The Effect of Bovine Parathyroid Hormone Withdrawal on MC3T3-E1 Cell Proliferation and Phosphorus Metabolism

Abstract

Hypocalcemia and hypophosphatemia are common complications after parathyroidectomy (PTX). Sudden removal of high circulating levels of parathyroid hormone (PTH) causes decreased osteoclastic resorption resulting in a decreased bone remodeling space. These phenomena are likely due to an increased influx of calcium and phosphorus into bone. However, there are currently no data to support this hypothesis. In this study, we found that PTX significantly reduced levels of PTH, calcium and phosphate. Compared with preoperative levels, after 1 year, postoperative PTH, calcium and phosphate levels were 295.6 ± 173.7 pg/mL (P < 0.05), 86.62 ± 15.98 mg/dL (P < 0.05) and 5.56 ± 2.03 mg/dL (P < 0.05), respectively. We investigated continuous bovine PTH administration as well as withdrawal of bovine PTH stimulation in the mouse osteoblast precursor cell line MC3T3-E1. MC3T3-E1 cells were cultured with continuous bovine PTH treatment for 20 days or with transient bovine PTH treatment for 10 days. High doses of continuous bovine PTH exposure strongly reduced cell proliferation, alkaline phosphatase activity and the number of mineralized calcium nodules. However, withdrawal of bovine PTH (100 ng/mL) significantly increased the number of mineralized calcium nodules and caused a rapid decline in calcium and phosphorus content of culture medium. In conclusion, continuous exposure to bovine PTH inhibited osteoblast differentiation and reduced the formation of mineralized nodules. However, this inhibition was removed and mineralized nodule formation resumed with withdrawal of bovine PTH. According to the results of our clinical examinations and in vitro experiments, we hypothesize that the sudden removal of high levels of PTH may cause an increased influx of calcium and phosphorus into bone after PTX.

Incidence of and risk factors for post-parathyroidectomy hungry bone syndrome in patients with secondary hyperparathyroidism

“…The incidence of HBS in our cohort was high, probably because of high preoperative serum iPTH concentrations (median, 2237 pg/mL) and a large percentage reduction in immediate postoperative iPTH concentrations (median, 92.5%). This finding might be explained by a net calcium translocation from the extracellular fluid into bone due to a precipitous fall in PTH concentration after a prolonged period of PTH exposure, which has been confirmed by a previous in vitro study [31]. Furthermore, this finding supports a previous hypothesis that a sudden decrease in serum PTH concentrations after sustained elevation following parathyroidectomy results in the unopposed action of osteoblasts and massive influx of calcium into bone, thereby causing severe hypocalcemia.…”

Risk factors for hypocalcemia in dialysis patients with refractory secondary hyperparathyroidism after parathyroidectomy: a meta-analysis

“…A large amount of circulating calcium ions are then transferred to the bone to participate in osteogenesis. Thereafter, the serum calcium level declined after PTX, which was confirmed in a previous in vitro study [ 38–41 ]. Based on the results of this meta-analysis, it was concluded that a high preoperative iPTH level was a risk factor for postoperative hypocalcemia.…”

Study of Rickets and Osteomalacia in Tibetan Gazelle

“…The typical characteristic of fluorine toxicity includes mottling and pitting of teeth and enlargements on the shafts of long bones. In the present study, fluorine contents in soil and herbage were lower than the critical contents of 30 to 40 ppm (Adedokun and Adeol, 2013;Liu et al, 2015;Burk et al, 2015). The fluorine contents in blood and hair were within the healthy range, therefore, the illness of the Tibetan gazelle was not related to fluorosis.…”