title: The Negative Impact of Selective Activation of Retinoic Acid Receptors on Bone Metabolism and Bone Mechanical Properties in Rats.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pharmacology, Wroclaw Medical University, Poland.
authors.forename: Beata
authors.initials: B
authors.lastname: Nowak
authors.affiliation: Department of Pharmacology, Wroclaw Medical University, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Matuszewska
authors.affiliation: Division of Biomedical Engineering and Experimental Mechanics, Wroclaw University of Technology, Poland.
authors.forename: Jarosław
authors.initials: J
authors.lastname: Filipiak
authors.affiliation: Division of Biomedical Engineering and Experimental Mechanics, Wroclaw University of Technology, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Nikodem
authors.affiliation: Department of Pharmacology, Wroclaw Medical University, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Merwid-Ląd
authors.affiliation: Department of Pharmacology, Wroclaw Medical University, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Pieśniewska
authors.affiliation: Department of Pharmacology, Wroclaw Medical University, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Kwiatkowska
authors.affiliation: Department of Pharmacology, Wroclaw Medical University, Poland.
authors.forename: Bartosz
authors.initials: B
authors.lastname: Grotthus
authors.affiliation: Department of Pharmacology, Wroclaw Medical University, Poland.
authors.forename: Adam
authors.initials: A
authors.lastname: Szeląg
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D016723:Bone Remodeling / Q000187:drug effects*; D055119:Elastic Modulus; D005269:Femur / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D009539:Nicotinic Acids / Q000633:toxicity*; D010024:Osteoporosis / Q000097:blood / Q000139:chemically induced* / Q000503:physiopathology; D017208:Rats, Wistar; D018168:Receptors, Retinoic Acid / Q000819:agonists* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D012176:Retinoids
chemical_list: D015415:Biomarkers; D009539:Nicotinic Acids; D018168:Receptors, Retinoic Acid; C086827:tazarotene; D012176:Retinoids
keywords: bone mechanical properties; bone turnover; osteoporosis; retinoic acid receptors; tazarotene