Effects of Clodronate on Cortical and Trabecular Bone in Ovariectomized Rats on a Low Calcium Diet

Abstract

The aim of this study was to evaluate the contribution of a low calcium diet to the cortical and trabecular osteoporosis seen in ovariectomized rats after 7 weeks on a low calcium diet and to investigate the effects of the bisphosphonate clodronate on this development of osteoporosis. Thirty-six mature, female Wistar rats were randomized into four groups: Ovx-B (bisphosphonate) and Ovx-C (control) were ovariectomized, and Sham-Ca (low calcium) and Sham+Ca (normal calcium) were sham operated. The first three groups were fed a low calcium diet (0.01%) and Sham+Ca normal rat chow (Ca 1.1%). The Ovx-B received 10 mg/kg s.c. clodronate daily for nine weeks, and Ovx-C, Sham-Ca, and Sham+Ca received the same volumes of saline. Bone mineral turnover measured as 85Sr-uptake was increased in all low calcium groups compared to Sham+Ca. The Sham+Ca femora had higher dry weight and ash weight than the other groups, and Ovx-C had higher dry weight compared with Ovx-B and Sham-Ca. Calcium content was lower in both Ovx groups compared to both Sham groups. Magnesium was lower in all groups compared to Sham+Ca and higher in Ovx-B compared with Ovx-C. In the femoral shaft, Sham+Ca had significantly higher ultimate bending moment, energy absorption, and deflection compared to the other three groups. Ultimate bending moment was higher in Sham-Ca than in Ovx-C. Stiffness was increased in both Sham+Ca and Ovx-B compared to Ovx-C. The maximum stress in the femoral midshaft was higher in Sham+Ca than in the other groups, and higher in Ovx-B than in Ovx-C. Histomorphometry showed increased medullary area in all low calcium groups compared to Sham+Ca and larger cortical area in Sham+Ca and Ovx-B compared to Ovx-C. Compared to Sham+Ca the trabecular bone volume was decreased to 30% in Sham-Ca and to 9% in Ovx-C, but was unchanged in Ovx-B. The low calcium diet generally increased bone mineral turnover and reduced the tibial bone volume. Femoral changes led to a reduction of cortical fracture strength and maximal stress. Ovariectomy in addition to a low calcium diet reduced femoral strength even more. Daily injections of clodronate to ovariectomized rats on a low calcium diet increased femoral shaft stiffness and maximum stress, and clodronate preserved both trabecular and cortical tibial bone volume completely.

The effect of zoledronate on bone remodeling during the healing process

“…It suggests that this drug has a stimulative effect on osteoblastic activity and an inhibitory effect on osteoclastic reabsorption and remodeling, shown by the increase of trabecular (lamela) bone. These findings confirm other published experimental studies 3,7,13,14,15,16 . Plotkin et al 3 conclude that pamidronate increased trabecular bone volume of patients with osteogenesis imperfecta in 6,3%; bone formation rate under the effect of pamidronate increased from 6,6 to 15,3mm 2 .…”

“…Clodronate did not alter the histology of the callus nor delayed the healing of the fracture, but it caused mild to moderate proeminence of the metaphyseal area in the fractred bone in a dose-and time-dependent manner. Kaastad et al 13 conclude that clodronate increased medullary area in ovariectomized rats and preserved both trabecular and cortical bone volume completely. Pyskywec et al 14 .…”

A Strategy for the Management of Elderly Women with Primary Hyperparathyroidism: A Comparison of Etidronate Therapy with Parathyroidectomy

“…In a prospective study, alendronate improved cancellous bone levels in osteoporosis and reduced fracture rates [15]. Bisphosphonates improved decreased osteoporotic BMD in both cancellous and cortical bone sites [16][17][18]. However, bisphosphonates have a greater effect on trabecular bone than on cortical bone [16].…”

Prevention of Osteoporosis in Mice after Ovariectomy via Allograft of Microencapsulated Ovarian Cells

“…In summary, our study demonstrates that ovariectomy induces osteopenia with an increase in bone turnover dominating bone resorption (Kaastad et al, 1997;Geng et al, 2000). In the treatment group, microencapsulated ovarian cells could continuously secrete estrogen to maintain the balance of bone absorption and formation.…”