How does Parathyroid Hormone (PTH) increase calcium levels?

From the Guidelines

Parathyroid hormone (PTH) increases calcium levels by stimulating bone resorption, enhancing kidney distal tubular calcium reabsorption, and activating renal hydroxylation of 25(OH)D3 to 1,25(OH)2 D3, as evidenced by the K/DOQI clinical practice guidelines for bone metabolism and disease in chronic kidney disease 1. The primary mechanism by which PTH increases calcium levels involves the coordinated action on three main target organs: bones, kidneys, and intestines.

• In bones, PTH stimulates bone resorption, releasing stored calcium into the bloodstream.
• In the kidneys, PTH increases calcium reabsorption in the distal tubules, preventing calcium loss in urine, and decreases phosphate reabsorption to maintain the calcium-phosphate balance.
• PTH also enhances the production of 1,25-dihydroxyvitamin D (calcitriol) in the kidneys, which then acts on the intestines to increase calcium absorption from food, as described in the K/DOQI guidelines 1. The combined effect of these actions—releasing calcium from bone, retaining calcium in the kidneys, and enhancing intestinal calcium absorption—rapidly and effectively raises blood calcium levels, which is crucial for maintaining proper nerve, muscle, and cellular function throughout the body. According to the K/DOQI guidelines, normal values for serum total calcium concentration vary among clinical laboratories, but a normal range is between 8.6 to 10.3 mg/dL (2.15 to 2.57 mmol/L) for adults 1. It is essential to note that free calcium, which can be measured using ion-selective electrodes, should be assessed if subtle changes are expected or total calcium measurements are not adequate, as free calcium levels are critical for various physiological processes, as indicated in the study 1.

From the FDA Drug Label

12 CLINICAL PHARMACOLOGY 12. 1 Mechanism of Action Endogenous 84-amino acid parathyroid hormone (PTH) is the primary regulator of calcium and phosphate metabolism in bone and kidney. Physiological actions of PTH include regulation of bone metabolism, renal tubular reabsorption of calcium and phosphate, and intestinal calcium absorption

Effects on Mineral Metabolism — Teriparatide affects calcium and phosphorus metabolism in a pattern consistent with the known actions of endogenous PTH (e.g., increases serum calcium and decreases serum phosphorus).

The primary ways PTH increases calcium levels are through:

• Regulation of bone metabolism: PTH stimulates the release of calcium from bone into the bloodstream.
• Renal tubular reabsorption of calcium: PTH increases the reabsorption of calcium in the kidneys, reducing the amount of calcium excreted in the urine.
• Intestinal calcium absorption: PTH indirectly increases the absorption of calcium from the intestine into the bloodstream. 2

From the Research

Mechanisms of PTH-Induced Calcium Level Increase

• Parathyroid hormone (PTH) acts on kidneys, bone, and intestine to increase calcium levels in the blood 3, 4, 5, 6.
• PTH promotes calcium release from bone by stimulating osteoclasts, which leads to bone resorption 5.
• In the kidneys, PTH increases calcium reabsorption and decreases phosphate reabsorption, leading to increased calcium levels in the blood 3, 4, 5, 6.
• PTH also stimulates the conversion of 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D-3, which increases intestinal calcium absorption 3, 4, 6.

Effects of PTH on Bone and Kidneys

• PTH stimulates osteoblasts, leading to an increase in RANKL expression and differentiation of osteoclasts, resulting in bone resorption 5.
• In the kidneys, PTH stimulates 1alpha-hydroxylase to synthesize active vitamin D, which increases intestinal calcium absorption 5.
• Primary hyperparathyroidism (PHPT) is characterized by skeletal or renal complications, including hypercalcemia, osteoporosis, and kidney stones 3, 5.

Regulation of Calcium Levels by PTH

• PTH is an essential regulator of extracellular calcium and phosphate levels, and its dysregulation can lead to various parathyroid diseases 6.
• The accurate assessment of PTH provides essential biochemical information to properly diagnose parathyroid disease 6.
• Therapeutic options for parathyroid disease include surgical removal of hypersecreting parathyroid tissue, administration of PTH, vitamin D, and calcium supplements, among others 6.