New options in treating osteoporosis

Women with osteoporosis now have a therapeutic option with a novel mechanism of action. The Food & Drug Administration recently approved teriparatide (rDNA origin) injection (Forteo, Eli Lilly), a recombinant form of human parathyroid hormone (PTH) for the treatment of postmenopausal women with osteoporosis who are at increased risk for fracture. (See Drug Topics, Jan. 6). Teriparatide is currently available in pharmacies.

Teriparatide is the first in a new class of drugs known as bone formation agents, which stimulate osteoblasts. It differs from the bisphosphonates and raloxifene (Evista, Eli Lilly), which preserve bone mass by suppressing osteoclasts and osteoblasts.

Teriparatide is administered as a once-daily subcutaneous injection into the thigh or abdominal wall. The recommended dosage is 20 mcg per day. Treatment with the drug for more than two years is not recommended. Teriparatide comes in injector pens, and each pen contains a one-month supply of the drug.

The manufacturer recommends that teriparatide be given only to those women at high risk for osteoporotic fractures. These include women with a history of osteoporotic fracture, or who have multiple risk factors for fracture, or who have failed or were intolerant of previous osteoporosis therapy.

The most common adverse effects associated with teriparatide therapy at the recommended dose in clinical trials were leg cramps and, at higher doses, nausea and headache. Women taking teriparatide should notify a healthcare provider if they experience persistent symptoms of hypercalcemia, such as nausea, vomiting, constipation, lethargy, and asthenia. Initial administration of teriparatide should take place under circumstances where the patient can immediately sit or lie down if symptoms of orthostatic hypertension occur.

Public Citizen's Health Research Group recently recommended that patients not take teriparatide (Forteo, Eli Lilly), because the drug has caused osteosarcoma in laboratory animals. The organization issued a "Do Not Use!" warning in the April issue of Worst Pills, Best Pills News, an on-line service and monthly newsletter it publishes. The article warning people not to use teriparatide can be found on the Worst Pills, Best Pills Web site at http://www.worstpills.org

Other therapies for osteoporosis are in the pipeline. Warren Levy, Ph.D., president and CEO of Unigene, Fairfield, N.J., said that the company is developing a nasal calcitonin product (Fortical) that has certain advantages over the existing product in terms of reduced manufacturing and packaging costs. He said the company expects to file the NDA for its product shortly.

Last year, Unigene signed a $150 million worldwide license agreement with GlaxoSmith-Kline for the development of an oral formulation of PTH for the treatment of osteoporosis, Levy said. In addition, the company is developing an oral calcitonin product that is currently in phase I/II clinical testing.

In addition, a once-yearly IV infusion of zoledronic acid is being developed by Novartis and is now in phase III clinical trials. It is currently marketed for oncologic purposes as Zometa.

Felicia Cosman, M.D., clinical director of the National Osteoporosis Foundation, said that other drugs in development for the prevention and treatment of osteoporosis include growth hormones and growth hormone derivatives. Statins are being evaluated as a treatment for osteoporosis, and the heavy metal strontium is being tested in Europe, added Cosman, who is also an endocrinologist specializing in osteoporosis at Helen Hayes Hospital, West Haverstraw, N.Y. Other researchers are searching for anabolic or bone-building drugs. Such therapies are far off, however. "These are things we'll hear more about in the future," Cosman said.

The primary roles of the pharmacist in osteoporosis management are recommending bone density testing and educating patients, said Jennifer Hardman, Pharm.D., clinical pharmacist, University of Illinois, and clinical assistant professor, departments of pharmacy practice and obstetrics/gynecology. All women 65 years of age and over should have a bone density scan, said Cosman. Women who are younger than 65 years of age but who are postmenopausal should have a bone density scan if they have certain risk factors, such as if they are a smoker, if they weigh less than 127 pounds (unless they are very petite), if they have a prior fracture in the absence of major trauma, or if they have a familial history of fracture or osteoporosis.

In addition, women with conditions such as inflammatory bowel disease, rheumatoid arthritis, endocrine diseases such as hyperparathyroidism or hyperthyroidism, and celiac disease should have a bone density scan before age 65, Cosman said. Women taking corticosteroids and thyroid medications should also have a bone density scan before age 65, she added. Bone density testing is particularly important for women taking thyroid medications if their thyroid hormone levels are not being carefully monitored, she cautioned.

If a bone density scan is indicative of osteopenia or osteoporosis, pharmacists can work with the clinical team to determine what therapy will best preserve bone mass in that particular patient, Hardman said. They can also counsel women about their new medication, so that women know what therapeutic benefits and adverse effects to expect, how quickly they can expect to see results, and how to take the medication properly.

According to the National Osteoporosis Foundation, 10 million Americans are believed to have osteoporosis. Of those, 80% are women. The risk of hip fracture for a woman is equal to her risk of breast, ovarian, and uterine cancer combined. The hip, spine, wrist, and ribs are the most common sites for osteoporotic fracture.

Among African-American women over the age of 50, 5% are estimated to have osteoporosis and an additional 35% are believed to be at risk for osteoporosis because of low bone mass. An estimated 10% of Hispanic women in the same age group have osteoporosis, and 49% are believed to have low bone mass. Among Caucasian and Asian women over age 50, an estimated 20% have osteoporosis, and 52% are believed to have low bone mass. Caucasian women 65 years and older have twice the incidence of hip fractures as African-American women.

Cosman and Hardman named the following as additional risk factors for osteoporosis: low calcium intake, excessive alcohol consumption, sedentary lifestyle, and Caucasian or Asian ethnicity. To prevent osteoporosis, they recommended a lifestyle that includes a diet rich in calcium and vitamin D, weight-bearing exercise several times per week, and no smoking or excessive alcohol consumption.

Osteoporosis is an expensive public health issue. In 2001, for example, the estimated direct national expenditures (i.e., hospitals and nursing homes) for osteoporotic and associated fractures was $17 billion—and the cost continues to rise annually.

More information about osteoporosis for both patients and clinicians is available form the National Osteoporosis Foundation at http://www.nof.org and the North American Menopause Society at http://www.menopause.org .

Charlotte LoBuono

THE FOLLOWING MEDICATIONS ARE APPROVED BY THE FDA FOR POSTMENOPAUSAL WOMEN TO PREVENT AND/OR TREAT OSTEOPOROSIS

Bisphosphonates

• Alendronate (Fosamax, Merck)

• Risedronate (Actonel, Procter & Gamble)

• Calcitonin (Miacalcin, Novartis)

Estrogen/hormone therapy

• Estrogens brand names: Climara, Estrace, Estraderm, Estrab, Ogen, Ortho-Est, Vivelle, Premarin

Parathyroid hormone

• Teriparatide (Forteo, Lilly)

Selective estrogen receptor modulators (SERMs)

• Raloxifene (Evista, Lilly)

Source: National Osteoporosis Foundation

 

Charlotte LoBuono. New options in treating osteoporosis. Drug Topics Women's Health Supplement;147:9s.