Glukosamin

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Synonymer

Glucosamin

Baggrund

Slidgigt eller artrose rammer 50% af alle over 70 år. Sygdommen medfører betydeligt funktionstab og nedsat livskvalitet. Artrose udvikles langsomt og kendetegnes ved smerter og stivhed, specielt ved belastning men kan også forekomme i hvile.

Patofysiologi

Artrose skyldes nedbrydning af brusken, enten pga. skade, belastning eller genetisk - særlig artrose i fingrene er arvelig. Man ser først og fremmest artrose ved rtg us (MR), hvor man finder reduceret bruskhøjde. Ledbrusken består af to hovedkomponenter: kollagen og proteoglykaner, som produceres af chondrocytterne. Det er proteoglykanerne, og særlig sukkerdelen af disse (hyaluron, chondroitin-sulfat og keratin-sulfat) som giver ledbrusken styrke og fleksibilitet til at tåle store belastninger. Biokemisk set er glukosamin udgangspunktet for syntesen af galactosamin, hyaluronsyre og chondroitin.

Prækliniske studier har vist ay glukosamin stimulerer syntesen af proteoglykaner og har antiinflammatorisk effekt ved at det hæmmer IL-1 beta. Mere end 90% absorberes fra tarmen. Biotilgængeligheden er dog kun ca. 26%, fordi en betydelig andel metaboliseres direkte i leveren.

Fremstilling

Glukosamin er et lille vandopløseligt molekyle (MW 178 da) som udvindes af skaldyr.

Forskning: Lancet 2001

I The Lancet i januar 2001 publicerede Reginster et al. det første revolutionerende 3-årige studie om effekten af glukosaminsulfat 1,5 g pulver en gang dagligt sammenlignet med placebo hos artrose-patienter. Glukosaminsulfat viste signifikant bedre effekt end placebo. Det nye var at på røntgenoptagelser taget før og efter medicinindtagelsen, var der praktisk talt ingen af patienterne i glukosaminsulfat-gruppen der havde reduktion af bruskhøjden, men alle havde det i placebogruppen.

• Lancet. 2001 Jan 27;357(9252):251-6.
• Long-term effects of glucosamine sulphate on osteoarthritis progression: a randomised, placebo-controlled clinical trial.
• Reginster JY, Deroisy R, Rovati LC, Lee RL, Lejeune E, Bruyere O, Giacovelli G, Henrotin Y, Dacre JE, Gossett C.

• BACKGROUND: Treatment of osteoarthritis is usually limited to short-term symptom control. We assessed the effects of the specific drug glucosamine sulphate on the long-term progression of osteoarthritis joint structure changes and symptoms. METHODS: We did a randomised, double-blind placebo controlled trial, in which 212 patients with knee osteoarthritis were randomly assigned 1500 mg sulphate oral glucosamine or placebo once daily for 3 years. Weightbearing, anteroposterior radiographs of each knee in full extension were taken at enrolment and after 1 and 3 years. Mean joint-space width of the medial compartment of the tibiofemoral joint was assessed by digital image analysis, whereas minimum joint-space width--ie, at the narrowest point--was measured by visual inspection with a magnifying lens. Symptoms were scored by the Western Ontario and McMaster Universities (WOMAC) osteoarthritis index.

• FINDINGS: The 106 patients on placebo had a progressive joint-space narrowing, with a mean joint-space loss after 3 years of -0.31 mm (95% CI -0.48 to -0.13). There was no significant joint-space loss in the 106 patients on glucosamine sulphate: -0.06 mm (-0.22 to 0.09). Similar results were reported with minimum joint-space narrowing. As assessed by WOMAC scores, symptoms worsened slightly in patients on placebo compared with the improvement observed after treatment with glucosamine sulphate. There were no differences in safety or reasons for early withdrawal between the treatment and placebo groups.

• INTERPRETATION: The long-term combined structure-modifying and symptom-modifying effects of gluosamine sulphate suggest that it could be a disease modifying agent in osteoarthritis.