A parathyroid hormone (PTH) analog is a synthetic, injectable version of a substance related to the naturally occurring parathyroid hormone. The body naturally produces PTH to manage calcium and phosphate levels. An “analog” is a compound that is structurally similar to a natural hormone and is designed to mimic its effects within the body. These synthetic substances interact with the same cellular receptors as the hormone the body produces.
The primary function of these medications is to replicate certain actions of the natural hormone, particularly its effects on bone. They are engineered proteins, often representing a fragment of the full-length human hormone, that can be administered to produce a targeted therapeutic effect.
The Role of Parathyroid Hormone in Bone Health
Natural parathyroid hormone, produced by the parathyroid glands, is a primary regulator of calcium and phosphate metabolism. Its main role is to increase calcium levels in the blood when they fall too low. It accomplishes this by acting on the bones to release calcium, on the kidneys to reduce calcium excretion, and on the intestines to increase calcium absorption.
An important aspect of PTH’s function is the “PTH paradox.” When PTH levels are continuously high, as in conditions like hyperparathyroidism, the hormone’s dominant effect is to break down bone tissue to release calcium. This process, known as resorption, leads to a net loss of bone mass over time.
Conversely, when the body is exposed to PTH in short, intermittent bursts, the opposite effect occurs. These brief pulses stimulate bone-building cells, leading to an increase in bone formation. This anabolic effect is the principle that underlies the therapeutic use of PTH analogs, which mimic these short pulses to build bone.
Mechanism of Anabolic Action
PTH analogs function by promoting the formation of new bone, an effect known as anabolic action. They achieve this by stimulating the activity of osteoblasts, the cells responsible for synthesizing new bone tissue. When administered intermittently as a daily injection, the analog binds to PTH receptors on osteoblasts, triggering signaling pathways that promote their survival and enhance their bone-building work.
The hormone analog helps to prevent osteoblast apoptosis (programmed cell death), which extends the lifespan of these bone-forming cells. This targeted action shifts the natural balance of bone remodeling toward a net gain in bone density and structural integrity.
The action of PTH analogs can be contrasted with antiresorptive medications, such as bisphosphonates. Antiresorptive drugs work by inhibiting the function of osteoclasts, the cells that break down bone tissue. By slowing this resorption process, they prevent further bone loss, while PTH analogs actively build new bone tissue.
Medical Uses and Specific Medications
The main medical application for PTH analogs is the treatment of severe osteoporosis, particularly in individuals who are at a high risk for fractures. These medications are prescribed for postmenopausal women or men who have not had a sufficient response to other osteoporosis therapies or are intolerant to them. They are also approved for treating osteoporosis associated with the long-term use of systemic glucocorticoid medications. Another use is to manage hypocalcemia (low blood calcium) in patients with hypoparathyroidism.
Several FDA-approved PTH analogs are available:
- Teriparatide (Forteo, Bonsity) is a recombinant form of the first 34 amino acids of human PTH, indicated for treating osteoporosis in men and postmenopausal women.
- Abaloparatide (Tymlos) is an analog of parathyroid hormone-related protein (PTHrP) and is approved for treating postmenopausal women with osteoporosis at high fracture risk.
- Natpara, a full-length recombinant human PTH approved for hypoparathyroidism, has since been discontinued.
- Yorvipath (palopegteriparatide) was approved as a long-acting replacement therapy for adults with chronic hypoparathyroidism.
Administration and Treatment Course
PTH analogs are administered via a subcutaneous injection, delivered into the fatty tissue just under the skin. Patients are taught how to perform these injections themselves at home, often using a pre-filled pen device that simplifies dosing. The most common injection sites are the thigh or the abdominal region. It is recommended that the first few doses be administered where the patient can sit or lie down in case of dizziness.
The course of treatment for osteoporosis is limited in duration. Cumulative use of PTH analogs like teriparatide and abaloparatide is restricted to a maximum of 18 to 24 months over a patient’s lifetime. This limitation exists because studies show the bone-building effects can wane after this period, and due to long-term safety considerations from early animal studies. Once the course is completed, patients are often transitioned to an antiresorptive medication to help maintain the new bone.
Potential Side Effects and Safety Profile
Treatment with PTH analogs is associated with a range of side effects. Common ones include nausea, headaches, dizziness, and leg cramps. Some individuals may experience orthostatic hypotension, a form of low blood pressure when standing up that can cause lightheadedness. Injection site reactions, such as redness or discomfort, can also occur.
A more significant consideration is the potential for hypercalcemia, an elevated level of calcium in the blood. This occurs because the hormone’s function is to increase serum calcium. Blood calcium levels are monitored during treatment, especially when therapy begins. In most cases, any elevation in calcium is slight and temporary, returning to normal within 16 to 24 hours.
These medications carry a boxed warning from the FDA regarding a potential risk of osteosarcoma, a type of bone cancer. This warning was based on studies in rats that were given very high doses of the drug for a significant portion of their lifespan, which led to the cancer. However, extensive surveillance of humans who have used these medications has not shown an increased risk of osteosarcoma.
Due to this theoretical risk, PTH analogs are contraindicated for individuals already at an increased risk for this cancer. This includes people with Paget’s disease of the bone, a history of radiation therapy to the skeleton, or unexplained high levels of alkaline phosphatase.