The parathyroid hormone (PTH) – the yin and yang of bone strength in osteoporosis and kidney failure

Prof. Tally Naveh-Many

Osteoporosis (porous bone) affects most women, 40% of whom will suffer from a fracture in their lifetime. The calcium content in all parts of our bodies, including the amount of calcium in our bones, is regulated by the parathyroid glands which secrete the parathyroid hormone (PTH). The parathyroid glands make more or less PTH in response to the level of calcium in the blood. When the calcium in our blood drops too low, the parathyroid glands make more PTH. PTH then causes bones to release calcium into the blood and the kidneys to reabsorb calcium from urine. PTH is a double-edged sword since on the one hand, FDA-approved PTH stimulates bone formation and is the most potent treatment for osteoporosis; however, high levels of PTH in patients suffering from kidney disease result in the destruction of bone with resultant high morbidity and mortality. According to Prof. Naveh-Many, it is essential to understand the mechanism(s) by which PTH synthesis and secretion are regulated in order to devise new therapeutic methods to manage the over-activity of the parathyroid glands in patients with kidney failure and improve bone quality in osteoporosis.

To solve this complex challenge, Prof. Naveh-Many was the first to use molecular biology tools to study how PTH secretion is regulated in kidney failure. “At the time, it was considered impossible to study the molecular biology of the rat parathyroid, especially since there was no functional parathyroid cell line available; thus, we had to develop unique strategies to define the mechanisms of PTH gene regulation” Prof. Naveh-Many said. Her studies were the first to show the molecular mechanism of the decreased PTH by vitamin D. This finding was the scientific basis for the use of vitamin D and its analogues for the management of secondary hyperparathyroidism in patients with chronic kidney disease both before and when receiving dialysis treatment. Vitamin D helps the body absorb calcium and is vital for bone health; it greatly increases the amount of calcium that the intestines can absorb from food, sometimes by as much as two to four times. In addition, she has characterized and continues to unravel the mechanisms leading to a high PTH gene expression in kidney failure patients. Her studies include experimental models of disease, transgenic mice, cell cultures and archival parathyroid tissue samples from patients. Her findings bridge basic science and disease states and are relevant to parathyroid physiology and to chronic kidney disease and its management.

Prof. Naveh-Many works at the Hadassah Minerva Center for Calcium and Bone Metabolism, Department of Nephrology, the only such center of the 50 Minerva Centers in Israel based in a hospital. She is a world class research leader in both molecular biology and translational research who has received prestigious international awards for outstanding achievements in nephrology and bone and mineral research. She was the commissioned editor of a book on 'Molecular biology of the parathyroid.' Prof. Naveh-Many’s already impressive contributions, namely PTH regulation and its biology in physiology and chronic kidney disease, stand as a major clinical milestone also for the management of osteoporosis that will benefit women after menopause. In addition, she is lauded as an outstanding teacher whose mission is to mentor and train young doctors and biology students in research activities towards building a career in academic medicine.