Disorders of microcirculation in the mechanism of bisphosphonate osteonecrosis: preliminary study in rats

Abstract

We investigated the possibilities of angioprotection and the reduction of osteonecrosis in rats that had been given bisphosphonates. In our experiment, 27 rats were divided into three groups: Group 1 was injected with saline; Group 2 was given zoledronic acid for six weeks; and Group 3 was given zoledronic acid for six weeks, with added doses of sulodexide after three weeks. After that we constructed a model of how the teeth should be extracted. The velocity of linear blood flow in the periodontal area of an extracted tooth in rats was studied using laser and high-frequency Doppler ultrasound (with the application of the vasoactive substance acetylcholine 3% for 1min). We evaluated changes in the structure of the bony tissues of the head using computed tomography, comparing the control group with the saline group. A rapid reduction in microcirculation was detected during the use of zoledronic acid for six weeks. A smaller reduction in microcirculation was detected after three weeks of treatment with sulodexide and zoledronic acid. There was a reduction in blood flow in the mucous membranes and, to a greater extent, in bony tissue. Zoledronic acid causes significant impairment of the periosteal blood flow to the mucous membranes because of a complex of disorders, which includes both the cellular component (impaired endothelium-dependent vasodilation of the mucous membrane vessels) and by reducing the intensity of microcirculation in the mucous membranes and bony tissues. Sulodexide, however, improves the restoration of blood flow and reduces the severity of osteonecrosis.

Keywords: Bisphosphonate osteonecrosis; dopplerography; sulodexide; zoledronate.