Magnesium deficiency induces joint cartilage lesions in juvenile rats which are identical to quinolone-induced arthropathy.
Quinolones accumulate in cartilage, and because they form chelate complexes with divalent cations, they possess the potential to induce a deficiency of functionally available magnesium. To test the hypothesis that quinolone-induced arthropathy is caused (or aggravated) by magnesium deficiency in cartilage, we induced magnesium deficiency by feeding juvenile rats a magnesium-deficient diet for 9 days and treated the rats with single oral doses of ofloxacin (0, 100, 300, 600, or 1,200 mg/kg of body weight) during this period. Additional groups of juvenile rats on a normal diet were treated with ofloxacin correspondingly. Typical cartilage lesions (e.g., swollen matrix, cleft formation) were found in knee joints of all magnesium-deficient rats, including those without ofloxacin treatment. Lesions in these groups were not distinguishable from lesions induced by a single dose of 600 mg of ofloxacin per kg of body weight or higher in rats on a normal diet. Ofloxacin levels in plasma after 600 mg/kg of body weight were approximately 10-fold higher than those in humans during therapy with this quinolone. Lesions in rats treated with ofloxacin plus magnesium deficiency were more pronounced than those in rats with normal magnesium concentrations. After intake of a magnesium-deficient diet for 9 days, the magnesium concentration in serum (mean +/- standard deviation) was 0.18 +/- 0.05 mmol/liter (control on normal diet, 0.82 +/- 0.10 mmol/liter). Magnesium concentrations in bone (femur) and cartilage (processus xiphoideus) samples were 64.7 +/- 10.5 and 14.3 +/- 3.9 mmol/kg of dry weight, respectively, which corresponded to approximately 50% of the concentrations measured in controls on a normal diet. It was concluded that quinolone-induced arthropathy is probably caused by a deficit of available magnesium in joint cartilage due to the formation of quinolone-magnesium chelate complexes. If juvenile patients must be treated with quinolones for serious infections, it seems prudent to ensure that these patients do not have a disturbed magnesium balance.
Institut für Toxikologie und Embryopharmakologie, Freie Universität Berlin, Germany.
R
R
Stahlmann
C
C
Förster
M
M
Shakibaei
J
J
Vormann
T
T
Günther
H J
HJ
Merker
D000818:Animals; D000890:Anti-Infective Agents / Q000633:toxicity*; D001842:Bone and Bones / Q000473:pathology; D002357:Cartilage Diseases / Q000139:chemically induced / Q000209:etiology / Q000473:pathology*; D002358:Cartilage, Articular / Q000473:pathology*; D004032:Diet; D005260:Female; D006614:Hindlimb / Q000473:pathology; D007596:Joints / Q000473:pathology; D008275:Magnesium Deficiency / Q000473:pathology*; D008297:Male; D008854:Microscopy, Electron; D015242:Ofloxacin / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar
D000890:Anti-Infective Agents; D015242:Ofloxacin