Effect of testosterone, raloxifene and estrogen replacement on the microstructure and biomechanics of metaphyseal osteoporotic bones in orchiectomized male rats

Abstract

Introduction: Currently, osteoporosis research is rarely undertaken in males but an increase in male life expectancy in the company of hypogonadism suggests the necessity for potential therapeutic options.

Materials and methods: In this study, the changes in bone structure under standardized testosterone- (T), raloxifene- (R) and estrogen (E)-supplemented diets were analyzed in osteoporotic castrated male rats.

Results: Unexpected biomechanical results could be only explained by the histomorphometry, but not by BMD measurements obtained from the qCT. All tested substances showed a significant improvement in the trabecular network (trabecular bone area for C: 2.55 mm(2), T: 4.25 mm(2), R: 4.22 mm(2) and E: 4.28 mm(2)), and suggests that the bone structure was preserved. For the metaphyseal cortical bone, a significant loss was detected in T (CBP: 18.7%) compared to R (CBP: 30.0%), E (CBP: 26.8%) and even to the osteoporotic control (CBP: 28.6%). This explains the observed early mechanical final failure after T supplementation. However, due to the preserved trabecular bone in T, the occurrence of the first microfractures (yL: 49 +/- 21.4 N) was significantly later than in the osteoporotic control (yL: 39.5 +/- 15.5 N). Raloxifene performed well in hindering the bone loss associated with osteoporosis. However, its effect (yL: 83.3 +/- 16.5 N) did not approach the protective effect of E (yL: 99.2 +/- 21.1 N).

Conclusion: Testosterone only preserved the deterioration of the trabecular bone but not of the cortical bone. Raloxifene prevented the bone loss associated with osteoporosis at all bony structures. This effect did not approach the protective effect of estrogen on trabecular bone, but it is more suitable for male individuals because it has no feminizing effects on the subject.

Fig. 1

Analysis of the trabecular structure of the metaphyseal tibia in male rats in the microradiography. a Trabecular bone area (mm²), b absolute number of nodes (No) and c trabecular bone area density (%). Comparison to d trabecular density (mg/cm³) measured by the qCT. Values are expressed as the mean ± SD (*P < 0.01 vs. control, #P < 0.01 vs. E, + P < 0.01 vs. R)

Fig. 2

Analysis of the cortical structure of the tibia in male rats. a Microradiographic evaluation of the metaphyseal cortical bone area (mm²), and b diaphyseal cortical density (mg/cm³) determined by the qCT. Values are expressed as the mean ± SD (*P < 0.01 vs. control, + P < 0.01 vs. R)

Fig. 3

Results of the biomechanical testing of the metaphyseal tibia in male rats. a Plastic deformation determined by the yield load (N) and b final failure determined by F_max (N). Values are expressed as the mean ± SD (*P < 0.01 vs. control, #P < 0.01 vs. E, + P < 0.01 vs. R)

Fig. 4

Microradiographic sections of the metaphyseal tibia made 2 mm distal to the growth plate of the tibia from an a osteoporotic control animal (ORX), b testosterone (T)-, c raloxifene (R)- and d estradiol (E)-treated rat, viewed under 30-fold (a–d) and 60-fold (e–h) magnification. Bursting of the osteoporotic bone with additional rupture of the lateral and medial cortical bone (a, e), winding fracture lines with a various number of comminutions in the treatment groups. Decreasing destruction of the bone from f the T- to g the R- up to h the E group