Crystalline glucosamine sulfate in the management of knee osteoarthritis: efficacy, safety, and pharmacokinetic properties

Abstract

Abstract:Glucosamine is an amino monosaccharide and a natural constituent of glycosaminoglycans in articular cartilage. When administered exogenously, it is used for the treatment of osteoarthritis as a prescription drug or a dietary supplement. The latter use is mainly supported by its perception as a cartilage building block, but it actually exerts specific pharmacologic effects, mainly decreasing interleukin 1-induced gene expression by inhibiting the cytokine intracellular signaling cascade in general and nuclear factor-kappa B (NF-kB) activation in particular. As a whole, the use of glucosamine in the management of osteoarthritis is supported by the clinical trials performed with the original prescription product, that is, crystalline glucosamine sulfate. This is the stabilized form of glucosamine sulfate, while other formulations or different glucosamine salts (e.g. hydrochloride) have never been shown to be effective. In particular, long-term pivotal trials of crystalline glucosamine sulfate 1500 mg once daily have shown significant and clinically relevant improvement of pain and function limitation (symptom-modifying effect) in knee osteoarthritis. Continuous administration for up to 3 years resulted in significant reduction in the progression of joint structure changes compared with placebo as assessed by measuring radiologic joint space narrowing (structure-modifying effect). The two effects combined may suggest a disease-modifying effect that was postulated based on an observed decrease in the risk of undergoing total joint replacement in the follow up of patients receiving the product for at least 12 months in the pivotal trials. The safety of the drug was good in clinical trials and in the postmarketing surveillance. Crystalline glucosamine sulfate 1500 mg once daily is therefore recommended in the majority of clinical practice guidelines and was found to be cost effective in pharmacoeconomic analyses. Compared with other glucosamine formulations, salts, or dosage forms, the prescription product achieves higher plasma and synovial fluid concentrations that are above the threshold for a pharmacologically relevant effect, and may therefore justify its distinct therapeutic characteristics.

Topical Issues of Osteoarthritis Treatment in Clinical Practice

“…Показаниями для назначения являются первичный и вторичный остеоартроз, в том числе коленного, тазобе-дренного суставов, и спондилоартроз [6,8,14,25,27,29,32].…”

“…Противопоказаниями являются повышенная чувствитель-ность к препарату, наличие фенилкетонурии при приеме порошка внутрь, так как он содержит аспартам. Пациентам с тяжелыми нарушениями проводимости сердца, острой сердечной недостаточностью, при указании в анамнезе на эпилептиформные судороги, детям в возрасте до 12 лет, при беременности и в период лактации, а также при повышенной чувствительности к лидокаину противопо-казан раствор для внутривенного введения, так как он содержит лидокаин [11,26,29].…”

Glucosamine and chondroitin use in canines for osteoarthritis: A review

“…Crystalline glucosamine sulfate is a pharmaceutical-grade prescription product in Europe (but not in the United States or Canada) that consists of glucosamine, sulfate, sodium and chloride ions in a specific stoichiometric ratio (Altman, 2009). The other glucosamine salt forms (HCl, sulfate salts) have demonstrated variable efficacy in humans ( Sawitzke et al, 2010;Rovati et al, 2012). This is primarily due to inconsistency in glucosamine content amongst nutraceutical products and poor oral bioavailability, especially in combination with other nutraceutical additives (Altman, 2009;Sawitzke et al, 2010;Wandel et al, 2010).…”

“…The sulfate salt is often stabilized with sodium chloride (NaCl) or potassium chloride (KCl), which may be undesirable in aging canines with potential co-morbid medical conditions such as heart failure, hypertension or renal decline. Although this is a theoretical concern, human clinical trials have not demonstrated increases in blood pressure with NaCl content of crystallized glucosamine sulfate (Herrero-Beaumont et al, 2007;Rovati et al, 2012). Last, the hydrochloride salt is much cheaper to produce; keeping in mind that crystalline glucosamine sulfate is manufactured as pharmaceutical-grade with strict quality control standards (Altman, 2009).…”

Pathogenetic Mechanisms of Action of Structural Modified Prolonged Action Anti-Inflammatory Drugs (Sysadoa)

“…Ряд исследований дока-зывает, что ХС достоверно влияет на клеточный компонент воспаления. Близким по фармакодинамике к ХС является ГС, который стимулирует хондроциты, повышает синтез протеогликанов, оказывая хондропротективное действие, а также подавляет выработку ИЛ-1, ИЛ-6, ФНОα, оказывая противовоспалительное действие [28][29][30][31]. Относительно недавно в научной литературе появился ряд исследова-ний по сочетанному применению ХС и ГС.…”