Introduction

Most drug treatments for osteoporosis are aimed at slowing the rate of bone destruction that occurs in the disease. Now there's a new approach - a synthetic drug that actually promotes bone formation. It's a close relative of a natural hormone secreted by the parathyroid glands (so named because they sit very close, or within, thyroid gland tissue). Teriparatide, as it is called, has to be given daily by injection under the skin.

Teriparatide increases the bone mineral density (BMD) and total bone mineral content in the spinal and thighbones of women with osteoporosis, and it reduces the risk of fractures involving the vertebrae and other sites by 50% to 65%. Scientists have analyzed to see if these improvements are seen in everyone with osteoporosis, or just certain groups of people.

What was done

Over 1500 postmenopausal women who had had previous vertebral fractures were enrolled. They all received daily calcium supplements (1000 mg) and vitamin D (400-1200 IU) throughout the study. They were divided into 3 groups: one was given dummy (placebo) injections, one received teriparatide (20 µg), and the third teriparatide (40 µg). The women gave themselves the daily injections. They had spinal X-rays at the start and the end of the study, as well as BMD measurements of their lumbar vertebrae at intervals during the study, which lasted an average of 19 months.

What was found

The average age of the women in the study was 70, and they were, on average, 21 years post-menopause. About 15% of them had been treated previously for their osteoporosis.

Both groups receiving had significant increases in their vertebral BMD, compared to placebo after 3 months. By the end of the study the BMDs were increased by 10% and 14% for the 20 µg and 40 µg dose levels, respectively.

Age didn't affect the results with teriparatide. Although the percentage increase was a bit larger in the older subjects, this was also the case for those given the placebo. It's likely that all the older subjects were relatively more lacking in calcium and vitamin D at enrollment, so that the supplements they got had an additional effect on BMDs.

The actual increases in vertebral BMD with teriparatide were the same, whether there was a lower BMD at baseline or not. (However, if the results were expressed as a percentage increase, these increases appeared greater in those women with lower starting BMDs, as one would expect.)

The risk for developing new fractures in the placebo subjects was greater in those with low baseline BMDs. But for both doses of teriparatide, the risk of new fractures didn't vary with baseline BMDs. Body weight was found to have no effect on the results of teriparatide.

Comment

Teriparatide has been reported to cause a slight increase in nausea, dizziness, and leg cramps, compared with those produced by a dummy (placebo) injection. The blood calcium level is slightly increased in as many as 11% of women given 20 µg daily doses. There can be slight pain and firmness at the injection site, but this is due to one or other of the inert chemicals in the injection solution, rather than teriparatide itself.

A 2-year study in rats using very high doses showed a slight increase in bone tumors in the animals given teriparatide. For this reason, people at risk for bone cancer - e.g. those with Paget's disease of bone, unexplained raised blood alkaline phosphatase levels, and those who have had prior radiation of the skeleton - should not take teriparatide. And it should not be given for longer than 2 years, at the present time.

In spite of this warning, it's clear that teriparatide represents a significant advance in the treatment of osteoporosis. It's effective in both men and women with osteoporosis. And it seems to be about twice as effective in raising the BMD as alendronate (Fosamax®). However, in view of the need for daily injections and the limits on the time it can be given, teriparatide should probably be reserved, in the first place, for people with severe osteoporosis.

Source

The skeletal response to teriparatide is largely independent of age, initial bone mineral density, and prevalent vertebral fractures in postmenopausal women with osteoporosis.
R. Marcus, O. Wang, J. Satterwhite,  et al., J Bone Miner Res, 2003, vol. 18, pp. 18--23

Links

• Calcium is Not All You Need for Strong Bones
• Winning the battle of the bones?
• Disease Digest: Osteoporosis
• Drugs Approved by the FDA: teriparatide (Forteo®)