PTH Replacement Therapy for Hypoparathyroidism

Hypoparathyroidism is characterized by low levels of calcium, which results from lower-than-normal levels of parathryoid hormone (PTH) in the body. Some patients respond to treatment with supplements of active calcium and vitamin D, while for others, replacement of PTH can help to ease symptoms.

What causes hypoparathyroidism?

Hypoparathyroidism is a rare disease that can be caused by various events all resulting in low levels of PTH. Low levels of PTH result in low levels of calcium (hypocalcemia) and high levels of phosphorus in the blood. Hypocalcemia can cause issues with the growth of bone, skin, and hair, as well as trouble with the neuromuscular system such as cramps, spasms, pain, tingling sensations, and even seizures.

The most common cause of hypoparathyroidism is damage or removal of the parathyroid glands during neck surgery. Autoimmune disorders where the immune system mistakenly attacks the parathyroid glands and rare genetic disorders such as DiGeorge syndrome can also cause hypoparathyroidism.

What is PTH?

PTH is a hormone produced by the parathyroid glands to control the levels of phosphate and calcium in the bloodstream.

When the levels of calcium drop, the parathyroid glands usually release PTH to increase the levels.

PTH stimulates bones to release calcium, which are the main storage areas of calcium in the body, through the stimulation of osteoclasts (cells that break down bone). It also triggers the kidneys to reabsorb more calcium.

PTH also reduces the amount of phosphate that the kidneys reabsorb, which decreases the phosphate levels in the blood. This is important because phosphate will often bind to calcium, making it less available.

In addition, PTH enables the production of active vitamin D in the kidneys. The increased vitamin D leads to an increase in calcium absorption from food by the small intestines.

What is PTH replacement therapy?

In PTH replacement therapy, patients receive subcutaneous (under-the-skin) injections of PTH to help replace or increase the levels of PTH the body produces.

Natpara is the only PTH replacement therapy approved by the U.S. Food and Drug Administration at present. It is injected into alternating thighs once per day. The idea is to replace PTH to naturally increase blood calcium levels without causing an increase in urine calcium levels and loss of bone density.

History of PTH replacement

The idea of administering PTH to solve issues of low calcium in the body was first reported in 1929 using PTH from cows. Researchers later found the human body would develop antibodies to quickly destroy the bovine PTH, which reduced its effectiveness.

In the 1990s, scientists were able to produce human PTH using recombinant DNA technologies. They have created two different forms of PTH, recombinant human PTH, known as rhPTH(1-84), such as Natpara, which is the full-size version that would normally be secreted by the parathyroid hormone, and the N-terminal PTH fragment, known as rhPTH(1-34) or teriparatide, which is a shorter but still active version of the hormone.

Research into the best method to administer PTH replacement therapy investigated four different options. Patients received an intravenous (IV) infusion directly into the bloodstream, and injections under the skin into the thigh, into the abdomen, or between the layers of the skin in the abdomen. The IV infusions raised the levels of PTH quickly, but the body also cleared it quickly. The subcutaneous injection into the thigh provided the longest-lasting dose.

Continuing research into PTH replacement therapy

Researchers are continuing to to investigate PTH replacement therapy for hypoparathyroidism. In particular, they are investigating teriparatide for the condition, which is FDA-approved to treat osteoporosis. They are also examining the optimum number of injections per day for both rhPTH(1-84) and rhPTH(1-34) and comparing the effect of multiple injections with continuous pump injections.

Last updated: Oct. 9, 2020

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