Association of the Vitamin D Metabolite Ratio with Bone Turnover Markers and Changes in Volumetric Bone Mineral Density

Abstract The vitamin D metabolite ratio (VMR), calculated as the ratio of 24,25-dihydroxyvitamin D to 25-hydroxyvitamin D (25[OH]D), is a marker of vitamin D stores that may provide a more accurate reflection of bone health outcomes than 25(OH)D alone. In this analysis we examined the relationship between VMR and 25(OH)D with bone turnover markers (BTM’s) and changes in volumetric bone mineral density (Tt.BMD) in older community-dwelling men participating in the Osteoporotic Fractures in Men (MrOS) study. Tt.BMD was measured at the distal radius and tibia by high resolution peripheral quantitative computed tomography (HR-pQCT) at two separate visits approximately 6 years apart. BTMs were measured at the time of the first HR-pQCT scan and included parathyroid hormone (PTH), C-terminal telopeptide of type I collagen (CTX-I), and N-terminal propeptide of type I procollagen (PINP). Linear regression was used to evaluate the association of VMR and 25(OH)D with BTM’s and annualized percent change in Tt.BMD. The mean (SD) age of the 254 men was 83(3) years, with an eGFR of 71(14) mL/min/1.73m2. Mean VMR and 25(OH)D were 6.5(2.2) (ng/mL)/(ng/mL) and 39(14) ng/mL, respectively. Both the VMR and 25(OH)D were inversely associated with PTH concentrations (P<0.02 for both). In fully adjusted models a twofold higher VMR was associated with a 34% [12%; 55%] lower CTX-I and a 16% [1.3%;30%] lower PINP while 25(OH)D was not associated with these BTMs. The relationship of VMR with BTM’s appeared stronger among men with chronic kidney disease (CKD, eGFR < 60 mL/min/1.73m2) than in persons with normal renal function. Neither VMR nor 25(OH)D were associated with annualized change in Tt.BMD in fully adjusted models.