Serum Calcium Concentration Is Inversely Associated With Radiographic Knee Osteoarthritis

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Abstract

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To examine the relationship between serum calcium (Ca) concentration and radiographic knee osteoarthritis (OA).

This study covered a total of 2855 subjects. The serum Ca concentration was detected by the Arsenazo III method. The radiographic OA of the knee was defined as changes equivalent to Kellgren–Lawrence grade 2 on 1 side at least. The serum Ca concentration was categorized into 4 quartiles, which are ≤2.27, 2.28–2.34, 2.35–2.41, and ≥2.42 mmol/L, respectively. The relationship between serum Ca and radiographic knee OA was examined using the multivariable logistic analysis after adjusting a series of potential confounding factors. For each quartile of the relationship between serum Ca concentration and radiographic knee OA, the OR with 95% CI was calculated, and the one with the lowest value was considered to be the reference.

An inverse association existed between serum Ca concentration and radiographic OA of the knee in the multivariable model and the model where the factors of age, sex, and BMI were adjusted. The multivariable-adjusted OR (95% CI) for radiographic knee OA in the second, third, and fourth quartiles of serum Ca concentration were 1.05 (95% CI: 0.83–1.31), 1.01 (95% CI: 0.80–1.27), and 0.79 (95% CI: 0.62–1.00), respectively, in comparison with the reference (first) quartile. A trend approaching to statistical significant (P = 0.06) was observed. Meanwhile, the relative odds of radiographic OA of the knee were decreased by 0.79 times in the fourth quartile in comparison with the reference.

There is likely to be an inverse association between serum Ca concentration and radiographic OA of the knee.

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Chapter One

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Introduction

Osteoarthritis (OA) is a degenerative disease of the joints which is characterized by degradation of articular cartilage, synovitis, and changes to subchondral bone which exhibits altered remodeling.1 It is a major public concern as it is one of the leading causes of morbidity and disability, thereby laying a huge medical and economic burden on health resources.2 Despite these concerns, the pathogenesis of OA remains unclear. A combination of local joint-specific factors acting in the context of systemic susceptibility may contribute to the development of OA. There seem to be many factors contributing to the occurrence and extent of the OA process including obesity, joint injury, metabolic diseases, bone and joint malformations, and genetic factors.3

It is hypothesized that nutritional imbalance is also involved in the pathogenesis of OA. The importance of nutrition in the maintenance of joint health is now widely recognized.4 In recent studies, our investigative group found that serum magnesium (Mg) concentration may have an inverse relationship with radiographic OA of the knee.5 Calcium, which belongs to the same family in the periodic table as Mg, shares the same homeostatic regulating system that involves calcium sensing receptor and (re)absorption with calcium.6,7Meanwhile, Mg and calcium antagonize each other in many physiological activities.7–10 So the relationship of the prevalence of radiographic knee OA with serum calcium concentration is also worth studying.

Calcium is an essential nutrient which plays a key role in regulating a great diversity of physiology processes, including muscle contraction, neurotransmitter release, endocrine and exocrine secretion, and blood clotting.11,12 In healthy individuals, serum levels of calcium are regulated by homeostatic mechanisms involving the calcium-sensing receptor, 1,25-dihydroxyvitamin D, and parathyroid hormone. Disorders of calcium homeostasis are related to an increased risk disease, such as cardiovascular disease, metabolic syndrome, and prostate cancer.13–18 There have been studies reporting associations between serum calcium and OA.

However, no association was found between OA and serum calcium concentration in these studies.19–21 It is notable that these studies have been performed on Western population, the lifestyle and eating habits of which are different from Asian people. Differences may exist among populations from the different regions. For example, a multicenter hospital-based case-control study conducted in Asian revealed an inverse association between serum concentrations of calcium and the risk of prostate cancer,18 while no association was found in Western populations.22,23

Hence, thorough investigation of serum calcium concentration in Asian countries such as China can potentially reveal further insight concerning probable association between OA and serum calcium in a different geographic setting. We, therefore, designed a cross-sectional study aimed to further evaluate the association of the prevalence of radiographic knee OA with serum calcium concentration.

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