Effect of intermittent administration of human parathyroid hormone on bone mineral density and arthritis in rats with collagen‐induced arthritis

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Abstract
Objective To investigate the effect of intermittent administration of human parathyroid hormone (PTH) on bone mineral density (BMD) and arthritis in rats with collagen‐induced arthritis (CIA). Methods Seven‐month‐old female Sprague‐Dawley rats were divided into 4 groups: rats without CIA (control), rats with CIA treated with vehicle, rats with CIA treated with PTH for 4 weeks, and rats with CIA treated with PTH for 6 weeks. PTH (20 μg/kg) was injected subcutaneously 3 times per week. BMD in the proximal metaphysis and the diaphysis of the tibia was measured by peripheral quantitative computed tomography every 2 weeks until week 8. Eight weeks after initial sensitization, the animals were killed, and the BMD and mechanical properties of excised limbs were evaluated. Histomorphometric analysis of tibiae and histologic evaluation of arthritis were also performed. Results In the PTH‐treated rats with CIA, the incidence and severity of arthritis were macroscopically and histologically similar to the findings in the vehicle‐treated rats with CIA. The decrease of BMD caused by CIA was suppressed by treatment with human PTH, in a manner that was dependent on the duration of administration. In the histomorphometric analysis, bone formation parameters were higher and bone resorption parameters were lower in the PTH‐treated arthritic rats compared with vehicle‐treated arthritic rats. Mechanical properties were also maintained in the PTH‐treated rats. Conclusion Our findings indicate that, in an animal model of arthritis, intermittent PTH administration activates bone formation, resulting in increased BMD and preventing deterioration of mechanical properties. However, PTH has no effect on the arthritis itself.

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