Parathyroid Hormone and 1.25 Vitamin D₃ Exert Opposite Effects on Bone

Abstract

Histologic studies of bone in patients with hyperparathyroid bone disease reveal that the hallmark of the pathologic changes is an increase in bone forming and resorbing cells (1,2). In contrast, administration of vitamin D to patients with secondary hyperparathyroidism results in a decrease in number of bone forming and resorbing cells (3). Based on these data we advanced the hypothesis that vitamin D and parathyroid hormone may have opposite effects on bone i.e., parathyroid hormone induces an increase and 1.25 Vit D₃ a decrease in number of bane cells. This hypothesis was tested in an animal model in which experimental beagle dogs were rendered deficient in 1.25 Vit D₃ and parathyroid hormone by 5/6 nephrectomy and thyroparathyroidectany. Thyroid hormone was replaced and then both parathyroid hormone and 1.25 Vit D₃ were exogenously substituted to produce all combinations between the two hormones, i.e., 1.25D+/PTH+ (n=5), 1. 25D−/PTH− (n=7), 1.25D+/PTH− (n=9), 1.25D−/PTH+ (n=5). Six normal control dogs were sham operated and injected with vehicle. Bone biopsies were done after eight months of experimental administration of these hormones. Histomorphometry of bone for static and dynamic parameters of bone cells revealed that deficiency in parathyroid hormone results in a decrease in the number of bone forming and resorbing cells. This decrease in cell number was observed independent of the presence or absence of deficiency in 1.25 Vit D₃. In addition, administration of parathyroid hormone increased the number of bane cells independent of the status in 1.25 Vit D3. In contrast, deficiency in 1.25 Vit D₃ resulted in a decreased cellular activity without an alteration in cell number and administration of 1.25 Vit D₃ increased the cellular activity without an increase in numbers of bone cells.