ABSTRACT
Vitamin D was identified as a key nutrient for bone health nearly 100 years ago [1]. Since then, the highest levels of clinical evidence confirm that adequate vitamin D status reduces the risks of musculoskeletal diseases including rickets in children, osteomalacia in adults, and osteoporosis in the frail elderly and also reduces the risks of falls, fractures, and premature death. Considerable controversy still surrounds the
7.1 Introduction .................................................................................................. 167 7.2 Vitamin D and Metabolic Bone Disorders ................................................... 168
7.2.1 Genetic Disorders ............................................................................. 168 7.2.2 Nutritional Deficiency, Rickets, and Osteomalacia .......................... 170 7.2.3 Osteoporosis, Falls, and Fractures .................................................... 170
7.3 Metabolism and Molecular Modes of Action ............................................... 171 7.3.1 Regulation of Plasma 1,25D Levels .................................................. 173 7.3.2 Regulation of Gene Transcription .................................................... 175 7.3.3 Regulation of Intracellular Signaling and Non-Genomic Actions ... 175 7.3.4 Actions of Receptor through Binding to Intracellular Proteins........ 176
7.4 Cellular Regulation of Bone Mineral Homeostasis ...................................... 177 7.4.1 Basic Multicellular Unit of Bone Remodeling and Resorption ........ 177 7.4.2 Mechanisms of Bone Formation ....................................................... 178 7.4.3 Vitamin D Activities within Osteoblasts and Osteocytes ................ 178
7.5 Endocrine Activities ..................................................................................... 179 7.5.1 Regulation of Plasma Calcium and Phosphate Homeostasis ............ 179 7.5.2 Endocrine Activities: Stimulation of Bone Resorption and
Inhibition of Bone Formation ........................................................... 179 7.6 Autocrine and Paracrine Activities ............................................................... 180
7.6.1 Synthesis of 1,25D by Mesenchymal Stem Cells, Osteoblasts, Osteocytes, and Osteoclasts ............................................................. 180
7.6.2 In Vitro and in Vivo Activities of Locally Synthesized 1,25D......... 181 7.7 Conclusions ................................................................................................... 181 References .............................................................................................................. 182
molecular actions of vitamin D in the skeleton, the levels required for musculoskeletal health, and the interaction of the vitamin with dietary calcium intake [2,3].
