|Picciano, Mary Frances|
Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/22/2009
Publication Date: 3/1/2010
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 y of age and older. Journal of Nutrition. 140(3):595-596. Interpretive Summary: Vitamin D insufficiency leads to a rise in the serum parathyroid hormone (PTH) level, and higher levels of PTH promote bone loss. One indicator of optimal vitamin D status is the level of serum 25OHD that is associated with maximal suppression of the PTH level, referred to as the change-point. Many investigators have sought the change-point and come up with different results. We undertook this analysis to determine the extent to which the statistical approach used affected the change-point identified. We applied both two- and three-phase regression analyses to a single data set, our STOP/IT database of over 300 men and women age 65 years and older. These analyses revealed that the three-phase model identified points at which rapid and slow change occurred. The variable reports in the literature cluster around either the rapid or the slow change points. We conclude that the three-phase model explains a significant amount of the variation in the optimal level of serum 25(OH)D levels reported to date and that it offers a more detailed description of the association between serum 25(OH)D and PTH. In the future, we recommend application of the three-phase model when addressing the level of serum 25(OH)D associated with maximal suppression of serum PTH.
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 two-phase regression approach used, two distinct clusters for a single 25(OH)D threshold have been reported, i.e. 16-20 ng/ml (40-50 nmol/L) and 30-32 ng/ml (75-80 nmol/L). To rationalize the apparently disparate results, we compared the thresholds from several regression models including a three-phase one to estimate simultaneously two thresholds before and after adjusting for possible confounding for age, body mass index (BMI), glomerular filtration rate (GFR), dietary calcium and season (April-September vs. October–March) within a single data set, i.e. data from the Tufts University STOP/IT study site consisting of 387 men (n=181) and women (n=206) ages 65-87y. Mean levels (+/- SD) of plasma 25(OH)D and serum iPTH were 22.1 +/- 7.44 ng/mL (55.25 +/- 18.6 nmol/L) and 36.6 +/- 16.03 pg/mL, respectively. The three-phase model identified two thresholds of 12 ng/ml (30 nmol/L) and 28 ng/ml (70 nmol/L); similar results were found from the two-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 didn’t change the results substantially. Accordingly, the three-phase model appears to be superior to the two-phase approach as it simultaneously estimates the two threshold clusters found from the two-phase approaches along with estimating confidence limits. If replicated, it may be of both clinical and public health significance.