Oxidative stress in bone remodeling: role of antioxidants

Abstract

ROS are highly reactive molecules which consist of a number of diverse chemical species, including radical and non-radical oxygen species. Oxidative stress occurs as a result of an overproduction of ROS not balanced by an adequate level of antioxidants. The natural antioxidants are: thiol compounds among which GSH is the most representative, and non-thiol compounds such as polyphenols, vitamins and also various enzymes. Many diseases have been linked to oxidative stress including bone diseases among which one of the most important is the osteoporosis. The redox state changes are also related to the bone remodeling process which allows the continuous bone regeneration through the coordinated action of bone cells: osteoclasts, osteoblasts and osteocytes. Changes in ROS and/or antioxidant systems seem to be involved in the pathogenesis of bone loss. ROS induce the apoptosis of osteoblasts and osteocytes, and this favours osteoclastogenesis and inhibits the mineralization and osteogenesis. Excessive osteocyte apoptosis correlates with oxidative stress causing an imbalance in favor of osteoclastogenesis which leads to increased turnover of bone remodeling and bone loss. Antioxidants either directly or by counteracting the action of oxidants contribute to activate the differentiation of osteoblasts, mineralization process and the reduction of osteoclast activity. In fact, a marked decrease in plasma antioxidants was found in aged or osteoporotic women. Some evidence shows a link among nutrients, antioxidant intake and bone health. Recent data demonstrate the antioxidant properties of various nutrients and their influence on bone metabolism. Polyphenols and anthocyanins are the most abundant antioxidants in the diet, and nutritional approaches to antioxidant strategies, in animals or selected groups of patients with osteoporosis or inflammatory bone diseases, suggest the antioxidant use in anti-resorptive therapies for the treatment and prevention of bone loss.

Keywords: antioxidant nutrient treatment; antioxidants; bone remodeling; osteoporosis; oxidative stress.

Figure 1

Effect of ROS and antioxidants on the activity of osteoclasts, osteoblasts and osteocytes in bone remodeling. ROS activate osteoclast differentiation and osteocyte apoptosis (+), while inhibit osteoblast activity (−) inducing bone resorption; antioxidants activate osteoblast differentiation (+) and inhibit osteoclast activity and osteocyte apoptosis (−) inducing bone formation.

Figure 2

Effect of antioxidants on bone cells at molecular and cellular level in bone resorption. Antioxidants inhibit and prevent oxidative stress and affect various enzymes, proteins and cytokines involved in bone remodeling.