Interaction between effects of parathyroid hormone and bisphosphonate on regulation of osteoclast activity by the osteoblast-like cell line UMR-106.

Treatment of osteoblasts by either parathyroid hormone (PTH) or bisphosphonate can affect their regulation of the bone-resorbing activity of osteoclasts in vitro, leading to increased and decreased resorption, respectively. To address this issue, we have examined the interaction between the effects of PTH and bisphosphonate on the regulation of osteoclast activity by the PTH-responsive osteoblast-like cell line UMR-106. When rat osteoclasts were cocultured with UMR-106 cells on bovine bone slices in the presence of 10(-8) mol/L PTH, the number of resorption pits was increased 4.2-fold, whereas the addition of UMR-106 cells or PTH alone had no effect. Pretreatment of the UMR-106 cells for 5 min with increasing concentrations of either of the bisphosphonates, clodronate, and ibandronate before coculture with osteoclasts in 10(-8) mol/L PTH, caused a dose-dependent reduction in the formation of resorption pits, reaching the maximal inhibition level (60%-75% below the control) at approximately 10(-9) mol/L clodronate and 10(-11) mol/L ibandronate. Addition of conditioned medium (CM) from untreated UMR-106 cells to rat osteoclasts had no effect on pit formation, whereas CM from UMR-106 cells pretreated with ibandronate reduced the osteoclastic bone resorption by approximately 40%. However, this effect was abolished by the subsequent culture of the ibandronate-pretreated UMR-106 cells in 10(-8) mol/L PTH before harvesting the CM, because both this CM and CM from non-pretreated UMR-106 cells cultured in 10(-8) mol/L PTH caused an approximately 75% increase in pit formation when added to rat osteoclasts. In conclusion, osteoclastic bone resorption can be directly affected independently as well as at the same time by the ibandronate-induced osteoclast-inhibiting factor and the PTH-induced osteoclast-stimulating factor. The final level of bone resorption depends on the relative concentration of these two factors.