Low Testosterone Linked to Fracture Risk in Older Men

by Zalman S. Agus, MD
SYDNEY, Australia, Jan. 15 -- Men older than 60 with low blood testosterone levels may have a higher risk for hip and non-vertebral fractures, researchers here reported.
The fracture rate was 30% higher for non-vertebral fractures for such men and almost 90% higher for hip fractures, Christian Meier, M.D., of the University of Sydney, and colleagues, reported in the Jan. 14 issue of the Archives of Internal Medicine.
Yet the investigators cautioned that if androgen therapy for the prevention of fragility fracture in healthy men is justified on efficacy and safety grounds, it should be so for only those with the most severe testosterone deficiency.
Androgens affect body composition, the researchers pointed out, and may result in a decrease in muscle mass, thereby impairing balance.
The investigators, noting that a third of all osteoporotic fractures occur in men, studied 609 community-dwelling men older than 60 (mean age 72.6) from January 1989 through December 2005, with a median follow-up of 5.8 years (up to 13 years).
Clinical risk factors, including bone mineral density and lifestyle factors, were assessed at baseline. Serum testosterone and estradiol levels were measured by tandem mass spectrometry.
During follow-up, 113 men had at least one low-trauma fracture, and 25 had multiple incident fractures. A total of 149 fractures were reported, including 55 vertebral, 27 hip, 28 rib, six wrist, and 16 upper- and 17 lower-extremity fractures.
A total of 79.3% of all new fractures occurred in men ages 70 or older, in whom the rate was 4.7% (95% CI: 4.6% to 4.8%), representing a 2.27-fold higher rate than among men younger than 70.
Analyzing testosterone levels, the researchers found that the risk of fracture was significantly increased in men with reduced testosterone levels (hazard ratio: 1.33, 95% CI: 1.09 to 1.62).
After adjustment for sex hormone-binding globulin, serum testosterone (HR: 1.48, 95% CI: 1.22 to 1.78) and serum estradiol levels (HR: 1.21, 95% CI: 1.00 to 1.47) were associated with overall fracture risk.
However, following further adjustment for major fracture risk factors (age, weight, bone mineral density, fracture history, smoking status, calcium intake, and sex hormone-binding globulin), only lower testosterone was still associated with increased risk of fracture, particularly with hip (HR: 1.88, 95% CI: 1.24 to 2.82) and non-vertebral fractures (HR: 1.32, 95% CI: 1.03 to 1.68).
After risk-factor adjustment, the risk of any fracture increased between 30% and 40% for each standard deviation decrease in serum testosterone levels, the researchers reported.
On the other hand, circulating testosterone was not significantly associated with the risk of vertebral fractures, the researchers said. This, they added, might reflect a limitation of the diagnostic method for identifying asymptomatic vertebral deformities.
Lower bone mineral density and accelerated bone resorption have been shown to be independent determinants of fractures risk in elderly men, the researchers wrote. However, serum testosterone levels and bone mineral density were independently associated with fracture risk in this study. So changes in bone mineral density only partly explain the fracture risk in this study.
Clearly, the researchers said, these findings cannot be interpreted as an indication of any causal relationship between circulating testosterone and fracture risk. Also, the homogeneity of ethnicity in this study suggests that its results cannot be generalized to other populations.
Furthermore, they said, as in any long-term study, serum samples were stored in the freezer for up to 13 years, although these samples are still likely to be stable, the researchers noted.
Finally, they said serum was not collected consistently in the morning, which could introduce random measurement error.
The researchers concluded that while low levels of estradiol and testosterone were associated with an increased fracture risk in these men, only testosterone was independent of other established risk fractures.
"While testosterone may affect fracture risk via skeletal and non-skeletal mechanisms, the present findings suggest that measurement of serum testosterone provides additional clinical information for the assessment of fracture risk in elderly men."
This study was supported by the National Health and Medical Research Council of Australia and the ARUP Institute for Clinical and Experimental Pathology.
Dr. Meier is the recipient of a medical research fellowship from the Swiss National Science Foundation and a research fellowship from the Margarete und Walter Lichtenstein Stiftung der Universität Basel.
No financial conflicts were reported.
Primary source: Archives of Internal MedicineSource reference:Meier C, et al "Endogenous sex hormones and incident fracture risk in older men: the Dubbo Osteoporosis Epidemiology Study" Arch Intern Med 2008; 168: 47-54.