The influence of bexarotene, a selective agonist of the retinoid receptor X (RXR), and tazarotene, a selective agonist of the retinoid acid receptor (RAR), on bone metabolism in rats. 2016

Beata Nowak, and Agnieszka Matuszewska, and Jarosław Filipiak, and Anna Nikodem, and Anna Merwid-Ląd, and Małgorzata Pieśniewska, and Lidia Fereniec-Gołębiewska, and Joanna Kwiatkowska, and Adam Szeląg
Department of Pharmacology, Wroclaw Medical University, Wrocław, Poland. Electronic address: beata.nowak@umed.wroc.pl.

OBJECTIVE The purpose of this study was to investigate the influence of selective agonists of the retinoid receptor X (RXR) and the retinoid acid receptor (RAR) on bone metabolism in rats. METHODS Thirty six male Wistar rats were divided into three groups: receiving bexarotene, or tazarotene, or to control group. Serum biochemical markers of bone turnover (osteocalcin - OC, tartrate resistant acid phosphatase 5 - TRACP5b and osteoprotegerin - OPG) and mechanical properties of bones were analyzed. RESULTS There was a significant decrease in the femur index value in groups receiving tazarotene and bexarotene on Day 14 (8% and 20% respectively, p=0.0039). On Day 28, 14 days after discontinuation of tazarotene and bexarotene, the difference in femur indexes was still significant (4% for T1-6 and B1-6, p=0.0270). In the bexarotene group an increase in mean plasma osteocalcin level and mean plasma TRACP5b level was detected. In the tazarotene group the mean osteocalcin level remained unchanged and the mean plasma TRACP5b level decreased. An increased yield stress was detected in groups receiving retinoids comparing to controls after 14 days of tazarotene and bexarotene administration. CONCLUSIONS Although bexarotene and tazarotene administration caused decrease in the femur index, mechanisms responsible for that effect seem to be different. Our results suggest that bexaroten increases bone turnover. On the contrary, tazaroten seems to have inhibitory effect on bone turnover. A counter influence of selective RAR and RXR agonists on the bone turnover might be the reason for inconsistency in results from published research concerning the influence of retinoids on bone metabolism.

UI MeSH Term Description Entries
D008297 Male Males
D009539 Nicotinic Acids 2-, 3-, or 4-Pyridinecarboxylic acids. Pyridine derivatives substituted with a carboxy group at the 2-, 3-, or 4-position. The 3-carboxy derivative (NIACIN) is active as a vitamin. Acids, Nicotinic
D001835 Body Weight The mass or quantity of heaviness of an individual. It is expressed by units of pounds or kilograms. Body Weights,Weight, Body,Weights, Body
D001842 Bone and Bones A specialized CONNECTIVE TISSUE that is the main constituent of the SKELETON. The principal cellular component of bone is comprised of OSTEOBLASTS; OSTEOCYTES; and OSTEOCLASTS, while FIBRILLAR COLLAGENS and hydroxyapatite crystals form the BONE MATRIX. Bone Tissue,Bone and Bone,Bone,Bones,Bones and Bone,Bones and Bone Tissue,Bony Apophyses,Bony Apophysis,Condyle,Apophyses, Bony,Apophysis, Bony,Bone Tissues,Condyles,Tissue, Bone,Tissues, Bone
D000077610 Bexarotene A rexinoid (an RXR-binding ligand), tetrahydronaphthalene derivative and RETINOID X RECEPTOR antagonist that is used in the treatment of CUTANEOUS T-CELL LYMPHOMA. 3-methyl-TTNEB,4-(1-(3,5,5,8,8-Pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)ethenyl)benzoic acid,LG69 compound,LGD 1069,LGD-1069,LGD1069,Targretin
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013764 Tetrahydronaphthalenes Partially saturated 1,2,3,4-tetrahydronaphthalene compounds. Tetralins
D015415 Biomarkers Measurable and quantifiable biological parameters (e.g., specific enzyme concentration, specific hormone concentration, specific gene phenotype distribution in a population, presence of biological substances) which serve as indices for health- and physiology-related assessments, such as disease risk, psychiatric disorders, ENVIRONMENTAL EXPOSURE and its effects, disease diagnosis; METABOLIC PROCESSES; SUBSTANCE ABUSE; PREGNANCY; cell line development; EPIDEMIOLOGIC STUDIES; etc. Biochemical Markers,Biological Markers,Biomarker,Clinical Markers,Immunologic Markers,Laboratory Markers,Markers, Biochemical,Markers, Biological,Markers, Clinical,Markers, Immunologic,Markers, Laboratory,Markers, Serum,Markers, Surrogate,Markers, Viral,Serum Markers,Surrogate Markers,Viral Markers,Biochemical Marker,Biologic Marker,Biologic Markers,Clinical Marker,Immune Marker,Immune Markers,Immunologic Marker,Laboratory Marker,Marker, Biochemical,Marker, Biological,Marker, Clinical,Marker, Immunologic,Marker, Laboratory,Marker, Serum,Marker, Surrogate,Serum Marker,Surrogate End Point,Surrogate End Points,Surrogate Endpoint,Surrogate Endpoints,Surrogate Marker,Viral Marker,Biological Marker,End Point, Surrogate,End Points, Surrogate,Endpoint, Surrogate,Endpoints, Surrogate,Marker, Biologic,Marker, Immune,Marker, Viral,Markers, Biologic,Markers, Immune
D016723 Bone Remodeling The continuous turnover of BONE MATRIX and mineral that involves first an increase in BONE RESORPTION (osteoclastic activity) and later, reactive BONE FORMATION (osteoblastic activity). The process of bone remodeling takes place in the adult skeleton at discrete foci. The process ensures the mechanical integrity of the skeleton throughout life and plays an important role in calcium HOMEOSTASIS. An imbalance in the regulation of bone remodeling's two contrasting events, bone resorption and bone formation, results in many of the metabolic bone diseases, such as OSTEOPOROSIS. Bone Turnover,Bone Turnovers,Remodeling, Bone,Turnover, Bone,Turnovers, Bone
D017208 Rats, Wistar A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain. Wistar Rat,Rat, Wistar,Wistar Rats

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