Understanding How Autoimmunity Impacts Bones: When Your Body Can’t Tell Friend from Foe

We’ve been discussing the fascinating connections between the immune and skeletal systems in our current blog series on Osteoimmunology. But what happens when those interactions turn hostile? This week, we dive deeper into how autoimmune diseases disrupt bone health and fracture repair, transforming the immune system from a protector and cooperative partner into a potential saboteur of skeletal integrity.

Your immune system displays a remarkable precision to recognize and tolerate your healthy cells while seeking out and destroying unfamiliar invaders, such as foreign cells and antigens like microbes and viruses. Autoimmunity arises when your body fails to recognize itself and mistakes your healthy cells and tissues for threats. In deeper medical terms, autoimmunity is linked to defects in the body’s natural immune checkpoints that normally eliminate self-reactive lymphocytes during maturation.

Nearly 1 in 10 people suffer from an autoimmune disease, making it highly likely that you or someone you know is affected by these conditions (1). Some of the most common autoimmune disorders include rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Type 1 diabetes, and celiac disease, just to name a few (2,3,5,6). These conditions involve aberrant immune activation, leading to autoantibody production and inflammation that impacts multiple organs – including bone.

How Autoimmune Diseases Weaken Bone Health

Many existing studies indicate that patients with autoimmune disease tend to have low total bone mineral density and an increased susceptibility to osteoporosis and fractures. The underlying cause?  Chronic inflammation, a hallmark of autoimmune disease, disrupts normal bone homeostasis.  

Three key mechanisms contribute to bone deterioration in autoimmune patients:

1. Increased Bone Resorption – Inflammatory cytokines such as IL-1, TNF, or IL-6 stimulate osteoclast activity, leading to accelerated bone resorption.

2. Impaired Osteogenesis – Autoimmune-related inflammation inhibits osteoblast function, reducing bone regeneration.

3. Calcium Metabolism – Autoimmunity reduces calcium absorption and increases calcium excretion. Calcium is an essential mineral for healthy bone maintenance. Reduced calcium concentrations mean fewer building blocks for mineralized bone maintenance, further compromising bone strength (3,4,7,8).

   
   

For patients with autoimmune diseases, fractures pose a greater challenge than simply healing. Studies suggest that fracture repair is significantly impaired due to chronic systemic inflammation with elevated levels of tumor necrosis factor (TNFα). This potent cytokine is involved in tissue catabolism as well as inflammation. Elevated TNF-α levels stimulate osteoclastogenesis resulting in an imbalance in bone homeostasis and impaired fracture healing and remodeling (5).

The Double-Edged Sword: Steroid Treatment and Bone Loss

Symptoms of many autoimmune diseases are treated with steroids because of their potent ability to reduce inflammation. Unfortunately, steroids have widespread effects, including unintended consequences for bone metabolism. From influencing the cells important in bone deposition and resorption, to controlling important ingredients needed for bone mineralization, steroids have a negative effect on bone health. They inhibit osteoblasts, stimulate osteoclasts, interfere with calcium and vitamin D uptake, and contribute to increased calcium secretion in urine. The net effect is significant bone loss, brittle bones, and a higher risk of fracture nonunion.

Bone Health Awareness is Key for Autoimmune Patients

Osteoimmunology has improved our understanding of the complex relationship between the immune system and bone health, revealing how autoimmune diseases can weaken skeletal integrity and delay fracture healing. Protecting bone health requires proactive measures, including nutrition, exercise, and careful medication management. By staying informed and working with healthcare professionals, patients can minimize bone loss, strengthen bones, and reduce fracture risks.

At Molecular Matrix, Inc., we are dedicated to advancing bone health and fracture repair through cutting-edge insights into autoimmunity, osteoimmunology, and skeletal biology. Our mission is to develop innovative solutions that enhance bone maintenance and healing. To explore more about our research and breakthroughs, visit  www.molecularmatrix.com.

References:

1. Conrad N., Misra, S., Verbakel, J.Y., Verbeke, G., Molenberghs, G., Taylor, P.N., Mason, J., Sattar, N., McMurray, J.J., McInnes, I.B., Khunti, K., & Cambridge, G. (2023). Incidence, prevalence, and co-occurrence of autoimmune disorders over time and by age, sex, and socioeconomic status: a population-based cohort study of 22 million individuals in the UK. The Lancet, 401(10391), 1878-1890. https://doi.org/10.1016/S0140-6736(23)00457-9.

2. Actor, J. K. (2019). Autoimmunity: Regulation of Response to Self. In Introductory Immunology (pp. 91–102). Elsevier. https://doi.org/10.1016/B978-0-12-816572-0.00007-3

3. Amarasekara, D. S., Yu, J., & Rho, J. (2015). Bone Loss Triggered by the Cytokine Network in Inflammatory Autoimmune Diseases. Journal of Immunology Research, 2015, 1–12. https://doi.org/10.1155/2015/832127

4. Lombardi, F., Franzese, A., Iafusco, D., Del Puente, A., Esposito, A., Prisco, F., Troncone, R., & Valerio, G. (2010). Bone involvement in clusters of autoimmune diseases: Just a complication? Bone, 46(2), 551–555. https://doi.org/10.1016/j.bone.2009.09.034

5. Lončar, S. R., Halcrow, S. E., & Swales, D. (2023). Osteoimmunology: The effect of autoimmunity on fracture healing and skeletal analysis. Forensic Science International: Synergy, 6, 100326. https://doi.org/10.1016/j.fsisyn.2023.100326

6. Miller, F. W. (2023). The increasing prevalence of autoimmunity and autoimmune diseases: An urgent call to action for improved understanding, diagnosis, treatment, and prevention. Current Opinion in Immunology, 80, 102266. https://doi.org/10.1016/j.coi.2022.102266

7. Schwarz, E. M., Looney, R. J., Drissi, M. H., O’Keefe, R. J., Boyce, B. F., Xing, L., & Ritchlin, C. T. (2006). Autoimmunity and Bone. Annals of the New York Academy of Sciences, 1068(1), 275–283. https://doi.org/10.1196/annals.1346.031

8. Wu, S., Ye, Z., Yan, Y., Zhan, X., Ren, L., Zhou, C., Chen, T., Yao, Y., Zhu, J., Wu, S., Ma, F., Liu, L., Fan, B., & Liu, C. (2023). The causal relationship between autoimmune diseases and osteoporosis: A study based on Mendelian randomization. Frontiers in Endocrinology, 14, 1196269. https://doi.org/10.3389/fendo.2023.1196269