Naheed Ali, MD, PhD

Osteoarthritis is a common medical condition usually affecting older people. Its etiology is not exactly known but is considered multifactorial. Biological aging and urinary metals play a role in the progression of osteoarthritis, and these factors shall be discussed briefly in this text. Various studies conducted in the past provide evidence that the risk of osteoarthritis is directly related to urinary metal exposure and is also governed by the degenerative changes resulting from aging.

Osteoarthritis (O.A.) is a disorder involving gradual and progressive degeneration of joint cartilage, subchondral remodeling, and synovial inflammation. As the lifespan of people is increasing, O.A. is becoming a serious health concern and the most prominent source of communal cost in the aged population. In 2017, the global age-standardized prevalence of osteoarthritis was 3.75% and was expected to increase many folds by 2030, with 67 million estimated sufferers of this disorder [1]. Its etiology is elusive, yet non-negligible environmental factors seem to play an important role.

Heavy metals are present all over the place in our environment, and we are widely exposed to them in various ways. Exposure to such hazardous metals leads to the development of various diseases like D.M., cancer, and O.A. Cadmium and lead are found to be specifically toxic to bones and bone cells. Strong evidence manifested that these heavy metals were associated with joint damage and inflammation. Human cartilage cells were treated with CdCl2, and the results showed loss and inflammation of cells. Lead was found to cause osteoarthritis of knee joints in a study conducted on postmenopausal Korean women [2]. Heavy metals have also been linked with Rheumatoid arthritis and Osteoporosis in the past. Though these metals have some association with the above-mentioned diseases, they are the exacerbating factors rather than the sole etiological cause.

Another factor with established importance in the pathology of O.A. is aging. Aging is a decline in body function with time. It is natural and inevitable, but heavy metals have been found to accelerate it by promoting cell senescence through mitochondrial dysfunction, DNA damage, oxidative stress, and telomere wear. Joints decay and degenerate over time, and anything which contributes to speeding up this process is a pathological factor of O.A. Experiments conducted on mice showed that removing the aged cartilage cells improved osteoarthritis in them [3]. It is inferred that heavy metals fasten the process of aging and thus increase the risk of developing O.A.

Further cross-sectional studies proved that exposure to different types of heavy metals rather than just one further increases the risk of O.A. Bone scans reveal that patients with O.A. have more amount of metal in their bones. Cadmium, cobalt, and cesium stimulate an inflammatory response by upregulating Interleukins in various organs of mice, and these three heavy metals have now been proved to be the strongest risk factors for O.A. Heavy metals have a positive relation with aging markers, and they can even upregulate Keap1-NRF2 like senescence cascades [4].

Mediation analyses also concluded that links of heavy metals with osteoarthritis could be governed by aging and by cell senescence-whole-body aging pathways. We need to find ways by which O.A. can be treated, countering all the environmental factors, but for that purpose, we need to make advancements in understanding the exact etiology and pathophysiology of O.A.

References:

[1] Mero A, Campisi M, Favero M, et al. A hyaluronic acid-salmon calcitonin conjugate for the local treatment of osteoarthritis: chondro-protective effect in a rabbit model of early OA. J Control Release. 2014;187:30-38.

[2] Park S, Choi NK. The relationships of blood lead level, body mass index, and osteoarthritis in postmenopausal women. Maturitas. 2019;125:85-90.

[3] Caramés B, Taniguchi N, Otsuki S, Blanco FJ, Lotz M. Autophagy is a protective mechanism in normal cartilage, and its aging-related loss is linked with cell death and osteoarthritis. Arthritis Rheum. 2010;62(3):791-801.

[4] Matsumaru D, Motohashi H. The KEAP1-NRF2 System in Healthy Aging and Longevity. Antioxidants (Basel). 2021;10(12):1929. Published 2021 Nov 30.