Presented in part at the Eighteenth Annual Meeting of the American Society for Bone and Mineral Research, September 7–11, 1996, Seattle, WA, U.S.A. (J Bone Miner Res 11 (Suppl 1):S151).
Alendronate/Interleukin-1β Cotreatment Increases Interleukin-6 in Bone and UMR-106 Cells: Dose Dependence and Relationship to the Antiresorptive Effect of Alendronate†
Article first published online: 1 MAY 1998
Copyright © 1998 ASBMR
Journal of Bone and Mineral Research
Volume 13, Issue 5, pages 786–792, May 1998
How to Cite
Sanders, J. L., Tarjan, G., Foster, S. A. and Stern, P. H. (1998), Alendronate/Interleukin-1β Cotreatment Increases Interleukin-6 in Bone and UMR-106 Cells: Dose Dependence and Relationship to the Antiresorptive Effect of Alendronate. J Bone Miner Res, 13: 786–792. doi: 10.1359/jbmr.1918.104.22.1686
- Issue published online: 4 DEC 2009
- Article first published online: 1 MAY 1998
- Manuscript Revised: 19 DEC 1997
- Manuscript Accepted: 19 DEC 1997
- Manuscript Received: 29 MAY 1997
Aminobisphosphonates inhibit bone resorption but have been shown to elicit acute-phase-like elevations in interleukin-6 (IL-6) in bone in vitro. The current studies were carried out to determine the relationship between the antiresorptive effects of the aminobisphosphonate alendronate and its effects on IL-6. Resorption was elicited in cultured 19-day fetal rat limb bones by 72 h treatment with interleukin-1β (IL-1β). Bone mass was quantitated at the end of the culture period to assess resorption. IL-6 was determined by bioassay (7TD1 cell proliferation). IL-1β (18 and 180 pM) stimulated bone resorption and increased IL-6. Alendronate (70 μM) inhibited the IL-1β–stimulated resorption. Alendronate alone did not affect IL-6 production by the bones. The IL-6 production from bones stimulated with 18 pM IL-1β was not significantly affected by alendronate, but the IL-6 production from bones stimulated with 180 pM IL-1β plus alendronate (21 and 70 μM) was higher than with IL-1β alone. Indomethacin (1 mM) inhibited the IL-6 increase elicited by 180 pM IL-1β and the enhanced IL-6 production elicited by cotreatment with IL-1β and alendronate. Since bone cultures contain multiple cell types, further experiments were carried out to determine whether alendronate could increase IL-1β–stimulated IL-6 production in an osteoblast cell line, UMR-106. Alendronate alone did not affect IL6 in UMR-106 cells. Alendronate (70 μM) in combination with IL-1β (180, 1.8, or 8 nM), or 7 μM alendronate, in combination with 8 nM IL-1β, significantly increased IL-6 in 48 h cell cultures. The results from the bone organ cultures show that alendronate can enhance IL-6 production elicited by higher concentrations of the cytokine IL-1β in bone, but that this effect on IL-6 does not prevent the inhibitory actions of alendronate on bone resorption. The results with the UMR106 cells indicate that one cellular site at which this enhancement of IL-6 production can occur is the osteoblast.