Osteoporosis and mild metabolic acidosis in the rat after orchiectomy and their prevention: should prophylactic therapy be administered to patients with androgen deprivation?
OBJECTIVE
To date there has been little research on the etiology and prophylaxis of osteopenia during androgen deprivation. This condition is gaining increasing attention, partially due to the considerable osteoporosis related side effects of hormone withdrawal symptoms in patients with prostate cancer. We characterized androgen deprivation and its prophylaxis.


METHODS
A total of 36 male Sprague-Dawley rats underwent laparotomy, orchiectomy or orchiectomy with subsequently treatment with calcium acetate and sodium citrate via the water supply. Postoperative observation was 19 weeks. Test parameters were weight development, testosterone, parathyroid hormone, vitamin D, osteocalcin, cross links, hydroxyproline and cyclic adenosine monophosphate as well as bone density, tensile strength, mineral content and histomorphometry.


RESULTS
Animals subjected to orchiectomy had a reduction in bone mineral content and fracture energy with mild metabolic acidosis. The markers of bone metabolism were statistically unchanged, while the ratio of trabeculae-to-tissue area decreased. Animals treated with orchiectomy, calcium acetate and sodium citrate had moderately compensated metabolic alkalosis and increased bone minerals. Fracture energy was likewise normal and there was a tendency toward higher bone metabolism.


CONCLUSIONS
Castration led to a reduced increase in body mass, considerable standard deviation from biochemical and histological criteria for tubular bone and, thus, an increased fracture risk. A possible cause may be reduced formation and unchanged bone loss combined with mild metabolic acidosis. Calcium and alkalization seem to be effective prophylaxis for androgen deprivation. Considering the large number of osteoporotic complications after androgen deprivation, further clinical studies are justified to show the benefits of prophylactic therapy.
Straub
B
B
Department of Urology, Universitätsklinikum Benjamin Franklin, Freie Universität Berlin, Berlin, Germany.
Müller
M
M
Schrader
M
M
Heicappell
R
R
Miller
K
K
D000085:Acetates / Q000627:therapeutic use*; D000138:Acidosis / Q000097:blood / Q000209:etiology* / Q000517:prevention & control*; D000728:Androgens / Q000502:physiology; D000818:Animals; D015519:Bone Density; D001842:Bone and Bones / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D002118:Calcium / Q000378:metabolism; D017610:Calcium Compounds; D002951:Citrates / Q000627:therapeutic use*; D005264:Femoral Fractures / Q000503:physiopathology; D006863:Hydrogen-Ion Concentration; D007408:Intestinal Absorption; D008274:Magnesium / Q000032:analysis; D008297:Male; D009919:Orchiectomy / Q000009:adverse effects*; D010024:Osteoporosis / Q000097:blood / Q000209:etiology* / Q000517:prevention & control*; D010758:Phosphorus / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077559:Sodium Citrate; D013314:Stress, Mechanical
D000085:Acetates; D000728:Androgens; D017610:Calcium Compounds; D002951:Citrates; D000077559:Sodium Citrate; D010758:Phosphorus; D008274:Magnesium; D002118:Calcium; C120662:calcium acetate