High serum Cu and Cu/Zn ratios correlate with impairments in bone density, physical performance and overall health in a population of elderly men with frailty characteristics

Abstract

Serum Cu levels rise with age and high Cu/Zn ratios are linked with multiple-cause mortality in the elderly. The relationships of these parameters to measures of musculoskeletal health and frailty have not yet been analyzed. We used inductively coupled mass spectrometry to assess serum levels of Cu and Zn and probed for relationships between serum Cu levels and the Cu/Zn ratio with specific measures of bone, physical and overall health in a cohort of 144 frail elderly men. Subjects were divided into quintiles based on serum metal levels and comparisons for functional measures were made between the reference (middle) group and the low and high groups. Subjects’ serum metal values were normally distributed. We found significant correlations between high Cu/Zn ratios and deficits in femoral bone mineral density, measures of speed and strength, muscle mass and hematocrit. High Cu/Zn ratios were also correlated with decreased triglycerides and increased reliance on ADL assistance. This study identifies specific deficits associated with high Cu/Zn ratios that span multiple organ systems and supports earlier studies indicating that serum Cu levels and the Cu/Zn ratio may serve as useful predictive biomarkers for poor health in the elderly.

The copper concentrations in selected tissues in animal models and human anorexia

“…There are many opinions that the copper/ zinc ratio, rather than copper or zinc concentrations alone, should be taken as a clinical parameter and biomarker, and have been explored as a marker of frailty [3,6,11]. Higher than normal (in human serum: 0.7 -1.0) copper/zinc ratios in serum or plasma have been associated with physical and mental disturbances of well-being in a population of elderly individuals [3,11].…”

“…Cuproenzymes are essential to the maintenance of multiple organ systems [3]. Its redox activity contributes to its utility as a co-factor for electron transfer reactions.…”

“…Cuproenzymes are essential to the maintenance of multiple organ systems [3]. Copper deficiency also affects the cardiovascular, musculoskeletal, hematopoietic and nervous system [3,17]. The Wilson's disease is one of the genetic disorders associated with copper, where among wide range of symptoms, behavioral psychiatric-like abnormalities occur [14].…”

“…Copper deficiency also affects the cardiovascular, musculoskeletal, hematopoietic and nervous system [3,17]. High tissues copper concentrations were often recognized in diabetic patients, Alzheimer's disease, depression, and cognition deficits patients [3,14,17,18]. On the other hand, the copper overload, which results fi"om oxidative stress and the generation of free-radicals, contributes to chronic, degenerative diseases and carcinogenesis [17].…”

“…The copper homeostasis is governed by a complex regulatory system to keep availability of copper at optimal levels [10]. Some authors are of the opinion that Cu/Zn ratio proved to be a better predictor of disease severity than Cu levels [3,11]. High tissues copper concentrations were often recognized in diabetic patients, Alzheimer's disease, depression, and cognition deficits patients [3,14,17,18].…”