Benefits of aspirin for treating osteoporosis

(Los Angeles CA) Researchers at the University of Southern California, School of Dentistry have uncovered the health benefits of aspirin in the fight against osteoporosis. Forty-four million Americans, 68 percent of whom are women, suffer from the debilitating effects of osteoporosis according to the National Institute of Health. One out of every two women and one in four men over 50 will have an osteoporosis-related fracture in their lifetime.

This latest study identifies aspirin's medicinal role on two fronts. In mice, the drug appears to prevent both improper bone resorption and the death of bone-forming stem cells. The findings will be published in PLoS ONE http://www.plosone.org/doi/pone.0002615 on Wednesday, July 9.

An aspirin regimen appears to help mice recover from osteoporosis in two useful ways, striking a balance between bone formation and resorption, according to Associate Professor Songtao Shi and Research Associate Takayoshi Yamaza of the USC School of Dentistry's Center for Craniofacial Molecular Biology (CCMB).

The silent disease affects both men and women. In women, bone loss is greatest during the first few years after menopause. Osteoporosis occurs when bone resorption (loss of bone) occurs too quickly or when formation (replacement) occurs to slowly.

According to Shi, the removal of the ovaries and the resulting decrease in estrogen induces osteoporosis in mice, much like the onset of the disease in post-menopausal women. It is commonly thought that T-lymphocytes, a type of immune system cell, play a pivotal part in this process by over-activating osteoclasts, the bone cells that reabsorb bone material from the skeleton. Most current osteoporosis therapies aim to curb overactive osteoclasts.

However, there seems to be another side to the T-lymphocytes', or T-cells', role in osteoporosis, Yamaza says. While the immune cells typically attack disease cells and other foreign entities, the T-cells can mistakenly attack healthy stem cells.

"After infusing the mice with T-cells, the T-cells impaired the function of bone marrow mesenchymal stem cells as well as caused osteoclast numbers to increase," he says.

The bone marrow mesenchymal stem cells, or BMMSC, differentiate to become many different cells including osteoblasts, the cells responsible for bone formation. If this processed is impaired by T-cells, bone formation cannot keep up with bone resorption caused by osteoclasts, and bone mineral density decreases – the hallmark of osteoporosis that leads to skeletal structural deterioration and fractures.

An aspirin regimen has been linked in earlier epidemiological studies to better bone mineral density, but the mechanisms of its interactions in regards to bone health had not yet been studied extensively, Shi said.

"We've shown how aspirin both inhibits bone resorption and promotes osteoblast formation," Shi says.

Another exciting aspect of the aspirin treatment is that the dose administered to the mice in order to increase their bone mineral density is the same as that of a typical human aspirin regimen when adjusted for body weight differences, he adds. While the species difference is still a factor, the results are promising.

"When we gave a large amount of aspirin to the mouse by injection, it did not work," Shi says, "but when we gave a low dose in the mice's water for a long period of time, similar to a human dosage, the bone mineral density increased."

Shi and Yamaza hope that their work will translate into new clinical strategies for osteoporosis.

"We have opened a door," Shi says. "We hope other scientists can confirm what we've found and move the treatment forward."

The use of aspirin offers hope to patients and doctors searching for a potential alternative to bisphophonates currently being used as a means of prevention and treatment for osteoporosis. This latest study opens up the possibility that aspirin some day will not only be prescribed to ward off heart disease but also osteoporosis.

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Scientists learn how food affects the brain

In addition to helping protect us from heart disease and cancer, a balanced diet and regular exercise can also protect the brain and ward off mental disorders.

"Food is like a pharmaceutical compound that affects the brain," said Fernando Gómez-Pinilla, a UCLA professor of neurosurgery and physiological science who has spent years studying the effects of food, exercise and sleep on the brain. "Diet, exercise and sleep have the potential to alter our brain health and mental function. This raises the exciting possibility that changes in diet are a viable strategy for enhancing cognitive abilities, protecting the brain from damage and counteracting the effects of aging."

Gómez-Pinilla analyzed more than 160 studies about food's affect on the brain; the results of his analysis appear in the July issue of the journal Nature Reviews Neuroscience and are available online at www.nature.com/nrn/journal/v9/n7/abs/nrn2421.html.

Omega-3 fatty acids — found in salmon, walnuts and kiwi fruit — provide many benefits, including improving learning and memory and helping to fight against such mental disorders as depression and mood disorders, schizophrenia, and dementia, said Gómez-Pinilla, a member of UCLA's Brain Research Institute and Brain Injury Research Center.

Synapses in the brain connect neurons and provide critical functions; much learning and memory occurs at the synapses, Gómez-Pinilla said.

"Omega-3 fatty acids support synaptic plasticity and seem to positively affect the expression of several molecules related to learning and memory that are found on synapses," Gómez-Pinilla said. "Omega-3 fatty acids are essential for normal brain function.

"Dietary deficiency of omega-3 fatty acids in humans has been associated with increased risk of several mental disorders, including attention-deficit disorder, dyslexia, dementia, depression, bipolar disorder and schizophrenia," he said. "A deficiency of omega-3 fatty acids in rodents results in impaired learning and memory."

Children who had increased amounts of omega-3 fatty acids performed better in school, in reading and in spelling and had fewer behavioral problems, he said.

Preliminary results from a study in England show that school performance improved among a group of students receiving omega-3 fatty acids. In an Australian study, 396 children between the ages 6 and 12 who were given a drink with omega-3 fatty acids and other nutrients (iron, zinc, folic acid and vitamins A, B6, B12 and C) showed higher scores on tests measuring verbal intelligence and learning and memory after six months and one year than a control group of students who did not receive the nutritional drink. This study was also conducted with 394 children in Indonesia. The results showed higher test scores for boys and girls in Australia, but only for girls in Indonesia.

Getting omega-3 fatty acids from food rather than from capsule supplements can be more beneficial, providing additional nutrients, Gómez-Pinilla said.

Scientists are learning which omega-3 fatty acids seem to be especially important. One is docosahexaenoic acid, or DHA, which is abundant in salmon. DHA, which reduces oxidative stress and enhances synaptic plasticity and learning and memory, is the most abundant omega-3 fatty acid in cell membranes in the brain.

"The brain and the body are deficient in the machinery to make DHA; it has to come through our diet," said Gómez-Pinilla, who was born and raised in salmon-rich Chile and eats salmon three times a week, along with a balanced diet. "Omega-3 fatty acids are essential."

A healthy diet and exercise can also reduce the effect of brain injury and lead to a better recovery, he said.

Recent research also supports the hypothesis that health can be passed down through generations, and a number of innovative studies point to the possibility that the effects of diet on mental health can be transmitted across generations, Gómez-Pinilla said.

A long-term study that included more than 100 years of birth, death, health and genealogical records for 300 Swedish families in an isolated village showed that an individual's risk for diabetes and early death increased if his or her paternal grandparents grew up in times of food abundance rather than food shortage.

"Evidence indicates that what you eat can affect your grandchildren's brain molecules and synapses," Gómez-Pinilla said. "We are trying to find the molecular basis to explain this."

Controlled meal-skipping or intermittent caloric restriction might provide health benefits, he said.

Excess calories can reduce the flexibility of synapses and increase the vulnerability of cells to damage by causing the formation of free radicals. Moderate caloric restriction could protect the brain by reducing oxidative damage to cellular proteins, lipids and nucleic acids, Gómez-Pinilla said.

The brain is highly susceptible to oxidative damage. Blueberries have been shown to have a strong antioxidant capacity, he noted.

In contrast to the healthy effects of diets that are rich in omega-3 fatty acids, diets high in trans fats and saturated fats adversely affect cognition, studies indicate.

Junk food and fast food negatively affect the brain's synapses, said Gómez-Pinilla, who eats fast food less often since conducting this research. Brain synapses and several molecules related to learning and memory are adversely affected by unhealthy diets, he said.

Emerging research indicates that the effects of diet on the brain, combined with the effects of exercise and a good night's sleep, can strengthen synapses and provide other cognitive benefits, he added.

In Okinawa, an island in Japan where people frequently eat fish and exercise, the lifespan is one of the world's longest, and the population has a very low rate of mental disorders, Gómez-Pinilla noted.

Folic acid is found in various foods, including spinach, orange juice and yeast. Adequate levels of folic acid are essential for brain function, and folate deficiency can lead to neurological disorders such as depression and cognitive impairment. Folate supplementation, either by itself or in conjunction with other B vitamins, has been shown to be effective in preventing cognitive decline and dementia during aging and enhancing the effects of antidepressants. The results of a recent randomized clinical trial indicate that a three-year folic acid supplementation can help reduce the age-related decline in cognitive function.

In patients with major depression and schizophrenia, levels of a signaling molecule known as brain-derived neurotrophic factor, or BDNF, are reduced. Antidepressants elevate BDNF levels, and most treatments for depression and schizophrenia stimulate BDNF. Here, too, omega-3 fatty acids are beneficial, as is the curry spice curcumin, which has been shown to reduce memory deficits in animal models of Alzheimer's disease and brain trauma. BDNF is most abundant in the hippocampus and the hypothalamus — brain areas associated with cognitive and metabolic regulation.

The high consumption of curcumin in India may contribute to the low prevalence of Alzheimer's disease on the subcontinent.

In humans, a mutation in a BDNF receptor has been linked to obesity and impairments in learning and memory.

"BDNF is reduced in the hippocampus, in various cortical areas and in the serum of patients with schizophrenia," Gómez-Pinilla said. "BDNF levels are reduced in the plasma of patients with major depression."

Smaller food portions with the appropriate nutrients seem to be beneficial for the brain's molecules, such as BDNF, he said.

Gómez-Pinilla showed in 1995 that exercise can have an effect on the brain by elevating levels of BDNF.

He noted that while some people have extremely good genes, most of us are not so lucky and need a balanced diet, regular exercise and a good night's sleep.

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