Abstract
Background
: Recent advances in measurement of total serum 25OHD (T25D) led to development of free 25OHD (F25D) assays. The free hormone hypothesis states that only F25D which is about 0.02% of T25D is available for conversion to the active metabolite 1,25(OH)2D, the rest is bound to D binding protein (DBP) and albumin. In a previous paper (J Int Med 2018 Aug 23 online)we did not find a change in BMD or bone markers compared to F25D or T25D. A one month vitamin D study reported F25D was more highly correlated than T25D with serum PTH. If confirmed then F25D measurement would be clinically important.
Methods:
In two 12 month vitamin D placebo/dosing studies in young, old white and black women, serum T25D, F25D and PTH were measured at baseline and 12 months. The main inclusion criteria was vitamin D insufficiency (Diasorin serum T25D ≤ 20ng/ml). Serum T25D was remeasured by LCMS and F25D was measured by Elisa (Future Diagnostics). Serum PTH was measured by immunoassay (Diasorin). Group means were compared by t-test. Linear regression was used to assess percent change in T25D and F25D on percent change in PTH, accounting for age (young, old), race (Caucasians, African Americans) and interactions.
Results:
In the older women, there were 109 Caucasians and 79 African Americans with baseline measurements of F25D, T25D and PTH. Mean age (± SD) was 69 (± 7.3) years. In the younger women, there were 81 Caucasians and 31 African Americans, mean age 37 (± 5.6) years. In older women, serum T25D was similar in black compared to white women 18.70(±5.57) and 19.63(±5.19) ng/ml, p=0.24. Serum F25D was lower in older African Americans compared to Caucasians 3.38(±1.21) vs 3.73(±1.39) pg/mL (p=0.075). In younger women T25D was significantly lower in blacks 14.33(±4.13) compared to 22.09 (±5.45)ng/ml in whites, p<0.001. F25D was lower in blacks 3.55(±1.17) versus 4.64(±1.25) pg/ml p<0.001. Baseline mean serum PTH was higher in the older black women 44(±21) compared to whites 38 (±14)pg/ml (p=0.03). In young black women serum PTH was higher 44(±18) than white women 31(±10)(p<0.01). Serum PTH decreased on vitamin D. The decrease in PTH compared to levels of serum F25D was similar in young and old, black and white women. The decrease in PTH was 6% for each 1% increase in F25D. The slope for the regression of PTH on serum T25D was steeper in blacks than whites (p<0.01) but did not differ by age. The percent decrease in PTH was 13% in blacks and 5% in whites for each 1% increase in T25D.
Summary:
The percent decrease in serum PTH after vitamin D was related to increasing free and total 25D in young and old, black and white women. However, black women showed a significantly larger decrease in PTH with T25D, possibly because of more secondary hyperparathyroidism. Because the parathyroid gland has the megalin and cubilin receptors mechanism for uptake of DBP it may not be unexpected that the correlations between serum PTH and free and total 25(OH)D are so similar.