Ann Rheum Dis 2005 Zhang 669 81

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com
669
EXTENDED REPORT
EULAR evidence based recommendations for the

management of hip osteoarthritis: report of a task
force of the EULAR Standing Committee for
International Clinical Studies Including Therapeutics
(ESCISIT)
W Zhang, M Doherty, N Arden, B Bannwarth, J Bijlsma, K-P Gunther,
H J Hauselmann, G Herrero-Beaumont, K Jordan, P Kaklamanis, B Leeb,
M Lequesne, S Lohmander, B Mazieres, E Martin-Mola, K Pavelka,
A Pendleton, L Punzi, B Swoboda, R Varatojo, G Verbruggen,
I Zimmermann-Gorska, M Dougados
...............................................................................................................................
Ann Rheum Dis 2005;64:669681. doi: 10.1136/ard.2004.028886
Appendixes are available

on the website at http://
www.annrheumdis.com/
supplemental
See end of article for
authors affiliations
.......................
Correspondence to:
Professor M Dougados,
Institute of Rheumatology,
Hardy B, Hospital Cochin,
27, rue du Faubourg, Saint
Jacques, 71054 Paris,
France;
maxime.dougados@
cch.ap-hop-paris.fr
Accepted
1 September 2004
Published Online First
7 October 2004
.......................
Objective: To develop evidence based recommendations for the management of hip osteoarthritis (OA).
Methods: The multidisciplinary guideline development group comprised 18 rheumatologists, 4
orthopaedic surgeons, and 1 epidemiologist, representing 14 European countries. Each participant
contributed up to 10 propositions describing key clinical aspects of hip OA management. Ten final
recommendations were agreed using a Delphi consensus approach. Medline, Embase, CINAHL,
Cochrane Library, and HTA reports were searched systematically to obtain research evidence for each
proposition. Where possible, outcome data for efficacy, adverse effects, and cost effectiveness were
abstracted. Effect size, rate ratio, number needed to treat, and incremental cost effectiveness ratio were
calculated. The quality of evidence was categorised according to the evidence hierarchy. The strength of
recommendation was assessed using the traditional AD grading scale and a visual analogue scale.
Results: Ten key treatment propositions were generated through three Delphi rounds. They included 21
interventions, such as paracetamol, NSAIDs, symptomatic slow acting disease modifying drugs, opioids,
intra-articular steroids, non-pharmacological treatment, total hip replacement, osteotomy, and two
general propositions. 461 studies were identified from the literature search for the proposed interventions
of efficacy, side effects, and cost effectiveness. Research evidence supported 15 interventions in the
treatment of hip OA. Evidence specific for the hip was strikingly lacking. Strength of recommendation
varied according to category of research evidence and expert opinion.
Conclusion: Ten key recommendations for the treatment of hip OA were developed based on research
evidence and expert consensus. The effectiveness and cost effectiveness of these recommendations were
evaluated and the strength of recommendation was scored.
he hip is the second most common large joint to be

affected by osteoarthritis (OA). The prevalence of hip OA
ranges from 3 to 11% in Western populations aged over
35 years.15 It is often associated with significant pain,
disability, and impaired quality of life. Although available
treatments for hip and knee OA are similar and include
pharmacological, non-pharmacological, and surgical options,
there are certain differences. Furthermore, the effect size of a
specific treatment might vary according to the site of the OA
involvement, owing to differences in anatomy, biomechanics,
risk factors for development and progression, and accessibility to local treatments. Therefore, having developed
evidence based recommendations for the management of
knee OA,6 7 the EULAR OA Task Force next focused on a
parallel document to consider the treatment of hip OA. As
before,6 7 recommendations were developed using a Delphi
consensus approach and assessed both by current available
research evidence and expert opinion.
METHODS
Participants
A multidisciplinary guideline development committee was
commissioned by ESCISIT. Twenty three experts in the field
of OA (18 rheumatologists, 4 orthopaedic surgeons, and 1
epidemiologist) representing 14 European countries agreed to
take part in the study. The objectives were (a) to agree 10 key
propositions for the management of hip OA; (b) to identify
and critically appraise research evidence for the effectiveness
Abbreviations: ASU, avocado soybean unsaponifiable; CI, confidence
interval; COX-2, cyclo-oxygenase-2; CS, chondroitin sulphate; CT,
controlled trial; CV, cardiovascular; ES, effect size; GI, gastrointestinal;
GS, glucosamine sulphate; HA, hyaluronic acid; ICER, incremental cost
effectiveness ratio; NNT, number needed to treat; NSAIDs, non-steroidal
anti-inflammatory drugs; QALY, quality of life year; OA, osteoarthritis;
OR, odds ratio; PPI, proton pump inhibitor; RCT, randomised controlled
trial; RR, relative risk; SYSADOA, symptomatic slow acting drugs for
OA; THR, total hip replacement; VAS, visual analogue scale
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670
Zhang, Doherty, Arden, et al
Table 1
Evidence hierarchy and traditional strength of recommendation
Category of evidence
Strength of recommendation
Ia Meta-analysis of RCTs
Ib RCT
A Category I evidence
IIa Controlled study without randomisation
B Category II evidence or extrapolated from

category I evidence
IIb Quasi-experimental study

III Non-experimental descriptive studies, such as
comparative, correlation, and case-control studies
C Category III evidence or extrapolated from

category I or II evidence
IV Expert committee reports or opinion or clinical

experience of respected authorities, or both
D Category IV evidence or extrapolated from

category II or III evidence
and cost effectiveness of the relevant treatments; and (c) to

generate recommendations based on a combination of the
best available evidence and expert opinion.
Experts consensus
Each committee member was asked to contribute independently up to 10 propositions describing key clinical interventions for OA of the hip. Consensus on the propositions was
reached using the Delphi technique. The initial propositions
were collated into a single list. Similar, overlapping propositions were combined. The list was returned to the experts and
they were asked to select the 10 most important from the list.
Propositions were accepted automatically if selected by over
half of participants in any round, whereas propositions
receiving only one to three votes were removed. Propositions
receiving less than 50% of the votes but more than three votes
entered the next Delphi round. The procedure was repeated
until 10 propositions were agreed.
Systematic literature search
A systematic search of the literature published between
January 1966 and March 2004 was undertaken using
Medline, Embase, CINHAL, and Cochrane Library databases.
The search included both a general search and an intervention-specific search. The general search strategy consisted of
two basic components: hip OA in whatever possible terms
in the databases (Appendix 1, available at http://www.
annrheumdis.com/supplemental) and types of research in
the forms of systematic review/meta-analysis, randomised
controlled trial (RCT)/controlled trial (CT), uncontrolled trial,
cohort study, case-control study, cross sectional study,
and economic evaluation (Appendix 2, available at http://
www.annrheumdis.com/supplemental). The general search
aimed at summarising the current available reported treatments for hip OA. The summary results of this search were
reported to the committee before the Delphi exercise.
After the Delphi exercise had generated the 10 propositions, the intervention-specific search was undertaken to
identify evidence for each specific intervention. The search
strategy included the terms for hip OA (Appendix 1, http://
www.annrheumdis.com/supplemental) and any possible
terms for the specific intervention. For example paracetamol,
acetaminophen, or simple analgesics were used for paracetamol. The results of the two searches were then combined
and duplications excluded. Medical subject heading search
(MeSH) was used for all databases and a keyword search was
used if the MeSH search was not available. All MeSH search
terms were exploded. The reference lists within reviews or
systematic reviews were examined and any additional studies
meeting the inclusion/exclusion criteria were included.
The search in the Cochrane Library included MeSH search
of the Cochrane Review, Abstracts of Quality Assessed
Systematic Reviews, the Cochrane Controlled Trial Register,
www.annrheumdis.com
NHS Economic Evaluation Databases, the Health Technology

Assessment Database, and NHS Economic Evaluation
Bibliography Details only. In addition, a topics search on
OA was undertaken.
Inclusion/exclusion criteria
Only studies with clinical outcomes for hip OA were
included. The main focus of interest was on systematic
reviews, RCTs/CTs, uncontrolled trials/cohort studies, casecontrol studies, cross sectional studies, and economic
evaluations. Studies that combined hip and knee (and/or
other joint) OA were excluded unless the results for patients
with hip OA were reported separately. Studies of other sites
of OA or other chronic joint conditions were excluded unless
the adverse effects were investigated as a primary outcome.
Other exclusions were case reports, animal studies, nonclinical outcome studies, narrative review articles, commentaries, and guidelines.
Categorising evidence
Evidence was categorised according to study design using a
hierarchy of evidence in descending order according to
qualities8 (table 1). Questions on efficacy were answered
using the best available evidence. For example, if a question
on the effect of an intervention could be answered by
category Ia evidence (that is, a systematic review of RCTs)
then studies of a weaker design (RCTs, category Ib) were not
reviewed. Questions on side effects were answered using both
RCTs and observational studies. Although the efficacy was
assessed specifically for hip OA, side effects were evaluated
specifically for the intervention irrespective of the musculoskeletal condition. Questions on cost effectiveness were
answered according to the outcome measure of the effectiveness. For example, if the effectiveness was measured as
pain relief or quality of life years (QALYs) gained, only
studies for hip OA were eligible. If the effectiveness was
measured as adverse events averted, any studies for the
proposed interventions were included.
Estimation of effectiveness and cost effectiveness
Effect size (ES) and 95% confidence interval (95% CI)
compared with placebo or active control as specified within
the propositions was calculated for continuous outcomes
such as pain relief and improvement in function.9 The ES is
the standard mean differencethat is, the mean difference
between a treatment and a control group, divided by the
standard deviation of the difference. It therefore has no units
and is comparable across the interventions. Clinically,
ES = 0.2 is considered small, ES = 0.5 is moderate, and
ES.0.8 is large.10 Results from the latest systematic review
were used if more than one systematic review was available
for the same intervention. Statistical pooling was undertaken
as appropriate11 when a systematic review was not available.

EULAR evidence based recommendations for the management of hip OA
671
Pharmaceuticals
19%
70
60
Nonpharmaceuticals
7%
50
%Studies
40
Surgery
74%
30
20
10
er
s
om
th
O
ot
TH
ste
O
er
s
th
O
ei
gh
tr
ed
uc
tio
un
sa
a/
Sp
un
ct
ur
er
bs
H
up
Ac
er
ci
se
uc
at
io
n
Ex
Ed
er
s
th
O
s
DO
A
H
or
m
on
es
To
In
pi
tra
ca
-a
l
rti
cu
la
r
SY
SA
pi
oi
d
ID
s
O
SA
Pa
ra
ce
ta
ol
Figure 1 Interventions for hip osteoarthritis from the general literature search. SYSADOA, symptomatic slow acting drugs for OA; THR, total hip
replacement.
The percentage of patients with moderate to excellent (or

.50%) pain relief or symptomatic improvement was calculated and the number needed to treat (NNT) was estimated.12
A positive value for the NNT means the treatment is more
beneficial than control; whereas a negative value for the NNT
means the treatment is less beneficial than control. NNT and
95% CI were reported only if it was statistically significant;
otherwise NS (not significant) was used to avoid the
Others
6%
Case -control
2%
EE
3%
SR
2%
RCT
15%
Cohort
24%
CT
7%
Non-CT
41%
Figure 2 Study designs for hip OA from the general literature search.
EE, economic evaluation; SR, systematic review; RCT, randomised
controlled trial; CT, controlled trial.
confusion due to its unique mathematical features.13 Relative

risk (RR) was calculated for adverse effects.14
When economic evaluation was available, study design,
comparator, perspective, time horizon, discounting, total
costs, effectiveness were reviewed. The incremental cost
effectiveness ratio (ICER) was calculated. QALYs were used
when available, otherwise disease-specific outcomes such as
pain relief and functional improvement were used.
Data were extracted by two investigators using a customised form. Any discrepancies were discussed and agreed
between the extractors before analysis. Non-English language studies were extracted by the native investigators.
Strength of recommendation
The strength of recommendation was graded AD based on
the category of efficacy evidence (table 1)8 by two members of
the committee (WZ, MD) and subsequently ratified by the
committee. When hip-specific data were absent and therefore
no hip-specific category was applicable, no strength of
recommendation could be applied. However, a visual
analogue scale (VAS) was also used. Each member of the
committee was asked to mark on a 0100 mm VAS their
strength of recommendation for each intervention, according
to the research evidence (efficacy, safety, and cost effectiveness) and clinical expertise (logistics, patient perceived
acceptance and tolerability). The means and standard error
of the mean (SEM) for the strength of recommendation were
calculated for each intervention. This system allowed
strength of recommendation to be applied when hip-specific
efficacy data were absent.
Future research agenda
Each committee member was asked to propose 10 topics for
the future research agenda based on current available
evidence and clinical experience in the management of hip
OA. A Delphi approach was used to reach a consensus on the
10 most important topics. The same criteria as those used to
select propositions were employed (that is, accepted when
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672
Table 2 Experts propositions developed through three Delphi roundsorder according

to topic (general, non-pharmacological, pharmacological, invasive and surgical)
No
Proposition
Optimal management of hip OA requires a combination of non-pharmacological and pharmacological

treatment modalities
Treatment of hip OA should be tailored according to:

(a) Hip risk factors (obesity, adverse mechanical factors, physical activity, dysplasia)
(b) General risk factors (age, sex, comorbidity, co-medication)
(c) Level of pain intensity, disability, and handicap
(d) Location and degree of structural damage
(e) Wishes and expectations of the patient
Non-pharmacological treatment of hip OA should include regular education, exercise, appliances (stick,
insoles), and weight reduction if obese or overweight
Because of its efficacy and safety paracetamol (up to 4 g/day) is the oral analgesic of first choice for mildmoderate pain and, if successful, is the preferred long term oral analgesic
NSAIDs, at the lowest effective dose, should be added or substituted in patients who respond
inadequately to paracetamol. In patients with increased gastrointestinal risk, non-selective NSAIDs plus a
gastroprotective agent, or a selective COX-2 inhibitor (coxib) should be used
Opioid analgesics, with or without paracetamol, are useful alternatives in patients in whom NSAIDs,
including COX-2 selective inhibitors (coxibs), are contraindicated, ineffective, and/or poorly tolerated
SYSADOA (glucosamine sulphate, chondroitin sulphate, diacerhein, avocado soybean unsaponifiable,

and hyaluronic acid) have a symptomatic effect and low toxicity, but effect sizes are small, suitable
patients are not well defined, and clinically relevant structure modification and pharmacoeconomic
aspects are not well established
Intra-articular steroid injections (guided by ultrasound or x ray) may be considered in patients with a flare
that is unresponsive to analgesic and NSAIDs
Osteotomy and joint preserving surgical procedures should be considered in young adults with
symptomatic hip OA, especially in the presence of dysplasia or varus/valgus deformity
10
Joint replacement has to be considered in patients with radiographic evidence of hip OA who have
refractory pain and disability
OA, osteoarthritis; NSAIDs, non-steroidal anti-inflammatory drugs; COX-2, cyclo-oxygenase-2; SYSADOA,

symptomatic slow acting drugs for osteoarthritis.
more than 50% votes; removed when less than three votes;
entered into the next round when less than 50% but more
than three votes).
RESULTS
Treatment modalities and types of research evidence
The general search yielded 1725 hits (Medline 1143, Embase
357, CINAHL 46, and Cochrane 179). After deleting duplications, 1341 hits remained. Of these, 898 were original
studies and 443 were narrative reviews, commentary, or
editorials. Figure 1 shows the breakdown of interventions
among the original 898 studies and fig 2 shows the types of
evidence.
Experts opinion approach
The experts were informed of the results of the general
literature search and then the Delphi exercise was undertaken. One hundred and twelve propositions were produced
initially and the 10 final propositions were agreed after three
anonymous Delphi rounds (table 2).
Assessment of propositions
The results from the intervention-specific search were
merged with the results from the general search. After
deleting the duplications and articles irrelevant to the
questions, 461 studies remained on the list. These included
44 concerning paracetamol; 287 associated with conventional
non-steroidal anti-inflammatory drugs (NSAIDs), cyclooxygenase-2 (COX-2) selective inhibitors (coxibs), and
gastroprotective agents; 41 in relation to symptomatic slow
acting drugs for OA (SYSADOA); 26 concerning opioid
www.annrheumdis.com
analgesics; 7 for intra-articular steroid injection; 22 related

to non-pharmacological treatments; and 34 relevant to the
two surgical propositions. The following propositions are
grouped by topic (general, non-pharmacological, pharmacological, invasive and surgical) with no weighting according to
order.
1. The optimal management of hip OA requires a

combination of non-pharmacological and
pharmacological treatment modalities
Although this statement is logical and represents common
clinical practice, there are no direct comparisons or evidence
from appropriately designed clinical trials using a factorial
design to support this statement. The statement is supported
by expert opinion alone (category IV).
2. The treatment of hip OA should be tailored

according to:
N
N
N
N
N
Hip risk factors (obesity, adverse mechanical factors, physical

activity, dysplasia)
General risk factors (age, sex, comorbidity, co-medication)
Level of pain intensity, disability, and handicap
Location and degree of structure damage
Wishes and expectations of the patient
This statement represents ideal practice and includes clinical

markers that are often used to guide clinical decisions.
However, although it has considerable commonsense face
validity, there is little experimental evidence to support it.
RCTs predominantly investigate the efficacy of one or two

673
Table 3 Evidence of efficacypooled effect size (ES) and number needed to treat (NNT)
Studies
Intervention
Category*
No
Duration
ESpain (95% CI)
ESfunction (95% CI)
NNT (95% CI)
Education
Weight loss
NSAIDs
Opioids
Chondroitin sulphate
Avocado soybean
unsaponifiable
Diacerhein
Hyaluronic acid
Intra-articular steroid
Osteotomy
THR
Ib
III
Ia
Ib
Ib
Ib
1
12
14
1
1
2
24 months
120 weeks
4 weeks
6 months
612 months
0.69 (0.12 to 1.26)

0.78 (0.38 to 1.18)
0.31 (20.64 to 1.26)
0.78 (0.26 to 1.30)
0.52 (20.36 to 1.40)
4 (3 to 6)
NS
Ib
III
Ib
III
III
1
3
1
9
118
3 years
312 months
3 months
220 years
220 years
0.00 (20.17 to 0.17)
0.00 (20.17 to 0.17)
NS
*See table 1 for definitions.

No, number of studies; ES, effect size of treatment compared with placebo unless otherwise stated; NNT, number needed to treat to obtain moderate to excellent
(.50%) pain relief or symptomatic improvement; , not available; NS, not significant.
specific monotherapies in highly selected homogeneous

populations of otherwise fit subjects with hip OA. The
evidence obtained from such experimental studies therefore
may not be directly applicable to the whole population of
subjects with hip OA. In addition, because of exclusion of
many variables that may influence outcome it is often
difficult to determine predictors of outcome. Therefore, better
evidence may be obtained from observational studies, such as
the large number of cohort studies undertaken to observe
possible risk factors or predictors at baseline for total hip
replacement (THR) or osteotomy. For example, age, level of
dysplasia, and degree of deformity are major predictors for
osteotomy,15 16 and pain intensity, radiographic severity, and
degree of disability are associated with clinical outcomes of
THR.1722 These factors become even more critical when one
moves on to consider the assessment of cost effectiveness.
For example, selective COX-2 inhibitors are only cost effective
for patients with greater risk of gastrointestinal (GI)
bleeding, and THR is more cost effective for younger women.
Any management plan requires consideration of patient
beliefs and expectations and a holistic approach that takes
into account comorbidity and other treatment requirements.
Clearly the patients beliefs and desire for a treatment are
likely to be a key component in the clinical decision for
THR.23 24
In conclusion, this statement reflects the reality of clinical
practice and a professional thoughtful approach to the
patient. A number of observational studies and economic
evaluations provide evidence to support its application
(category III).
3. Non-pharmacological treatment of hip OA should

include regular education, exercise, appliances
(stick, insoles) and weight reduction if obese or
overweight
Two systematic reviews have been undertaken for education,25 26 but neither of them contains subgroup data for hip
OA. Both show non-statistically significant effects for an
education programme compared with control. The ES from
the one covering more trials was 0.15 (95% CI 20.43 to 1.18)
and 20.02 (95% CI 20.51 to 0.47) for pain relief and
functional improvement, respectively.25 One 24 month open
RCT was undertaken in patients with hip OA awaiting THR.
All patients were given the usual information and an
information leaflet before randomisation. They were then
assigned randomly to two groups: group 1 attended a
collective multidisciplinary information session 26 weeks
before surgery and group 2 did not and acted as a control. The
results showed that the patients receiving education had less

pain than the control group.27
Five systematic reviews have been undertaken for exercise,2832 but again none of them are specific for the hip. The
latest one with the most RCTs provided an ES of 0.39 (95% CI
0.30 to 0.47) for pain relief and an ES of 0.31 (95% CI 0.23 to
0.39) for functional improvement. There is no RCT evidence
for the benefits of weight loss. However, one systematic
review of observational studies (1 cohort and 11 case-control
studies) on obesity and risk of hip OA demonstrated that
there was a positive relationship between obesity and hip OA
in the case-control studies (odds ratio (OR) = 2.3, 95% CI 1.2
to 4.4) but not in the cohort study (RR = 1.03, 95% CI 0.40 to
2.60).33 To determine whether exercise has an effect on
weight reduction, which in turn might improve clinical
outcome for patients with hip OA, further evidence is needed.
There is no research evidence for appliances such as stick and
insoles for hip OA, although they may help to reduce the
adverse forces across the joint.
In summary, only one RCT (category Ib) has been
undertaken for education in hip OA alone and it suggests
that education reduces pain. However, evidence (category Ia)
for OA at any joint showed that education may have very
little value and may not reach statistical significance. In
contrast, although direct evidence for hip OA is lacking,
exercise appears to be beneficial for OA of any kind (category
Ia). There is some evidence to support the benefit of weight
reduction for hip OA (category III), but no evidence for
appliances (stick and insoles) (table 3). Nevertheless, despite
the absence of trial data, interventions that reduce adverse
mechanical forces across a compromised hip joint have
obvious face validity.
4. Because of its efficacy and safety paracetamol (up

to 4 g/day) is the oral analgesic of first choice for
mild-moderate pain and, if successful, is the
preferred long term oral analgesic
There have been no placebo controlled RCTs, and no
comparative efficacy studies in hip OA alone, although
paracetamol is widely prescribed for hip OA. Three systematic
reviews were identified.33 34 35 The most recent covered four
placebo controlled trials, of which two were undertaken in
patients with hip or knee OA over a 6 week period.35 The
effect size for pain relief was 0.21 (95% CI 0.02 to 0.41) and
the NNT to obtain clinical benefit, defined as moderate to
excellent pain relief from paracetamol over placebo, was 4
(95% CI 2 to 43). However, paracetamol was inferior to, but
safer than, NSAIDs.
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674
Table 4 Evidence of safetypooled relative risk (RR*) and 95% confidence interval (CI)
Intervention
Adverse events
RR (95% CI)
Category of evidence
Paracetamol
GI discomfort
GI perforation/bleed
GI bleeding
Renal failure
Renal failure
0.80 (0.27
3.60 (2.60
1.2 (0.8 to
0.83 (0.50
2.5 (1.7 to
RCTs
Case-control study
Case-control studies
Cohort study
Case-control study
NSAIDs
GI perforation/ulcer/bleed
5.36 (1.79 to 16.10)

2.70 (2.10 to 3.50)
3.00 (2.70 to 3.70)
RCTs
Cohort studies
Coxibs v NSAIDs
Endoscopic GI ulcer
CV events
0.18 (0.14 to 0.23)

0.79 (0.40 to 1.55)
RCTs
RCTs
Coxibs v naproxen
CV events
1.69 (1.07 to 2.69)
RCTs
Misoprostol
Endoscopic GI ulcer
Diarrhoea
0.26 (0.17 to 0.39)

1.81 (1.52 to 2.16)
RCTs
RCTs
H2 Blockers (double doses)
Endoscopic GI ulcer
0.44 (0.03 to 0.74)
RCTs
PPIs
Endoscopic GI ulcer
0.40 (0.32 to 0.51)
RCTs
Opioids+paracetamol v
paracetamol
GI upset/constipation
14.00 (1.86 to 105.16) RCT
Diacerhein
Diarrhoea
Skin rash/pruritus
3.73 (2.61 to 5.32)

2.40 (1.01 to 5.69)
to 2.37)
to 5.10)
1.7)
to 1.39)
3.6)
RCT
RCT
*RR, relative risk between treatment group and control group; RR = 1, no different from the control population;
RR.1, more risky than the control population; RR,1, less risky than the control population. Pooled RR was
estimated for more than one study; compared with placebo/non-exposure unless otherwise stated.
H2 Blockers, histamine type 2 receptor antagonists; PPIs, proton pump inhibitors; GI, gastrointestinal; CV,
cardiovascular; CNS, central nervous system.
Recently, concern has been raised over the possible GI

toxicity of paracetamol. One case-control study indicated that
paracetamol taken at a dose of more than 2 g daily was
associated with a greater risk of GI perforation or bleed
(OR = 3.6, 95% CI 2.6 to 5.1),36 and one cohort study reported
a dose-response relationship between paracetamol and
dyspepsia.37 However, evidence from a systematic review of
RCTs shows that paracetamol has no more GI upsets than
placebo (RR = 0.80, 95% CI 0.27 to 2.37).35 A meta-analysis of
case-control studies also showed no increased risk of GI
bleeding with paracetamol 24 g daily (OR = 1.2, 95% CI 0.8
to 1.7) and no dose dependent effect in the range of ,2 g,
24 g, and .4 g per day,38 an observation that fits with
endoscopic studies.3941
Although there are some concerns about renal toxicity of

long term regular use of paracetamol,42 evidence to support
this is sparse4345 (table 4).
In conclusion, there is no direct evidence to support the use
of paracetamol in hip OA. However, evidence in OA of any
site (category Ia) demonstrates that paracetamol is effective
in relieving pain arising from OA. Although it is inferior to
conventional NSAIDs, it is safer when taken within the
recommended dose range. There are no long term data on the
efficacy or safety of paracetamol and no direct evidence for its
cost effectiveness in the treatment of hip OA. However, a
study in knee OA shows that paracetamol is better than
NSAIDs, NSAIDs plus gastroprotective agents, and coxibs for
the cost of each GI adverse effect avoided46 (table 5).
Table 5 Evidence of cost effectiveness for the proposed interventions

Intervention
Comparator
Perspective
Duration
Discounting
Effectiveness
C1-C2
E1-E2
Paracetamol
Ibuprofen
Rofecoxib
Celecoxib
Ibuprofen+GI protector
Ibuprofen
NSAIDs
Ibuprofen
Ibuprofen
NSAIDs
Institutional/payer
Institutional/payer
Institutional/payer
Institutional/payer
Institutional/payer
Institutional/payer
Institutional/payer
Institutional/payer
Canadian Health services
6
6
6
6
6
1
6
6
3
months
months
months
months
months
year
months
months
months
No
No
No
No
No
3%
No
No
No
PUB
PUB
PUB
PUB
PUB
PUB
PUB
PUB
PUB
$63000112000
$63000471000
$63000474000
$63000556000
$471000112000
$474000112000
$556000112000
$3239625622
995980
995991
995990
995988
991980
990980
988980
9686
23182
299512
289347
268472
31770
4738
33518
54146
684
NSAIDs
Canadian Health services
3 months
No
PUB averted
$2897125622
9186
644
Standard treatment
Conventional treatment
Conventional treatment
No THR
No THR
No THR
Societal
Societal
Societal
Societal
NHS
Irish institutional
9 months
Life
Life
1 year
Life
2 years
No
5%
5%
No
6%
No
Lequesne function
QALYs
QALYs
QALYs
QALYs
QALYs
F23602272
$47649165440
$3058021432
$99900
48040
472.060
2.21.2
4.162.16
4.162.16
0.840.29
8.390
74.248.8
88
217121
4754
18164
573
19
Rofecoxib
Celecoxib
Ibuprofen+GI protector
NSAIDs+misoprostol (all
patients with OA)
NSAIDs+misoprostol (patients
with OA aged >65 years)
Dicerhein+standard treatment
THR (women, 60 years)
THR (men, >85 years)
THR
THR
THR
averted
averted
averted
averted
averted
averted
averted
averted
averted
ICER
C1, total costs with intervention; C2, total costs with comparator; E1, effect with intervention; E2, effects with comparator; ICER, incremental cost effectiveness ratio, base case scenario; PUB,
perforation, ulcer, or bleed; QALYs, quality adjusted life years.
www.annrheumdis.com

5. NSAIDs, at the lowest effective dose, should be

added or substituted in patients who respond
inadequately to paracetamol. In patients with
increased gastrointestinal risk, non-selective
NSAIDs plus a gastroprotective agent, or a selective
COX-2 inhibitor (coxib) should be used
One systematic review has been undertaken for non-aspirin
NSAIDs in the treatment of hip OA, in which 14 placebo
controlled trials were reviewed.47 The ES for pain relief was
0.69 (95% CI 0.12 to 1.26) and the NNT to obtain clinical
benefit over placebo was 4 (95% CI 3 to 6), supporting the use
of NSAIDs for hip OA (table 3). However, the GI safety of
NSAIDs counters their benefits. Six systematic reviews have
been undertaken to assess the GI safety of NSAIDs using
evidence from RCTs, cohort, and case-control studies.38 4852
The results show that NSAIDs cause an increased risk of GI
bleeding (table 4), which is dose dependent (for example,
OR = 2.2 (95% CI 0.8 to 5.8), 3.2 (1.9 to 5.5), and 12.2 (5.6 to
26.7) for diclofenac ,75 mg, 75150 mg, and .150 mg a
day, respectively).38
A number of strategies have been used to minimise the GI
risk due to NSAIDs. Two systematic reviews demonstrated a
significant reduction of GI toxicity with coxibs,53 54 but five
systematic reviews provided evidence to support the coadministration of non-selective conventional NSAIDs with
gastroprotective agents such as misoprostol, double doses of
H2 blockers, and proton pump inhibitors (PPIs).5458 Table 4
presents the pooled relative risks of endoscopic gastric ulcer
between coxibs or co-administration of gastroprotective
agents and NSAIDs from the latest systematic review.54 A
similar pattern is seen for other definitions of peptic ulcer and
ulcer complications, but standard dose H2 blockers are less
effective than other GI protectors, and care must be taken
when using misoprostol as it causes an increase in diarrhoea
(RR = 1.81 95% CI 1.52 to 2.16).55
In addition, there is concern over potential cardiovascular
(CV) side effects (for example, myocardial infarction or
stroke) of rofecoxib. However, a systematic review of 23
clinical trials showed that rofecoxib is only associated with a
greater CV risk in comparison with naproxen (RR = 1.69, 95%
CI 1.07 to 2.69). The risk was not statistically significant
when compared with placebo (RR = 0.84 95% CI 0.51 to
1.38), or non-naproxen NSAIDs (RR = 0.79, 95% CI 0.40 to
1.55).59 The extra CV thrombotic events with rofecoxib may
therefore reflect more the antiplatelet or some other
protective effects of naproxen than a side effect of rofecoxib.
Further investigation of this issue is continuing.
The other important issue related to the use of coxibs or GI
protectors is whether the extra benefits can balance the extra
cost. Three economic evaluations of the treatment of OA at
any site have been undertaken.46 60 61 Because they all use
clinical GI events (perforation, ulcer, or bleed) averted as an
effectiveness outcome measure, the results may be generalisable to patients with hip OA. The results from one study
showed that the ICER of coxibs versus ibuprofen was
$31 769.9 for each adverse event averted for rofecoxib and
$33 518.5 for celecoxib. The ICER reduced when the patients
GI risk increased, indicating that the use of coxibs is more
cost effective for patients with a higher risk of GI bleeding.
Similar results were obtained with GI protective agents but
with a greater ICER, suggesting that co-prescription of GI
protectors is the more expensive strategy (table 5).
In summary, NSAIDs are effective in relieving the pain of hip
OA (category Ia). However, the GI side effects of NSAIDs offset
their benefits (category Ia). Although coxibs or the addition of
GI protectors (misoprostol, double doses of H2 blockers, and
PPIs) to conventional NSAIDs can significantly reduce GI
bleeding (category Ia), these strategies are more expensive and
only cost effective in patients with greater GI risk.
675
6. Opioid analgesics, with or without paracetamol,

are useful alternatives in patients in whom NSAIDs,
including COX-2 selective inhibitors (coxibs) are
contraindicated, ineffective, and/or poorly
tolerated
One systematic review reported that a single dose of a
combination of paracetamol and codeine increases by about
5% the analgesic strength of treatment of any type of pain,
including pain due to hip OA.62 Unfortunately, the review
failed to separate hip OA from other conditions. The review
additionally showed that paracetamol plus codeine caused
more adverse events than paracetamol alone (RR = 2.5, 95%
CI 1.5 to 4.2). Four RCTs were identified for hip OA, one
comparing codeine with placebo63 and three comparing
paracetamol plus opioid with placebo,64 paracetamol,65 or
diclofenac.66 Opioid (codeine) on it own was better than
placebo for pain relief (ES = 0.78, 95% CI 0.38 to 1.18) and
functional improvement (ES = 0.78, 95% CI 0.26 to 1.30), but
it also caused more adverse events (RR = 1.43, 95% CI 1.09 to
1.86).63 Although the combination of paracetamol and opioid
provided better analgesia than placebo (ES = 0.30, 95% CI
0.05 to 0.53),64 this treatment was no better than paracetamol
(RR for moderate to excellent pain relief 1.27, 95% CI 0.82 to
1.98)65 and was inferior to diclofenac (ES = 20.18, 95% CI
20.33 to 20.04).66 More importantly, the combination caused
more side effects (RR = 7.25, 95% CI 2.61 to 20.13), GI
upsets, constipation (RR = 14, 95% CI 1.86 to 105.16), and
dizziness or drowsiness (RR = 5.00, 95% CI 1.48 to 16.92)64
and resulted in greater withdrawal rates (RR = 3.57, 95% CI
1.92 to 6.62)66 (table 4).
In summary, opioid analgesics with or without paracetamol are effective for hip OA (category Ib). However, the effect
may be no better than paracetamol alone and inferior to
NSAIDs (category Ib). In addition, they cause more side
effects and resultant cessation of treatment (category Ia and
Ib). Such evidence supports the statement and reinforces the
suggestion that opioid analgesics should only be considered
for patients in whom paracetamol, conventional NSAIDs or
coxibs have insufficient efficacy, or in whom there are
contraindications to NSAIDs/coxibs.
7. SYSADOA (glucosamine sulphate, chondroitin

sulphate, diacerhein, avocado soybean
unsaponifiable, and hyaluronic acid) have a
symptomatic effect and low toxicity, but effect sizes
are small, suitable patients are not well defined, and
clinically relevant structure modification and
pharmacoeconomic aspects are not well established
The term SYSADOA covers a range of agents, including
glucosamine sulphate (GS), chondroitin sulphate (CS),
diacerhein, avocado soybean unsaponifiable (ASU), and
hyaluronic acid (HA). The classification varies from country
to country. In the UK, for example, GS and CS are classified
as health food supplements and are available over the
counter. A number of systematic reviews have been undertaken to support the use of oral GS67 68 and CS.67 69 However,
none of them are specific for the hip. In the mixed trials with
hip and knee OA, the pooled ES of GS versus placebo were
0.44 (95% CI 0.24 to 0.64) for pain relief and 0.41 (95% CI
0.14 to 0.69) for functional improvement, while those for CS
were 0.78 (95% CI 0.60 to 0.95) and 0.63 (95% CI 0.32 to
0.94), respectively. One hip-specific placebo controlled RCT
was undertaken for CS, demonstrating that CS was statistically better than placebo in reducing pain and improving
function over 6 months of treatment. However, the ES could
not be calculated as standard deviations were not reported.70
The systematic literature search failed to identify other levels
of evidence specific for hip OA. Evidence for structure
modifying effects of these two agents has not been
www.annrheumdis.com

676
established. One RCT demonstrated that intramuscular

glycosaminoglycan peptide complex (now withdrawn from
the market) given twice a year for 5 years had no more
structural benefits than placebo for hip OA.71
Two systematic reviews72 73 have been undertaken for
herbal treatment, including two RCTs74 75 for ASU in OA of
various sites. A subgroup of patients with hip OA (n = 50)
were available from one of the trials with a 24 week
treatment period.75 The results showed a significantly greater
pain relief than placebo (ES = 0.76, 95% CI 0.17 to 1.34).
However, this was not supported by a recent trial with a
larger sample size (n = 163) and longer treatment period
(1 year for symptomatic outcomes and 2 years for structural
changes).76 The pooled ES for pain relief and functional
improvement of these two trials were not statistically
significant (table 3). In addition, there were no structural
benefits with ASU over the 2 year treatment period.76
Evidence for diacerhein is inconclusive. One multicentre
RCT with 507 patients with hip OA showed that diacerhein
had no more pain relief (ES = 0.00, 95% CI 20.17 to 0.17) or
functional improvement (ES = 0.00, 95% CI 20.17 to 0.17)
than placebo over a 3 year treatment period.77 However, this
study was designed to investigate structure modification
rather than symptom benefit. Another RCT of 207 patients
with hip or knee OA demonstrated that the combination of
diacerhein and standard treatment was more effective in
reducing pain (ES = 0.29, 95% CI 0.05 to 0.57) and improving
function (ES = 0.35, 95% CI 0.08 to 0.63) than standard
treatment alone over a 6 month period,78 though data for hip
OA alone was not presented.
However, regardless of efficacy diacerhein causes an
increase in the incidence of side effects such as diarrhoea
(RR = 3.73, 95% CI 2.61 to 5.32), and skin rash or pruritus
(RR = 2.40, 95% CI 1.01 to 5.69).77 Nevertheless, diacerhein
may slow the progression of joint space narrowing in hip
OA.77 The relative risk of the progression, defined as a joint
space narrowing >0.5 mm, during a 3 year treatment period
compared with placebo was 0.84 (95% CI 0.71 to 0.99), with
an NNT of 10 (95% CI 5 to 171). However, although it may be
more cost effective than standard treatment in the short term
without considering its long term side effects,78 the clinical
benefit-risk ratio of diacerhein for patients with hip OA has
yet to be confirmed.
Contrary to knee OA, there is no RCT evidence to support
the use of intra-articular HA in hip OA, though three
uncontrolled studies7981 all show significant pain reduction
from baseline.
In conclusion, there is no direct evidence to support the
clinical benefits (pain relief and functional improvement) of
GS in hip OA, though there is category Ia evidence for OA of

any joint. One RCT (category Ib) demonstrates that CS
effectively reduces pain and functional disability due to hip
OA. The symptomatic benefits of ASU and diacerhein are
inconclusive (category Ib) and the evidence for HA is poor
(category III). The structure modifying effect and cost
effectiveness of SYSADOA have yet to be established.
8. Intra-articular steroid injections (guided by

ultrasound or X ray) may be considered in patients
with a flare that is unresponsive to analgesic and
NSAIDs
Three trials have been undertaken for hip OA,8284 but only
one is an RCT comparing a steroid-anaesthetic combination
with anaesthetic alone.82 Only a dichotomous outcome is
available from this trial and therefore the ES was not
calculated. The rate ratio for pain relief was 1.18 (95% CI 0.68
to 2.15) and 0.61 (0.23 to 1.60) at 1 month and 3 months,
respectively, indicating that the combination was no better
than anaesthetic alone for hip OA. Although two uncontrolled trials showed some short term ((3 months) pain
reduction from intra-articular corticosteroid,83 84 the results
are open to bias due to placebo effects. Thus unlike for knee
OA there is no robust evidence to support the efficacy of
steroid injection for hip OA, irrespective of its increased
technical difficulty. Also, there are no comparative data to
show increased accuracy using ultrasound or x ray guidance,
and no data available for the occurrence of a flare.
In conclusion, there is category Ib evidence for this
statement, but the results are inconclusive and placebo
controlled trials in hip OA are required.
9. Osteotomy and joint preserving surgical

procedures should be considered in young adults
with symptomatic hip OA, especially in the presence
of dysplasia or varus/valgus deformity
Osteotomies of the pelvis and/or femoral osteotomies can
alter force transmission through the hip joint and thus
potentially influence clinical symptoms and the course of the
OA process. Symptomatic and structural effects have been
evaluated, especially in patients with acetabular dysplasia
and valgus deformity of the femoral neck. As with THR,
however, most published investigations are cohort studies,
and we failed to identify any RCT for either symptoms or
structural change. At least seven retrospective cohort
studies15 16 8589 and two prospective cohort studies90 91 with
follow up times ranging from 2 to 20 years have investigated
both outcomes and baseline predictors relevant to the
proposition. Patients showed significant improvement in
Table 6 Radiographic severity, pain, and function and relative risk of total hip
replacement
Risk factors
Overall x ray change*
Croft grade
0/1
2
3
4
5
Pain (>50%)
Lequesne function (>10)
Cohort studies
No of
studies
RR (95% CI)
No of
studies
OR (95% CI)
2.39 (1.74 to 3.29)
1.98 (1.23 to 3.19)
1
3.36 (0.31 to 38.91)
15.23 (3.29 to 70.49)
44.51 (10.04 to 197.48)
57.29 (12.12 to 270.71)
1.86 (1.23 to 3.88)
2.75 (1.98 to 3.82)
1
1
1.91 (1.43 to 2.56)

1.75 (1.24 to 2.48)
4
1
1
2
*Defined as Croft grade >2, or joint space of (2 mm.

All values are adjusted by age, sex, and body mass index. A pooled RR/OR was estimated for more than one
study.
www.annrheumdis.com

clinical outcomes (pain, walking ability, and overall functional scores) and radiographic outcome after the operation.
Advanced age,15 91 radiographic severity,16 8588 degree of
dysplasia,15 88 and radiographic deformity15 16 at baseline were
associated with worse clinical outcomes and with surgical
failure, mainly defined as requirement for THR. As the vast
majority of studies have been performed in young adults with
at least mild or moderate symptoms (mainly hip pain) and
data on the natural course of femoral and acetabular
deformities is lacking, the effectiveness of osteotomy in
asymptomatic patients and in different age groups has yet to
be established.
Data from observational studies also support more recently
advocated joint preserving surgical procedures such as
arthroscopic debridement92 93 and surgical dislocation of the
hip with offset reconstruction.94 95 Although improvement of
symptoms has been reported in these studies, the lack of
control groups with an alternative treatment hinders interpretation of their results.
In conclusion, evidence for osteotomy and joint preserving
surgical procedures in patients with hip OA is sparse
(category III). It appears to be a useful procedure for younger
patients with painful hip dysplasia or deformity for whom
THR is not yet justified. However, its effectiveness and cost
effectiveness as compared with THR in patients with
advanced age and/or OA stages have yet to be established.
10. Joint replacement has to be considered in

patients with radiographic evidence of hip OA who
have refractory pain and disability
Because of methodological and ethical problems, comparison
of THR with placebo or standard care is not readily evaluated
by an RCT. Our literature search failed to identify any placebo
or standard care controlled RCT for THR. However, there are a
large number of head to head comparisons between different
types of prosthesis and uncontrolled follow up studies.96 97
One systematic review identified 118 uncontrolled follow up
studies involving a total of 77 375 patients for an average
follow up period of 9.4 years (range 220 years).97 The
percentage of patients free from pain at the end point ranged
from 43.2% (95% CI 34 to 49) to 84.1% (95% CI 46 to 100)
Table 7
677
depending upon the type of prosthesis. The mean reduction

of Harris hip score (maximum 100, including pain 040,
function 047, motion 05, and deformity 08) from baseline
ranged from 36% to 46%. The revision rate, one of the major
concerns for THR, was 0.18 (standard error of mean (SEM)
0.04) to 2.04 (SEM 0.19) per 100 person-years adjusted by
age, sex, and type of hip arthritis. More information about
the difference between prostheses is available,96 97 but this
falls beyond the scope of this statement.
For concurrent comparison, better pain relief and quality of
life were obtained with THR in one small Asian cohort study
of THR versus non-surgical treatment. However, although in
the first year THR was better than non-surgical treatment, by
5 years this benefit was reversed.98 Because the study had a
very small sample size (62 v 45) and no adjustment for
confounders, the results are subject to bias. Two other cohort
studies have been undertaken, one comparing WOMAC and
SF-36 scores99 and the other comparing survival rates100
between patients with THR and the source populations.
Apart from worse functional scores, the THR group had a
similar quality of life and survival rate to those of the source
populations.
Whether radiographic change should be one of the criteria
for THR is still open to debate. Six cohort studies1722 (four
with data available for re-analysis) and one case-control
study101 demonstrated a positive relationship between radiographic severity and risk of THR (table 6). A greater risk of
THR was also seen with severe pain and disability. Thus the
severity of radiographic change, pain, and disability are good
predictors for THR. However, whether they are independent
risk factors for THR or are factors that surgeons currently use
to guide the decision process is hard to determine.
Nevertheless, as long as the diagnosis of OA is confirmed
(most commonly by radiographic change) it has obvious
validity for the severity of patient centred problems (pain,
disability) to largely determine the need for major surgery.
Another important consideration for THR is whether it is
cost effective compared with other treatments. Five economic
evaluations of THR were identified, though one compared
different prostheses96 so is not relevant to this statement.
Four studies compared THR either with conventional
Future research agendapropositions developed through three Delphi rounds
No
Proposition
More RCTs of both pharmacological and non-pharmacological treatments that give outcomes
specific to hip OA are needed
Biological markers for evaluation of the progression of hip OA should be further evaluated
Clinical predictors of response to pharmacological and non-pharmacological interventions for

hip OA should be determined
Whether long term use of SYSADOA can retard the progression of hip OA and delay joint
replacement should be investigated
RCTs of injection treatments (corticosteroid, hyaluronan) in hip OA are required
The most efficient and effective exercise programme for hip OA should be determined
Studies with appropriate design to determine the comparative effectiveness and cost
effectiveness of non-surgical and surgical treatment modalities are needed
Agreed criteria relating to indications and timing of THR are needed
Prospective population based studies are required to improve our knowledge of risk factors for
the development and progression of hip OA
10
Newer imagining techniques (MRI, ultrasound) require validation for the diagnosis and
assessment of outcome in trials of hip OA
www.annrheumdis.com

678
Table 8 Strength of recommendation
Intervention
Efficacy
Side effects
Cost effectiveness
SOR based on
efficacy (AD)
SOR based on all

evidence and clinical
expertise (VAS, mean
(SEM))
Pharmacological + non-pharmacological
treatment
Treatment tailored according to risk factors,
severity of hip OA, and patient expectations
Education
Exercise
Insole/stick
Weight loss
Paracetamol
NSAIDs
Coxibs
IV +
86.94 (5.82)
III +
92.19 (3.39)
Ib +
IV +
III +
Ia +
Ia + (GI protection)
Ia 2, III (GI)
Ia +, III+ (GI)
Ia (CV)
A
N/A
D
D
N/A
A
A
71.75
71.58
61.72
68.28
79.19
79.36
79.44
Misoprostol
Ia + (diarrhoea)
46.06 (5.62)
H2 Blockers (double dose)
31.28 (6.81)
PPIs
Opioids
Glucosamine
Chondroitin
Diacerhein
Avocado soybean unsaponifiable
Hyaluronic acid
Intra-articular steroid
Osteotomy
THR
Ib +
Ib +
Ib
Ib 2
III +
Ib 2
III +
III +
Ia + (any, GI, CNS)
Ib + (dyspepsia)
Cost saving
Higher GI risk
population
Higher GI risk
population
High GI risk
population
Short term
Women with
younger age
A
A
N/A
A
Inconclusive
Not recommended
C
Not recommended
C
C
73.86
43.97
37.06
34.44
27.83
31.72
22.83
41.47
59.64
86.86
Research evidence*
(6.42)
(6.30)
(6.91)
(5.79)
(3.82)
(4.18)
(3.51)
(3.97)
(4.36)
(5.03)
(4.76)
(5.38)
(4.79)
(4.17)
(5.74)
(5.19)
(2.42)
*Evidence was categorised according to the hierarchy in table 1.

, not supportive, +, supportive; , uncertain. For example, Ia + (GI) means there is category Ia evidence to support the statement that the treatment causes GI
side effects.
SOR, strength of recommendation; VAS, visual analogue scale (0100 mm, 0 = not recommended at all, 100 = fully recommended); SEM, standard error; GI,
gastrointestinal; CV, cardiovascular; CNS, central nervous system. , not available; N/A, not applicable owing to absent hip-specific data.
treatment102 or non-THR treatment, assuming there was no

cost or effects for the non-THR group.97 103 104 The results
showed that THR did require additional cost to gain its
additional benefits over conventional treatment or non-THR
treatment (table 5). However, it was more cost effective in
younger women. For example, compared with conventional
treatment THR was cost saving for a woman aged 60 years
(ICER 2$17121 per QALY gained), whereas it was less cost
effective for a man aged more than 85 years (ICER $4,754 per
QALY gained).
Given the benefits and costs of THR, determination of the
ideal point at which to perform surgery in the course of OA is
crucial. A number of priority criteria have been proposed for
patients awaiting THR,20 103 104 but none of them are universally agreed. While the importance of the degree of
radiographic change remains unclear, pain and function
appear the most important and agreed measures for THR
and they are directly associated with postoperative
outcomes.21 99 105 106
In conclusion, THR is effective in hip OA in improving
clinical outcomes such as pain and function (category III). In
general, THR is more cost effective in younger women.
Radiographic change is usually sufficient to confirm the
diagnosis of hip OA, and the severity of radiographic change,
as well as pain and disability are risk factors for THR. There is
obvious face validity and evidence for the severity of pain and
disability to be key determinants of the need for major
surgery (category III).
Future research agenda

Ninety five research topics were recommended initially.
Table 7 shows the 10 that were agreed eventually as the
most important topics for future research according to
current available research evidence and clinical practice.
www.annrheumdis.com
DISCUSSION
This is the first comprehensive document to provide
recommendations for the management of hip OA. Unlike
previous guidelines that are specific for,107 or inclusive108 109 of,
hip OA, these recommendations are based both on expert
opinion and research evidence, with clear separation between
the two. We have employed explicit methods such as the
Delphi technique to generate consensus and an evidence
based medicine approach to identify and appraise the
research evidence. A similar hybrid technique was used to
develop the EULAR recommendations for the management of
knee OA.6 7 However, for these recommendations on hip OA
we introduced three important methodological changes.
Firstly, we did not score the quality of the studies. We had
found this exercise to be unhelpful in assessing the research
evidence because quality scores are subject to bias that results
from the quality of reporting. For example, RCTs that appear
before the CONSORT statement110 may have lower quality
scores than those reported afterwards. Thus quality scores do
not necessarily reflect the accuracy or credibility of a study
and cannot be used to weight clinical trial results. We
therefore used only the evidence hierarchy, which clearly
differentiates studies according to their methodological
rather than reporting qualities, to rank the quality of the
evidence.
Secondly, we used the pooled effect size from the latest
systematic review (or synthesised evidence if necessary) and
95% confidence intervals to present the overall estimation
and the precision of the treatment effects.
Thirdly, we assessed the efficacy, side effects, and cost
effectiveness of each treatment rather than just their efficacy
from RCTs and applied the VAS 0100 mm scale for the
strength of recommendation to facilitate the multidimensional issues for each treatment.

Of the 21 interventions included within the 10 propositions, 15 were positively supported by evidence of grades Ia to
IV (table 8), but 6 of them had either no direct evidence
(paracetamol, glucosamine, and exercise) or inconclusive
benefits (ASU, diacerhein, and intra-articular steroid injection) for hip OA. In contrast, these treatments are effective
and have been recommended for knee OA.6 7 More data on
these interventions for hip OA are required, but the current
evidence suggests that there may be true treatment differences for OA according to the site affected. Such differences
support the requirement by regulatory bodies to obtain
separate research evidence for the benefit of treatments at
each key site of OA. Similar site-specific differences for OA
are known to occur for risk factors for development and
progression of OA and for the correlation between pain and
structural change, reflecting the heterogeneity of the OA
process.111
Although the evidence hierarchy is widely used to rank the
quality of evidence,8 its value in surgical treatment and side
effects has been questioned.112 113 THR, for example, has been
accepted as a clinically effective treatment for hip OA,
particularly for the patient with refractory pain and disability,
or for those who fail to response to conventional treatment.
However, because of ethical and practical issues over blinding
of the treatments, there are no placebo controlled or
concurrent non-surgical controlled RCTs. The evidence to
support THR comes from uncontrolled or cohort studies and
is thus graded as category III, which is discordant with the
high strength of support for THR when all forms of evidence,
not just research evidence, are considered (table 8). Furthermore, in the absence of hip-specific data and therefore no
category of evidence, strength of recommendation based on
the evidence hierarchy could not be applied. Such problems
challenge the current closely linked methods for categorising
evidence and affording a strength of recommendation.112
To overcome this, we undertook a post hoc study by asking
the committee members to mark the strength of recommendation for each intervention on a VAS (0100 mm).
Compared with the traditional grading scale for strength of
recommendation, the VAS scale considers research evidence
of all kinds (efficacy, safety, and cost effectiveness) and
clinical expertise. More importantly, the VAS scale allows
both downgrading and upgrading of the strength of
recommendation, offering a different dimension from the
category of evidence. For example, the strength of recommendation for NSAIDs is 79% given the highest category of
evidence (Ia) for efficacy, whereas the strength of recommendation for total hip replacement is 86%, although it only
obtained category III evidence for efficacy (table 8).
These recommendations have several limitations. Firstly,
although management of hip OA was the primary interest,
for some interventions, such as paracetamol and exercise, we
failed to identify any studies specific to hip OA or studies in
which the data for hip OA could be separated. In this
situation, we specified lack of hip-specific data but considered the evidence from mixed studies when determining the
strength of recommendation. This may cause some imprecision and the values are yet to be confirmed. Secondly, the
effect sizes were selected from the latest systematic review
with the maximum number of the studies involved, but not
necessarily the review with the best quality and relevancy.
Subgroup analyses were often required, but in most cases the
data were not available. Thirdly, only effect sizes for
symptomatic outcomes such as pain and function were
examined for efficacy. Efficacy beyond these patient centred
outcomes remains unknown. Finally, the existing evidence
hierarchy centres on treatment efficacy, whereas evidence for
safety and cost effectiveness is best examined by designs
other than RCTs and therefore requires its own specific
679
system to judge category of evidence. In the absence of such a

specific system we used the existing hierarchy, but would
favour future development of an equivalent system for these
other aspects of management.
In conclusion, we have developed recommendations for the
management of hip OA based on both clinical practice and
the best available research evidence. Fifteen of 21 interventions included within 10 key propositions have research
evidence (category IaIV) to support their use in the
management of hip OA, although they vary in their efficacy,
side effect, and cost effectiveness profiles. Three interventions
(paracetamol, GS, and exercise) had no hip-specific evidence
and three interventions (ASU, diacerhein, and intra-articular
injection) had category I evidence to show either no
symptomatic benefit or inconclusive evidence for hip OA,
even though these treatments are effective for knee OA.
Clearly, more clinical trial data specific to hip OA are
required, especially because some interventions appear to
show different efficacy according to the joint site. It is
hoped that wide dissemination and discussion of these
recommendations within healthcare provider groups will
improve knowledge and interest in the management of hip
OA and result in higher standards of care for patients with
hip OA.
ACKNOWLEDGEMENTS
We thank Bristol Myers Squibb, in particular its representativeDr
Manuela Le Bars, for financial support, and Mrs Helen Richardson
and Dr Jinying Lin for logistical support.
.....................
Authors affiliations
M Dougados, Service de Rhumatologie B, Hospital Cochin, Paris, France

M Doherty, W Zhang, Academic Rheumatology, University of
Nottingham, Nottingham, UK
N Arden, K Jordan, Southampton General Hospital, MRC
Environmental Epidemiology Unit, Southampton, UK
B Bannwarth, Service de Rhumatologie, Ho
pital Pellegrin, Bordeaux,
France
J Bijlsma, Department of Rheumatology and Immunology, University
Hospital, Utrecht, The Netherlands
K-P Gunther, Department of Orthopaedic Surgery, University of
Dresden, Dresden, Germany
H J Hauselmann, Centre for Rheumatology and Bone Diseases, Clinic Im
Park, University of Zurich, Zurich, Switzerland
G Herrero-Beaumont, Rheumatology Department, Clinique de la
Conception, Madrid, Spain
P Kaklamanis, 16 Anaperon Polemon, 11521, Athens, Greece
B Leeb, Rheumatology, Stockerau Hospital, Stockerau, Austria
M Lequesne, Department of Rheumatology, Ho
pital Leopold Bellan,
75014, Paris, France
S Lohmander, Department of Orthopaedics, Lund University Hospital,
SE-22185, Lund, Sweden
B Mazieres, Service de Rheumatologie, Hospital de Rangueil, Toulouse,
France
E Martin-Mola, Division de Rheumatologia, Hospital La Paz, Madrid,
Spain
K Pavelka, Institute of Rheumatology, 12850, Praha 2, Czech Republic
A Pendleton, Rheumatology, Belfast City Hospital, Belfast, UK
L Punzi, Department of Medical Sciences, University of Padova, Padova,
Italy
B Swoboda, Orthopaedics, University of Erlangen-Nuremberg,
Erlangen, Germany
R Varatojo, No32B 1400107, Lisbon, Portugal
G Verbruggen, Rheumatology Unit, UZRUG, Gent, Belgium
I Zimmermann-Gorska, Department of Rheumatology and
Rehabilitation and Internal Medicine, Poznan
, University of Medical
Sciences, Czerwca, Poland
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EULAR evidence based recommendations for

the management of hip osteoarthritis: report of
a task force of the EULAR Standing Committee
for International Clinical Studies Including
Therapeutics (ESCISIT)
W Zhang, M Doherty, N Arden, B Bannwarth, J Bijlsma, K-P Gunther, H J
Hauselmann, G Herrero-Beaumont, K Jordan, P Kaklamanis, B Leeb, M
Lequesne, S Lohmander, B Mazieres, E Martin-Mola, K Pavelka, A
Pendleton, L Punzi, B Swoboda, R Varatojo, G Verbruggen, I
Zimmermann-Gorska and M Dougados
Ann Rheum Dis 2005 64: 669-681 originally published online October 7, 2004
doi: 10.1136/ard.2004.028886
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Downloaded from http://ard.bmj.com/ on May 3, 2015 - Published by group.bmj.

EULAR evidence based recommendations for the

Appendixes are available

he hip is the second most common large joint to be

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Zhang, Doherty, Arden, et al

Evidence hierarchy and traditional strength of recommendation

IIa Controlled study without randomisation

B Category II evidence or extrapolated from

IIb Quasi-experimental study

C Category III evidence or extrapolated from

IV Expert committee reports or opinion or clinical

D Category IV evidence or extrapolated from

and cost effectiveness of the relevant treatments; and (c) to

NHS Economic Evaluation Databases, the Health Technology

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The percentage of patients with moderate to excellent (or

confusion due to its unique mathematical features.13 Relative

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Zhang, Doherty, Arden, et al

Table 2 Experts propositions developed through three Delphi roundsorder according

Optimal management of hip OA requires a combination of non-pharmacological and pharmacological

Treatment of hip OA should be tailored according to:

SYSADOA (glucosamine sulphate, chondroitin sulphate, diacerhein, avocado soybean unsaponifiable,

OA, osteoarthritis; NSAIDs, non-steroidal anti-inflammatory drugs; COX-2, cyclo-oxygenase-2; SYSADOA,

analgesics; 7 for intra-articular steroid injection; 22 related

1. The optimal management of hip OA requires a

2. The treatment of hip OA should be tailored

Hip risk factors (obesity, adverse mechanical factors, physical

This statement represents ideal practice and includes clinical

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ESpain (95% CI)

ESfunction (95% CI)

NNT (95% CI)

0.69 (0.12 to 1.26)

0.31 (20.64 to 1.26)

0.78 (0.26 to 1.30)

0.52 (20.36 to 1.40)

0.00 (20.17 to 0.17)

0.00 (20.17 to 0.17)

*See table 1 for definitions.

specific monotherapies in highly selected homogeneous

3. Non-pharmacological treatment of hip OA should

results showed that the patients receiving education had less

4. Because of its efficacy and safety paracetamol (up

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Zhang, Doherty, Arden, et al

5.36 (1.79 to 16.10)

0.18 (0.14 to 0.23)

1.69 (1.07 to 2.69)

0.26 (0.17 to 0.39)

H2 Blockers (double doses)

0.44 (0.03 to 0.74)

0.40 (0.32 to 0.51)

14.00 (1.86 to 105.16) RCT

3.73 (2.61 to 5.32)

Recently, concern has been raised over the possible GI

Although there are some concerns about renal toxicity of