Study Design |
No. of Subjects |
Treatment |
Results |
In vivo, rats[31] |
53 |
Aspirin vs controls |
Rats given 75 and 150 mg/kg before and after incision had a 22% inhibition of tensile strength. A dose of 150 mg/kg the day before surgery led to a 40% inhibition. Aspirin retards wound healing. |
In vitro, rat tissue[32] |
20 |
Ketorolac vs placebo |
A significant decrease in mean breaking strength and mean collagen concentration was noted in ketorolac-treated rats. |
Rabbit tissue[33] |
68 |
Indomethacin vs placebo |
After 4 wks, in the indomethacin-treated group, a significant decrease in 4-hydroxyproline and proline content in tendons was found, indicating a decrease in collagen synthesis. |
In vitro, rat skin[34] |
10 |
Ibuprofen vs diclofenac vs placebo |
16-36% reduction in wound strength was noted in treatment groups as measured by tensile strength. |
Rat tissue[35] |
45 |
Ibuprofen vs placebo |
Ibuprofen was found to decrease neutrophil activity, lymphocyte blastogenesis, and helper or inducer T-lymphocyte infiltration on a sponge model matrix. |
In vitro, human tendon[36] |
10 |
Diclofenac vs aceclofenac vs indomethacin vs naproxen |
Diclofenac and aceclofenac had no significant effect, but indomethacin and naproxen significantly reduced tendon cell proliferation and glycosaminoglycan synthesis in patellar tendon cultures. |
Retro, human[37] |
165 |
NSAIDsa vs no NSAIDs |
Patients taking more NSAIDs had more postoperative bleeding complications than did patients not taking NSAIDs. Complications were more frequent with NSAIDs with a half-life > 6 hrs. |
MC, P, R, DB[38] |
175 |
Parecoxib |
Postoperative administration of parecoxib 20 and 40 mg i.v. significantly reduced PCA morphine use over a 24- and 36-hr period with no difference in adverse events. |
P, R, MC, PC, DB, PG, human[39] |
418 |
Celecoxib vs hydrocodone-APAP vs placebo |
Single doses of each were administered within 24 hrs after anesthesia. Over 8 hrs, celecoxib and hydrocodone-APAP offered equal analgesia. Over a 5-day period, celecoxib 200 mg t.i.d. was superior in analgesia and tolerability than hydrocodone-APAP 10 mg-1000 mg t.i.d. This study was not designed to evaluate wound healing or adverse effects. |
P, rats[40] |
~75 |
Diclofenac vs naproxen vs nabumetone vs etodolac vs L745,337 |
Administration of the potent COX-2 inhibitor, L745,337, to rats with induced colitis led to excessive mortality compared with other NSAIDs. |
P, mice[41] |
NR |
NS-398 vs control |
NS-398, a selective COX-2 antagonist, impairs healing of induced gastric ulceration in mice. |
P, R, in vivo, mice[42] |
NR |
Diclofenac vs SC-791 (COX-2 inhibitor) vs dexamethasone (used as control) |
Diclofenac did not have any significant effect on the wound healing morphology. Tensile strength was not affected by the use of diclofenac or dexamethasone |
In vitro, rats[43] |
5 |
Celecoxib vs naproxen vs HCT-3012 |
Celecoxib did not significantly affect collagen deposition into subcutaneously implanted sponges. |
P, R, PC, DB, human knee[44] |
21 |
Rofecoxib vs placebo |
Though not designed to evaluate wound healing issues, no adverse effects or complications were reported after total knee replacement. Rofecoxib was started 3 days before and continued for 48 hrs after surgery. |
In vivo, rat femur[45] |
129 |
Indomethacin vs placebo |
Indomethacin group had significantly more angulation at 24 days, and significantly decreased tensile strength, indicating poor fracture repair compared with placebo group. |
In vivo, rabbit tibia[46] |
32 |
Indomethacin vs placebo |
Formative foci were reduced at 2 and 6 wks after tibial osteotomy, indicating inhibition of bone formation. |
In vivo, rabbit ulnae[47] |
27 |
Ketorolac 2 mg/kg vs methylprednisolone vs ketorolac 4 mg/kg vs control |
Demineralized bone implanted into rabbits had lower torsional stiffness in treatment groups compared with controls and higher doses of ketorolac. Methylprednisolone led to decreased number of well-differentiated osteocytes. |
In vivo, rat tibia[48] |
59 |
Ibuprofen vs placebo |
Treatment groups had significantly lower calcium levels. Rats in the fracture group also had lower hydroxyproline levels compared with rats in the placebo group. |
In vivo, rabbit L5-L6 arthrodesis[49] |
70 |
Indomethacin vs control |
Starting indomethacin 2 and 4 wks postoperatively led to lower fusion rates compared with controls. |
Retro, PC, PG, human[50] |
288 |
Ketorolac vs control |
Patients who received ketorolac postoperatively had significantly higher nonunion rates compared with patients who received no NSAIDs. |
P, R, in vivo, rat femur[51] |
253 |
Indomethacin vs celecoxib vs rofecoxib vs placebo |
COX-2 inhibitor groups still had fracture evidence at wk 8 vs normal healing in controls. Rofecoxib led to a significantly reduced torque and torsional rigidity at 4 and 8 wks after fracture. Indomethacin and rofecoxib groups had significantly reduced normalized shear stress at 4 and 6 wks after fracture, which remained significantly lower at 8 weeks in the rofecoxib group. |
In vitro, rats[52] |
50 |
Celecoxib vs no treatment |
Celecoxib-treated and injured rats were determined to have a 32% lower load to failure than untreated and noninjured rat ligaments, but the long-term effect on healing is not known. |
P, R, in vivo, rat femur[53] |
8 |
Etodolac vs placebo |
Etodolac delayed femur fracture union and callus formation in rats 3 wks after fracture. Strength and stiffness were significantly lower in the etodolac treatment group than in the placebo group. |
In vivo, rat femur[54] |
48 |
Ketorolac vs parecoxib |
3 wks after femur fracture, 25% of the ketorolac group fractures and 8% of the high-dose parecoxib group fractures failed to unite. |
In vivo, rat femur[55] |
57 |
Indomethacin vs celecoxib vs control |
At 4 and 8 wks after fracture, both selective and nonselective COX-inhibited treatment groups had significantly more fibrous tissue and less woven bone formation vs nontreatment group. |
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