Background: Tooth extraction is conventionally performed without any additional tissue manipulation and left for healing by secondary intention. Maintaining hard and soft tissue volume after tooth extraction may be crucial to achieve a highly aesthetic restoration and it may also facilitate stability of the results on the long-term. Therefor, different approaches have been proposed to eliminate post-extraction ridge reduction. Today, however, no technique seems to be able to preserve the entire socket volume. Aim/Hypothesis: To evaluate histomorphometrically the influence of local administration of pamidronate, adsorbed on a deproteinized porcine bone substitute, on extraction socket healing. Material and methods: Two American Fox-hound dogs were used within this proof-of-principle study. Following endodontic treatment of the distal root of the three lower premolars, the teeth were hemisected and the mesial roots were extracted flapless. The sockets were then loosely filled, in a split-mouth fashion, with a deproteinized porcine bone substitute in particulate form (Osteobiol Gen-Os; DPB), rehydrated either with sterile saline (control) or 90 mg/ml pamidronic acid solution (Aredia ; test). Extraction sockets were sealed with connective tissue punches obtained from the palate and secured with sutures. After 4 months of healing, specimens containing the sockets sites and remaining roots were retrieved and histomorphometrically evaluated. Vertical and horizontal ridge changes were evaluated comparing the section containing the remaining root and the corresponding extraction sites. Results: Histological evaluation of the sections revealed significant differences in healing patterns between test and controls. While the latter group presented complete closure of the sockets with newly formed bone, pamidronate treated sites presented with open socket entrances, only sealed with soft connective tissue. Within the socket, control sites presented with various amounts of newly formed bone and no evidence of DPB; limited amounts of bone healing were observed within test sites, that were filled with DPB mainly embedded in connective tissue. Socket (bone) wall loss in a vertical dimension showed only minor differences between tests and controls sites (buccal: – 1.01 vs – 1.15 mm; lingual: – 0.92 vs – 1.15 mm;). Horizontal bone loss, measured at a level corresponding to 3 mm below the cemento-enamel-junction (CEJ), was nearly three times higher in control sites ( 2.19 1.81 mm vs. – 0.80 0.91 mm;), while no differences were observed between groups at a level corresponding to 5 mm below the CEJ. Conclusion and clinical implications: Local administration of pamidronate adsorbed on a deproteinized porcine bone substitute in particulate form appeared to delay extraction socket healing, but may also reduce post-extraction dimensional changes in the alveolar ridge, in terms of horizontal bone loss. Additionally, pamidronate appears to obstruct resorption of the porcine bone substitute.