Keeping you up to date on recent developments in orthopedics

An extra 5 years of life an unexpected benefit of osteoporosis treatment . . . Australian clinical researchers have noted an extraordinary and unexpected benefit of osteoporosis treatment – that people taking bisphosphonates are not only surviving well, better than people without osteoporosis, they appear to be gaining an extra five years of life. Associate Professor Jacqueline Center and Professor John Eisman, from Sydney's Garvan Institute of Medical Research, based their findings on data from the long running Dubbo Osteoporosis Epidemiology Study. Out of a total cohort of around 2,000, a sub-group of 121 people were treated with bisphosphonates for an average of 3 years. When compared with other sub-groups taking other forms of treatment, such as Vitamin D (with or without calcium) or hormone therapy, the longer life associated with bisphosphonate treatment was marked and clear. These findings are published in the Journal of Clinical Endocrinology and Metabolism, now online. "While the results seemed surprisingly good, they are borne out by the data – within the limitations of any study – and appear to apply to men as well as women," said Associate Professor Center. "When we first looked at the figures, we thought that there had to be a fallacy, that we were missing something. One of the most obvious things might be that these are people who seek medical attention, so may be healthier and live longer. So we compared the bisphosphonate group with people taking Vitamin D and calcium or women on hormone therapy. In a group of women with osteoporotic fractures over the age of 75, you would expect 50% to die over a period of five years. Among women in that age group who took bisphosphonates, the death rate dropped to 10%. Similarly, in a group of younger women, where you would expect 20%-25% to die over 5 years, there were no deaths. The data were consistent with about a 5 year survival advantage for people on bisphosphonates." The authors are intrigued by their findings. "We speculate that it may have something to do with the fact that bone acts as a repository for toxic heavy metals such as lead and cadmium," said Professor Eisman. So when people get older, they lose bone. When this happens, these toxic materials are released back into the body and may adversely affect health. By preventing bone loss, bisphosphonates prevent some of this toxic metal release. While we know that this is the case, we don't yet have evidence that this produces the survival benefit." It has already been shown by Garvan and others that osteoporotic fractures increase a person's risk of dying, even after relatively minor fractures if that person is elderly. "Only about 30% of women and 10% of men with osteoporosis receive treatment, which is unacceptable when you consider that people could be helped, and death could be delayed by several years. There is good evidence – even without this study - that treating osteoporosis reduces fractures and reduces mortality," Eisman said.

Approval of new drug for use in bone scans . . . The FDA has approved a New Drug Application (NDA) from the National Cancer Institute (NCI), part of the National Institutes of Health, for a new strength of a previously approved drug, Sodium Fluoride F18, for use in bone scans. In contrast to Technetium-99m (Tc-99m), which has been the only approved radioactive tracer for bone scans, Sodium Fluoride F18 is not subject to the supply problems that have led to recent nationwide shortages of Tc-99m. Many diagnostic imaging tests, including bone scans that utilize Single Photon Emission Computed Tomography (SPECT), require the use of Tc-99m. Bone scans are essential tools in the diagnosis of bone metastases in cancer patients, especially those with cancers (such as breast and prostate) that tend to metastasize to bone. Sodium Fluoride F18 was approved in 1972 but withdrawn in 1975, when the less expensive tracer Tc-99m became available. Tc-99m is derived from an isotope called molybdenum-99 (Mo-99), which is made mostly in highly enriched uranium nuclear reactors. Because both Mo-99 and Tc-99m have fairly short half-lives (66 hours and six hours, respectively), these drugs cannot be stockpiled. Seven nuclear reactors worldwide currently produce Mo-99 for medical use, with much of the U.S. supply coming from a nuclear reactor in Canada that has had frequent outages, the latest one lasting more than a year. Although Sodium Fluoride F18 is more expensive than Tc-99, it can be produced in medical cyclotrons, which are available at many academic universities and commercial suppliers in the U.S. This drug also provides better images because it uses Position Emission Tomography (PET) instead of SPECT imaging, allowing for improved, earlier detection. The previous strength of Sodium Fluoride F18 was discontinued for market reasons, not for reasons of safety or efficacy. NCI hopes that multiple companies and institutions will submit Abbreviated New Drug Applications (ANDAs) so that generic versions of the drug can be produced, allowing for a reduction in cost. A decision by the Centers for Medicare & Medicaid Services regarding coverage for Sodium Fluoride PET scans was posted on Feb. 26, 2010. It allowed Coverage with Evidence Development (CED), and a formal registry is being established by the National Oncologic PET Registry (NOPR) that should help facilitate this coverage.

Breast cancer survivors at greater risk of painful hip fractures . . . A hip fracture is not common in a 54-year-old woman, unless she is a 54-year-old breast cancer survivor, according to a new Northwestern Medicine (Chicago) study. Researchers found that a combination of early menopause due to breast cancer treatment and common drugs used to treat breast cancer, could be weakening the bones of breast cancer survivors once they hit middle age, leading to hip fractures. Results of the study are published in the February 2011 issue of Clinical Cancer Research. Hip fractures are rare in people under 70. Yet, Northwestern Medicine physician Beatrice Edwards, M.D., found that several breast cancer survivors in their early 50s were coming to her for treatment of hip fractures. Edwards is director of the Bone Health and Osteoporosis program and associate professor of medicine and of orthopedic surgery at Northwestern University Feinberg School of Medicine. She also is a physician at Northwestern Memorial Hospital and a member of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. Researchers studied six of these women over one year and assessed the type of breast cancer they had, the treatment they underwent and a hip fracture's effect on quality of life, said Edwards, lead author of the study. "One year after the fracture the women still reported difficulty with climbing stairs, shopping and heavy housekeeping," Edwards said. "Their healthcare costs may increase and their fractures contribute to losing some independence." Edwards was surprised to find that the majority of the women did not have osteoporosis, but did have lower than normal bone mineral density (osteopenia). This suggests that rapid change in bone architecture from chemotherapy, early menopause and adjuvant therapy may not be evident on bone mineral density test, Edwards said. The women had early-stage breast cancer and received treatment including lumpectomy, radiation therapy and chemotherapy with cytoxan and adriamycin one to four years before the fracture occurred. They were all perimenopausal at the time of the fracture. Four of the six women had breast cancer that grew in response to estrogen and received aromatase inhibitors (AIs) as part of their cancer therapy to block their bodies from making estrogen. Recent studies have linked AIs with possible bone loss in women. Edwards' team also reviewed reports from the FDA's adverse event reporting system and other databases and found that AIs were the most common drug class associated with hip fractures. "Although the majority of women with breast cancer can expect to be fully cured from the disease, the prevention of cancer treatment-induced bone loss is important to consider in cancer survival," Edwards said. "More research needs to be done before treatment guidelines are changed, but greater awareness of the adverse effects of certain breast cancer drugs is needed." Edwards said the next step is for researchers to conduct a clinical trial and give bone density screenings to women before they enter breast cancer chemotherapy. High-risk patients would be flagged and given preventive bone loss therapy and monitored for premature hip fractures.

– Compiled by Holland Johnson, MDD Managing Editor

holland.johnson@ahcmedia.com

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