News — August 2009

Endocrine Society Issues Response to Recently Published Insulin Glargine Studies
Five articles recently posted online in Diabetologia studied the possible connection between the use of insulin glargine [rDNA] injection (Lantus, Sanofi Aventis) and the development of cancer.

One of these studies suggested an increased risk of cancer, however, the other four did not come to the same conclusion, stated a news release from the Endocrine Society. Taken together, the results of all these studies do not conclusively show that insulin glargine causes cancer or is otherwise harmful to a patient's overall health, according to the statement. In terms of clinical practice, there does not appear to be sufficient evidence to recommend against the use of insulin glargine.

The Endocrine Society anticipates that as medical experts perform new studies, the potential risks and benefits of insulin glargine will become more clearly defined. To address concerns about the potential relationship between insulin glargine and cancer, the Society has issued a statement for patients and one for physicians. The Society provides a summary of the studies published in Diabetologia and offers recommendations regarding treatment of patients with diabetes.

The Society recommends that physicians continue to individualize their therapy based on a patient's situation and encourage their patients to follow current recommendations for screening tests for cancer and avoid dangerous habits, such as smoking. Taken together, the studies do not clearly indicate that inclusion of insulin glargine in a treatment regimen for diabetes leads to worse overall health or, for that matter, better overall health, the Endocrine Society said.

Nevertheless, the possibility of increased cancer occurrence with insulin glargine use under some circumstances does raise concern. In evaluating all information, the Society concluded: "The evidence presented in this set of papers is sufficient to establish that there is a case to answer, but is entirely insufficient to bring in a verdict. Certain reassurances do, however, seem justified.

"There is no evidence that insulin, however formulated, causes cancer. There is no evidence of an overall increase in the rate of cancer development in patients on insulin glargine, and some suggestion that the risk may actually be reduced. There is no evidence of harm in diabetes or in premenopausal breast cancer."

For the complete statement, visit: www.endo-society.org/advocacy/policy/upload/Glargine-Cancer-Statement-for-Providers.pdf.

Long-Term Safety Results of Lantus Compared With NPH
The results of the long-term, 5-year study of insulin glargine (Lantus, Sanofi Aventis) versus neutral protamine Hagedorn (NPH) insulin on progression of retinopathy in patients with type 2 diabetes, published in Diabetologia showed similar effects on retinopathy and overall safety in the two treatment groups. This is the longest controlled study ever reported using insulin glargine, according to a news release from Sanofi Aventis.

Diabetic retinopathy—a major cause of blindness in patients with diabetes—is a progressive disease that results from cellular proliferation within the eye. The stimulation of insulin-like growth factor 1 receptors is involved in this process. In the study of patients with retinopathy, the progression of diabetic retinopathy was similar in the two treatment groups over the long-term course of treatment. This indicates that insulin glargine does not have mitogenic effects different from the human NPH insulin within the eye.

"This 5-year study is the longest randomized controlled study with insulin glargine versus NPH human insulin," said lead investigator Julio Rosenstock, MD, Director of the Dallas Diabetes and Endocrine Center at Medical City and also Clinical Professor of Medicine, University of Texas Southwestern Medical School. "This study demonstrated no evidence of a greater risk of progression of retinopathy with insulin glargine," he said in the news release.

Takeda Receives FDA Complete Response Letter for Alogliptin
Takeda Pharmaceutical Company has received a complete response letter from the US Food and Drug Administration (FDA) regarding the new drug application (NDA) for alogliptin, a selective dipeptidyl peptidase IV inhibitor under investigation for the treatment of type 2 diabetes as an adjunct to diet and exercise. In recent months, the FDA and Takeda have been in discussions about conducting an additional cardiovascular study for alogliptin, according to a company news release.

As previously announced in March, the FDA informed Takeda that, although the alogliptin NDA was filed prior to the release of the December 2008 FDA "Guidance for Industry: Diabetes Mellitus Evaluating Cardiovascular Risk in New Antidiabetic Therapies to Treat Type 2 Diabetes," the FDA did not believe that the amount of existing alogliptin clinical data was sufficient to meet certain statistical requirements outlined in that guidance. The FDA has asked Takeda to conduct an additional cardiovascular safety trial that satisfies the 2008 guidance.

"We expect to resubmit the application in about 2 years," said Takeda spokesperson Hisashi Tokinoya. Alogliptin "is the most important drug development agenda for Takeda. We expect to lose patent protection on … (pioglitazone [Actos]), and with the decision by the FDA it is difficult to have the drug in time for the patent expiration."

Takeda has submitted an application for an additional indication of alogliptin for combination therapy with thiazolidinediones, the company stated, and an NDA of fixed-dose combination of alogliptin and pioglitazone HCl in Japan.

Aliskiren Approved in Japan for Hypertension Treatment
The first-in-class renin inhibitor aliskiren (Rasilez, Tekturna), the first new type of high blood pressure medicine in more than a decade, has been approved for use in Japan. The Japanese Ministry of Health, Labour, and Welfare approved aliskiren alone for the treatment of hypertension or in combination with other antihypertensives.

"In Japan, nearly 70% of patients are not reaching their blood pressure goal, demonstrating a strong need for therapies with a new mechanism of action," said Prof. Toshiro Fujita, Department of Nephrology and Endocrinology, University of Tokyo, in a news release from Novartis, the agent's manufacturer in the United States. "It is expected that [aliskiren's] unique mechanism of action will provide significant blood pressure reductions that last for 24 hours."

Aliskiren works by directly inhibiting renin to reduce the effects caused by an overactive renin system. By inhibiting renin at the point of activation, aliskiren provides significant blood pressure reductions alone or in combination with other antihypertensives. The potential long-term benefits of aliskiren are currently being investigated further in the landmark ASPIRE HIGHER program, the largest ongoing cardiorenal outcomes program worldwide, involving more than 35,000 patients in 14 trials, according to the company. The agent was approved for use in the United States in 2007.

EU Approves Zoledronic Acid for Steroid-Induced Osteoporosis
Zoledronic acid 5 mg (Aclasta, Novartis) has been approved in the European Union to treat men and postmenopausal women with osteoporosis caused by the long-term use of glucocorticoids. The new indication for the treatment of glucocorticoid-induced osteoporosis (GIO) is important because glucocorticoids are widely used to treat inflammatory conditions such as asthma, rheumatoid arthritis, and inflammatory bowel disease. Patients receiving long-term steroid therapy are at increased risk of fracture, as their use is associated with side effects such as bone loss and consequently osteoporosis, according to Novartis.

"Oral bisphosphonates have been used for many years for the treatment of glucocorticoid-induced osteoporosis, but they are associated with poor compliance as patients frequently fail to take them as prescribed," said Prof. David M. Reid, Head of the Division of Applied Medicine at the University of Aberdeen, UK. "Available data show that patients who remember to take their medicines only half of the time receive little or no protection," he said in the news release.

"The approval of [zoledronic acid] is a significant step forward for the treatment of glucocorticoid-induced osteoporosis and has the advantage of year long compliance and sustained osteoprotection."

The new indication for glucocorticoid-induced osteoporosis is based on a study published in The Lancet this year. These data show that at 12 months of treatment a yearly infusion of zoledronic acid 5mg increases bone mineral density (BMD) at the lumbar spine significantly more than oral risedronate (Actonel, Proctor & Gamble Pharmaceuticals UK Ltd) 5 mg taken daily (a current established therapy) for the treatment of glucocorticoid-induced osteoporosis (zoledronic acid 4.1%, risedronate 2.7%; P=.0001). The greater efficacy of zoledronic acid 5 mg was evident at the lumbar spine at 6 months after treatment initiation.

Zoledronic acid 5 mg is an annual infusion currently used to treat osteoporosis in men and postmenopausal women at increased risk of fracture, including those who have experienced a low trauma hip fracture. It is also indicated for the treatment of Paget's disease of the bone, according to Novartis.

Study Explains Potential Failure of Oral Contraceptives Among Obese Women
Researchers have identified a potential biological mechanism that could explain why oral contraceptives may be less effective at preventing pregnancy in obese women, as some epidemiological studies have indicated. The study is published in Contraception.

Although conventional oral contraceptives appear to eventually reach the effective blood concentrations needed in the body to prevent conception in obese women, it appears to take twice as long, leaving a window of opportunity every month where the contraceptive may not be at a high enough level to prevent a pregnancy, according to a news release from Oregon State University.

The findings are of particular importance, researchers noted in their study, because about 30% of all adults in the United States are obese and the birth control pill is one of the most popular forms of contraception in the nation.

"We don't have enough data yet to recommend that physicians change their clinical practice for use of oral contraceptives with patients who are very overweight," said Ganesh Cherala, PhD, College of Pharmacy, Oregon State University, Portland. "However, until more studies are done, women may wish to consult with their physicians about this issue and consider a backup method of contraception at some times of the month."

The underlying problem, Dr. Cherala said, is that oral contraceptives, like most drugs, are initially tested in healthy people, which rarely includes people who are more than 130% of their ideal body weight.

"When we first test drugs for safety and efficacy, we generally do not include people with a high body mass index [BMI]," Dr. Cherala said. "But body weight and amounts of fat can seriously change the pharmacokinetics, or way drugs act and are processed in the body. There's a growing awareness that we need to more carefully consider obesity and other factors that affect drug absorption, distribution, metabolism and other factors."

The researchers in this study said they were somewhat surprised to find that the affinity of these drugs for fat tissue was not significantly different between obese and normal-weight individuals. Rather, the researchers found that contraceptive drug levels in both obese women and those of normal weight eventually were about the same, but it took longer to achieve that level in very overweight women.

The study showed it took an average of about 5 days for the drugs to achieve their maximum concentration in women of normal weight, an average of 10 days for obese women, and even longer than that for some individuals. One woman in the study took more than 20 days to reach a steady state drug concentration.

Women of normal weight who follow their oral contraceptive directions should have appropriate protection against pregnancy. But the delay in reaching a steady state drug concentration raises questions about how well oral contraceptives may work for obese women.

Increasing the drug dosage might help address this issue, Dr. Cherala said, but also adds other health concerns. In fact, the researchers noted in their report that many clinicians actually prescribe lower-dose oral contraceptives to obese patients in an effort to decrease their risk of venous thrombosis. The study was done among 20 women aged 18 to 35 years, all healthy and seeking contraception, 10 of whom were of normal weight and 10 with a BMI of >30 kg/m2.

Hormone Therapy Use Associated With Increased Ovarian Cancer Risk
Compared with women who have never taken hormone therapy (HT), those who currently take it or who have taken it in the past are at increased risk of ovarian cancer, regardless of the duration of use, the formulation, estrogen dose, regimen or route of administration, according to a study published in the Journal of the American Medical Association (JAMA).

Primary prevention of ovarian cancer is challenging because little is known about its cause, according to a JAMA news release. Studies have suggested an increased risk of ovarian cancer among women taking postmenopausal HT, the article stated. Data have been limited on the differing effects of formulations, regimens and routes of administration.

Lina Steinrud Mørch, MSc, Copenhagen University, Copenhagen, Denmark, and colleagues conducted a study to examine the risk of ovarian cancer associated with hormone therapy use. The study included all Danish women aged 50 through 79 years from 1995 through 2005 through linkage to Danish national registers. Prescription data from the National Register of Medicinal Product Statistics provided individually updated information on hormone therapy use. The National Cancer Register and Pathology Register provided ovarian cancer incidence data.

According to JAMA, the analysis included a total of 909,946 women without hormone-sensitive cancer or who had not had both ovaries removed. At the end of follow-up, 63% of the women had not been taking hormone therapy, 22% were previous users of hormones, and 9% were current users of hormones. Among the current users, 46% had used hormones for more than 7 years.

During an average of 8 years of follow-up, 3,068 ovarian cancers were detected. Of these, 2,681 were epithelial tumors. Compared with never users, current users of HT had an overall 38 % increased risk of ovarian cancer. When restricting the analyses to epithelial ovarian cancer, the relative risk (RR) among current HT users was 44% higher, with previous HT users having a 15% increased risk compared with women who had never used HT. The risk for ovarian cancer and epithelial ovarian cancer did not increase significantly with increasing durations of HT.

The risk of ovarian cancer declined with longer time since last HT use. The risk of ovarian cancer did not differ significantly by formulation, regimen, type of progestin or route of administration. The absolute risk indicated approximately one extra ovarian cancer for roughly 8,300 women taking hormone therapy each year.

"If this association is causal, use of hormones has resulted in roughly 140 extra cases of ovarian cancer in Denmark over the mean follow-up of 8 years, ie, 5% of the ovarian cancers in this study. Even though this share seems low, ovarian cancer remains highly fatal, so accordingly this risk warrants consideration when deciding whether to use hormone therapy," the authors wrote.

Metabolic Factors May Play a Role in Risk for Breast Cancer
Physiological changes associated with the metabolic syndrome may play a role in the risk of postmenopausal breast cancer, according to a study published in Cancer Epidemiology, Biomarkers & Prevention.

One characteristic of the metabolic syndrome is elevated insulin levels, and in recent years scientists have proposed that insulin may contribute directly or indirectly to the development of breast cancer. Researchers suspect that the metabolic syndrome could influence the risk for breast cancer by affecting interrelated hormones, such as insulin, estrogen, cytokines, and growth factors, according to a news release from the American Association for Cancer Research.

"This study suggests that having the metabolic syndrome itself or some of its components may increase a woman's risk of postmenopausal breast cancer. Much more work is needed to understand the role of these metabolic factors and their interplay with better established breast cancer risk factors, such as reproductive and hormonal factors," said Geoffrey C. Kabat, PhD, Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY. Studies to date have evaluated individual components of the metabolic syndrome and breast cancer, with inconsistent results, according to Dr. Kabat. He and colleagues assessed whether women who met the criteria of having the metabolic syndrome were at greater risk for postmenopausal breast cancer.

In the longitudinal study, the researchers used existing data from the WHI (Women's Health Initiative), a large, national study designed to assess major causes of chronic disease in women. Participants included postmenopausal women aged 50 to 79 years at enrollment who had repeated measurements of components of the metabolic syndrome over an 8-year period. These included blood levels of glucose, high-density lipoprotein cholesterol and triglycerides, as well as waist girth and blood pressure.

Results showed a modest positive association of having the metabolic syndrome as a whole, according to Dr. Kabat. Of the 4,888 women with baseline measurements who did not have diabetes, 165 incident cases of breast cancer were diagnosed during the follow-up period. Presence of the metabolic syndrome at baseline was not associated with breast cancer risk In analyses that made use of the repeated measurements, however, "women who had the metabolic syndrome during the 3 to 5 years prior to breast cancer diagnosis had roughly a doubling of risk," he said.

Findings also showed significant associations with elevated blood glucose levels, triglycerides, and diastolic blood pressure. For diastolic blood pressure, the result was stronger, with more than a two-fold increased risk (RR = 2.4). Generally, for both triglycerides and glucose the RR was about 1.7 for all breast cancer.

"We know a great deal about breast cancer, but we can't identify who is likely to get it. The effect of different variables associated with increased glucose and insulin levels needs to be evaluated further in larger studies," Dr. Kabat said. "We need to deepen our understanding of these different interrelated behaviors and physiological factors to see how they affect breast cancer."

Higher Adiponectin Levels Lower Type 2 Diabetes Risk
Individuals with higher levels of adiponectin, a protein that is produced by fat cells and that has antiinflammatory and insulin-sensitizing properties, have an associated lower risk of type 2 diabetes, according to an analysis of previous studies reported in JAMA.

Some studies have suggested several mechanisms through which adiponectin may decrease the risk of type 2 diabetes, although the strength and consistency of the relation between plasma adiponectin and risk of type 2 diabetes has been unclear, according to background information in the article.

Shanshan Li, MD, MSc, Harvard School of Public Health, Boston, and colleagues conducted a review and meta-analysis to assess the consistency of the association of adiponectin levels and risk of type 2 diabetes. The researchers identified 13 studies with a total of 14,598 participants and 2,623 new cases of type 2 diabetes that met criteria for inclusion in the meta-analysis.

The authors found that higher adiponectin levels were associated with a lower risk of type 2 diabetes. This inverse association was consistently observed in whites, East Asians, Asian Indians, African Americans, and Native Americans. The results did not differ substantially by method of diabetes ascertainment, study size, follow-up duration, BMI, or proportions of men and women, according to JAMA.

"Although these epidemiologic studies cannot establish causality, the consistency of the association across diverse populations, the dose-response relationship, and the supportive findings in mechanistic studies indicate that adiponectin is a promising target for the reduction of risk of type 2 diabetes," the authors wrote.

The researchers added that recent studies have shown that adiponectin levels can be increased through pharmaceutical and lifestyle interventions.

"Adiponectin levels may be useful for identifying persons likely to benefit most from interventions to treat 'dysfunctional adipose tissue' and its metabolic complications. Future studies should also evaluate whether adiponectin is useful for prediction of type 2 diabetes in addition to established risk factors."

Computer Games May Encourage Healthy Eating
Children who play an online game promoting healthy foods and beverages appear more likely to choose nutritious snacks than those who play a game promoting unhealthy products, according to a report in the Archives of Pediatrics & Adolescent Medicine.

Obesity rates among US children and youth have tripled during the past 40 years, according to the article. "One potential contributor to the rise in obesity is media exposure, primarily because television advertising markets high-calorie foods and beverages that have little nutritional value," the authors wrote. "We know far less about how newer media influence children's food preferences, but Internet use is a very popular activity among youth aged 8 to 18 years. Marketers have taken notice of this online revenue-generating opportunity in which exposure to products costs less than traditional television advertisements and legal restrictions and regulations are virtually nonexistent."

According to a news release from the journal's publisher, Advergames—online computer games developed specifically to promote a brand, often featuring logos and characters—are present on many food and beverage Web sites. Tiffany A. Pempek, PhD, and Sandra L. Calvert, PhD, of Georgetown University, Washington, DC, conducted a study involving 30 low-income, African American children aged 9 to 10 years. One group played a game, based on Pac-Man, that rewarded them for having their computer character choose bananas, orange juice, and other healthy foods and beverages. A second group played a different version of the same game that instead rewarded consumption of soda, candy bars, cookies, and bags of potato chips.

These two groups were instructed to select a snack from among options featured in the game after playing, whereas a third, control group selected a snack and beverage before playing the healthy version of the game. The children reported liking both versions of the game and played for an average of 9 minutes and 32 seconds.

Children who played the healthy version before selecting a snack were significantly more likely than those playing the unhealthy version to choose a banana and orange juice instead of soda and potato chips. "With only 10 minutes of exposure, our results revealed that children selected and ate whatever snacks were being marketed by the Advergame, healthy or not," the authors wrote.

The findings suggest that public concerns about online games that market unhealthy foods are justified, the authors note, but also that the technology could be used to promote nutritious foods.

"Eating patterns established during childhood affect health throughout the lifespan. Thus, it is important that we find ways to promote a healthy lifestyle for our children from an early age, particularly those who come from low-income neighborhoods where the risk of obesity is greatest," the authors wrote.

Despite concerns that low-income children do not have Internet access, children in the study reported being online daily or at least several times per week. "Overall, our results suggest that reaching low-income African American children via the Internet is feasible and that the use of Advergames is a potential way to alter their eating habits in favor of more nutritious foods," the authors concluded.

Young Black Women Prone to Gain More Unhealthy Abdominal Fat Than Hispanics
Black women aged 20 to 29 years are more prone to pack on unhealthy abdominal and visceral fat than Hispanic women the same age, and as compared to their elders, according to researchers from Wake Forest University Baptist Medical Center and colleagues.

The new research, according to a news release from the medical center, shows that accumulation of abdominal fat that increases risk of type 2 diabetes is greatest in young adulthood for blacks and Hispanics, said Kristen G. Hairston, MD, MPH, lead author of an article in Diabetes Care. The study is the first to look at a large minority cohort using computed tomography (CT) scanning to measure longitudinal changes over time in visceral and subcutaneous adipose tissue, which are different types of abdominal fat.

The study followed 389 blacks and 844 Hispanics ages 20 to 69, men and women, grouped by age in 10-year increments. The researchers took baseline measurements of visceral adipose tissue (VAT) and subcutaneous abdominal tissue (SAT) from 1999 to 2002 with follow-up measurements in 2005 to 2007. VAT is fat that resides within the abdominal cavity around internal organs and has been linked to metabolic disturbances. SAT is the kind of fat that one can pinch.

The study found that the young adult age group (ages 20 to 29 years) had the largest 5-year increase in measured adiposity, or fat, regardless of race or gender. The increase in VAT averaged 18 and 12 cm2 among young black and Hispanic women, respectively, and 13 and 7 cm2 among young men. The 5-year increase in (SAT) was 89 and 53 cm2 among young black and Hispanic women, respectively, and 76 and 30 cm2 among young men. In general, fat accumulation declined in the older age groups. Abdominal fat accumulation, particularly the visceral type, is significant because previous studies show that VAT changes of this magnitude differentiate those who develop diabetes from those who don't.

Until this study, this pattern of excessive abdominal fat accumulation in young adults has not been reported using CT-measured "fat depots." The findings, however, are consistent with several other studies that used measurements such as BMI and waist circumference. In this study, abdominal tissue area was measured at the L4/L5 vertebral region by CT.

"Our data may help to further identify unique populations at risk for type 2 diabetes and those for whom behavioral intervention might be most effective," said Dr. Hairston, Assistant Professor of Endocrinology and Metabolism.

Active Investigation of Resveratrol Pills Announced, Consumer Precautions Urged
Red wine (resveratrol) pills appear to be the rage these days and a local group of cardiologists wants to lead the way for patients and consumers to learn more about them. They may be among the first US cardiologists to do so, according to a news release from the Advanced Cardiology Institute.

In response to growing inquiries about the heart-healthy properties of red wine pills, a cardiology group says it will soon begin to study the effects of these pills among their patients with heart problems and suggests consumers consult with knowledgeable doctors before launching into unguided self use.

Jacqueline Hollywood, MD, cardiologist with the Advanced Cardiology Institute in Ft. Lee, NJ, said so many patients are hearing about the promises of red wine pills that their group decided to learn with their patients rather than leave them to pursue unguided use. Dr. Hollywood said human studies are largely derived from users of red wine, not red wine pills, so there is a need for research studies, but is confident that red wine pills are safer than an alcoholic beverage.

According to the news release, Nate Lebowitz MD, also a cardiologist with the Advanced Cardiology Institute, said the goal is to find out if red wine pills can actually mimic the French Paradox, the fact that red-wine drinking adults in France, who consume a high-fat and calorie-rich diet, experience a much lower mortality rate from heart disease than North Americans.

Red wine resveratrol pills first gained attention late in 2003 shortly after Harvard researchers noted that a resveratrol, a molecule found in red wine, prolonged the life of yeast cells in a lab dish. Since then resveratrol has been proven to extend the life of fruit flies, roundworms, cold-water fish and high-fat fed mice.

"We will cautiously begin some studies, to measure markers, like inflammation, cholesterol, blood clotting, and maybe even imaging of coronary or carotid arteries, to see if these pills live up to their promise," said Dr. Lebowitz.

Resveratrol is fast becoming a household word as it now widely extolled as a potential longevity molecule. Resveratrol and other small molecules found in red wine can enter living cells and influence genetic machinery. One widely studied gene pathway, activated by resveratrol, is the Sirtuin1 gene, known as a survival gene. The current idea is to develop pills that will mimic the effects of a calorie-restricted diet, which is known to double the lifespan of all living organisms.

"These pills may be a boon to cardiology," said Dr. Hollywood, "if they do in humans what they have been shown to do in animals, and among the red wine drinkers in France. Hopefully, we will know soon."

Osteoporosis Drug May Strengthen the Immune System
An osteoporosis drug proven to save lives after hip fractures may do so by strengthening the body's immune system, according to geriatrics researchers at Duke University Medical Center.

In 2007, Duke researchers reported a 28% reduction in death among patients who received zoledronic acid (Reclast, Novartis) within 90 days of surgery for a hip fracture. Zoledronic acid is a yearly intravenous injection of bisphosphonate that inhibits the progression of bone loss. The researchers also reported that the 2,111 people who participated in the study were 35% less likely to suffer another fracture.

"The findings marked the first time an osteoporosis medication was shown to have an effect on mortality, but they didn't tell us why the mortality rate was lower," said Cathleen Colon-Emeric, MD, an Associate Professor of Medicine at Duke, in a university news release. "People assumed it was due to a reduction in secondary fractures. We wanted to know if that was the reason or were other conditions being affected by the medication."

In the current study in the Journal of Bone and Mineral Research, Dr. Colon-Emeric and her colleagues report that the reduction in additional broken bones accounts for only 8% of the mortality benefit. "Even after adjusting for secondary fractures and other risk factors, we found the risk of mortality was still 23% lower in the zoledronic acid-treated participants. That suggests the drug must work in other ways."

According to a news release from Duke University Medical Center, the link between osteoporosis and an increased risk of death has been observed for some time. Up to 25% of the 345,000 Americans hospitalized annually with hip fractures die within a year of their fracture. Typically, most patients die from cardiovascular problems like MI, arrhythmias and strokes, infections such as pneumonia, and cancer.

"People who received the drug experienced common complications at the same rate as those who didn't," said Dr. Colon-Emeric. But the people in the zoledronic acid group were better able to survive these events. "In particular, people with certain cardiac problems such as arrhythmias and pneumonias were much less likely to die from those conditions."

Patients who lived in a nursing home before their broken hip, or who had high levels of cognitive impairment did not receive a mortality benefit from the drug.

It still remains unclear what role zoledronic acid plays. "We know it affects the immune system and inflammation, and both of those are important in fighting infection and cardiovascular disease [CVD]," Dr. Colon-Emeric said. "It may be that the drug is changing the body's ability to fight off and recover from those illnesses." That idea will require confirmation in new studies.

Application of Innovative Laser Research Could Lead to Earlier Bone Disorder Diagnosis
A new laser technique that could lead to bone disorders being diagnosed earlier is to be tested in a hospital for the first time. The study, which it's hoped will pave the way for future clinical trials, will apply a revolutionary approach known as SORS (Spatially Offset Raman Spectroscopy), to examine specific substances in non-see-through surfaces deeper than has previously been possible, without damaging the surface.

The research team hope ultimately that the method can be used both to detect and screen for early signs of osteoarthritis and osteoporosis, according to a news release from Science and Technology Facilities Council (STFC), Swindon, UK.

"This exciting new approach has been developed by combining expertise in multidisciplinary research collaboration over a number of years. This has now culminated in a system for minimally invasive assessment of skeletal tissues and could with further development—form the basis of a rapid safe economical screening system for musculoskeletal disease," said Prof. Allen Goodship, University College London, the project's Principal Investigator.

The basic technique, devised and patented in the Central Laser Facility at the STFC, was developed for this application through an ongoing collaboration with the Institute of Orthopaedics and Musculoskeletal Science, University College London. The concept has been evaluated on bone samples with differing chemical composition but never before in a hospital on patients—as will happen in the next few years.

Prof. Pavel Matousek who is an STFC physicist and an honorary professor at University College London is the lead inventor of the technique, he said: "The new method effectively suppresses otherwise blinding interfering signals from skin, making it possible to see subtle chemical changes within all the components of bone through the skin, without the need for a biopsies."

The new approach is also able to provide far more information than conventional X-ray based systems that are limited to the mineral components only. The data can be related to the chemistry of bone tissue in its entirety and the analytical chemistry side of the work is supported by STFC's Professor Tony Parker, head of the Lasers for Science Facility at the Central Laser Facility and also an honorary Professor at University College London.

Periodontal Bone Loss Linked to Stroke Risk in Men
Peridontal bone loss is significantly associated with risk of stroke or transient ischaemic attack (TIA) in men aged <65 years, according to a study published in the Annals of Neurology.

The study found that only periodontal bone loss, which would indicate a history of periodontal disease, not probing depth, which would indicate current inflammation, was associated with the incidence of cerebrovascular disease. The study is the first prospective cohort study to use clinical measures of periodontitis to evaluate the association between this disease and the risk of cerebrovascular disease, according to a news release from the journal's publisher.

Thomas Dietrich, DDS, University of Birmingham School of Dentistry, Birmingham, Alabama, and Elizabeth Krall, DDS, Boston University School of Dental Medicine, Boston, and colleagues analyzed data from 1,137 men in the VA Normative Aging and Dental Longitudinal Study, an ongoing study which began in the 1960s with healthy male volunteers from the greater Boston area.

A periodontist conducted dental exams every 3 years that included full mouth X-rays and periodontal probing at each tooth. Cerebrovascular disease was defined as a stroke or TIA and follow-up lasted an average of 24 years. The results showed a significant association between periodontal bone loss and the incidence of stroke or TIA, independent of cardiovascular risk factors. This association was much stronger among men aged <65 years.

There are several possible pathways that could explain the association found in the study, according to the investigators. There could be direct or indirect effects of the periodontal infection and the inflammatory response, or some people may have an increased proinflammatory susceptibility that could contribute to both cerebrovascular disease and periodontal disease.

The stronger association in younger men seen in this and other studies may indicate a proinflammatory susceptibility in some men that is reflected in periodontal destruction at a younger age, according to the investigators. They noted that if periodontitis is caused cerebrovascular disease, it could be an important risk factor, given its relatively high prevalence and the strength of the association in younger men. It is also possible that people with periodontitis may pay less attention to health in general.

"Large epidemiologic studies using molecular and genetic approaches in various populations are necessary to determine the strength of the association between periodontitis and cerebrovascular disease and to elucidate its biologic basis," the authors concluded.

Why African Americans Have a Greater Risk of Hypertension, Kidney Disease
Physician-scientists from NewYork-Presbyterian Hospital/Weill Cornell Medical Center believe that a heightened level of a plasma growth factor may explain why blacks have a greater prevalence of hypertension and kidney disease compared with whites. Results from a new study are the first to show that an elevated level of a protein, called transforming growth factor b1 (TG-b1), raises the risk of hypertension and renal disease in humans.

African Americans constitute about 32% of all patients treated for kidney failure in the US and are four times more likely to develop renal disease than whites, according to the National Institutes of Health's US Renal Data System. The researchers' findings, published in Kidney International, may someday lead to the development of a new class of antihypertensive and kidney disease drugs that target the TGF-b1 protein, according to a news release from NewYork-Presbyterian Hospital/Weill Cornell Medical Center.

"I believe we may now understand a great puzzle: why the black population has a greater prevalence of hypertension and kidney disease," said Manikkam Suthanthiran, MD, th first author of the study and attending physician at NewYork-Presbyterian/Weill Cornell, Stanton Griffis Distinguished Professor of Medicine, Professor of Biochemistry and Professor of Medicine in Surgery at Weill Cornell Medical College.

Results from the study revealed that the TGF-b1 protein was significantly higher in 186 black study participants compared with 147 white participants.

After controlling for race, sex and age, TGF-b1 protein levels were highest in hypertensive blacks (46 ng/mL). Non-hypertensive blacks also had higher levels (42 ng/mL) compared to hypertensive whites (40 ng/mL) and nonhypertensive whites (39 ng/mL), demonstrating that even healthy black patients may be at higher risk for future hypertension and renal disease compared to healthy and hypertensive whites.

"Many black patients may have a disadvantage from the start—having a higher baseline level of TGF-b1," said Phyllis August, MD, senior author and attending physician in the Division of hypertension at NewYork-Presbyterian Hospital/Weill Cornell Medical Center, Ralph A. Baer Professor of Medical Research and professor of medicine atWeill Cornell Medical College.

While the exact mechanisms of TGF-b1 require further study, the authors believe that in black patients, higher levels of the growth factor are correlated with lower renin activity. Hypertension is the leading risk factor for end-stage renal disease (ESRD).

The authors believe it may be possible that higher levels of TGF-b1 boost retention of sodium salt within the kidneys, leading to higher blood pressure in the kidney and also lower levels of renin.

Greater levels of TGF-b1 in blacks were also positively associated with BMI and and metabolic syndrome. "Future clinical studies must be done so we may fully understand the specific role of TGF-b1 in how the kidney handles sodium, blood pressure and kidney disease," said Dr. August.

Dialysis Safe for Patients With Previous MI
Dialysis treatments do not affect the heart health of patients with kidney disease who have had a myocardial infarction (MI), according to a study published in the Clinical Journal of the American Society Nephrology.

Because CVD is the most common cause of death in kidney disease patients, the findings are good news for individuals who need the treatments. People with even mild forms of kidney disease have an elevated risk of MI. Those with ESRD are particularly vulnerable and often experience an MI while undergoing kidney disease treatments such as dialysis. Unfortunately, it is unclear how safe the dialysis procedure is for MI patients, according to a news release from the American Society of Nephrology.

To investigate the issue, George Coritsidis, MD, Elmhurst/Queens Hospital Center, Elmhurst, NY, and colleagues reviewed the medical charts of 131 patients with ESRD who had an MI while they were on dialysis. They looked to see if the timing of dialysis had any effect on patients' heart health following their MI. About half of the patients received dialysis within the first 24 hours of their MI. A quarter received dialysis 24 to 48 hours after their MI, and a quarter received dialysis more than 48 hours after.

The researchers found no link between the timing of dialysis treatments and cardiac symptoms such as chest pains or emergency department admissions. A similar number of patients in each of the three groups experienced cardiac symptoms. The investigators, however, identified several predictors that might indicate which dialysis patients have a particularly high risk of having an MI. These include the seriousness of the patient's condition, prior heart disease, high predialysis potassium blood levels, and a large drop in potassium blood levels after dialysis.

"In conclusion, our study does not indicate that timing of dialysis poses a risk. What may be of greater importance is the potassium status, its treatment, and the severity of the patients' condition on admission," the authors wrote. "Given that this is a retrospective as well as a small study, we cannot make any clear recommendations, however our findings suggest that rather than delay dialysis, concern should be placed on the degree and rate that potassium levels change."