What is the role of testosterone replacement therapy (TRT) in patients with hip fractures, particularly those with hypogonadism?

Testosterone Replacement Therapy in Hip Fracture Patients with Hypogonadism

Testosterone replacement therapy (TRT) should be used as an adjunctive treatment alongside established anti-osteoporosis medications in hypogonadal men with hip fractures, as TRT alone is insufficient to adequately reduce fracture risk despite improving bone mineral density (BMD). 1, 2, 3

Diagnostic Assessment

• Serum free or total testosterone levels should be measured as part of the investigatory work-up for osteoporosis in men with hip fracture 1, 2
• Hypogonadism is a significant risk factor for osteoporosis and fractures, particularly in men receiving androgen deprivation therapy for prostate cancer 1
• Men with androgen deprivation therapy have a dose-dependent increased risk for osteoporotic fracture, with relative risks of 1.45 and 1.54 for those receiving 9+ doses of gonadotropin-releasing hormone agonist or orchiectomy, respectively 1

Treatment Recommendations

• Oral bisphosphonates (alendronate or risedronate) should be prescribed as first-line therapy for hypogonadal men with hip fracture 1, 2, 4
• Intravenous bisphosphonates or denosumab should be considered as second-line therapy if oral bisphosphonates are not tolerated or contraindicated 1, 4
• TRT should be initiated concurrently in men with confirmed testosterone deficiency, particularly when symptoms of testosterone deficiency are present 2, 3
• The T-trial demonstrated a significant 7% increase in lumbar spine trabecular volumetric BMD after just one year of TRT 1, 3
• Bone micro-architectural benefits occur with TRT, including significant 3% increases in cortical volumetric BMD and improvements in areal BMD at both the lumbar spine and hip after two years of treatment 1, 3

Limitations of TRT for Fracture Prevention

• Despite improvements in BMD with TRT, there is limited data on its effect on actual fracture incidence in hypogonadal men 1, 3
• Testosterone therapy alone is insufficient to adequately reduce fracture risk in men with osteoporosis and hypogonadism 1, 2, 3
• In a systematic review and meta-analysis of testosterone therapy, benefit was only observed in lumbar spine BMD and only in a hypogonadal population 1

Supplementary Measures

• Ensure adequate calcium intake (1,000-1,200 mg daily) and vitamin D supplementation (800-1,000 IU daily) 2, 4
• Regular weight-bearing exercise and resistance training should be recommended to maintain BMD and reduce fall risk 2, 4
• Counsel patients to avoid smoking and limit alcohol consumption, as alcohol use of 3-4 drinks per day is associated with a relative risk of about 2.0 for osteoporotic fractures 1, 2

Monitoring

• Measure bone turnover markers at baseline and at 3 months to monitor treatment response and adherence to therapy 1, 2, 4
• Repeat BMD measurement approximately 2 years after initiating treatment 1, 2, 3
• Monitor testosterone levels to ensure they remain in the therapeutic range 2, 3

Clinical Considerations

• The decision to use TRT should be made based on a holistic assessment considering bone health alongside cardiometabolic and sexual function, ideally in consultation with endocrinology expertise 1, 3
• Poor adherence is a significant issue with oral bisphosphonates, with up to 64% of men being non-adherent by 12 months 4
• The full effect of testosterone on BMD may take up to 24 months to manifest 5