Investigation of the Vitamin D Metabolite Ratio (VMR) as a Marker of Functional Vitamin D Deficiency: Findings from the SarcoPhAge Cohort

The vitamin D metabolite ratio (VMR) has recently been identified as a potentially better indicator of vitamin D deficiency than 25-hydroxyvitamin D (25(OH)D) alone. This study aims to validate these findings by demonstrating that VMR is more strongly correlated with parathyroid hormone (PTH) levels than 25(OH)D and 24,25-dihydroxyvitamin D (24,25(OH) D). In addition, the study investigates VMR as a more effective predictor of mortality than 25(OH)D and 24,25(OH) D. The SarcoPhAge cohort is a Belgian cohort of community-dwelling older adults. Levels of 25(OH)D and 24,25(OH) D were measured in 204 serum samples collected at the second year of follow-up using liquid chromatography-tandem mass spectrometry (LC-MS/MS), and VMR was calculated using the formula: VMR = (24,25(OH)D/25(OH)D) × 100. Vitamin D deficiency cut-offs were defined at 25(OH)D < 20 ng/mL, 24,25(OH) D < 1.2 ng/mL, or VMR < 4% according to previously proposed cut-offs. Participants were followed for up to 9 years. A total of 35 individuals (17.2%) had 25(OH)D < 20 ng/mL, 40 individuals (19.6%) had 24,25(OH) D < 1.2 ng/mL, and 14 individuals (7.0%) had VMR < 4%. All three markers, 25(OH)D, 24,25(OH) D, and VMR, were independently associated with PTH levels, with VMR showing the strongest correlation (rho: -0.292; < 0.0001). When categorized into quartiles, only 24,25(OH)2D and VMR showed significant increases in PTH levels across quartiles ( = 0.002 and < 0.0001, respectively). When cut-offs for low vitamin D status were applied, patients with low VMR had the highest rate of all-cause mortality. However, in a Cox proportional hazard regression model, both low VMR profile and low 25(OH)D profile were risk factors for all-cause mortality. This study confirms that VMR is an efficient biomarker for assessing functional vitamin D deficiency.