Testosterone replacement enhances bone remodeling in type 2 diabetes
Men with type 2 diabetes and suboptimal free testosterone levels experienced an increase in osteoblastic activity with a concomitant increase in bone turnover when assigned to 22 weeks of biweekly intramuscular testosterone injections when compared with similar men who received placebo, according to findings published in the Journal of the Endocrine Society.
In a secondary analysis of a randomized controlled trial, Husam Ghanim, PhD, of the division of endocrinology, diabetes and metabolism at the State University of New York at Buffalo, and colleagues analyzed data from 94 men with type 2 diabetes, including 50 men with normal free testosterone levels (mean age, 52 years; mean BMI, 34 kg/m²; mean free testosterone, 7.6 ng/dL) and 44 men with subnormal free testosterone concentrations (mean age, 55 years; mean BMI, 39.8 kg/m²; mean free testosterone, 4.4 ng/dL). Researchers randomly assigned men with subnormal free testosterone concentrations to intramuscular injections of testosterone or placebo every 2 weeks for 22 weeks. All men underwent DXA scans at baseline and at 23 weeks.
Researchers found that men with subnormal free testosterone had a similar bone mineral density vs. men with normal free testosterone. However, bone strength indices were lower in men with subnormal free testosterone.
Researchers found that BMD was related to free estradiol concentrations (P = .004 at hip), whereas bone strength was related to free testosterone concentrations (P < .001). Men assigned to testosterone replacement experienced an increase in osteocalcin concentration (mean change, 3.52; 95% CI, 0.45-6.59). C-terminal telopeptide (CTX) concentrations also increased at 15 weeks before reverting to baseline levels by 22 weeks, according to researchers. There were no changes in other bone turnover markers or BMD.
“Our data show clearly that testosterone replacement induced a twofold increase in plasma concentrations of osteocalcin, a secretory product of the osteoblast and an indicator of osteoblastic activity in the bone,” the researchers wrote. “This increase was observed at 15 weeks and was maintained at 23 weeks at the end of the study. Contrary to our hypothesis, there was also a transient increase in plasma concentrations of CTX, an indicator of increased bone breakdown. The nature of bone remodeling necessitates that an effect on either bone formation or bone breakdown is reciprocated by a compensatory change in the other.”
The researchers noted that the study duration was too short, and likely too underpowered, to evaluate changes in BMD or bone strength parameters, and baseline comparisons of bone turnover markers with sex hormones were hampered by the small number of men and large variation in bone turnover markers.
“It should also be specified that bone strength indices are currently not validated for clinical use and their precision needs to be derived in future studies,” the researchers wrote. – by Regina Schaffer
Disclosures: One of the study authors reports he has received research support from AbbVie, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb and Novo Nordisk, and honorarium from Eli Lilly, GlaxoSmithKline, Merck, Novartis, Novo Nordisk, Sanofi and Takeda. Please see the study for all other authors’ relevant financial disclosures.