Androgen deprivation therapy, osteoporosis in prostate cancer: An evaluation of risk factors and patient awareness

Abstract Introduction: Androgen deprivation therapy (ADT) decreases bone mineral density and increases osteoporotic fracture (OsteoFx) risk. Hypothesis: To assess OsteoFx clinical risk factors (CRF) most predictive of future OsteoFx among men with prostate cancer on ADT. Methods: 4370 electronic medical records were reviewed of adult men with prostate cancer on cancer therapy +/- anti-osteoporosis therapy (Anti-OsteoRx) from 2011–2019. Cancer therapy included ADT (anti-androgens, GnRH agonists & antagonists, orchiectomy) and supplemental cancer therapy (SupplRx) (prostatectomy, brachytherapy, radiation, immunotherapy, and chemotherapy). Anti-OsteoRx included bisphosphonates, denosumab, and parathyroid hormone analogs. Patients with other cancers within 5 years of initial visit, metastasis, and traumatic fractures were excluded. Retrospective analysis was done to determine baseline characteristics, type and duration of ADT, Anti-OsteoRx, SupplRx, and osteoporosis CRF. Results: 615 men on ADT +/- SupplRx +/- Anti-OsteoRx were included in the study. 10.08% had OsteoFx irrespective of SupplRx or Anti-OsteoRx. Comparing the OsteoFx group to the non-fracture group, the following CRF were found to be statistically significant (p <0.05): age at prostate cancer diagnosis (75.10 +/- 11.80 vs 71.59 +/- 9.80 y), diabetes mellitus (DM) (33.9 vs 19%), pre-existing comorbidities affecting bone (PreCo) (41.9 vs 24.8%), steroid use (11.3 vs 4.0%), and anti-convulsant and proton-pump inhibitor (med) use (45.2 vs 26.8%). 9.89% of 374 men on ADT only without (wo) Anti-OsteoRx fractured. Statistically significant CRF for OsteoFx were age (76.86 +/- 10.55 vs 73.02 +/- 10.06 y), DM (40.5 vs 19.6%), PreCo (45.9 vs. 26.4%), and med use (48.6 vs. 25.5%). In the following subgroups there were no statistically significant difference in CRF:•7.64% of 170 men on ADT + SupplRx wo Anti-OsteoRx •19.23% of 52 men on ADT only + Anti-OsteoRx •10.52% of 19 men on ADT + SupplRx + Anti-OsteoRx To increase statistical power, patients on ADT +/- SupplRx were assessed:•Among 71 men on ADT +/- SupplRx + Anti-OsteoRx, there were no statistically significant differences in CRF•Among the 544 men on ADT +/- SupplRx wo Anti-OsteoRx, significant CRF for OsteoFx were age (75.16 + 11.70 vs 71.37 + 9.85 y), DM (38 vs 19.4%), PreCo (38 vs 24.1%), steroid use (12 vs 3.8%), and med use (48 vs 24.3%) Discussion: Men with prostate cancer requiring ADT have a higher incidence of osteoporosis defined by DXA prior to initiating ADT compared to age-matched cohorts (Hussain et al). Our study revealed ADT with CRF is associated with OsteoFx irrespective of SupplRx or Anti-OsteoRx. Limitations include inability to evaluate efficacy of Anti-OsteoRx due to insufficient power. Conclusion: OsteoFx risk assessment utilizing CRF, FRAX, DXA with timely intervention may prevent OsteoFx in these high-risk patients.

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Identifying men at greatest risk of weight gain from androgen deprivation therapy.

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.4_suppl.80 ◽

2014 ◽

Vol 32 (4_suppl) ◽

pp. 80-80

Author(s):

Daniel Martin Seible ◽

Xiangmei Gu ◽

Andrew Hyatt ◽

Clair Beard ◽

Jason Alexander Efstathiou ◽

...

Keyword(s):

Prostate Cancer ◽

Risk Factors ◽

Weight Gain ◽

Androgen Deprivation Therapy ◽

Weight Change ◽

Androgen Deprivation ◽

Baseline Risk ◽

Diabetic Patients ◽

Diabetic Status ◽

One Year

80 Background: Androgen deprivation therapy (ADT) is a mainstay of prostate cancer therapy. Weight gain is among the adverse metabolic changes associated with ADT, and may contribute to cardiovascular comorbidity. A better understanding of the risk factors for weight gain on ADT is important for optimal management of ADT-associated morbidity. Methods: A retrospective review assessed weight change among 118 men with nonmetastatic prostate cancer treated with ADT. The primary endpoint was weight change at one year from ADT initiation, with the secondary aim to stratify risk of weight gain by baseline patient characteristics. Statistical analyses were performed using two-tailed t-tests and linear regression. Results: Men in our cohort exhibited a significant increase in weight (p=0.0005) in the one year following ADT initiation. Three risk factors for weight gain on ADT were identified: younger than age 65 (5.98 pounds gained, p=0.001 vs. 1.63 pounds, p= 0.09 for age 65+), body mass index (BMI) less than 30 (4.36 pounds gained, p=0.00002 vs. 0.22 pounds, p=0.87 for BMI 30+), and non-diabetic status (3.43 pounds gained, p=0.0003 vs. 0.57 pounds, p=0.74 for diabetics). An aggregate risk scoring system was contrived to allow for weight change prediction by total number of risk factors present: scores of 0, 1, 2, and 3 risk factors corresponded to weight changes of -2.42 (p=0.43), +0.9 (p=0.56), +2.9 (p=0.01) and +8.3 pounds (p= 0.0001) respectively. Weight gain increased significantly with increasing risk score (p-trend= 0.0005), decreasing baseline age (p-trend= 0.004) and decreasing baseline BMI (p-trend= 0.01). Conclusions: Younger than age 65, BMI less than 30, and non-diabetic status were each significantly associated with weight gain one year after starting ADT. Increasing weight gain was strongly associated with increasing number of baseline risk factors. Although metabolic consequences were previously considered most significant for patients with preexisting comorbidity, these data suggest younger, slimmer, and non-diabetic patients may be at higher risk for gaining weight on ADT. As these three categories of men generally have higher endogenous testosterone (T) levels prior to ADT compared to older, obese, and diabetic men, the magnitude of T decline following ADT might explain these findings.

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