Prophylaxis of heterotopic ossification – an updated review


Nurse Director
Jun 8, 2007
The North
United Kingdom United Kingdom
Extract from Prophylaxis of heterotopic ossification – an updated review

Karunakar et al[26]. conducted a randomized, prospective double-blind placebo-controlled clinical trial on the effect of indomethacin after the operative treatment of fractures of the acetabulum. Though as the authors point out the study is lacking in power, it is significant in that it was determined that there was no significant difference in the incidence of HO between the indomethacin and placebo treatment groups.

However, it was noted that one of the indomethacin patients developed gastrointestinal hemorrhage and one had a perforated ulcer, while 13 total patients withdrew from the study due to side effects of the medication, compared with only 1 withdrawing in the placebo treatment. Others such as Banovac[24] have used misoprostol to aid in the prevention of gastrointestinal complications. Another problem with non-selective (i.e. those actively inhibiting cyclo-oxygenase 1 and 2, or COX-1 and COX-2) NSAIDs such as indomethacin is increased perioperative bleeding secondary to inhibition of COX-1, leading to reduced production of thromboxane A2, which is essential to platelet aggregation[29].

Fransen et al. followed up her 2004 Cochrane review with a randomized controlled trial comparing postoperative pain and physical function in patients taking either ibuprofen or placebo following total hip arthroplasty and revision total hip arthroplasty surgery[30]. Though the overall risk of HO was reduced by 31% (as assessed radiographically) with use of ibuprofen, the study demonstrated no clinically significant difference in either pain or physical function 6 to 12 months postoperatively. Further, there was a significant increase in major bleeding complications in the ibuprofen treatment group, again serving to emphasize untoward side effects of this treatment modality[30].

One method of circumventing the pitfalls of NSAIDs use is by employing COX-2 selective NSAIDs, such as meloxicam. Weber et al. have shown that use of this selective NSAID following total hip arthroplasty was associated with a 17% reduction in intraoperative and postoperative (first 24 hours following surgery) blood loss[29].

Furthermore, fewer gastrointestinal side-effects have been noted as a result of preferential use of COX-2 selective NSAIDs [31, 32, 33, 34, 35]. However, it is notable that the practice of prescribing COX-2 specific NSAIDs is not without consequences, as several trials have shown an increased risk of cardiovascular events associated with their use [38, 39, 40]. Despite this, a few trials have shown either no increased risk for cardiovascular events when compared to non-slective NSAID use[41, 42] (albeit with lower rates of GI side effects) or a decreased risk (in the case of celecoxib[43]) as shown in one study. Due to the current lack of evidence for safety of routine use of COX-2 selective NSAIDs as prophylaxis for postoperative HO, indomethacin remains the gold standard of treatment when employing NSAIDs therapy[44].

A serious problem with the use of high-dose indomethacin and other NSAIDS for HO prophylaxis is that while new heterotopic bone may be prevented from forming, the formation of bone for healing the fracture site may also be impaired. Thus, the large number of reports of nonunion or malunion as well as poor ligament healing[5, 25, 45]. One such study by Burd et al. noted 29% incidence of nonunion of long bone fractures following indomethacin prophylaxis, whereas in the radiation arm the incidence was just 7%[25].

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