Parathyroid hormone injections
prevent medically induced osteoporosis
Follow-up MGH study shows full year of therapy increases benefits

BOSTON – September 22, 1998 – A new study from the Massachusetts General Hospital (MGH) shows that long-term treatment with parathyroid hormone (PTH) can safely prevent the development of osteoporosis in women taking medications that induce artificial menopause. The study, in which women received daily injections of PTH for a year, is a follow-up to a 1994 study that evaluated six months of treatment.

Compared with the earlier research, the new report finds that longer-term treatment results in even greater increases in spinal bone density than seen in the earlier report and preserves density in the hip area, something not seen in the six-month study. The report appears in the Sept. 23 Journal of the American Medical Association.

"This report sets an important precedent for further studies defining a role for PTH in prevention of osteoporosis," says Joel Finkelstein, MD, of the MGH Endocrine Unit, the study’s lead author. "Based on this work, we are embarking on a three-year study examining whether PTH can prevent bone loss in early menopause."

Osteoporosis is a thinning of the bone that often appears in women after menopause, when natural production of estrogen declines. Affecting more than 20 million Americans, osteoporosis can lead to fractures of the wrist, hip, pelvis and spine, sometimes causing serious disability. Among elderly patients with hip fractures, 15 percent die as a result of their injury.

The current study followed 43 women treated for endometriosis with nafarelin, a medication that suppresses the natural release of reproductive hormones and causes temporary menopause. Nafarelin is one of a group of drugs called gonadotropin-releasing hormone analogs used to treat conditions that improve when levels of the sex hormones estrogen or testosterone are suppressed. Because these drugs can cause osteoporosis, their use in treating conditions such as endometriosis is usually limited to six months, after which symptoms eventually recur.

The study participants were assigned randomly to receive daily injections of either nafarelin alone or nafarelin and PTH. Produced by the parathyroid glands, PTH normally helps control the exchange of calcium between the bones and the bloodstream. Although continuous exposure to high levels of PTH can weaken the skeleton, intermittent injections of low-dose PTH increase the amount and strength of bone.

After the yearlong study, women who had taken PTH showed increases in the bone density of the lumbar spine (lower back) while women taking nafarelin alone showed decreases in spinal bone density. The increases were greater than those seen in the six-month study. For example, lateral (side-to-side) density increased about 4 percent after six months of treatment but had increased 7.5 percent after one year of treatment.

Measurements of the proximal (upper) end of the femur, or thighbone, showed that bone density after one year of PTH treatment was virtually the same as before nafarelin treatment began; the same measurements in women receiving nafarelin alone showed decreases in density of 4 to 5 percent. In contrast the six-month study did not show a protective effect in the upper thigh – an area involved in many hip fractures. In fact, women receiving PTH showed a decrease in density in that area at six months – similar to the decrease seen in women receiving nafarelin alone – but density returned to original levels after a year of treatment.

"This is the first time we’ve shown that PTH can prevent bone loss in the hip, which is particularly significant because of the serious risk of hip fractures in women with osteoporosis," says Finkelstein. He adds that total-body bone density also was preserved in women taking PTH, while it decreased in those taking nafarelin alone.

Although women now have several FDA-approved medication options for preventing osteoporosis – including estrogen replacement therapy and the new drugs alendronate and raloxifene – each of these therapies has side effects that may be undesirable to individual women, Finkelstein notes. In addition, PTH therapy has a different mechanism of action than do the current treatments: Estrogen and the other approved therapies act by inhibiting the natural breakdown of bone, but PTH directly stimulates formation of new bone tissue.

"Osteoporosis causes about 1.3 million fractures in this country every year," Finkelstein says. "Although we still have to answer lot of questions before PTH can become an approved therapy, it may give us an entirely new approach to preventing this serious problem."

The senior author of the JAMA study is Robert M. Neer, MD, director of the MGH Osteoporosis Center. Other coauthors are Anne Klibanski, MD, Amy Arnold, and Thomas Toth, MD, of the MGH; and Mark Hornstein of Brigham and Women’s Hospital. The study was supported by grants from the National Institutes of Health.

The Massachusetts General Hospital, established in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of more than $200 million and major research centers in AIDS, the neurosciences, cardiovascular research, cancer, cutaneous biology, transplantation biology and photomedicine. In 1994, the MGH joined with Brigham and Women’s Hospital to form Partners HealthCare System, an integrated health care delivery system comprising the two academic medical centers, specialty and community hospitals, a network of physician groups and nonacute and home health services.

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Contact: Susan McGreevey in the MGH Public Affairs Office

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