Effects of tiludronate on bone mass, structure, and turnover at the epiphyseal, primary, and secondary spongiosa in the proximal tibia of growing rats after sciatic neurectomy

Abstract

To evaluate the effects of tiludronate on the mass, structure, and turnover of cancellous bone regions in immobilized rat tibiae, we performed a 4 week dosing experiment. The right hindlimbs of 84 Sprague-Dawley rats (5 weeks old) wee neurectomized or sham operated. Animals were assigned to seven groups (n = 12 each); group 1 was sham operated, and groups 2-7 were neurectomized. Groups 1 and 2 were given vehicle only (distilled water), and groups 3, 4, and 5 were given tiludronate orally at doses of 25, 50, and 100 mg/kg body weight (BW)/day, respectively, throughout the experimental period. Group 6 was given 100 mg/kg BW/day of the agent for the first 2 weeks only, and group 7 received vehicle only for the first 2 weeks and then 100 mg/kg BW/day of the agent for the last 2 weeks. After tetracycline labeling was performed, the right tibiae were removed from the animals and processed to yield undecalcified sections. Histomorphometry was performed in the epiphyseal, primary, and secondary spongiosa of the proximal tibia. In group 2, trabecular bone volume (BV/TV) and trabecular number (Tb.N) were significantly decreased in the primary and secondary spongiosae, but this did not occur in the epiphyseal spongiosa. Osteoid surface (OS/BS) was decreased and osteoclast surface (Oc.S/BS) was increased in the secondary spongiosa. Tiludronate increased BV/TV and Tb.N in the primary spongiosa by reducing the values for the parameters of osteoclast surface (Oc.S/BS) and osteoclast number (Oc.N/BS). Osteoid surface in this region was not decreased by the agent. In groups 4 and 5, tiludronate prevented bone loss in the secondary spongiosa by reducing both OS/BS and Oc.S/BS. In group 6, BV/TV in the primary spongiosa was maintained at the level of group 1, but Oc.S/BS and Oc.N/BS were elevated. In the secondary spongiosa, bone mass was preserved and the reduction in these parameters was maintained. In group 7, however, BV/TV was increased in the primary spongiosa as a result of a reduction in osteoclastic resorption; in the secondary spongiosa, however, BV/TV was decreased and trabecular turnover was not reduced at the end of the experiment in these growing animals. Mineral apposition rates were not reduced by tiludronate. This study clearly demonstrated that this agent prevented immobilization bone loss by inhibiting resorption.(ABSTRACT TRUNCATED AT 400 WORDS)

Ostreae Testa prevent ovariectomy-induced bone loss in mice by osteoblast activations

“…In the osteoporosis, some histomorphometrical indices are clearly decreased including TBV, Cbt, Tbt, Tbl and osteoblasts/bone perimeter or increased as osteoclasts/bone perimeter, and they provided trustworthy information to predict the efficacy of anti-osteoporotic agents (Murakami et al, 1994;Weinreb et al, 1997). As results of OVX-induced osteoporotic process, dramatic decreases of trabecular and cortical bone masses were detected in vehicle control compared to non-OVX Sham with classic histomorphometrical changes of bones including decrease of TBV, Tbt, Tbl, Tbn, Cbt and increase of Ocn.…”

Combination therapy with dexamethasone and osteoprotegerin protects against arthritis-induced bone alterations in antigen-induced arthritis of the rat

“…Structural homogeneity of bone architecture is an important aspect relating to the method used for investigating bone structure. Primary spongiosa of growing rats is characterized by partial resorption of calcified longitudinal cartilage septa by osteoclasts followed by blood vessel invasion and formation of woven bone on the basis of these septa by osteoblasts [32,33]. The growing process results in an inhomogeneity of the bone structure of primary spongiosa.…”

“…The primary spongiosa, identified by means of morphological criteria (presence of cartilage cores) and by its distance from the growth plate [33,36] was subsequently analyzed employing linear scanning [36,37] (Table 2).…”

The Anti-osteoporotic Effect of Aqueous Extracts of Gastrodiae Rhizoma In Vitro and In Vivo

“…38,39) The FL of mid-shaft regions of left tibia of GR extracts-dosing groups were increased compared to that of vehicle control group. These increases of FL was considered that GR extracts has direct effect to inhibit the decrease of bone strength induced by OVX, and as direct evidence that GR extracts has a favorable effects to improve the bone strength.…”