Indomethacin for prevention of heterotopic ossification: A randomized controlled study in 41 hip arthroplasties

Kjærsgaard‐Andersen, Per; Nafei, Adel; Teichert, G; Kristensen, Ole; Schmidt, Steen Asmus; Keller, Johnny; Lucht, Ulf

doi:10.3109/17453679308994587

Cited by 78 publications

(26 citation statements)

References 14 publications

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“…Therefore, the use of NSAIDs is considered to be therapeutic in osteoporosis and bone loss prevention in older women [61]. Additionally, NSAIDs have been proven to be useful in the prevention of heterotopic ossifi cation following joint replacement and as a prophylactic against heterotopic bone formation in humans and animals [62][63][64][65][66][67][68].…”

Section: Effects Of Non-selective Nsaids On Bone Healingmentioning

confidence: 99%

Effects of cyclooxygenase inhibition on bone, tendon, and ligament healing

Radi

Khan

2005

Inflamm. res.

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Cyclooxygenases (COX-1 and COX-2) catalyze the conversion of arachidonic acid to prostaglandins (PGs). PGs play a significant role in bone metabolism in health and disease. Conventional non-selective, non-steroidal anti-inflammatory drugs (NSAIDs) and selective COX-2 inhibitors (COXIBs) are widely used in patients with musculoskeletal conditions and as a post-surgical analgesics. Due to their effects on PG synthesis, these drugs have been hypothesized to affect the healing process of bone fractures and orthopedic surgical sites. A variety of experimental models of bone, ligament, and tendon repair have assessed the effects of these selective and non-selective COX inhibitors in animals, but with variable outcomes. At this time, large-scale, robust clinical study data do not exist, limiting the relevant assessment of experimental animal data to humans. Here, we provide a critical review of available data on the role of PGs and the effect of COX inhibitors on bone, tendon, and ligament repair. Collectively, this assessment suggests potential involvement of PGs in the healing process of these tissues via modulation by non-selective NSAIDs and selective COX-2 inhibitors.

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Section: Effects Of Non-selective Nsaids On Bone Healingmentioning

confidence: 99%

Effects of cyclooxygenase inhibition on bone, tendon, and ligament healing

Radi

Khan

2005

Inflamm. res.

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“…Clinically, NSAIDs have been found to retard healing of diaphyseal femur fractures and spinal fusions (Glassman et al 1998, Giannoudis et al 2000. In addition, several randomized clinical studies have provided evidence of the high efficacy of NSAIDs in preventing heterotopic ossification, which strongly suggests that these drugs also have effects on human bone metabolism (Schmidt et al 1988, Kjaersgaard-Andersen et al 1993, Gebuhr et al 1996, Persson et al 1998. As in the case of fracture healing, the surgical trauma of THA induces reparative processes, which are necessary for a durable prosthetic fixation by bone regeneration on and into the bone cement or the prosthesis.…”

mentioning

confidence: 99%

Do non-steroidal anti-inflammatory drugs cause endoprosthetic loosening? A 10-year follow-up of a randomized trial on ibuprofen for prevention of heterotopic ossification after hip arthroplasty

2005

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Background Non-steroidal anti-inflammatory drugs (NSAIDs) are known to be potent inhibitors of new bone formation. We investigated whether NSAIDs given at surgery influence the long-term results after total hip arthroplasty (THA).Patients and methods We performed a 10-year follow-up on 142 of 144 patients who had taken part in a randomized trial on the preventive effects of the NSAID ibuprofen on heterotopic ossification after THA. 96 patients were treated with ibuprofen: 48 for 1 week postoperatively, 48 for 2 weeks postoperatively, and 48 patients were not treated.Results 13 patients had been revised. All revisions except 1 belonged to groups treated with ibuprofen. The 10-year risk for revision was significantly higher in the ibuprofen-treated patients (p = 0.05). Eleven of the revisions occurred due to fractures of the femur (2) or aseptic loosening (9), reasons that may be attributed to negative effects of ibuprofen. For these patients, the 10-year risk for revision was not statistically significantly different between treated and untreated patients (p = 0.08). In addition to the revised patients, 94 other patients were alive at the 10-year follow-up and 84 underwent radiographic examination. 9 loose prostheses were found radiographically, but these were equally distributed between ibuprofen-treated and untreated hips.Interpretation The high proportion of revisions in the ibuprofen groups, in combination with clinical and experimental evidence of inhibitory effects on new bone formation of NSAIDs, warrants further investigation of the effects of these drugs on prosthetic fixation.

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“…Despite complete resection, the offending bone has a strong propensity to recur in the absence of adjunctive measures. Although contemporary methods of prophylaxis, including radiation therapy and NSAIDS, eliminate meaningful HO for most patients, they are not without inherent risks [2,21,23,28,33,38,48]. The ideal strategy remains to prevent the initial formation of heterotopic bone through better understanding of the pathophysiology by which ossification occurs in the soft tissues after injury.…”

Section: Discussionmentioning

confidence: 99%

Heterotopic Bone Formation About the Hip Undergoes Endochondral Ossification: A Rabbit Model

Tannous¹,

Stall²,

Griffith³

et al. 2013

Clinical Orthopaedics &Amp; Related Research

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Background Heterotopic ossification (HO) occurs most commonly after trauma and surgery about the hip and may compromise subsequent function. Currently available animal models describing the cellular progression of HO are based on exogenous osteogenic induction agents and may not reflect the processes following trauma.Questions/purposes We therefore sought to characterize the histologic progression of heterotopic bone formation in an animal model that recapitulates the human condition without the addition of exogenous osteogenic material. Methods We used a rabbit model that included intramedullary instrumentation of the upper femur and ischemic crush injury of the gluteal muscle. Bilateral surgical induction procedures were performed on 30 animals with the intention of inciting the process of HO; no supplemental osteogenic stimulants were used. Three animals were sacrificed at each of 10 predetermined times between 1 day and 26 weeks postoperatively and the progression of tissue maturation was graded histologically using a five-item scale. Results Heterotopic bone reliably formed de novo and consistently followed a pathway of endochondral ossification. Chondroid elements were found in juxtaposition with immature woven bone in all sections that contained mature osseous elements. Conclusions These results establish that HO occurs in an animal model mimicking the human condition following surgical trauma about the hip; it is predictable in its histologic progression and follows a pathway of endochondral bone formation. Clinical Relevance By showing a consistent pathway of endochondral ossification leading to ectopic bone formation, this study provides a basis for understanding the mechanisms by which HO might be mitigated by interventions.

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Indomethacin for prevention of heterotopic ossification: A randomized controlled study in 41 hip arthroplasties

Cited by 78 publications

References 14 publications

Effects of cyclooxygenase inhibition on bone, tendon, and ligament healing

Effects of cyclooxygenase inhibition on bone, tendon, and ligament healing

Do non-steroidal anti-inflammatory drugs cause endoprosthetic loosening? A 10-year follow-up of a randomized trial on ibuprofen for prevention of heterotopic ossification after hip arthroplasty

Heterotopic Bone Formation About the Hip Undergoes Endochondral Ossification: A Rabbit Model

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