Alami, S.

Boutron, I.

Desjeux, D.

Hirschhorn, M.

Meric, G.

Poiraudeau, S.

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Osteoarthritis and Cartilage Vol. 15, Supplement C C133
234
EXPECTATIONSREGARDING KNEE OSTEOARTHRITIS
MANAGEMENT: VIEWS FROM PATIENTS AND
PRACTITIONERS. A QUALITATIVE INTERVIEW STUDY
S. Alami1, I. Boutron2, D. Desjeux3, M. Hirschhorn4, G. Meric5,
S. Poiraudeau6
1Interlis, Paris, France; 2AP-HP, Université Paris 7, Paris,
France; 3Département d’anthropologie, Université Paris 5, Paris,
France; 4Département de sociologie, Université Paris 5, Paris,
France; 5Pﬁzer, Paris, France; 6AP-HP, Université Paris 5,
INSERM IFR 25, Paris, France
Purpose: Knee Osteoarthritis (OA) is highly prevalent and affects
health-related quality of life and healthcare costs. Our objectives
were to identify expectations of patients regarding knee OA
management, to reveal potential obstacles for improvements of
health care strategies, and to explore care providers’ perceived
difﬁculties in treating patients with knee OA.
Methods: A qualitative study based on semi structured inter-
views was performed with a stratiﬁed sample of 81 patients (59
women, 21 using alternative medicine) and 29 practitioners (8
women, 11 general practitioners (GPs), 6 rheumatologists, 4
orthopedic surgeons, 8 (4 GPs) delivering alternative medicine).
Results: Patients did not express problems with the way knee
OA is diagnosed but GPs sometimes feel uncomfortable with
the diagnosis, begin treatment without announcing OA to pa-
tients and consider knee x-rays as the gold standard to conﬁrm
knee OA. Some practitioners consider knee OA as a common,
ineluctable, age-related disease with limited treatment options.
This attitude appears to have a negative impact on patient man-
agement: it tends to conﬁne treatments to pain medication, and
patients feel that their complaints are not taken seriously enough
which leads to less compliance to the treatment. Patients also
feel that practitioners often act as technicians paying much at-
tention to the knee but less to the individual, and consider that
not enough time is spent for information and counseling. This is
the reason most often cited for being suspicious of drugs, hav-
ing the feeling of medical uncertainty toward OA, and switching
to alternative medicine. Practitioners, mainly GPs, felt frustrated
about the impact of counseling on weight loss but admitted to
feel uncomfortable to tackle the subject and sometimes to avoid
it. Regarding pharmacological treatments, patients consider that
having to take pills at regular interval is a constraint which weak-
ens compliance. They have ambivalent attitude towards NSAIDs,
considering that they are effective on pain but with an overall
negative opinion due to adverse effects and fears and beliefs
about their harmfulness when taken for long time. GPs expect
more formation on the disease and more funds for research.
Conclusions: Our results suggest several potential improve-
ments to maximize patients’ management: more attention and
time should be devoted to patient/practitioner relationship and en-
vironmental factors. Patients’ proﬁles should be more precisely
deﬁned regarding coping strategies and treatment preferences
to propose more adapted and speciﬁc options.
235
CLINICAL MEASUREMENTS OF GAG SYNTHESIS IN
HUMAN ARTICULAR CARTILAGE IN VIVO
K.W. Li1, E.W. Cheng1, C.R. Allen2, M.K. Hellerstein2,
S.M. Turner1
1KineMed, Inc, Emeryville, CA; 2UCSF, San Francisco, CA
Purpose: Chondroitin sulfate (CS) and hyaluronic acid (HA) are
key components of articular cartilage and their regulation may
be important in the treatment of OA. An in vivo assay has been
developed for animal models in which heavy water (2H2O) is
incorporated into newly-synthesized GAG. The objective of this
study was to adapt this assay for use in people to determine the
synthesis rates of CS and HA in human articular cartilage after
obtaining either cartilage biopsies or synovial ﬂuid (SF) aspirates.
Methods: Patients scheduled for ACL reconstruction surgery
were recruited for this IRB-approved study. Five patients were
given 2-3 oral doses of 2H2O per day for 15-42 days prior to
surgery, resulting in 2H2O enrichment in body water of 1.5±0.3%.
On the day of surgery, small biopsies of articular cartilage (1-2
mg) were harvested during routine notchplasty. A sample of SF
also was obtained from all subjects. Body water enrichment was
monitored from saliva samples, obtained weekly during the la-
beling period. Following surgery, HA and CS were isolated from
cartilage and SF samples and analyzed by gas chromatogra-
phy/mass spectrometry. Speciﬁcally, fractional synthesis, or the
fraction of HA and CS that was newly-synthesized, was de-
termined from the 2H-enrichment of N-acetyl glucosamine and
N-acetyl galactosamine, respectively. Data are mean±SD.
Results: 2H-enrichments in CS ranged from 0.3-1.3% and in-
creased 0.04% per day (p<0.01, r2=1). These 2H-enrichments
were above the sensitivity limit of GC/MS. Expressed as frac-
tional synthesis, the CS in the articular cartilage was synthesized
at a rate of 0.8±0.3% per day (Fig. 1; n=5). This represented
an interpatient CV of 40%. For patients from which multiple
cartilage specimens were obtained, intra-patient variability was
higher, with an average CV of 48% (n=4).
Fractional HA synthesis in the cartilage was 0.4±0.2%, 50%
lower than the CS turnover rate (p=0.02; n=5). Inter- and intra-
patient variability in HA synthesis was 48% (n=5) and 19% (n=3),
respectively.
Figure 1. Fractional synthesis rates of CS & HA in individual cartilage biopsies
taken from ﬁve patients.
The CS from SF had a fractional synthesis rate of 1.9±0.6%
(n=5), 2.5X greater than that in the articular cartilage (p=0.03),
suggesting that newly-synthesized CS rather than degraded ma-
trix was lost preferentially to the SF. Regression analysis did not
indicate a relationship between the CS synthesis measurements
in cartilage and SF (n=5, p=0.7, r2=0.07). The HA in SF was
nearly completely turned over in this study. Shorter labeling du-
rations would be necessary to measure this parameter. Unlike
SF CS, which typically originates from cartilage, the production
of SF HA is predominantly mediated by synovium.
Conclusions: We present the ﬁrst direct in vivo measurement of
the synthesis rates of CS and HA in “normal” human cartilage,
which had half-lives of 92 and 181 days, respectively. These
half-lives were much less than those previously shown in in vitro
systems, which may reﬂect stimulation from the joint environ-
ment induced by traumatic knee injury. This study establishes
a physiological baseline for evaluating metabolic alterations that
may occur during OA progression and in response to therapeutic
intervention.
The majority of CS in SF is bound to aggrecan, indicating that


234 EXPECTATIONS REGARDING KNEE OSTEOARTHRITIS MANAGEMENT: VIEWS FROM PATIENTS AND PRACTITIONERS. A QUALITATIVE INTERVIEW STUDY 

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234 EXPECTATIONS REGARDING KNEE OSTEOARTHRITIS MANAGEMENT: VIEWS FROM PATIENTS AND PRACTITIONERS. A QUALITATIVE INTERVIEW STUDY

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