Guidelines for Preventing and Treating Vitamin D Deficiency and Insufficiency Revisited

Abstract

Vitamin D is currently a topic of intense interest to the scientific and lay communities. Recently a committee convened by the Institute of Medicine (IOM) released a report identifying dietary reference intakes; subsequently, The Endocrine Society Clinician Vitamin D Guideline was published (1, 2). Because these recommendations are not entirely congruent, in this issue of the Journal, we put into perspective how the goals of the guidelines differed from those of the IOM Committee. The guideline's intent was to provide guidance for clinicians caring for patients, not to make recommendations for normal healthy populations as covered by the IOM report. It is axiomatic that the physician's role is to provide recommendations to maximize the health of their individual patient, not to provide population-based care. Thus, because the target for these recommendations differ, it is not surprising that the guidance might also differ. It is not the intent of this commentary to revisit exhaustive data reviews. However, it is important to emphasize that the IOM report focused only on bone health (calcium absorption, bone mineral density, osteomalacia/rickets, etc.) and found no evidence that a serum 25-hydroxyvitamin D [25(OH)D] concentration above 20 ng/ml has beneficial effects at a population level. However, on an individual level, a salient publication by Priemel et al. (3) found elevated unmineralized osteoid (a hallmark of vitamin D deficiency bone disease) in 21% (six of 28) of otherwise healthy men and women whose 25(OH)D was between 20 and 30 ng/ml (3, 4) (Fig. 1) Moreover, remarkable between-individual variability of the 25(OH)D/osteoid relationship was observed. Similar variability is widely recognized for the relationship between 25(OH)D and PTH. Clearly the relationship of 25(OH)D to PTH in a given individual is the result of a complex interplay of factors including age, sex, genetics, renal function, mobility level, calcium intake, and phosphate and magnesium status, which makes selection of a single inflection point challenging at best and impossible in studies with a small number of subjects like that of Rucker et al. (5). For example, in a report of 33,055 women and 77,118 men, both sex and age influenced the level at which 25(OH)D caused the PTH levels to plateau. In men aged 21–30 yr, PTH levels plateaued when 25(OH)D was 35–39 ng/ml (87.5–97.3 nmol/liter), whereas in females of the same age range, the plateau was reached when 25(OH)D was 30–34 ng/ml (75–85 nmol/liter). This difference was more dramatic in men aged 41–50 yr in whom the PTH levels plateaued when the 25(OH)D reached 30–34 ng/ml (75–85 nmol/liter), whereas in females of the same age range, the PTH levels plateaued at 20–24 ng/ml (50–60 nmol/liter) (6, 7). Therefore, the target range for 25(OH)D to minimize PTH levels may be both gender and age dependent, with men requiring a higher serum 25(OH)D than women of the same age. These findings are consistent with the observation in postmenopausal women that the prevalence of secondary hyperparathyroidism (PTH >40 pg/ml) was lowest when serum 25(OH)D was above 30 ng/ml (75 nmol/liter) (8) (Fig. 2). Although many of these women were on a bisphosphonate, which can potentially increase PTH levels, there is no evidence that vitamin D status independently influences this effect. Such variations in PTH levels could lead clinicians to conclude that a 25(OH)D concentration of 20 ng/ml does not assure optimal calcium metabolism and bone health in an individual patient. Taken together, these data suggest that a 25(OH)D concentration of 20 ng/ml does not assure optimal calcium metabolism and bone health in all individuals.