Neridronate and human osteoblasts in normal, osteoporotic and osteoarthritic subjects

The objective of this study was to evaluate the metabolic in vitro effect of the bisphosphonate neridronate on normal and pathological human osteoblasts. Primary human osteoblast cultures were obtained from cancellous bone of osteoarthritic (OA) and osteoporotic (OP) patients and a corresponding healthy control group. Osteocalcin production was evaluated by cultured cells in neridronate 10-4M and 10-6M, both under basal conditions and after vitamin D3 stimulation. In the absence of neridronate, vitamin D3 increased osteocalcin production in all cell cultures; under the same conditions, and in the absence of vitamin D3, OA osteoblasts showed a significantly higher osteocalcin production whereas OP osteoblasts showed a significantly lower osteocalcin production compared to the normal osteoblasts, respectively. In all cellular populations neridronate at a higher concentration (10-4M) induced a reduction in osteocalcin synthesis, but in normal and osteoarthritic osteoblasts did not reduce the stimulatory effect of vitamin D3, whereas it inhibited the vitamin D3-induced increase of osteocalcin synthesis in the osteoporotic cells. In normal and osteoporotic osteoblasts stimulation with the lower neridronate concentration (10-6M) significantly increased osteocalcin production, which was further enhanced by vitamin D3 as an additional effect of the combined treatment. In OA osteoblasts, neridronate 10-6M did not induce an increase in osteocalcin synthesis and the additional effect of combined treatment with vitamin D3 was not observed. Neridronate can modify the metabolic activity of human osteoblasts by enhancing or decreasing their biosynthetic activity, both in normal and in pathological conditions, depending on compound concentration and on different cell types. These results confirm the validity of using neridronate at doses usually administered in treating osteoporosis, and they suggest using it to treat other diseases which show an altered osteoblast metabolism, such as osteoarthritis.