CONCORD, New South Wales, Australia—Men >60 years with serum testosterone levels <294ng/dL are more than twice as likely as men with higher testosterone to suffer a nontraumatic hip fracture within the next 5 years, according to the Dubbo Osteoporosis Epidemiology Study reported by Christian Meier, MD, et al in Archives of Internal Medicine.¹

"This is a remarkable study," Abraham Morgentaler, MD, told Musculoskeletal Report. "We have known that there was some relationship between testosterone and bone density because if men have low testosterone and we raise it, bone density increases. Similarly, men with prostate cancer treated with drugs that lower testosterone levels also have decreases in bone mineral density (BMD). The missing piece was data linking decreases in BMD to an increase in fracture. This paper puts it together." Dr. Morgentaler is associate clinical professor of surgery at Harvard Medical School and director of Men's Health Boston in Massachusetts.

Very low testosterone doubles fracture risk

Meier et al prospectively examined the relationship between serum testosterone and estradiol levels and the incidence of low-trauma fracture over a median 5.8 years of follow-up in 609 community-dwelling men >60 years. Baseline assessment included BMD, calcium intake, and lifestyle factors such as smoking.

During follow-up, 133 men had at least 1 low-trauma fracture and the incidence of new fractures was 3.4 per 100 person-years. The incidence of new fractures was 2.7-fold higher in men >70 years than in those ages 60 to 70.

"In a multivariate analysis with all known risk factors of fracture being considered simultaneously, baseline serum testosterone, SHBG, age, femoral neck bone mineral density, weight, and calcium intake were significantly and independently associated with any low-trauma fracture," the authors wrote.

Risk of fracture increased 1.37-fold for each standard deviation decrease in serum testosterone. What's more, even after adjusting for risk factors, fracture risk increased between 30% and 40% for each 1-standard deviation drop in serum testosterone. The hazard was greatest for men with serum testosterone in the lowest quartile (<294 ng/dL) compared with those in the normal range. The investigators comment, "The present prospective study shows that men with lower serum testosterone levels had increased risk of osteoporotic fracture, and this effect was independent of established risk factors, such as age and BMD. In contrast, there was no significant association between serum E2 levels and fracture in the presence of BMD and age."

But this is not an argument for testosterone replacement—yet

Dr. Morgentaler noted that the limit of <294 ng/dL used in the Meier analysis is close to the FDA's 250 ng/dL definition for hypogonadism in guidance documents on testosterone replacement therapy. "The paper identifies a population of men at increased risk for nontraumatic fracture. It makes a strong case for monitoring testosterone levels in older men, whether they are symptomatic or not. Since it was not an intervention study, it provides no guidance on the use of testosterone replacement in such men, but it seems clear that low testosterone is an indication to send the patient for bone density testing," Dr. Morgentaler ended.

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