Testosterone Therapy May Reduce Bone Loss in Older Men

(HealthDay News) -- Injections of testosterone appear to improve bone density and reduce bone loss in older men who have low testosterone levels and may help to prevent osteoporosis, a new study suggests.

Testosterone therapy has been used to improve bone strength and muscle mass in some men. However, the hormone treatment is controversial, because it has been associated with increasing the risk of prostate cancer and high levels of red blood cells. And other potential effects of long-term use of testosterone therapy aren't known.

"These preliminary data show beneficial effects of testosterone therapy on bone turnover markers in older men with low-to-normal testosterone concentrations using both continuous and monthly cycled testosterone replacement," lead researcher E. Lichar Dillon, of the Department of Internal Medicine at the University of Texas Medical Branch in Galveston, said in a prepared statement. "The effects of sex hormones on markers of bone formation are complex, but this is an important step in understanding how the process works."

Preliminary study results were expected to be presented April 7 at the American Physiological Society's annual meeting, during the Experimental Biology 2008 conference, in San Diego.

For the study, Dillon's team studied 13 men, ranging in age from 60 to 85. During the five-month trial, the men were either given weekly injections of testosterone, weekly injections of testosterone every other month, or a placebo.

The researchers found that men receiving testosterone had reduced bone turnover, compared with men on a placebo. While the effects of testosterone therapy over the long term aren't clear, the researchers said they believed the treatment would be beneficial by preserving bone mass and preventing osteoporosis.

One expert said the study was too small to prove or disprove the value of testosterone therapy in preventing bone loss and, perhaps, preventing osteoporosis.

"This small, short-term study indicates that men with low levels of testosterone respond to appropriate replacement as far as turnover markers indicate," said John Eisman, director of the Bone and Mineral Research Program at the Garvan Institute of Medical Research, in Sydney, Australia.

While calling the study "too small and too short to provide any insight into fracture-risk reduction or safety outcomes," Eisman said it does complement research he has done. "Our study showed that men with testosterone in the lowest quartile of the population had much higher risk of osteoporotic fractures," he said.

A large, long-term trial testing whether testosterone can prevent osteoporosis in men is needed to settle the question, Eisman said.

More information
To learn more about men and osteoporosis, visit the U.S. National Institute of Arthritis and Musculoskeletal and Skin Diseases.

Arthritis-related disability can have a major impact on a person's employment, forcing them to change work hours, the type and na

(HealthDay News) -- Living farther away from transplant centers doesn't explain why black Americans with end-stage renal (kidney) disease are less apt than whites to be placed on the kidney transplant waiting list, researchers say.

A team that analyzed data on end-stage renal (kidney) disease patients in Georgia and the Carolinas from 1998 to 2002 found that black patients in poorer neighborhoods were 56 percent less likely to than whites to be placed on the transplant waiting list.

"This finding warrants further exploration but suggests that racial disparity in the wait-listing process may indeed be a reflection of differential access to health care," study co-author Dr. Sandra Amaral, of Emory University in Atlanta, said in a prepared statement.

Of the almost 12,600 patients (62 percent of them black) included in the study, 17 percent were placed on the kidney transplant waiting list during the study period. Black patients were more likely than whites (27 percent versus 9 percent) to live in areas where more than 25 percent of the population lived below the poverty line.

The researchers had hypothesized that patients who lived farther from transplant centers would be less likely to be placed on the kidney transplant waiting list. But they found that distance to the transplant center didn't have a major impact on the likelihood of being placed on the list. They did find that black patients living in poorer neighborhoods were 56 percent less likely than whites to make it on the list.

"Racial disparities persist in the U.S. transplantation process," Amaral said. "The reasons for this are poorly understood, but multiple factors are likely involved."

"To our knowledge, this is the first study to examine the impact of community poverty on racial disparity in transplant wait-listing. It also introduces a potential new approach to addressing the disparities: reaching out to poorer communities with advocacy and education," she said.

The study was scheduled to be presented at the American Society of Nephrology annual meeting, in San Francisco.

More information
The U.S. National Institute of Diabetes and Digestive and Kidney Diseases has more about kidney transplantation.

Protein May Be Key to Rheumatoid Arthritis

(HealthDay News) -- In the quest for the causes of and potential treatments for rheumatoid arthritis, Japanese researchers have identified a protein that could be a target for future therapy.

Rheumatoid arthritis (RA) is a chronic and disabling autoimmune disease that first attacks the fluid that surrounds the joints, causing it to thicken and grow abnormally, damaging the joints and surrounding cartilage rather than protecting them. More than 2 million Americans suffer from the illness, according to the Arthritis Foundation.

By identifying a protein that appears to be one of the culprits in the unhealthy buildup of this fluid, which is called synovial fluid, Dr. Yasushi Miura and his colleagues at Kobe University School of Medicine hope that a new, targeted medication can be developed to treat the disease.
"The protein Decoy receptor 3 (DcR3) is one of the pathological factors of RA and can be a new therapeutic target for treatment," said Miura, an associate professor in the division of orthopedic sciences at the medical school.

His findings are published in the April issue of Arthritis & Rheumatism, the journal of the American College of Rheumatology.

DcR3 is a member of the large tumor necrosis factor receptor (TNFR) "super family," which has been identified in the last decade as important in the regulation of cell growth and cell death, fundamental processes in biology, said Dr. Robert Hoffman, director of the division of rheumatology and immunology at the University of Miami Miller School of Medicine in Florida.
"We have known of the importance of cell growth and cell death in studying cancer but more recently have found that it is also important in autoimmune diseases like RA and lupus," he said.
It was the similarity between the growth of malignant tumors and the abnormal growth of synovial tissue, called hyperplasia, that sparked Miura's research into DcR3 and rheumatoid arthritis. DcR3 is known to be produced in tumor cells, including lung and colon cancers.
What Miura and his colleagues found was that DcR3 works with another member of the TNFR family to slow the normal cell death of synovial fluid cells, resulting in the hyperplasia that causes some of the inflammation characteristic of rheumatoid arthritis.

Hoffman said: "This is a novel application of the connection between this specific member of the TNFR super family and RA, and studies like this are how we advance science. But it is currently a giant leap to suggest that this could be a therapy for RA."

For their study, Miura and his colleagues isolated and cultured cells from synovial fluid from19 patients with rheumatoid arthritis, obtained during total knee replacement surgery. For comparison, they also extracted synovial fluid cells in the same manner from 14 patients with osteoarthritis.

The researchers then exposed the synovial fluid cells to another TNFR protein called Fas, which induces cell death, called apoptosis. Finally, the cells were incubated with a pro-inflammatory member of the TNFR family, called TNFa. The TNFR family includes proteins that both induce and retard cell death, Miura explained.

While DcR3 was present in the same amounts in the synovial fluid cells of both the rheumatoid arthritis and osteoarthritis patients, when the TNFa was introduced, DcR3 production increased in the cells of the RA patients, slowing down the Fas-induced cell death. The rate of cell death did not change in the fluid of the osteoarthritis patients, perhaps, Miura suggested, because the TNFa levels were higher in the fluid of RA patients to begin with.

Miura said the results show that DcR3 acts in conjunction with TNFa to suppress the cell death necessary to keep synovial fluid healthy, and research aimed at reducing the amount of DcR3 in the synovial fluid in rheumatoid arthritis patients could be productive.

Dr. Stephen Lindsey, head of rheumatology at the Ochsner Clinic Foundation in Baton Rouge, La., said, "We are always looking for better and more specific targets to control immune response, and this study is very intriguing."

Lindsey said there are drugs available that inhibit those proteins that suppress cell death, but because they are "global," rather than targeted to particular proteins, there are many side effects, including infection.

More information
The Arthritis Foundation offers more information on rheumatoid arthritis.

Psoriasis Often Goes Untreated: Survey

(HealthDay News) -- Many Americans with chronic moderate or severe psoriasis receive no treatment or inadequate treatment, a new survey from the National Psoriasis Foundation (NPF) shows.

The poll also revealed a link between severe psoriasis and low income.

Psoriasis is a non-contagious disease in which the immune system causes skin to grow at an accelerated rate.

The surveys, conducted from 2003 to 2005, found that nearly 40 percent of people with chronic moderate or severe psoriasis were receiving no treatment, and that 57 percent of people with severe psoriasis, and 73 percent of those with moderate psoriasis, were receiving topical treatment only. Over half of patients with moderate to severe psoriasis were not receiving treatment that meets American Academy of Dermatology guidelines.

Those guidelines say that people with chronic moderate to severe psoriasis are candidates for phototherapy or systemic therapy, including biologic agents. However, many of those patients were receiving topical treatment alone, according to the survey data.

"Psoriasis is not a cosmetic disease but rather a chronic inflammation condition that can have a profound negative impact on a person's ability to function," Dr. Mark Lebwohl, chairman of the NPF's medical board, said in a prepared statement. "It's important for patients to openly discuss with their dermatologist how the condition may be impacting them, so that together they can determine the most appropriate treatments."

The survey data also revealed a possible association between psoriasis and low income -- 21 percent of people with severe psoriasis had a low household income (less than $30,000 per year), compared to 13 percent for people with mild psoriasis.

"These are the first data to show a relationship between psoriasis severity and household income," Liz Horn, NPF director of research, said in a prepared statement. "Psoriasis is a serious disease that can significantly affect a person's life by interfering with everyday activities, including work."

The survey findings were to be presented Friday at a meeting of the American Academy of Dermatology in Washington, D.C.

As many as 7.5 million people in the United States have psoriasis, according to the National Institutes of Health.

More information
The U.S. National Institute of Arthritis and Musculoskeletal and Skin Diseases has more about psoriasis.

FDA OKs Celebrex for Kids With Arthritis

(HealthDay News) -- The U.S. Food and Drug Administration Friday gave the green light to Celebrex for use in kids older than two as a treatment for juvenile rheumatoid arthritis.
The agency's action followed an advisory panel recommendation just over two weeks ago, which found that the benefits of the painkiller for children outweighed the shortage of proof on its safety

The panel, a committee of doctors and other specialists, voted 15-1 to approve the expanded use. But it also voted 8-7, with one abstention, that available data doesn't demonstrate that Celebrex is safe in treating JRA and that a registry should be established to track these young patients for 10 to 20 years.

As part of the approval process, the FDA said Friday, the drug's manufacturer, Pfizer, has agreed to conduct two Phase 4 post-marketing studies: a short-term controlled trial to evaluate high blood pressure, and a several-year registry study to further evaluate long-term safety issues, including renal toxicity, high blood pressure, and cardiovascular events.

"JRA is often a devastating disease," Dr. Steven Galson, director of the FDA's Center for Drug Evaluation and Research, said in a prepared statement. "While there are other medicines approved for the treatment of this disorder, for some children they may have limited effectiveness or cause intolerable side effects. Celebrex will be a needed additional treatment option for children."

His sentiment had been echoed by other experts after the advisory panel sent in its recommendation on Nov. 29.

The painkiller will quietly become one more option in the array already available, doctors said at the time.

"There will not be a mad rush to switch kids over to Celebrex," said Dr. Stephen Lindsey, section head of rheumatology at Ochsner Health System in Baton Rouge, La.

"I don't think there's going to be a huge move to this drug," added Dr. Norman Ilowite, chief of the division of rheumatology at Montefiore Children's Hospital in New York City. "Doctors will try this on patients with gastrointestinal problems who are on conventional NSAIDs (nonsteroidal anti-inflammatory drugs)."

"We're not sure exactly what the role of this drug is going to be in the treatment of juvenile rheumatoid arthritis," Ilowite continued. "The biggest issue is that there will be more choices. There's not really good evidence that Celebrex spares side effects or is particularly effective more than other choices, but for individualized patients it might be."

It's estimated that as many as 60,000 children in the United States have JRA, which causes painful joint swelling and can affect growth and development.

Up until now, Celebrex (celecoxib) was approved to treat adults with osteoarthritis and rheumatoid arthritis. In its application to expand that approval to include treatment of JRA, Pfizer included a six-month study that concluded that Celebrex works as well as naproxen in treating young patients.

Celebrex is a member of the controversial group of painkillers called cox-2 inhibitors, which have been linked to an increased risk of heart attack and stroke.

Two other cox-2s, Vioxx and Bextra, have been withdrawn from the market because of heart risk concerns. Celebrex remains available to consumers, but in 2005, the FDA required that the drug carry a "black box" warning on the possible risk of heart attack or stroke.

More information
For more on with juvenile rheumatoid arthritis, visit the U.S. National Library of Medicine.

Newly Released Data Stirs Naproxen Debate

(HealthDay News) -- Just-released data from a trial that was stopped early in 2004 for safety reasons is re-igniting debate on the safety of two popular painkillers.

The trial suggested the over-the-counter painkiller Aleve boosted heart risks, while another controversial prescription painkiller known as Celebrex did not.

Now, the data from that trial has finally been made available. But that has not silenced one critic, who says this early data is unreliable and questions the reasons the trial was stopped prematurely.

"The trial was improperly stopped by what appears to be political considerations. When you do that, you generate data which we know is unreliable," said Dr. Steven Nissen, a cardiologist at the Cleveland Clinic Foundation.

Nissen is author of an accompanying commentary in the Nov. 17 online edition of PLoS Clinical Trials, which has published the data from the Alzheimer's Disease Anti-inflammatory Prevention Trial (ADAPT).

Specifically, Nissen charges that ADAPT was cut short not on the advice of its safety-review board but by nervous officials at the U.S. National Institutes of Health, which had funded the trial. Those officials were worried about the media furor over the safety of now-withdrawn painkiller Vioxx, Nissen claims.

The medications in question all fall into the class of nonsteroidal anti-inflammatory drugs (NSAIDs), which include aspirin, naproxen, ibuprofen and cox-2 inhibitor medications such as Celebrex and the now-withdrawn Bextra and Vioxx.

Beginning in late 2004, major studies began to show that heart risks to users rose with long-term use of cox-2s. This led to the eventual withdrawal from the market of Vioxx and Bextra, and the U.S. Food and Drug Administration slapping a "black box" cardiovascular warning on the remaining cox-2, Celebrex.

In December of 2004, officials at the NIH announced the premature termination of the ADAPT trial, which had been set up to look at the possible usefulness of NSAIDs in preventing Alzheimer's disease.

Early results from that trial came as a surprise to many, because they suggested that long-term use of Celebrex did not significantly boost heart risks, while the use of an over-the-counter rival, naproxen (Aleve), did.

"We ended up stopping the trial early, when another trial brought up some safety concerns about these drugs," said study author Barbara Martin, an assistant professor of epidemiology at Johns Hopkins Bloomberg School of Public Health.

"We found a small but not statistically significant risk with celecoxib, and a larger and statistically significant increased risk with naproxen," Martin said.

But the actual data from the trial was not released at the time, adding to the confusion. It has now been published.

The 2,500 elderly participants in the ADAPT trial took either celecoxib, naproxen or placebo for up to 3.5 years.

Compared to those taking placebo, people taking celecoxib had a 10 percent increased risk of heart attack and stroke, while those taking naproxen had a 63 percent increase risk, the researchers found.

Martin said she wasn't sure why these drugs might have different risk profiles. Other trials have suggested that naproxen was actually cardioprotective, but these results indicated that it is not, she said.

Martin believes that the ADAPT results would also apply to people who take the painkillers over the long-term to help relieve arthritis.

"As yet, the specifics of the risks aren't really well-defined, but the clinical benefits of the drug are established," Martin said. "What is most clear is that when you take NSAIDs for a long period of time, there is a risk associated with them. What exactly it is, how big it is, is still not clear, but there is no completely safe NSAID."

There did not seem to be any protective effect from the drugs in terms of warding off Alzheimer's, she added. "Part of the reason we stopped was that there was some evidence of risk, and there wasn't any overwhelming evidence of benefit to counter that," Martin said.
But Nissen strongly disagreed with the findings, noting that they run counter to the results of other large trials.

"The published results of the ADAPT trial with regard to cardiovascular risk are completely unreliable," said Nissen. In his editorial, he explained that because the trial was stopped early, the data lacks the statistical power to deliver any clear verdict on either Celebrex or naproxen.
"These results cannot be used in any way to assess the relative risks of naproxen," Nissen said.

He added that he is not surprised that the premature termination of the trial in late 2004 -- coming at the height of the Vioxx debacle -- caused such a media uproar. Newspapers at the time trumpeted headlines such as "Heart Risk Seen in Naproxen" (Wall Street Journal) and "Patients, Doctors Agonize Over Risks of Painkillers", (Los Angeles Times).

"A warning was issued to the public that we now know was wrong," he said.

But Martin said she blames the media for creating a false impression of why the trial was stopped. "All of the publicity when the trial was stopped -- it was not what we intended," she said. "It's difficult in a political maelstrom of events to have the true rationale come through."

According to Martin, the trial was stopped because of data from another major trial was raising questions about the safety of Celebrex, triggering the premature closure of that arm of the ADAPT trial. When that happened, the researchers decided against continuing with the naproxen arm alone.

"We weren't seeing a risk with celecoxib (Celebrex), so it put us in a very uncomfortable position. We were imagining three years later if the adverse effects with naproxen were really real getting roundly criticized for not having stopped it earlier," she said.

Martin agreed, then, that there were political as well as safety concerns in stopping the trial.
"There was this domino effect and we felt that even though the results in and of themselves would not have led us to stop the trial, this domino effect made it necessary," she said.

Despite all the controversy, Martin feels that the trial data remains valid. She also believes it was right to have stopped the trial early. As to the safety of naproxen, Martin said there's not yet enough data to answer that question.

But Nissen said the accumulated evidence on NSAIDS supports the notion that the drug is, on the whole, safe.

"There is overwhelming evidence that of all the drugs in the class, the safest drug is naproxen," he said. "Analyses involving millions of patients have shown, consistently, that it is probably the safest drug."

Nissen doesn't believe naproxen actually protects against heart attack, however. "It's neutral," he said.

More information
There's more on NSAIDs at the U.S. National Library of Medicine.