The effects of Risedronate and Teriparatide to Lymphocyte Ratio

Objective: The long-term administration of bisphosphonate is associated with increased risk for bisphosphonate-related osteonecrosis of the jaw (BRONJ). However at present, there is no standard treatment therapy for BRONJ.  And patients are often treated with palliative treatment such as antibiotics, antimicrobial mouth rinses and debridement of necrotic bone. Teriparatide, a drug composed of the first 34 amino acids of recombinant human parathyroid hormone is one of the antiosteoporotic durgs like bisphosphonate. Several recent studies have demonstrated that teriparatide therapy can be an effective for BRONJ. These studies have suggested clinical and radiological improvement and some biochemical makers of bone remodeling were investigated. On the other hand, while lymphocytes play established roles in bone homeostasis, few studies have described distribution of these immune cells about bisphosphonate or teriparatide treatment. The aims of this study were to investigate the influences of risedronate and teriparatide to lymphocytes. For this purpose, ovariectomized mice were treated with risedronate or teriparatide and ratio of T, B cells, NK cells, and Dendritic cells were analyzed.

Methods and Materials: Ovariectomized ICR mice (10 weeks old) were divide into three groups: Risedronate (n=5), Teriparatide (n=5) and Vehicle (n=5). The dose of risedronate was set at 10 microg/kg/day and subcutaneous injections were given 5 days/week for 8 weeks. And the dose of teriparatide was set at 40 microg/kg/day and subcutaneous injections were given as the same way. At the end of the administration period, blood and spleen cells were collected for flow cytometry analysis. These cells were labeled with fluorescein isothyiocyanate-, phycoerythrin-cyanine-7-, allophycocyanin-, phycoerythrin-, V450-, phycoerythrin- or phycoerythrin-cyanine-7- conjugated monoclonal antibodies against mouse CD45, CD3e, CD19, CD49b, CD11c, CD4 and CD8a. After labeling, these cells were analyzed by FACSCanto II (Becton, Dickinson), and data analysis was conducted with FlowJo version 7.5 (Tree star, Inc.) Results: Blood cells of Vehicle group showed that 18% of CD3e+ (T cell), 71% of CD19+ (B cell), 0.7 % of CD49+ (NK cell) and 1.9 % of CD11c+ (Dendritic cell) . Blood cells of risedronate group showed that 26 % of CD3e+ (T cell) , 64% of CD19+(B cell), 0.9 % of CD49+(NK cell) and 2.1 % of CD11c+ (Dendritic cell). Blood cells of teriparatide group showed that 17% of CD3e+ (T cell), 78% of CD19+(B cell),  0.5% of CD49+(NK cell) and 0.9 % of CD11c+ (Dendritic cell) . Percent of T cells in blood cells were increased and percent of B cells in blood cells were decreased by risedronate treatment. However, Percent of T cells and B cells in blood cells were not different between teriparatide group and vehicle group. Conclusions: It is said that bisphosphonates inhibit bone resorption for low bone turnover, although teriparatide promotes bone formation for high bone turnover. And our study showed that their influence to the lymphocyte was different.

References:

Dayisoylu EH1, Şenel FÇ, Üngör C, Tosun E, Çankaya M, Ersöz S, Taskesen F. The effects of adjunctive parathyroid hormone injection on bisphosphonate-related osteonecrosis of the jaws: an animal study. Int J Oral Maxillofac Surg. 2013 Nov;42(11):1475-80. doi: 10.1016/j.ijom.2013.05.001. Epub 2013 Jun 6.

Kim KM1, Park W, Oh SY, Kim HJ, Nam W, Lim SK, Rhee Y, Cha IH. Distinctive role of 6-month teriparatide treatment on intractable bisphosphonate-related osteonecrosis of the jaw. Osteoporos Int. 2014 Feb 20. [Epub ahead of print]