Effects of testosterone and growth hormone on the structural and mechanical properties of bone by micro-MRI in the distal tibia of men with hypopituitarism

Abstract

Context: Severe deficiencies of testosterone (T) and GH are associated with low bone mineral density (BMD) and increased fracture risk. Replacement of T in hypogonadal men improves several bone parameters. Replacement of GH in GH-deficient men improves BMD.

Objective: Our objective was to determine whether T and GH treatment together improves the structural and mechanical parameters of bone more than T alone in men with hypopituitarism.

Design and subjects: This randomized, prospective, 2-year study included 32 men with severe deficiencies of T and GH due to panhypopituitarism.

Intervention: Subjects were randomized to receive T alone (n = 15) or T and GH (n = 17) for 2 years.

Main outcome measures: We evaluated magnetic resonance microimaging-derived structural (bone volume fraction [BVF] and trabecular thickness) and mechanical (axial stiffness [AS], a measure of bone strength) properties of the distal tibia at baseline and after 1 and 2 years of treatment.

Results: Treatment with T and GH did not affect BVF, thickness, or AS differently from T alone. T treatment in all subjects for 2 years increased trabecular BVF by 9.6% (P < .0001), trabecular thickness by 2.6% (P < .001), and trabecular AS by 9.8% (P < .001). In contrast, testosterone treatment in all subjects significantly increased cortical thickness by 2.4% (P < .01) but decreased cortical BVF by -4.7% (P < .01) and cortical AS by -6.9% (P < .01).

Conclusion: Combined T and GH treatment of men with hypopituitarism for 2 years did not improve the measured structural or mechanical parameters of the distal tibia more than T alone. However, testosterone significantly increased the structural and mechanical properties of trabecular bone but decreased most of these properties of cortical bone, illustrating the potential importance of assessing trabecular and cortical bone separately in future studies of the effect of testosterone on bone.

Figure 1.

Separation of cortical bone from trabecular bone. BVF maps were derived from midaxial FLASE μMRI images obtained from the right tibial metaphysis. BVF represents fractional occupancy of bone linearly scaled between 0% (pure marrow, shown as black) and 100% (pure bone, shown as white) in each voxel. A single operator, starting with whole bone (WB), delineated the endosteal and periosteal boundaries of cortical bone to separate cortical bone (CB) from surrounding soft tissue and trabecular bone (TB) from the cortex.

Figure 2.

Serum concentrations of testosterone (A), estradiol (B), and IGF-1 (C) at baseline and after 3, 6, 12, 18, and 24 months of treatment with testosterone (n = 15) or testosterone and growth hormone (n = 17).

Figure 3.

Contrast between the effects of testosterone and GH on trabecular bone structure (A and B) and their effects on cortical bone structure (C and D). Illustrated are the percent changes in trabecular BVF (A), Tb.Th (B), cortical BVF (C), and Ct.Th (D) of the distal tibia from baseline to 12 and 24 months after treatment with testosterone (n = 15) and testosterone and GH (n = 17) and in all subjects (n = 32). There was no significant difference between the 2 treatment groups at any time point. *, P < .01; **, P < .001; ***, P < .0001 compared with baseline; †, P < .05, 24 months compared with 12 months in all subjects.

Figure 4.

Comparison of the effects of testosterone and GH on trabecular bone strength (A), cortical bone strength (B), and whole bone strength (C). Illustrated are the percent changes in AS of the distal tibia from baseline to 12 and 24 months after treatment with testosterone (n = 15) and testosterone and GH (n = 17) and in all subjects (n = 32). AS was determined by μMRI-based FEA of trabecular bone (A), cortical bone (B), and whole bone (C). There was no significant difference between the 2 treatment groups at any time point. *, P < .01; **, P < .001, compared with baseline; †, P < .05; ††, P < .001, 24 months compared with 12 months in all subjects.