19876583]
[http://dx.doi.org/10.1016/S0531-5565(01)00125-5] [PMID: 11672994]
[http://dx.doi.org/10.1002/jcla.23016] [PMID: 31423643]
[http://dx.doi.org/10.1007/BF02405002] [PMID: 6839188]
[http://dx.doi.org/10.2174/1871530319666191202120301] [PMID: 31789135]
[http://dx.doi.org/10.2174/1871530319666190204165207] [PMID: 30727928]
[http://dx.doi.org/10.1186/1742-4933-2-14] [PMID: 16271143]
[http://dx.doi.org/10.1111/j.1365-2613.2009.00661.x] [PMID: 19765105]
[http://dx.doi.org/10.1073/pnas.251534698] [PMID: 11717453]
[http://dx.doi.org/10.1038/nrendo.2016.91] [PMID: 27312863]
[http://dx.doi.org/10.7150/ijbs.53050] [PMID: 33613105]
[http://dx.doi.org/10.1016/j.imbio.2017.05.007] [PMID: 28554684]
[http://dx.doi.org/10.1172/JCI117424] [PMID: 8083350]
[http://dx.doi.org/10.1359/jbmr.2000.15.3.541] [PMID: 10750569]
[http://dx.doi.org/10.1038/35046196] [PMID: 11117729]
[http://dx.doi.org/10.3389/fimmu.2018.00657] [PMID: 29675022]
[http://dx.doi.org/10.1016/j.pharmthera.2017.02.017] [PMID: 28185913]
[http://dx.doi.org/10.1146/annurev-physiol-022516-034339] [PMID: 27813830]
[http://dx.doi.org/10.4049/jimmunol.181.2.1232] [PMID: 18606677]
[http://dx.doi.org/10.1186/s13287-016-0276-5] [PMID: 26801095]
[http://dx.doi.org/10.1038/boneres.2017.19] [PMID: 29263936]
[http://dx.doi.org/10.3389/fendo.2019.00236] [PMID: 31057482]
[http://dx.doi.org/10.1007/s00281-019-00757-0] [PMID: 31552471]
[http://dx.doi.org/10.1159/000110454] [PMID: 17982276]
[http://dx.doi.org/10.1002/jbmr.3364] [PMID: 29281118]
[http://dx.doi.org/10.1074/mcp.M111.011700]
[http://dx.doi.org/10.1074/jbc.M501164200] [PMID: 15965235]
[http://dx.doi.org/10.1359/jbmr.090724]
[http://dx.doi.org/10.1155/2015/196589] [PMID: 26063949]
[http://dx.doi.org/10.1186/ar2141] [PMID: 17381830]
[http://dx.doi.org/10.2741/1560]
[http://dx.doi.org/10.1177/154405910608500302] [PMID: 16498066]
[http://dx.doi.org/10.4049/jimmunol.0903560] [PMID: 20581147]
[http://dx.doi.org/10.1016/j.gendis.2020.03.009] [PMID: 34179305]
[http://dx.doi.org/10.1016/j.bone.2020.115616] [PMID: 32866681]
[http://dx.doi.org/10.4049/jimmunol.177.5.3314] [PMID: 16920972]
[http://dx.doi.org/10.1038/35046102] [PMID: 11117749]
[http://dx.doi.org/10.1038/nm1096-1132] [PMID: 8837613]
[http://dx.doi.org/10.1016/j.smim.2016.02.002] [PMID: 26936034]
[http://dx.doi.org/10.1186/ar2137] [PMID: 17341304]
[http://dx.doi.org/10.1136/ard.2004.034132] [PMID: 15778239]
[http://dx.doi.org/10.1007/BF02390837] [PMID: 11683537]
[http://dx.doi.org/10.1159/000016639] [PMID: 10940670]
[http://dx.doi.org/10.1111/j.1365-2796.1993.tb00723.x] [PMID: 8340736]
[http://dx.doi.org/10.1002/jbmr.3234] [PMID: 28777474]
[http://dx.doi.org/10.1016/j.molimm.2006.09.030] [PMID: 17084457]
[http://dx.doi.org/10.1016/j.autrev.2017.04.001] [PMID: 28411167]
[http://dx.doi.org/10.1016/j.immuni.2011.09.015] [PMID: 22101159]
[http://dx.doi.org/10.1016/j.joca.2015.11.011] [PMID: 26671522]
[http://dx.doi.org/10.7554/eLife.39905]
[http://dx.doi.org/10.1007/s10067-006-0495-8] [PMID: 17205215]
[http://dx.doi.org/10.1002/art.37741] [PMID: 23055095]
[http://dx.doi.org/10.3109/17453676708989624] [PMID: 4166390]
[http://dx.doi.org/10.1097/00005131-199509060-00005] [PMID: 8592261]
[http://dx.doi.org/10.1111/j.1365-2567.2007.02638.x] [PMID: 17521371]
[http://dx.doi.org/10.1002/art.1780371205] [PMID: 7986219]
[http://dx.doi.org/10.1038/nm0297-189] [PMID: 9018238]
[http://dx.doi.org/10.1016/0167-4889(93)90202-Z] [PMID: 7779165]
[http://dx.doi.org/10.1111/imm.12449] [PMID: 25684021]
[http://dx.doi.org/10.2174/1871530319666181211161721] [PMID: 30539706]
[PMID: 28930556]
[http://dx.doi.org/10.1111/j.1365-2567.2006.02321.x] [PMID: 16556256]
[http://dx.doi.org/10.1074/jbc.M112.380493] [PMID: 22942286]
[http://dx.doi.org/10.1089/ten.tea.2009.0495] [PMID: 19769530]
[http://dx.doi.org/10.1111/j.0105-2896.2009.00848.x] [PMID: 20192995]
[http://dx.doi.org/10.4110/in.2020.20.e50] [PMID: 33425435]
[http://dx.doi.org/10.1186/s12979-020-00202-z] [PMID: 33072163]
[http://dx.doi.org/10.1038/nri2062] [PMID: 17380158]
[http://dx.doi.org/10.1016/j.cyto.2014.09.011] [PMID: 25458968]
[http://dx.doi.org/10.1016/j.bcp.2006.04.018] [PMID: 16750176]
[http://dx.doi.org/10.1016/j.bone.2014.06.006] [PMID: 24933342]
[http://dx.doi.org/10.4049/jimmunol.2100215] [PMID: 34544813]
[http://dx.doi.org/10.1136/bmj.k2179] [PMID: 29899036]
[http://dx.doi.org/10.1126/science.aad8588] [PMID: 26912894]
[http://dx.doi.org/10.1073/pnas.1607235113] [PMID: 27821775]
[http://dx.doi.org/10.1002/jbmr.3114] [PMID: 28244143]
[http://dx.doi.org/10.4049/jimmunol.2100528] [PMID: 34544815]
[http://dx.doi.org/10.1093/jn/137.3.838S] [PMID: 17311984]
[http://dx.doi.org/10.1080/07315724.2016.1257961] [PMID: 28318400]
[http://dx.doi.org/10.4049/jimmunol.2100419] [PMID: 34544814]
[http://dx.doi.org/10.1210/jc.2012-4262] [PMID: 23609838]
[http://dx.doi.org/10.1007/s11914-020-00627-x] [PMID: 33030683]
[http://dx.doi.org/10.1016/j.copbio.2012.08.005] [PMID: 22940212]
[http://dx.doi.org/10.4049/jimmunol.2000986] [PMID: 34544802]
[http://dx.doi.org/10.1038/s41575-019-0157-3] [PMID: 31123355]
[http://dx.doi.org/10.1038/nature12721] [PMID: 24226770]
[http://dx.doi.org/10.3109/08820139.2015.1122613] [PMID: 27018846]
[http://dx.doi.org/10.1038/s41467-019-08711-2] [PMID: 30770822]
[http://dx.doi.org/10.3389/fimmu.2018.01525] [PMID: 30034392]
[http://dx.doi.org/10.1016/j.bone.2019.05.016] [PMID: 31100533]
[http://dx.doi.org/10.1038/s41467-017-02490-4] [PMID: 29302038]
[http://dx.doi.org/10.1016/j.archoralbio.2008.02.016] [PMID: 18406397]
[http://dx.doi.org/10.1016/j.immuni.2018.10.013] [PMID: 30446387]
[http://dx.doi.org/10.1016/j.cmet.2020.08.012] [PMID: 32916104]
[http://dx.doi.org/10.1007/s11248-014-9836-6] [PMID: 25231394]
[http://dx.doi.org/10.18632/aging.103283] [PMID: 32482913]
[http://dx.doi.org/10.3389/fphys.2017.00836] [PMID: 29163188]
[PMID: 26769827]
[http://dx.doi.org/10.3390/nu10050546] [PMID: 29702603]
[http://dx.doi.org/10.1007/s40618-016-0434-8] [PMID: 26969462]
[http://dx.doi.org/10.1080/19390211.2018.1472715] [PMID: 29985715]
[http://dx.doi.org/10.1038/bonekey.2014.24] [PMID: 24876930]
[PMID: 32470236]
[http://dx.doi.org/10.4103/0971-3026.107178] [PMID: 23599564]
[http://dx.doi.org/10.1089/jwh.2013.4611] [PMID: 24766381]
[http://dx.doi.org/10.1056/NEJMoa0809493] [PMID: 19671655]
[http://dx.doi.org/10.1210/clinem/dgz322] [PMID: 31899506]
[http://dx.doi.org/10.1007/s00223-018-0389-1] [PMID: 29396698]
[http://dx.doi.org/10.1210/er.2004-0006] [PMID: 15769903]
[http://dx.doi.org/10.1007/s00198-016-3534-6] [PMID: 26902094]
[http://dx.doi.org/10.2147/DDDT.S127568] [PMID: 28458516]
[http://dx.doi.org/10.1007/s11914-020-00652-w] [PMID: 33409990]
[http://dx.doi.org/10.1093/ndt/gfy129] [PMID: 29846712]
[http://dx.doi.org/10.1002/jbmr.3525] [PMID: 29905973]
[http://dx.doi.org/10.1002/jbmr.3198] [PMID: 28608571]
[http://dx.doi.org/10.1038/nrdp.2016.69] [PMID: 27681935]
[http://dx.doi.org/10.1359/jbmr.070207] [PMID: 17295604]
[http://dx.doi.org/10.3389/fimmu.2021.687551] [PMID: 34276675]
[http://dx.doi.org/10.3390/ijms21051653] [PMID: 32121265]
[http://dx.doi.org/10.1016/j.maturitas.2011.09.001] [PMID: 21958941]
[http://dx.doi.org/10.1017/S0007114510001789] [PMID: 20487580]
[http://dx.doi.org/10.1038/bjp.2008.305] [PMID: 18695641]
[http://dx.doi.org/10.1002/jcp.24158] [PMID: 22777826]
[http://dx.doi.org/10.2147/CIA.S4164] [PMID: 19503771]
[http://dx.doi.org/10.3390/nu4111610] [PMID: 23201836]
[http://dx.doi.org/10.1016/j.tem.2021.03.008] [PMID: 33895073]
[http://dx.doi.org/10.1155/2021/6331630] [PMID: 34539970]
[http://dx.doi.org/10.1016/j.jbiosc.2019.04.021] [PMID: 31186185]
[http://dx.doi.org/10.3892/ijmm.2019.4099] [PMID: 30816431]
[http://dx.doi.org/10.1016/j.lfs.2021.119074] [PMID: 33497739]
[http://dx.doi.org/10.3389/fbioe.2020.00858] [PMID: 32793581]
[http://dx.doi.org/10.1016/S0006-2952(00)00277-X] [PMID: 10799655]
[http://dx.doi.org/10.4049/jimmunol.172.10.5940] [PMID: 15128775]
[http://dx.doi.org/10.3390/antiox9010035] [PMID: 31906123]
[http://dx.doi.org/10.3389/fnut.2019.00182] [PMID: 31850361]
[http://dx.doi.org/10.1186/s12967-018-1509-4] [PMID: 29792199]
[http://dx.doi.org/10.2174/138161208786264043] [PMID: 18991693]
[http://dx.doi.org/10.2174/138161212798919057] [PMID: 22211682]
[http://dx.doi.org/10.3945/cdn.117.000406] [PMID: 29955675]
[http://dx.doi.org/10.1016/j.bone.2008.11.018] [PMID: 19118658]
[http://dx.doi.org/10.1254/jphs.11082FP]
[http://dx.doi.org/10.1080/21655979.2022.2056825] [PMID: 35358011]
[http://dx.doi.org/10.3390/antiox3010144] [PMID: 26784669]
[http://dx.doi.org/10.1016/j.jnutbio.2007.09.004] [PMID: 18328688]
[http://dx.doi.org/10.1007/s00223-005-0060-5] [PMID: 16307390]
[http://dx.doi.org/10.1002/mnfr.201100831] [PMID: 22700286]
[http://dx.doi.org/10.1155/2021/3582989] [PMID: 34394379]
[http://dx.doi.org/10.3390/nu12010222] [PMID: 31952249]
[http://dx.doi.org/10.1080/19490976.2017.1371893] [PMID: 28961041]
[http://dx.doi.org/10.1016/j.freeradbiomed.2017.03.011] [PMID: 28323128]
[http://dx.doi.org/10.1016/j.niox.2018.03.007] [PMID: 29550520]
[http://dx.doi.org/10.3390/biology11111683] [PMID: 36421397]
[http://dx.doi.org/10.1155/2014/235060] [PMID: 25147565]
[http://dx.doi.org/10.1177/0300060519860027] [PMID: 31436117]
[http://dx.doi.org/10.1016/j.bone.2020.115736] [PMID: 33171312]
[http://dx.doi.org/10.1016/S0899-9007(00)00262-8] [PMID: 10793310]
[http://dx.doi.org/10.4049/jimmunol.171.12.6856] [PMID: 14662892]
[http://dx.doi.org/10.1096/fj.05-4724fje] [PMID: 16373400]
[http://dx.doi.org/10.1038/bjp.2008.367] [PMID: 18806821]
[http://dx.doi.org/10.3390/nu6072584] [PMID: 25010555]
[http://dx.doi.org/10.1359/jbmr.1999.14.7.1153] [PMID: 10404015]
[http://dx.doi.org/10.1016/j.jnutbio.2010.04.011] [PMID: 20934863]
[http://dx.doi.org/10.1016/j.plefa.2019.04.005] [PMID: 31088624]
[http://dx.doi.org/10.1007/s11745-017-4245-2] [PMID: 28324248]
[http://dx.doi.org/10.1039/C5FO01598G] [PMID: 26822538]
[http://dx.doi.org/10.1021/acs.jafc.2c06081] [PMID: 36260738]
[http://dx.doi.org/10.1186/s12986-019-0393-0] [PMID: 31636691]
[http://dx.doi.org/10.1017/S0007114512001638]
[http://dx.doi.org/10.1093/ajcn/85.3.803] [PMID: 17344503]
[http://dx.doi.org/10.1007/BF03339885] [PMID: 9932142]
[http://dx.doi.org/10.1186/1475-2891-6-2] [PMID: 17227589]
[http://dx.doi.org/10.1161/01.CIR.0000079224.46084.C2] [PMID: 12821543]
[http://dx.doi.org/10.1159/000337302] [PMID: 22507833]
[http://dx.doi.org/10.1007/s00223-019-00584-3] [PMID: 31346665]