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

Pountos, Ippokratis; Georgouli, T.; Calori, G.M.; Giannoudis, Peter V.

doi:10.1100/2012/606404

Cited by 238 publications

(182 citation statements)

References 142 publications

(167 reference statements)

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“…More recently, beneficial effects of ketolorac in rib fractures have been reported. The drug reduces pain, decreases incidence of pneumonia and number of hours of postoperative ventilation [107,108]. The effectiveness of a selective and a nonselective NSAIDs, Etoricoxib 90-120 mg and ibuprofen 1800 mg compared with placebo in postoperative period after total knee replacement has been confirmed in a randomized study on 713 patients.…”

Section: Postoperative Effects In Orthopaedic Surgerymentioning

confidence: 75%

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The Use of NSAIDs in the Postoperative Period: Advantage and Disadvantages

2015

JACCOA

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Section: Postoperative Effects In Orthopaedic Surgerymentioning

confidence: 75%

“…These conflicting results are due to different factors: different kind of surgery, e.g. hip replacement, periodontal surgery and some studies are retrospective [104][105][106]. Furthermore the negative effects of NSAIDs on bone healing could be due to high dose of drugs administered for a long period.…”

Section: Postoperative Effects In Orthopaedic Surgerymentioning

confidence: 99%

The Use of NSAIDs in the Postoperative Period: Advantage and Disadvantages

2015

JACCOA

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“…37 Actually, selective COX-2 inhibitors may have a lower incidence of gastrointestinal bleeding, 13,32 but their effect on bone healing remains uncertain. 23,29,31 There has been limited literature demonstrating the effectiveness of NSAIDs to prevent the formation of HO after cervical arthroplasty. The US FDA trials commonly incorporated 2 weeks of postoperative NSAIDs in the management protocol.…”

Section: Discussionmentioning

confidence: 99%

Postoperative nonsteroidal antiinflammatory drugs and the prevention of heterotopic ossification after cervical arthroplasty: analysis using CT and a minimum 2-year follow-up

Huang

et al. 2015

SPI

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OBJECT Heterotopic ossification (HO) after cervical arthroplasty is not uncommon and may cause immobility of the disc. To prevent HO formation, study protocols of clinical trials for cervical arthroplasty undertaken by the US FDA included perioperative use of nonsteroidal antiinflammatory drugs (NSAIDs). However, there are few data supporting the use of NSAIDs to prevent HO after cervical arthroplasty. Therefore, this study aimed to evaluate the efficacy of NSAIDs in HO formation and clinical outcomes. METHODS Consecutive patients who underwent 1- or 2-level cervical arthroplasty with a minimum follow-up of 24 months were retrospectively reviewed. All patients were grouped into 1 of 2 groups, an NSAID group (those patients who had used NSAIDs postoperatively) and a non-NSAID group (those patients who had not used NSAIDs postoperatively). The formation of HO was detected and classified using CT in every patient. The incidence of HO formation, disc mobility, and clinical outcomes, including visual analog scale (VAS) scores of neck and arm pain, neck disability index (NDI) scores, and complications were compared between the two groups. Furthermore, a subgroup analysis of the patients in the NSAID group, comparing the selective cyclooxygenase (COX)-2 to nonselective COX-2 NSAID users, was also conducted for each of the above-mentioned parameters. RESULTS A total of 75 patients (mean age [± SD] 46.71 ± 9.94 years) with 107 operated levels were analyzed. The mean follow-up duration was 38.71 ± 9.55 months. There were no significant differences in age, sex, and levels of arthroplasty between the NSAID and non-NSAID groups. There was a nonsignificantly lower rate of HO formation in the NSAID group than the non-NSAID group (47.2% vs. 68.2%, respectively; p = 0.129). During follow-up, most of the arthroplasty levels remained mobile, with similar rates of immobile discs in the NSAID and non-NSAID groups (13.2% and 22.7%, respectively; p = 0.318). Furthermore, there was a nonsignificantly lower rate of HO formation in the selective COX-2 group than the nonselective COX-2 group (30.8% vs 52.5%, respectively; p = 0.213). The clinical outcomes, including VAS neck, VAS arm, and NDI scores at 24 months postoperatively, were all similar in the NSAID and non-NSAID groups, as well as the selective and nonselective COX-2 groups (all p > 0.05). CONCLUSIONS In this study there was a trend toward less HO formation and fewer immobile discs in patients who used postoperative NSAIDs after cervical arthroplasty than those who did not, but this trend did not reach statistical significance. Patients who used selective COX-2 NSAIDs had nonsignificantly less HO than those who used nonselective COX-2 NSAIDs. The clinical outcomes were not affected by the use of NSAIDs or the kinds of NSAIDs used (selective vs nonselective COX-2). However, the study was limited by the number of patients included, and the efficacy of NSAIDs in the prevention of HO after cervical arthroplasty may need further investigation to confirm these results.

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“…Smoking [6,12], diabetes [8], obesity [6], and endocrinopathies [3] such as hypogonadism, vitamin D deficiencies, and calcium imbalances have all been identified as patientspecific risk factors for delayed union and nonunion. Iatrogenic concerns for impaired healing have also been linked to medications such as nonsteroidal antiinflammatory drugs [2,8,13]; this research has resulted in decreased use of these drugs in patients with fracture.…”

Section: Introductionmentioning

confidence: 99%

Postoperative Opioid Administration Inhibits Bone Healing in an Animal Model

Chrastil

Sampson

Jones

et al. 2013

Clinical Orthopaedics &Amp; Related Research

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Background The current mainstay of orthopaedic pain control is opioid analgesics but there are few studies in the literature evaluating the effects of opioids on bone healing. Questions/purposes The purpose of this study was to use a rat fracture model to evaluate the effects of opioid administration on osseous union in the acute (4 weeks) and subacute (8 weeks) setting in an operatively stabilized fracture. We asked the following question: does morphine administration alter (1) fracture callus strength; (2) callus volume and formation; and (3) morphology and early remodeling to final osseous union? Methods A 0.4-mm femoral osteotomy gap was created in 50 Sprague-Dawley rats using an established model. Postoperatively, rats were randomized to control versus morphine-treated study groups. Equal numbers of rats from each group were euthanized at 4 weeks and 8 weeks postoperatively. Three-point bend biomechanical testing was performed to evaluate postoperative callus strength. Micro-CT scans and histological analyses were used to evaluate postoperative callus volume and formation, morphology, and features of early remodeling. Results Biomechanical testing identified a statistically significant (p = 0.048) reduction in callus strength in morphine-treated animals 8 weeks postoperatively compared with controls. Radiographic and histological analysis showed delayed callus maturation and lack of remodeling in the morphine group compared with control animals at 8 weeks. Micro-CT analysis expressed remodeling and resorption as a decrease in callus volume over the two time points. The control group had significant levels of resorption decreasing 29% (p = 0.023) over the 4-week to 8-week time interval. Morphine administration inhibited callus resorption and remodeling with only a 13% decrease (p = 0.393) in callus volume comparing these time points. The callus inhibition associated with morphine administration was not as evident in the acute, 4-week time setting. Conclusions Morphine administration inhibited callus strength in this animal model. This finding is likely consistent with the observation that the callus and healing bone appear to have a decreased rate of maturation and remodeling seen at 8 weeks.Clinical Relevance This study identifies that administration of an opioid pain medication leads to weaker callus and impedes callus maturation compared with controls.

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

Cited by 238 publications

References 142 publications

The Use of NSAIDs in the Postoperative Period: Advantage and Disadvantages

The Use of NSAIDs in the Postoperative Period: Advantage and Disadvantages

Postoperative nonsteroidal antiinflammatory drugs and the prevention of heterotopic ossification after cervical arthroplasty: analysis using CT and a minimum 2-year follow-up

Postoperative Opioid Administration Inhibits Bone Healing in an Animal Model

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