Pathological fracture as initial manifestation of malignancy and survival based on diagnoses: a register-based cohort study from the Swedish Fracture Register and the Swedish Cancer Register
DOI:
https://doi.org/10.2340/17453674.2026.46894Keywords:
Arthroplasty, Bone tumours, Metastatic bone disease, Oncology, Pathological fractures, SpineAbstract
Background and purpose: Pathological fracture as the initial manifestation of malignancy is a clinical challenge requiring rapid treatment despite limited prognostic information. We aimed to describe definitive diagnoses and survival in patients presenting with a pathological fracture as initial manifestation of malignancy.
Methods: We performed a nationwide register-based cohort study using the Swedish Fracture Register (SFR) and Swedish Cancer Register (SCR), 2014–2023. We included patients with a pathological fracture classified as unknown in the SFR at treatment. Survival was analyzed using Kaplan–Meier and Cox regression.
Results: We included 319 patients with a pathological fracture. Median age was 75 years (17–100), 50% men. A definitive tumor diagnosis was established in 215 patients (67%), most commonly a hematogenous malignancy. Age was associated with mortality (HR 1.03, 95% confidence interval [CI] 1.01–1.04). Compared with hematogenous malignancies, mortality was higher for bone (HR 2.9, CI 1.2–7.2), breast (HR 2.5, CI 1.2–5.1), kidney (HR 3.3, CI 1.7–6.5), lung (HR 6.3, CI 3.7–10.5), unknown (HR 8.1, CI 4.2–15.5), other (HR 10.3, CI 5.6–19.0), and gastrointestinal malignancies (HR 10.3, CI 4.5–23.7), and for patients without SCR registration (HR 19.7, CI 11.7–33.2). Prostate cancer, sex, fracture site, and treatment were not associated with increased mortality.
Conclusion: Hematogenous and lung malignancies were the most common in pathological fracture as initial manifestation of malignancy. Survival was short and varied substantially by tumor type. Age and primary tumor site were prognostic factors, emphasizing the importance of comprehensive diagnostic work-up to guide acute treatment.
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Kirkinis M N, Lyne C J, Wilson M D, Choong P F. Metastatic bone disease: a review of survival, prognostic factors and outcomes following surgical treatment of the appendicular skeleton. Eur J Surg Oncol 2016; 42(12): 1787-97. doi: 10.1016/j.ejso.2016.03.036.
Bryson D J, Wicks L, Ashford R U. The investigation and management of suspected malignant pathological fractures: a review for the general orthopaedic surgeon. Injury 2015; 46(10): 1891-9. doi: 10.1016/j.injury.2015.07.028.
Zuelzer D A, Weaver D, Zuelzer A P, Hessel E A. Current strategies in medical management of the geriatric hip fracture patient. J Am Acad Orthop Surg 2023; 31(12): 620-6. doi: 10.5435/JAAOS-D-22-00815.
Wolf O, Mukka S, Ekelund J, Möller M, Hailer N P. How deadly is a fracture distal to the hip in the elderly? An observational cohort study of 11,799 femoral fractures in the Swedish Fracture Register. Acta Orthop 2021; 92(1): 40-6. doi: 10.1080/17453674.2020.1831236.
Ruggieri P, Mavrogenis A F, Casadei R, Errani C, Angelini A, Calabrò T, et al. Protocol of surgical treatment of long bone pathological fractures. Injury 2010; 41(11): 1161-7. doi: 10.1016/j.injury.2010.09.018.
Gainor B J, Buchert P. Fracture healing in metastatic bone disease. Clin Orthop Relat Res 1983; (178): 297-302. PMID: 6883864.
Holm C E, Bardram C, Riecke A F, Horstmann P, Petersen M M. Implant and limb survival after resection of primary bone tumors of the lower extremities and reconstruction with mega-prostheses: fifty patients followed for a mean of fourteen years. Int Orthop 2018; 42(5): 1175-81. doi: 10.1007/s00264-018-3861-7.
Wänman J, Farhang M, Nyström H, Styrke J, Häggström C, Stattin P, et al. Survival after spinal surgery for metastases in men with castration-sensitive vs castration-resistant prostate cancer: a nationwide register-based study. Sci Rep 2026; 16(1): 887. doi: 10.1038/s41598-025-34335-2.
Wänman J, Kjartansdóttir S, Wolf O, Sundkvist J, Wennergren D, Mukka S. Age, sex, primary tumor type and site are associated with mortality after pathological fractures: an observational study of 1453 patients from the Swedish Fracture Register. J Orthop Surg Res 2023; 18(1): 150. doi: 10.1186/s13018-023-03620-z.
Wänman J, Grabowski P, Nyström H, Gustafsson P, Bergh A, Widmark A, et al. Metastatic spinal cord compression as the first sign of malignancy. Acta Orthop 2017; 88(4): 457-62. doi: 10.1080/17453674.2017.1319179.
Edman S, Lindberg J, Tabatabaei P, Parai C, Westin O, Hemmingsson O, et al. The St. Gallen Classification of breast cancer subtype and its association with survival after surgery for spinal metastases. Global Spine J 2026: 21925682261424224. doi: 10.1177/21925682261424224.
Möller M, Wolf O, Bergdahl C, Mukka S, Rydberg E M, Hailer N P, et al. The Swedish Fracture Register: ten years of experience and 600,000 fractures collected in a National Quality Register. BMC Musculoskelet Disord 2022; 23(1): 141. doi: 10.1186/s12891-022-05062-w.
Barlow L, Westergren K, Holmberg L, Talbäck M. The completeness of the Swedish Cancer Register: a sample survey for year 1998. Acta Oncol 2009; 48(1): 27-33. doi: 10.1080/02841860802247664.
Wong S K, Mohamad N V, Giaze T R, Chin K Y, Mohamed N, Ima-Nirwana S. Prostate cancer and bone metastases: the underlying mechanisms. Int J Mol Sci 2019; 20(10): 2587. doi: 10.3390/ijms20102587.
Kakhki V R, Anvari K, Sadeghi R, Mahmoudian A S, Torabian-Kakhki M. Pattern and distribution of bone metastases in common malignant tumors. Nucl Med Rev Cent East Eur 2013; 16(2): 66-9. doi: 10.5603/NMR.2013.0037.
O’Sullivan G J, Carty F L, Cronin C G. Imaging of bone metastasis: an update. World J Radiol 2015; 7(8): 202-11. doi: 10.4329/wjr.v7.i8.202.
Bailey S, Hackney D, Vashishth D, Alkalay R N. The effects of metastatic lesion on the structural determinants of bone: current clinical and experimental approaches. Bone 2020; 138: 115159. doi: 10.1016/j.bone.2019.115159.
Izuka Y, Iizuka H, Tsutsumi S, Nakagawa Y, Nakajima T, Sorimachi Y, et al. Diagnosis of a previously unidentified primary site in patients with spinal metastasis: diagnostic usefulness of laboratory analysis, CT scanning and CT-guided biopsy. Eur Spine J 2009; 18(10): 1431-5. doi: 10.1007/s00586-009-1061-2.
Aizenberg M R, Fox B D, Suki D, McCutcheon I E, Rao G, Rhines L D. Surgical management of unknown primary tumors metastatic to the spine. J Neurosurg Spine 2012; 16(1): 86-92. doi: 10.3171/2011.9.SPINE11422.
Hill T, D’Alessandro P, Murray K, Yates P. Prognostic factors following pathological fractures. ANZ J Surg 2015; 85(3): 159-63. doi: 10.1111/ans.12830.
Narazaki D K, de Alverga Neto C C , Baptista A M, Caiero M T, de Camargo O P. Prognostic factors in pathologic fractures secondary to metastatic tumors. Clinics (Sao Paulo) 2006; 61(4): 313-20. doi: 10.1590/s1807-59322006000400007.
Riihimäki M, Hemminki A, Sundquist K, Hemminki K. Time trends in survival from cancer of unknown primary: small steps forward. Eur J Cancer 2013; 49(10): 2403-10. doi: 10.1016/j.ejca.2013.02.022.
Takagi T, Katagiri H, Kim Y, Suehara Y, Kubota D, Akaike K, et al. Skeletal metastasis of unknown primary origin at the initial visit: a retrospective analysis of 286 cases. PLoS One 2015; 10(6): e0129428. doi: 10.1371/journal.pone.0129428.
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Copyright (c) 2026 Jonas Sundkvist, Jenny Giaever, David Wennergren, Sead Crnalic, Johan Wänman
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