Abstract
J Clin Endocrinol Metab 2012;
The serum concentration of 25-hydroxyvitamin D (25OHD) that is required for optimal bone health, vitamin D sufficiency, may be defined as that concentration at which parathyroid hormone (PTH) is not stimulated, demonstrated by either a plateau or point of inflection on a graph of PTH concentration plotted against 25OHD. The 25OHD concentrations suggested in the literature for sufficiency range from <25 nmol/L to >100 nmol/L. This lack of consensus may be due to differences in populations studied, sample size or statistical methods.
Valcour et al. present data from almost 313,000 paired 25OHD and PTH samples submitted for analysis to Lab Corp. laboratories across the USA in one year. All samples were included with no filtering for clinical details or other results. Less than 5% had a request for calcium and less than 1% for creatinine, prompting the authors to conclude that most requests were part of an osteoporosis screen.
To study the relationship between PTH and 25OHD, they divided the samples into 63 bins of 5000 samples with increasing 25OHD concentration and plotted the median PTH of each group against the mean 25OHD. The result is a smooth curve from high PTH at low 25OHD to low PTH at high 25OHD with very little scatter. There is no evidence of a point of inflection or that PTH plateaus at high 25OHD concentrations. A graph of the percentage of PTH results >6.9 pmol/L against mean 25OHD also gave a smooth curve. They examined the effect of age on the relationship between PTH and 25OHD by dividing the samples into <20 years, 20–40 years, 40–60 years and >60 years within each bin of 5000 samples and plotting four graphs. It is clear that with increasing age any 25OHD concentration is associated with higher PTH results. This may be because the older population has a greater burden of chronic kidney disease and primary hyperparathyroidism or may reflect depletion of calcium stores or the effects of chronic 25OHD insufficiency. The greater scatter around the plotted line for individuals <20 years may be due to the small numbers (only 3500) or more heterogeneous indications for simultaneous PTH and 25OHD measurement compared to the >60 years group.
A significant number of individuals had 25OHD <50 nmol/L and raised PTH (9% of the whole population, 37% of the >60 years group). As well as the effect on bone health, secondary hyperparathyroidism is a known risk factor for cardiovascular disease. The authors suggest that those with 25OHD <25 nmol/L and a normal PTH should be checked for hypomagnesaemia.
In conclusion, this is the largest study to date of the relationship between PTH and 25OHD concentrations. There was no evidence of a population cut-off that would indicate optimal vitamin D status. For investigation of the individual more understanding of the effects of age, renal function and length of time with suboptimal vitamin D status on the relationship between PTH and 25OHD are required.