Relationship between vitamin D, parathyroid hormone, and bone health

Abstract

Context: There is a controversy regarding the definition of vitamin D insufficiency as it relates to bone health.

Objective: The objective of the study was to examine the evidence for a threshold value of serum 25-hydroxyvitamin D (25OHD) that defines vitamin D insufficiency as it relates to bone health.

Design and participants: This was a cross-sectional analysis of baseline data in 488 elderly Caucasian women, mean age 71 yr, combined with a literature review of 70 studies on the relationship of serum PTH to serum 25OHD.

Setting: The study was conducted in independent-living women in the midwest United States.

Main outcome measure: The relationship between serum 25OHD, serum PTH, and serum osteocalcin and 24-h urine N-telopeptides was evaluated.

Results: Serum PTH was inversely correlated with serum 25OHD (r = -0.256, P < 0.0005), but no threshold as defined by suppression of serum PTH was found within the serum 25OHD range 6-60 ng/ml (15-150 nmol/liter). However, in contrast, there was a threshold for bone markers, serum osteocalcin and urine N-telopeptides, that increased only below a serum 25OHD of approximately 18 ng/ml (45 nmol/liter). Calcium absorption was not correlated with serum PTH and serum 25OHD, and no threshold was found. A literature review of 70 studies generally showed a threshold for serum PTH with increasing serum 25OHD, but there was no consistency in the threshold level of serum 25OHD that varied from 10 to 50 ng/ml (25-125 nmol/liter).

Conclusions: Vitamin D insufficiency should be defined as serum 25OHD less than 20 ng/ml (50 nmol/liter) as it relates to bone.

Fig. 1.

Various levels of serum 25OHD (nanograms per milliliter) at which serum PTH (picograms per milliliter) plateaus and/or is maximally suppressed. A, Data here are presented from 59 studies (not shown, eight studies in which serum PTH continually decreased with increasing serum 25OHD and three studies that found no relationship between serum 25OHD and serum PTH). B–D, Location, age, and gender of study populations included in these studies.

Fig. 2.

Relationship between serum 25OHD, serum PTH, bone markers, and calcium intake. A, Serum PTH was inversely correlated with serum 25OHD (r = −0.338, P < 0.0005) was continually decreasing with increasing serum 25OHD. Nonlinear regression failed to identify a threshold for serum PTH. Calcium intake was significantly positively correlated with serum 25OHD (r = 0.295, P < 0.0005; B). For serum osteocalcin, nonlinear regression converged on a threshold of 17.034 ng/ml (95% CI 12.61–21.46). Piecewise linear regression indicated an optimal threshold of 17 ng/ml (42.4 nmol/liter; P = 0.007; adjusted R² = 0.016). Before this threshold value, statistically significant decreases in serum osteocalcin were indicated with increases in serum 25OHD; however, this effect plateaued after threshold (C). For uNTx/Cr, nonlinear regression converged on a threshold of 18.0 ng/ml (95% CI 14.347–21.653), with an optimal threshold of 17.5 ng/ml (43.7 nmol/liter; P = 0.0002; adjusted R² = 0.036). Similarly, a plateau effect was evidenced after the threshold (D).

Fig. 3.

Relationship between calcium absorption and vitamin D metabolites. A, Calcium absorption was not associated with serum 25OHD after adjustment for age, body weight, calcium intake, serum 1,25(OH)₂D, and serum creatinine (r = 0.05, P = 0.247). B, Calcium absorption was significantly correlated positively with serum 1,25(OH)₂D after adjustment for age, body weight, calcium intake, serum 25OHD, and serum creatinine (r = 0.224, P < 0.0005).