Date of this Version
Long-term administration of intravenous bisphosphonates like pamidronate is associated with jaw osteonecrosis but axial and appendicular bones are unaffected. Pathogenesis of bisphosphonate-associated jaw osteonecrosis may relate to skeletal-site specific effects of bisphosphonates on osteogenic differentiation of bone marrow stromal cells (BMSCs) of orofacial and axial/appendicular bones. This study evaluated and compared skeletal site-specific osteogenic response of mandible (orofacial bone) and iliac crest (axial bone) human BMSCs to pamidronate.
MATERIALS AND METHODS
Mandible and iliac crest BMSCs from six normal healthy volunteers were established in culture and tested with pamidronate to evaluate and compare cell survival, osteogenic marker alkaline phosphatase, osteoclast differentiation in co-cultures with CD34+ hematopoietic stem cells, gene expression of receptor activator of NFκB ligand (RANKL) and osteoprotegerin, and in vivo bone regeneration.
Mandible BMSCs were more susceptible to pamidronate than iliac crest BMSCs based on decreased cell survival, lower alkaline phosphatase production and structurally less organized in vivo bone regeneration. Pamidronate promoted higher RANKL gene expression and osteoclast recruitment by mandible BMSCs.
Mandible and iliac crest BMSC survival and osteogenic differentiation are disparately affected by pamidronate to favor dysregulated mandible bone homeostasis.
This is the pre-peer reviewed version of the following article: [Stefanik, D., Sarin, J., Lam, T., Levin, L., Leboy, P., & Akintoye, S. (2008). Disparate osteogenic response of mandible and iliac crest bone marrow stromal cells to pamidronate.Oral Diseases, 14(5), 465-471. doi:10.1111/j.1601-0825.2007.01402.x], which has been published in final form at [https://doi.org/10.1016/j.bbrc.2009.06.106]. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.
Bisphosphonate, Osteonecrosis, Jaw, Stem cells, Bone
Stefanik, D., Sarin, J., Lam, T., Levin, L., Leboy, P., & Akintoye, S. O. (2008). Disparate Osteogenic Response of Mandible and Iliac Crest Bone Marrow Stromal Cells to Pamidronate. Oral Diseases, 14 (5), 465-471. http://dx.doi.org/10.1016/j.bbrc.2009.06.106
Date Posted:28 June 2018
This document has been peer reviewed.