Vitamin D therapy of osteoporosis: Plain vitamin D therapy versus active vitamin D analog (D-hormone) therapy

Normal intestinal calcium (Ca) absorption is an essential feature of bone h omeostasis. As with many other organ systems, intestinal Ca absorption decl ines with aging, and this is one pathological factor that has been identifi ed as a cause of senile osteoporosis in the elderly. This abnormality leads to secondary hyperparathyroidism, which is characterized by high serum par athyroid hormone (PTH) and an increase in bone resorption. Secondary hyperp arathyroidism due to poor intestinal Ca absorption has been implicated not only in senile osteoporosis but also in age-related bone loss. Accordingly, in population-based studies, there is a gradual increase in serum PTH from about 20 years of age onward, which constitutes a maximum increase at 80 y ears of age of 50% of the basal value seen at 30 years of age. The cause of the increase in PTH is thought to be partly due to impaired intestinal Ca absorption that is associated with aging, a cause that is not entirely clea r but at least in some instances is related to some form of vitamin D defic iency. There are three types of vitamin D deficiency: (1) primary vitamin D deficiency, which is due to a deficiency of vitamin D, the parent compound ; (2) a deficiency of 1,25(OH)(2)D-3 resulting from decreased renal product ion of 1,25(OH)(2)D-3; and (3) resistance to 1,25(OH)(2)D-3 action owing to decreased responsiveness to 1,25(OH)(2)D-3 of target tissues. The cause fo r the resistance to 1,25(OH)(2)D-3 could be related to the finding that the vitamin D receptor level in the intestine tends to decrease with age. All three types of deficiencies can occur with aging, and each has been implica ted as a potential cause of intestinal Ca malabsorption, secondary hyperpar athyroidism, and senile osteoporosis. There are two forms of vitamin D repl acement therapies: plain vitamin D therapy and active vitamin D analog (or D-hormone) therapy. Primary vitamin D deficiency can be corrected by vitami n supplements of 1000 U a day of plain vitamin D whereas 1,25(OH)(2)D-3 def iciency/resistance requires active vitamin D analog therapy [1,25(OH)(2)D-3 or 1 alpha(OH)D-3] to correct the high serum PTH and the Ca malabsorption. In addition, in the elderly, there are patients with decreased intestinal Ca absorption but with apparently normal vitamin D metabolism. Although the cause of poor intestinal Ca absorption in these patients is unclear, these patients, as well as all other patients with secondary hyperparathyroidism (not due to decreased renal function), show a decrease in serum PTH and an increase in Ca absorption in response to therapy with 1,25(OH)(2)D-3 or 1 alpha(OH)D-3. In short, it is clear that some form of vitamin D therapy, ei ther plain vitamin D or 1,25(OH)(2)D-3 or 1 alpha(OH)D-3, can be used to co rrect all types of age-dependent impairments in intestinal Ca absorption an d secondary hyperparathyroidism during aging. However, from a clinical stan dpoint, it is important to recognize the type of vitamin D deficiency in pa tients with senile osteoporosis so that primary vitamin D deficiency can be appropriately treated with plain vitamin D therapy, whereas 1,25(OH)(2)D-3 deficiency/resistance will be properly treated with 1,25(OH)(2)D-3 or 1 al pha(OH)D-3 therapy. With respect to postmenopausal osteoporosis, there is s trong evidence that active vitamin D analogs (but not plain vitamin D) may have bone-sparing actions. However, these effects appear to be results of their pharmacologic actions on bone formation and resorption rather than through replenishing a deficie ncy.