A systematic survey of 13 randomized trials of non-steroidal anti-inflammatory drugs for the prevention of heterotopic bone formation after major hip surgery

Neal, Bruce; Rodgers, Anthony; Clark, Taane G.; Gray, Harley; Reid, Ian R.; Dunn, Louisa; MacMahon, Stephen

doi:10.1080/000164700317413076

Cited by 99 publications

(55 citation statements)

References 21 publications

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“…In this work, the smallest formation of bony trabeculae in the animals of the group II seems to be related with the use of nonsteroidal anti-inflammatory drug (sodic diclofenac) in the beginning phases of the bony repair, where the inflammatory process is of fundamental importance. Our results are similar to the of Neal et al 14 , where the inhibition of bone formation in humans only requires treatment with Cox inhibitors during the first 5-7 days after the operation. This suggests that the initial inflammation is crucial for starting the bone formation response.…”

Section: Discussionsupporting

confidence: 81%

Bone repair in rats treated with sodic diclofenac and calcitonin<A NAME="volta1"></A>

Sassioto¹,

Inouye²,

Aydos³

et al. 2006

Acta Cir. Bras.

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Purpose:To investigate clinical and histologically the bone repair in treated animals with calcitonin and sodic diclofenac. Methods: Ninety-six femoral defects were created in forty-eight animals distributed in four groups (n=24): either left untreated, treated with the sodic diclofenac or calcitonin or both. Follow-up was 7, 14 and 21 days. Histological sections stained by haematoxylin-eosin was observed under light microscopy (100X) and quantitatively scored for their trabecular formation. The groups and subgroups were compared being used the Kruskall-Wallis test. Results: Smaller trabecular formation was observed in the animals of the group II and larger trabecular formation in the animals of the group III. Was found significant differences in the comparison between all the groups (Kruskall-Wallis, p <0.05). Conclusion: The obtained data suggest that the bone repair is a time-dependent process, which can be delayed by the sodic diclofenac and accelerated by the calcitonina, when used separately. The associated use of calcitonina and sodic diclofenac didn't show to be the best therapeutic option in the treatment of bone defects surgically created. Key words: Osteogenesis. Anti-inflammatory agents. Calcitonin. Rats. RESUMO Objetivo:Investigar clínica e histologicamente o reparo ósseo em animais tratados com calcitonina e diclofenaco sódico. Métodos: Foram criados 96 defeitos femorais, em 48 animais distribuídos em quatro grupos (n = 24): não tratados, tratados com diclofenaco sódico ou calcitonina ou ambos. O período de seguimento foi 7, 14 e 21 dias. As secções coradas por hematoxilina e eosina foram observadas sob microscopia óptica (100x) e analisadas quantitativamente em relação à neoformação trabecular. Os grupos e subgrupos foram comparados utilizando-se o teste de Kruskall-Wallis. Resultados: Foi observada menor formação de trabéculas ósseas nos animais do grupo II e maior formação de trabéculas ósseo nos animais do grupo III. Foram encontradas diferenças significantes na comparação entre todos os grupos (Kruskall-Wallis, p <0.05). Conclusão: Os dados obtidos sugerem que o reparo ósseo é um processo tempo-dependente, que pode ser retardado pelo diclofenaco e acelerado pela calcitonina, quando utilizados isoladamente. O uso associado de calcitonina e diclofenaco sódico não mostrou ser a melhor opção terapêutica no tratamento de defeitos ósseos criados operatoriamente.

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Section: Discussionsupporting

confidence: 81%

Bone repair in rats treated with sodic diclofenac and calcitonin<A NAME="volta1"></A>

Sassioto¹,

Inouye²,

Aydos³

et al. 2006

Acta Cir. Bras.

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“…NSAIDs are also effective in preventing heterotopic ossification (HO) after total hip arthroplasty (Neal et al 2000), strongly suggesting that these drugs also have effects on human bone formation on ectopic places. Theoretically, these NSAIDs inhibit bone restoration, which may result in a less stable or unstable implant (Persson et al 2005a).…”

mentioning

confidence: 99%

No effect of ketoprofen and meloxicam on bone graft ingrowth: A bone chamber study in goats

et al. 2008

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Background and purpose There is increasing awareness that non-steroidal anti-inflammatory drugs (NSAIDs), and especially the cyclooxygenase-2 (COX-2) selective ones, may retard bone healing. We have used NSAIDs (indomethacin for at least 7 days) to prevent heterotopic ossification after acetabular reconstructions using impacted bone grafts. The long-term clinical results have been satisfying, making it difficult to believe that there is an important negative effect of NSAIDs on graft incorporation. We studied the effect of two different NSAIDs on bone and tissue ingrowth in a bone chamber model in goats, using autograft, rinsed allograft, and allograft that had been rinsed and subsequently irradiated.Methods 9 goats received no NSAIDs, 9 received ketoprofen, and 9 received meloxicam-all for 6 weeks. In each goat 6 bone chambers were implanted: 2 filled with autograft, 2 with rinsed allograft, and 2 with allograft that had been rinsed and irradiated. The amount of bone ingrowth and total tissue ingrowth was compared between the groups.Results There were no statistically significant differences in bone ingrowth between the different groups. Also, no differences in bone ingrowth were found with respect to the type of graft used. Furthermore, there was no statistically significant difference in the total amount of ingrowth of fibrous tissue between the treatment groups.Interpretation No differences in bone ingrowth in titanium bone chambers could be detected with both ketoprofen and meloxicam compared to untreated control animals. This confirms our hypothesis that the effect of NSAIDs on the incorporation and ingrowth of bone graft is limited.

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“…Although indomethacin is effective in preventing heterotopic ossification (HO) after primary total hip arthroplasty (Knelles et al 1997, Neal et al 2000, side effects are frequently observed. The minimum treatment period for NSAIDs appears to be 7 days (Neal et al 2000).…”

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confidence: 99%

Similar effects of rofecoxib and indomethacin on the incidence of heterotopic ossification after hip arthroplasty

et al. 2007

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Background Although indomethacin is effective in preventing heterotopic ossification (HO) after primary total hip arthroplasty, side effects are frequently observed. In the last decade a new class of drugs-the COX-2 selective nonsteroidal anti-inflammatory drugs-has been developed. To investigate the effect of these COX-2 selective NSAIDs on heterotopic ossification (HO) after primary total hip arthroplasty (THA), we conducted a randomized controlled trial using either indomethacin or rofecoxib for 7 days.Methods 186 patients received either indomethacin 3 times daily, or rofecoxib twice, and 1 placebo, daily for 7 days. HO was graded according to the 1-year postoperative radiographs according to the Brooker classification.Results 12 of the 186 patients included discontinued their medication before the end of the trial due to side effects. The remaining 174 patients were included in the analysis. In the indomethacin group (n = 89), 77 patients (87%) showed no HO, 9 showed HO of grade 1 and 3 showed HO of grade 2 according to the Brooker classification. In the rofecoxib group (n = 85) 73 patients (86%) showed no ossification, 9 showed grade 1, and 3 showed grade 2.Interpretation The prophylactic effect of rofecoxib for 7 days in preventing heteropic ossification after primary total hip arthroplasty is comparable to the effect of indomethacin given for 7 days. These results indicate that the development of HO follows a COX-2 pathway.

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A systematic survey of 13 randomized trials of non-steroidal anti-inflammatory drugs for the prevention of heterotopic bone formation after major hip surgery

Cited by 99 publications

References 21 publications

Bone repair in rats treated with sodic diclofenac and calcitonin<A NAME="volta1"></A>

Bone repair in rats treated with sodic diclofenac and calcitonin<A NAME="volta1"></A>

No effect of ketoprofen and meloxicam on bone graft ingrowth: A bone chamber study in goats

Similar effects of rofecoxib and indomethacin on the incidence of heterotopic ossification after hip arthroplasty

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