Monday, September 28, 2009

Broken bones? Blame it on autoimmune disease. TNF alpha the culprit

After having had three broken arms, a broken collar bone, a broken pelvis, a broken hand bone, and 12 or so broken ribs, I think I am an expert on broken bones. I know how they feel when they break (like a stick snapping inside--but with a bit of dizzying shock sensation mixed with relatively minor pain initially--later the pain at the site of the break can be excruciating when the spot is lightly touched).

I used to blame my many broken bones on having small diameter bones. Later I found out that the particular kind of immune problems I have caused mal absorbtion in the intestines so that bones did not receive enough calcium and phosphorous. Now I read that it is caused by too much systemic inflammation as in too much TNF alpha--the inflammatory immune signaling molecule that has been found to be a problem in many autoimmune diseases--RA, PsA, AS, and psoriasis to mention a few. Remicade, Enbrel, and Humira are medications that absorb or block TNF alpha thus reducing the effects of several autoimmune diseases.

I remember when my father got made at me for breaking my arm AGAIN! He told me it was expensive to get fixed and I must be more careful. I thought I was being careful. Certainly more so than my friends were being. So when I broke my collar bone and could not raise my right arm, I did not tell my parents. They never noticed. I just laid my right arm against the edge of the table at dinner and used that as a pivot to pick up food with my fork on my plate, then bend my head down and ate. I wanted to use my left hand but thought they would notice I was using the wrong hand. After several weeks the collar bone got better. It healed a little crooked but still works. Later as an adult during a physical, my doctor noticed the crooked bone and mentioned it to me. Other than that I got away with not telling my parents.

I have found over the years that most bones heal on their own with no need for doctors if you do not mind a little pain and a bit of a crooked bone here and there (can't turn over my left hand because one of the wrist bones is pretty crooked but arm works well otherwise.)

Here is the article about TNF alpha causing broken bones and slow healing bones.

American Journal of Pathology

Diabetes weakens your bones

Boston, MA and Newark, NJ – Current research suggests that the inflammatory molecule TNF-α may contribute to delayed bone fracture healing in diabetics. The related report by Alblowi et al, "High Levels of TNF-α Contribute to Accelerated Loss of Cartilage in Diabetic Fracture Healing" appears in the October 2009 issue of the American Journal of Pathology.

Diabetes, a condition where the body either does not produce enough, or respond to, insulin, affects at least 171 million people worldwide, a figure that is likely to double by 2030. Long-term complications of diabetes include cardiovascular disease, chronic renal failure, retinal damage that may lead to blindness, nerve damage, and blood vessel damage, which may cause erectile dysfunction and poor wound healing.

Diabetic patients often experience low bone density, which is associated with increased risk of bone fractures and delayed fracture repair. To examine how diabetes affects bone, Dr. Dana Graves and colleagues of the University of Medicine and Dentistry of New Jersey and the Boston University School of Medicine explored bone repair in a mouse model of diabetes. They observed increased levels of inflammatory molecules, including TNF-α during fracture healing. The diabetic animals had rapid loss of cartilage in the healing bones, which was due to increased numbers of osteoclasts, cells that remove bone and cartilage. Factors that stimulate osteoclast formation were regulated by both TNF-α and a downstream mediator, FOXO1. These results suggest that diabetes-mediated increases in TNF-α and FOXO1 may underlie the impaired healing of diabetic fractures.

Alblowi et al suggest that "TNF-α dysregulation plays a prominent role in the recently identified catabolic events associated with diabetic fracture healing." In future studies, Dr. Graves and colleagues plan to "examine the effect of FOXO1 on mineralized tissue to examine how it may regulate factors that control bone resorption and osteoclastogenesis, in addition to effects it may have on osteoblastic cells."


This work was supported by grants from the National Institutes of Health.

Alblowi J, Kayal RA, Siqueira M, McKenzie E, Krothapalli N, McLean J, Conn J, Nikolajczyk B, Einhorn TA, Gerstenfeld L, Graves DT: High Levels of TNF-α Contribute to Accelerated Loss of Cartilage in Diabetic Fracture Healing. Am J Pathol 2009 175: 1574-1585


The American Journal of Pathology, official journal of the American Society for Investigative Pathology, seeks to publish high-quality, original papers on the cellular and molecular biology of disease. The editors accept manuscripts that advance basic and translational knowledge of the pathogenesis, classification, diagnosis, and mechanisms of disease, without preference for a specific analytic method. High priority is given to studies on human disease and relevant experimental models using cellular, molecular, animal, biological, chemical, and immunological approaches in conjunction with morphology.

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