[Effects of selective and non-selective cyclooxygenase 2 inhibitors on heterotopic ossification in rat model with Achilles tenotomy].
OBJECTIVE
To compare the efficacy of selective cyclooxygenase 2 (COX2) inhibitor and non-selective COX2 inhibitor drugs in prevention of heterotopic ossification in rats model so as to provide reference for clinical drugs selection of heterotopic ossification prevention.


METHODS
Fifty male Sprague Dawley rats, 6 to 8 weeks old, weight (190.0 +/- 8.5) g, were selected; the right Achilles tendon was cut off to induce ectopic bone formation. The rats were randomly divided into 5 groups (n = 10): on the 1st day after modeling, celecoxib was given in groups A [2 mg/(kg x d)] and B [10 mg/(kg x d)], indomethacin in groups C [(2 mg/(kg x d) and D [10 mg/(kg x d)], and 2 mL of saline in group E for 10 weeks. The general condition of rats was observed after operation. At 5 and 10 weeks after operation, X-ray films of the right lower limb were taken to observe new bone formation. At 10 weeks after operation, the right Achilles tendon tissue was harvested for histological observation. Based on X-ray and histological results, heterotopic ossification was assessed. Immunohistochemical staining was used to evaluate COX2 and bone morphogenetic protein 2 (BMP-2) expression levels in local Achilles tendon.


RESULTS
During the experiment, 5 rats died (2 in group B, 1 in group C, and 2 in group D), the other rats survived to the end of the experiment. General observation of Achilles tendon tissue showed that the tendon tissue volume of group B was the smallest, with soft texture and no cartilage-like tissue; the tendon tissue volume of group E was the biggest, with hard texture and cartilage-like tissue. The incidence of heterotopic ossification was 80.0% (8/10), 25.0% (2/8), 88.9% (8/9), 50.0% (4/8), and 100% (10/10) in groups A-E respectively at 10 weeks after operation; significant differences were found between groups B, D and group E (P = 0.002, P = 0.023) and between groups B and C (P = 0.015), but no significant difference was found among the other groups (P > 0.05). COX2 expression level in groups B and D was significantly lower than that in group E (P < 0.05 ), but no significant difference was found among the other groups (P > 0.05); BMP-2 expression level in group B was significantly lower than that in groups A, C, and E (P < 0.05), but no significant difference was found among the other groups (P > 0.05).


CONCLUSIONS
Celecoxib at a dose of 10 mg/(kg x d) can effectively reduce the incidence of heterotopic ossification in rats.
Jiang
J
Wu
Haijun
H
Xiao
Feng
F
Xue
Weizhe
W
Shi
Hang
H
Zhao
D000125:Achilles Tendon / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism; D000068579:Celecoxib; D051546:Cyclooxygenase 2 / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D007213:Indomethacin / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D009999:Ossification, Heterotopic / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D011720:Pyrazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013449:Sulfonamides / Q000008:administration & dosage / Q000627:therapeutic use*; D058971:Tenotomy / Q000009:adverse effects
C525720:Bmp2 protein, rat; D055396:Bone Morphogenetic Protein 2; D052246:Cyclooxygenase 2 Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; D000068579:Celecoxib; D007213:Indomethacin