Could Elevated Zinc, Copper Levels Cause Osteoarthritis?

Could elevated levels of zinc or copper or both be a contributing cause to the onset of osteoarthritis (OA)? Using a novel genetic statistical method for inferring causation, a new study, “Genetically predicted circulating levels of copper and zinc are associated with osteoarthritis but not with rheumatoid arthritis,” appears in the July 1, 2021 edition of Osteoarthritis and Cartilage and provides evidence that, yes, elevated zinc or copper levels are not only correlated with OA incidence, they may also have a causal connection.

Kaixiong Ye, Ph.D., study co-author and assistant professor in the Department of Genetics | Institute of Bioinformatics at the University of Georgia explained to OTW that, “In previous epidemiological studies, the circulating levels of minerals, such as copper, zinc, iron, calcium, and magnesium, have been previously associated with the risk of osteoarthritis or rheumatoid arthritis. However, the circulating levels of minerals are correlated with other risk factors and influenced by the disease progression. In other words, these associations do not imply causality between these minerals and OA (or rheumatoid arthritis-RA).”

Using Mendelian Randomization to Infer Causation

“A novel method, called Mendelian randomization, is less affected by confounding and reverse causation, and thus more likely to infer causal relationships between a risk factor and a disease. In a nutshell, this method uses ‘genetically predicted mineral levels,’ instead of the ‘directly measured mineral levels.’ The genetically predicted levels are only controlled by genetic backgrounds and not influenced by lifestyle or disease status.”

“Genetically determined copper and zinc status were associated with OA, but not with RA,” said the authors. “Per standard deviation (SD) increment in copper increases the risk of OA and one of its subtypes, localized OA. Per standard deviation increment in zinc is positively associated with risks of OA, generalized OA, and unspecified OA. Additionally, per standard deviation increment in calcium decreases the risk of localized OA.”

Cut Copper and Zinc Levels to Treat OA?

“The genetically predicted levels of copper and zinc are associated with a higher risk of osteoarthritis. Copper and zinc likely play causal roles in the development of osteoarthritis. Reducing circulating levels of copper and zinc may be effective preventative or therapeutic approaches for osteoarthritis.”