Bone Abstracts

Objective: To examine the efficacy and safety of direct administration of zoledronate acid (ZOL) on local osteoporotic lesion of ovariectomized rats.

Methods: Six weeks later after ovariectomy, 16 6-month-old female S.D. rats were divided into the two groups with no differences of body weight and BMD of the proximal tibia. In the group L, 50 μl ZOL at a dose of 67 μg/kg were locally injected into the bone marrow between the two drilled holes and 50 μl saline was systemically administrated by s.c. injection. In the group S, 50 μl saline was locally injected, and 50 μl ZOL at a dose of 67 μg/kg was systemically administrated. Local osteoporotic lesions induced by ovariectomy (Area 1: cancellous bone area of right proximal tibia between the two holes, Area 2: left side mirror area) were analysed using in vivo micro-CT at 2, 4, 6, and 8 weeks later after administration.

Results: In the group L, BMD of the locally injected Area 1 continuously increased until week 8 (+41%), but BMD increased and stayed constant in the group S (+17%). In the group L, BMD of the Area 2 continuously decreased until week 8 (−12%), but BMD maintained at the pre-treated level in the group S. In the group L, BMD and microstructural parameters of the Area 1 were significantly higher than the group S at week 4, 6, 8, and these parameters of the Area 2 were significantly lower than the group S at week 6, and 8.

Conclusions: ZOL is the most potent bisphosphonate that strongly inhibits osteoclast function with high binding affinities for bone. Taking advantage of these characteristics, we showed that direct administration of high-dose ZOL to local osteoporotic lesion have more beneficial effects on local bone structure than the systemic administration, and have no influence on other bone tissue.