Pediatr Nephrol (2011) 26:1937–1946 1939 Bone formation Collagens Osteopontin Osteonectin Mineralization CNS Calcium & Phosphate Vitamin D Dietary intake IGF-I S N S PTH Osteocyte Mechanical stimulation OPG RANK-L Osteoblasts & bone-lining cells Osteoclast Bone resorption Fig. 1 The bone remodeling process. Bone remodeling is a dynamic process in which old bone is removed and new bone is formed. It consists of two distinct stages—formation and resorption—that involves the activity of special cells termed osteoblasts and osteo- clasts. a Mature mineralizing osteoblasts differentiate terminally into osteocytes. Osteocytes communicate with each other but also communicate with osteocytes through gap junctions and respond to changes in fluid flow arising from stress or mechanical stimulation. Important extrinsic anabolic signals, such as PTH, IGF-I, and mechanotransduction, stimulate bone formation whereas hypothalamic leptinergic signals transmitted through adrenergic nerves inhibit bone formation. Dietary intake of vitamin D influences calcium and phosphate metabolism and impacts the bone mineralization and formation. Bone formation is completed when the bone surface is restored and covered by a layer of protective bone cells called bone- lining cells. b Bone resorption. In this phase, osteoclasts act on the trabecular bone surface to erode the mineral and matrix. Osteoclasts are terminally differentiated bone-absorbing cells. Bone resorption is accomplished by a series of tightly orchestrated molecular and biochemical changes that eventually results in the creation of small cavities on the surface of the trabecular bone. The main switch for osteoclastic bone resorption is the RANK-L that is released by activated osteoblasts. Its action on the RANK receptor is regulated by OPG, which is also derived from osteoblasts. CNS central nervous system; IGF-I insulin-like growth-hormone I; OPG osteoprotegerin; PTH parathyroid hormone; RANK-L receptor activator for NF-κβ- ligand, SNS sympathetic nervous system inactivity diminishes mechanical loads by influencing linear growth and muscle mass and may alter the functional muscle-bone set point [31]. The risk for hip fractures decreases as physical activity increases. Non- randomized trials have shown that exercise protects against bone loss [32]. Pro-inflammatory cytokines stimulate RANKL expres- sion in osteoblasts. Enhanced production of RANKL promotes osteoclast differentiation and stimulates bone resorption activity of osteoclasts. TNF-α and IL-1 syner- gize with RANKL and stimulate bone resorption by osteoclasts [33, 34]. Rate of bone resorption is in equilibrium with the rate of bone formation during bone remodeling. Newly formed bone completely replaces the bone lost in the resorption phase. Inflammation may uncouple this tightly regulated bone remodeling cycle,