Parathyroid hormone (PTH) is a naturally occurring hormone from the four parathyroid glands in the neck. Its primary function is to regulate calcium and phosphate levels in the bloodstream through its actions on the bones and kidneys. When blood calcium levels drop, these glands release PTH, signaling the bones to release calcium into the blood. Synthetic medications known as parathyroid hormone analogs are derived from this natural hormone and are a specific class of treatment for certain bone-related conditions.
The Anabolic Effect on Bone
Parathyroid hormone analogs distinguish themselves from other osteoporosis treatments through their anabolic, or bone-building, mechanism. When administered intermittently in low doses, these medications stimulate osteoblasts, the cells responsible for forming new bone tissue. This process increases overall bone mass and improves the microarchitecture of the skeleton. The result is a stronger skeletal structure that is more resilient to fractures.
This bone-building effect is different from the action of more common osteoporosis drugs, such as bisphosphonates. Bisphosphonates are antiresorptive agents, meaning they work by slowing down bone resorption, where cells called osteoclasts break down old bone. While this prevents further loss of bone mass, it does not rebuild bone that has been lost. The distinction is like construction work: antiresorptive therapies prevent deterioration, while anabolic agents like PTH analogs add new material to strengthen the structure.
The anabolic window created by PTH analogs is a period where bone formation outpaces resorption. This effect is most pronounced in the spine, an area rich in trabecular bone, the spongy type of bone tissue vulnerable to osteoporotic changes. The targeted stimulation of osteoblasts leads to a significant increase in bone mineral density in this region.
Conditions Treated with PTH Analogs
The primary use for PTH analogs is treating severe osteoporosis in individuals at high risk for fractures. This includes postmenopausal women who have had an osteoporotic fracture or have very low bone mineral density scores. Men with primary or hypogonadal osteoporosis at high fracture risk may also be prescribed these medications. The treatment is not a first-line therapy and is reserved for cases where other treatments, like bisphosphonates, have failed or were not tolerated.
Another application is for patients with glucocorticoid-induced osteoporosis. Long-term use of steroid medications, such as prednisone, can suppress bone formation and increase fracture risk. Clinical studies show that PTH analogs can counteract this by increasing bone density and reducing vertebral fractures in this patient population.
Beyond osteoporosis, a form of PTH is also approved for treating hypoparathyroidism, a condition of abnormally low parathyroid hormone production. The lack of natural PTH leads to low blood calcium levels (hypocalcemia). Administering a PTH analog helps normalize calcium levels, addressing the hormonal deficiency.
Treatment Process and Potential Side Effects
Treatment with parathyroid hormone analogs involves a daily self-injection under the skin of the thigh or abdomen. Patients are trained to administer the injection at home using a pre-filled pen device. This delivery method is necessary because the drugs are protein-based and would be broken down if taken orally. It is the daily, intermittent exposure to the hormone that triggers the bone-building response.
The duration of treatment is limited to a maximum of 18 to 24 months over a person’s lifetime. This limitation is a precaution based on early rodent studies that linked long-term, high-dose exposure to a risk of osteosarcoma, a type of bone cancer. The relevance of this finding to humans receiving low, therapeutic doses is unknown.
After completing a PTH analog course, the bone-building effects begin to wane. To preserve the new bone mass, patients are transitioned to an antiresorptive medication, such as a bisphosphonate. This sequential therapy helps lock in the gains in bone density and strength achieved during the anabolic treatment phase.
Common side effects during treatment can include:
- Dizziness
- Nausea
- Headaches
- Leg cramps
- Reactions at the injection site, such as redness, swelling, or itching
Specific PTH Analog Medications
The main parathyroid hormone analogs for osteoporosis are teriparatide and abaloparatide. Teriparatide (Forteo) is a recombinant version of the first 34 amino acids of the human PTH molecule. As the first anabolic agent approved for osteoporosis, it works by directly stimulating the same receptor as the natural hormone. Biosimilar versions of teriparatide are also available.
Abaloparatide (Tymlos) is an analog of a related substance called parathyroid hormone-related protein (PTHrP). It also promotes bone formation but interacts with the PTH receptor differently than teriparatide. This difference may influence its effects on various parts of the skeleton, particularly cortical bone, the dense outer layer of bone.
Both medications have demonstrated effectiveness in reducing the risk of vertebral and nonvertebral fractures in postmenopausal women with osteoporosis.