The Negative Impact of Selective Activation of Retinoic Acid Receptors on Bone Metabolism and Bone Mechanical Properties in Rats.

Abstract

Drug-induced osteoporosis is a significant health problem, as many drugs have deleterious effects on bone metabolism. Data from several studies concerning the influence of retinol on bone homeostasis are inconsistent. The purpose of this study was to investigate the influence of tazarotene, a selective agonist of the retinoic acid receptor (RAR), on bone metabolism and bone mechanical properties in rats. Sixteen male Wistar rats were assigned either to the group receiving tazarotene or to the control group. Serum biochemical markers of bone turnover (osteocalcin: OC, tartrate resistant acid phosphatase 5: TRACP5b, and osteoprotegerin: OPG) and the mechanical properties of bones were analyzed. The mean Young's modulus was 24% higher (p < 0.05) in the control group than in the group receiving tazarotene. The stiffness of femur bones was 25% lower (p < 0.05) in rats receiving tazarotene. Flexural yield stress was slightly (2%) decreased in the tazarotene group, but the difference was not statistically significant. In the tazarotene group significantly lower serum concentration of bone turnover markers were obeserved (TRACP5b: 0.86 ± 0.30 ng/mL vs. 2.17 ± 0.67 ng/mL, OC: 7.77 ± 2.28 ng/mL vs. 13.04 ± 3.54 ng/mL and OPG: 0.09 ± 0.04 ng/mL vs. 0.27 ± 0.10) than in the control group. Tazarotene worsened bone mechanical properties and inhibited bone turnover in rats. These results suggest that tazarotene has a negative impact on bone metabolism and that it exerts osteoporotic activity.