Page 142 - JSOM Winter 2018

runners tend to have a lower risk of OA than do nonrunners. Information Sources and Search
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There is considerable evidence that once an individual devel- National Library of Medicine’s PubMed and Ovid Embase
ops OA, moderate and regular exercise of many types (e.g., databases were searched to find studies on the effects of
aerobic exercise, resistance training, flexibility training) can orally consumed GS on pain and structural changes in joints.
reduce pain and disability. 12–21 Limited research suggests that Keywords used in the search included {osteoarthritis OR ar-
exercise is most effective if conducted at least three times per thritis OR gonarthritis AND glucosamine OR “glucosamine
week, but there is no firm evidence that any particular type of sulfate”}. The reference lists of obtained articles and other
exercise is more effective than another form. 17,18,22 reviews found in the search 34–36,40–48 were examined for other
articles not found in the retrieval services. The search was lim-
It has been suggested that glucosamine may reduce OA- related ited to human studies; no other animal species were included.
pain and slow the progression of this disease. Glucosamine is The final search was completed in July 2018. Two authors of
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a noncellular component of articular cartilage and is contained studies included in the review were contacted successfully to
in the synovial fluid surrounding the cartilage. It is natu- clarify data and methods in their studies.
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rally synthesized in the body from glucose and incorporated
into substances (namely, glycosaminoglycans and proteogly- Study Selection and Data Extraction
cans) contained in the articular cartilage matrix and synovial Studies were selected for review if they were randomized,
fluid. 24,25 Glucosamine in various forms and combinations is double-blinded trials including independent oral GS and oral
readily available in the United States as a dietary supplement placebo groups in which either pain, joint structural changes,
(DS). In terms of sales, glucosamine products ranked third or both were assessed as outcomes. Where multiple pain mea-
among all DSs after multivitamins and calcium in 2002, with sures were included, the primary pain outcome as defined in
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global sales estimated at $2 billion and an annual growth rate the article or the first-mentioned pain measure was used. Only
of 7% from 2004 to 2009. In the United States, sales peaked full text articles (i.e., no abstracts or presentations) in peer-
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in 2008 at $117 million and decreased to $86 million in 2013, reviewed journals written in English were selected. Publication
similar to the level in 2002. In the United States, DSs, unlike titles were first examined, and abstracts were reviewed if the
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drugs, do not require Food and Drug Administration moni- article appeared to involve glucosamine. The full text of the
tored testing of efficacy and safety or the agency’s approval. article was retrieved for further consideration of eligibility of
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Most DSs sold in the United States are not effective and many inclusion if the abstract suggested that the study examined the
have been shown to be dangerous, especially those used by effects of glucosamine on pain and/or joint structure. Some
Servicemembers. 30,31 studies did not include in their abstract the type of glucos-
amine used and this could only be determined by reviewing
Glucosamine for oral consumption comes in several forms, the full-text article.
including glucosamine sulfate (GS), glucosamine hydrochlo-
ride, and N-acetyl-glucosamine. These are derived from chitin, Excluded from the review were trials involving (1) intravenous
which is present in marine invertebrate exoskeletons. 23,32 Only administration of GS; (2) individuals with conditions other than
one study, to our knowledge, has investigated the effectiveness OA; (3) compounds used in combination with GS (e.g., chon-
of N-acetyl-glucosamine, and several systematic reviews, 34–36 droitin); (4) glucosamine in forms other than GS; (5) studies
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which included a large National Institutes of Health–funded in which glucosamine was already being taken on entry to the
study, indicated that glucosamine hydrochloride was not study; or (6) studies that did not assess pain or joint structural
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effective in reducing OA-related pain. In other systematic re- changes as outcome measures. The results of the search and se-
views, however, it was reported that GS showed more prom- lection process were documented in a PRISMA flow diagram. 51
ise in reducing pain. 34–36 In isolated human cartilage, GS has
greater anticatabolic effects than glucosamine hydrochloride. To guide the data extraction, a spreadsheet was constructed
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Sulfates contained in GS may play a role in its effectiveness, that contained the study name, participant characteristics
because sulfates are required for synthesis of cartilage compo- (inclusion/exclusion criteria, age, sex), joint examined, initial
nents (i.e., glycosaminoglycans). 23,39 sample size, number of participants who dropped out and/or
numbers lost to follow-up, length of treatment, outcome(s),
This article reports on a systematic review of the effectiveness type of analysis (i.e., per protocol or intention to treat), the
of oral GS consumption on OA-related pain and structural GS dose and dosing schedule, and whether there was industry
changes in the joint. Other systematic reviews have assessed involvement in the investigation. A study was considered “in-
the effectiveness of various forms of glucosamine and vari- dustry involved” if one or more of the authors on the paper
ous modes of intake, 34–36,40–48 but the present review focuses were affiliated with a company that manufactured GS, or if
specifically on orally ingested GS in individuals with clinical the study indicated industry sponsorship. Outcome data were
and/or radiographic evidence of OA. Uniformed Servicemem- extracted by two authors and any discrepancies were resolved
bers take much greater amounts of DSs, including compounds through discussion and consensus.
purported to treat musculoskeletal disorders, than does the
general population. Special Forces Operators take even more Methodological Quality
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DSs than do Servicemembers in conventional units. 50 Methodological quality of the articles was assessed using the
checklist of Downs and Black. The five major areas rated by
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the checklist were (1) reporting quality, (2) external validity,
Methods
(3) bias, (4) confounding, and (5) statistical power. The check-
For this investigation, the Preferred Reporting Items for Sys- list had 27 items, most of which were rated on a two-point
tematic Reviews and Meta-Analyses (PRISMA) guidelines scale as either “yes” (1 point) or “no” (no point). One report-
were followed. We followed a review protocol described in ing item (relating to confounding) had a possible score of 2.
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the following paragraphs. For the purposes of this review, the single statistical power

140 | JSOM Volume 18, Edition 4 / Winter 2018