The level of vitamin D thought to be necessary for good health is being reexamined with the appreciation that vitamin D acts on a large number of cell types beyond those responsible for bone and mineral metabolism. A level of 25(OH)D above 10 ng/mL is necessary for preventing rickets or osteomalacia. However, substantial epidemiologic and some prospective trial data indicate that a higher level, such as 20–30 ng/mL, is required to optimize intestinal calcium absorption, optimize the accrual and maintenance of bone mass, reduce falls and fractures, and prevent a wide variety of diseases including diabetes mellitus, hyperparathyroidism, autoimmune diseases, and cancer. An expert panel for the Institute of Medicine (IOM) has recommended that a level of 20 ng/mL (50 nM) was sufficient, although up to 50 ng/mL (125 nM) was considered safe. For individuals between the ages of 1 and 70 years, 600 IU/d vitamin D was thought to be sufficient to meet these goals, although up to 4000 IU was considered safe. These recommendations are based primarily on data from randomized placebo-controlled clinical trials (RCTs) that evaluated falls and fractures; data supporting the nonskeletal effects of vitamin D were considered too preliminary to be used in their recommendations because of lack of RCTs for these other actions. The lower end of these recommendations has been considered too low and the upper end too restrictive by a number of vitamin D experts, and the Endocrine Society has published a different set of recommendations suggesting that 30 ng/mL was a more appropriate lower limit. Nevertheless, the call for better clinical data from RCTs, especially for the nonskeletal actions, is appropriate. The IOM guidelines—at least with respect to the lower recommended levels of vitamin D supplementation—are unlikely to correct vitamin D deficiency in individuals with obesity, dark complexions, limited capacity for sunlight exposure, or malabsorption. Vitamin D deficiency or insufficiency can be treated by higher dosages (either D2 or D3, 1000–4000 IU/d or 50,000 IU/week for several weeks). No other vitamin D metabolite is indicated. Because the half-life of vitamin D3 metabolites in blood is greater than that of vitamin D2, there are advantages to using vitamin D3 rather than vitamin D2 supplements, although when administered on a daily or weekly schedule these differences may be moot. The diet should also contain adequate amounts of calcium as several studies indicate a synergism between calcium and vitamin D with respect to a number of their actions.
The major sequelae of chronic kidney disease (CKD) that impact bone mineral homeostasis are deficient 1,25(OH)2D production, retention of phosphate with an associated reduction in ionized calcium levels, and the secondary hyperparathyroidism that results from the parathyroid gland response to lowered serum ionized calcium and low 1,25(OH)2D. FGF23 levels rise early in this disorder for unclear reasons and this can further reduce 1,25(OH)2D production by the kidney. Moreover, the increase in FGF23 is associated with increased morbidity and mortality in CKD in part due to its impact on the heart. Although still investigational, antibodies to FGF23 in the early stages of renal failure result in normalization of 1,25(OH)2D levels, and may prove useful in CKD treatment. However, inhibition of FGF23 may further the rise in serum phosphate with the potential for increased vascular calcification, a major issue in CKD. With impaired 1,25(OH)2D production, less calcium is absorbed from the intestine, and less bone is resorbed under the influence of PTH. As a result hypocalcemia usually develops, furthering the development of secondary hyperparathyroidism. The bones show a mixture of osteomalacia and osteitis fibrosa.