Salmon calcitonin, a single chain polypeptide hormone consisting of 32 amino acids, was chosen as a "model" drug for this study, as sCT therapy is known to inhibit and/or slow osteoclast-mediated resorptive bone loss, whilst positively influencing osteoinduction and bone formation (28) . Hence, we designed a conjugative strategy whereby calcitonin would be coupled to an antibody directed predominantly against osteoclast-specific receptors, in order to impart osteoclast specificity to the attached calcitonin "cargo." Delivery of sCT to the osteoclast cells by virtue of an antibody-mediated targeting platform would ensure that the calcitonin drug remained primarily localized to bone tissue after systemic administration. This would directly contrast with the passive interaction of calcitonin with other tissues that express the calcitonin receptor, such as kidneys, liver, lungs, spleen, heart and thyroid. Hence, a delivery system capable of improving sCT targeting and localization to osteoclast could have a potential to positively impact Fig. 8 Demonstration of resorption pit formation on osteologic substrate plate. After 7 days of culture, adherent cells were removed, and integrated density value of the remaining osteologic layer was calculated using alphaimager densitometer. RAW: cells cultured in media with 0 ng/ml RANKL+0 ng/ml MCSF; OC: cells cultured in media with 50 ng/ml RANKL+25 ng/ml MCSF; mAb-sCT: cells cultured in media with 50 ng/ml RANKL+25 ng/ml MCSF+ 100 nM conjugate; mAb: cells cultured in media with 50 ng/ml RANKL+25 ng/ml MCSF+ 100 nM mAb; sCT: cells cultured in media with 50 ng/ml RANKL+25 ng/ml MCSF+100 nM sCT. *P <0.05 versus OC; ** P<0.05 versus sCT. No statistically significant difference was observed for antibody versus conjugate and antibody versus calcitonin. Fig. 9 In vitro cytotoxicity of mAb, mAb-sCT & sCT on RAW 264.7 cells was determined by MTT assay. No demonstrable cytotoxicity was seen as measured by the absorbance of formazan solution formed after 4 h incubation with compounds, compared to that seen with untreated media. Samples were not statistically significant compared to the control at all concentrations. sCT therapy, whilst reducing the drug concentration in non-bone loci containing the calcitonin receptors.