EFFECTS OF MAGNESIUM-DEFICIENCY ON MAGNESIUM AND CALCIUM CONTENT IN BONE AND CARTILAGE IN DEVELOPING RATS IN CORRELATION TO CHONDROTOXICITY

Quinolone-induced arthropathy has been described in juvenile rats betw een 3 and 6 weeks of age, but not in adult rats. The mechanism of this chondrotoxic effect is probably related to the Mg2+-chelating propert ies of the drugs, since identical cartilage lesions were observed in m agnesium-deficient juvenile rats without quinolone treatment. However, the reasons for the phase-specificity of the effect are unknown. In t he present study, we fed a magnesium-deficient diet to Wistar rats at different postnatal developmental stages. Cartilage lesions were only observed in magnesium-deficient rats between 3 and 5 weeks of age, but not in rats receiving the magnesium-deficient diet during weeks 5 to 8, weeks 8 to 11, or months 15 to 16. The formation of cartilage lesio ns was not related to the magnesium concentration in plasma, since mag nesium concentrations in plasma were similarly reduced in rats with an d without cartilage lesions. However, chondrotoxicity correlated with magnesium content in articular cartilage. In articular cartilage (arti cular and epiphyseal cartilage in immature rats) and bone, magnesium c ontent was more reduced in rats receiving the magnesium-deficient diet between 3 and 5 weeks of age as compared with rats receiving the magn esium-deficient diet during weeks 8 to 11 postnatally. It was not poss ible to reduce the magnesium content in bone tissue of 15-month-old Wi star rats, which suggests a lower magnesium turnover in aged rats. Mag nesium content in epiphyseal cartilage of 2-week-old rats (total femor al head) was 41.9 +/- 16.9 mmol/kg dry weight, The magnesium content i n joint hyaline cartilage was significantly lower in 4-week-old rats ( 19.5 +/- 3.6 mmol/kg dry weight) and increased subsequently again to 4 8.5 +/- 9.2 mmol/kg dry weight (mean +/- SD; n = 8 to 16). Increase of the magnesium content in femoral bone between weeks 4 and 6 postnatal ly was less pronounced (139 +/- 10 and 175 +/- 15 mmol/kg dry weight, respectively). Taken together, these data show that in 4-week-old rats , magnesium concentration in joint hyaline cartilage is significantly lower than at other times during postnatal development. Only at this d evelopmental stage can cartilage lesions be induced by feeding rats a magnesium-deficient diet. This period correlates well with the sensiti ve phase of immature rats toward the chondrotoxic action of quinolones .