As early as 1987, researchers began to study the relationship between vitamin D and iPTH by cross-sectional studies or randomized controlled trials to search the plateau period of iPTH and the corresponding 25(OH)D concentration among different groups, including the elderly, female, healthy adults, vitamin D-deficient people, etc [14-15]. Survey data from NHANES 2003-2004 and 2004-2005 shows that the relationships among 25(OH)D, BMD and PTH in American adults vary according to race/ethnicity. Significant inverse relationship between 25(OH)D and iPTH values was only observed when 25(OH)D concentrations were below 26 ng/ml among blacks, while inverse relationship was observed above and below a 25(OH)D level of 20 ng/ml in whites and Mexican-Americansin . Aloia et al.  found that iPTH reached plateau stage when the serum 25(OH)D concentration was between 40-50 nmol/L (16-20 ng/mL) of African American women. In addition to the above studies, there are also studies that failed to find the threshold [10, 17]. Different races and genetic backgrounds might explain the phenomenon, and it is necessary to study whether the same cutoffs are suitable for different ethnicity.
This is the first national cross-sectional study on the threshold of 25(OH)D among Chinese population. In our study, we analyzed the threshold when iPTH reaching plateau stage by sex, because of the significant difference in the distribution of 25(OH)D levels between male and female. We found that the concentration of 25(OH)D was 19.2 ng/mL (48 nmol/L) while not adjusted by covariates when iPTH entered into its plateau in Chinese women aged 18-44y. It is close to the threshold of 50.8 nmol/L (20.3 ng/mL) in adult of both sex aged 20-45y in Shanghai city, China reported by Yao et al . The threshold for 25(OH)D was 17.6 ng/mL after adjusted by sex, age, latitude, BMI, waist and season of blood draw. It was close to IOM' recommendation and similar with most study reported . The threshold of male (16.2 ng/mL) was obviously lower than that of female (25.6 ng/mL). Both of the thresholds were within the most frequent range of literature reports. There are few studies about the threshold of male reported, scattered in the range of 15-20ng/mL, followed by 30-35ng/mL . The threshold for the deficiency of sex could be better explored and analyzed with more relevant indicators, such as calcium and vitamin D intake, renal function, bone health indicators, endocrine indicators, etc. Arabi et al.  think that age but not gender modulate the relationship between 25(OHD) and PTH among adolescents (10-17 years) and elderly (65-85 years) of the same ethnic group living in Lebanon. No age specific difference was found in terms of relationship between 25(OH)D and iPTH in this study, probably because of the concentrated age distribution. However, the sex differences of threshold was found in the relationship of 25(OH)D and PTH in our study. Similar sex differences were reported by a cross-sectional study conducted among adolescents aged 12-15y in North Ireland, where the researchers found a threshold at 60 nmol/L (24 ng/mL) in girls, however, no cutoff was found in boy . Although 25(OH)D level of male was significantly higher than that of female, iPTH did not differ significantly. This might also indicate that the corresponding iPTH was no longer decreased when the level of 25(OH)D increases to a certain range. The secretion of sex hormones and growth hormone might also be associated with the sex difference. The results from different studies is controversial regarding the relationships of 25(OH)D concentration with levels of sex hormones and gonadotropins . Frank et al consider that the impact of sex hormone on skeletal metabolism was different between sexes [22, 23]. Besides the intake of vitamin D and calcium, the nutritional status, such as vitamin K nutritional status which has synergetic effect with vitamin D, extent of outdoor activities might be others reason for the disparity between sexes in terms of 25(OH)D. Further study should also be made to reveal the difference between sexes. We also found the disparity of 25(OH)D concentration in different seasons. Though no samples for summer in our study, the seasonal distribution of 25(OH)D concentration is consistent with our former study  and the report from Kroll et al. in the United States . In their study, they found the lowest concentration of iPTH occurs 3.5 weeks after the 25(OH)D3 reaches its highest concentration and vice versa. We can hardly tell the impact of relationship between iPTH concentration and 25(OH)D concentration, because our samples are limited and not distributed to every month of a year. Further study should also be made to explore the impact of seasonal factor on the relationship between iPTH and 25(OH)D.
The vitamin D insufficiency and deficiency of Chinese adults aged 18-44y was 34.5% and 19.4%, respectively, according to IOM’s recommendation. The vitamin D insufficiency and deficiency reached to 30.7% and 53.9%, respectively, and only 15.4% was sufficient when adopting TES’s recommendation. The median 25(OH)D concentration was 19.1(13.2-26.1) ng/mL, and it is apparently lower than 10 years ago . Less outdoor time, the use of sunscreen might partly explain the reduction of 25(OH)D concentration. Higher 25(OH)D concentration in southern area attributes to stronger ultraviolet radiation in southern area than in the northern area. We suggest exploring sex specific thresholds by taking into consideration potential impact of physiological differences between male and female. Although there are significant differences in 25(OH)D levels between the northern and southern populations in Chinese adults, it is difficult to distinguish individuals strictly according to regions due to population mobility, topographic differences, and etc. For these reasons, we do not recommend setting different boundaries for different regions.
We acknowledge several limitations. First, the limited samples size. Although samples in this study covered all the provincial administrative regions in China, the sample size was only up to 623 cases. In particular, there were only 10 samples in April, which may also lead to the deviation of results. Since this study is an exploratory study in this field of China, the sample size was small indeed, and we will increase the sample size in subsequent studies. Secondly, the dietary sources of vitamin D and calcium intake , bone health indicators, inflammatory factors, and other factors that may influence the relationship between iPTH and 25(OH)D, were not included in this study. Due to the above factors, it may lead to bias in the relationship or threshold between iPTH and 25(OH)D in this study.