Degenerative Changes Identified in Spinal Discs and Reversed With Drug Cocktail In Diabetic Mice
The study, led by James C. Iatridis, PhD, was published in the journal PLOS ONE on May 17.
Degenerative changes to the area of the spinal disc that absorbs most of shock felt with compression, known as the nucleus pulposus, has been demonstrated and reversed in a diabetic mouse model, according to a new study led by researchers at the Icahn School of Medicine at Mount Sinai. The study, published today in the journal PLOS ONE, reinforces the importance of diabetes in inducing degenerative changes to the vertebrae and intervertebral discs, and it is the first study to demonstrate that these changes can be slowed with oral drugs that inhibit both advanced glycation end products (AGEs) and inflammation.
AGEs are altered sugars that are formed by chemical reactions when foods are heated, pasteurized, dried, smoked, fried, or grilled and are often increased in western diets. When absorbed in high amounts AGEs can build up in the body, stick to tissues and oxidize them, causing inflammation.
"This is the first study to show that oral drugs may slow the natural history of diabetes-induced changes within the spine in animals, and we think that this approach holds promise in developing early effective treatments for the epidemics of diabetes and back pain," said the study's senior author, James C. Iatridis, PhD, Professor in the Leni and Peter W. May Department of Orthopaedics at the Icahn School of Medicine at Mount Sinai.
Low back pain and intervertebral disc problems accounted for 40.5 million in patient visits in 2005, high medical costs, and lost productivity. Diabetes is now at epidemic levels in the United States (26.5 million in the United States) and around the world (346 million).
In this study, researchers examined whether diabetes directly resulted in pathological changes to intervertebral discs and vertebrae of the lumbar spine, via accumulation of advanced glycation end products and increased inflammation. A second goal was to see whether a combination of oral anti-inflammatory drugs and blockers of advanced glycation end products could slow degenerative disc and vertebral changes.
The diabetic mice showed decreased trabecular bone, reduced disc height, and increased disc wedging, a sign of hyperlordosis. "What really surprised us is the effect on the nucleus pulposus, which had focal areas of loose disorganized tissue and cells," said Dr. Iatridis.
"AGEs accumulate in intervertebral discs as the body ages and contribute to a chronic inflammatory state in degenerated discs," said Svenja Illien-Jünger, PhD, the study's lead author, and postdoctoral fellow in the Iatridis Spine Laboratory in the Department of Orthopaedics at the Icahn School of Medicine. "Diabetes is a disease involving accelerated aging and degeneration." Dr. Illien-Jünger explained that the drugs used in the study are all approved by the FDA: pentosan polysulfate as an anti-inflammatory drug, pyridoxamine for the prevention of AGE formation, and enalapril, an AGE inhibitor and they expected an additive effect.
Researchers compared three groups of age-matched, middle-aged mice: non-diabetic, diabetic, and diabetic mice treated with pentosan polysulfate, pyridoxamine and enaprinil, an angiotensin converting enzyme inhibitor, which is standard treatment for diabetic patients with kidney disease. Mice ingested standard rodent food, known to be an abundant source of AGEs.
The study was funded by the National Institute of Arthritis and Musculoskeletal and Skin Disease of the National Institutes of Health and the Juvenile Diabetes Research Foundation. In addition to Dr. Iatridis and Dr. Illien-Jünger, other Mount Sinai investigators involved in the study include Gary E. Striker, MD, Professor, Geriatrics and Palliative Medicine; Helen Vlassara, MD, Professor, Experimental Diabetes and Aging; Damien M. Laudier, BS , Senior Associate Researcher; and Fabrizio Grosjean, MD, Assistant Professor, Nephrology at the Foundation Policlinico San Matteo IRCCS of Pavia, Italy.
The Mount Sinai Medical Center
The Mount Sinai Medical Center encompasses both The Mount Sinai Hospital and Icahn School of Medicine at Mount Sinai. Established in 1968, the Icahn School of Medicine is one of the leading medical schools in the United States. The Medical School is noted for innovation in education, biomedical research, clinical care delivery, and local and global community service. It has more than 3,400 faculty in 32 departments and 14 research institutes, and ranks among the top 20 medical schools both in National Institutes of Health (NIH) funding and by U.S. News & World Report.
The Mount Sinai Hospital, founded in 1852, is a 1,171-bed tertiary- and quaternary-care teaching facility and one of the nation's oldest, largest and most-respected voluntary hospitals. In 2011, U.S. News & World Report ranked The Mount Sinai Hospital 16th on its elite Honor Roll of the nation's top hospitals based on reputation, safety, and other patient-care factors. Of the top 20 hospitals in the United States, Mount Sinai is one of 12 integrated academic medical centers whose medical school ranks among the top 20 in NIH funding and U.S. News & World Report and whose hospital is on the U.S. News & World Report Honor Roll. Nearly 60,000 people were treated at Mount Sinai as inpatients last year, and approximately 560,000 outpatient visits took place.
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