Searching for a cure: Active substances against osteoporosis can damage bones

Searching for a cure: Active substances against osteoporosis can damage bones

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Millions of people in this country suffer from the widespread disease osteoporosis. With this disease of the skeleton, the bones lose their strength more quickly, which means that they break faster and serious fractures can result from small vibrations. Active substances that regulate the signal substance sclerostin are considered to be hope in therapy. Many pharmaceutical companies are already testing these in costly patient studies. But now researchers at the University Clinic in Münster have found that the signal substance can obviously also cause damage and even intensify other complaints.

A widespread disease, osteoporosis, occurs primarily at an older age
Osteoporosis is the most common bone disease that affects around eight million people in Germany alone. The so-called "bone loss" occurs especially in older age, more than 25% of women after menopause get it. It is characteristic of the disease that the bone mass decreases more than normal, which has an adverse effect on the structure and function of the bones. At the beginning, those affected have hardly any complaints. In the further course, however, the changes in the skeleton lead to apparently inexplicable bridges, which can be very painful and lead to consequential damage such as lead a rounded back.

Sclerostin inhibits bone formation
A number of different medications are already available to treat the disease. In research, the signal substance sclerostin (SOST) is considered a promising starting point for new treatment options. This is a protein primarily formed in the bones, which inhibits the bone-forming function of the so-called "osteoblasts".

Active ingredients that regulate this substance could accordingly offer new hope for many sufferers and are therefore already being researched in several large pharmaceutical studies with hundreds of patients.
But apparently there is also a flip side to the coin. Because a study with mice has now shown that scientists from the University Hospital of Münster have recognized that these active ingredients can also be harmful to health. According to the researchers in the journal Science Translational Medicine, it is possible that existing rheumatoid arthritis will be “significantly increased”. A treatment aimed at Sclerostin is therefore “probably not recommended” for patients with inflammatory joint disease, the experts continue.

Researchers had assumed the opposite
A great surprise for the scientists because they had actually assumed the opposite and expected that the substances would have a soothing effect even in rheumatoid arthritis. The researchers came up with this after discovering greater amounts of sclerostin in the inner skin of these patients than in those with non-inflammatory forms of arthritis. If the signal substance could be blocked, regulation of the inflammation of the joints might also be conceivable, so the idea.

But in the mouse experiment it turned out quite differently, because sclerostin inhibitors were used, and bone loss was even increased. However, this only applied to animals with so-called “TNF-alpha-driven arthritis”. The tumor necrosis factor (TNF-alpha for short) is also a signal substance of the immune system, which plays an important role in local and systemic inflammation and promotes bone loss in rheumatoid arthritis. In mice whose disease was not influenced by TNF-alpha, the active substances against sclerostin had little effect or even improved the symptoms, the scientists further explain.

New study will lead to restrictions
From this it can be concluded that only inflammatory reactions in which TNF-alpha is involved are apparently affected, study author Thomas Pap told the news agency "dpa". "The effect can be determined relatively strictly on this one inflammation factor."

The next step, therefore, is to make a precise assessment based on further investigations. This could result in a severe setback for the pharmaceutical industry. According to Christian Kasperk from Heidelberg University Medical Center, leading corporations have already invested many millions of euros in the development of sclerostin inhibitors. "One had hoped for the broadest possible use of active ingredients without compromising aspects," the expert told the "dpa". But with the new study, a finger is now painfully put in the wound.

In many cases, osteoporosis is caused by chronic inflammatory diseases (e.g. the gastrointestinal tract), in which TNF messengers play a role. "The study result therefore probably means a serious restriction of the widespread use hoped for," continues Kasperk. In addition, negative aspects had already been hinted at before the current study. Because sclerostin is also formed in the vessel walls, a blockage of the signal substance could possibly stimulate the calcification of the vessels, Kasperk points out.

Better to stay with tried and true medication
Instead of experimenting, many osteoporosis patients should therefore rely on proven means, the possible side effects of which have been known through decades of research. "What is new and expensive does not have to be better," says the doctor. "With many new active ingredients, we still have no idea whether we are doing nonsense with them." It is therefore a "stroke of luck" that the possible consequences of sclerostin inhibitors have come to light long before approval.
Since sclerostin is mainly formed in the bones, experts have not yet assumed that it has other effects in the body, wrote Frank Rauch from McGill University in Montreal and Rick Adachi from McMaster University in Hamilton in a commentary on the study.

However, the new investigation clearly shows that the signal substance can do more than slow down bone growth. The results of the mouse tests cannot be transferred directly to humans, but the potential clinical significance is great for the Canadian scientists. Because many osteoporosis patients have comorbidities that could influence the effect of sclerostin. (Nr)

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  1. Osbeorht

    cognitive topic

  2. Wekesa

    the first is the best

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