{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,8]],"date-time":"2026-08-08T12:45:19Z","timestamp":1786193119171,"version":"build-2736575974"},"reference-count":22,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,8,8]],"date-time":"2026-08-08T00:00:00Z","timestamp":1786147200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,8,8]],"date-time":"2026-08-08T00:00:00Z","timestamp":1786147200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Universit\u00e0 degli Studi di Roma La Sapienza"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Endocrine"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>Single nucleotide polymorphisms (SNPs) have been associated with BMD and bone fracture risk. The aim of this study was to assess the possible association between FRAX scores and specific SNPs in Italian osteopenic and osteoporotic postmenopausal women.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We enrolled 54 postmenopausal women with osteoporosis or osteopenia. FRAX (a computer-based free algorithm that provides the 10-year probability of fractures on the basis of classic risk factors) and BMD were obtained in every patient. We included 13 SNPs in the ESR1, OPG, RANK-L, VDR, PTH, CASR, COL1A1, CALCR, ACTN3 and TPRV6 candidate genes. We tested the association of principal component analysis scores based on individual multi-locus genotypes with FRAX.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A FRAX_M\u2009&gt;\u2009=\u200920% was found in 20.3% and a FRAX_H\u2009&gt;\u2009=\u20093% in 51.8% of patients. Twenty-four patients had a fragility fracture. At the level of single-locus associations, a significant difference (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.046) was obtained for FRAX_H and the haplotype ESR1(GC), with mean values of 3.9 vs. 7.7 among non-carriers vs. carriers. In particular, patients characterized by high FRAX_M and FRAX_H values shared haplotype (GT) at PTH and allele G at OPG. On the opposite, patients in the low-risk FRAX score were characterized by COL1A1 allele A, CASR allele T, VDR haplotypes (GA) and (AA).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In postmenopausal Italian women an appropriate combination of haplotypes\/alleles at PTH and OPG genes is associated with high mean FRAX values. Long term studies would allow to assess if combining multi-locus genetic analyses with FRAX scores could empower physicians to tailor personalized preventive early strategies for osteoporosis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s12020-026-04739-9","type":"journal-article","created":{"date-parts":[[2026,8,8]],"date-time":"2026-08-08T11:55:13Z","timestamp":1786190113000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Association between candidate genes and FRAX scores in postmenopausal women"],"prefix":"10.1007","volume":"91","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3088-0673","authenticated-orcid":false,"given":"Jessica","family":"Pepe","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arianna","family":"Viviani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristiana","family":"Cipriani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bianca Maria","family":"Ciminelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"Jodice","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luciano","family":"Colangelo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Forti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachele","family":"Santori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Terreri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salvatore","family":"Minisola","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Latini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Occhiuto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrizia","family":"Malaspina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Novelletto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,8,8]]},"reference":[{"issue":"4","key":"4739_CR1","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1007\/s40618-017-0761-4","volume":"41","author":"C Cipriani","year":"2018","unstructured":"C. Cipriani, J. Pepe, F. Bertoldo et al., The epidemiology of osteoporosis in Italian postmenopausal women according to the National Bone Health Alliance (NBHA) diagnostic criteria: a multicenter cohort study. J. Endocrinol. Invest. 41(4), 431\u2013438 (2018). https:\/\/doi.org\/10.1007\/s40618-017-0761-4","journal-title":"J. Endocrinol. Invest."},{"issue":"2","key":"4739_CR2","doi-asserted-by":"publisher","first-page":"484","DOI":"10.1007\/s12020-020-02553-5","volume":"71","author":"J Pepe","year":"2021","unstructured":"J. Pepe, P. Agosti, C. Cipriani et al., Underdiagnosis and undertreatment of osteoporotic patients admitted in internal medicine wards in Italy between 2010 and 2016 (the REPOSI Register). Endocrine. 71(2), 484\u2013493 (2021). https:\/\/doi.org\/10.1007\/s12020-020-02553-5","journal-title":"Endocrine"},{"issue":"5","key":"4739_CR3","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1210\/er.2009-0044","volume":"31","author":"SH Ralston","year":"2010","unstructured":"S.H. Ralston, A.G. Uitterlinden, Genetics of osteoporosis. Endocr. Rev. 31(5), 629\u2013662 (2010). https:\/\/doi.org\/10.1210\/er.2009-0044","journal-title":"Endocr. Rev."},{"issue":"4","key":"4739_CR4","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1007\/s00198-007-0543-5","volume":"19","author":"J Kanis","year":"2008","unstructured":"J. Kanis, O. Johnell, A. Oden, H. Johansson, E. McCloskey, FRAX\u2122 and the assessment of fracture probability in men and women from the UK. Osteoporos. Int. 19(4), 385\u2013397 (2008). https:\/\/doi.org\/10.1007\/s00198-007-0543-5","journal-title":"Osteoporos. Int."},{"issue":"1","key":"4739_CR5","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1210\/jc.2016-280","volume":"102","author":"J Pepe","year":"2017","unstructured":"J. Pepe, E. Biver, N. Bonnet et al., Within- and Across-Sex Inheritance of Bone Microarchitecture. J. Clin. Endocrinol. Metab. 102(1), 40\u201345 (2017). https:\/\/doi.org\/10.1210\/jc.2016-280","journal-title":"J. Clin. Endocrinol. Metab."},{"issue":"3","key":"4739_CR6","doi-asserted-by":"publisher","first-page":"e0150070","DOI":"10.1371\/journal.pone.0150070","volume":"11","author":"L Qin","year":"2016","unstructured":"L. Qin, Y. Liu, Y. Wang, G. Wu, J. Chen, W. Ye et al., Computational Characterization of Osteoporosis Associated SNPs and Genes Identified by Genome-Wide Association Studies. PLoS One. 11(3), e0150070 (2016). https:\/\/doi.org\/10.1371\/journal.pone.0150070","journal-title":"PLoS One"},{"issue":"3","key":"4739_CR7","doi-asserted-by":"publisher","first-page":"646","DOI":"10.1007\/s12020-023-03476-7","volume":"82","author":"A Viviani","year":"2023","unstructured":"A. Viviani, L. Colangelo, B.M. Ciminelli et al., Genetic aspects underlying the normocalcemic and hypercalcemic phenotypes of primary hyperparathyroidism. Endocrine. 82(3), 646\u2013653 (2023). https:\/\/doi.org\/10.1007\/s12020-023-03476-7","journal-title":"Endocrine"},{"issue":"6","key":"4739_CR8","doi-asserted-by":"publisher","first-page":"746","DOI":"10.1007\/s00223-021-00809-4","volume":"108","author":"X Xiao","year":"2021","unstructured":"X. Xiao, Q. Wu, The utility of genetic risk score to improve performance of frax for fracture prediction in us postmenopausal women. Calcif Tissue Int. 108(6), 746\u2013756 (2021). https:\/\/doi.org\/10.1007\/s00223-021-00809-4","journal-title":"Calcif Tissue Int."},{"issue":"5","key":"4739_CR9","doi-asserted-by":"publisher","first-page":"672","DOI":"10.1111\/j.1365-2265.2012.04452.x","volume":"77","author":"J Pepe","year":"2012","unstructured":"J. Pepe, A.M. Isidori, M. Falciano, Clin et al., Endocrinol. (Oxf). 77(5), 672\u2013678 (2012). https:\/\/doi.org\/10.1111\/j.1365-2265.2012.04452.x","journal-title":"Endocrinol. (Oxf)"},{"issue":"11","key":"4739_CR10","doi-asserted-by":"publisher","first-page":"3239","DOI":"10.1007\/s00198-017-4180-3","volume":"28","author":"S Minisola","year":"2017","unstructured":"S. Minisola, L. Cianferotti, P. Biondi et al., Correction of vitamin D status by calcidiol: pharmacokinetic profile, safety, and biochemical effects on bone and mineral metabolism of daily and weekly dosage regimens. Osteoporos. Int. 28(11), 3239\u20133249 (2017). https:\/\/doi.org\/10.1007\/s00198-017-4180-3","journal-title":"Osteoporos. Int."},{"issue":"4","key":"4739_CR11","doi-asserted-by":"publisher","first-page":"978","DOI":"10.1086\/319501","volume":"68","author":"M Stephens","year":"2001","unstructured":"M. Stephens, N.J. Smith, P.A. Donnelly, New statistical method for haplotype reconstruction from population data. Am. J. Hum. Genet. 68(4), 978\u2013989 (2001). https:\/\/doi.org\/10.1086\/319501","journal-title":"Am. J. Hum. Genet."},{"key":"4739_CR12","doi-asserted-by":"publisher","first-page":"564","DOI":"10.1111\/j.1755-0998.2010.02847.x","volume":"10","author":"L Excoffier","year":"2010","unstructured":"L. Excoffier, H.E. Lischer, Arlequin suite ver 3.5: a new series of programs to perform population genetics analyses under Linux and Windows. Mol. Ecol. Resour. 10, 564\u2013567 (2010). https:\/\/doi.org\/10.1111\/j.1755-0998.2010.02847.x","journal-title":"Mol. Ecol. Resour."},{"issue":"2","key":"4739_CR13","doi-asserted-by":"publisher","first-page":"977","DOI":"10.1137\/18M1211350","volume":"80","author":"NB Erichson","year":"2020","unstructured":"N.B.Erichson, P. Zheng, K. Manohar, S.L. Brunton, J.N. Kutz, A.Y. Aravkin, Sparse Principal Component analysis via variable projection. SIAM J. Appl. Math. 80(2), 977\u20131002 (2020). https:\/\/doi.org\/10.1137\/18M1211350","journal-title":"SIAM J. Appl. Math."},{"issue":"1","key":"4739_CR14","doi-asserted-by":"publisher","first-page":"346","DOI":"10.1186\/s12891-020-03359-2","volume":"21","author":"J Shu","year":"2020","unstructured":"J. Shu, L.J. Fu, Y. Hui, X. Jin, Y. Chen, M. Zheng, X. Shi, Association of ESR1 polymorphism rs2234693 and rs9340799 with postmenopausal osteoporosis in a Chinese population. BMC Musculoskelet. Disord. 21(1), 346 (2020). https:\/\/doi.org\/10.1186\/s12891-020-03359-2","journal-title":"BMC Musculoskelet. Disord"},{"issue":"8","key":"4739_CR15","doi-asserted-by":"publisher","first-page":"3777","DOI":"10.1210\/jc.2002-021861","volume":"88","author":"EM Colin","year":"2003","unstructured":"E.M. Colin, A.G. Uitterlinden, J.B.J. Meurs et al., Interaction between vitamin D receptor genotype and estrogen receptor alpha genotype influences vertebral fracture risk. Clin. Trial J. Clin. Endocrinol. Metab. 88(8), 3777\u20133784 (2003). https:\/\/doi.org\/10.1210\/jc.2002-021861","journal-title":"Clin. Trial J. Clin. Endocrinol. Metab."},{"issue":"2","key":"4739_CR16","doi-asserted-by":"publisher","first-page":"200","DOI":"10.3390\/genes12020200","volume":"12","author":"S Abdi","year":"2021","unstructured":"S. Abdi, R.A. Binbaz, A.K. Mohammed et al., Association of RANKL and OPG Gene Polymorphism in Arab Women with and without Osteoporosis. Genes (Basel). 12(2), 200 (2021). https:\/\/doi.org\/10.3390\/genes12020200","journal-title":"Genes (Basel)"},{"issue":"7","key":"4739_CR17","doi-asserted-by":"publisher","first-page":"1245","DOI":"10.1359\/jbmr.2002.17.7.1245","volume":"17","author":"BL Langdahl","year":"2021","unstructured":"B.L. Langdahl, M. Carstens, L. Stenkjaer, E.F. Eriksen, Polymorphisms in the osteoprotegerin gene are associated with osteoporotic fractures. J. Bone Min. Res. 17(7), 1245\u20131255 (2021). https:\/\/doi.org\/10.1359\/jbmr.2002.17.7.1245","journal-title":"J. Bone Min. Res."},{"issue":"6","key":"4739_CR18","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1530\/eje.0.1480603","volume":"148","author":"F Cetani","year":"2003","unstructured":"F. Cetani, E. Pardi, S. Borsari et al., Calcium-sensing receptor gene polymorphism is not associated with bone mineral density in Italian postmenopausal women. Eur. J. Endocrinol. 148(6), 603\u2013607 (2003). https:\/\/doi.org\/10.1530\/eje.0.1480603","journal-title":"Eur. J. Endocrinol."},{"issue":"2","key":"4739_CR19","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1159\/000204960","volume":"2","author":"MM Laaksonen","year":"2009","unstructured":"M.M. Laaksonen, T.A. Outila, M.U. Karkkainen et al., Associations of vitamin D receptor, calcium-sensing receptor and parathyroid hormone gene polymorphisms with calcium homeostasis and peripheral bone density in adult Finns. J. Nutrigenet Nutrigenomics. 2(2), 55\u201363 (2009). https:\/\/doi.org\/10.1159\/000204960","journal-title":"J. Nutrigenet Nutrigenomics"},{"issue":"2","key":"4739_CR20","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1007\/s00774-024-01558-8","volume":"43","author":"N Huynh","year":"2025","unstructured":"N. Huynh, De K. Dios, T.S. Tran, J.R. Center, T.V. Nguyen, Association between the Sp1-binding-site polymorphism in the collagen type I alpha 1 (COLIA1) gene and bone phenotypes: the Dubbo Osteoporosis Epidemiology Study. J. Bone Min. Metab. 43(2), 114\u2013122 (2025). https:\/\/doi.org\/10.1007\/s00774-024-01558-8","journal-title":"J. Bone Min. Metab."},{"issue":"1","key":"4739_CR21","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s00296-015-3319-9","volume":"36","author":"S Noordin","year":"2016","unstructured":"S. Noordin, J. Glowacki, Parathyroid hormone and its receptor gene polymorphisms: implications in osteoporosis and in fracture healing. Rheumatol. Int. 36(1), 1\u20136 (2016). https:\/\/doi.org\/10.1007\/s00296-015-3319-9","journal-title":"Rheumatol. Int."},{"issue":"1","key":"4739_CR22","doi-asserted-by":"publisher","first-page":"285","DOI":"10.3390\/jcm9010285","volume":"9","author":"W Qing","year":"2020","unstructured":"W. Qing, X. Xiangxue, X. Yingke, Performance of FRAX in Predicting Fractures in US Postmenopausal Women with Varied Race and Genetic Profiles. J. Clin. Med. 9(1), 285 (2020). https:\/\/doi.org\/10.3390\/jcm9010285","journal-title":"J. Clin. Med."}],"container-title":["Endocrine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12020-026-04739-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12020-026-04739-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12020-026-04739-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,8]],"date-time":"2026-08-08T11:55:15Z","timestamp":1786190115000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12020-026-04739-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,8]]},"references-count":22,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["4739"],"URL":"https:\/\/doi.org\/10.1007\/s12020-026-04739-9","relation":{},"ISSN":["1559-0100"],"issn-type":[{"value":"1559-0100","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,8]]},"assertion":[{"value":"24 January 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"31 July 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 August 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The study was approved by the local Ethic Committee (\u201cComitato etico Lazio Area 1\u201d; protocol number 7356). The Research was carried out complying with the World Medical Association Declaration of Helsinki. Written informed consent was obtained from the parents.","order":1,"name":"Ethics","label":"Ethics approval","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"S.M. served as a speaker for Abiogen, Beijing Society Biomedical Engineering, Geopharma, Sandoz, UCB. He also served on the advisory board of Kyowa Kirin and Faes Farma. CC served as speaker, consultant and received travel reimbursement from Abiogen. She also served as consultant and on advisory board of IBSA and received travel reimbursement from Amgen. The other authors have no conflicts to declare.","order":2,"name":"Ethics","label":"Conflict of interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"264"}}