Bone-loss discovery points to new treatment for Rheumatoid arthritis

Bone-loss discovery points to new treatment for osteoporosis


Kodi Ravichandran (left) consults with Sanja Arandjelovic at the University of Virginia School of Medicine. CREDIT Dan Addison | UVA Communications

A new discovery about osteoporosis suggests a potential treatment target for that brittle-bone disease and for bone loss from rheumatoid arthritis.

The findings from University of Virginia School of Medicine researchers and their collaborators help explain why specialized bone cells called osteoclasts begin to break down more bone than the body replaces. With more research, scientists one day may be able to target that underlying cause to prevent or treat bone loss.

The discovery also suggests an answer for why some previous attempts to develop osteoporosis treatments produced disappointing results.

“Bone degradation and subsequent repair are fine-tuned through complex interactions between the cells that degrade the bone, osteoclasts, and those that produce new bone matrix. Simple elimination of osteoclasts is, therefore, not always the best approach to treat pathologic bone loss. Instead, we found a ‘signaling node’ in osteoclasts that regulates their function in degrading the bone but doesn’t reduce osteoclast numbers,” said researcher Sanja Arandjelovic, PhD, of UVA’s Department of Medicine and UVA’s Carter Immunology Center.

Researcher Kodi Ravichandran, PhD, chairman of UVA’s Department of Microbiology, Immunology and Cancer Biology and director of UVA’s Center for Cell Clearance, noted the potential of the findings to inform efforts to develop better treatments for osteoporosis: “In this study,” he said, “we identified previously unappreciated factors that contribute to osteoclast function that is truly exciting and opens up new avenues to pursue.”

Understanding Bone Loss

Osteoporosis affects more than 200 million people around the world, and it causes bone fractures in 1 in 3 women and 1 in 5 men over age 50. Bone loss is also seen in rheumatoid arthritis, a painful inflammatory condition that affects up to 1% of people, including more than 1.3 million Americans.

Scientists are eager to understand what causes this bone loss, and to develop new ways to treat and prevent it. Arandjelovic, Ravichandran and their collaborators have found an important contributor, a cellular protein called ELMO1. This protein, they found, promotes the activity of the bone-removing osteoclasts. While osteoclasts may seem like ‘bad guys’ because they remove bone, they are critical for bone health, as they normally remove just enough to stimulate new bone growth. The problem arises when the osteoclasts become too aggressive and remove more bone than the body makes. Then bone density suffers and bones grow weaker.

This excessive bone degradation is likely influenced by genetic factors, the researchers say. They note that many of the genes and proteins linked to ELMO1 have been previously associated with bone disorders and osteoclast function.

Treating Osteoporosis and Rheumatoid Arthritis

Encouragingly, the researchers were able to prevent bone loss in lab mice by blocking ELMO1, including in two different models of rheumatoid arthritis. That suggests clinicians may be able to target the protein in people as a way to treat or prevent bone loss caused by osteoporosis and RA, the researchers say.

They note that prior efforts to treat osteoporosis by targeting osteoclasts have had only mixed success, and they offer a potential explanation for why: Osteoclasts not only remove bone but play a role in calling in other cells to do bone replacement. As such, targeting ELMO1 may offer a better option than simply waging war on the osteoclasts.

“We used a peptide to target ELMO1 activity and were able to inhibit degradation of the bone matrix in cultured osteoclasts without affecting their numbers,” Ravichandran said. “We hope that these new osteoclast regulators identified in our study can be developed into future treatments for conditions of excessive bone loss such as osteoporosis and arthritis.”

Potential breakthrough for osteoporosis announced

Osteoporosis

Osteoporosis

“Bone could be regrown to treat osteoporosis after breakthrough,” The Daily Telegraph reports. This headline follows the development of a new drug that may increase bone formation, which could potentially combat osteoporosis. But this has only been tested in the lab so far and has not yet been proven to work in humans.

The researchers took inspiration from a class of drugs called thiazolidinediones, which are used to treat type 2 diabetes by improving sensitivity to the hormone insulin.

A side effect of these types of drugs is they reduce the number of stem cells that turn into bone-producing cells. The researchers turned this side effect on its head by developing a drug that appears to have the opposite effect, increasing the number of stem cells that develop into bone-producing cells. Another potential positive is that these early results in mice suggest the drug does not appear to have a negative effect on insulin sensitivity.

The drug has so far been tested on human stem cells in the laboratory and in mice over 21 days to look for side effects. While it could potentially regrow bone lost through conditions such as osteoporosis, this has not yet been demonstrated. The drug increased the number of human cells that turned into bone-forming cells, but bone production was not assessed in the mice.

The researchers say their results are promising enough to commence further animal studies. This process takes time, and not all drugs get through these tests. If the drug does prove to be successful and safe enough in animal studies, it would then progress to human trials.

Where did the story come from?

The study was carried out by researchers from the Scripps Research Institute in Florida and the University of Adelaide. It was funded by the US National Institutes of Health, the Abrams Charitable Trust, and the Klorfine Family Fellowship. The study was published in the peer-reviewed medical journal, Nature Communications.

The Daily Telegraph incorrectly reported that the drug “already exists, because it [is] used in the treatment of diabetes to regulate insulin production”. This is not the case – the drug used to treat diabetes causes a reduction in bone formation. The drug in development has been designed to have the opposite effect.

The Telegraph also said the drug “increased the rate of bone grown in mice”. While the researchers may now have progressed to testing this, it was not reported to be the case in this study. Even if these tests have now been done, they would not have undergone peer review and publication yet, so we can’t judge how robust they are.

What kind of research was this?

This was a combination of laboratory experiments on human stem cells in the laboratory and in mice.

Peroxisome proliferator-activated receptor gamma (PPAR?) is a receptor present on stem cells, the immature cells from bone marrow that can become different types of cells.

Receptors are protein molecules that react to specific chemical signals, much in the way a lock can be opened by a key.

Stimulation of PPAR? causes the stem cells to turn into adipocytes (fat cells) rather than osteoblasts (the cells involved in bone formation).

A class of drugs called thiazolidinediones, or glitazones, target PPAR? to improve insulin sensitivity for people with type 2 diabetes. A side effect of this drug is that fewer osteoblasts are formed.

A chemical compound called SR1664 develops, which partially blocks the receptor, still improving the insulin sensitivity but without reducing the number of stem cells that turn into osteoblasts.

From this, the researchers have developed another chemical compound called SR2595, which stimulates the PPAR? receptor to have the opposite effect, causing the stem cells to turn into osteoblasts.

What did the research involve?

The researchers carried out various experiments to look at the structure of PPAR? and how it interacts with SR1664. They used this information to help them design SR2595.

Human stem cells grown in the laboratory were exposed to SR2595, and researchers looked at whether this made the cells become bone-forming osteoblasts.

Mice were given the drug for 21 days to find out whether the SR2595 would worsen insulin sensitivity. The researchers assessed the level the drug reached in the mice’s bodies and looked at their insulin sensitivity, as well as food consumption and body weight.

What were the basic results?

The number of human stem cells that became osteoblasts increased when they were treated with SR2595 in the lab.

Mice given SR2595 did not have any change in insulin sensitivity, fasting insulin levels, food consumption or body weight.

How did the researchers interpret the results?

The researchers concluded that the results on SR2595 were sufficient to now conduct further animal experiments.

Conclusion

This research has shown that a new chemical compound called SR2595 appears to stimulate human stem cells in the laboratory to develop into bone-forming cells rather than fat cells.

It is not yet known whether this would occur in humans or other mice. Even if this is the case, it is also not known whether the increased numbers of bone-forming cells would have the desired effect of increasing bone growth for people with osteoporosis.

Early results from mice indicate the compound may not have a negative effect on insulin sensitivity, but this was only assessed over a period of 21 days in seven-week-old mice. Further animal studies of longer duration will be required to evaluate whether the drug works, and then whether it is safe.

While weakening of the bones is often an inevitable part of ageing, there are still steps you can take to improve your bone health. The recipe for strong bones is a healthy balanced diet that includes calcium, exposure to summer sunlight for most of our vitamin D, and regular exercise, as well as avoiding certain risk factors, such as smoking and too much alcohol.

Read more about bone health.

Osteoporosis – what are the causes of osteoporosis?




Osteoporosis

Osteoporosis

Osteoporosis causes bones to become less dense and more fragile. Some people are more at risk than others.




Bones are at their thickest and strongest in your early adult life and their density increases until your late 20s. You gradually start losing bone density from around the age of 35.

This happens to everyone, but some people develop osteoporosis and lose bone density much faster than normal. This means they’re at greater risk of a fracture.

Risk groups

Osteoporosis can affect men and women. It’s more common in older people, but it can also affect younger people.

Women

Women are more at risk of developing osteoporosis than men because the hormone changes that occur in the menopause directly affect bone density.

The female hormone oestrogen is essential for healthy bones. After the menopause (when monthly periods stop), oestrogen levels fall. This can lead to a rapid decrease in bone density.

Women are at even greater risk of developing osteoporosis if they have:

an early menopause (before the age of 45)

hysterectomy (removal of the womb) before the age of 45, particularly when the ovaries are also removed

absent periods for more than six months as a result of overexercising or too much dieting

Men

In most cases, the cause of osteoporosis in men is unknown. However, there’s a link to the male hormone testosterone, which helps keep the bones healthy.

Men continue producing testosterone into old age, but the risk of osteoporosis is increased in men with low levels of testosterone.




In around half of men, the exact cause of low testosterone levels is unknown, but known causes include:

the use of certain medications, such as oral corticosteroids

alcohol misuse

hypogonadism (a condition that causes abnormally low testosterone levels)

Risk factors

Many hormones in the body can affect the process of bone turnover. If you have a condition of the hormone-producing glands, you may have a higher risk of developing osteoporosis.

Hormone-related conditions that can trigger osteoporosis include:

hyperthyroidism (overactive thyroid gland)

disorders of the adrenal glands, such as Cushing’s syndrome

reduced amounts of sex hormones (oestrogen and testosterone)

disorders of the pituitary gland

hyperparathyroidism (overactivity of the parathyroid glands)

Other risk factors

Other factors thought to increase the risk of osteoporosis and broken bones include:

a family history of osteoporosis

a parental history of hip fracture

body mass index (BMI) of 19 or less

long-term use of high-dose oral corticosteroids (widely used for conditions such as arthritis and asthma), which can affect bone strength

having an eating disorder, such as anorexia or bulimia

heavy drinking and smoking

rheumatoid arthritis

malabsorption problems, as experienced in coeliac disease and Crohn’s disease

some medications used to treat breast cancer and prostate cancer which affect hormone levels

long periods of inactivity, such as long-term bed rest

Pomegranate: superfood or fad?




Pomegranate: superfood or fad?

Pomegranate: superfood or fad?




Pomegranate and its distinctive ruby-red jewel-like seeds have been used for medicinal purposes for thousands of years.

The Middle Eastern fruit is claimed to be effective against heart disease, high blood pressure, inflammation and some cancers, including prostate cancer.

Pomegranate is a good source of fibre. It also contains vitamins A, C and E, iron and other antioxidants (notably tannins).

We’ve teamed up with the British Dietetic Association (BDA) to examine whether the health claims made about the fruit are supported by the evidence.

The evidence on pomegranates

Can pomegranate strengthen bones?

2013 study found evidence that pomegranate strengthened bones and helped prevent osteoporosis. The catch was the study involved mice, not humans.




While the biology of mice and humans are surprisingly similar, we can never be sure that these results will be applicable to us.

Does pomegranate juice slow prostate cancer progress?

One small study from 2006 found that drinking a daily 227ml (8oz) glass of pomegranate juice significantly slowed the progress of prostate cancer in men with recurring prostate cancer. This was a well-conducted study, but more are needed to support these findings.

more recent study from 2013 looked at whether giving men pomegranate extract tablets prior to surgery to remove cancerous tissue from the prostate would reduce the amount of tissue that needed to be removed. The results were not statistically significant, meaning they could have been down to chance.

Can pomegranate reduce carotid artery stenosis?

A good-quality study from 2004 on patients with carotid artery stenosis (narrowed arteries) found that a daily 50ml (1.7oz) glass of pomegranate juice over three years reduced the damage caused by cholesterol in the artery by almost half, and also cut cholesterol build-up. However, these effects are not clearly understood and the study did not say what the results mean for conditions such as stroke.

Is heart disease prevented by pomegranates?

A well-conducted trial from 2005 on 45 patients with coronary heart disease demonstrated that a daily 238ml (8.4oz) glass of pomegranate juice administered over three months resulted in improved blood flow to the heart and a lower risk of heart attack. The study did not say what the results mean for conditions such as heart attacks, and with such a small trial the positive results reported could be down to chance.

The dietitian’s verdict on pomegranates

Alison Hornby, a dietitian and BDA spokesperson, says the evidence around the health benefits of pomegranates are inconclusive.

She says: “Research suggests there may be a benefit, but we’ve not shown it yet. The studies that have found an improvement in existing health conditions were very small and more investigation into the role pomegranate plays in these improvements is needed.

“A 150ml glass of pomegranate juice counts as one of your 5 A Day. Make sure to avoid brands with added sugar. You could also add pomegranate seeds to cold dishes and salads. It’s a healthy and appetising way to increase the nutritional value of your meal.”

Joint Pain from Osteoporosis and Arthritis – some tips

Joint Pain

Joint Pain




Two of the most common joint-related diseases include Osteoporosis and Arthritis. While these two are very common, they attack the joints in different ways and each has its own risks and symptoms. The NIH Osteoporosis and Related Bone Diseases National Resource Center provides a more detailed explanation of both of these conditions. They explain Osteoporosis as a condition where bone-density decreases and increases the risk of fracturing. There are around 53 million people within the United States with diagnosed Osteoporosis or, at least, at high risk due to a low bone-density in their body. They explain Arthritis as a general term that medical professionals use for various conditions that affect the tissue around joints, as well as the joints directly. The two most popular types of Arthritis include Osteoarthritis and Rheumatoid arthritis.

Arthritis is also known to cause several disabilities when it comes to normal daily activities. Patients with arthritis have reported difficulty grasping small objects, sitting for more than 2 hours, carry objects that weighs more than 10 pounds, stand on their feet for more than 2 hours and even difficulty when trying to bend or kneel. Around 9.8% of American citizens have reported that they suffer from Arthritis and have activity limitations due to the condition, as recorded by Centers for Disease Control and Prevention.

Treatments For Joint Problems

 




There are numerous types of treatments available for joint problems. Joint problems do not necessarily mean a joint-related disease such as Osteoporosis or Arthritis. Many people who suffer from joint pain, stiffness and a decrease in flexibility within their joints does not have any of these diseases, but are at risk of developing such a disease should the problems be ignored.

NHS declares several symptoms that are commonly associated with Arthritis conditions. Should patients experience these symptoms, they are advised to seek a professional diagnosis from their doctor. Treatment in order to avoid further development of these problems are also highly recommended. Some of the most common conditions of Arthritis include pain and tenderness in joints, joint stiffness, joint inflammation, limited flexibility of joints, warm and red skin around joint areas and weakness.

With Rheumatoid arthritis being one of the most commonly diagnosed forms of arthritis, WebMD recommends several treatment options that can be used to prevent further damage from occurring, to minimize the effects of the disease and to treat the damage already done. Popular treatments include prescription medication, rest, physical exercise, arthritis aids, stress management, consuming foods that are known to reduce inflammation, avoiding foods that are known to cause inflammation, going for physical therapy, frequent visits to your doctor for checkups and also surgery should the condition be severe.

Permanently Increase Joint Functionality

 

While medicated treatments, regular exercise and several other tips are recommended to treat problems such as arthritis, many of these treatments will only have immediate affects without providing a longer lasting benefit. There are, however, several alternative options available for individuals suffering from joint conditions that involves pain, inflammation, stiffness and movement limitations. When looking at these alternative options, several additional long-term benefits can usually be expected that would help reduce the risk of damaging joints further, while also improving the condition joints are in when consuming these alternative options.

Flexoplex is one of the best alternatives on the market at the moment. The solution is a scientifically formulated substance that provides several benefits to any individual suffering from joint issues, whether they have been diagnosed with a joint disease or are simply experiencing symptoms that might put them at risk of developing such a disease. The supplement provides numerous benefits, including:

  • Assists with rebuilding and repairing damaged joints
  • Assists with joint stiffness by properly lubricating joints
  • Assists with pain management
  • Assists with reducing inflammation in and around affected joint areas
  • Assists with improving joint flexibility in order to provide an improved range of motion
  • Assists with enhancing joint mobility

The supplement has been formulated by medical professionals and only include potent ingredients that have been researched and proven to provide effective support for joints, including joint related diseases. The formula contains a wide variety of natural ingredients that assists the body with repairing damage and improving the overall condition of the joints. Some of the most vital ingredients include Rutin, which reduces inflammation, Cat’s Claw bark, which soothes away pain, and Hyaluronic acid to improve joint movement. A combination of Glucosamine sulfate and Chondroitin sulfate also provides an effective repair element that gets to work by rebuilding bones that have been damaged and worn out. Added MSM also provides effected relieve of discomfort and muscle aches associated with osteoarthritis.

Conclusion

 

Considering the many options available for joint-related conditions, patients should always ensure they weigh all their options. While many of the medication that can be obtained from a doctor provides effective relieve of the symptoms associated with arthritis and other related diseases, many of them also come with several risks and only a few assists with repairing the damage that has already been done. Taking a supplement such as Flexoplex can provide a patient with more benefits due to the permanent improvement in joint flexibility, mobility and functionality.

 

Author Bio:

Annie Lizstan works as a health and beauty consultant for online websites and an independent researcher by profession. She had completed her studies from university of Arizona and live in Wasilla, Alaska. She always like to explore her ideas about health, fitness and  beauty . In her recent period ,she got an opportunity to explore on under eye bags .She has experience researching as a passion as well as profession. You can also connect with her on Facebook, Twitter and Pinterest.