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Celecoxib Prevented Development of Heterotopic Ossification Better

Than Ibuprofen After Total Hip Replacement
Michael J. Dunbar
J Bone Joint Surg Am. 2007;89:2556. doi:10.2106/JBJS.8911.ebo1

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EBO1-Saudan-Dunbar.fm Page 2556 Thursday, October 11, 2007 11:50 AM

2556
THE JOURNAL OF BONE & JOINT SURGER Y JBJS.ORG
VO L U M E 89-A N U M B E R 11 N O VE M B E R 2007

E V I D E N C E -B A S E D O R T H O P A E D I C S

Evidence-Based Orthopaedics
Celecoxib Prevented Development of Heterotopic Ossification
Better Than Ibuprofen After Total Hip Replacement
Saudan M, Saudan P, Perneger T, Riand N, Keller A, Hoffmeyer P. Celecoxib Versus Ibuprofen in the Prevention of Heterotopic
Ossification Following Total Hip Replacement. A Prospective Randomised Trial. J Bone Joint Surg Br. 2007 Feb;89:155-9.
Question: In patients having total hip replace-

hibitors. 240 patients (96%) were available for

follow-up.

ment, is celecoxib as effective as ibuprofen in

preventing heterotopic ossification 3 months
after surgery?

Intervention: Patients were allocated to receive

celecoxib, 200 mg twice daily (n = 123), or ibuprofen, 400 mg 3 times daily (n = 127) for 10
days after surgery. All patients had total hip replacement by a direct lateral approach, with an
uncemented acetabular component and a cemented femoral stem, and received prophylaxis
for deep venous thrombosis with low-molecularweight heparin for 5 days after surgery and oral
anticoagulation for the next 6 weeks.

Design: Randomized (allocation concealed),

blinded (outcome assessors), controlled trial

with 3-month follow-up.
Setting: A university hospital in Geneva,
Switzerland.
Patients: 250 patients (mean age, 70 y; 54%
women) with severe osteoarthritis of the hip
who were scheduled for total hip replacement.
Exclusion criteria were moderate to severe renal impairment, a history of gastrointestinal
ulcers, and immediate-type hypersensitivity
to nonsteroidal anti-inflammatory drugs
(NSAIDs) or cyclooxygenase-2 (COX-2) in-

Main outcome measures: Presence of heterotopic ossification on an anteroposterior radiograph of the pelvis at 3 months. Heterotopic
ossification was assessed according to the
Brooker classification (class I = islands of bone
within soft tissue around the hip; class II = bone

Celecoxib vs ibuprofen to prevent heterotopic ossification (HO) 3 months after total hip replacement*
Outcomes

Celecoxib

Ibuprofen

No HO

59%

41%

Brooker class II/III HO

5.1%

13%

RBI (95% confidence

interval)
45% (12 to 89)
RRR (CI)
61% (6 to 84)

spurs from the pelvis or proximal aspect of the

femur, leaving 1 cm between opposing bone
surfaces; class III = bone spurs from the pelvis or
proximal aspect of the femur, leaving <1 cm between opposing bone surfaces; and class IV =
apparent ankylosis of the hip). Adverse events
(renal impairment, electrolyte disorders, and
gastrointestinal disturbances) were also assessed.
Main results: Analysis was by intention to
treat. Celecoxib was more effective than ibuprofen in preventing heterotopic ossification,
and fewer celecoxib recipients had Brooker
classes II and III heterotopic ossification (Table). Adjustment for age, sex, duration of surgery, and preoperative anti-inflammatory
treatment did not alter the results.
Conclusion: In patients having total hip re-

placement through a direct lateral approach,

celecoxib was more effective than ibuprofen in
preventing heterotopic ossification 3 months
after surgery.

NNT (CI)
6 (4 to 18)

Source of funding: Not reported.

13 (7 to 165)

For correspondence: Dr. M. Saudan, Division of

Nephrology, University Hospitals of Geneva, Rue
Micheli-du-Crest 24, CH-1211 Geneva 14, Switzerland. E-mail address: marc.saudan@hcuge.ch

*RBI = relative benefit increase; RRR = relative risk reduction; NNT = number needed to treat;
CI = confidence interval. Numbers calculated from data in article.

Commentary
The study by Saudan and colleagues is a well-designed and executed
randomized controlled trial that clearly answers the question of whether
celecoxib is better than ibuprofen in preventing the radiographic appearance of heterotopic ossification after total hip replacement.
Some aspects of this study that make it scientifically valid also lead to
difficulties in interpreting the data and applying it clinically. For example,
all of the procedures were performed through a direct lateral approach.
Thus, the results are not generalizable to other approaches. Furthermore,
all of the femoral components were cemented. Concern has previously
been raised regarding the effect that NSAIDs and COX-2 drugs may have
on osteointegration1. This issue cannot be addressed in this study. This
study is limited to the radiographic appearance of heterotopic ossification
and does not investigate differences in clinical outcomes, such as pain and
function, between the 2 groups.
Clinicians should be cautious in applying the findings of this study
to a larger clinical population. For example, the authors recommend that
caution be used with COX-2 drugs in patients prone to cardiovascular
disorders. As a previous study has reported a surprisingly high number
J Bone Joint Surg Am. 2007;89:2556 doi:10.2106/JBJS.8911.ebo1

of cardiovascular events after total hip replacement2, this message must

be reemphasized. Side effects such as increased serum creatinine levels
were reported with both drugs; however, the study was not powered to
investigate differences in side-effect profiles between the 2 drugs.
If a surgeon is concerned about heterotopic ossification in a specific
patient receiving a total hip replacement through a direct lateral approach, then this study clearly and validly shows that celecoxib is better
than ibuprofen in preventing radiographic heterotopic ossification. The
findings do not suggest that celecoxib should be used as a standard of
care. Caution is warranted if an uncemented stem is to be used.
Michael J. Dunbar, MD, PhD
Dalhousie University
Halifax, Nova Scotia
1. Aspenberg P. Postoperative Cox inhibitors and late prosthetic loosening
suspicion increases! Acta Orthop. 2005;76:733-4.
2. Gandhi R, Petruccelli D, Devereaux PJ, Adili A, Hubmann M, de Beer J. Incidence and timing of myocardial infarction after total joint arthroplasty. J Arthroplasty. 2006;21:874-7.