Vitamin D Binding Protein and Bone Health

Abstract

Vitamin D binding protein (DBP) is the major carrier protein of 25-hydroxyvitamin D (25(OH) D) in the circulation, where it may serve roles in maintaining stable levels during times of decreased 25(OH) availability and in regulating delivery of 25(OH) D to target tissues. Several genetic polymorphisms of DBP have been described that lead to phenotypic changes in the protein that may affect affinity, activity, and concentration. These polymorphisms have been linked with alterations in bone density in several populations. One of the mechanisms by which DBP may alter bone health involves regulating vitamin D bioavailability. DBP-bound vitamin is thought to be relatively unavailable to target tissues, and thus alterations in DBP levels or affinity could lead to changes in vitamin D bioactivity. As a result, functional vitamin D status may differ greatly between individuals with similar total 25(OH) D levels. Additionally, DBP may have independent roles on macrophage and osteoclast activation. This review will summarize recent findings about DBP with respect to measures of bone density and health.

Clinical Utility of Measurement of Vitamin D-Binding Protein and Calculation of Bioavailable Vitamin D in Assessment of Vitamin D Status

“…Vitamin D deficiency is defined as total 25(OH)D concentration less than 20 ng/mL, regardless of its bioavailability. Because VDBP levels can be altered by changes in estrogen levels or by hepatic diseases, the actual vitamin D status may have a different relation with the total 25(OH)D concentration in patients with abnormal VDBP level [6792122]. However, there are no studies on the calculated bioavailable 25(OH)D levels in pregnant women and ICU patients with changed VDBP level.…”

“…VDBP levels increase by up to 50% in a high-estrogen state, such as pregnancy, and decrease in certain disease states, such as severe hepatic disease [6789]. Moreover, VDBP has a high rate of polymorphism, and differences in affinity for 25(OH)D have been reported [10].…”

Longitudinal increase in vitamin D binding protein levels after initiation of tenofovir/lamivudine/efavirenz among individuals with HIV

“…During each step of this process, 85-90% of the body’s vitamin D metabolites circulate tightly bound to the carrier protein, vitamin D binding protein (DBP). The non DBP-bound portion, known as bioavailable vitamin D, circulates less tightly bound to albumin, with <1% in the free form [12,13]. It is this free form which acts upon target cells in the intestine, kidney and bone to maintain calcium homeostasis.…”

Polymorphisms affecting vitamin D–binding protein modify the relationship between serum vitamin D (25[OH]D3) and food allergy

“…11 Higher levels of bound 25(OH)D are associated with indicators of decreased vitamin D function (decreased bone density and increased parathyroid hormone levels). 12 Lower DBP levels, by increasing the biological availability of serum vitamin D, may therefore counteract adverse effects of apparently low serum 25-hydroxyvitamin D 3 (25[OH]D 3 ). 11 There are 3 main phenotypic alleles of DBP, which differ both in the associated concentration of DBP in the serum and in their affinity for 25(OH)D. These are distinguished by genetic polymorphisms in the gene encoding vitamin D binding protein (group-specific component [GC]).…”