Finding Healing Agents for osteoporosis can damage bones

Millions of people in this country suffer from the widespread disease osteoporosis. In this disease of the skeleton, the bones lose strength faster, making them break faster and can be caused by small shocks severe fractures. As a hopefuls in the therapy are drugs that regulate the signaling substance sclerostin. Many pharmaceutical companies are already testing these in costly patient trials. But now researchers at the University Hospital Münster have found out that the signal substance apparently can cause damage and even aggravate other complaints.
Common disease Osteoporosis occurs especially at an older age
Osteoporosis is the most common bone disease, affecting about eight million people in this country alone. The so-called "bone loss" occurs especially at an older age, more than 25% of women after the menopause get sick. Characteristic of the disease is that the bone mass decreases more than normal, which adversely affects the structure and function of the bones. At the beginning, those affected hardly have any complaints. In the further course, however, the skeletal changes lead to seemingly inexplicable bridges, which can be very painful and lead to consequential damage, such as damage. lead a round back.

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Signaling Sclerostin inhibits bone formation
For the treatment of the disease are already a number of different drugs available. In research, the signaling substance sclerostin (SOST) is considered a promising starting point for new treatment options. This is a protein predominantly formed in the bone, which inhibits the bone-forming function of the so-called "osteoblasts".

As a result, agents that regulate this substance may provide new hope for many sufferers and are therefore being explored in several large pharmaceutical trials involving hundreds of patients.
But apparently there is also a flip side of the coin. Because scientists from the University Hospital Münster have now recognized by a study with mice, that these drugs of health may also harm. Thus, it is possible that an existing rheumatoid arthritis will be "significantly strengthened," according to the researchers in the journal "Science Translational Medicine". A sclerostin-directed treatment is therefore "probably not recommended for patients with inflammatory joint disease," the experts write.

Researchers had assumed the opposite conclusion
For the scientists a big surprise because they had actually assumed the exact opposite and had expected that the substances have a soothing effect on rheumatoid arthritis. The researchers came to this after discovering larger amounts of sclerostin in the synovial surface of these patients than those with noninflammatory forms of arthritis. If the signaling substance could be blocked, this could possibly also be a regulation of joint inflammation, so the idea.

But in the mice experiment it finally turned out quite differently, because sclerostin inhibitors were used, even increased the bone loss. However, this only applied to the animals with a so-called "TNF-alpha-driven arthritis". Tumor necrosis factor (TNF-alpha for short) is also a signaling agent of the immune system, which plays an important role in local and systemic inflammation and promotes bone resorption in rheumatoid arthritis. In mice whose disease was not affected by TNF-alpha, the drugs against sclerostin had little effect or even improved the symptoms, the researchers explain.

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

Next, the exact clarification must be made on the basis of further investigations. For the pharmaceutical industry, this could result in a major setback. According to Christian Kasperk from the Heidelberg University Medical Center, leading corporations have already invested many millions of euros in the development of sclerostin inhibitors. "Experts had hoped for the widest possible range of active ingredients without any compromising aspects," the expert told dpa. But with the new study, a finger is now painfully placed in the wound.

Accordingly, osteoporosis is caused in many cases by chronic inflammatory diseases (for example of the gastrointestinal tract) in which TNF messenger substances play a role. "Therefore, the study result probably means a serious limitation of the hoped-for broad application," Kasperk continues. In addition, even before the current study would have indicated negative aspects. Since 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 stay with well-tried medications
Instead of experimenting, many osteoporosis patients should therefore better rely on proven remedies whose potential side effects are known through decades of research. "What is new and expensive does not have to be better," says the doctor. "For many new drugs, we have no idea whether we do not also mischief." Therefore, it was a "stroke of luck" that the possible consequences of sclerostin inhibitors now long before the approval came to light.
Since sclerostin is mainly produced in the bones, experts have not yet assumed that it has other effects in the body, write Frank Rauch of McGill University in Montreal and Rick Adachi of McMaster University in Hamilton in a commentary to the study.

However, the new investigation clearly shows that the signal substance can do more than slow down bone growth. Although the results from the mouse studies could not be directly transferred to humans, the potential clinical significance of the Canadian scientists was still great. Because many osteoporosis patients have concomitant diseases that could influence the action of sclerostin. (Nr)