Intermittent administration of parathyroid hormone (1-37) improves growth and bone mineral density in uremic rats

Background. Parathyroid hormone (PTH) is secreted in a pulsatile fashion. C ontinuous infusion of PTH(1-84) resulted in a net decrease in trabecular bo ne volume. Differential effects have been reported following an intermitten t application of PTH. We investigated the effects of a continuous infusion and of an intermittent (2 times daily subcutaneously) administration of PTH (1-37) on growth and bone mineral density (BMD) in healthy and uremic rats. Methods. Two-stage subtotal nephrectomy was performed on 130 g female Sprag ue-Dawley rats. PTH(1-37) or solvent was administered through minipumps in sham-operated and uremic rats (60 mu g/kg x day for 2 weeks). The effect of intermittent administration was tested with a subcutaneous injection of so lvent: 30 mu g/kg PTH(1-37) two times per day, 100 pmol calcitriol (C)/kg t wo times per day, or both. The length (snout tailtip) and BMD were measured at the start of uremia and at sacrifice. BMD was measured by peripheral qu antitative computer tomography at the proximal tibia, 6 and 12 mm distal of the kneejoint space. Femur bone morphology was assessed by x-rays, and cal cium content was measured by atomic absorption spectrophotometry. Results. Length gain was not altered by the continuous infusion of PTH. In contrast, it was significantly increased by intermittent PTH (control solve nt 5.35 +/- 037 cm vs, control PTH 6.19 +/- 0.47 cm: uremia solvent 3.78 +/ - 0.20 cm vs, uremia PTH 6.17 +/- 0.36 cm: P < 0.05). Intermittent PTH but not C increased BMD in uremic rats (Delta total BMD 134 +/- 13.3 vs. 76.3 /- 11.5 mg/mL; P < 0.05). X-rays revealed increased bone mass following tre atment with PTH but not with C. Uremia decreased bone calcium content (64 /- 0.3 vs. 73.3 +/- 2.5 mg/mL). which was normalized by PTH (80 +/- 3.6 mg/ mL P < 0.05) but not by C (69 +/- 1.9 mg/mL). Conclusion. Pulsatile administration of PTH does not adversely affect, but improves longitudinal growth independent of concomitant treatment with C. A t the same time PTH increases BMD and the calcium content of bone.