# Metastatic renal cell carcinoma: risk of rapid progression to pathological fractures and factors influencing post-treatment survival – a Swedish Nationwide cohort study

**Authors:** Josefin Åkerstedt, Tova Åström, David Wennergren, Johan Wänman

PMC · DOI: 10.1016/j.jbo.2026.100749 · 2026-02-12

## TL;DR

This study finds that aggressive kidney cancer is linked to faster bone fractures and poor survival, emphasizing the need for early risk assessment.

## Contribution

The study identifies Fuhrman grade and AJCC stage as predictors of rapid fracture progression in RCC patients.

## Key findings

- Higher Fuhrman grade and AJCC stage correlate with quicker onset of pathological fractures in RCC.
- Median survival after a pathological fracture is only 8 months.
- Femur and humerus are the most common fracture sites in RCC patients.

## Abstract

•Pathological fractures in RCC signal poor prognosis, with a median post-fracture survival of 8 months.•Higher Fuhrman grade and AJCC stage are linked to quicker onset of pathological fractures, indicating more aggressive disease progression.•Femur and humerus were the most frequent fracture sites, highlighting common skeletal targets of RCC metastases.

Pathological fractures in RCC signal poor prognosis, with a median post-fracture survival of 8 months.

Higher Fuhrman grade and AJCC stage are linked to quicker onset of pathological fractures, indicating more aggressive disease progression.

Femur and humerus were the most frequent fracture sites, highlighting common skeletal targets of RCC metastases.

Renal Cell Carcinoma (RCC) represents about 2% of all cancers in Sweden. While RCC is known for its potential to metastasize to the skeleton, few studies have examined the risk factors for pathological fractures and their impact on survival. The Fuhrman grade and AJCC staging systems are commonly used to assess disease aggressiveness, but their relationship to fracture risk and post-fracture outcomes remains unclear.

This study cross-linked data from the Swedish Fracture Register (SFR) and the Swedish Renal Cancer Register (SNR) to identify RCC patients with pathological fractures. Fracture characteristics, cancer staging (Fuhrman, TNM, AJCC), and histological subtypes were analysed. Survival was estimated using the Kaplan-Meier method.

One hundred four RCC patients (72 men, 32 women) with pathological fractures were included, with clear cell carcinoma being most common (n = 93). Fuhrman grade 3 (n = 34) and fractures in the femur (n = 44) and humerus (n = 37) predominated. Median time from cancer diagnosis to fracture was 11 months. Higher Fuhrman grade, TNM, and AJCC stages were significantly associated with shorter time to fracture (p < 0.001). The median overall survival was 31 months and was related to Fuhrman grade (p = 0.013) and AJCC stage (p < 0.001). The median survival post-fracture was 8 months, with no significant association with cancer grade or stage.

Advanced Fuhrman grade and AJCC stage predict faster progression to pathological fractures in RCC. Given the poor prognosis after pathological fractures, early risk stratification and individualized treatment approaches are essential to improve outcomes.

## Linked entities

- **Diseases:** Renal Cell Carcinoma (MONDO:0005086), pathological fractures (MONDO:0043606)

## Full-text entities

- **Genes:** TENM1 (teneurin transmembrane protein 1) [NCBI Gene 10178] {aka ODZ1, ODZ3, TEN-M1, TEN1, TNM, TNM1}, TNFSF11 (TNF superfamily member 11) [NCBI Gene 8600] {aka CD254, ODF, OPGL, OPTB2, RANKL, TNLG6B}
- **Diseases:** Metastatic renal cell carcinoma (MESH:C538445), Pathological fractures (MESH:D005598), pelvic fractures (MESH:D034161), femoral fractures (MESH:D005264), RCC (MESH:D002292), skeletal instability (MESH:D043171), Renal Cancer (MESH:D007680), spinal lesions (MESH:D013122), hip fractures (MESH:D006620), Fracture (MESH:D050723), pain (MESH:D010146), Fractures of the radius and ulna (MESH:D000092503), fractures of the humeral (MESH:D006810), Bone metastases (MESH:D009362), spinal fractures (MESH:D016103), skeletal disease (MESH:D004194), bone disease (MESH:D001847), vertebral fractures (MESH:C535781), Cancer (MESH:D009369)
- **Chemicals:** denosumab (MESH:D000069448)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12924727/full.md

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Source: https://tomesphere.com/paper/PMC12924727