Clodronate Prevents Bone Loss in Aged Ovariectomized Rats

Abstract

The purpose of this study was to investigate the ability of clodronate to prevent ovariectomy (OVX)-induced osteopenia in aged rats. Fourteen-month-old female Sprague-Dawley rats (n = 166) were randomized into six groups. One group was sacrificed at the start of the study, four groups were ovariectomized, and one group was sham-operated (Sham). The OVX rats were given subcutaneously either vehicle (veh) or clodronate at doses of 3, 7, or 25 mg/kg once a week for 3 months, and the Sham rats were given the vehicle. At all dose levels clodronate inhibited trabecular bone loss in the distal femur and in the fourth lumbar vertebral body (L4), and decreased bone resorption as evidenced by urinary deoxypyridinoline excretion. The lowest dose of clodronate preserved serum osteocalcin and endosteal bone formation of secondary spongiosa in L4 at the level of the Sham/veh group. The OVX-induced increase in periosteal bone formation of femoral diaphysis was unaffected by two smaller doses of clodronate, but was decreased to the level of Sham rats after the highest dose. After 3 mg/kg clodronate, the percentage of femoral cortical bone area and the mean relative cortical thickness were higher compared with the OVX/veh group. There was a good positive correlation between the maximum load in three-point bending of the tibia and tibial ash weight. Normal lamellar pattern of newly formed cancellous and cortical bone was found after clodronate treatment. No signs of adverse accumulation of osteoid or any deleterious effect on mechanical strength of long bones and lumbar vertebrae were found.

Clodronate Prevents Osteopenia and Loss of Trabecular Connectivity in Estrogen-Deficient Rats

“…Daily oral clodronate treatment depressed the OVX‐induced increase in bone turnover as evidenced by decreased values of urinary excretion of deoxypyridinoline/creatinine and serum osteocalcin. Similar findings were made previously with comparable subcutaneous doses given once a week (22,24,25) . In addition, the high dose of clodronate inhibited the increase in the activity of serum S‐ALP.…”

“…Longitudinal 5‐μm‐thick sections were cut with a Polycut S heavy‐duty microtome (Leica Instruments GmbH, Heidelberg, Germany) from the femoral neck at two levels spaced 100 μm apart, and the sections were stained by the von Kossa method with hematoxylin/McNeal's tetrachrome counterstain (26) . Twenty‐micrometer‐thick microground femoral mid‐diaphyseal cross‐sections were processed as described previously (22,25) …”

“…(16,20 -23) We have shown previously the bone sparing effect of clodronate on cancellous bone in proximal tibia, distal femur, and lumbar vertebral body of OVX rats. (22,24,25) In the present study, we investigated effects of clodronate on the architecture, geometry, and bone strength of femoral neck in OVX rats. As an index of trabecular interconnection, trabecular bone pattern factor was determined on secondary spongiosa.…”

Pamidronate for the treatment of osteoporosis secondary to chronic cholestatic liver disease in Wistar rats

“…Similar to our study, there are data showing that distinct bisphosphonates are able to prevent trabecular osteopenia in ovariectomy, a classical experimental model of osteoporosis (13,30). These studies observed improvement in the ultimate force for bone fracture only in lumbar spine bone and, similar to our results, no effect was verified in long bones of animals subjected to bisphosphonate treatment (13,30,31). Kippo et al (31) suggested that in the rat the amount of cortical bone and external bone dimensions would contribute more to the structural strength of the femur than the amount and microarchitecture of trabecular bone.…”

“…These studies observed improvement in the ultimate force for bone fracture only in lumbar spine bone and, similar to our results, no effect was verified in long bones of animals subjected to bisphosphonate treatment (13,30,31). Kippo et al (31) suggested that in the rat the amount of cortical bone and external bone dimensions would contribute more to the structural strength of the femur than the amount and microarchitecture of trabecular bone. In addition to those studies, the present investigation showed that pamidronate used as preventive treatment may impair bone strength in rats submitted to surgically induced cholestasis.…”