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We hereby describe the design of the EraSmus medIcal CeNTer skEletal fRagility (SINTER) Study, which integrates polygenic scores for BMD (PGS\n                    <jats:sub>BMD<\/jats:sub>\n                    ) with a multidimensional phenotyping approach in diverse outpatient clinics, as a methodological framework for musculoskeletal research. The study aims at assessing the additional value of combining genetic information with comprehensive musculoskeletal phenotyping to better elucidate the mechanisms of skeletal fragility in chronic conditions. SINTER is an observational, cross-sectional\n                    <jats:italic>Recall-by-Genotype<\/jats:italic>\n                    (\n                    <jats:italic>RbG<\/jats:italic>\n                    ) study drawn in two stages: (1) genotyping 5,650 patients from nine internal medicine clinics; (2) recalling 1,500 patients from the extremes of the PGS\n                    <jats:sub>BMD<\/jats:sub>\n                    distribution for multidimensional musculoskeletal phenotyping together with 400 patients with a rare condition (mastocytosis). Phenotyping includes imaging (DXA, EOSEdge, pQCT), macro- and tissue-level skeletal properties (ultrasound, reference point indentation), functional assessments (mechanography, handgrip), lifestyle and systemic exposures (diet, physical activity), and patient perceptions obtained via in-depth interview and questionnaires. The study design is unique in combining a\n                    <jats:italic>RbG<\/jats:italic>\n                    framework with multidimensional phenotyping in outpatient clinics, enabling systematic evaluation of genetic and disease-specific contributors to skeletal fragility. SINTER provides a methodological template for RbG designs with particular emphasis on musculoskeletal clinical research.\n                  <\/jats:p>","DOI":"10.1007\/s10654-026-01419-w","type":"journal-article","created":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T10:30:39Z","timestamp":1782469839000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The SINTER study: a recall-by-genotype design with multidimensional musculoskeletal phenotyping across internal-medicine outpatient clinics"],"prefix":"10.1007","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-5094-608X","authenticated-orcid":false,"given":"Kirsty","family":"Huininga","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fjorda","family":"Koromani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siwen","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katerina","family":"Trajanoska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirsten A.","family":"Berk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mari\u00ebtte R.","family":"Boon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Layal","family":"Chaker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"van Daele","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Hofland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mandy H.","family":"van Hoek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc H.","family":"Hemmelder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeanine E.","family":"Roeters van Lennep","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Medici","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanne F.","family":"Olieman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Behiye","family":"Ozcan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin P.","family":"Peeters","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Mattace-Raso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eskeatnaf","family":"Mulugeta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth F. 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E.F.S. vV. reports honoraria from UCB Pharma, Kyowa Kirin and Theramex and Amgen not related to this work. M.C.Z. reports honoraria for lectures or consulting from UCB Pharma, Kyowa Kirin and Theramex and Amgen not related to this work. E.F.C.vR reports honoraria from Dutch Obesity Academy, E-wise and Medscape\/WebMD not related to this work. L.C has received funding for investigator-initiated research from Abbott Diabetes Care not related to this work.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}