{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:55:00Z","timestamp":1785412500860,"version":"3.56.0"},"reference-count":21,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T00:00:00Z","timestamp":1781136000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004442","name":"National Science Center of Poland","doi-asserted-by":"publisher","award":["2018\/02\/X\/NZ4\/00128"],"award-info":[{"award-number":["2018\/02\/X\/NZ4\/00128"]}],"id":[{"id":"10.13039\/501100004442","id-type":"DOI","asserted-by":"publisher"}]},{"award":["2018\/02\/X\/NZ4\/00128"],"award-info":[{"award-number":["2018\/02\/X\/NZ4\/00128"]}],"id":[{"id":"https:\/\/ror.org\/03ha2q922","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008781","name":"Pomeranian Medical University in Szczecin","doi-asserted-by":"crossref","award":["WNOZ-321-01\/S\/01\/21"],"award-info":[{"award-number":["WNOZ-321-01\/S\/01\/21"]}],"id":[{"id":"10.13039\/501100008781","id-type":"DOI","asserted-by":"crossref"}]},{"award":["WNOZ-321-01\/S\/01\/21"],"award-info":[{"award-number":["WNOZ-321-01\/S\/01\/21"]}],"id":[{"id":"https:\/\/ror.org\/01v1rak05","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>This study aimed to identify environmental and hormonal determinants of steroid receptor expression in the bone tissue of men with osteoarthritis. Twenty-six men undergoing total hip arthroplasty were included. Serum hormones, bone turnover markers, and elemental concentrations were assessed, and bone samples were analyzed using immunohistochemistry and multivariate regression models. Results: Estrogen receptor alpha (ER\u03b1) expression was a significant positive predictor of the bone formation marker procollagen type I N-terminal propeptide (PINP) (p = 0.0386), indicating its key role in anabolic processes. Androgen receptor (AR) expression showed a positive trend with the resorption marker CTX-I (p = 0.0956). A strong negative association was observed between Body Mass Index (BMI) and ER\u03b1 expression (\u03b2 = \u22120.50; p = 0.0018), suggesting reduced estrogen sensitivity in individuals with higher adiposity. Local accumulation of metals significantly influenced receptor expression. Lead in bone was strongly associated with increased AR expression (\u03b2 = +1.457; p = 0.0009), whereas manganese was positively associated with ER\u03b1 expression (\u03b2 = +2.112; p = 0.0409). These findings indicate that local bone tissue analysis provides more accurate insight into hormonal regulation than serum measurements and highlight the role of environmental factors in modulating bone metabolism in men.<\/jats:p>","DOI":"10.3390\/ijms27125294","type":"journal-article","created":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T06:53:10Z","timestamp":1781247190000},"page":"5294","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Assessment of Factors Regulating Androgen Receptor (AR) and Estrogen Receptor Alpha (ER\u03b1) Expression in Men with End-Stage Hip Osteoarthritis"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5954-4489","authenticated-orcid":false,"given":"Aleksandra","family":"Ry\u0142","sequence":"first","affiliation":[{"name":"Department of Medical Rehabilitation and Clinical Physiotherapy, Pomeranian Medical University in Szczecin, 54 \u017bo\u0142nierska, 71-210 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0861-0738","authenticated-orcid":false,"given":"Marta","family":"Grabowska","sequence":"additional","affiliation":[{"name":"Department of Histology and Developmental Biology, Pomeranian Medical University in Szczecin, 48 \u017bo\u0142nierska, 71-210 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2822-858X","authenticated-orcid":false,"given":"Alina","family":"Jurewicz","sequence":"additional","affiliation":[{"name":"Department of Specialized Nursing, Pomeranian Medical University in Szczecin, 48 \u017bo\u0142nierska Street, 71-210 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrzej","family":"Bohatyrewicz","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Traumatology and Musculoskeletal Oncology, Pomeranian Medical University in Szczecin, 1 Unii Lubelskiej, 71-252 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6105-5329","authenticated-orcid":false,"given":"Aleksandra","family":"Szyli\u0144ska","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery, Pomeranian Medical University in Szczecin, 72 Powsta\u0144c\u00f3w Wielkopolskich, 70-111 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weronika","family":"Ratajczak","sequence":"additional","affiliation":[{"name":"Department and Division of Functional Diagnostics and Physical Medicine, Pomeranian Medical University in Szczecin, 54 \u017bo\u0142nierska, 71-210 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5914-2121","authenticated-orcid":false,"given":"Ma\u0142gorzata","family":"Piasecka","sequence":"additional","affiliation":[{"name":"Department of Histology and Developmental Biology, Pomeranian Medical University in Szczecin, 48 \u017bo\u0142nierska, 71-210 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7201-328X","authenticated-orcid":false,"given":"Katarzyna","family":"Micha\u0142ek","sequence":"additional","affiliation":[{"name":"Department of Physiology, Cytobiology and Proteomics, Faculty of Biotechnology and Animal Sciences, West Pomeranian University of Technology in Szczecin, 29 Klemensa Janickiego, 71-270 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5378-5409","authenticated-orcid":false,"given":"Anna","family":"Lubkowska","sequence":"additional","affiliation":[{"name":"Department and Division of Functional Diagnostics and Physical Medicine, Pomeranian Medical University in Szczecin, 54 \u017bo\u0142nierska, 71-210 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iwona","family":"Rotter","sequence":"additional","affiliation":[{"name":"Department of Medical Rehabilitation and Clinical Physiotherapy, Pomeranian Medical University in Szczecin, 54 \u017bo\u0142nierska, 71-210 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1134","DOI":"10.1002\/jbmr.2529","article-title":"New Insights into Androgen and Estrogen Receptor Regulation of the Male Skeleton","volume":"30","author":"Khosla","year":"2015","journal-title":"J. Bone Miner. Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"4023","DOI":"10.1007\/s00018-013-1317-1","article-title":"The role of estrogen receptor \u03b1 in the regulation of bone and growth plate cartilage","volume":"70","author":"Lagerquist","year":"2013","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Chen, J.F., Lin, P.W., Tsai, Y.R., Yang, Y.C., and Kang, H.Y. (2019). Androgens and Androgen Receptor Actions on Bone Health and Disease: From Androgen Deficiency to Androgen Therapy. Cells, 8.","DOI":"10.3390\/cells8111318"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/S0301-2115(02)00315-9","article-title":"Androgen receptor (AR) gene microsatellite polymorphism in postmenopausal women: Correlation to bone mineral density and susceptibility to osteoporosis","volume":"107","author":"Chen","year":"2003","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Mariano, A., Scotto d\u2019Abusco, A., and Ammendola, S. (2026). Gene Polymorphisms Associated with Osteoarthritis: Potential Implications for Nutrigenetics and Precision Nutrition. Nutrients, 18.","DOI":"10.3390\/nu18061003"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Yan, Y.S., Qu, Z., Yu, D.Q., Wang, W., Yan, S., and Huang, H.F. (2021). Sex Steroids and Osteoarthritis: A Mendelian Randomization Study. Front. Endocrinol., 12.","DOI":"10.3389\/fendo.2021.683226"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e19310","DOI":"10.7717\/peerj.19310","article-title":"Mechanical loading regulates osteogenic differentiation and bone formation by modulating non-coding RNAs","volume":"13","author":"Deng","year":"2025","journal-title":"PeerJ"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1359\/jbmr.091008","article-title":"Estrogen Augments Shear Stress-Induced Signaling and Gene Expression in Osteoblast-like Cells via Estrogen Receptor-Mediated Expression of beta1-Integrin","volume":"25","author":"Yeh","year":"2010","journal-title":"J. Bone Miner. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"666","DOI":"10.33594\/000000818","article-title":"Knee Joint Response to Mechanical Loading: Bounding Mechanotransduction with Rehabilitation","volume":"59","author":"Swinnen","year":"2025","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"ziae064","DOI":"10.1093\/jbmrpl\/ziae064","article-title":"Iron and bones: Effects of iron overload, deficiency and anemia treatments on bone","volume":"8","author":"Oheim","year":"2024","journal-title":"JBMR Plus"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1038\/s41392-023-01330-w","article-title":"Osteoarthritis: Pathogenic signaling pathways and therapeutic targets","volume":"8","author":"Yao","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1111\/jne.12065","article-title":"Nuclear receptor coactivators: Regulators of steroid action in brain and behaviour","volume":"25","author":"Tetel","year":"2013","journal-title":"J. Neuroendocrinol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Li, Y., Yang, B., Xu, S., Xian, T., and Zhang, M. (2026). Steroid receptor coactivator-1: Integrating steroid hormone signals to regulate brain function and disease. Front. Neurosci., 20.","DOI":"10.3389\/fnins.2026.1837573"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"112614","DOI":"10.1016\/j.exger.2024.112614","article-title":"The interplay between osteoarthritis and osteoporosis: Mechanisms, implications, and treatment considerations\u2014A narrative review","volume":"197","author":"Huang","year":"2024","journal-title":"Exp. Gerontol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"120740","DOI":"10.1016\/j.envpol.2022.120740","article-title":"Exposure to heavy metals and hormone levels in midlife women: The Study of Women\u2019s Health Across the Nation (SWAN)","volume":"317","author":"Wang","year":"2023","journal-title":"Environ. Pollut."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Taskozhina, G., Batyrova, G., Umarova, G., Issanguzhina, Z., and Kereyeva, N. (2024). The Manganese-Bone Connection: Investigating the Role of Manganese in Bone Health. J. Clin. Med., 13.","DOI":"10.3390\/jcm13164679"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Mei, Y., Yan, Y., Ke, S., Su, W., Luo, Z., Chen, X., Xu, H., Su, W., and Li, A. (2026). Age-Dependent Effects of Heavy Metals on the Hypothalamic-Pituitary-Testicular Axis-Related Hormones in Men. Toxics, 14.","DOI":"10.3390\/toxics14010055"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"118352","DOI":"10.1016\/j.ecoenv.2025.118352","article-title":"Toxic metals and trace elements, markers of inflammation, and hyperandrogenemia in women and testosterone deficiency in men: Associations and potential mediating factors","volume":"299","author":"Lu","year":"2025","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"127520","DOI":"10.1016\/j.jtemb.2024.127520","article-title":"Serum trace elements and osteoarthritis: A meta-analysis and Mendelian randomization study","volume":"86","author":"Shi","year":"2024","journal-title":"J. Trace Elem. Med. Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3666","DOI":"10.1210\/jcem.84.10.6079","article-title":"A Critical Evaluation of Simple Methods for the Estimation of Free Testosterone in Serum","volume":"84","author":"Vermeulen","year":"1999","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1530\/eje.0.1510241","article-title":"A Mathematical Comparison of Techniques to Predict Biologically Available Testosterone in a Cohort of 1072 Men","volume":"151","author":"Morris","year":"2004","journal-title":"Eur. J. Endocrinol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/12\/5294\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T04:28:08Z","timestamp":1781324888000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/12\/5294"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,11]]},"references-count":21,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["ijms27125294"],"URL":"https:\/\/doi.org\/10.3390\/ijms27125294","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,11]]}}}