{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T14:47:36Z","timestamp":1789915656770,"version":"4.0.1"},"reference-count":52,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2022,7,22]],"date-time":"2022-07-22T00:00:00Z","timestamp":1658448000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Deanship of Scientific Research, King Saud University"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and objective: There is limited information as to the association of several key bone markers with bone mineral density (BMD) in understudied ethnic groups. This study investigated the relationship between circulating levels of osteoprotegerin (OPG) and receptor activator of nuclear factor kappa-\u0392 ligand (RANKL) with BMD in Arab postmenopausal women. Materials and methods: In this cross-sectional study, a total of 617 Saudi postmenopausal women from the Osteoporosis Registry of the Chair for Biomarkers of Chronic Diseases were included. Anthropometric data, BMD, and biochemical data were retrieved from the registry. Participants were stratified into three groups based on T-score; n = 169 with osteoporosis, n = 282 with osteopenia, and n = 166 normal. Analysis of bone markers including RANKL, OPG, osteocalcin, and N-terminal telopeptide (NTx) was completed using commercially available bioassays. Results: The results suggested that OPG was significantly and positively correlated with age in the osteoporosis group (r = 0.29, p &lt; 0.05), while it was inversely correlated with BMD femoral neck left (r = \u22120.56, p &lt; 0.001) and BMD femoral neck right (r = \u22120.37, p &lt; 0.05) in the same group. Moreover, RANKL showed a significant inverse correlation with NTx in the osteopenia group (r = \u22120.37, p &lt; 0.05). Furthermore, the RANKL\/OPG ratio had a positive and significant correlation with BMI (r = 0.34, p &lt; 0.05), BMD femoral neck left (r = 0.36, p &lt; 0.05) and BMD femoral neck right (r = 0.35, p &lt; 0.05) in the osteopenia group. By contrast, it showed a significant inverse correlation with waist to hip ratio in the osteoporosis group (r = \u22120.38, p &lt; 0.05). Multiple regression analysis showed that OPG contributes to BMD variations in the osteopenia group (p = 0.03). Conclusions: In conclusion, changes in circulating levels of RANKL and OPG might be a protective mechanism contrary to the increased bone loss in postmenopausal women.<\/jats:p>","DOI":"10.3390\/medicina58080976","type":"journal-article","created":{"date-parts":[[2022,7,25]],"date-time":"2022-07-25T01:42:13Z","timestamp":1658713333000},"page":"976","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Associations of Bone Mineral Density with RANKL and Osteoprotegerin in Arab Postmenopausal Women: A Cross-Sectional Study"],"prefix":"10.3390","volume":"58","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8657-0682","authenticated-orcid":false,"given":"Osama E.","family":"Amer","sequence":"first","affiliation":[{"name":"Chair for Biomarkers of Chronic Diseases, Biochemistry Department, College of Science, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9568-6516","authenticated-orcid":false,"given":"Kaiser","family":"Wani","sequence":"additional","affiliation":[{"name":"Chair for Biomarkers of Chronic Diseases, Biochemistry Department, College of Science, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4307-7679","authenticated-orcid":false,"given":"Mohammed G. A.","family":"Ansari","sequence":"additional","affiliation":[{"name":"Chair for Biomarkers of Chronic Diseases, Biochemistry Department, College of Science, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdullah M.","family":"Alnaami","sequence":"additional","affiliation":[{"name":"Chair for Biomarkers of Chronic Diseases, Biochemistry Department, College of Science, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naji","family":"Aljohani","sequence":"additional","affiliation":[{"name":"Obesity, Endocrine and Metabolic Center, King Fahad Medical City, Riyadh 59046, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2024-4171","authenticated-orcid":false,"given":"Saba","family":"Abdi","sequence":"additional","affiliation":[{"name":"Chair for Biomarkers of Chronic Diseases, Biochemistry Department, College of Science, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Syed D.","family":"Hussain","sequence":"additional","affiliation":[{"name":"Chair for Biomarkers of Chronic Diseases, Biochemistry Department, College of Science, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5472-1725","authenticated-orcid":false,"given":"Nasser M.","family":"Al-Daghri","sequence":"additional","affiliation":[{"name":"Chair for Biomarkers of Chronic Diseases, Biochemistry Department, College of Science, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Majed S.","family":"Alokail","sequence":"additional","affiliation":[{"name":"Protein Research Chair, Biochemistry Department, College of Science, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.4158\/EP.16.6.1016","article-title":"American Association of Clinical Endocrinologists Medical Guidelines for Clinical Practice for the diagnosis and treatment of postmenopausal osteoporosis","volume":"16","author":"Watts","year":"2010","journal-title":"Endocr. Pract."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1038\/nm.3074","article-title":"WNT signaling in bone homeostasis and disease: From human mutations to treatments","volume":"19","author":"Baron","year":"2013","journal-title":"Nat. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/S0092-8674(00)80209-3","article-title":"Osteoprotegerin: A novel secreted protein involved in the regulation of bone density","volume":"89","author":"Simonet","year":"1997","journal-title":"Cell"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3597","DOI":"10.1073\/pnas.95.7.3597","article-title":"Osteoclast differentiation factor is a ligand for osteoprotegerin\/osteoclastogenesis-inhibitory factor and is identical to TRANCE\/RANKL","volume":"95","author":"Yasuda","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/S0092-8674(00)81569-X","article-title":"Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation","volume":"93","author":"Lacey","year":"1998","journal-title":"Cell"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"5050","DOI":"10.1210\/endo.142.12.8536","article-title":"Minireview: The opg\/rankl\/rank system","volume":"142","author":"Khosla","year":"2001","journal-title":"Endocrinology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"613","DOI":"10.2174\/1381612013397807","article-title":"Osteoprotegerin A Physiological and Pharmacological Inhibitor of Bone Resorption","volume":"7","author":"Kostenuik","year":"2001","journal-title":"Curr. Pharm. Des."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1186\/ar2165","article-title":"Biology of RANK, RANKL, and osteoprotegerin","volume":"9","author":"Boyce","year":"2007","journal-title":"Arthritis Res. Ther."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1007\/s001980070028","article-title":"Osteoprotegerin and its ligand: A new paradigm for regulation of osteoclastogenesis and bone resorption","volume":"11","author":"Aubin","year":"2000","journal-title":"Osteoporos. Int."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1007\/s12178-009-9046-7","article-title":"RANK, RANKL and osteoprotegerin in bone biology and disease","volume":"2","author":"Wright","year":"2009","journal-title":"Curr. Rev. Musculoskelet. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"367","DOI":"10.2334\/josnusd.50.367","article-title":"Root resorption and the OPG\/RANKL\/RANK system: A mini review","volume":"50","author":"Tyrovola","year":"2008","journal-title":"J. Oral Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.molmed.2004.12.004","article-title":"Osteoclast-derived activity in the coupling of bone formation to resorption","volume":"11","author":"Martin","year":"2005","journal-title":"Trends Mol. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"125705","DOI":"10.1155\/2013\/125705","article-title":"The role of inflammatory cytokines, the RANKL\/OPG axis, and the immunoskeletal interface in physiological bone turnover and osteoporosis","volume":"2013","author":"Weitzmann","year":"2013","journal-title":"Scientifica"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1016\/j.autrev.2008.07.038","article-title":"Osteoimmunology\u2014The hidden immune regulation of bone","volume":"8","author":"Canhao","year":"2009","journal-title":"Autoimmun. Rev."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1007\/s001980200045","article-title":"Correlates of osteoprotegerin levels in women and men","volume":"13","author":"Khosla","year":"2002","journal-title":"Osteoporos. Int."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1111\/j.0105-2896.2005.00334.x","article-title":"The role of the immune system in the pathophysiology of osteoporosis","volume":"208","author":"Clowes","year":"2005","journal-title":"Immunol. Rev."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.abb.2010.07.006","article-title":"Female reproductive system and bone","volume":"503","author":"Clarke","year":"2010","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1016\/j.coph.2005.06.005","article-title":"Osteoprotegerin and RANKL regulate bone resorption, density, geometry and strength","volume":"5","author":"Kostenuik","year":"2005","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3318","DOI":"10.1172\/JCI27071","article-title":"Pathogenesis of osteoporosis: Concepts, conflicts, and prospects","volume":"115","author":"Raisz","year":"2005","journal-title":"J. Clin. Investig."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1177\/000456320203900602","article-title":"Receptor activator for nuclear factor kappaB ligand and osteoprotegerin: Regulators of bone physiology and immune responses\/potential therapeutic agents and biochemical markers","volume":"39","author":"Buckley","year":"2002","journal-title":"Ann. Clin. Biochem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"4470","DOI":"10.1210\/jc.2002-020396","article-title":"Circulating estradiol and osteoprotegerin as determinants of bone turnover and bone density in postmenopausal women","volume":"87","author":"Rogers","year":"2002","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1016\/S8756-3282(03)00090-5","article-title":"Serum levels of osteoprotegerin increase with age in a healthy adult population","volume":"32","author":"Kudlacek","year":"2003","journal-title":"Bone"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1064","DOI":"10.1182\/blood-2003-02-0380","article-title":"Soluble receptor activator of nuclear factor \u03baB ligand\u2013osteoprotegerin ratio predicts survival in multiple myeloma: Proposal for a novel prognostic index","volume":"102","author":"Terpos","year":"2003","journal-title":"Blood"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1002\/art.10834","article-title":"Serum osteoprotegerin and its ligand in Paget\u2019s disease of bone: Relationship to disease activity and effect of treatment with bisphosphonates","volume":"48","author":"Alvarez","year":"2003","journal-title":"Arthritis Rheum."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1744","DOI":"10.1002\/art.10388","article-title":"High levels of osteoprotegerin and soluble receptor activator of nuclear factor \u03baB ligand in serum of rheumatoid arthritis patients and their normalization after anti\u2013tumor necrosis factor \u03b1 treatment","volume":"46","author":"Ziolkowska","year":"2002","journal-title":"Arthritis Rheum."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1007\/s11657-018-0540-7","article-title":"Prevalence of osteoporosis with the World Health Organization diagnostic criteria in the Eastern Mediterranean Region: A systematic review and meta-analysis","volume":"13","author":"Zamani","year":"2018","journal-title":"Arch. Osteoporos."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Wani, K., Yakout, S.M., Ansari, M.G.A., Sabico, S., Hussain, S.D., Alokail, M.S., Sheshah, E., Aljohani, N.J., Al-Saleh, Y., and Reginster, J.-Y. (2019). Metabolic syndrome in Arab adults with low bone mineral density. Nutrients, 11.","DOI":"10.3390\/nu11061405"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1007\/s11657-020-00778-5","article-title":"Diagnosis and management of osteoporosis in postmenopausal women in Gulf Cooperation Council (GCC) countries: Consensus statement of the GCC countries\u2019 osteoporosis societies under the auspices of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO)","volume":"15","author":"Sabico","year":"2020","journal-title":"Arch. Osteoporos."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1359\/jbmr.1999.14.4.518","article-title":"Immunological characterization of circulating osteoprotegerin\/osteoclastogenesis inhibitory factor: Increased serum concentrations in postmenopausal women with osteoporosis","volume":"14","author":"Yano","year":"1999","journal-title":"J. Bone Miner. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.bone.2018.07.010","article-title":"Pulsed electromagnetic fields modulate bone metabolism via RANKL\/OPG and Wnt\/\u03b2-catenin pathways in women with postmenopausal osteoporosis: A pilot study","volume":"116","author":"Catalano","year":"2018","journal-title":"Bone"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1007\/BF03040334","article-title":"Osteoprotegerin serum levels in women: Correlation with age, bone mass, bone turnover and fracture status","volume":"115","author":"Dobnig","year":"2003","journal-title":"Wien. Klin. Wochenschr."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Jung, K., Lein, M., H\u00f6sslin, K.v., Grosse, A., Roth, S., Possinger, K., and L\u00fcftner, D. (2002). Osteoprotegerin and receptor activator of nuclear factor-\u03baB ligand (RANKL) in the serum of healthy adults. Int. J. Biol. Markers, 177\u2013181.","DOI":"10.1177\/172460080201700306"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1172\/JCI200317215","article-title":"Role of RANK ligand in mediating increased bone resorption in early postmenopausal women","volume":"111","author":"Khosla","year":"2003","journal-title":"J. Clin. Investig."},{"key":"ref_34","first-page":"631","article-title":"Associations of serum osteoprotegerin levels with diabetes, stroke, bone density, fractures, and mortality in elderly women","volume":"86","author":"Browner","year":"2001","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1368","DOI":"10.1007\/s00198-005-1844-1","article-title":"The contribution of serum osteoprotegerin to bone mass and vertebral fractures in postmenopausal women","volume":"16","author":"Alonso","year":"2005","journal-title":"Osteoporos. Int."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1530\/EJE-06-0753","article-title":"The sex-specific association of serum osteoprotegerin and receptor activator of nuclear factor \u03baB legend with bone mineral density in older adults: The Rancho Bernardo study","volume":"156","author":"Stern","year":"2007","journal-title":"Eur. J. Endocrinol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"950","DOI":"10.1097\/gme.0b013e3181a181b8","article-title":"Relationships among serum receptor of nuclear factor-\u03baB ligand, osteoprotegerin, high-sensitivity C-reactive protein, and bone mineraldensity in postmenopausal women: Osteoimmunity versus osteoinflammatory","volume":"16","author":"Nabipour","year":"2009","journal-title":"Menopause"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1159\/000196280","article-title":"Implications of measuring soluble receptor activators of nuclear factor-\u03baB ligand and osteoprotegerin in bone metabolism of elderly women","volume":"55","author":"Chiba","year":"2009","journal-title":"Gerontology"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1007\/s00198-004-1699-x","article-title":"Serum osteoprotegerin and its relationship with bone mineral density and markers of bone turnover","volume":"16","author":"Indridason","year":"2005","journal-title":"Osteoporos. Int."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00223-004-0007-2","article-title":"Relationships between the changes of serum levels of OPG and RANKL with age, menopause, bone biochemical markers and bone mineral density in Chinese women aged 20\u201375","volume":"76","author":"Liu","year":"2005","journal-title":"Calcif. Tissue Int."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1007\/s10195-005-0087-4","article-title":"Osteoprotegerin: A valid new marker of bone turnover in post-menopausal osteoporosis?","volume":"6","author":"Ulivieri","year":"2005","journal-title":"J. Orthop. Traumatol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1093\/ije\/23.3.559","article-title":"Reproducibility of a questionnaire on risk factors for osteoporosis in a multicentre prevalence survey: The European Vertebral Osteoporosis Study","volume":"23","author":"Cooper","year":"1994","journal-title":"Int. J. Epidemiol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/S8756-3282(02)00953-5","article-title":"The effects of estrogen on osteoprotegerin, RANKL, and estrogen receptor expression in human osteoblasts","volume":"32","author":"Bord","year":"2003","journal-title":"Bone"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"4367","DOI":"10.1210\/endo.140.9.7131","article-title":"Estrogen stimulates gene expression and protein production of osteoprotegerin in human osteoblastic cells","volume":"140","author":"Hofbauer","year":"1999","journal-title":"Endocrinology"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2205","DOI":"10.1210\/endo.142.6.8220","article-title":"17\u03b2-Estradiol stimulates expression of osteoprotegerin by a mouse stromal cell line, ST-2, via estrogen receptor-\u03b1","volume":"142","author":"Saika","year":"2001","journal-title":"Endocrinology"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1550","DOI":"10.1210\/jcem.87.4.8397","article-title":"Effect of estrogen versus testosterone on circulating osteoprotegerin and other cytokine levels in normal elderly men","volume":"87","author":"Khosla","year":"2002","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1530\/eje.0.1470269","article-title":"Regulation of osteoprotegerin production by androgens and anti-androgens in human osteoblastic lineage cells","volume":"147","author":"Hofbauer","year":"2002","journal-title":"Eur. J. Endocrinol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1002\/jbmr.3014","article-title":"The effects of aging and sex steroid deficiency on the murine skeleton are independent and mechanistically distinct","volume":"32","author":"Ucer","year":"2017","journal-title":"J. Bone Miner. Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"3798","DOI":"10.1002\/jcp.25862","article-title":"Estrogens and androgens inhibit association of RANKL with the pre-osteoblast membrane through post-translational mechanisms","volume":"232","author":"Martin","year":"2017","journal-title":"J. Cell. Physiol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/S0140-6736(01)05494-0","article-title":"Osteoprotegerin: A link between osteoporosis and arterial calcification?","volume":"358","author":"Hofbauer","year":"2001","journal-title":"Lancet"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1530\/eje.0.1490039","article-title":"Increased plasma concentrations of osteoprotegerin in type 2 diabetic patients with microvascular complications","volume":"149","author":"Knudsen","year":"2003","journal-title":"Eur. J. Endocrinol."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Al-Musharaf, S., Fouda, M.A., Turkestani, I.Z., Al-Ajlan, A., Sabico, S., Alnaami, A.M., Wani, K., Hussain, S.D., Alraqebah, B., and Al-Serehi, A. (2018). Vitamin D Deficiency Prevalence and Predictors in Early Pregnancy among Arab Women. Nutrients, 10.","DOI":"10.3390\/nu10040489"}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/58\/8\/976\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:55:00Z","timestamp":1760140500000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/58\/8\/976"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,22]]},"references-count":52,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2022,8]]}},"alternative-id":["medicina58080976"],"URL":"https:\/\/doi.org\/10.3390\/medicina58080976","relation":{},"ISSN":["1648-9144"],"issn-type":[{"value":"1648-9144","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,22]]}}}