Fig. 8.20
The active form of vitamin D: • Stimulates intestinal absorption of calcium through upregulation of calcium transport, in enterocytes http://ebooksmedicine.net 1,25 (OH)2D Ca Ca P P
Ultraviolet irradiation of 7-dehydrocholesterol in skin
Vitamin D in bloodSmall intestine absorption of dietary sources
Normal serum levels of Ca A (normocalcemia) and P
Ca and P absorption Serum Ca and P Serum Ca x P product Poor bone mineralization 1,25 (OH)2D PTHPTH Mobilization of Ca and P ˜-1-hydroxylase Ca CaP P P P 2 7 3 6a 6b 4 5
Fig. 8.20 (A)NormalvitaminDmetabolism.(B)VitaminDdeficiency.Thereisinadequatesubstratefortherenalhydroxylase(1),yieldingadeficiencyof1,25-(OH)2D(2),anddeficientabsorptionofcalciumandphosphorusfromthegut(3),withconsequentdepressedserumlevelsofboth(4).Thehypocalcemiaactivatestheparathyroidglands(5),causingmobilizationofcalciumandphosphorusfrombone(6a).Simultaneously,parathyroidhormone(PTH)induceswastingofphosphateintheurine(6b) andcalciumretention.Consequently,theserumlevelsofcalciumarenormalornearlynormal,butthephosphateislow;hence,mineralizationisimpaired(7).
Stimulates calcium resorption in renal distal tubules.
Collaborates with PTH to regulate blood calcium. This occurs in part through upregulation of RANK ligand on osteoblasts, which in turn activates RANK receptors on osteoclast precursors. RANK activation produces signals that increase osteoclast differentiation and bone resorptive activities (Chapter 21).
Promotes the mineralization of bone. Vitamin D is needed for the mineralization of osteoid matrix and epiphyseal cartilage during the formation of flat and long bones. It stimulates osteoblasts to synthesize the calcium-binding protein osteocalcin, which promotes calcium deposition.
Of note, effects of vitamin D on bone depend on the plasma levels of calcium: On the one hand, in hypocalcemic states 1,25-(OH)2-D together with PTH increases the resorption of calcium and phosphorus from bone to support blood levels. On the other hand, in normocalcemic states, vitamin D is required for calcium deposition in epiphyseal cartilage and osteoid matrix.
Vitamin D deficiency causes rickets in growing children and osteomalacia in adults; these skeletal diseases have worldwide distribution. They may result from diets deficient in calcium and vitamin D, but probably more important is limited exposure to sunlight (for instance, in heavily veiled women; children born to mothers who have frequent pregnancies followed by lactation, which leads to vitamin D deficiency; and inhabitants of northern climates with scant sunlight). Other, less common causes of rickets and osteomalacia include renal disorders causing decreased synthesis of 1,25-(OH)2-D or phosphate depletion, and malabsorption disorders. Although rickets and osteomalacia rarely occur outside high-risk groups, milder forms of vitamin D deficiency (also called vitamin D insufficiency) leading to bone loss and hip fractures are common among elderly persons. Studies also suggest that vitamin D may be important for preventing demineralization of bones. It appears that certain genetically determined variants of the vitamin D receptor are associated with an accelerated loss of bone minerals with aging and certain familial forms of osteoporosis (Chapter 21).