The future of osteoporosis drugs: annual injection?
Certain osteoporosis drugs known as bisphosphonates increase bone density and reduce the risk of fracture in postmenopausal women. Common oral bisphosphonates include alendronate (Fosamax) and risedronate (Actonel). However, taking these medications can be tricky. You have to take them on an empty stomach while sitting or standing upright, drink a full glass of water, and remain upright for 30 minutes while eating or drinking nothing. Because low bone density does not cause symptoms unless a fracture occurs, and this drug regimen is inconvenient, many patients do not take the drugs consistently. In addition, oral bisphosphonates can be given only in small doses, because larger doses cause stomach upset.
Small, short-term studies have suggested that bisphosphonates given intravenously (into a vein) increase bone density in patients with osteoporosis. Now, research recently published in The New England Journal of Medicine suggests that the bisphosphonate zoledronic acid (Zometa) increases bone density as effectively as Fosamax and Actonel. But the best part is that it can be given intravenously as infrequently as once a year.
About the study
Researchers in 10 countries around the world collaborated on this study, which was sponsored and designed by Novartis Pharma, the manufacturers of zoledronic acid. The researchers enrolled 351 postmenopausal women ages 45 to 80 who had low bone density but did not have full-blown osteoporosis. Women were excluded from the study if they had osteoporosis, liver or kidney disease, thyroid or parathyroid disorders, vitamin D deficiency, or a history of cancer. Women were also excluded if they had previously taken bisphosphonates or fluoride, estrogen therapy in the last three months, or any other drug known to affect bones.
All women took calcium supplements during the study. At the start of the study, the women were randomly assigned to receive either a placebo (injection of inactive salt water solution) or one of the following intravenous zoledronic acid treatments:
- 0.25 mg at the start of the study and every 3 months thereafter
- 0.5 mg at the start of the study and every 3 months thereafter
- 1.0 mg at the start of the study and every 3 months thereafter
- 4.0 mg once at the beginning of the study
- 2.0 mg at the start of the study and again at 6 months
Using dual x-ray absorptiometry (DEXA), researchers measured the women's bone density of the spine, femoral neck (upper thighbone), forearm, and total body at 6, 9, and 12 months. At the end of the study, researchers compared the bone densities of the women in each of the treatment groups.
Over the 12-month study period, bone density increased in all the zoledronic acid groups. However, in the placebo group, bone density of the spine remained stable and bone density of the femoral neck decreased slightly. Specifically, bone density measurements of the spine in the zoledronic acid groups were 4.3% to 5.1% higher than in the placebo group. Bone density measurements of the femoral neck ranged from 3.1% to 3.5% higher in the zoledronic acid groups than in the placebo group.
Of note, there was no significant difference in the effectiveness of the various doses of zoledronic acid. Even in the group that received only one 4-mg dose at the beginning of the study, bone integrity was maintained 12 months later. Further study is needed to determine the optimal dosing of intravenous zoledronic acid.
There are limitations to this study, however. All but two of the women in this study were white, so these results may not apply to women of other racial and ethnic groups. In addition, the women in this study did not have full-blown osteoporosis, so it is not clear how effective zoledronic acid will be in women who do have osteoporosis. Finally, no information was collected regarding weight-bearing exercise or dietary calcium and vitamin D intake—both factors that help strengthen bones.
How does this affect you?
Will an injection of zoledronic acid once a year prevent osteoporosis in women with low bone density? Sometime in the future it may. These results suggest that intravenous zoledronic acid given as infrequently as once a year can increase bone density in postmenopausal women with low bone density. What has not yet been proven, however, is whether zoledronic acid reduces the risk of fractures—the ultimate goal of osteoporosis therapies.
More research is needed to determine the optimal dose and frequency of dosing. In an editorial accompanying this article, Dr. Caren G. Solomon adds that more research is also needed to determine if the drug reduces the risk of fractures and is safe for long-term use.
Many patients find taking oral bisphosphonates inconvenient and therefore don't take them as prescribed. This isn't surprising when you consider that most women take these drugs long before they have any symptoms. In fact, there are no symptoms of low bone density, unless it progresses to the point where you have a fracture. If zoledronic acid can be given intravenously once a year or even less frequently, patients may be more likely to comply with the treatment regimen and substantially reduce the health risk—and financial burden—of osteoporosis.
Reid IR, et al. Intravenous zoledronic acid in postmenopausal women with low bone mineral density.
New England Journal of Medicine . February 28, 2002;346(9):653-661.
Solomon CG. Bisphosphonates and osteoporosis.
New England Journal of Medicine . February 28, 2002;346(9):642.
Last reviewed Feb 28, 2002 by
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