BISPHOSPHONATES CLODRONATE AND ETIDRONATE IN THE PREVENTION OF OVARIECTOMY-INDUCED OSTEOPENIA IN GROWING RATS

The aim of this study was to evaluate the ability of the bisphosphonat e compounds clodronate and etidronate to prevent ovariectomy-induced b one changes, Three-month-old Sprague-Dawley rats were either ovariecto mized (OVX) or sham-operated (SHAM) and further divided into, groups r eceiving either vehicle (n = 30), 25 mg/kg/week of clodronate (n = 25) or 25 mg/kg/week of etidronate (n = 25), The subcutaneous drug admini stration was started immediately after the surgery and was continued f or 12 weeks, OVX rats had accelerated bone turnover rates compared wit h the SHAM animals, as indicated by the results of dynamic histomorpho metry and biochemical markers in serum and urine, Femoral and vertebra l mineralized trabecular bone volume and maximum loads in compressions of the femoral neck and lumbar vertebra were lower after OVX compared with the SHAM operation, Both clodronate and etidronate prevented the decrease in trabecular bone volume and suppressed the increase in the bone turnover rate, Clodronate and etidronate also blocked the loss o f bone strength in the femoral neck and lumbar vertebra of OVX rats, B oth compounds resulted in an absence of double fluorochrome labels on the endocortical surface of the femoral metaphysis, which seemed, howe ver, to be a dose-dependent response, Furthermore, etidronate also low ered serum osteocalcin and diaphyseal endocortical bone formation belo w the vehicle level both in the OVX and SHAM rats,In conclusion, clodr onate and etidronate were effective in preventing the estrogen deficie ncy-induced decreases in trabecular bone volume and bone strength in r ats, Treatment with a high dose of clodronate induced minor signs of a bnormally low bone formation but not any impairment of bone mineraliza tion, whereas both of these events were seen, with high-dose etidronat e administration.