Recent studies suggest that hypercalcemia of sarcoidosis is due to high blood concentrations of calcitriol and that this compound may be synthesized at an extra-renal site. We report that sarcoid lymph node homogenate metabolized calcifediol to a substance indistinguishable from calcitriol, whereas six nonsarcoid lymph nodes failed to produce this compound.

The effects of intraperitoneal aluminum chloride (1.5 mg aluminum/kg/day for 9 weeks) were studied in normal and uremic rats. Parameters measured included tissue aluminum, serum vitamin D metabolites, and quantitative bone histology. Aluminum administration increased tissue concentrations of this metal in uremic and nonuremic animals. Bone aluminum concentrations were higher in uremic rats (121 +/- 27 mg/kg compared to 47 +/- 4), whereas liver values were higher in the nonuremic group (175 +/- 47 mg/kg compared to 100 +/- 36). Serum concentrations of 25-hydroxyvitamin D and 24,25-dihydroxyvitamin D were reduced in uremia, but aluminum was without apparent effect on any vitamin D metabolite. Aluminum, in the doses administered, caused no skeletal changes in nonuremic animals. Some uremic, non-aluminum-treated rats developed osteomalacia and marrow fibrosis. However, osteomalacia was more severe and the osteoclast count was higher in the uremic, aluminum-treated rats. In this group of animals the mineral apposition rate was reduced at the metaphyseal endosteum but increased at the periosteum, indicating different control mechanisms at the two sites.

Controversy exists over a direct effect of 1,25(OH)2D3 on PTH secretion. To investigate the possibility that the suppressive effect of 1,25(OH)2D3 on PTH secretion may be demonstrable in 1,25(OH)2D3-depleted tissue and/or after prolonged periods of exposure to 1,25(OH)2D3, primary monolayer cultures of bovine parathyroid cells were established in 1:1 DMEM/Ham's F-12 media supplemented with 2% calf serum but not 1,25(OH)2D3. Ionized calcium was maintained at 1.0 mM. Experiments were performed on 4-day-old culture cells. PTH concentration was measured using both a mid-region/carboxyl and an amino-terminal PTH antisera. 1,25(OH)2D3 at a concentration of 0.1 ng/ml suppressed PTH secretion by 32 +/- 7% after 48 hours. High calcium concentration (2.0 mM) suppressed PTH secretion by 37 +/- 10% and this effect was not additive over that of 1,25(OH)2D3. PTH secretion rate recovered fully 48 hours after normalization of the external calcium concentration but not after the removal of 1,25(OH)2D3. It is concluded that 1,25(OH)2D3 directly suppresses PTH secretion by monolayer culture of bovine parathyroid cells.

Hypocalcemia is the main factor responsible for the genesis of secondary hyperparathyroidism in chronic renal disease. Studies with parathyroid cells obtained from uremic patients indicate that there is a shift in the set point for calcium-regulated hormone (parathyroid hormone [PIH) secretion. Studies were performed in dogs to further clarify this new potential mechanism. Hypocalcemia was prevented in uremic dogs by the administration of a high calcium diet. Initially, ionized calcium was 4.79±0.09 mg/dl and gradually increased up to 5.30±0.05 mg/dl. Despite a moderate increase in ionized calcium, immunoreactive PTH (iPTH) increased from 64±7.7 to 118±21 pg/ml. Serum 1,25(0H-)D3 decreased from 25.4±3.8 to 12.2±3.6 pg/ml. Further studies were performed in two other groups of dogs. One group received 150-200 ng and the second group 75-100 ng of 1,25(OH)2D3 twice daily. The levels of 1,25(OH)2D3 increased from 32.8±3.5 to a maximum of 69.6±4A pg/ml. In the second group the levels of serum 1,25(0H)D3 after nephrectomy remained normal during the study. Amino-terminal iPTH did not increase in either of the two groups treated with 1,25(OH)2D3.In summary, the dogs at no time developed hypocalcemia however, there was an 84% increase in iPTH levels, suggesting that hypocalcemia, per se, may not be the only factor responsible for the genesis of secondary hyperparathyroidism.

Biochemical data and skeletal histomorphometric measurements are presented for normal rats and for two groups of rats rendered uremic by partial nephrectomy. In one of these groups chronic acidosis was induced by the oral administration of hydrochloric acid. Uremic animals had higher urine calcium excretion rates and lower serum concentrations of vitamin D metabolites than normal rats. Chronic acid loading of uremic rats resulted in hypercalcemia, elevated serum parathyroid hormone concentrations, and a significant loss of trabecular bone in addition to the above changes. greater osteoclast densities and higher resorption surfaces wee seen in the uremic acidotic animals than in the other two groups. The acidotic uremic state induced more potent changes in calcium metabolism and bone structure than uremia alone.