Meta-analyses of randomised trials had suggested androgen receptor pathway inhibitors raise fracture risk, which has made clinicians hesitate over intensification in men with bone metastases. This secondary analysis used the STAMPEDE platform: 3,893 patients randomised between November 2011 and March 2016 to standard of care, standard of care plus abiraterone with prednisolone, or in a later comparison that combination plus enzalutamide, with 3,102 English patients linked to Hospital Episode Statistics. Fracture-related hospitalisation was identified by a prespecified coding framework, analysed with competing-risk models treating death as the competing event.
In metastatic disease, five-year fracture-related hospitalisation was lower with abiraterone added: 22% versus 30% (subdistribution hazard ratio 0.77, 95% CI 0.59 to 0.99, P = .04), and 28% versus 38% with abiraterone plus enzalutamide (0.69, 0.54 to 0.88, P = .002). There was no significant difference in non-metastatic disease.
The most plausible explanation is that better control of metastatic bone disease prevents more fractures than the drug's effect on bone density causes. That is worth saying out loud, because the fracture worry has been a genuine reason for undertreatment. The caveats are honest ones from the authors: non-hospitalised fractures were not counted, baseline bone density was not assessed, and bone-protective therapy use over time was not captured. None of that changes the direction. Continue calcium, vitamin D and a bone-protective agent where indicated — this result does not make those unnecessary.
- Do not withhold abiraterone intensification in metastatic disease over fracture concern.
- Continue calcium, vitamin D and bone-protective therapy where indicated; this study did not test stopping them.
- Assess falls risk and bone health at baseline — the analysis could not, and you can.
- The benefit was confined to metastatic disease; no difference appeared in non-metastatic patients.
- Only hospitalised fractures were counted, so the total fracture burden in both arms is understated.
The statistics, in plain English
A subdistribution hazard ratio accounts for death competing with fracture, which matters enormously here: a treatment that keeps men alive longer gives them more time to fracture, and ignoring that would make an effective drug look harmful. The interval 0.59 to 0.99 only just excludes 1.0, so the metastatic result is real but not far from the boundary. Routinely coded hospital data captures serious fractures reliably and outpatient ones not at all.
Read the rest in the app
You have read your two free briefings this month. The app carries all 27 specialties, every morning, free — and this finding is waiting in it.
Scan to keep reading on your phone. No account needed to start.
Tomorrow morning, before your first patient
One edition a day for urology, written by the desk, every claim tied to its paper. Six minutes.
Get the app — free