Results
Study Population
Baseline characteristics of the 961 men diagnosed with non-metastatic prostate cancer who provided patient-reported outcomes 15 years following diagnosis are included in Table 1. In this population, 684 did not report ADT use, 120 men reported ≤1 year of ADT and 157 reported >1 year of ADT exposure (Table 1). Rates of survey completion were similar among ADT exposure groups, with 86% of no ADT and 85% of the short-term and prolonged ADT groups returning surveys at all time points. There were small but significant differences between participants in different treatment groups in terms of age at diagnosis, race and education level. A greater percentage of men reporting ADT use had high-grade disease (Gleason scores of 8–10), were treated with radiation rather than prostatectomy and had slightly higher comorbidity scores than men not reporting ADT.
Study Outcome
The risk of self-reported fracture was 10% in the entire cohort, 9.5% in untreated men, 9% in men reporting treatment with short-term ADT (≤1 year) and 15% among men reporting treatment with prolonged ADT (>1 year) (P=0.18). The overall reported frequency of BMD testing in the cohort was 27%, with 28% of men reporting short-term ADT exposure, and 49% of men reporting prolonged ADT exposure (P<0.001). On univariable analysis, men reporting short-term ADT exposure (≤1 year) did not have an increased probability of reporting fracture, BMD testing or bone medication use compared with men not reporting treatment with ADT (Table 2). Men reporting treatment with prolonged ADT had increased odds of reporting fracture, BMD testing and bone medication use compared with men not reporting treatment with ADT (Table 2).
Bone medication use varied by duration of exposure to ADT and medication type. Among men reporting prolonged ADT, 50.3% reported treatment with bone medications, compared with 24.7% and 31.7% of men not reporting treatment with ADT and men reporting short-term ADT treatment, respectively (P<0.001). Of men reporting bone medication use, 94% reported calcium or vitamin D use and 6% reported bisphosphonate use (including intravenous and oral formulations) (P<0.001).
We used weighted logistic regression to assess the association between reported ADT treatment duration and reported development of fracture at 15 years accounting for patient-level covariates (Table 3). Men reporting short-term use of ADT did not have increased odds of fracture or bone medication use compared with men reporting no treatment with ADT, although there was a trend toward increased odds of fracture in this group when compared with men who did not receive any ADT (P=0.08). Men reporting treatment with prolonged ADT had significantly increased risk of fracture (OR 2.5; 95% confidence interval (CI): 1.1–5.7) and bone medication use (OR 4.3; 95% CI 2.3–8.0) compared with men who denied treatment with ADT. BMD testing was more likely among men reporting treatment with both short-term and prolonged ADT than among men not reporting ADT treatment (OR 2.6, 95% CI: 1.2–5.8 for short-term ADT; OR 5.9, 95% CI: 3.0–12 for prolonged ADT). A sensitivity analysis performing the same analysis while excluding patients who experienced fracture yielded virtually identical results (data not shown).
Age, marital status, comorbidity and Gleason grade were not associated with risk of fracture at 15 years, but African Americans had a lower risk of fracture compared with Caucasians (OR 0.15; 95% CI: 0.04–0.60). Participants were more likely to report BMD testing as they aged (OR 1.5 per 10 years, P=0.04), but less likely to report testing with increasing comorbid illness, with adjusted ORs of 0.18 (P<0.001) for Charlson score 2 and 0.24 (P=0.009) for Charlson score ≥3, using persons with a score of 0 as the reference group (data not shown). Compared with participants not exposed to ADT, those with long-term ADT use had significantly increased likelihood of bone medication use with an adjusted OR of 4.3 (P<0.001). There were no significant associations between bone medication use and any other independent variables including age, marital status, comorbidity, race or Gleason grade (data not shown).