teriparatite- forteo

Teriparatide (trade name Forteo) is a medication to treat osteoporosis that works in a different way than other drugs for osteoporosis. It is the first drug to cause new bone to be formed. Teriparatide has been FDA approved to treat osteoporosis in postmenopausal women and in men with hypogonadal or idiopathic osteoporosis who are at high risk for fracture.
Osteoporosis-related fractures are a serious problem for older people. It is often a hip fracture that leads to decline in the health of the elderly. A third of all hip fractures occur in men, and almost 38% of those men will die in the following year. Osteoporosis in men is underdiagnosed. Generally defined as the thinning of bone tissue and decrease in density, osteoporosis is the most common type of bone disease.

The existing treatments for osteoporosis are medications that prevent bone resorption. Bisphosphonates alendronate (Fosamax) and risedronate (Actonel) are oral medications. Other treatments include salmon calcitonin (Miacalsin) which is available as a nasal spray or injection. Raloxifene (Evista) is a selective estrogen receptor modulator. By preventing bone resorption, these medications are used to prevent bone loss.

Teriparatide is a synthetic form of the naturally occuring parathyroid hormone. Unlike other osteoporosis drugs, it actually causes bone density to increase. In the body, parathyroid hormone is released by the parathyroid glands in the neck (behine the thyroid glands) and is an important regulator in the bloodstream's levels of calcium and phosphorus. Laboratory tests can determine the level of this hormone in the blood.

The most important endpoint for treatment with any of these drugs is prevention of fractures, especially hip and vertebral fractures.

Bone metabolism is a complex process. Bone remodels throughout a person’s life, so that there is new bone being made along with bone resorption. Among the substances that affect bone metabolism are vitamin D, calcium, estrogen, testosterone, and parathyroid hormone which regulates the calcium and bone formation in the body. Other external factors influence bone metabolism and increase the risk of osteoporosis, including prolonged use of corticosteroids, alcoholism, smoking, and in men, hypogonadism.

Early trials of teriparatide leading to its FDA approval were completed separately for men and women. Evaluation of drugs for osteoporosis are complicated by the difficulty of knowing how severe the bone loss is, and also because treatment is needed not just to prevent thinning bone but to definitively protect against fracture.

One randomized trial of postmenopausal women who had already fractured vertebra compared teriparatide at either 20 or 40 micrograms per day with placebo. After about 19 months, 14% of the women taking placebo had new vertebral fractures, as compared with 5% of the women taking 20 micrograms of teriparatide and 4% of the women taking 40 micrograms. There were also a statistically significant lower number of non-vertebral fractures in the teriparatide treated group. 20 micrograms of teriparatide increased spine and hip bone mineral density. However, this study had to be terminated because 1.6% of the women taking 40 micrograms of teriparatide and 0.2% of those taking 20 micrograms developed significant increases in serum calcium, the amount of calcium in the blood, which can be dangerous.

Another trial compared 40 micrograms of teriparatide to alendronate. After about 14 months later, bone density increased more in the spine and femoral neck (part of the hip) in the patients treated with teriparatide. Bone density in the wrist decreased with teriparatide. Fewer patients treated with teriparatide suffered nonvertebral fractures.

A randomized trial using teriparatide to treat men with osteoporosis (half of whom had low testosterone levels) showed that teriparatide doses of both 20 micrograms and 40 micrograms increased bone density in the lumbar spine and the femoral neck. In this study bone density in the wrist decreased.

Side Effects of Teriparatide

Generally, teriparatide is well tolerated.

The most common side effects, among others, are dizziness, nausea, heartburn, diarrhea, headache and leg cramps, pain, weakness, and depression. Lowered blood pressure (hypotension) when standing can occur with the first few doses but does go away in a matter of hours. Patients may be told to lie down after the injection. There have been some cases of slightly elevated serum calcium, and elevated calcium in the urine (which can lead to kidney stones). Ooccasionally transient hypercalcemia occurs 4 to 6 hours after injection, reducing blood serum calcium concentrations.

If any of these side effects persist or worsen, the prescribing doctor should be informed. More serious reactions have included chest pain, fainting, difficulty breathing, more severe nausea, vomiting, constipation, and muscle weakness. Allergic reactions can occur, from itching at the injection site to more serious symptoms of allergy including swelling, and difficulty breathing. Serious side effects warrant immediate medical attention.

When teriparatide was given to growing young rats, they developed osteogenic sarcoma, a very malignant tumor. The drug should not be given to anyone at risk for developing this bony cancer. That would include patients with Paget’s disease, those with elevated alkaline phosphatase (which could indicate a problem in bone), patients who had radiation therapy to their bones, or children and young adults whose bones are still growing.
At this time, the recommended length of treatment is two years. There are many ongoing clinical trials to determine the best way to use teriparatide, with other medicines like alendronate, how long treatment should last, and which patients with osteoporosis will benefit the most from it. There have been attempts to deliver the medication as a nasal spray instead of injection. It is also being tested for other conditions. One, called osteogenesis imperfecta is a genetic bone disease causing brittle bones. Teriparatide is being tried as a treatment for adults with osteogenesis imperfecta. It is also being tested as an aid to fracture healing. There are some 50 trials in various stages at this time, and new uses for teriparatide will probably be found.

The approved dose (20Fg daily by subcutaneous injection) and duration of treatment have not been found to be associated with an increased