The Effects of Dietary Supplements of Calcium, Vitamin D and Estrogen Hormone on Serum Levels of OPG and RANKL Cytokines and their Relationship with Increased Bone Density in Rats

Abstract

IntRoductIonBone is considered to be one of the hardest living tissues which has an extensive blood supply and is constantly undergoing change [1]. Osteoblasts account for the organic components of bone matrix. Bone surface growth is promoted by deposition of calcium salts in a newly formed matrix [2]. Alkaline phosphatase secreting Osteoblasts, generate matrix vesicles in which crystals of hydroxyapatite (calcium and phosphate deposits) are shaped [3].Osteoclasts secrete collagenase and other enzymes into the subcellular space to make a local acidic environment which dissolves hydroxyapatite and accelerates localized absorption of collagen. Therefore, both cells (osteoblasts, osteoclasts) are coordinated and essential for bone remodeling [4].The bone remodeling process happens with a rate of close to a 100% in the first year of life and 10% in the adult population [5]. The most important micronutrients in maintaining bone health which contribute most to bone mineral density at all ages are calcium, phosphorus, vitamin D [6]. Other studies showed that taking supplements such as calcium and vitamin D promotes bone absorption and resorption [7]. Studies on laboratory animals have also shown that calcium deficiency leads to inhibition of bone formation [8]. Vicky Tai et al., studied the special effects of a diet rich in calcium on bone metabolism in rats. Results indicated that Bone Mineral Density (BMD) of the femur in groups which had consumed calcium rich nutrients were notably higher than that of the control group [9]. During the process of bone formation, fluctuations in estrogen affect bone formation [10].Receptor activator of nuclear factor kappa-B ligand (RANKL), a member of the Tumour Necrosis Factor (TNF) superfamily, is an effective stimulator of both, osteoclast formation and their boneresorbing activity [11]. Upon binding to its receptor, RANK located on osteoclasts, RANKL signaling increases differentiation and activation of the osteoclasts resulting in expression of osteoclast specific molecules. During normal bone remodeling, marrow stromal cells and osteoblasts produce RANKL, which binds to the transmembrane receptor RANK on osteoclast precursors and induces differentiation and activation [12]. This occurs through the transcription factor, nuclear-factor kappa B(NFkB), which is responsible not only for activating osteoclastogenesis but also the body's inflammatory response. Although it has been proposed for a long time that the main source of RANKL are stromal and osteoblastic cells, a very recent study examiners proved that the main RANKL production site resides within osteocytes [13].Osteoprotegerin (OPG) is a secreted by TNF receptor super family member acting as a decoy receptor molecule for RANKL, thereby counteracting its osteoclastogenic activity. It is produced by a variety of cells, including stromal cells, B lymphocytes and dendritic cells [14].Estrogen, the major hormone regulating bone remodeling, is essential for both men and women. Estrogen's role in maintaining bone health is far rea...

Vitamin D Supplementation Guidelines for General Population and Groups at Risk of Vitamin D Deficiency in Poland—Recommendations of the Polish Society of Pediatric Endocrinology and Diabetes and the Expert Panel With Participation of National Specialist Consultants and Representatives of Scientific Societies—2018 Update

“…Calcitriol increases RANKL expression in osteoblasts, which in turn activates RANK receptors in osteoclast precursors leading to formation of mature osteoclasts. The resorption action of osteoclasts releases calcium and phosphates from the skeletal system into circulation ( 28 ).…”

High calcium diet alleviates 5/6 nephrectomy-induced bone deteriorations of lumbar vertebrae in mice

“…Thus, these findings suggest that HCD supplementation may increase bone Ca content and bone remodeling via inhibiting RANKL-induced bone resorption in 5/6 Nx mice. Piri et al (36) assessed the levels of OPG and RANKL associated with dietary supplements of Ca, vitamin D and estrogen, revealing that Ca intake led to an increase in OPG and reduction in RANKL, which ultimately caused an increase in BMD. According to the results of the present study, OPG/RANKL signaling is associated with 5/6 Nx-induced bone deterioration of lumbar vertebrae in mice, which suggests that OPG/RANKL may be an important target for the treatment of CKD-induced bone injury.…”

Рекомендації Зі Споживання Вітаміну D Для Здорового Населення Польщі Й Груп Ризику Дефіциту Вітаміну D

“…Кальцитріол збільшує експресію RANKL в остеобластах, що, зі свого боку, активує RANK рецептори в попередниках остеокластів і призводить до формування зрілих остеобластів. Резорбційна дія остеобластів вивільнює кальцій і фосфати зі скелета в кров [28].…”