Bone Loss: Perforated bone tissue from too little sugar

Date:
October 9, 2020
Source:
Norwegian University of Science and Technology
Summary:
Bone marrow cancer is currently an incurable disease that affects
about 400 people in Norway every year. One Norwegian researcher
has now found an important reason for bone destruction in people
with this disease.



FULL STORY ========================================================================== Could something as simple as a certain type of sugar water be medicine
for perforated bones, and even bone marrow cancer itself?

========================================================================== Inside our bodies are some jellyfish-like cells that actually eat away
at our bones. Every year, they eat about ten per cent of the bone mass
in our body.

Fortunately, other cells usually follow and build up new bone.

We undergo a kind of continuous remodelling and repair that enables most
of us to traipse around with steel in our legs and arms.

In people with bone marrow cancer, the bone-eating cells run amok. They
become too numerous and eat too much. The bone-building gang doesn't have
time to rebuild the bone mass, despite overtime and long shifts. Bone
tissue gets gobbled up.

Many people with bone marrow cancer often end up with perforated bones,
a condition that is very painful to live with. They sometimes experience collapsed vertebrae or suffer broken bones just by turning in bed.

For decades, scientists around the world have been scratching their
heads and wondering what the cause could be. Various theories have been launched, but researchers have not reached a consensus on the main cause.



==========================================================================
Bone marrow cancer remains an incurable disease so far. Available
treatments can prolong life, but not cure the disease.

Now Standal and her research group at the Centre of Molecular Inflammation Research (CEMIR) at the Norwegian University of Science and Technology
(NTNU) have discovered a piece of the puzzle that looks very promising.

They have come to the conclusion that the cause of the bone destruction is
too little sugar. We're not talking about the sugar we eat in our cakes
and biscuits, but sugar that resides in a substance that is important
for the immune system.

To get to the bottom of how sugar is related to bone loss, we need to get
into the bone marrow. This is the soft cavity that inside all our bones.

Within the bones are plasma cells. When bacteria or viruses enter
the body, the plasma cells begin their job of getting rid of the
invaders. Antibodies are produced which are sent via the blood, ready
to do battle.



==========================================================================
So far so good, but in people with bone marrow cancer, far too much
of one type of antibody is produced. It's going amok here, too. The
antibody that the cancer makes is also completely useless. It doesn't
knock out either the cold or the flu but just takes up too much space
and displaces other types of antibodies.

"I thought simply. If people with bone marrow cancer have too much of the antibody and too many bone-eating cells, then they must be connected,"
Standal says.

The search for an answer gobbled a lot of her working hours for almost
five years. The hard work was fortunately not in vain, and has led to
a completely new and fundamental understanding.

This is how Standal arrived at the answer: The vast majority of patients
with bone marrow cancer develop perforated bones, but not all. Standal
asked nicely, and received samples from patients with bone loss. She
also took samples from patients without this kind of bone loss.

The researchers extracted antibodies from the samples and cultured
bone-eating cells in the laboratory.

When Standal placed the bone-eating cells into the antibody of the
patients with bone perforations, she discovered that the number of
bone-eating cells increased.

When she put the bone-eating cells into the antibody of the patients
without bone perforations, she discovered that the number of bone-eating
cells did not increase.

"Why that was the case became the next interesting thing to figure out," Standal says.

The antibody carries a type of sugar that "decorates" it, in a way. The
sugar has an effect on how the antibody works. Standal found her way
to Manfred Wuhrer at the Center for Proteomics and Metabolomics of the
Leiden University Medical Center in the Netherlands. He is a specialist
in this type of sugar, and Standal sent the samples to him.

He found that individuals with bone loss were missing two sugar molecules
at the end of a long chain inside the antibody.

"There was too little sugar," says Standal.

But this answer wasn't sufficient, either.

Although a difference was detected between the two groups, the researchers could not confirm that the missing sugar molecules were the reason
patients developed more bone-eating cells. Several further experiments
had to be conducted.

The research team went to the lab and put more sugar on the antibody. This
did not lead to more bone-eating cells. Standal also did the opposite,
removing sugar from the antibody. This did lead to more bone-eating cells.

The researchers then had sufficient test results to show that too little
sugar can be decisive for the number of bone-eating cells. But this is
not enough in medical research -- at least not if the goal is to use
the knowledge to make medicine for humans.

The next step involved animal experiments with mice that have bone marrow cancer. The mice were divided into two groups and were given two different types of sugar water. In theory, one type of sugar water would lead to
more sugar on the antibody.

"The theory actually worked. The mice that received this type of sugar
water had smaller perforations in their bone tissue. They also developed
less cancer," says Standal.

Now she has to carry out more animal experiments to move forward on the
path towards a treatment that can give patients with bone marrow cancer
a better life.

"I think it might be realistic to try this on a small group of patients
in four to five years," says Standal.


========================================================================== Story Source: Materials provided by Norwegian_University_of_Science_and_Technology. Original written by Anne
Sliper Midling. Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Therese Standal, Manfred Wuhrer, Tobias Slo/rdahl, Anders Waage,
Anders
Sundan, Glenn Buene, Kristine Misund, Stephanie Holst, Albert Bondt,
Tonje Marie Vikene Nedal, Siv Helen Moen, Zejian Zhang, Vlado
Kovcic, Marita Westhrin. Monoclonal immunoglobulins promote bone
loss in multiple myeloma. Blood, 2020; DOI: 10.1182/blood.2020006045 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/10/201009094952.htm

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