CORR Insights®: Heterotopic Ossification After an Achilles Tendon Rupture Cannot Be Prevented by Early Functional Rehabilitation: A Cohort Study

Where Are We Now?

Papers about heterotopic ossification (HO) after Achilles tendon injury previously were limited to small case series and case reports. In the current study, Magnusson and colleagues [5] illuminated this condition that has been likely hiding in our collective plain sight, and they did so through the simplest of means—by taking radiographs.

Their study grew out of another that required radiographs to measure the location of tantalum beads placed to measure elongation after Achilles repair. That the heterotopic bone was first discovered incidentally and not because of symptoms challenges us to understand what, if any, clinical importance it may have. Although previously published studies tantalize us with occasional reports of fractured exotic new bones within the Achilles [1], the authors of the current study found no effect of radiographically visible HO on pain or function after Achilles tendon repair [5]. The lesson here is that although heterotopic ossification may be more common than we previously thought, symptoms from it are not.

But even a rare complication may have major implications for the patient unlucky enough to experience it. As always, a balance must be struck between the morbidity of the problem itself and the risk, cost, or inconvenience of any population-wide interventions required to avoid it. This study looks at one of the cheapest and safest such interventions—a change in the rehabilitation protocol.

The authors should be commended for reporting negative results. Positive-outcome bias is common, with more than 85% of published studies across many disciplines reporting favorable results, and has been increasing with time [2]. Negative or no-difference results may be even more useful than positive ones in guiding the next line of investigation [4].

Where Do We Need to Go?

Somewhere between the case reports of major complications from HO of the Achilles and the complete absence of negative effects found by Magnusson and colleagues [5] must lie a calculable risk of a patient developing symptoms from this condition. Defining that rate is the critical step in improving treatment. The two known interventions for heterotopic ossification prophylaxis, radiation therapy and nonsteroidal anti-inflammatory (NSAID) treatment, both have potential morbidity.

On the basis of practicality and cost, radiation therapy is not appropriate for general use with every Achilles rupture. That leaves NSAIDs and their known risks.

By far our best clinical model of HO continues to be the many thousands of primary and revision THAs performed each day. Numerous permutations of different NSAIDs, dosages, and durations have been trialed. Generally, indomethacin and naproxen are often used, but meta-analyses have demonstrated that selective and nonselective NSAIDs are comparably effective at preventing heterotopic ossification [3, 5].

Although effective, both indomethacin and naproxen carry a substantial risk of gastrointestinal bleeding, with a relative risk for the complication compared to placebo of over 5 for both drugs [7]. Both medications are riskier than celecoxib. In a recent study comparing long-term celecoxib use with naproxen [4], that risk reduction was roughly two-fold (hazard ratio .51, 95% CI 0.32-0.81).

Cardiac risk represents another area of concern with some NSAIDs. Rofecoxib was famously removed from the US market in 2004 due to an increased risk of major cardiac events [8]. Naproxen, although once thought to have a protective effect against cardiac events, has recently been demonstrated to be essentially risk-neutral [8]. Indomethicin is less commonly used and its risk profile for cardiac events is not established.

Combining the evidence of prophylactic efficacy from the THA studies with the safety data suggests that if an NSAID is to be used for HO prophylaxis, celecoxib should be the primary choice, although naproxen may be supported in patients without any history of gastrointestinal concerns on the basis of cost and availability. With the risks of these medications already quantified, the current challenge is to quantify and compare the potential rewards from their use in the setting of Achilles injury.

Because symptomatic heterotopic ossification after operative Achilles repair is so uncommon, it is highly likely that the risks of NSAID use in this setting will outweigh any benefit to the general population. Investigators might therefore seek to determine whether any subgroups of patients are at particular risk of developing this complication, as is the case among patients undergoing THA.

How Do We Get There?

For future clinical studies, the morbidity of gastrointestinal bleeding and cardiac event risk would have to be compared with any protective benefits against the development of symptomatic heterotopic calcification. Two possible approaches may be reasonable. First, studies could focus upon patients likely to be at risk of heterotopic ossification due to the presence of the conditions in other locations, diffuse idiopathic skeletal hyperostosis, or the HLA-B27 genotype [6]. The most obvious risk factor, though, is right on the radiograph—the presence of a calcaneal enthesophyte. Limiting the analysis to those patients with calcaneal enthesophytes identified below a midsubstance Achilles rupture may yield useful data for identifying patients likely to benefit from prophylaxis. Second, a small shift in the anatomic location studied may prove to be important. If postoperative heterotopic ossification was previously underestimated following the operative repair of a midsubstance Achilles rupture, it is even more likely to have been underestimated following the elective repair of insertional disease, a procedure that takes place at the level of the enthesophyte itself. The largest reports of insertional repair have relied almost exclusively upon patient-reported rather than radiographic outcomes [1] and symptomatic HO is occasionally encountered in the clinical setting. A randomized controlled trial of chemical HO prophylaxis in that population may be the single most likely study to demonstrate an effect.