NSAID’s reduce the risk for Revision due Aseptic

Loosening in Cemented Total Hip Replacement.

Results form the Danish Hip Arthroplasty Register

Per Kjærsgaard-Andersen
Vejle Hospital
Denmark
 Scientific staff

Søren Overgaard (1,3), MD, PhD

Alma B. Petersen (2), MD, PhD
Søren Paaske Johnsen (2), MD
Anders Riis (2), MSc
Per Kjærsgaard-Andersen (1,4), MD

(1) Danish Hip Arthroplasty Register

(2) Dept. Epidemiology, Aarhus University
(3) Odense University Hospital
(4) Clinical Research Unit, Vejle Hospital
 Denmark
 Denmark has 5.5 million inhabitants

 Every Danish citizen has a civil register number

which encodes gender and date of birth and
allows linkage of information

 Many central databases link to each other

 According to rules from the Danish National

Board of Health both public and private clinics
have to report to DHR (National database)
 Primary THA
Fixation of the acetabular component

Cement + antibiotics Cement - antibiotics Cementless + HA

Cementless – HA
 Primary THA
Fixation of the femoral component

Cement + antibiotics Cement - antibiotics Cementless + HA

Cementless – HA
 Postoperative treatment with
NSAID after Total Hip Arthroplasty

Postoperative pain treatment

Prevention of heterotopic bone formation

Does NSAID influence survival
of THA components?
 NSAID’s impair bone healing
experimentally

• Implant fixation

• Fracture healing

• Spinal fusion

Trancik T et al. Clin Orthop 1989;249:113-21.

Keller JC et al. J Orthop Res 1989;7:28-34
Jacobsson SE et al. JBJS 1994;76B:831-3
Goodman SB et al. Trans Orthop 2003;paper 0066
Goodman SB et al. Trans Orthop 2004;poster 2004
 Clinical studies on Implant Fixation
Does NSAID influence implant fixation?
YES vs NO

• NO: Gebuhr P et al: Orthop Int 1997;5(1):21-3.

• NO: Wurnig C et al. Clin Orthop 1999;361:150-8.
• NO: Kienapfel H et al. Arch Orthop Tr Surg 1999;119:296-302.
• NO: Trnka HJ et al. Arch Orthop Tr Surg 1999;199:456-60.

Problems with these studies:

• Designed to show difference in ectopic bone formation
• Low power
Scandinavian Hip Arthroplasty Registers

Sweden Norway
Danish Hip Arthroplasty Register
Register Evaluation form
 Can data from the Danish Hip
Arthroplasty Register show any risk
or benifit of NSAID’s on implant
survival?
 Treatment with NSAID
Denmark

• 52 Clinics report annually to the Danish Hip Arthroplasty Register

– 2 Clinics have never used NSAID after THA
– 28 Clinics very rarely used NSAID
• < 20 NSAID treated cases during 1995-2006
• < 3% NSAID treated cases during 1995-2006

• Remaining 20 departments used NSAID regularly

– 8.531 cases treated with NSAID during 1995-2006
– Total 97% of all cases treated with NSAID
 Statistics

• Multivariate Cox Regression Analysis

– Estimates for relative risks (RR) for revision due to

aseptic loosening if treated with NSAID

– Adjust for confounders including:

• Sex
• Age
• Side of operation
• Indication for surgery
• Type of fixation
 NSAIDs used as prophylaxis against ectopic bone
formation after THA.
1995 – 2006

(%) No All Aseptic

primary Revisions loosening
THA
THA – NSAID 56,603 2,536 (4.3) 866 (1.5)
THA + NSAID 8,122 409 (4.8) 155 (1.8)

All revisions
+NSAID RR = 0.88 (0.79-0.98) p=0.02

Revision due to aseptic loosening

+NSAID RR = 0.76 (0.64-0.90) p<0.001
NSAIDs used as prophylaxis against ectopic bone
formation after THA
1995 – 2006

(%) No All Aseptic

primary Revisions loosening
THA
Cemented – NSAID 24,612 1,272 (4.1) 577 (1.9)
Cemented + NSAID 4,943 203 (3.9) 84 (1.6)

All revisions
+NSAID RR = 0.82 (0.70-0.95) p=0.01

Revision due to aseptic loosening

+NSAID RR = 0.69 (0.55-0.87) p<0.001
NSAIDs used as prophylaxis against ectopic bone
formation after THA
1995 – 2006

Subgroup analysis cemented cup

+ NSAID’s
Cup cemented RR = 0.81 (0.68-0.97) p= 0.02
All revisions
Cup cemented RR = 0.71 (0.54-0.92) p=0.01
Aseptic loosening
NSAIDs used as prophylaxis against ectopic bone
formation after THA
1995 – 2006

Subgroup analysis cemented stem

+ NSAID’s
Stem cemented RR = 0.84 (0.70-1.02) p=0.07
All stem revisions
Stem cemented RR = 0.71 (0.58-0.88) P<0.001
Aseptic loosening
NSAIDs used as prophylaxis against ectopic bone
formation after THA
1995 – 2006

(%) No All Aseptic

revision Revisions loosening
THA
Cementless – NSAID 17,750 636 (3.6) 100 (0.5)
cementless + NSAID 758 40 (5.0) 9 (1.1)

All revisions
+NSAID RR = 1.19 (0.86-1.63) p=0.30

Revision due to aseptic loosening

+NSAID RR = 1.72 (0.87-3.43) p=0.12
NSAIDs used as prophylaxis against ectopic bone
formation after THA
1995 – 2006

Subgroup analysis cementless cup

+ NSAID’s
Cup cementless RR =1.00 (0.83-1.20) p= 0.98
All cup revisions
Cup cementless RR = 1.04 (0.65-1.68) p= 0.86
Aseptic loosening
NSAIDs used as prophylaxis against ectopic bone
formation after THA
1995 – 2006

Subgroup analysis cementless stem

+ NSAID’s
Stem cementless RR = 1.00 (0.65-1.56) p=0.99
All stem revisions
Stem cementless RR = 2.24 (0.88-5.67) p=0.09
Aseptic loosening
 Conclusions
• NSAIDs reduced the risk for revision of the
cemented THA due to any reason and
aseptic loosening

• NSAIDs reduced the risk for revison of both

the cemented cup and stem

• NSAIDs might increase the risk for revision of

the cementless THA (stem), due to aseptic
loosening
 Clinical perspectives

• Cemented THA
– Use NSAID’s as painkillers and for prevention of
ectopic bone formation for at least 7 days after
surgery: Reduction of risk for revision

• Cementless THA
– Caution for using NSAID’s in clinical doses
postoperatively should be taken due to increased risk
for revision
Thank you for your attention
 Non-cemented implants
• NSAID inhibits the osteoblasts
• Osteoblasts are needed for promoting
early fixation of the implant
• Primary fixation weakened when
osteoblast are inhibited due to
treatment with NSAID
 Cemented implants
• NSAID inhibits the osteoclasts
• Cemented implants are immediate well fixed
due the macro-texture between cement and
bone
• If bone resorption takes place in the early
postoperative period it may increase
periprostetic bone resorption
• NSAID treatment during the early
postoperative period will inhibit this
resorption – and therefore reduce the risk for
aseptic loosening
 Draw-backs
• Results are based on register data with its limitations
(validation; compliance i.e.)

• ”True” risk cannot be presented as NSAIDs also have been

used as ”pain killers” without being recorded in the National
Register (equal in both groups??)

• Unknown biases may influence the outcome as the

observations are not based on data from randomized, blinded
studies

• The true risk for aseptic loosening may be even higher than
presented as:
– Possible NSAID treated cases are positioned in the group ”Not
treated”
– Pain treatment not recorded
NSAIDs used as prophylaxis against ectopic bone
formation after THA. 1995 – 2006
(%) No All Aseptic
revision Revisions loosening
THA
THA – NSAID 56,603 2,536 (4.3) 866 (1.5)
THA + NSAID 8,122 409 (4.8) 155 (1.8)

All revisions
+NSAID RR = 0.88 (0.79-0.98) p=0.02

Revision due to aseptic loosening

+NSAID RR = 0.76 (0.64-0.90) p<0.001
Higher percentage but reduced risk of revision is explained by a longer follow-up time for
NSAID and the used of cox-regression analysis
 Treatments strategies in Denmark

• Ibuprofen 7 • 5-6 days 3

• Indomethacin 4 • 7-8 days 6
• Vioxx 4 • 10-14 days 4
• Diclofenac 4 • 14 days 5
• Various drugs 2 • 21 days 3
• Tilcortil 1 • 28 days 1
Effects of NSAIDS: Molecular level
Effects of NSAIDS: Cell function