Faculty Collaboration Database

WR-2721 reduces bone loss after hindlimb tenotomy in rats. J Bone Miner Res 1989 Dec;4(6):885-90

Date

12/01/1989

Pubmed ID

2558504

DOI

10.1002/jbmr.5650040613

Scopus ID

2-s2.0-0024800994 (requires institutional sign-in at Scopus site)   25 Citations

Abstract

WR-2721 is a thiophosphate analog of cysteamine that produces hypocalcemia in vivo. Previous studies suggest that WR-2721 produces hypocalcemia by independent inhibitory effects on parathyroid hormone (PTH) secretion, osteoclastic bone resorption, and tubular reabsorption of calcium. We sought to determine if WR-2721 would decrease bone loss in an animal model of disuse osteoporosis produced by unilateral knee tenotomy in the rat. Tenotomy significantly increased osteoclast number in tibias on the side of the procedure compared with tibias on the opposite side which had not undergone the procedure at 3 and 14 days. Femoral weight of tenotomized limbs were also reduced significantly compared with the contralateral limb at 3 and 14 days. WR-2721 treatment (240 mg/kg daily) prevented 26% of the loss of femoral dry weight and 29% of the loss of femoral ashed weight produced 14 days after tenotomy. In addition, WR-2721 treated (240 mg/kg daily) animals had fewer osteoclasts in tenotomized tibias than control animals at 3 days (6.6 +/- 0.7/mm versus 10.3 +/- 0.9/mm, p less than 0.02) and at 14 days (5.8 +/- 0.3/mm versus 8.7 +/- 0.4/mm, p less than 0.02). These data suggest that WR-2721 decreases bone loss in this model by decreasing osteoclastic bone resorption.

Author List

Shaker JL, Fallon MD, Goldfarb S, Farber J, Attie MF

Author

Joseph L. Shaker MD Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Amifostine
Animals
Bone Resorption
Calcium
Data Interpretation, Statistical
Disease Models, Animal
Femur
Hindlimb
Male
Organ Size
Organothiophosphorus Compounds
Rats
Rats, Inbred Strains
Tendons