{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T08:18:45Z","timestamp":1768465125309,"version":"3.49.0"},"reference-count":24,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,5,7]],"date-time":"2025-05-07T00:00:00Z","timestamp":1746576000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Patients with myasthenia gravis (MG) are susceptible to fractures due to glucocorticoid (GC) use and disease-related functional impairment affecting activities of daily living (ADL). The Fracture Risk Assessment Tool (FRAX\u00ae) estimates fracture probability but does not incorporate disease-specific functional status. We investigated whether combining FRAX\u00ae with the Myasthenia Gravis Activities of Daily Living (MG-ADL) scale improves fracture risk stratification in MG patients. Methods: This single-center prospective cohort study followed 53 MG patients for 10 years (2012\u20132022) at Toho University Ohashi Medical Center, Japan. Patients were categorized into four groups based on baseline FRAX\u00ae probability (calculated with bone mineral density [BMD]) and MG-ADL scores using median splits: high FRAX\u00ae\/high MG-ADL (HH), high FRAX\u00ae\/low MG-ADL (HL), low FRAX\u00ae\/high MG-ADL (LH), and low FRAX\u00ae\/low MG-ADL (LL). The primary outcome was incident major osteoporotic fracture (MOF). Results: Over 10 years, nine MOFs occurred: seven in the HH group (43.8%), two in the HL group (16.7%), and none in the LH or LL groups. Fracture-free survival differed significantly among the groups (log-rank p &lt; 0.001), with the HH group exhibiting the lowest survival rate. Baseline characteristics, including age, disease duration, MG severity scores, BMD, and FRAX\u00ae scores, differed significantly among groups. Specific MG-ADL items reflecting greater impairment (impairment of ability to arise from a chair, double vision, and ptosis) were significantly more pronounced in the HH group at baseline. Conclusions: Combining baseline FRAX\u00ae scores with the MG-ADL assessment effectively stratifies long-term MOF risk in patients with MG. Individuals with both high FRAX\u00ae and high MG-ADL represent a particularly high-risk subgroup. This dual-assessment approach may improve the identification of patients requiring targeted preventive interventions.<\/jats:p>","DOI":"10.3390\/jcm14093260","type":"journal-article","created":{"date-parts":[[2025,5,7]],"date-time":"2025-05-07T11:46:19Z","timestamp":1746618379000},"page":"3260","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Functional Status Enhances the FRAX\u00ae Prediction of Fractures in Myasthenia Gravis: A 10-Year Cohort Study"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8731-0663","authenticated-orcid":false,"given":"Shingo","family":"Konno","sequence":"first","affiliation":[{"name":"Department of Neurology, Toho University Ohashi Medical Center, 2-22-36 Ohashi Meguro Ku, Tokyo 153-8515, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takafumi","family":"Uchi","sequence":"additional","affiliation":[{"name":"Department of Neurology, Toho University Ohashi Medical Center, 2-22-36 Ohashi Meguro Ku, Tokyo 153-8515, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hideo","family":"Kihara","sequence":"additional","affiliation":[{"name":"Department of Neurology, Toho University Ohashi Medical Center, 2-22-36 Ohashi Meguro Ku, Tokyo 153-8515, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hideki","family":"Sugimoto","sequence":"additional","affiliation":[{"name":"Department of Neurology, Toho University Ohashi Medical Center, 2-22-36 Ohashi Meguro Ku, Tokyo 153-8515, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1093\/jbmr\/zjae043","article-title":"Risk of fracture in patients with myasthenia gravis: A nationwide cohort study in Korea","volume":"39","author":"Park","year":"2024","journal-title":"J. Bone Miner. Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1111\/cen.13537","article-title":"Effects of alendronate and alfacalcidol on bone in patients with myasthenia gravis initiating glucocorticoids treatment","volume":"88","author":"Lv","year":"2018","journal-title":"Clin. Endocrinol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Konno, S., Suzuki, S., Masuda, M., Nagane, Y., Tsuda, E., Murai, H., Imai, T., Fujioka, T., Suzuki, N., and Utsugisawa, K. (2015). Association between Glucocorticoid-Induced Osteoporosis and Myasthenia Gravis: A Cross-Sectional Study. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0126579"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"863","DOI":"10.2165\/00007256-200131120-00003","article-title":"Musculoskeletal fitness, health outcomes and quality of life","volume":"31","author":"Kell","year":"2001","journal-title":"Sports Med."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"O\u2019Connor, L., Westerberg, E., and Punga, A.R. (2020). Myasthenia Gravis and Physical Exercise: A Novel Paradigm. Front. Neurol., 11.","DOI":"10.3389\/fneur.2020.00675"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Iolascon, G., Paoletta, M., Liguori, S., Curci, C., and Moretti, A. (2019). Neuromuscular Diseases and Bone. Front. Endocrinol., 10.","DOI":"10.3389\/fendo.2019.00794"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1016\/j.jocn.2018.01.047","article-title":"Low serum vitamin D levels in patients with myasthenia gravis","volume":"50","author":"Kang","year":"2018","journal-title":"J. Clin. Neurosci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"3301","DOI":"10.1007\/s00198-017-4189-7","article-title":"Inflammatory diseases and bone fragility","volume":"28","author":"Briot","year":"2017","journal-title":"Osteoporos. Int."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"625","DOI":"10.3233\/JND-200612","article-title":"Fracture Risk in Patients with Myasthenia Gravis: A Population-Based Cohort Study","volume":"8","author":"Kassardjian","year":"2021","journal-title":"J. Neuromuscul. Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e2840","DOI":"10.1002\/brb3.2840","article-title":"Prevalence of depression and anxiety among myasthenia gravis (MG) patients: A systematic review and meta-analysis","volume":"13","author":"Nadali","year":"2023","journal-title":"Brain Behav."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1016\/j.jagp.2013.01.008","article-title":"The Complex Interplay of Depression and Falls in Older Adults: A Clinical Review","volume":"21","author":"Iaboni","year":"2013","journal-title":"Am. J. Geriatr. Psychiatry"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"123017","DOI":"10.1016\/j.jns.2024.123017","article-title":"Ten-year fracture risk in Japanese patients with myasthenia gravis: A comprehensive assessment using the fracture risk assessment tool","volume":"460","author":"Konno","year":"2024","journal-title":"J. Neurol. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Konno, S., Uchi, T., Kihara, H., and Sugimoto, H. (2024). Long-Term Bone Density Changes and Fracture Risk in Myasthenia Gravis: Implications for FRAX\u00ae Tool Application. Healthcare, 12.","DOI":"10.3390\/healthcare12171793"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1487","DOI":"10.1212\/WNL.52.7.1487","article-title":"Myasthenia gravis activities of daily living profile","volume":"52","author":"Wolfe","year":"1999","journal-title":"Neurology"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1212\/WNL.55.1.16","article-title":"Myasthenia gravis: Recommendations for clinical research standards","volume":"55","author":"Jaretzki","year":"2000","journal-title":"Neurology"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1434","DOI":"10.1212\/WNL.0b013e3181dc1b1e","article-title":"The MG Composite: A valid and reliable outcome measure for myasthenia gravis","volume":"74","author":"Burns","year":"2010","journal-title":"Neurology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1038\/bmt.2012.244","article-title":"Investigation of the freely available easy-to-use software \u2018EZR\u2019 for medical statistics","volume":"48","author":"Kanda","year":"2013","journal-title":"Bone Marrow Transplant."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1002\/mus.23398","article-title":"The MG-QOL15 Japanese version: Validation and associations with clinical factors","volume":"46","author":"Masuda","year":"2012","journal-title":"Muscle Nerve"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1007\/s00198-007-0543-5","article-title":"FRAX and the assessment of fracture probability in men and women from the UK","volume":"19","author":"Kanis","year":"2008","journal-title":"Osteoporos. Int."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/s12931-015-0192-8","article-title":"Fracture prevention in COPD patients; a clinical 5-step approach","volume":"16","author":"Romme","year":"2015","journal-title":"Respir Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1321","DOI":"10.1111\/j.1532-5415.2005.53405.x","article-title":"Frailty: Emergence and consequences in women aged 65 and older in the Women\u2019s Health Initiative Observational Study","volume":"53","author":"Woods","year":"2005","journal-title":"J. Am. Geriatr. Soc."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2133","DOI":"10.1007\/s00415-020-09770-y","article-title":"\u2018Minimal symptom expression\u2019 in patients with acetylcholine receptor antibody-positive refractory generalized myasthenia gravis treated with eculizumab","volume":"267","author":"Vissing","year":"2020","journal-title":"J. Neurol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1002\/mus.24213","article-title":"Health-related quality-of-life and treatment targets in myasthenia gravis","volume":"50","author":"Utsugisawa","year":"2014","journal-title":"Muscle Nerve"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1007\/s12020-018-1588-2","article-title":"Glucocorticoid-induced osteoporosis: An update","volume":"61","author":"Compston","year":"2018","journal-title":"Endocrine"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/9\/3260\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:28:57Z","timestamp":1760030937000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/9\/3260"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,7]]},"references-count":24,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2025,5]]}},"alternative-id":["jcm14093260"],"URL":"https:\/\/doi.org\/10.3390\/jcm14093260","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,7]]}}}