Testosterone Therapy Effects on Bone Mass and Turnover in Hypogonadal Men with Type 2 Diabetes.

CONTEXT Male hypogonadism is associated with low bone mineral density (BMD) and increased fragility fracture risk. Patients with type 2 diabetes (T2D) have relatively higher BMD, but greater fracture risk. OBJECTIVE Evaluate the skeletal response to testosterone therapy in hypogonadal men with T2D compared to hypogonadal men without T2D. DESIGN, METHOD AND PARTICIPANTS Single arm, open-label clinical (NCT01378299) trial involving 105 men (40-74 years old), with average morning testosterone<300ng/dl. Subjects were injected intramuscularly with testosterone cypionate (200mg) every 2 weeks for 18 months. Testosterone and estradiol assessed by liquid-chromatography/mass-spectroscopy; serum C-telopeptide (CTX), osteocalcin and sclerostin by ELISA; A1C by high performance liquid chromatography, areal BMD (aBMD) and body composition by dual-energy x-ray absorptiometry; tibial volumetric BMD (vBMD) and bone geometry by peripheral quantitative computed tomography. RESULTS Among our population of hypogonadal men, 49 had T2D and 56 were non-T2D. After 18 months of testosterone therapy, there were no differences in circulating testosterone and estradiol between the groups. Hypogonadal men with T2D had increased osteocalcin, reflecting increased osteoblast activity, compared to non-T2D men (p<0.01). T2D men increased lumbar spine aBMD (p<0.05), total area at 38% tibia (p<0.01) and periosteal and endosteal circumferences at the same site (p<0.01 for both). T2D men had reduced tibial vBMD (p<0.01), but with preserved bone mineral content (p=0.01). Changes in A1c or body composition were similar between the 2 groups. CONCLUSIONS Testosterone therapy results in greater improvements in the skeletal health of hypogonadal men with T2D than their non-diabetic counterparts.