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This retrospective study characterizes AFF without bisphosphonate exposure (AFFwB) in older adults and evaluates biochemical patterns using principal component analysis. Patients aged ≥65 years with femoral fractures were identified via ICD-9 codes and confirmed by 2014 ASBMR criteria. Among 21 AFFwB cases, vitamin D insufficiency/deficiency, osteoporosis, and endocrine-mineral, turnover, renal, and BMD domains were identified, highlighting distinct pathways to atypical fractures.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/atypical-femur-fractures-without-bisphosphonate-exposure-affwb-a-retrospective-report-of-21-cases/461516/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/atypical-femur-fractures-without-bisphosphonate-exposure-affwb-a-retrospective-report-of-21-cases/461516.png","ImageObject",300,407,{"name":92,"@type":93},"Indoniesian Boy","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-08","2026-09-30",true,{"@type":102,"interactionType":103,"userInteractionCount":29},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What is the focus of this study on atypical femoral fractures?","Question",{"text":112,"@type":113},"The study focuses on atypical femoral fractures without bisphosphonate exposure (AFFwB) in older adults, characterizing clinical features and biochemical patterns and comparing them conceptually with bisphosphonate-exposed AFF.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How were AFFs and AFFwB cases identified and confirmed?",{"text":117,"@type":113},"Potential cases were selected using ICD-9-CM codes for femoral fracture categories, then radiographic images were reviewed and confirmed according to the 2014 ASBMR criteria by two blinded reviewers.",{"name":119,"@type":110,"acceptedAnswer":120},"What biochemical patterns were explored and what did PCA show?",{"text":121,"@type":113},"Correlations among biochemical variables were assessed, and principal component analysis was applied to PTH, vitamin D, BMD, ALP, calcium, and creatinine. PCA yielded four components accounting for 88.2% of variance, reflecting endocrine–mineral regulation, bone turnover, renal function, and BMD as an independent domain.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},461516,1790794829,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":29,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145},962090760608,"https://ap-avatar.wpscdn.com/davatar_276721f389ce27ea32af1340a28f341c","Article  \nAtypical Femur Fractures Without Bisphosphonate Exposure (AFFwB): A Retrospective Report of 21 Cases  \nLorenzo Lucchetta 1, *, Carmelinda Ruggiero 2, Samuele Berardi 1, Alice Franceschi 3, Michele Bisaccia 1 and Giuseppe Rinonapoli 1  \nAcademic Editor: Johannes Dominik Bastian  \nReceived: 17 November 2025  \nRevised: 11 December 2025  \nAccepted: 15 December 2025  \nPublished: 19 December 2025  \nCopyright: © 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license.  \n1 Orthopedics and Traumatology Department, Medical School, University of Perugia,  \nS. Maria della Misericordia Hospital, 06123 Perugia, Italy  \n2 Orthogeriatric and Geriatric Units, Gerontology and Geriatrics Section, Department Medicine and Surgery, Geriatric Institute, Medical School, University of Perugia, S. Maria della Misericordia Hospital, 06123 Perugia, Italy  \n3 Orthopedics and Traumatology Department, Università Cattolica del Sacro Cuore, 00168 Rome, Italy  \n* Correspondence: [drlorenzolucchetta@pm.me](drlorenzolucchetta@pm.me)  \nAbstract  \nBackground/Objectives: Atypical femoral fractures (AFFs) are rare and classically linked to long-term bisphosphonate therapy, but many occur without such exposure. We aimed to characterize atypical femoral fractures without bisphosphonate exposure (AFFwB) in older adults and to explore biochemical patterns using principal component analysis (PCA) . Methods: We conducted a retrospective study of patients ≥65 years admitted with femoral fractures (January 2019–September 2024) . AFFs were identified from ICD-9 codes and confirmed according to 2014 ASBMR criteria by two blinded reviewers. Demographic, clinical, densitometric, and metabolic data were collected. Correlations between biochemical variables were assessed, and PCA was applied to PTH, vitamin D, BMD, ALP, calcium, and creatinine. Results: Among 932 femoral fractures, 36 met AFF criteria, including 21 AFFwB cases. AFFwB patients were mostly women, and fractures were predominantly diaphyseal. Vitamin D insufficiency/deficiency and osteoporosis were observed in 77% and 66.7% of cases, respectively. Strong correlations were found between PTH and vitamin D and between PTH and ALP. PCA identified four components explaining 88.2% of variance, corresponding to endocrine–mineral regulation, bone turnover, renal function, and BMDas an independent domain. Exploratory comparison with bisphosphonate-exposed AFF suggested higher vitamin D levels and lower ALP in treated patients. Conclusions: In this cohort, AFFs occurred both in patients without bisphosphonate exposure and in those receiving antiresorptive therapy, indicating that AFFs may arise through different pathways. These findings suggest that both insufficient bone quality and excessive remodeling suppression can ultimately lead to atypical fractures. Further studies are needed to clarify these findings.  \nKeywords: atypical femoral fracture; bisphosphonates; osteoporosis; vitamin D; bone turnover; principal component analysis  \n1. Introduction  \nAtypical femoral fractures (AFFs) are rare, low-energy fractures that occur in the subtrochanteric or diaphyseal region of the femur. They are described by the American Society for Bone and Mineral Research (ASBMR) criteria to distinguish AFFs from typical osteoporotic femur fractures. Key features are the minimal or no trauma, transverse or  \nshort oblique orientation, involvement of the lateral cortex, minimal comminution, and localized cortical thickening at the fracture site [1,2] .  \nAFFs have been most reported in patients undergoing long-term treatment with bisphosphonates [3,4] . Although these drugs are effective in reducing osteoporotic fractures, prolonged use has been linked to impaired bone remodeling and microdamage accumulation, with an estimated incidence of 112 AFF per 100,000 patient-years after > 8 years of therapy [5","cbCaiknqtNdIHZh0","https://ap.wps.com/l/cbCaiknqtNdIHZh0","pdf",395260,13,"English","# Abstract\n## Background/Objectives\n## Methods\n## Results\n## Conclusions\n# 1. Introduction\n# 2. Materials and Methods","[{\"question\":\"What is the focus of this study on atypical femoral fractures?\",\"answer\":\"The study focuses on atypical femoral fractures without bisphosphonate exposure (AFFwB) in older adults, characterizing clinical features and biochemical patterns and comparing them conceptually with bisphosphonate-exposed AFF.\"},{\"question\":\"How were AFFs and AFFwB cases identified and confirmed?\",\"answer\":\"Potential cases were selected using ICD-9-CM codes for femoral fracture categories, then radiographic images were reviewed and confirmed according to the 2014 ASBMR criteria by two blinded reviewers.\"},{\"question\":\"What biochemical patterns were explored and what did PCA show?\",\"answer\":\"Correlations among biochemical variables were assessed, and principal component analysis was applied to PTH, vitamin D, BMD, ALP, calcium, and creatinine. PCA yielded four components accounting for 88.2% of variance, reflecting endocrine–mineral regulation, bone turnover, renal function, and BMD as an independent domain.\"}]","Atypical Femur Fractures Without Bisphosphonate Exposure (AFFwB) - A Retrospective Report of 21 Cases | PDF",1790761772,33]