Do nonsteroidal anti-inflammatory drugs affect bone healing? A critical analysis

TheScientificWorldJournal

Volumn 2012, Issue , 2012, Pages

  Pountos, Ippokratis ^a   Georgouli, Theodora ^a   Calori, Giorgio M ^b   Giannoudis, Peter V ^a,c  

^a UNIVERSITY OF LEEDS   (United Kingdom)

^b UNIVERSITY OF MILAN   (Italy)

^c LEEDS TEACHING HOSPITALS NHS TRUST   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ACETYLSALICYLIC ACID; CELECOXIB; DICLOFENAC; FLUNIXIN; IBUPROFEN; INDOMETACIN; KETOROLAC; LORNOXICAM; MELOXICAM; NAPROXEN; NIMESULIDE; NONSTEROID ANTIINFLAMMATORY AGENT; PARECOXIB; PHENYLBUTAZONE; PIROXICAM; PROSTAGLANDIN;

DOSE RESPONSE; DRUG EFFECT; DRUG MECHANISM; FRACTURE HEALING; HUMAN; IN VITRO STUDY; MESENCHYMAL STEM CELL; NONHUMAN; OSTEOBLAST; POSTOPERATIVE ANALGESIA; REVIEW; SYSTEMATIC REVIEW; ANIMAL; BONE; PHYSIOLOGY;

ANIMALIA;

ANIMALS; ANTI-INFLAMMATORY AGENTS, NON-STEROIDAL; BONE AND BONES; FRACTURE HEALING; HUMANS; PROSTAGLANDINS;

EID: 84856397304     PISSN: None     EISSN: 1537744X     Source Type: Journal    
DOI: 10.1100/2012/606404     Document Type: Review

References (156)

1. McKibbin B., The biology of fracture healing in long bones Journal of Bone and Joint Surgery B 1978 60 2 150 162 (Pubitemid 8356852)
2. Rahn B. A., Direct and indirect bone healing after operative fracture treatment Otolaryngologic Clinics of North America 1987 20 3 425 440
3. Dimitriou R., Tsiridis E., Giannoudis P. V., Current concepts of molecular aspects of bone healing Injury 2005 36 12 1392 1404 (Pubitemid 41618169)
4. Einhorn T. A., The cell and molecular biology of fracture healing Clinical Orthopaedics and Related Research 1998 355 S7 S21
5. Puzas J. E., O'Keefe R. J., Schwarz E. M., Zhang X., Pharmacologic modulators of fracture healing: the role of cyclooxygenase inhibition Journal of Musculoskeletal Neuronal Interactions 2003 3 4 308 312 (Pubitemid 38111614)
6. Radi Z. A., Khan N. K., Effects of cyclooxygenase inhibition on bone, tendon, and ligament healing Inflammation Research 2005 54 9 358 366
7. Gajraj N. M., The effect of cyclooxygenase-2 inhibitors on bone healing Regional Anesthesia and Pain Medicine 2003 28 5 456 465 (Pubitemid 37211091)
8. Cruess R. L., Dumont J., Fracture healing Canadian Journal of Surgery 1975 18 5 403 413
9. Augat P., Margevicius K., Simon J., Wolf S., Suger G., Claes L., Local tissue properties in bone healing: influence of size and stability of the osteotomy gap Journal of Orthopaedic Research 1998 16 4 475 481 (Pubitemid 28427699)
10. Vigorita J. V., Orthopaedic Pathology 1999 1st Lippincott Wilkins
11. Castell F. B., Garcia F. B., Berry E. M., Perello E. B., Sanchez-Alepuz E., Gabarda R., Nonunion of the humeral shaft: long lateral butterfly fracturea nonunion predictive pattern? Clinical Orthopaedics and Related Research 2004 424 227 230 (Pubitemid 38890883)
12. Claes L. E., Wilke H. J., Augat P., Rubenacker S., Margevicius K. J., Effect of dynamization on gap healing of diaphyseal fractures under external fixation Clinical Biomechanics 1995 10 5 227 234
13. Yamaji T., Ando K., Wolf S., Augat P., Claes L., The effect of micromovement on callus formation Journal of Orthopaedic Science 2001 6 6 571 575 (Pubitemid 34019567)
14. Day S. M., DeHeer D. H., Reversal of the detrimental effects of chronic protein malnutrition on long bone fracture healing Journal of Orthopaedic Trauma 2001 15 1 47 53 (Pubitemid 33602165)
15. Pountos I., Georgouli T., Blokhuis T. J., Pape H. C., Giannoudis P. V., Pharmacological agents and impairment of fracture healing: what is the evidence? Injury 2008 39 4 384 394
16. Pountos I., Georgouli T., Bird H., Kontakis G., Giannoudis P. V., The effect of antibiotics on bone healing: current evidence Expert Opinion on Drug Safety 2011 10 6 935 945
17. Pountos I., Georgouli T., Bird H., Giannoudis P. V., Nonsteroidal anti-inflammatory drugs: prostaglandins, indications, and side effects International Journal of Interferon, Cytokine and Mediator Research 2011 3 1 19 27
18. Mcadam B. F., Catella-Lawson F., Mardini I. A., Kapoor S., Lawson J. A., Fitzgerald G. A., Systemic biosynthesis of prostacyclin by cyclooxygenase (COX)-2: the human pharmacology of a selective inhibitor of COX-2 Proceedings of the National Academy of Sciences of the United States of America 1999 96 1 272 277 (Pubitemid 29036089)
19. Warner T. D., Mitchell J. A., Cyclooxygenases: new forms, new inhibitors, and lessons from the clinic FASEB Journal 2004 18 7 790 804 (Pubitemid 38544498)
20. Whelton A., Nephrotoxicity of nonsteroidal anti-inflammatory drugs: physiologic foundations and clinical implications American Journal of Medicine 1999 106 5 supplement 2 13S 24S (Pubitemid 29268660)
21. Trautman M. S., Edwin S. S., Collmer D., Dudley D. J., Simmons D., Mitchell M. D., Prostaglandin H synthase-2 in human gestational tissues: regulation in amnion Placenta 1996 17 4 239 245 (Pubitemid 26166915)
22. Vane J. R., Botting R. M., Mechanism of action of nonsteroidal anti-inflammatory drugs American Journal of Medicine 1998 104 3 supplement 1 2S 8S (Pubitemid 28186987)
23. van Ryn J., Pairet M., Clinical experience with cyclooxygenase-2 inhibitors Inflammation Research 1999 48 5 247 254 (Pubitemid 29257615)
24. Green G. A., Understanding NSAIDs: from aspirin to COX-2 Clinical Cornerstone 2001 3 5 50 58 (Pubitemid 32904246)
25. Warner T. D., Giuliano F., Vojnovic I., Bukasa A., Mitchell J. A., Vane J. R., Nonsteroid drug selectives for cyclo-oxygenase-1 rather than cyclo-oxygenase-2 are associated with human gastrointestinal toxicity: a full in vitro analysis Proceedings of the National Academy of Sciences of the United States of America 1999 96 13 7563 7568 (Pubitemid 29299702)
26. Brooks P., Emery P., Evans J. F., Fenner H., Hawkey C. J., Patrono C., Smolen J., Breedveld F., Day R., Dougados M., Ehrich E. W., Gijon-Baos J., Kvien T. K., Van Rijswijk M. H., Warner T., Zeidler H., Interpreting the clinical significance of the differential inhibition of cyclooxygenase-1 and cyclooxygenase-2 Rheumatology 1999 38 8 779 788
27. Fracon R. N., Tefilo J. M., Satin R. B., Lamano T., Prostaglandins and bone: potential risks and benefits related to the use of nonsteroidal anti-inflammatory drugs in clinical dentistry Journal of Oral Science 2008 50 3 247 252
28. Ringel R. E., Brenner J. I., Haney P. J., Burns J. E., Moulton A. L., Berman M. A., Prostaglandin-induced periostitis: a complication of long-term PGE1 infusion in an infant with congenital heart disease Radiology 1982 142 3 657 658 (Pubitemid 12180944)
29. Suponitzky I., Weinreb M., Differential effects of systemic prostaglandin E2 on bone mass in rat long bones and calvariae Journal of Endocrinology 1998 156 1 51 57 (Pubitemid 28049863)
30. Jee W. S., Ueno K., Deng Y. P., Woodbury D. M., The effects of prostaglandin E2 in growing rats: increased metaphyseal hard tissue and cortico-endosteal bone formation Calcified Tissue International 1985 37 2 148 157 (Pubitemid 15064731)
31. Lin C. H., Jee W. S., Ma Y. F., Setterberg R. B., Early effects of prostaglandin E2 on bone formation and resorption in different bone sites of rats Bone 1995 17 supplement 4 255S 259S
32. Nefussi J. R., Baron R., PGE2 stimulates both resorption and formation of bone in vitro: differential responses of the periosteum and the endosteum in fetal rat long bone cultures Anatomical Record 1985 211 1 9 16 (Pubitemid 15174468)
33. Kawaguchi H., Pilbeam C. C., Harrison J. R., Raisz L. G., The role of prostaglandins in the regulation of bone metabolism Clinical Orthopaedics and Related Research 1995 313 36 46
34. Dekel S., Lenthall G., Francis M. J., Release of prostaglandins from bone and muscle after tibial fracture. An experimental study in rabbits Journal of Bone and Joint Surgery B 1981 63 2 185 189 (Pubitemid 11098763)
35. Pilbeam C. C., Fall P. M., Alander C. B., Raisz L. G., Differential effects of nonsteroidal anti-inflammatory drugs on constitutive and inducible prostaglandin G/H synthase in cultured bone cells Journal of Bone and Mineral Research 1997 12 8 1198 1203 (Pubitemid 27334965)
36. Zhang X., Schwarz E. M., Young D. A., Puzas J. E., Rosier R. N., O'Keefe R. J., Cyclooxygenase-2 regulates mesenchymal cell differentiation into the osteoblast lineage and is critically involved in bone repair Journal of Clinical Investigation 2002 109 11 1405 1415 (Pubitemid 34596166)
37. Gerstenfeld L. C., Einhorn T. A., COX inhibitors and their effects on bone healing Expert Opinion on Drug Safety 2004 3 2 131 136 (Pubitemid 38765196)
38. Arikawa T., Omura K., Morita I., Regulation of bone morphogenetic protein-2 expression by endogenous prostaglandin E2 in human mesenchymal stem cells Journal of Cellular Physiology 2004 200 3 400 406 (Pubitemid 39006932)
39. Jurado S., Garcia-Giralt N., Dez-Pérez A., Esbrit P., Yoskovitz G., Agueda L., Urreizti R., Pérez-Edo L., Sal G., Mellibovsky L., Balcells S., Grinberg D., Nogués X., Effect of IL-1, PGE2, and TGF- 1 on the expression of OPG and RANKL in normal and osteoporotic primary human osteoblasts Journal of Cellular Biochemistry 2010 110 2 304 310
40. Paralkar V. M., Grasser W. A., Mansolf A. L., Baumann A. P., Owen T. A., Smock S. L., Martinovic S., Borovecki F., Vukicevic S., Ke H. Z., Thompson D. D., Regulation of BMP-7 expression by retinoic acid and prostaglandin E(2) Journal of Cellular Physiology 2002 190 2 207 217 (Pubitemid 34027823)
41. Coetzee M., Haag M., Joubert A. M., Kruger M. C., Effects of arachidonic acid, docosahexaenoic acid and prostaglandin E(2) on cell proliferation and morphology of MG-63 and MC3T3-E1 osteoblast-like cells Prostaglandins Leukotrienes and Essential Fatty Acids 2007 76 1 35 45 (Pubitemid 46038719)
42. Machwate M., Rodan S. B., Rodan G. A., Harada S. I., Sphingosine kinase mediates cyclic AMP suppression of apoptosis in rat periosteal cells Molecular Pharmacology 1998 54 1 70 77 (Pubitemid 28337588)
43. Machwate M., Harada S., Leu C. T., Seedor G., Labelle M., Gallant M., Hutchins S., Lachance N., Sawyer N., Slipetz D., Metters K. M., Rodan S. B., Young R., Rodan G. A., Prostaglandin receptor EP(4) mediates the bone anabolic effects of PGE(2) Molecular Pharmacology 2001 60 1 36 41 (Pubitemid 32595231)
44. Zhang M., Ho H. C., Sheu T. J., Breyer M. D., Flick L. M., Jonason J. H., Awad H. A., Schwarz E. M., O'Keefe R. J., EP1(-/-) mice have enhanced osteoblast differentiation and accelerated fracture repair Journal of Bone and Mineral Research 2011 26 4 792 802
45. Beck A., Salem K., Krischak G., Kinzl L., Bischoff M., Schmelz A., Nonsteroidal anti-inflammatory drugs (NSAIDs) in the perioperative phase in traumatology and orthopedics. Effects on bone healing Operative Orthopadie und Traumatologie 2005 17 6 569 578 (Pubitemid 43124726)
46. Holdgate A., Pollock T., Systematic review of the relative efficacy of non-steroidal anti-inflammatory drugs and opioids in the treatment of acute renal colic British Medical Journal 2004 328 7453 1401 1404 (Pubitemid 38789190)
47. Monzn D. G., Vazquez J., Jauregui J. R., Iserson K. V., Pain treatment in post-traumatic hip fracture in the elderly: regional block vs. systemic non-steroidal analgesics International Journal of Emergency Medicine 2010 3 4 321 325
48. Stacher G., Steinringer H., Schneider S., Experimental pain induced by electrical and thermal stimulation of the skin in healthy man: sensitivity to 75 and 150mg diclofenac sodium in comparison with 60mg codeine and placebo British Journal of Clinical Pharmacology 1986 21 1 35 43 (Pubitemid 17170750)
49. Kantor T., Cavaliere M. B., Hopper M., Roepke S., A double-blind parallel comparison of ketoprofen, codeine, and placebo in patients with moderate to severe postpartum pain Journal of Clinical Pharmacology 1984 24 5-6 228 234 (Pubitemid 14085334)
50. Ebell M. H., NSAIDs vs. opiates for pain in acute renal colic American Family Physician 2004 70 9 1682
51. Camu F., Beecher T., Recker D. P., Verburg K. M., Valdecoxib, a COX-2-specific inhibitor, is an efficacious, opioid-sparing analgesic in patients undergoing hip arthroplasty American Journal of Therapeutics 2002 9 1 43 51
52. Turner D. M., Warson J. S., Wirt T. C., Scalley R. D., Cochran R. S., Miller K. J., The use of ketorolac in lumbar spine surgery: a cost-benefit analysis Journal of Spinal Disorders 1995 8 3 206 212
53. O'Neill W. M., Hanks G. W., Simpson P., Fallon M. T., Jenkins E., Wesnes K., The cognitive and psychomotor effects of morphine in healthy subjects: a randomized controlled trial of repeated (four) oral doses of dextropropoxyphene, morphine, lorazepam and placebo Pain 2000 85 1-2 209 215 (Pubitemid 30110761)
54. Marret E., Elia N., Dahl J. B., McQuay H. J., Miniche S., Moore R. A., Straube S., Tramr M. R., Susceptibility to fraud in systematic reviews: lessons from the reuben case Anesthesiology 2009 111 6 1279 1289
55. Rittner H. L., Kranke P., Schfer M., Roewer N., Brack A., What can we learn from the Scott Reuben case? scientific misconduct in anaesthesiology Anaesthesist 2009 58 12 1199 1209
56. Trnkvist H., Danielsson B. R., Dencker L., Nilsson O. S., Lack of effect of indomethacin on mesenchymal limb-bud cells in vitro Acta Orthopaedica Scandinavica 1984 55 3 378 380 (Pubitemid 14077619)
57. Ho M. L., Chang J. K., Chuang L. Y., Hsu H. K., Wang G. J., Effects of nonsteroidal anti-inflammatory drugs and prostaglandins on osteoblastic functions Biochemical Pharmacology 1999 58 6 983 990
58. Evans C. E., Butcher C., The influence on human osteoblasts in vitro on non-steroidal anti-inflammatory drugs which act on different cyclooxygenase enzymes Journal of Bone and Joint Surgery B 2004 86 3 444 449 (Pubitemid 38559501)
59. Wang J. L., Lin K. L., Chen J. S., Lu Y. C., Jiann B. P., Chang H. T., Hsu S. S., Chen W. C., Huang J. K., Ho C. M., Jan C. R., Effect of celecoxib on Ca 2+ movement and cell proliferation in human osteoblasts Biochemical Pharmacology 2004 67 6 1123 1130
60. Chang J. K., Wang G. J., Tsai S. T., Ho M. L., Nonsteroidal anti-inflammatory drug effects on osteoblastic cell cycle, cytotoxicity, and cell death Connective Tissue Research 2005 46 4-5 200 210
61. Wang Y., Chen X., Zhu W., Zhang H., Hu S., Cong X., Growth inhibition of mesenchymal stem cells by aspirin: involvement of the wnt/ -catenin signal pathway Clinical and Experimental Pharmacology and Physiology 2006 33 8 696 701 (Pubitemid 44060760)
62. Wiontzek M., Matziolis G., Schuchmann S., Gaber T., Krocker D., Duda G., Burmester G. R., Perka C., Buttgereit F., Effects of dexamethasone and celecoxib on calcium homeostasis and expression of cyclooxygenase-2 mRNA in MG-63 human osteosarcoma cells Clinical and Experimental Rheumatology 2006 24 4 366 372 (Pubitemid 44363536)
63. Wolfesberger B., Hoelzl C., Walter I., Reider G. A., Fertl G., Thalhammer J. G., Skalicky M., Egerbacher M., In vitro effects of meloxicam with or without doxorubicin on canine osteosarcoma cells Journal of Veterinary Pharmacology and Therapeutics 2006 29 1 15 23
64. Chang J. K., Li C. J., Wu S. C., Yeh C. H., Chen C. H., Fu Y. C., Wang G. J., Ho M. L., Effects of anti-inflammatory drugs on proliferation, cytotoxicity and osteogenesis in bone marrow mesenchymal stem cells Biochemical Pharmacology 2007 74 9 1371 1382
65. Kellinsalmi M., Parikka V., Risteli J., Hentunen T., Leskel H. V., Lehtonen S., Selander K., Vnnen K., Lehenkari P., Inhibition of cyclooxygenase-2 down-regulates osteoclast and osteoblast differentiation and favours adipocyte formation in vitro European Journal of Pharmacology 2007 572 2-3 102 110 (Pubitemid 47429646)
66. Arpornmaeklong P., Akarawatcharangura B., Pripatnanont P., Lee S. H., Ohkubo C., Factors influencing effects of specific COX-2 inhibitor NSAIDs on growth and differentiation of mouse osteoblasts on titanium surfaces International Journal of Oral and Maxillofacial Implants 2008 23 6 1071 1081
67. Abukawa H., Phelps M., Jackson P., Smith R. M., Vacanti J. P., Kaban L. B., Troulis M. J., Effect of ibuprofen on osteoblast differentiation of porcine bone marrow-derived progenitor cells Journal of Oral and Maxillofacial Surgery 2009 67 11 2412 2417
68. Chang J. K., Li C. J., Liao H. J., Wang C. K., Wang G. J., Ho M. L., Anti-inflammatory drugs suppress proliferation and induce apoptosis through altering expressions of cell cycle regulators and pro-apoptotic factors in cultured human osteoblasts Toxicology 2009 258 2-3 148 156
69. Kolar P., Lach S., Gaber T., Maschmeyer P., Dziurla R., Tripmacher R., Krocker D., Matziolis G., Perka C., Burmester G. R., Buttgereit F., Effects of celecoxib on the expression of osteoprotegerin, energy metabolism and cell viability in cultured human osteoblastic cells Clinical and Experimental Rheumatology 2009 27 1 99 107
70. Yoon D. S., Yoo J. H., Kim Y. H., Paik S., Han C. D., Lee J. W., The effects of COX-2 inhibitor during osteogenic differentiation of bone marrow-derived human mesenchymal stem cells Stem Cells and Development 2010 19 10 1523 1533
71. Guez L. D. A. R., Nez O. G. A. M., Arroyo-Morales M., Guez-Pérez L. R., Rubio-Ruiz B., Ruiz C., Effects of indomethacin, nimesulide, and diclofenac on human MG-63 osteosarcoma cell line. Biological Research For Nursing. In press
72. Mller M., Raabe O., Addicks K., Wenisch S., Arnhold S., Effects of non-steroidal anti-inflammatory drugs on proliferation, differentiation and migration in equine mesenchymal stem cells Cell Biology International 2011 35 3 235 248
73. Pountos I., Giannoudis P. V., Jones E., English A., Churchman S., Field S., Ponchel F., Bird H., Emery P., Mcgonagle D., NSAIDS inhibit in vitro MSC chondrogenesis but not osteogenesis: implications for mechanism of bone formation inhibition in man Journal of Cellular and Molecular Medicine 2011 15 3 525 534
74. Gerstenfeld L. C., Thiede M., Siebert K., Mielke C., Phippard D., Svagr B., Cullinane D., Einhorn T. A., Differential inhibition of fracture healing by non-selective and cyclooxygenase-2 selective non-steroidal anti-inflammatory drugs Journal of Orthopaedic Research 2003 21 4 670 675 (Pubitemid 36763489)
75. Martin G. J. Jr., Boden S. D., Titus L., Recombinant human bone morphogenetic protein-2 overcomes the inhibitory effect of ketorolac, a nonsteroidal anti-inflammatory drug (NSAID), on posterolateral lumbar intertransverse process spine fusion Spine 1999 24 21 2188 2193
76. Ho M. L., Chang J. K., Wang G. J., Effects of ketorolac on bone repair: a radiographic study in modeled demineralized bone matrix grafted rabbits Pharmacology 1998 57 3 148 159
77. Martins M. V., da Silva M. A., Medici Filho E., de Moraes L. C., Castilho J. C. D. M., da Rocha R. F., Evaluation of digital optical density of bone repair in rats medicated with ketoprofen Brazilian Dental Journal 2005 16 3 207 212 (Pubitemid 43271774)
78. Reikeraas O., Engebretsen L., Effects of ketoralac tromethamine and indomethacin on primary and secondary bone healing. An experimental study in rats Archives of Orthopaedic and Trauma Surgery 1998 118 1-2 50 52 (Pubitemid 29037645)
79. Riew K. D., Long J., Rhee J., Lewis S., Kuklo T., Kim Y., Yukawa Y., Zhu Y., Time-dependent inhibitory effects of indomethacin on spinal fusion Journal of Bone and Joint Surgery A 2003 85 4 632 634 (Pubitemid 36538710)
80. Brown K. M., Saunders M. M., Kirsch T., Donahue H. J., Reid J. S., Effect of COX-2-specific inhibition on fracture-healing in the rat femur Journal of Bone and Joint Surgery A 2004 86 1 116 123 (Pubitemid 38057344)
81. Persson P. E., Sisask G., Nilsson O., Indomethacin inhibits bone formation in inductive allografts but not in autografts: studies in rat Acta Orthopaedica 2005 76 4 465 469 (Pubitemid 41232774)
82. Sudmann E., Bang G., Indomethacin-induced inhibition of haversian remodelling in rabbits Acta Orthopaedica Scandinavica 1979 50 6 621 627 (Pubitemid 10162502)
83. Dimar J. R. II, Ante W. A., Zhang Y. P., Glassman S. D., The effects of nonsteroidal anti-inflammatory drugs on posterior spinal fusions in the rat Spine 1996 21 16 1870 1876 (Pubitemid 26279596)
84. Allen H. L., Wase A., Bear W. T., Indomethacin and aspirin: effect of nonsteroidal anti-inflammatory agents on the rate of fracture repair in the rat Acta Orthopaedica Scandinavica 1980 51 4 595 600 (Pubitemid 10090468)
85. Karachalios T., Boursinos L., Poultsides L., Khaldi L., Malizos K. N., The effects of the short-term administration of low therapeutic doses of anti-COX-2 agents on the healing of fractures: an experimental study in rabbits Journal of Bone and Joint Surgery B 2007 89 9 1253 1260 (Pubitemid 350057968)
86. Keller J., Bnger C., Andreassen T. T., Bak B., Lucht U., Bone repair inhibited by indomethacin. Effects on bone metabolism and strength of rabbit osteotomies Acta Orthopaedica Scandinavica 1987 58 4 379 383 (Pubitemid 17149867)
87. Keller J., Bayer-Kristensen I., Bak B., Bnger C., Kjaersgaard-Andersen P., Lucht U., Melsen F., Indomethacin and bone remodeling. Effect on cortical bone after osteotomy in rabbits Acta Orthopaedica Scandinavica 1989 60 1 119 121 (Pubitemid 19090577)
88. Trnkvist H., Lindholm T. S., Netz P., Strmberg L., Lindholm T. C., Effect of ibuprofen and indomethacin on bone metabolism reflected in bone strength Clinical Orthopaedics and Related Research 1984 187 255 259 (Pubitemid 14063255)
89. Hgevold H. E., Grgaard B., Reikers O., Effects of short-term treatment with corticosteroids and indomethacin on bone healing. A mechanical study of osteotomies in rats Acta Orthopaedica Scandinavica 1992 63 6 607 611
90. Engesaeter L. B., Sudmann B., Sudmann E., Fracture healing in rats inhibited by locally administered indomethacin Acta Orthopaedica Scandinavica 1992 63 3 330 333
91. Sato S., Kim T., Arai T., Maruyama S., Tajima M., Utsumi N., Comparison between the effects of dexamethasone and indomethacin on bone wound healing Japanese Journal of Pharmacology 1986 42 1 71 78 (Pubitemid 16053841)
92. Goodman S., Ma T., Trindade M., Ikenoue T., Matsuura I., Wong N., Fox N., Genovese M., Regula D., Smith R. L., COX-2 selective NSAID decreases bone ingrowth in vivo Journal of Orthopaedic Research 2002 20 6 1164 1169 (Pubitemid 35363972)
93. Kaygusuz M. A., Turan C. C., Aydin N. E., Temel I., Firat S., Bulut T., Kuku I., The effects of G-CSF and naproxen sodium on the serum TGF- 1 level and fracture healing in rat tibias Life Sciences 2006 80 1 67 73 (Pubitemid 44809293)
94. Leonelli S. M., Goldberg B. A., Safanda J., Bagwe M. R., Sethuratnam S., King S. J., Effects of a cyclooxygenase-2 inhibitor (rofecoxib) on bone healing American Journal of Orthopedics 2006 35 2 79 84
95. O'Connor J. P., Capo J. T., Tan V., Cottrell J. A., Manigrasso M. B., Bontempo N., Parsons J. R., A comparison of the effects of ibuprofen and rofecoxib on rabbit fibula osteotomy healing Acta Orthopaedica 2009 80 5 597 605
96. Obeid G., Zhang X., Wang X., Jeffcoat M., Effect of ibuprofen on the healing and remodeling of bone and articular cartilage in the rabbit temporomandibular joint Journal of Oral and Maxillofacial Surgery 1992 50 8 843 859
97. Beck A., Krischak G., Sorg T., Augat P., Farker K., Merkel U., Kinzl L., Claes L., Influence of diclofenac (group of nonsteroidal anti-inflammatory drugs) on fracture healing Archives of Orthopaedic and Trauma Surgery 2003 123 7 327 332 (Pubitemid 37236194)
98. Krischak G. D., Augat P., Sorg T., Blakytny R., Kinzl L., Claes L., Beck A., Effects of diclofenac on periosteal callus maturation in osteotomy healing in an animal model Archives of Orthopaedic and Trauma Surgery 2007 127 1 3 9 (Pubitemid 44964028)
99. Sen C., Erdem M., Gunes T., Koseoglu D., Filiz N. O., Effects of diclofenac and tenoxicam on distraction osteogenesis Archives of Orthopaedic and Trauma Surgery 2007 127 3 153 159 (Pubitemid 46487089)
100. Giordano V., Giordano M., Knackfuss I. G., Apfel M. I., Gomes R. D., Effect of tenoxicam on fracture healing in rat tibiae Injury 2003 34 2 85 94 (Pubitemid 36143629)
101. Simon A. M., O'Connor J. P., Dose and time-dependent effects of cyclooxygenase-2 inhibition on fracture-healing Journal of Bone and Joint Surgery A 2007 89 3 500 511 (Pubitemid 46365350)
102. Bergenstock M., Min W., Simon A. M., Sabatino C., O'Connor J. P., A comparison between the effects of acetaminophen and celecoxib on bone fracture healing in rats Journal of Orthopaedic Trauma 2005 19 10 717 723 (Pubitemid 44378210)
103. Ribeiro F. V., César-Neto J. B., Nociti F. H. Jr, Sallum E. A., Sallum A. W., de Toledo S., Casati M. Z., Selective cyclooxygenase-2 inhibitor may impair bone healing around titanium implants in rats Journal of Periodontology 2006 77 10 1731 1735 (Pubitemid 44680238)
104. Endo K., Sairyo K., Komatsubara S., Sasa T., Egawa H., Yonekura D., Adachi K., Ogawa T., Murakami R. -I., Yasui N., Cyclooxygenase-2 inhibitor inhibits the fracture healing Journal of Physiological Anthropology and Applied Human Science 2002 21 5 235 238
105. Endo K., Sairyo K., Komatsubara S., Sasa T., Egawa H., Ogawa T., Yonekura D., Murakami R. I., Yasui N., Cyclooxygenase-2 inhibitor delays fracture healing in rats Acta Orthopaedica 2005 76 4 470 474 (Pubitemid 41232775)
106. Utvg S. E., Fuskevg O. M., Shegarfi H., Reikers O., Short-term treatment with COX-2 inhibitors does not impair fracture healing Journal of Investigative Surgery 2010 23 5 257 261
107. Gerstenfeld L. C., Al-Ghawas M., Alkhiary Y. M., Cullinane D. M., Krall E. A., Fitch J. L., Webb E. G., Thiede M. A., Einhorn T. A., Selective and nonselective cyclooxygenase-2 inhibitors and experimental frature-healing: reversibility of effects after short-term treatment Journal of Bone and Joint Surgery A 2007 89 1 114 125 (Pubitemid 46059150)
108. Goodman S. B., Ma T., Mitsunaga L., Miyanishi K., Genovese M. C., Smith R. L., Temporal effects of a COX-2-selective NSAID on bone ingrowth Journal of Biomedical Materials Research A 2005 72 3 279 287 (Pubitemid 40270998)
109. Murnaghan M., Li G., Marsh D. R., Nonsteroidal anti-inflammatory drug-induced fracture nonunion: an inhibition of angiogenesis? Journal of Bone and Joint Surgery A 2006 88 supplement 3 S140 S147
110. Fracon R. N., Tefilo J. M., Moris L. C., Lamano T., Treatment with paracetamol, ketorolac or etoricoxib did not hinder alveolar bone healing: a histometric study in rats Journal of Applied Oral Science 2010 18 6 630 634
111. Mullis B. H., Copland S. T., Weinhold P. S., Miclau T., Lester G. E., Bos G. D., Effect of COX-2 inhibitors and non-steroidal anti-inflammatory drugs on a mouse fracture model Injury 2006 37 9 827 837
112. Urrutia J., Mardones R., Quezada F., The effect of ketoprophen on lumbar spinal fusion healing in a rabbit model. Laboratory investigation Journal of Neurosurgery: Spine 2007 7 6 631 636 (Pubitemid 350291547)
113. van der Heide H. J., Hannink G., Buma P., Schreurs B. W., No effect of ketoprofen and meloxicam on bone graft ingrowth: a bone chamber study in goats Acta Orthopaedica 2008 79 4 548 554
114. Elves M. W., Bayley I., Roylance P. J., The effect of Indomethacin upon experimental fractures in the rat Acta Orthopaedica Scandinavica 1982 53 1 35 41 (Pubitemid 12184149)
115. Keller J., Kjaersgaard-Andersen P., Bayer-Kristensen I., Melsen F., Indomethacin and bone trauma. Effects on remodelling of rabbit bone Acta Orthopaedica Scandinavica 1990 61 1 66 69 (Pubitemid 20147404)
116. Boiskin I., Epstein S., Ismail F., Fallon M. D., Levy W., Long term administration of prostaglandin inhibitors in vivo fail to influence cartilage and bone mineral metabolism in the rat Bone and Mineral 1988 4 1 27 36
117. Mbugua S. W., Skoglund L. A., Lkken P., Effects of phenylbutazone and indomethacin on the post-operative course following experimental orthopaedic surgery in dogs Acta veterinaria Scandinavica 1989 30 1 27 35
118. Sudmann E., Tveita T., Hald Jr. J. Jr, Lack of effect of indomethacin on ordered growth of the femur in rats Acta Orthopaedica Scandinavica 1982 53 1 43 49 (Pubitemid 12184150)
119. Long J., Lewis S., Kuklo T., Zhu Y., Riew K. D., The effect of cyclooxygenase-2 inhibitors on spinal fusion Journal of Bone and Joint Surgery 2002 84 10 1763 1768 (Pubitemid 35176467)
120. Mullis B., Copeland S., Weinhold P., Helms J., Miclau T., Lester G., Bos G., Effect of COX-2 inhibitors and NSAIDs on fracture healing in a mouse model Transactions of the Annual MeetingOrthopaedic Research Society 2002 27 712
121. Trnkvist H., Lindholm T. S., Effect of ibuprofen on mass and composition of fracture callus and bone. An experimental study on adult rat Scandinavian Journal of Rheumatology 1980 9 3 167 171 (Pubitemid 11194376)
122. Huo M. H., Troiano N. W., Pelker R. R., Gundberg C. M., Friedlaender G. E., The influence of Ibuprofen on fracture repair: biomechanical, biochemical, histologic, and histomorphometric parameters in rats Journal of Orthopaedic Research 1991 9 3 383 390
123. Tiseo B. C., Namur G. N., de Paula E. J., Junior R. M., de Oliveira C. R., Experimental study of the action of COX-2 selective nonsteroidal anti-inflammatory drugs and traditional anti-inflammatory drugs in bone regeneration Clinics 2006 61 3 223 230 (Pubitemid 44047810)
124. Tefilo J. M., Giovanini G. S., Fracon R. N., Lamano T., Histometric study of alveolar bone healing in rats treated with the nonsteroidal anti-inflammatory drug nimesulide Implant Dentistry 2011 20 2 e7 e13
125. Hak D. J., Schulz K. S., Khoie B., Hazelwood S. J., The effect of Cox-2 specific inhibition on direct fracture healing in the rabbit tibia Journal of Orthopaedic Science 2011 16 1 93 98
126. Nyangoga H., Aguado E., Goyenvalle E., Baslé M. F., Chappard D., A non-steroidal anti-inflammatory drug (ketoprofen) does not delay -TCP bone graft healing Acta Biomaterialia 2010 6 8 3310 3317
127. Altman R. D., Latta L. L., Keer R., Renfree K., Hornicek F. J., Banovac K., Effect of nonsteroidal antiinflammatory drugs on fracture healing: a laboratory study in rats Journal of Orthopaedic Trauma 1995 9 5 392 400
128. Deguchi M., Rapoff A. J., Zdeblick T. A., Posterolateral fusion for isthmic spondylolisthesis in adults: analysis of fusion rate and clinical results Journal of Spinal Disorders 1998 11 6 459 464 (Pubitemid 29024381)
129. Glassman S. D., Rose S. M., Dimar J. R., Puno R. M., Campbell M. J., Johnson J. R., The effect of postoperative nonsteroidal anti-inflammatory drug administration on spinal fusion Spine 1998 23 7 834 838 (Pubitemid 28169215)
130. Vitale M. G., Choe J. C., Hwang M. W., Bauer R. M., Hyman J. E., Lee F. Y., Roye D. P. Jr, Use of ketorolac tromethamine in children undergoing scoliosis surgery: an analysis of complications Spine Journal 2003 3 1 55 62 (Pubitemid 38351773)
131. Park S. Y., Moon S. H., Park M. S., Oh K. S., Lee H. M., The effects of ketorolac injected via patient controlled analgesia postoperatively on spinal fusion Yonsei Medical Journal 2005 46 2 245 251
132. Pradhan B. B., Tatsumi R. L., Gallina J., Kuhns C. A., Wang J. C., Dawson E. G., Ketorolac and spinal fusion: does the perioperative use of ketorolac really inhibit spinal fusion? Spine 2008 33 19 2079 2082
133. Sucato D. J., Lovejoy J. F., Agrawal S., Elerson E., Nelson T., McClung A., Postoperative ketorolac does not predispose to pseudoarthrosis following posterior spinal fusion and instrumentation for adolescent idiopathic scoliosis Spine 2008 33 10 1119 1124 (Pubitemid 351630223)
134. Lumawig J. M., Yamazaki A., Watanabe K., Dose-dependent inhibition of diclofenac sodium on posterior lumbar interbody fusion rates Spine Journal 2009 9 5 343 349
135. Horn P. L., Wrona S., Beebe A. C., Klamar J. E., A retrospective quality improvement study of ketorolac use following spinal fusion in pediatric patients Orthopaedic Nursing 2010 29 5 342 343
136. Davis T. R., Ackroyd C. E., Non-steroidal anti-inflammatory agents in the management of Colles' fractures British Journal of Clinical Practice 1988 42 5 184 189
137. Adolphson P., Abbaszadegan H., Jonsson U., Dalen N., Sjoberg H. E., Kalen S., No effects of piroxicam on osteopenia and recovery after Colles' fracture. A randomized, double-blind, placebo-controlled, prospective trial Archives of Orthopaedic and Trauma Surgery 1993 112 3 127 130 (Pubitemid 23194371)
138. Butcher C. K., Marsh D. R., Non-steroidal anti-inflammatory drugs delay tibial fracture union Injury 1996 27 5 375
139. Wurnig C., Schwameis E., Bitzan P., Kainberger F., Six-year results of a cementless stem with prophylaxis against heterotopic bone Clinical Orthopaedics and Related Research 1999 361 150 158 (Pubitemid 29169804)
140. Giannoudis P. V., MacDonald D. A., Matthews S. J., Smith R. M., Furlong A. J., de Boer P., Nonunion of the femoral diaphysis. The influence of reaming and non-steroidal anti-inflammatory drugs Journal of Bone and Joint Surgery 2000 82 5 655 658
141. Bhandari M., Tornetta P. III, Sprague S., Najibi S., Petrisor B., Griffith L., Guyatt G. H., Predictors of reoperation following operative management of fractures of the tibial shaft Journal of Orthopaedic Trauma 2003 17 5 353 361 (Pubitemid 36701599)
142. Burd T. A., Hughes M. S., Anglen J. O., Heterotopic ossification prophylaxis with indomethacin increases the risk of long-bone nonunion Journal of Bone and Joint Surgery 2003 85 5 700 705 (Pubitemid 36927035)
143. Sculean A., Berakdar M., Donos N., Auschill T. M., Arweiler N. B., The effect of postsurgical administration of a selective cyclo-oxygenase-2 inhibitor on the healing of intrabony defects following treatment with enamel matrix proteins Clinical Oral Investigations 2003 7 2 108 112
144. Bhattacharyya T., Levin R., Vrahas M. S., Solomon D. H., Nonsteroidal antiinflammatory drugs and nonunion of humeral shaft fractures Arthritis Care and Research 2005 53 3 364 367 (Pubitemid 40799874)
145. Meunier A., Aspenberg P., Good L., Celecoxib does not appear to affect prosthesis fixation in total knee replacement: a randomized study using radiostereometry in 50 patients Acta Orthopaedica 2009 80 1 46 50
146. Aerssens J., Boonen S., Lowet G., Dequeker J., Interspecies differences in bone composition, density, and quality: potential implications for in vivo bone research Endocrinology 1998 139 2 663 670 (Pubitemid 28513217)
147. Miyatake S., Ichiyama H., Kondo E., Yasuda K., Randomized clinical comparisons of diclofenac concentration in the soft tissues and blood plasma between topical and oral applications British Journal of Clinical Pharmacology 2009 67 1 125 129
148. Rahal A., Kumar A., Ahmad A. H., Malik J. K., Pharmacokinetics of diclofenac and its interaction with enrofloxacin in sheep Research in Veterinary Science 2008 84 3 452 456 (Pubitemid 351486847)
149. Pountos I., Georgouli T., Giannoudis P. V., The effect of autologous serum obtained after fracture on the proliferation and osteogenic differentiation of mesenchymal stem cells Cellular and Molecular Biology 2008 54 1 33 39
150. Pountos I., Georgouli T., Perry S., Morley J., Giannoudis P., Systemic signals after fracture: their effect in osteogenesis Injury Extra 2007 38 161 162
151. Arnold P. M., Klemp J. A., Assessment of malunion in spinal fusion Neurosurgery Quarterly 2005 15 4 239 247 (Pubitemid 44481186)
152. Fransen M., Neal B., Non-steroidal anti-inflammatory drugs for preventing heterotopic bone formation after hip arthroplasty Cochrane Database of Systematic Reviews 2004 3
153. McCarthy E. F., Sundaram M., Heterotopic ossification: a review Skeletal Radiology 2005 34 10 609 619 (Pubitemid 41440002)
154. Bossche L. V., Vanderstraeten G., Heterotopic ossification: a review Journal of Rehabilitation Medicine 2005 37 3 129 136 (Pubitemid 40775150)
155. Song L., Tuan R. S., Transdifferentiation potential of human mesenchymal stem cells derived from bone marrow FASEB Journal 2004 18 9 980 982 (Pubitemid 39561498)
156. Dahners L. E., Mullis B. H., Effects of nonsteroidal anti-inflammatory drugs on bone formation and soft-tissue healing The Journal of the American Academy of Orthopaedic Surgeons 2004 12 3 139 143