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WR‐2721 reduces bone loss after hindlimb tenotomy in rats
Author(s) -
Shaker Joseph L.,
Fallon Michael D.,
Goldfarb Stanley,
Farber Joshua,
Attie Maurice F.
Publication year - 1989
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1002/jbmr.5650040613
Subject(s) - tenotomy , hindlimb , endocrinology , resorption , osteoclast , medicine , bone resorption , osteoporosis , femur , chemistry , tendon , anatomy , surgery , receptor
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 < 0.02) and at 14 days (5.8 ± 0.3/mm versus 8.7 ± 0.4/mm, p < 0.02). These data suggest that WR‐2721 decreases bone loss in this model by decreasing osteoclastic bone resorption.