Vol.2, No.7, 705-707 (2010)
doi:10.4236/health.2010.27107
Copyright © 2010 SciRes. Openly accessible at http://www.scirp.org/journal/HEALTH/
Health
Pharmacotherapeutic aspects of treating knee
osteoarthritis with glucosamine sulfate
Steven Simoens*, Gert Laekeman
Research Cent re for Pharma ceut ic al Ca re an d Phar maco-ec onomic s, Katholie ke Univ er sitei t Leu ven , Onde rwij s en Navo rsi ng,
Leuven, Belgium; *Corresponding Author:
Received 5 February 2010; revised 11 March 2010; accepted 15 March 2010.
ABSTRACT
Glucosamine sulfate is a natural constituent of
cartilage and is used in the treatment of knee
osteoarthritis. The aim of this study is to pro-
vide a short but comprehensive pharmaco-
therapeutic update on treating knee osteoarthri-
tis with glucosamine sulfate. A literature search
was conducted of PubMed, Centre for Reviews
and Dissemination databases, Cochrane Re-
views and EconLit up to January 2010. The lit-
erature review indicated that the mechanism of
action of glucosamine sulfate is based on hy-
pothesis, but its treatment effects in knee os-
teoarthritis are symptomatic. With steady-state
peak concentrations at the 1,500 mg dosage in
the range of 10 µM, it is estimated that only 2%
of glucosamine is incorporated in the cartilage.
A once-daily dosage of 1,500 mg of glucosa-
mine sulfate is licensed for the treatment of
symptomatic osteoart hritis and has been shown
to reduce pain, improve function and exhibit
similar safety to placebo. Glucosamine sulfate
is likely to be a cost-effective treatment of knee
osteoarthritis. In conclusion, a once-daily dos-
age of 1,500 mg of glucosamine sulfate is likely
to be a safe, effective and cost-effective treat-
ment of knee osteoarthritis as compared to
placebo.
Keywords: Pharmacotherapy; Glucosamine
Sulfate, Knee Osteoarthritis; Pharmacokinetics;
Indication; Safety; Effectiveness;
Cost-Effectiveness
1. INTRODUCTION
Knee osteoarthritis is associated with significant mor-
bidity, impaired quality of life, and sub stantial health care
costs [1]. Pharmacological treatment of knee osteoarthri-
tis includes analgesics, non-steroidal anti-inflammatory
drugs (NSAIDs), corticosteroids and opiods, and gluco-
samine sulfate. Glucosamine sulfate is a natural subs-
tance that is a constituent of cartilage. Glucosamine sul-
fate is sold as a dietary supplement in the United States,
but is registered as a medicine throughout much of
Europe.
To date, there is uncertainty over various pharmaco-
therapeutic aspects of treating knee osteoarthritis with
glucosamine sulfate. Therefore, the aim of this study is
to provide a short but comprehensive pharmacothera-
peutic update on treating knee osteoarthritis with gluco-
samine sulfate.
2. METHOD
2.1. Search Strategy
A literature search was conducted of PubMed, Centre for
Reviews and Dissemination databases, Cochrane Data-
base of Systematic Reviews and EconLit up to January
2010. Additionally, the bibliography of included studies
was checked for other relevant studies. Search terms
included “knee osteoarthritis”, “knee joint”, “glucosa-
mine sulfate”, “pharmacokinetics”, “bioavailability”, “in-
dications”, “dosage”, “safety”, “effectiveness”, “cost-
effectiveness”, “economic evaluation” alone and in com-
bination wi t h each ot her.
The literature search included articles published in
peer-reviewed journals and congress abstracts. Also, the
researchers contacted manufacturers of glucosamine
sulfate for any unpublished studies. The review was lim-
ited to studies published in English for practical reasons.
2.2. Inclusion and Exclusion Criteria
The review was limited to the use of glucosamine sulfate
in its indication of knee osteoarthritis.
To explore the pharmacotherapy of glucosamine sul-
fate from a multidisciplinary perspective, the literature
review assessed the following aspects: pharmacokinetics,

S. Simoens et al. / HEALTH 2 (2010) 705-707
Copyright © 2010 SciRes. Openly accessible at http://www.scirp.org/journal/HEALTH/
706
indications and dosage, safety and effectiveness, and
cost-effectiveness. Evidence about cost-effectiveness was
derived from economic evaluations. An economic ev alu a -
tion was defined as a study comparing glucosamine sul-
fate with an alternative treatment in terms of both costs
and consequences.
3. RESULTS
3.1. Search Results
The results of the literature search are displayed in Fig-
ure 1. The review summarized three studies on pharma-
cokinetics, a Cochrane literature review on safety and
effectiveness, and three economic evaluations of gluco-
samine sulfate in knee osteoarthritis.
3.2. Pharmacokinetics
A literature review analysed the absorption, distribution,
metabolism and excretion of different administration
forms of glucosamine sulfate [2]. The absolute bioavail-
ability of oral glucosamine sulfate amounted to 44%.
The fecal excretion was 11.3% of the dosage, indicating
that at least 88.7% of the dosage was absorbed through
the gastrointestinal tract. With an absolute bioavailability
of 44% calculated after oral 14C-glucosamine, a first-
pass effect can be hypothe sized.
A study examined the dosage-proportionality of glu-
cosamine sulfate in 12 healthy volunteers [3]. The phar-
macokinetics were linear in the 750 mg and 1,500 mg
dosages, but not at 3,000 mg, where the plasma concen-
tration-time profiles were less than expected based on
dosage-proportionality. More recent research showed
that glucosamine concentrations in plasma and synovial
fluid were correlated [4]. There remains controversy
over whether steady-state peak concentrations at the
1,500 mg dosage were in line with those found to be
effective in selected in vitro studies.
117 articles identi-
fied and abstracts
retrieved
11 full articles
retrieved
Exclusion because of:
- animal model of glucosamine sulfate
- disease other than knee osteoarthritis
- study not involving glucosamine
sulfate
- absence of data on pharmacokinetics,
safety, effectiveness or
cost-effectiveness
- study measuring resource use (but
not costs)
7 articles included
Figure 1. Flow chart of literature search.
3.3. Indications and Dosage
The indication of glucosamine sulfate in Europe is lim-
ited to the symptomatic treatment of knee osteoarthritis.
An expansion of indication to osteoarthritis of the hip,
spine, hands and other locations was refused, as a result
of which some companies have refused to register their
preparation as a medicine. Glucosamine sulfate can be
used alone or in combination with NSAIDs. The li-
censed dosage is 1,500 mg, once daily. Symptom relief
may not be experienced until after several weeks of
treatment, and optimal effects on joint mobility have
been observed aft e r 12 wee ks of administrat ion .
3.4. Safety and Effectiveness
A Cochrane review assessed randomized controlled trials
(RCTs) evaluating the effectiveness and toxicity of glu-
cosamine in osteoarthritis up to the end of 2008 [1]. Of
the 25 studies included in the review, 20 RCTs focused
on the knee exclusively and five RCTs examined os-
teoarthritis at other or multiple sites. All studies were
double-blinded randomized parallel-group trials, enroll-
ing a total of 4,963 patients (mean age of 60.7 years,
69% were female). Fourteen RCTs had affiliations with
Rotta Pharmaceuticals (an Italian manufacturer of glu-
cosamine sulfate).
A pooled analysis of the relevant RCTs showed that,
as compared to baseline, glucosamine sulfate taken
orally in amounts of 1,500 mg/day produced an increase
in the total score of the Lequesne Index (a multidimen-
sional index measuring knee pain or discomfort, activi-
ties of daily living and maximum distance walked) of
11% (standardized mean difference of –0.47; 95% con-
fidence interval: –0.82 to –0.12). A subgroup analysis of
the Rotta preparation showed significant benefit over
placebo in terms of pain (standardized mean difference
of –1.11; 95% confidence interval: –1.66 to –0.57) and
in terms of the total score of the Lequesne Index (stan-
dardized mean difference of –0.47; 95% confidence in-
terval: –0.82 to –0.12). Studies using a non-Rotta prep a-
ration failed to show benefit over placebo in terms of
pain and function as measured by the Western Ontario
and McMaster Universities Index (a disease-specific
index measuring pain, stiffness and function). Two RCTs
suggested that the Rotta preparation of glucosamine sul-
fate may slow radiological progression of knee os-
teoarthritis over a three-year period (average difference
of 0.32; 95% confiden ce interval: 0.05 to 0.58).
Glucosamine therapy exhibited a safety profile similar
to placebo in terms of the number of patients with
side-effects (relative risk ratio of 0.99; 95% confidence
interval: 0.91 to 1.07) and significantly better than
NSAIDs (relative risk ratio of 0.29; 95% confidence
interval: 0.19 to 0.44).

S. Simoens et al. / HEALTH 2 (2010) 705-707
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3.5. Cost-Effectiveness
A Belgian economic evaluation indicated that treatment
of knee osteoarthritis with glucosamine sulfate for at
least one year and up to three years was associated with
a lower incidence of total knee replacement over an ob-
servation period of eight years [5]. Costs of glucosamine
sulfate treatment were offset by lower hospitalization
costs, resulting in overall savings. To tal costs per patient
amounted to € 1,103 in the placebo group and € 901 in
the glucosamine sulfate group. In other words, treatment
of knee osteoarthritis with glucosamine sulfate for up to
three years is associated with savings of € 202 per pa-
tient during the over all observation period of eight years
(i.e. up to three years of treatment and five years of fol-
low-up). This study indicated that glucosamine sulfate
treatment was more effective and less expensive than
placebo in knee osteoarthritis. If costs of other os-
teoarthritis medicines and other health care resource use
are taken into account, the cost-effectiveness of gluco-
samine sulfate would even be more favourable.
Openly accessible at
The National Institute for Health and Clinical Excel-
lence in England and Wales compared the likely cost-
effectiveness of selected treatments for knee osteoarthri-
tis [6]. This study did not provide a full economic
evaluation, but presented UK healthcare costs alongside
the effectiveness of each treatment option. The scope of
costs was limited to treatment costs (such as medicine
costs), but did not include other healthcare costs such as
adverse event costs or decreased use of other medical
resources. The results suggested that glucosamine sulfate
(1,500 mg/day) is likely to be cost-effective as compared
with placebo.
A recent US analysis explored the cost-effectiveness
of glucosamine sulfate treatment versus placebo in a
hypothetical cohort of 100,000 patients who were 65
years old and had knee osteoarthritis for five years [7]. A
hybrid Markov-decision tree model was constructed us-
ing published effectiveness data and US fee schedules.
Treatment with a daily dosage of 1,500 mg of glucosa-
mine sulfate turned out to be more effective and less
expensive than placebo by delaying time to joint re-
placement surgery. However, cost-effectiveness results
were sensitive to changes in several input parameters
and the authors recommended additional research to
inform decision making.
4. CONCLUSIONS
This study provided a pharmacotherapeutic update on
treating knee osteoarthritis with glucosamine sulfate.
Additionally, an economic evaluation explored the cost-
effectiveness of treating knee osteoarthritis with gluco-
samine sulfate in Belgium. The main messages can be
summarized as follows. The mechanism of action of
glucosamine sulfate is based on hypothesis, but its
treatment effects in knee osteoarthritis are symptomatic.
A once- daily dosage of 1,500 mg of glucosamine sulfate
has been licensed for the symptomatic treatment of knee
osteoarthritis. Glucosamine sulfate has been shown to
reduce pain and improve function of patients with knee
osteoarthritis. Glucosamine sulfate therapy exhibits a
safety profile similar to placebo and significantly better
than NSAIDs. Finally, glucosamine sulfate is likely to be
a cost-effective treatment of knee osteoarthritis.
5. ACKNOWLEDGEMENTS
No funding was provided to support this study. The authors have no
conflicts of interest that are relevant to the content of this manuscript.
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