NSAID’s Reduce the Risk for Revision Due

8/14/2019 NSAIDs Reduce the Risk for Revision Due

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NSAIDs reduce the risk for Revision due AsepticNSAIDs reduce the risk for Revision due AsepticLoosening in Cemented Total Hip Replacement.Loosening in Cemented Total Hip Replacement.

Results form the Danish Hip Arthroplasty RegisterResults form the Danish Hip Arthroplasty Register

Per Kjrsgaard-AndersenPer Kjrsgaard-Andersen

Vejle HospitalVejle Hospital

DenmarkDenmark


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Scientific staffScientific staff

Sren OvergaardSren Overgaard (1,3), MD, PhD(1,3), MD, PhD

Alma B. PetersenAlma B. Petersen (2), MD, PhD(2), MD, PhD

Sren Paaske JohnsenSren Paaske Johnsen (2), MD(2), MD

Anders RiisAnders Riis (2), MSc(2), MSc

Per Kjrsgaard-AndersenPer Kjrsgaard-Andersen (1,4), MD(1,4), MD

(1)(1) Danish Hip Arthroplasty RegisterDanish Hip Arthroplasty Register

(2)(2) Dept. Epidemiology, Aarhus UniversityDept. Epidemiology, Aarhus University

(3)(3) Odense University HospitalOdense University Hospital

(4)(4) Clinical Research Unit, Vejle HospitalClinical Research Unit, Vejle Hospital


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DenmarkDenmark

Denmark has 5.5 million inhabitants

Every Danish citizen has a civil register numberwhich encodes gender and date of birth andallows linkage of information

Many central databases link to each other

According to rules from the Danish NationalBoard of Healthboth public and private clinicshave to report to DHR (National database)


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Primary THAPrimary THAFixation of the acetabular component

Cement + antibiotics Cement - antibiotics

Cementless HA

Cementless + HA


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Primary THAPrimary THA

Cement + antibiotics Cement - antibiotics

Cementless HA

Cementless + HA

Fixation of the femoral component

P


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Postoperat ve treatment w tos opera ve rea men wNSAID after Total HipNSAID after Total Hip

ArthroplastyArthroplasty

Prevention of heterotopic bone formation

Postoperative pain treatment


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Does NSAID influence survivalDoes NSAID influence survival

of THA components?of THA components?


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NSAIDs impair bone healingNSAIDs impair bone healing

experimentallyexperimentally

Implant fixationImplant fixation

Fracture healingFracture healing

Spinal fusionSpinal 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


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Clinical studies on Implant FixationClinical studies on Implant Fixation

Does NSAID influence implant fixation?Does NSAID influence implant fixation?YES vs NOYES vs NO

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

NO:NO: Wurnig C et al. Clin Orthop 1999;361:150-8.Wurnig C et al. Clin Orthop 1999;361:150-8. NO:NO: Kienapfel H et al. Arch Orthop Tr Surg 1999;119:296-302.Kienapfel H et al. Arch Orthop Tr Surg 1999;119:296-302.

NO:NO: Trnka HJ et al. Arch Orthop Tr Surg 1999;199:456-60.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


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Scandinavian Hip ArthroplastyScandinavian Hip Arthroplasty

RegistersRegisters

Sweden Norway


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Danish Hip ArthroplastyDanish Hip Arthroplasty

RegisterRegister


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Can data from the Danish HipCan data from the Danish Hip

Arthroplasty Register show anyArthroplasty Register show any

risk or benifit of NSAIDs onrisk or benifit of NSAIDs onimplant survival?implant survival?


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Treatment with NSAIDTreatment with NSAIDDenmarkDenmark

52 Clinics report annually to the Danish Hip Arthroplasty52 Clinics report annually to the Danish Hip Arthroplasty

RegisterRegister

2 Clinics have never used NSAID after THA2 Clinics have never used NSAID after THA

28 Clinics very rarely used NSAID28 Clinics very rarely used NSAID < 20 NSAID treated cases during 1995-2006< 20 NSAID treated cases during 1995-2006

< 3% NSAID treated cases during 1995-2006< 3% NSAID treated cases during 1995-2006

RemainingRemaining 20 departments20 departments used NSAID regularlyused NSAID regularly

8.531 cases treated with NSAID during 1995-20068.531 cases treated with NSAID during 1995-2006

Total 97% of all cases treated with NSAIDTotal 97% of all cases treated with NSAID


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StatisticsStatistics

Multivariate Cox Regression AnalysisMultivariate Cox Regression Analysis

Estimates forEstimates for relative risks (RR)relative risks (RR) for revision due tofor revision due to

aseptic loosening if treated with NSAIDaseptic loosening if treated with NSAID

Adjust forAdjust for confoundersconfounders including:including: SexSex

AgeAge

Side of operationSide of operation

Indication for surgeryIndication for surgeryType of fixationType of fixation


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NSAIDs used as prophylaxis against ectopicNSAIDs used as prophylaxis against ectopic

bone formation after THAbone formation after THA

1995 20061995 2006

(%) No primary

THA

All

Revisions

Aseptic

loosening

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


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1995 20061995 2006

+ NSAIDs

Cup cemented

All revisions

RR = 0.81 (0.68-0.97) p= 0.02

Cup cemented

Aseptic loosening

RR = 0.71 (0.54-0.92) p=0.01

Subgroup analysis cemented cup


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1995 20061995 2006

+ NSAIDs

Stem cemented

All stem revisions

RR = 0.84 (0.70-1.02) p=0.07

Stem cemented

Aseptic loosening

RR = 0.71 (0.58-0.88) P


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1995 20061995 2006

(%) Norevision

THA

All

Revisions

Aseptic

loosening

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


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1995 20061995 2006

+ NSAIDs

Cup cementless

All cup revisions

RR =1.00 (0.83-1.20) p= 0.98

Cup cementless

Aseptic loosening

RR = 1.04 (0.65-1.68) p= 0.86

Subgroup analysis cementless cup


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1995 20061995 2006

+ NSAIDs

Stem cementless

All stem revisions

RR = 1.00 (0.65-1.56) p=0.99

Stem cementless

Aseptic loosening

RR = 2.24 (0.88-5.67) p=0.09

Subgroup analysis cementless stem


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ConclusionsConclusions

NSAIDs reduced the risk for revision ofNSAIDs reduced the risk for revision ofthethe cemented THAcemented THA due to any reasondue to any reasonand aseptic looseningand aseptic loosening

NSAIDs reduced the risk for revison ofNSAIDs reduced the risk for revison ofboth theboth the cementedcementedcup and stemcup and stem

NSAIDs might increase the risk forNSAIDs might increase the risk forrevision of therevision of the cementless THAcementless THA(stem)(stem), due to aseptic loosening, due to aseptic loosening


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Clinical perspectivesClinical perspectives

Cemented THACemented THA

Use NSAIDs as painkillers and for preventionUse NSAIDs as painkillers and for prevention

of ectopic bone formation for at least 7 daysof ectopic bone formation for at least 7 days

after surgery:after surgery: Reduction of risk for revisionReduction of risk for revision

Cementless THACementless THA

Caution for using NSAIDs in clinical dosesCaution for using NSAIDs in clinical dosespostoperatively should be taken due topostoperatively should be taken due to

increased risk for revisionincreased risk for revision


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Thank you for your attention


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Non-cemented implantsNon-cemented implants

NSAID inhibits the osteoblastsNSAID inhibits the osteoblasts

Osteoblasts are needed forOsteoblasts are needed for

promoting early fixation of thepromoting early fixation of theimplantimplant

Primary fixation weakened whenPrimary fixation weakened when

osteoblast are inhibited due toosteoblast are inhibited due totreatment with NSAIDtreatment with NSAID


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Cemented implantsCemented implants

NSAID inhibits the osteoclastsNSAID inhibits the osteoclasts Cemented implants are immediate wellCemented implants are immediate well

fixed due the macro-texture betweenfixed due the macro-texture between

cement and bonecement and bone If bone resorption takes place in theIf bone resorption takes place in the

early postoperative period it mayearly postoperative period it mayincrease periprostetic bone resorptionincrease periprostetic bone resorption

NSAID treatment during the earlyNSAID treatment during the earlypostoperative period will inhibit thispostoperative period will inhibit thisresorption and therefore reduce theresorption and therefore reduce therisk for aseptic looseningrisk for aseptic loosening


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Draw-backsDraw-backs

Results are based on register data with its limitationsResults are based on register data with its limitations(validation; compliance i.e.)(validation; compliance i.e.)

True risk cannot be presented as NSAIDs also have beenTrue risk cannot be presented as NSAIDs also have beenused as pain killers without being recorded in the Nationalused as pain killers without being recorded in the National

Register (equal in both groups??)Register (equal in both groups??)

Unknown biases may influence the outcome as theUnknown biases may influence the outcome as theobservations are not based on data from randomized, blindedobservations are not based on data from randomized, blindedstudiesstudies

The true risk for aseptic loosening may be even higher thanThe true risk for aseptic loosening may be even higher than

presented as:presented as: Possible NSAID treated cases are positioned in the group NotPossible NSAID treated cases are positioned in the group Not

treatedtreated Pain treatment not recordedPain treatment not recorded


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Treatments strategies inTreatments strategies in

DenmarkDenmark

IbuprofenIbuprofen 77

IndomethacinIndomethacin 44

VioxxVioxx 44 DiclofenacDiclofenac 44

Various drugsVarious drugs 22

TilcortilTilcortil 11

5-6 days5-6 days

33

7-8 days7-8 days66

10-14 days10-14 days 44

14 days14 days 55

21 days21 days 33

28 days28 days 11


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ff f S S C ll


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Effects of NSAIDS: CellEffects of NSAIDS: Cell

functionfunction

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NSAID’s Reduce the Risk for Revision Due