Vitamin D metabolism in rats with adjuvant-induced arthritis

Adjuvant-induced arthritis in rats shares many of the features of humans with rheumatoid arthritis, including the development of osteopenia in areas distal to erosive joint disease. We established adjuvant arthritis in male and female Sherman strain rats and then studied external calcium balances and vitamin D metabolism during the period of acute active clinical, serologic, and pathologic arthritis and osteopenia and in the preclinical period. While ingesting a calcium-sufficient vitamin D-replete diet (0.6% calcium, 0.65% phosphorus, and 2.2 IU D3 per g food), female rats with arthritis demonstrated reduced calcium balance (arthritic, 36 + 8 versus control, 169 + 13 mg per 6 days, p < 0.02) because of inefficient gastrointestinal absorption of calcium (arthritic 9.7% versus control 37%). This was associated with calcitriol deficiency (arthritic 52 + 7 versus control 70 + 10 pg/ml) and reduced osteocalcin levels. Male rats with arthritis demonstrated an inability to raise serum calcitriol levels to the same degree as control rats (200 + 30 versus 440 + 70, respectively) while ingesting a calcium-deficient diet (0.002% calcium, 0.34% phosphorus, and 2.2 IU D3 per g food) and also had reduced balance (59 + 7 versus 85 + 10 mg per 6 days, respectively) due in part to decreased efficiency of absorption (55 versus 67%). No abnormalities in calcium balance or in serum calcitriol levels on the sufficient diet were present in the preclinical period. Physiologic calcitriol replacement to arthritic female rats increased osteoid available for mineralization and increased mineral apposition rates. Calcitriol deficiency in adjuvant-induced arthritis is responsible, in part, for reduced calcium balance and likely contributes to the development of osteopenia during the acute stage of the systemic inflammatory disease.