How do Parathyroid Hormone (PTH), Calcium (Ca), and Phosphate interact with each other?

From the Guidelines

Parathyroid hormone (PTH), calcium (Ca), and phosphate interact in a complex regulatory system that maintains mineral homeostasis in the body, with PTH acting to increase blood calcium levels and decrease phosphate levels, while high phosphate levels can stimulate PTH secretion to restore calcium homeostasis. This relationship is crucial for managing disorders like hyperparathyroidism, hypercalcemia, hypocalcemia, and chronic kidney disease. The interaction between these minerals is as follows:

• PTH is released from the parathyroid glands when calcium levels in the blood fall below normal, and it acts to increase blood calcium levels through three main mechanisms: stimulating bone resorption, enhancing calcium reabsorption in the kidneys, and increasing production of active vitamin D (calcitriol) which improves intestinal calcium absorption 1.
• Simultaneously, PTH decreases phosphate levels by reducing phosphate reabsorption in the kidneys, causing increased phosphate excretion in urine, creating an inverse balance between calcium and phosphate levels 1.
• When calcium levels rise, PTH secretion is suppressed through negative feedback, while high phosphate levels can stimulate PTH secretion both directly and indirectly by binding to calcium, which lowers free calcium levels, triggering PTH release to restore calcium homeostasis 1.
• In kidney disease, phosphate retention often occurs, leading to elevated PTH levels (secondary hyperparathyroidism) as the body attempts to normalize mineral balance, highlighting the importance of managing phosphate levels to prevent hyperparathyroidism and its associated complications 1. Some key points to consider in the management of these disorders include:
• Maintaining normal calcium balance and serum calcium levels depend on integrated regulation of calcium absorption and secretion by the intestinal tract, the excretion of calcium by the kidney, and calcium release from and calcium deposition into bone 1.
• The adult human body contains approximately 1,300 g of calcium, with 99% in skeleton, 0.6% in soft tissues, and 0.1% in extracellular fluid, and normal values for serum total calcium concentration vary among clinical laboratories 1.
• Free calcium can be measured using ion-selective electrodes, and values in adults range between 4.65 and 5.28 mg/dL, but this measurement is not routinely performed due to its complexity and expense 1.

From the FDA Drug Label

In both studies, reduction in mean PTH, corrected serum calcium, and serum phosphate levels from baseline to the end of study were observed in the PARSABIV arm, and differences between PARSABIV and placebo were statistically significant.

The relationship between PTH, calcium, and phosphate can be described as follows:

• PTH reduction is associated with a decrease in corrected serum calcium and serum phosphate levels.
• The studies show that as PTH levels decrease, corrected serum calcium and serum phosphate levels also decrease.
• The exact mechanism of how PTH, calcium, and phosphate affect each other is not explicitly stated in the drug label, but it can be inferred that PTH plays a role in regulating calcium and phosphate levels in the body 2. Key points:
• PTH reduction is associated with decreased calcium and phosphate levels.
• PARSABIV treatment leads to a reduction in PTH, calcium, and phosphate levels.

From the Research

Interaction Between PTH, Ca, and Phosphate

• The relationship between parathyroid hormone (PTH), calcium (Ca), and phosphate is complex and interdependent 3, 4, 5, 6, 7.
• PTH is a hypercalcemic hormone that promotes calcium release from the bone, renal calcium reabsorption, and phosphate excretion 7.
• High levels of phosphate can lead to an increase in PTH, which in turn can cause an increase in calcium levels 3, 4, 5.
• Low calcium levels can also stimulate the release of PTH, which can lead to an increase in calcium levels and a decrease in phosphate levels 4, 7.
• The management of secondary hyperparathyroidism, a common complication of chronic kidney disease, requires careful control of PTH, Ca, and phosphate levels to prevent bone disease, vascular calcification, and other complications 3, 4, 5, 6.

Effects of PTH on Ca and Phosphate

• PTH increases calcium levels by promoting bone resorption and increasing renal calcium reabsorption 7.
• PTH decreases phosphate levels by increasing renal phosphate excretion 7.
• Elevated PTH levels can lead to hypercalcemia and hypophosphatemia, which can cause vascular calcification and other complications 3, 5.

Effects of Ca and Phosphate on PTH

• Low calcium levels stimulate the release of PTH, which can lead to an increase in calcium levels and a decrease in phosphate levels 4, 7.
• High phosphate levels can lead to an increase in PTH, which can cause an increase in calcium levels 3, 4, 5.
• The relationship between Ca, phosphate, and PTH is critical in the management of secondary hyperparathyroidism, and requires careful monitoring and control of these parameters to prevent complications 3, 4, 5, 6.