Bone loss is another hidden pathology caused by malaria infection

June 2, 2017, Osaka University
Malaria induces chronic bone loss due to sustained accumulation of Plasmodium products even after the cure of malaria disease. Credit: Osaka University

Malaria caused by Plasmodium parasites is a life-threatening infectious disease that kills at least half a million people annually while causing over 200 million new infections. In some cases, complications can quickly develop such as cerebral malaria, respiratory distress and severe anemia, often leading to death. The majority of patients recover from disease, however, there is increasing evidence to suggest that survivors experience long-term 'hidden' pathologies due to infection that are as yet poorly defined.

Now, the Laboratory of Malaria Immunology Team at the Immunology Frontier Research Center (IFReC), Osaka University, headed by Professor Cevayir COBAN, have used mouse malaria models to show that robust immune activation and invasion of parasite by-products into the bone marrow during and after leads to an adverse balance in -a process usually tightly controlled- by bone forming osteoblasts and bone resorbing osteoclasts.

"Even after a one time malaria infection (it does not matter if the disease is completely cured or chronic low level infection continues), substantial chronic occurs", Dr. Coban, corresponding author of the study, says. Michelle Lee, a PhD candidate and the first author of the study explains, "We found that Plasmodium products continuously accumulate in the niche which turns the bone noticeably black in color, and results in it being "eaten-up" by bone resorbing cells known as osteoclasts, eventually disrupting bone homeostasis". These products, including the major malarial by-product hemozoin, malarial proteins and as yet undefined virulence factors, induce MyD88-dependent inflammatory responses in osteoclast and osteoblast precursors, leading to increased RANKL expression (a key molecule inducing osteoclast differentiation), and over-stimulation of osteoclastogenesis favoring (Figure 1)". The Coban Team infected mice with a mutant Plasmodium parasite producing less by-products such as hemozoin, and discovered in this case bone loss did not occur, thereby confirming their findings.

Dr. Coban explains, "Although chronic inflammatory conditions are known to facilitate , our study -for the first time- shows that malaria can do the same thing, with hallmark "signatures" left in the bone tissue, a very unique feature of malaria infection. One may think that the infection has been completely cured by anti-malarial treatment, and be feeling fully recovered, however, sustained long-term accumulation of parasite by-products leave the bone in a state of chronic inflammation, leading to long term bone loss. This is particularly worrisome in the young of age, where it may cause growth problems and osteoporotic, fragile bones."

Importantly, the study shows that there is a simple way to reverse the side effects of malaria infection on bone. Oral supplementation with alfacalcidol, a vitamin D3 analog, could completely prevent bone loss. Therefore, anti-malarials coupled with bone therapy may be beneficial in improving health in malaria-infected individuals.

Explore further: Choloroquine reduces formation of bone resorbing cells in murine osteoporosis

More information: M.S.J. Lee el al., "Plasmodium products persist in the bone marrow and promote chronic bone loss," Science Immunology (2017). immunology.sciencemag.org/look … 6/sciimmunol.aam8093

Related Stories

Choloroquine reduces formation of bone resorbing cells in murine osteoporosis

December 9, 2013
Bone homeostasis requires precise balance between deposition of new bone by osteoblasts and resorption of old bone by osteoclasts. Bone diseases, including osteoporosis and rheumatoid arthritis, are the result of increased ...

HIV-infected young males have higher rates of bone loss than females

March 10, 2016
Accumulating evidence suggests that rates of low bone mass are greater in HIV-infected males than in females. Researchers led by Grace Aldrovandi, MD, chief of the Division of Infectious Diseases at Children's Hospital Los ...

Study offers new hope for treatment of osteoporosis

March 22, 2016
An international study by The University of Western Australia may lead to a new treatment for osteoporosis caused by age-related bone loss in elderly women.

Study shows how atherosclerosis and osteoporosis are linked

May 6, 2016
Patients with atherosclerosis—the buildup of cholesterol and fat in arteries—are at a higher risk of osteoporosis. A new study published in the American Journal of Physiology—Endocrinology and Metabolism shows how the ...

Study provides insights on optimal treatment of Paget's disease of bone

February 8, 2017
In a study of patients with Paget's disease of bone—a common skeletal disorder that can lead to bone deformity, fractures, osteoarthritis, and bone pain—long-term intensive bisphosphonate therapy conferred no clinical ...

Identification of a molecule linking bone loss and bone formation

August 1, 2013
Bone integrity requires skeletal remodeling, which involves both bone formation and resorption. It has been previously shown that the formation of new bone is triggered by degradation of older bone. However, it is unknown ...

Recommended for you

A synthetic approach to helping the immune system thwart infections

February 22, 2018
Yale researchers have developed a set of synthetic molecules that may help boost the strength of a key, virus-fighting protein.

Scientists find molecular link between Vitamin A derivative and mouse intestinal health

February 22, 2018
New research shows that all-trans-retinoic acid (atRA), the active form of vitamin A, regulates immune system responses in the mouse intestine by controlling expression of the protein HIC1 in cells known as innate lymphoid ...

Animal study shows how to retrain the immune system to ease food allergies

February 21, 2018
Treating food allergies might be a simple matter of teaching the immune system a new trick, researchers at Duke Health have found.

'Icebreaker' protein opens genome for T cell development, researchers find

February 20, 2018
Almost all cells in the human body have identical DNA sequences, yet there are 200-plus cell types with different sizes, shapes, and chemical compositions. Determining what parts of the genome are read to make protein and ...

Preventive treatment for peanut allergies succeeds in study

February 20, 2018
The first treatment to help prevent serious allergic reactions to peanuts may be on the way. A company said Tuesday that its daily capsules of peanut powder helped children build tolerance in a major study.

Infection site affects how a virus spreads through the body

February 20, 2018
A person is more likely to get infected by HIV through anal intercourse than vaginal, but no one knows quite why. A new study by scientists at the Gladstone Institutes shows that infection sites could affect the immune system's ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.