The Effects of Vitamin D Replacement with a High-Dose Treat-to-Goal Strategy.

The intervention protocol successfully raised and maintained 25(OH)D concentrations at approximately 40 ng/mL over 5 years.

• Baseline vitamin D in the intervention group was 21.9 ng/mL.
• At 2 months, levels reached 41.0 ng/mL and remained stable: 1 year: 39.4; 2 years: 39.0; 3 years: 39.3; 4 years: 40.4; and 5 years: 39.4 ng/mL.
• Mean 25(OH)D and rates of adequacy were significantly higher over time in the intervention arm (p < 0.0001).
• The protocol involved two steps: a loading dose (LD) for 2 months followed by a maintenance dose (MD) thereafter using cholecalciferol.

Vitamin D adequacy was achieved in 91.6% of intervention patients compared to only 16.9% of controls.

• The difference in adequacy rates between groups was statistically significant (p < 0.0001).
• Vitamin D deficiency was defined as 25(OH)D < 30 ng/mL per the 2011 Endocrine Society definition.
• Controls self-reported never taking vitamin D supplements.
• The study included 1575 intervention subjects and 673 controls.

Vitamin D concentrations in the control group did not change significantly over the 5-year follow-up period.

• Baseline vitamin D in controls was 22.6 ng/mL.
• Subsequent measurements in controls were: 2 months: 22.2; 1 year: 21.7; 2 years: 22.0; 3 years: 23.8; 4 years: 21.8; and 5 years: 22.1 ng/mL.
• Controls consistently remained below the 30 ng/mL sufficiency threshold throughout follow-up.

The intervention protocol did not increase the incidence of renal adverse events or hypervitaminosis compared to controls.

• The incidence of renal adverse events or hypervitaminosis did not differ between groups (p > 0.05).
• Adverse events tracked included history of nephrolithiasis, nephrocalcinosis, and renal colics.
• This safety finding was observed despite the intervention group achieving mean 25(OH)D levels of approximately 40 ng/mL over 5 years.

The study included 2248 subjects with adequate follow-up data drawn from a larger pool of 8329 cases with vitamin D measurements.

• Total follow-up amounted to 3524.5 patient-years with an average follow-up of 18.8 months per subject.
• The study included 1575 intervention subjects and 673 controls.
• Recorded variables included baseline, 2-month, and annual 25(OH)D measurements, along with age, sex, BMI, and history of osteoporosis, nephrolithiasis, nephrocalcinosis, and renal colics.
• The review period spanned 5 years.