Effect of the interaction of parathyroid hormone and cyclosporine A on bone mineral metabolism in the rat

Cyclosporine A (CsA) induces high turnover osteopenia in the rat and there is evidence for this in humans. Recent studies suggest that increases in pa rathyroid hormone (PTH) may be involved in posttransplantation bone loss. H owever, human studies are difficult to interpret since transplant patients usually receive a cocktail of immunosuppressants and have underlying diseas e disease. Our aim was to try to resolve the influence of the absence or pr esence of PTH on CsA-induced bone disease. Male Sprague Dawley rats aged 7- 9 months, either sham operated or parathyroidectomized (PTX), were randomly divided into vehicle and CsA groups. All PTX rats were given oral calcium supplementation ad libitum. The rats were divided into groups: basal, sham/ vehicle, sham/CsA, PTX/vehicle, and PTX/CsA. Serial biochemistry was perfor med 0, 14, and 28 days after the start of the experimental period: bone his tomorphometry was performed 28 days after the start of the experimental per iod. Statistical analysis consisted of group comparisons and factorial anal yses. The results showed that CsA alone produced a high turnover osteopenia consistent with previous studies. In the PTX animals there was an increase in bone mass. PTX also decreased osteoblast activity and recruitment, and serum 1,25(OH)(2)D levels. Serum levels of osteocalcin (BGP) were unaffecte d by PTX. The combination group (PTX/CsA) did not differ statistically from the controls in most of the histomorphometric parameters measured, with th e exception of reduced mineral apposition and bone formation rates, reflect ing the effects of PTX. Serum BGP and 1,25(OH),D levels did not differ, but PTH was reduced from the control. Explanations for these results art: (1)C sA and PTX exert their effects via separate mechanisms, negating each other ; (2) in the absence of PTH, CsA managed to cause bone loss, and thus PTH m ay not be essential for CsA-induced bone loss; or (3) the profound accelera ted bone loss produced by CsA in normal rats requires PTH, These findings m ay help explain the discrepancies found in clinical studies where bone loss occurs with either elevated or normal PTH levels.