Influence of Naproxen on Heterotropic Bone Formation Following Hip Arthroscopy
Condition: Heterotopic Ossification
MeSH terms: Ossification, Heterotopic
Study type: Interventional
Phase: Early Phase 1

Summary: 
      In a brief summary the study would like to evaluate the effectiveness of Naproxen in
      preventing radiographically detected heterotopic ossification following hip arthroscopy for
      the treatment of femoroacetabular impingement.
    

Detailed description: 
      Heterotopic bone formation (HO) is a potentially serious complication of hip surgery. HO,
      defined as the formation of normal bone in an abnormal soft tissue location, results from
      alteration in the normal regulation of skeletogenesis. Although most patients remain
      asymptomatic despite HO development, two articles that included 10,826 patients from 37
      studies suggest HO may be associated with substantial compromise of function and range of
      motion even at low grades.In a large pooled incidence study, HO was estimated to be 43% in
      59,121 patients undergoing total hip arthroplasty, and 51% in 998 patients after acetabular
      trauma.

      Few studies have reported on the incidence of HO following hip arthroscopy. However, HO is an
      increasingly reported complication of arthroscopic treatment for femoroacetabular
      impingement(FAI). In a comparison of complications following arthroscopic treatment of FAI in
      8 case-series, ectopic ossification occurred in up to 6% of cases and accounted for 10 of the
      19 reported complications. Additionally, one recent study reported an HO incidence of 33% (5
      out of 15 patients) following hip arthroscopy in patients not prophylaxed with NSAID therapy.
      In our experience, HO occurs at a comparable or higher rate of 10% in those undergoing this
      procedure. The formation of ectopic ossification is triggered as a result of muscle damage
      during introduction of hip portals and is potentially augmented by seeding of bone shavings
      in the soft tissues created during burring of the femoral neck.

      Prophylaxis of HO targets the biochemical mechanisms of heterotopic bone formation by: 1)
      Disrupting inductive signaling pathways, 2) Altering osteoprogenitor cells in target tissues,
      and 3) Modifying the environment conductive to formation of heteroptic bone. The two
      mainstays of therapy are low dose radiation treatment and non-steroidal anti-inflammatory
      medications (NSAIDs). The efficacies of these treatments were found to be equivalent by Burd
      et al in 166 randomized patients. However, NSAID therapy was shown to be considerably more
      cost effective with lower rates of morbidity. Large randomized studies have subsequently
      shown large reductions in the incidence of HO using NSAID therapy in the perioperative
      period. The Cochrane review of 16 randomized trials in 5000 patients found one-half to
      two-thirds reduction in HO with indomethacin.Even less potent NSAID therapy has been
      effective in reducing rates of HO. Fransen et al reported a 30% reduction in HO during the
      HIPAID trial comparing perioperative ibuprofen with placebo in nearly 1000 patients. The two
      groups had no statistical difference in functional outcome despite the higher incidence of HO
      in the prophylaxed group.

      While NSAID therapy has been effective in reducing the incidence of HO, it is associated with
      potentially serious side affects. Fransen et al found 202 GI side effects in a metaanalysis
      of 4328 patients taking NSAIDs for HO prophylaxis.1 Of these, 138 were minor (e.g. nausea,
      dyspepsia, diarrhea) and 64 were major (e.g. hematemesis or melena). Overall, there was a 31%
      increase in the risk of GI side effects among patients taking NSAIDs. Furthermore, NSAID
      therapy could impair bone and/or soft tissue healing following this. These side affects could
      negate the benefit of NSAID therapy, especially if HO is asymptomatic in the majority of
      patients.

      We hypothesize that NSAID prophylaxis of HO may have a role in hip arthroscopy for the
      treatment of femoroacetabular impingement. All NSAIDs tested, with the exception of aspirin,
      have resulted in significant decreases in the incidence of HO following hip surgery including
      less potent regimens such as ibuprofen 1200 mg/day. Naproxen offers the advantage of twice
      daily dosing with similar potency to ibuprofen. It is readily available and inexpensive.
      Furthermore, in an unpublished series of 50 patients prescribed naproxen following hip
      arthroscopy for FAI, we have had no cases of HO at 6 month follow up compared to a 5-10% rate
      in patients who received no prophylaxis. We propose testing our hypothesis that perioperative
      naproxen will reduce the incidence of HO following hip arthroscopy in a placebo controlled,
      double-blinded, randomized controlled trial.
    

Intervention name(s): Naproxen; placebo
Intervention type(s): Drug; Drug
Intervention description(s): • Group 1: Naproxen 500 mg twice daily for three weeks following surgery beginning postoperative day #1; • Group 2: Placebo twice daily for three weeks following surgery beginning postoperative day #1
Other intervention name(s): Placebo Control
Intervention MeSH terms: Naproxen
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Hip arthroscopy; Femoroacetabular impingement; Heterotopic ossification; Heterotopic bone formation