Osteoclasts and Megakaryocytes in Interradicular Bone of Bisphosphonate Treated Animals

Objective: Bisphosphonates inhibit osteoclast (OC) mediated bone resorption (BR), and are used to treat osteoporosis. Over the last years experimental research has been conducted to evaluate their application in dental specialties. Recent in vitro studies evidenced that megakaryocytes (MKs) appear to play a dual role in regulating skeletal mass. On the one hand MKs secrete a factor that inhibits OC formation and, on the other hand, they stimulate osteoblast proliferation and differentiation. MKs have been shown to secrete several bone-related proteins such as osteoprotegerin (OPG) and receptor activator of NFkappaB ligand (RANKL). The aim of the present study was to evaluate OC-MK interaction in interradicular bone of healthy animals treated with a bisphosphonate (olpadronate: OPD, Gador SA) by means of histomorphometric studies and immunohistochemical detection of RANKL. Methods: Twenty female Wistar rats were divided into two groups: GI: 0.3 mg/kg/week OPD during five weeks and GII: vehicle. Six weeks after the onset of the experiment, the animals were killed and the mandibles were processed histologically to obtain mesio-distal sections of the lower first molar. The following parameters were evaluated: 1.-Bone volume, 2.-Number of Ocs, 3.-Number of MKs , 4.- MK RANKL+ , 5.- Bone surface RANKL+ . Results: 1.-BV/TV (%): GI: 41±4, GII: 35±6 p<0.05; 2.-OC/mm2: GI: 4.6±2.2, GII: 2.0±0.9 p<0.05; 3.-MK/mm2: GI: 66±31, GII: 31±13 p<0.05; 4.-RANKL+ MK(%): GI: 62±26, GII: 41±17; 5.-RANKL+ S/BS (%): GI: 49±14, GII:. 47±13. Conclusion: The results obtained show that OPD inhibits BR and increases the number of MK and OC. These results suggest that inhibition of BR is not mediated by the decrease in the number of OC, or by the increased expression of RANKL. It is possible that the increase in MKs induced by bisphosphonate administration may play a direct or indirect role in the observed OPD induced inhibition of BR. UBACyTO013.