Recent influential reviews have stated that a serum 25(OH)D level of 30 ng/mL should be used as the threshold for vitamin D inadequacy. In the study analyzed in those reviews, serum iPTH showed a plateau at serum 25(OH)D of approximately 30 ng/mL. However, recent studies show that the 25(OH)D level at which iPTH levels attain a plateau cannot be used by itself to estimate the vitamin D inadequacy threshold (15
). There are also studies that showed no iPTH plateau in the 25(OH)D-iPTH relation, which makes the choice of an optimal 25(OH)D concentration based only on iPTH arbitrary (14
). Moreover, since results from recent studies suggest relatively higher iPTH levels in old people, it would be necessary to separately address the 25(OH)-iPTH relation in the elderly (15
Using the exponential decay model to describe the 25(OH) D-iPTH relationship in our study, iPTH levels reached a plateau when 25(OH)D concentration was 36.7 ng/mL in men and iPTH levels failed to reach a plateau in women. The 25(OH)D concentration of 36.7 ng/mL in men far exceeds the consensus threshold for vitamin D inadequacy. When femur neck BMD values around 36.7 ng/mL were compared in men, there were no differences. This may partly be attributable to the small number of men with 25(OH)D levels ≥ 36.7 ng/mL, but further results from our study suggest otherwise.
When femur neck BMD values were compared around specific 25(OH)D values from 10 ng/mL to 30 ng/mL, femur neck BMD values differed when the cut off 25(OH)D concentrations were 15-27.5 ng/mL in men. Also, in postmenopausal women, femur neck BMD values were different when they were compared around 25(OH)D concentrations of 12.5-20 ng/mL. The coefficient of determination was greatest in both sex when 25(OH)D concentration was 15 ng/mL.
Our results show that the threshold vitamin D value cannot be determined in the context of iPTH levels alone, and that the adequate 25(OH)D levels should also be evaluated in the context of other factors concerning bone health, such as BMD. In order to further determine the threshold vitamin D level, measurements on bone turnover markers, and intestinal calcium and phosphorus absorption should also be performed.
Though lumbar spine BMD did not correlate with 25(OH)D and iPTH levels, femur neck BMD was positively correlated with 25(OH)D and negatively correlated with iPTH, in both men and women. (However, femur neck BMD values did not have a statistically significant correlation with iPTH levels in women.) Similar associations have been reported in other studies (21
). Degenerative changes in the lumbar spine, aortic and extraskeletal calcification associated with aging may falsely elevate lumbar spine BMD and hence result in a non-specific association between 25(OH)D and lumbar spine BMD (22
). Also, it is known that iPTH-mediated bone resorption preferentially involves cortical bone than trabecular bone. Since the femur contains more cortical bone, it is likely that elevated iPTH levels secondary to decreased serum 25(OH)D concentrations may have affected the femur more than the spine.
When study subjects were categorized into 3 age groups and iPTH concentrations were compared among those who had similar 25(OH)D levels, iPTH concentration of the oldest age group was consistently higher than that of younger age groups. This probably implies that older people need higher 25(OH)D levels to offset age-associated hyperparathyroidism. These results are in line with data from women in our cohort.
Older women had higher iPTH levels compared with younger women throughout the year though vitamin D levels were not significantly different among the age groups. The rise in iPTH level was most prominent in women aged ≥ 80 yr in the winter season, which may have been attributable to the especially lower levels of serum 25(OH)D in this season caused by less sunshine exposure.
Similar results have been obtained in other studies (13
), but these studies included young individuals, and age-related changes of 25(OH)D and iPTH levels limited to old people have not been evaluated so far. This study excluded individuals aged less than 50 yr, thus giving a perspective into 25(OH)D and iPTH levels in old people. Our results also suggest that older women may be less efficient at preventing secondary hyperparathyroidism caused by low 25(OH)D levels, compared with men and younger women.
Some studies have shown that intestinal calcium absorption decreases with aging, probably due to intestinal resistance to 1,25(OH)2
D, which leads to compensatory increases in iPTH secretion and 1,25(OH)D production, to maintain calcium absorption and serum ionic calcium (23
). Such factors may have contributed to the relatively high iPTH levels in the older individuals in our study. Also, the higher iPTH levels in older women in the winter season may be attributable to the fact that these women had the lowest 25(OH)D levels among all the study subjects. The low 25(OH)D levels, in turn, would have probably resulted from the limited outdoor activities of old women compared to the rest of the individuals in the winter season. Since there were relatively small numbers of individuals aged ≥ 80 yr, more study subjects would be required to further evaluate this phenomenon.
There are some limitations in our study that should be acknowledged. The cross-sectional design of our study limits any causal inferences. Also, our study was performed on very old people dwelling in a rural area and whose educational and economical statuses were very poor. Therefore the results of our study cannot be extended to the general population. However, this study was performed on a relatively large population, and the exclusion of young people from the study allowed the authors to focus on age-related changes of serum 25(OH)D and iPTH in elderly people, and to assess the correlation between 25(OH)D and iPTH with BMD in such a population.
In conclusion, this study shows that the desirable level of serum 25(OH)D cannot be estimated based on iPTH alone, and that other factors concerning bone health, such as BMD, should also be considered to evaluate the optimal level of vitamin D. This study also shows that older people have higher iPTH levels compared with younger people with similar 25(OH)D levels. Therefore older people would require higher levels of 25(OH)D to offset age-related compensatory hyperparathyroidism. This phenomenon was most prominent in the oldest women in our cohort, especially in the winter season, which implies that elderly vitamin D-inadequate women in the winter are most vulnerable to age-associated hyperparathyroidism.