ARS | Publication request: Three-Phase Model Harmonizes Estimates of the Maximal Suppression of Parathyroid Hormone by 25-Hydroxyvitamin D in Persons 65 Years of Age and Older 1

Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: December 22, 2009
Publication Date: March 1, 2010
Citation: Durazo-Arvizu, R.A., Dawson-Hughes, B., Sempos, C.T., Yetley, E.A., Looker, A.C., Cao, G., Harris, S.S., Burt, V.L., Carriquiry, A.L., Picciano, M. 2010. Three-Phase Model Harmonizes Estimates of the Maximal Suppression of Parathyroid Hormone by 25-Hydroxyvitamin D in Persons 65 Years of Age and Older 1–3. Journal of Nutrition. 140(3):595-599.

Interpretive Summary: Low vitamin D levels cause an increase in serum parathyroid hormone (PTH) and higher PTH levels cause increased bone loss. One way to define vitamin D adequacy is to use the level of vitamin D needed to maximally suppress serum PTH. This vitamin D level varies widely from one study to another (from 10 to 50 ng/ml). This study was done to determine how much of this variation might be attributable to different analytical approaches used by different investigators, as opposed to biological differences from one population to another. Our STOP/IT data on 445 men and women age 65 and older were analyzed using several statistical approaches. We found that the three-phase model was the best fit with the data and that it identified two thresholds at serum vitamin D levels. That agreed with estimates found by other investigators. These findings suggest that the differences observed in the literature are in large part attributable the statistical method used rather than to inherent biological differences.

Technical Abstract: The concentration or threshold of 25-hydroxyvitamin D [25(OH)D] needed to maximally suppress intact serum parathyroid hormone (iPTH) has been suggested as a measure of optimal vitamin D status. Depending upon the definition of maximal suppression of iPTH and the 2-phase regression approach used, 2 distinct clusters for a single 25(OH)D threshold have been reported: 16–20 ng/mL (40–50 nmol/L) and 30–32 ng/mL (75–80 nmol/L). To rationalize the apparently disparate published results, we compared thresholds from several regression models including a 3-phase one to estimate simultaneously 2 thresholds before and after adjusting for possible confounding for age, BMI, glomerular filtration rate, dietary calcium, and season (April–September vs. October–March) within a single data set, i.e. data from the Tufts University Sites Testing Osteoporosis Prevention/Intervention Treatment study, consisting of 181 men and 206 women (total n = 387) ages 65–87 y. Plasma 25(OH)D and serum iPTH concentrations were (mean 6 SD) 22.1 6 7.44 ng/mL (55.25 6 18.6 nmol/L) and 36.6 6 16.03 pg/mL (3.88 6 1.7 pmol/L), respectively. The 3-phase model identified 2 thresholds of 12 ng/mL (30 nmol/L) and 28 ng/mL (70 nmol/L); similar results were found from the 2-phase models evaluated, i.e. 13–20 and 27–30 ng/mL (32.5–50 and 67.5–75 nmol/L) and with previous results. Adjusting for confounding did not change the results substantially. Accordingly, the 3-phase model appears to be superior to the 2-phase approach, because it simultaneously estimates the 2 threshold clusters found from the 2-phase approaches along with estimating confidence limits. If replicated, it may be of both clinical and public health importance.