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 signiWcant 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 signiWcant 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 Wnal failure after T supplementation. However, due to the preserved trabecular bone in T, the occurrence of the Wrst microfractures (yL: 49 § 21.4 N) was signiWcantly 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 eVect (yL: 83.3 § 16.5 N) did not approach the protective eVect 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 eVect did not approach the protective eVect of estrogen on trabecular bone, but it is more suitable for male individuals because it has no feminizing eVects on the subject.

Divergent responsiveness of the dentary and vertebral bone to a selective estrogen-receptor modulator (SERM) in the teleost Sparus auratus

“…Raloxifene caused a large decrease from 4.18 to 1.97 in the TRAP/ALP ratio of the dentary, which is congruent with a reduction in bone resorption. The results suggest as observed in male rats [35] and in OVX female rats [36] that raloxifene prevents bone loss and has an anti-resorptive role and osteoblast stimulatory role in fish. Further, raloxifene in sea bream has a similar effect to E 2 , which stimulates ALP enzyme activity in regenerating scales of goldfish [42].…”

“…cavity (Sigma-Aldrich, 200 ll/100 g body weight (wt)) while treated fish (n = 6) were injected with coconut oil containing raloxifene (EVISTA™, 3.33 mg/kg body wt). The administered dose of raloxifene was based on the dose that prevented the bone loss associated with osteoporosis in male rats [35] and preserves bone density and strength in ovariectomized rats [9,37]. Six days after the start of treatment fish were anaesthetised (2-phenoxyethanol, 1:10,000) and blood samples collected from the caudal vein with heparinized syringes (150 U/ml ammonium heparin, Sigma-Aldrich), centrifuged (10,000 rpm for 5 min) and stored at À20°C.…”

“…A number of selective estrogen-receptor modulators (SERMs) have been developed to combat the bone loss typical of osteoporosis, including raloxifene, which binds to ERs in bone cells and activates tissue-specific genes and proteins and/or reduces osteoclast stimulating cytokines [18]. In ovariectomized rats raloxifene preserves bone density, acting as an ER agonist, while in other tissues it acts as ER antagonist [15,37], while in male rats it prevents the bone loss associated with osteoporosis [35]. Raloxifene is also suggested to negatively modulate osteoclasts and positively affect osteoblasts, suggesting not only an antiresorptive role, but also an osteoblast stimulatory role [36].…”

Effects of Co-Administration of Clenbuterol and Testosterone Propionate on Skeletal Muscle in Paraplegic Mice

“…In accordance with this, clenbuterol was reported to prevent bone tissue loss under conditions of disuse, such as in the denervated hindlimb or tail-suspended model (Apseloff et al, 1993;Bloomfield et al, 1997;Zeman et al, 1991). There is also evidence suggesting that testosterone can prevent bone tissue loss in rats (Stuermer et al, 2009), and increase bone density in hypogonadal men (Katznelson et al, 1996;Snyder et al, 2000). Therefore, clenbuterol-and clenbuterol þ testosterone-induced effects on body weight may have also been partially caused by protecting against bone tissue loss in Tx animals.…”

The Effects of Raloxifene on Osteocalcin, as a Bone Turnover Marker in Orchiectomized Rats

“…In mature male rats, raloxifene has been found to significantly increase bone mass/body mass ratio and bone mineral content/body mass ratio while not affecting bone mechanical properties and histomorphometric parameters (10). In another experimental study, raloxifene has significantly prevented bone loss and increased strength in metaphyseal osteoporotic bones in castrated male rats (11).…”