Alendronate alters osteoblast activities

Abstract

Objective: Due to accumulation in the bone matrix and a half-life of at least 10 years, it is important to understand the cellular impact of bisphosphonates (BPs). This study assessed the effects of alendronate (ALN) on human primary osteoblasts.

Material and methods: Osteoblasts were incubated with ALN (5, 20 and 100 μM), and both cells and cell culture media were harvested after d 1, 3, 7 or 14. Proliferation was evaluated by ³H-thymidine incorporation and tetrazolium dye (MTT) colorimetric assay, and viability by the lactate dehydrogenase (LDH) activity in the medium. Differentiation was evaluated using protein Luminex multiplex assays and RT-PCR.

Results: ALN had no significant effects on cell viability. The lower concentrations enhanced the proliferation, whereas 100 μM diminished the proliferation. mRNA expression of osteocalcin (OC), alkaline phosphatase (ALP) and α-1 type 1 collagen were reduced, whereas ALN enhanced the expression of leptin mRNA and the secretion of interleukin-8 (IL-8) and regulated on activation normal T cell expressed and secreted (RANTES).

Conclusions: ALN enhanced the secretion of immune factors from human osteoblasts. Combined with a lower rate of proliferation and a decline in differentiation, this indicates that higher dosages or accumulation may cause undesirable local changes in bone.

Keywords:

• Bisphosphonates
• osteonecrosis
• cytotoxic
• bone

Acknowledgements

The authors would like to thank Aina-Mari Lian for her invaluable skills and moral support (Clinical Oral Research Laboratory, Faculty of Dentistry, University of Oslo).

Disclosure statement

None to declare.

Notes on contributors

Tormod B. Krüger, DDS, PhD-student and trainee in oral and maxillofacial surgery at the Department of Oral Surgery and Oral Medicine, Institute of Clinical Dentistry, Faculty of Dentistry, University of Oslo, Norway. Has experience in working with patients on antiresorptive drugs, and with in vitro work on primary human bone cells.

Bente B. Herlofson, DDS, dr.odont./PhD, specialist in oral and maxillofacial surgery, associate professor at the Department of Oral Surgery and Oral Medicine, Institute of Clinical Dentistry, Faculty of Dentistry, University of Oslo, Norway. Has long experience working with patients on antiresorptive treatment both in osteoporosis and cancer and with patients who have developed medication-related osteonecrosis of the jaw.

Maria A. Landin, Dr Scient, PhD, is a toxicologist, specialized in toxicogenomics. During her PhD, she investigated and mapped the global gene expression in murine tooth buds using molecular biological methods. She works as Senior engineer, Faculty of Dentistry, University of Oslo, Norway.

Janne E. Reseland, Dr Scient in Biochemistry, professor at the Department of Biomaterials, and Head of Oral Research Laboratory, Institute of Clinical Dentistry, Faculty of Dentistry, University of Oslo, Norway. Has long experience working with primary human bone cells, bone remodeling and quality, and was instrumental in identifying the expression of adipokines (leptin, adiponectin and resistin) in bone.