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Association between 5-alpha reductase inhibition and risk of hip fracture
Steven J Jacobsen1, T Craig Cheetham, Reina Haque
1Department of Research and Evaluation, Kaiser Permanente Southern California, 100 S Los Robles Ave, Second Floor, Pasadena, CA 91101, USA. steven.j.jacobsen@kp.org
Context:
For more than 15 years, 5-alpha reductase inhibitors, which block the conversion of testosterone to dihydrotestosterone, have been used in the treatment of benign prostatic hyperplasia (BPH). Short-term studies show no effects of these agents on bone metabolism,but long-term data are not available.
Objective:
To assess the association between use of 5-alpha reductase inhibitors (eg, finasteride) for BPH and occurrence of hip fracture.
Design, Setting, And Patients:
Population-based case-control study using data from Kaiser Permanente Southern California, a managed care organization with more than 3 million members. Case patients included 7076 men 45 years and older with incident hip fracture from 1997-2006. Control patients were 7076 men without incident hip fracture, optimally matched at a 1:1 ratio to case patients on age and medical center. Electronic information on pharmaceutical use was used to identify use of finasteride from 1991 forward.
Results:
Overall, 2547 (36%) and 2488 (35%) case and control patients, respectively, had a diagnosis of BPH (P = .30), and 109 (1.5%) and 141 (2.0%) of case and control patients, respectively, had been exposed to finasteride prior to the index date (matched odds ratio, 0.77; 95% confidence interval, 0.59-1.00; P = .04). There was no suggestion of a dose-response relationship between exposure to 5-alpha reductase inhibitors when the exposure was stratified into tertiles of total exposure (P = .12). By contrast, there was a slightly higher prevalence of alpha-blocker use in case vs control patients (32% vs 30%, respectively; P = .04).
Conclusions:
Exposure to 5-alpha reductase inhibitors was not associated with increased risk of hip fracture. The reduction in risk observed with exposure to 5-alpha reductase inhibitors and the modest increase in risk associated with exposure to alpha-blockers require replication and warrant further investigation.
Insights
Long-term use of 5-alpha reductase inhibitors for benign prostatic hyperplasia (BPH) was not linked to a higher hip fracture risk. Further studies are needed to confirm these findings and investigate alpha-blocker effects.
Area of Science:
- Urology
- Geriatrics
- Pharmacology
Background:
- 5-alpha reductase inhibitors are widely used for benign prostatic hyperplasia (BPH).
- Long-term effects on bone metabolism and fracture risk remain unclear.
- Previous short-term studies showed no impact on bone metabolism.
Purpose of the Study:
- To investigate the association between 5-alpha reductase inhibitor use for BPH and hip fracture incidence.
- To evaluate long-term safety data regarding bone health in men treated for BPH.
Main Methods:
- Population-based case-control study utilizing data from Kaiser Permanente Southern California.
- Inclusion of 7076 men aged 45+ with incident hip fractures (cases) and 7076 matched controls without fractures.
- Electronic health records were used to identify finasteride exposure from 1991 onwards.
Main Results:
- No significant association was found between 5-alpha reductase inhibitor exposure and increased hip fracture risk (OR, 0.77; P = .04).
- No dose-response relationship was observed with increasing tertiles of exposure.
- A slight increase in alpha-blocker use was noted in hip fracture cases compared to controls (P = .04).
Conclusions:
- Exposure to 5-alpha reductase inhibitors does not appear to increase hip fracture risk in men with BPH.
- The observed risk reduction with 5-alpha reductase inhibitors and increased risk with alpha-blockers warrant further investigation.
- Replication of these findings is recommended to confirm the observed associations.
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