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


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).


CONCLUSIONS
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.
Stuermer
E K
EK
Department of Trauma and Reconstructive Surgery, Georg-August-University of Goettingen, Robert-Koch-Str. 40, 37099 Goettingen, Germany. e.k.stuermer@med.uni-goettingen.de
Sehmisch
S
S
Tezval
M
M
Tezval
H
H
Rack
T
T
Boekhoff
J
J
Wuttke
W
W
Herrmann
T R W
TR
Seidlova-Wuttke
D
D
Stuermer
K M
KM
D000284:Administration, Oral; D000818:Animals; D001696:Biomechanical Phenomena; D015519:Bone Density / Q000187:drug effects / Q000502:physiology; D001862:Bone Resorption / Q000188:drug therapy / Q000503:physiopathology; D001842:Bone and Bones / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D004967:Estrogens / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D020249:Hormone Replacement Therapy; D008297:Male; D009919:Orchiectomy / Q000009:adverse effects*; D010024:Osteoporosis / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D020849:Raloxifene Hydrochloride / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013739:Testosterone / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*
D004967:Estrogens; D013739:Testosterone; D020849:Raloxifene Hydrochloride