Introduction
Pathological fractures result from abnormal bone remodeling and are commonly associated with skeletal tumors, including primary and metastatic bone tumors. In normal bone metabolism, bone resorption and formation occur via a balanced process known as coupling. However, tumor-derived secretory factors disrupt this balance in the bone microenvironment, leading to abnormal remodeling ( Nakajima et al. , 2016a ; Nakajima and Raz, 2020 ; Nakajima et al. , 2021 ). As a result, tumor-induced bone tissue becomes mechanically fragile and unable to withstand external forces effectively. Even minor stresses can induce high stress concentrations at the defective site, increasing the risk of pathological fractures ( Nakajima et al. , 2016b ).
Bone tumors can manifest as osteolytic and osteosclerotic lesions, both of which contribute to compromised bone integrity. Bisphosphonates, which induce osteoclast apoptosis, are commonly used to counteract excessive local bone resorption. Surgical treatments for pathological fractures typically involve either amputation or limb-sparing reconstruction of the affected area while preserving as much of the normal bone and spine integrity as possible ( van Ee et al. , 1989 ; Heidner et al. , 1991 ; Pernell et al. , 1992 ; Montgomery et al. , 1993 ; Emmerson and Muir, 1997 ; Cooley and Waters, 1998 ; Chauvet et al. , 1999 ; Emmerson and Pead, 1999 ; Banks et al. , 2003 ; Cabassu and Moissonnier, 2007 ; Bhandal and Boston, 2011 ; Boston et al. , 2011a ; Boston et al. , 2011b ; Boston et al. , 2017 ; Choate and Arnold, 2011 ; Covey et al. , 2014 ; Hayes et al. , 2020 ; Melilli, 2020 ). However, due to the limited number of published case reports, the therapeutic efficacy of pathological fracture repair remains unclear, and no comprehensive review on treatment outcomes exists.
Clinical decision-making should be based on robust evidence rather than individual case studies. While single studies have inherent limitations, a meta-analysis provides a statistical approach to synthesizing results, offering a more precise and comprehensive assessment of treatment efficacy. By integrating multiple studies, a meta-analysis increases the overall sample size and enhances the strength of the evidence ( Page et al. , 2021 ).
This large-scale cohort study aims to characterize pathological fractures and address the clinical question of survival time and functional prognosis following surgical repair using meta-analysis.
Materials and Methods
To ensure research quality, we employed a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) compliant protocol to enhance the credibility and confidence of the review methodology. The protocol for this systematic review and meta-analysis has been previously published ( Page et al. , 2021 ).
Systematic review
We surveyed existing studies to address the clinical question: What is the survival duration or functional prognosis following surgical repair of pathological fractures? To identify eligible cases, we reviewed the medical records (2018–2025) of dogs with pathological fractures. Dogs with imaging evidence of a pathological fracture—including radiography, computed tomography, and magnetic resonance imaging—and a confirmed bone biopsy were included.
Additionally, eligible canine patients were identified through a comprehensive search of publications on MEDLINE (PubMed) using the search terms “Pathologic fracture,” “Pathological fracture,” and “dog” on May 23, 2023. A manual search of Google Scholar was also conducted on June 30, 2023, to identify additional publications. Finally, the database was updated on March 1, 2025.
Screening and selection
Two veterinary clinical researchers of small animals (K.N., D.S.) independently reviewed the titles and abstracts of the first 92 records during the initial screening. Studies involving clinical research on human patients, traumatic fractures, or in vivo/in vitro molecular analyses, among others, were excluded. Discrepancies were resolved through discussions until a consensus was reached. Subsequently, the researchers independently examined the titles and abstracts of all retrieved articles. In cases of disagreement, consensus on the full screening of articles was achieved through discussion. After removing duplicates, we reviewed 29 full-text documents.
For the second screening, both researchers independently evaluated the full-text articles for inclusion. Disagreements were again resolved through discussion to determine inclusion or exclusion. The inclusion criteria comprised bona fide case reports or case series documenting pathologic fractures in dogs. Eleven studies were excluded through the second screening from the review, with the main reason being that pathological fractures resulted from complications of local stereotactic radiotherapy.
Risk of bias assessment
The two researchers independently assessed the risk of bias for each evidence certainty domain in the studies included in the meta-analyses. The final database comprised 18 studies and 70 dogs, as summarized in the PRISMA flow diagram ( Fig. 1 ).
Meta-analysis
Among the 18 studies comprising 70 dogs, we analyzed all identified surgical interventions for pathological fractures. We collected data on study characteristics (author, year, and source of publication), patient characteristics (breed, diagnosis, and fracture location), intervention details (treatment type and implant used), adjuvant therapies (duration, dose, timing, and mode of delivery), functional prognosis, and survival time.
Studies were excluded from the meta-analysis if they contained missing or unclear critical information. The primary outcome measures were functional prognosis and survival time following fracture repair. The functional prognosis was defined as the number of days from fracture repair until the onset of lameness, as evaluated by orthopedic veterinarians. Survival time was defined as the number of days from diagnosis to natural death or euthanasia. Information on the date and cause of death or euthanasia was obtained through telephone interviews with referring veterinarians and medical record reviews.
A standardized data extraction form was developed, and both reviewers extracted data from the 18 eligible studies. The included studies for the meta-analysis were summarized in Supplementary Table 1 for reproducibility. The extracted data were compared, and discrepancies were resolved through discussion. The reviewers then entered the data into statistical software and independently verified accuracy through double-checking.
Statistical analysis
For all 70 dogs, the diagnosis, fracture location, treatment type, implant used for stabilization, and adjuvant therapy data were summarized using standard descriptive statistics. Survival time and functional prognosis were analyzed using the Kaplan–Meier method.
For the meta-analysis, statistical evaluation of the subgroup analysis comparing postoperative adjuvant chemotherapy (presence vs. absence) was conducted using the log-rank test. Differences were considered statistically significant at p < 0.05.
Statistical graphics, including pie charts and Kaplan–Meier curves, were generated to illustrate the descriptive analysis, survival time, and functional prognosis for each group. All statistical analyses were performed using EZR software ( Kanda, 2013 ), based on the R Project for Statistical Computing (R Foundation for Statistical Computing, Vienna, Austria).
Ethical approval
Not needed for this study.
Results
Patients and fracture characteristics
Seventy dogs met the inclusion criteria. Osteosarcoma was the most common cause of pathological fractures ( n = 55; 78.6%), followed by multiple myeloma ( n = 3; 4.3%), undifferentiated sarcoma ( n = 3; 4.3%), bone metastases from prostate carcinoma and transitional cell carcinoma ( n = 2; 2.9%), bone cyst ( n = 2; 2.9%), osteomyelitis ( n = 2; 2.9%), fibrosarcoma ( n = 1; 1.4%), discospondylitis ( n = 1; 1.4%), and avascular necrosis ( n = 1; 1.4%) ( Fig. 2A ).
Pathological fractures most commonly occurred in the appendicular skeleton, including the femur ( n = 18; 25.7%; classification: proximal, n = 8; diaphyseal, n = 5; distal, n = 5), humerus ( n = 16; 22.9%; classification: proximal, n = 9; diaphyseal, n = 1; distal, n = 6), radius ( n = 15; 21.4%; all distal), and tibia ( n = 11; 15.7%; all distal). Less frequently affected sites included the thoracic spine ( n = 2; 2.9%, vertebral body), lumbar spine ( n = 2; 2.9%, vertebral body), cervical spine ( n = 1; 1.4%, vertebral body), ulna ( n = 1; 1.4%, distal), metacarpus ( n = 1; 1.4%), and calcaneus ( n = 1; 1.4%) ( Fig. 2B ).
Among the breeds, Rottweilers ( n = 16), Greyhounds ( n = 6), mixed-breed dogs ( n = 5), German Shepherds ( n = 5), Golden Retrievers ( n = 4), and Labrador Retrievers ( n = 4) were most affected by pathological fractures.
Therapeutic interventions
The most common therapeutic intervention was surgical stabilization ( n = 40; 57.1%), followed by euthanasia ( n = 20; 28.6%), amputation ( n = 5; 7.1%), chemoradiotherapy ( n = 2; 2.9%), palliative care ( n = 1; 1.4%), and partial removal ( n = 1; 1.4%) ( Fig. 2C ). The surgical techniques used included plate stabilization ( n = 20; including arthrodesis, 28.6%), followed by interlocking nails ( n = 13; 18.6%), external fixation ( n = 4; 5.7%), and spinal fixation ( n = 3; 4.3%) ( Fig. 2D ). The mean follow-up duration was 302 days.
Functional prognosis and complications
The long-term postoperative follow-up of functional prognosis was available for 21 patients, with a median time to lameness occurrence of 163 days (95% confidence interval (CI): 130–510 days) ( Fig. 3A ). Subgroup analysis of implant types revealed no significant differences between plates and interlocking nails ( p = 0.415). Postoperative complications included local infections ( n = 4), local recurrence ( n = 3), implant fractures ( n = 2), and implant-induced fractures ( n = 1).
Survival analysis
For osteosarcoma cases, long-term follow-up was possible in 28 patients, with a median survival time of 292 days (95% CI: 163–518 days) ( Fig. 3B ). Of these, 14 received adjuvant therapy (radiation therapy with or without chemotherapy, including carboplatin, doxorubicin, and cisplatin), while the other 14 received no treatment ( n = 14) ( Fig. 3C ). Subgroup analysis showed no significant differences in survival between the adjuvant therapy and non-therapy groups ( p = 0.675) ( Fig. 3D ).
Discussion
Previous retrospective studies have reported that the median survival time for canine osteosarcoma is 4 to 6 months with amputation alone ( Mauldin et al. , 1988 ; Straw et al. , 1991 ) and approximately 12 months with amputation and chemotherapy ( Morello et al. , 2011 ). In terms of life expectancy, survival following pathological fracture repair is shorter than that observed with amputation and chemotherapy. These findings suggest that repair surgery for pathological fractures, particularly in load-bearing bones of the extremities, may serve as a palliative treatment option for owners who decline amputation, as well as for dogs with progressive diseases, including metastatic lesions. Additionally, repair surgery may be considered in cases of malignant progression of localized disease, which can lead to poor pain control. In such cases, repair surgery for pathological fractures can be considered as a surgical option.
In the present study, multiple patients were euthanized after experiencing pathological fractures. These findings suggest that palliative treatment for pathological fractures may be beneficial, as it allows for moderate gait function and offers a relatively promising survival time. The absence of significant differences between cohorts with or without adjuvant therapy may be attributed to type II error.
A discrepancy was observed between the median time to lameness and the median survival time. This indicates that pain management is essential for maintaining quality of life during the months when limb function is impaired. Pain control strategies may include the use of nonsteroidal anti-inflammatory drugs, opioids, bisphosphonates, and novel analgesics. In this regard, we are currently developing a new drug candidate that targets osteoclast precursor cell fusion to suppress abnormal bone remodeling (unpublished data). This therapy may improve the prognosis of canine patients.
Regarding complications, the risk of infection is negligible in tumor-associated orthopedic surgeries, such as limb-sparing procedures, as reported in previous studies ( Morello et al. , 2001 ; Morello et al. , 2003 ; Ehrhart, 2005 ; Liptak et al. , 2006 ; Hodge et al. , 2011 ). The use of currently available silver-coated implants—featuring an ultrathin antimicrobial coating with pure elemental silver particles embedded in a biocompatible plasma polymer—may be necessary to mitigate infection-related complications in future studies ( Azab et al. , 2016 ; Engel et al. , 2024 ).
The potential for bone healing following surgical stabilization of pathological fractures remains a subject of ongoing debate. Hayes et al reported a case of complete bone regeneration after plate fixation of a pathological femoral fracture caused by sarcoma ( Hayes et al. , 2020 ). Progressive bone healing in such cases is likely influenced by a complex interplay of anatomical, mechanical, and biological factors, including regional variations in vascular supply ( Shah et al. , 2025a ; Shah et al. , 2025b ). To preserve periosteal and intraosseous vascularity, we advocate the use of minimally invasive osteosynthesis with interlocking nailing or minimally invasive plate osteosynthesis.
This study has some limitations. Due to the nature of the meta-analysis, follow-up data were limited. In addition to our cases, we incorporated clinical information from published case reports and case series, some of which lacked follow-up data, although a high percentage of our cases included follow-up data. Furthermore, because case reports and case series were integrated, clinical and statistical heterogeneity were not assessed. Clinical heterogeneity arises from variations in patient backgrounds, diagnostic tests, and treatments across studies. In contrast, statistical heterogeneity reflects the degree to which it is reasonable to assume that the effect sizes from all studies represent the same population effects. Additionally, reporting bias may have influenced the findings, as studies with positive results are more likely to be published than those with negative results ( Stern and Simes, 1997 ).
In conclusion, this study demonstrates the clinical efficacy of repair in pathological fractures, highlighting the functional prognosis and survival time following the procedure. Reduction and stabilization surgery for pathological fractures may serve as a third treatment option in addition to limb-sparing surgery and amputation.
Acknowledgments
We thank Dr Daniel A Degner, DVM, Diplomate ACVS (small animal), Animal Surgical Center of Michigan, 5045 Miller Rd, Flint, MI 48507, USA for the data presentation.
Funding
This research received no specific grant.
Authors’ contributions
Conceptualization: K.N.; Data curation: K.N., D.S.; Formal analysis: K.N., D.S.; Investigation: K.N., D.S.; Methodology: K.N.; Visualization: K.N., D.S.; Writing-original draft: K.N.; Writing - review & editing: D.S., M.A., K.B.
Conflict of interest
The authors declare no conflict of interest.
Data availability
The datasets used and analyzed in the current study are available from the corresponding author upon reasonable request.
References
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Supplementary Table 1.
The 18 studies in the table were included in this meta-analysis.
| Author, Journal, volume(issue), page, and published year |
| Banks T et al. , Aust Vet Practit, 33(2), 98–102, 2003. |
| Bhandal J et al. , Vet Surg, 40(4), 423–430, 2011. |
| Boston SE et al. , Can Vet J, 52(6), 650–655, 2011. |
| Boston SE et al. , Vet Surg, 40(4), 431–437, 2011. |
| Boston SE et al. , Vet Surg, 46(6), 829–837, 2017. |
| Cabassu J et al. , Vet Comp Orthop Traumatol, 20(3), 227–230, 2006. |
| Chauvet AE et al. , Vet Surg, 28(6), 480–448, 1999. |
| Choate CJ et al. , Vet Comp Orthop Traumatol, 24(5), 398–401, 2011. |
| Cooley DM et al. , J Vet Intern Med, 12(4), 288–293, 1998. |
| Covey JL et al. , Vet Surg, 43(2), 174–181, 2014. |
| Emmerson TD et al. , J Small Anim Pract, 40(5), 233–235, 1999. |
| Emmerson TD et al. , Vet Rec, 141(21), 551–552, 1997. |
| Hayes MA et al. , Aust Vet J, 98(3), 84–89, 2020. |
| Heidner GL et al. , J Vet Interm Med, 5(6), 313–316, 1991. |
| Melilli A et al. , Open Vet J, 9(4), 313–316, 2019. |
| Montgomery RD et al. , J Am Vet Med Assoc, 203(11), 1535–1536, 1993. |
| Pernell RT et al. , J Am Vet Med Assoc, 201(12), 1897–1899, 1992. |
| Rene T et al. , J Am Vet Med Assoc, 194(2), 285–286, 1989. |