Do Nonsteroidal Anti-Inflammatory Drugs Affect Bone Healing? A Critical Analysis

Nonsteroidal anti-inflammatory drugs (NSAIDs) play an essential part in our approach to control pain in the posttraumatic setting. Over the last decades, several studies suggested that NSAIDs interfere with bone healing while others contradict these findings. Although their analgesic potency is well proven, clinicians remain puzzled over the potential safety issues. We have systematically reviewed the available literature, analyzing and presenting the available in vitro animal and clinical studies on this field. Our comprehensive review reveals the great diversity of the presented data in all groups of studies. Animal and in vitro studies present so conflicting data that even studies with identical parameters have opposing results. Basic science research defining the exact mechanism with which NSAIDs could interfere with bone cells and also the conduction of well-randomized prospective clinical trials are warranted. In the absence of robust clinical or scientific evidence, clinicians should treat NSAIDs as a risk factor for bone healing impairment, and their administration should be avoided in high-risk patients.

[1]  L. Díaz-Rodríguez,et al.  Effects of Indomethacin, Nimesulide, and Diclofenac on Human MG-63 Osteosarcoma Cell Line , 2012, Biological research for nursing.

[2]  P. Giannoudis,et al.  The effect of antibiotics on bone healing: current evidence , 2011, Expert opinion on drug safety.

[3]  T. Lamano,et al.  Histometric Study of Alveolar Bone Healing in Rats Treated With the Nonsteroidal Anti-Inflammatory Drug Nimesulide , 2011, Implant dentistry.

[4]  K. Addicks,et al.  Effects of non‐steroidal anti‐inflammatory drugs on proliferation, differentiation and migration in equine mesenchymal stem cells , 2011, Cell biology international.

[5]  P. Giannoudis,et al.  Nonsteroidal anti-inflammatory drugs: prostaglandins, indications, and side effects , 2011 .

[6]  T. Lamano,et al.  Treatment with paracetamol, ketorolac or etoricoxib did not hinder alveolar bone healing: a histometric study in rats , 2010, Journal of applied oral science : revista FOB.

[7]  K. Iserson,et al.  Pain treatment in post-traumatic hip fracture in the elderly: regional block vs. systemic non-steroidal analgesics. , 2010, International journal of emergency medicine.

[8]  E. Schwarz,et al.  EP1−/− Mice Have Enhanced Osteoblast Differentiation and Accelerated Fracture Repair , 2010, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[9]  O. Reikerås,et al.  Short-Term Treatment with COX-2 Inhibitors Does Not Impair Fracture Healing. , 2010, Journal of investigative surgery : the official journal of the Academy of Surgical Research.

[10]  P. Horn,et al.  A Retrospective Quality Improvement Study of Ketorolac Use Following Spinal Fusion in Pediatric Patients , 2010, Orthopedic nursing.

[11]  D. Chappard,et al.  A non steroidal anti inflammatory drug (Ketoprofen) does not delay βeta-TCP bone graft healing , 2010 .

[12]  A. Díez-Pérez,et al.  Effect of IL‐1β, PGE2, and TGF‐β1 on the expression of OPG and RANKL in normal and osteoporotic primary human osteoblasts , 2010, Journal of cellular biochemistry.

[13]  Y. Kim,et al.  The effects of COX-2 inhibitor during osteogenic differentiation of bone marrow-derived human mesenchymal stem cells. , 2010, Stem cells and development.

[14]  P. Giannoudis,et al.  NSAIDS inhibit in vitro MSC chondrogenesis but not osteogenesis: implications for mechanism of bone formation inhibition in man , 2010, Journal of cellular and molecular medicine.

[15]  Sebastian Straube,et al.  Susceptibility to Fraud in Systematic Reviews: Lessons from the Reuben Case , 2009, Anesthesiology.

[16]  N Roewer,et al.  [What can we learn from the Scott Reuben case? Scientific misconduct in anaesthesiology]. , 2009, Der Anaesthesist.

[17]  J. Vacanti,et al.  Effect of ibuprofen on osteoblast differentiation of porcine bone marrow-derived progenitor cells. , 2009, Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons.

[18]  J. Capo,et al.  A comparison of the effects of ibuprofen and rofecoxib on rabbit fibula osteotomy healing , 2009, Acta orthopaedica.

[19]  J. M. T. Lumawig,et al.  Dose-dependent inhibition of diclofenac sodium on posterior lumbar interbody fusion rates. , 2009, The spine journal : official journal of the North American Spine Society.

[20]  Gwo‐Jaw Wang,et al.  Anti-inflammatory drugs suppress proliferation and induce apoptosis through altering expressions of cell cycle regulators and pro-apoptotic factors in cultured human osteoblasts. , 2009, Toxicology.

[21]  P. Aspenberg,et al.  Celecoxib does not appear to affect prosthesis fixation in total knee replacement , 2009, Acta orthopaedica.

[22]  P. Pripatnanont,et al.  Factors influencing effects of specific COX-2 inhibitor NSAIDs on growth and differentiation of mouse osteoblasts on titanium surfaces. , 2008, The International journal of oral & maxillofacial implants.

[23]  P. Giannoudis,et al.  The effect of autologous serum obtained after fracture on the proliferation and osteogenic differentiation of mesenchymal stem cells. , 2008, Cellular and molecular biology.

[24]  Jeffrey C. Wang,et al.  Ketorolac and Spinal Fusion: Does the Perioperative Use of Ketorolac Really Inhibit Spinal Fusion? , 2008, Spine.

[25]  T. Lamano,et al.  Prostaglandins and bone: potential risks and benefits related to the use of nonsteroidal anti-inflammatory drugs in clinical dentistry. , 2008, Journal of oral science.

[26]  J. Malik,et al.  Pharmacokinetics of diclofenac and its interaction with enrofloxacin in sheep. , 2008, Research in veterinary science.

[27]  J. Lovejoy,et al.  Postoperative Ketorolac Does Not Predispose to Pseudoarthrosis Following Posterior Spinal Fusion and Instrumentation for Adolescent Idiopathic Scoliosis , 2008, Spine.

[28]  P. Giannoudis,et al.  Pharmacological agents and impairment of fracture healing: what is the evidence? , 2008, Injury.

[29]  B. W. Schreurs,et al.  No effect of ketoprofen and meloxicam on bone graft ingrowth: A bone chamber study in goats , 2008, Acta orthopaedica.

[30]  J. Urrutia,et al.  The effect of ketoprophen on lumbar spinal fusion healing in a rabbit model. Laboratory investigation. , 2007, Journal of neurosurgery. Spine.

[31]  Gwo‐Jaw Wang,et al.  Effects of anti-inflammatory drugs on proliferation, cytotoxicity and osteogenesis in bone marrow mesenchymal stem cells. , 2007, Biochemical pharmacology.

[32]  Hannu-Ville Leskelä,et al.  Inhibition of cyclooxygenase-2 down-regulates osteoclast and osteoblast differentiation and favours adipocyte formation in vitro. , 2007, European journal of pharmacology.

[33]  T. Karachalios,et al.  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. , 2007, The Journal of bone and joint surgery. British volume.

[34]  P. Giannoudis,et al.  Systemic signals after fracture: Their effect in osteogenesis , 2007 .

[35]  A. M. Simon,et al.  Dose and time-dependent effects of cyclooxygenase-2 inhibition on fracture-healing. , 2007, The Journal of bone and joint surgery. American volume.

[36]  C. Şen,et al.  Effects of diclofenac and tenoxicam on distraction osteogenesis , 2007, Archives of Orthopaedic and Trauma Surgery.

[37]  I. Temel,et al.  The effects of G-CSF and naproxen sodium on the serum TGF-beta1 level and fracture healing in rat tibias. , 2006, Life sciences.

[38]  Gang Li,et al.  Nonsteroidal anti-inflammatory drug-induced fracture nonunion: an inhibition of angiogenesis? , 2006, The Journal of bone and joint surgery. American volume.

[39]  F. V. Ribeiro,et al.  Selective cyclooxygenase-2 inhibitor may impair bone healing around titanium implants in rats. , 2006, Journal of periodontology.

[40]  P. Weinhold,et al.  Effect of COX-2 inhibitors and non-steroidal anti-inflammatory drugs on a mouse fracture model. , 2006, Injury.

[41]  L. Claes,et al.  Effects of diclofenac on periosteal callus maturation in osteotomy healing in an animal model , 2006, Archives of Orthopaedic and Trauma Surgery.

[42]  H. Zhang,et al.  GROWTH INHIBITION OF MESENCHYMAL STEM CELLS BY ASPIRIN: INVOLVEMENT OF THE WNT/β‐CATENIN SIGNAL PATHWAY , 2006, Clinical and experimental pharmacology & physiology.

[43]  T. Gaber,et al.  Effects of dexamethasone and celecoxib on calcium homeostasis and expression of cyclooxygenase-2 mRNA in MG-63 human osteosarcoma cells. , 2006, Clinical and experimental rheumatology.

[44]  B. Tiseo,et al.  Experimental study of the action of COX-2 selective nonsteroidal anti-inflammatory drugs and traditional anti-inflammatory drugs in bone regeneration. , 2006, Clinics.

[45]  M. Skalicky,et al.  In vitro effects of meloxicam with or without doxorubicin on canine osteosarcoma cells. , 2006, Journal of veterinary pharmacology and therapeutics.

[46]  B. Goldberg,et al.  Effects of a cyclooxygenase-2 inhibitor (rofecoxib) on bone healing. , 2006, American journal of orthopedics.

[47]  E. Medici Filho,et al.  Evaluation of digital optical density of bone repair in rats medicated with ketoprofen. , 2005, Brazilian dental journal.

[48]  Eleftherios Tsiridis,et al.  Current concepts of molecular aspects of bone healing. , 2005, Injury.

[49]  J. A. Klemp,et al.  Assessment of Malunion in Spinal Fusion , 2005 .

[50]  G. Krischak,et al.  Nonsteroidal anti-inflammatory drugs (NSAIDs) in the perioperative phase in traumatology and orthopedics effects on bone healing. , 2005, Operative Orthopadie und Traumatologie.

[51]  A. M. Simon,et al.  A Comparison Between the Effects of Acetaminophen and Celecoxib on Bone Fracture Healing in Rats , 2005, Journal of orthopaedic trauma.

[52]  Z. Radi,et al.  Effects of cyclooxygenase inhibition on bone, tendon, and ligament healing , 2005, Inflammation Research.

[53]  M. Sundaram,et al.  Heterotopic ossification: a review , 2005, Skeletal Radiology.

[54]  Jorge Andrade,et al.  Characterization of monoclonal antibodies against altered (T103I) amidase from Pseudomonas aeruginosa , 2005, Molecular biotechnology.

[55]  D. Solomon,et al.  Nonsteroidal antiinflammatory drugs and nonunion of humeral shaft fractures. , 2005, Arthritis and rheumatism.

[56]  G. Vanderstraeten,et al.  Heterotopic ossification: a review. , 2005, Journal of rehabilitation medicine.

[57]  S. Moon,et al.  The Effects of Ketorolac Injected via Patient Controlled Analgesia Postoperatively on Spinal Fusion , 2005, Yonsei medical journal.

[58]  M. Genovese,et al.  Temporal effects of a COX-2-selective NSAID on bone ingrowth. , 2005, Journal of biomedical materials research. Part A.

[59]  O. Nilsson,et al.  Indomethacin inhibits bone formation in inductive allografts but not in autografts , 2005, Acta orthopaedica.

[60]  Gwo‐Jaw Wang,et al.  Nonsteroidal Anti-Inflammatory Drug Effects on Osteoblastic Cell Cycle, Cytotoxicity, and Cell Death , 2005, Connective tissue research.

[61]  K. Sairyo,et al.  Cyclooxygenase-2 inhibitor delays fracture healing in rats , 2005, Acta orthopaedica.

[62]  M. Ebell NSAIDs vs. opiates for pain in acute renal colic. , 2004, American family physician.

[63]  I. Morita,et al.  Regulation of bone morphogenetic protein‐2 expression by endogenous prostaglandin E2 in human mesenchymal stem cells , 2004, Journal of cellular physiology.

[64]  E. Sánchez-Alepuz,et al.  Nonunion of the humeral shaft: long lateral butterfly fracture--a nonunion predictive pattern? , 2004, Clinical orthopaedics and related research.

[65]  A. Holdgate,et al.  Systematic review of the relative efficacy of non-steroidal anti-inflammatory drugs and opioids in the treatment of acute renal colic , 2004, BMJ : British Medical Journal.

[66]  R. Tuan,et al.  Transdifferentiation potential of human mesenchymal stem cells derived from bone marrow , 2004, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[67]  J. Mitchell,et al.  Cyclooxygenases: new forms, new inhibitors, and lessons from the clinic , 2004, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[68]  L. Dahners,et al.  Effects of nonsteroidal anti-inflammatory drugs on bone formation and soft-tissue healing. , 2004, The Journal of the American Academy of Orthopaedic Surgeons.

[69]  C. E. Evans,et al.  The influence on human osteoblasts in vitro of non-steroidal anti-inflammatory drugs which act on different cyclooxygenase enzymes. , 2004, The Journal of bone and joint surgery. British volume.

[70]  Hong‐Tai Chang,et al.  Effect of celecoxib on Ca2+ movement and cell proliferation in human osteoblasts. , 2004, Biochemical pharmacology.

[71]  T. Einhorn,et al.  COX inhibitors and their effects on bone healing. , 2004, Expert opinion on drug safety.

[72]  J. Puzas,et al.  Pharmacologic modulators of fracture healing: the role of cyclooxygenase inhibition. , 2003, Journal of musculoskeletal & neuronal interactions.

[73]  N. Gajraj The Effect of Cyclooxygenase-2 Inhibitors on Bone Healing , 2002, Regional Anesthesia & Pain Medicine.

[74]  J. Anglen,et al.  Heterotopic ossification prophylaxis with indomethacin increases the risk of long-bone nonunion. , 2003, The Journal of bone and joint surgery. British volume.

[75]  K. Seibert,et al.  Differential inhibition of fracture healing by non‐selective and cyclooxygenase‐2 selective non‐steroidal anti‐inflammatory drugs , 2003, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[76]  L. Claes,et al.  Influence of diclofenac (group of nonsteroidal anti-inflammatory drugs) on fracture healing , 2003, Archives of Orthopaedic and Trauma Surgery.

[77]  G. Guyatt,et al.  Predictors of reoperation following operative management of fractures of the tibial shaft , 2003, Journal of orthopaedic trauma.

[78]  A. Sculean,et al.  The effect of postsurgical administration of a selective cyclo-oxygenase-2 inhibitor on the healing of intrabony defects following treatment with enamel matrix proteins , 2003, Clinical Oral Investigations.

[79]  K. Riew,et al.  Time-Dependent Inhibitory Effects of Indomethacin on Spinal Fusion , 2003, The Journal of bone and joint surgery. American volume.

[80]  M. Giordano,et al.  Effect of tenoxicam on fracture healing in rat tibiae. , 2003, Injury.

[81]  M. Genovese,et al.  COX‐2 selective NSAID decreases bone ingrowth in vivo , 2002, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[82]  K. Riew,et al.  The Effect of Cyclooxygenase-2 Inhibitors on Spinal Fusion , 2002, The Journal of bone and joint surgery. American volume.

[83]  K. Sairyo,et al.  Cyclooxygenase-2 inhibitor inhibits the fracture healing. , 2002, Journal of physiological anthropology and applied human science.

[84]  E. Schwarz,et al.  Cyclooxygenase-2 regulates mesenchymal cell differentiation into the osteoblast lineage and is critically involved in bone repair. , 2002, The Journal of clinical investigation.

[85]  S. Vukicevic,et al.  Regulation of BMP‐7 expression by retinoic acid and prostaglandin E2 , 2002, Journal of cellular physiology.

[86]  F. Camu,et al.  Valdecoxib, a COX-2–Specific Inhibitor, Is an Efficacious, Opioid-Sparing Analgesic in Patients Undergoing Hip Arthroplasty , 2002, American journal of therapeutics.

[87]  L. Claes,et al.  The effect of micromovement on callus formation , 2001, Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association.

[88]  C. Leu,et al.  Prostaglandin receptor EP(4) mediates the bone anabolic effects of PGE(2). , 2001, Molecular pharmacology.

[89]  D. Deheer,et al.  Reversal of the Detrimental Effects of Chronic Protein Malnutrition on Long Bone Fracture Healing , 2001, Journal of orthopaedic trauma.

[90]  D. Macdonald,et al.  Nonunion of the femoral diaphysis. The influence of reaming and non-steroidal anti-inflammatory drugs. , 2000, The Journal of bone and joint surgery. British volume.

[91]  A. Livingston Mechanism of action of nonsteroidal anti-inflammatory drugs. , 2000, The Veterinary clinics of North America. Small animal practice.

[92]  D. Macdonald,et al.  Nonunion of the femoral diaphysis , 2000 .

[93]  G. Hanks,et al.  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 , 2000, Pain.

[94]  L. Titus,et al.  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. , 1999, Spine.

[95]  M. Ho,et al.  Effects of nonsteroidal anti-inflammatory drugs and prostaglandins on osteoblastic functions. , 1999, Biochemical pharmacology.

[96]  M. Dougados,et al.  Interpreting the clinical significance of the differential inhibition of cyclooxygenase-1 and cyclooxygenase-2. , 1999, Rheumatology.

[97]  J. Vane,et al.  Nonsteroid drug selectivities for cyclo-oxygenase-1 rather than cyclo-oxygenase-2 are associated with human gastrointestinal toxicity: a full in vitro analysis. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[98]  A. Whelton Nephrotoxicity of nonsteroidal anti-inflammatory drugs: physiologic foundations and clinical implications. , 1999, The American journal of medicine.

[99]  J. van Ryn,et al.  Clinical experience with cyclooxygenase-2 inhibitors , 1999, Inflammation Research.

[100]  F. Kainberger,et al.  Six-year results of a cementless stem with prophylaxis against heterotopic bone. , 1999, Clinical orthopaedics and related research.

[101]  G. FitzGerald,et al.  Systemic biosynthesis of prostacyclin by cyclooxygenase (COX)-2: the human pharmacology of a selective inhibitor of COX-2. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[102]  A. Rapoff,et al.  Posterolateral fusion for isthmic spondylolisthesis in adults: analysis of fusion rate and clinical results. , 1998, Journal of spinal disorders.

[103]  T A Einhorn,et al.  The cell and molecular biology of fracture healing. , 1998, Clinical orthopaedics and related research.

[104]  Gwo‐Jaw Wang,et al.  Effects of Ketorolac on Bone Repair: A Radiographic Study in Modeled Demineralized Bone Matrix Grafted Rabbits , 1998, Pharmacology.

[105]  Lutz Claes,et al.  Local tissue properties in bone healing: Influence of size and stability of the osteotomy gap , 1998, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[106]  S. Rodan,et al.  Sphingosine kinase mediates cyclic AMP suppression of apoptosis in rat periosteal cells. , 1998, Molecular pharmacology.

[107]  John R. Johnson,et al.  The Effect of Postoperative Nonsteroidal Anti‐inflammatory Drug Administration on Spinal Fusion , 1998, Spine.

[108]  S. Boonen,et al.  Interspecies differences in bone composition, density, and quality: potential implications for in vivo bone research. , 1998, Endocrinology.

[109]  L. Raisz,et al.  Differential Effects of Nonsteroidal Anti‐Inflammatory Drugs on Constitutive and Inducible Prostaglandin G/H Synthase in Cultured Bone Cells , 1997, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[110]  William A. Ante,et al.  The Effects of Nonsteroidal Anti‐inflammatory Drugs on Posterior Spinal Fusions in the Rat , 1996, Spine.

[111]  D. Marsh,et al.  Nonsteroidal anti-inflammatory drugs delay tibial fracture union , 1996 .

[112]  M. Saleh,et al.  Dynamization of the fixator is associated with successful outcome in the treatment of recent tibial fractures with the Othofix external fixator , 1996 .

[113]  M. Mitchell,et al.  Prostaglandin H synthase-2 in human gestational tissues: regulation in amnion. , 1996, Placenta.

[114]  Y. Ma,et al.  Early effects of prostaglandin E2 on bone formation and resorption in different bone sites of rats. , 1995, Bone.

[115]  K Banovac,et al.  Effect of Nonsteroidal Antiinflammatory Drugs on Fracture Healing: A Laboratory Study in Rats , 1995, Journal of orthopaedic trauma.

[116]  P Augat,et al.  Effect of dynamization on gap healing of diaphyseal fractures under external fixation. , 1995, Clinical biomechanics.

[117]  D. M. Turner,et al.  The use of ketorolac in lumbar spine surgery: a cost-benefit analysis. , 1995, Journal of spinal disorders.

[118]  H. Kawaguchi,et al.  The role of prostaglandins in the regulation of bone metabolism. , 1995, Clinical orthopaedics and related research.

[119]  H. Sjöberg,et al.  No effects of piroxicam on osteopenia and recovery after Colles' fracture , 1993, Archives of Orthopaedic and Trauma Surgery.

[120]  X. Wang,et al.  Effect of ibuprofen on the healing and remodeling of bone and articular cartilage in the rabbit temporomandibular joint. , 1992, Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons.

[121]  R. Pelker,et al.  The influence of ibuprofen on fracture repair: Biomechanical, biochemical, histologic, and histomorphometric parameters in rats , 1991, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[122]  F. Melsen,et al.  Indomethacin and bone trauma. Effects on remodeling of rabbit bone. , 1990, Acta orthopaedica Scandinavica.

[123]  L. A. Skoglund,et al.  Effects of Phenylbutazone and Indomethacin on the Post-operative Course following Experimental Orthopaedic Surgery in Dogs , 1989, Acta Veterinaria Scandinavica.

[124]  F. Melsen,et al.  Indomethacin and bone remodeling. Effect on cortical bone after osteotomy in rabbits. , 1989, Acta orthopaedica Scandinavica.

[125]  T. Davis,et al.  Non‐steroidal anti‐inflammatory agents in the management of Colles' fractures , 1988, The British journal of clinical practice.

[126]  S. Epstein,et al.  Long term administration of prostaglandin inhibitors in vivo fail to influence cartilage and bone mineral metabolism in the rat. , 1988, Bone and mineral.

[127]  C. Bünger,et al.  Bone repair inhibited by indomethacin. Effects on bone metabolism and strength of rabbit osteotomies. , 1987, Acta orthopaedica Scandinavica.

[128]  B. Rahn Direct and indirect bone healing after operative fracture treatment. , 1987, Otolaryngologic clinics of North America.

[129]  N. Utsumi,et al.  Comparison between the effects of dexamethasone and indomethacin on bone wound healing. , 1986, Japanese journal of pharmacology.

[130]  R. Baron,et al.  PGE2 stimulates both resorption and formation of bone in vitro: Differential responses of the periosteum and the endosteum in fetal rat long bone cultures , 1985, The Anatomical record.

[131]  P. Netz,et al.  Effect of ibuprofen and indomethacin on bone metabolism reflected in bone strength. , 1984, Clinical orthopaedics and related research.

[132]  O. Nilsson,et al.  Lack of effect of indomethacin on mesenchymal limb-bud cells in vitro. , 1984, Acta orthopaedica Scandinavica.

[133]  T. Kantor,et al.  A Double‐Blind Parallel Comparison of Ketoprofen, Codeine, and Placebo in Patients with Moderate to Severe Postpartum Pain , 1984, Journal of clinical pharmacology.

[134]  J. Brenner,et al.  Prostaglandin-induced periostitis: a complication of long-term PGE1 infusion in an infant with congenital heart disease. , 1982, Radiology.

[135]  M. Elves,et al.  The effect of indomethacin upon experimental fractures in the rat. , 1982, Acta orthopaedica Scandinavica.

[136]  S. Dekel,et al.  Release of prostaglandins from bone and muscle after tibial fracture. An experimental study in rabbits. , 1981, The Journal of bone and joint surgery. British volume.

[137]  A. Wase,et al.  Indomethacin and aspirin: effect of nonsteroidal anti-inflammatory agents on the rate of fracture repair in the rat. , 1980, Acta orthopaedica Scandinavica.

[138]  E. Sudmann,et al.  Indomethacin-induced inhibition of haversian remodelling in rabbits. , 1979, Acta orthopaedica Scandinavica.

[139]  B. Mckibbin,et al.  The biology of fracture healing in long bones. , 1978, The Journal of bone and joint surgery. British volume.

[140]  D. Hak,et al.  The effect of Cox-2 specific inhibition on direct fracture healing in the rabbit tibia , 2011, Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association.

[141]  T. Gaber,et al.  Effects of celecoxib on the expression of osteoprotegerin, energy metabolism and cell viability in cultured human osteoblastic cells. , 2009, Clinical and experimental rheumatology.

[142]  K. Yasuda,et al.  Randomized clinical comparisons of diclofenac concentration in the soft tissues and blood plasma between topical and oral applications. , 2009, British journal of clinical pharmacology.

[143]  A. Joubert,et al.  Effects of arachidonic acid, docosahexaenoic acid and prostaglandin E(2) on cell proliferation and morphology of MG-63 and MC3T3-E1 osteoblast-like cells. , 2007, Prostaglandins, leukotrienes, and essential fatty acids.

[144]  E. Krall,et al.  Selective and nonselective cyclooxygenase-2 inhibitors and experimental fracture-healing. Reversibility of effects after short-term treatment. , 2007, The Journal of bone and joint surgery. American volume.

[145]  D. Woodbury,et al.  The effects of prostaglandin E2 in growing rats: Increased metaphyseal hard tissue and cortico-endosteal bone formation , 2007, Calcified Tissue International.

[146]  H. Donahue,et al.  Effect of COX-2-specific inhibition on fracture-healing in the rat femur. , 2004, The Journal of bone and joint surgery. American volume.

[147]  Francis Y. Lee,et al.  Use of ketorolac tromethamine in children undergoing scoliosis surgery. an analysis of complications. , 2003, The spine journal : official journal of the North American Spine Society.

[148]  G A Green,et al.  Understanding NSAIDs: from aspirin to COX-2. , 2001, Clinical cornerstone.

[149]  A. Rodgers,et al.  Non-steroidal anti-inflammatory drugs for preventing heterotopic bone formation after hip arthroplasty. , 2004, The Cochrane database of systematic reviews.

[150]  M. Weinreb,et al.  Differential effects of systemic prostaglandin E2 on bone mass in rat long bones and calvariae. , 1998, The Journal of endocrinology.

[151]  L. Engebretsen,et al.  Effects of ketoralac tromethamine and indomethacin on primary and secondary bone healing , 1998, Archives of Orthopaedic and Trauma Surgery.

[152]  E. Sudmann,et al.  Fracture healing in rats inhibited by locally administered indomethacin. , 1992, Acta orthopaedica Scandinavica.

[153]  O. Reikerås,et al.  Effects of short-term treatment with corticosteroids and indomethacin on bone healing. A mechanical study of osteotomies in rats. , 1992, Acta orthopaedica Scandinavica.

[154]  O. Reikerås,et al.  Effects of short-term treatment with corticosteroids and indomethacin on bone healing , 1992 .

[155]  G. Gaupmann,et al.  Experimental pain induced by electrical and thermal stimulation of the skin in healthy man: sensitivity to 75 and 150 mg diclofenac sodium in comparison with 60 mg codeine and placebo. , 1986, British journal of clinical pharmacology.

[156]  J. Hald,et al.  Lack of effect of indomethacin on ordered growth of the femur in rats. , 1982, Acta orthopaedica Scandinavica.

[157]  H Törnkvist,et al.  Effect of ibuprofen on mass and composition of fracture callus and bone. An experimental study on adult rat. , 1980, Scandinavian journal of rheumatology.

[158]  D. Baksi Fracture healing. , 1980, Journal of the Indian Medical Association.