Context: Whether ergocalciferol (D2) and cholecalciferol (D3) are equally effective to increase and maintain serum 25-hydroxyvitamin D [25(OH)D] concentration is controversial. Objective: The aim of the study was to evaluate the effect of daily and once monthly dosing of D2 or D3 on circulating 25(OH)D and serum and urinary calcium. Design, Setting and Participants: In a university clinical research setting, 64 community dwelling adults age 65+ were randomly assigned to receive daily (1,600 IU) or once-monthly (50,000 IU) D2 or D3 for 1 yr. Main Outcome Measures: Serum 25(OH)D, serum calcium, and 24-h urinary calcium were measured at months 0, 1, 2, 3, 6, 9, and 12. Serum PTH, bone-specific alkaline phosphatase, and N-telopeptide were measured at months 0, 3, 6, and 12. Results: Serum 25(OH)D was less than 30 ng/ml in 40% of subjects at baseline; after 12 months of vitamin D dosing, levels in 19% of subjects (n = 12, seven receiving daily doses and five monthly doses) remained low, despite compliance of more than 91%. D2 dosing increased 25(OH)D2 but produced a decline (P < 0.0001) in 25(OH)D3. Substantial between-individual variation in 25(OH)D response was observed for both D2 and D3. The highest 25(OH)D observed was 72.5 ng/ml. Vitamin D administration did not alter serum calcium, PTH, bone-specific alkaline phosphatase, N-telopeptide, or 24-h urine calcium. Conclusions: Overall, D3 is slightly, but significantly, more effective than D2 to increase serum 25(OH)D. One year of D2 or D3 dosing (1,600 IU daily or 50,000 IU monthly) does not produce toxicity, and 25(OH)D levels of less than 30 ng/ml persist in approximately 20% of individuals. Substantial between-individual response to administered vitamin D2 or D3 is observed.

Many osteoporotic vertebral fractures are not clinically recognized but increase fracture risk. We hypothesized that a newer generation densitometer increases the number of evaluable vertebrae and vertebral fractures detected. We also explored the impact of reader experience on vertebral fracture assessment (VFA) interpretation.

CONTEXT Measurement of circulating 25-hydroxy-vitamin D [25(OH)D]) is the accepted clinical indicator of vitamin D status. However, between-laboratory differences in measurement of this analyte exist, which may confound clinical care. OBJECTIVES We investigated the current agreement of 25(OH)D measurement in clinical laboratories and explored the possibility that simple calibration would improve between-laboratory agreement. DESIGN AND PARTICIPANTS Serum obtained from healthy volunteers (age 20-60 yr) and one "calibrator," selected to have a 25(OH)D value near 30 ng/ml, were sent for 25(OH)D measurement in four clinical laboratories (laboratories A-D) using HPLC, liquid chromatography tandem mass spectroscopy, and RIA methodologies. MAIN OUTCOME MEASURES Serum 25(OH)D. Based upon self-report, the laboratory with the lowest interassay percent coefficient of variation was assigned as the reference to which the others were compared using linear regression and Bland-Altman analyses (Analyse-it; Analyse-it Software, Ltd., Leeds, UK). RESULTS Good correlation was observed for 25(OH)D measurement between laboratory A and laboratories B-D (R(2) = 0.99, 0.81, and 0.95, respectively). Modest between-laboratory variation was noted; the mean bias ranged from 2.9-5.2 ng/ml. Consistent with a systematic offset, each value in laboratory B was higher than in laboratory A, and 89% of values from laboratories B-D were higher than laboratory A. The use of a single calibrator and correction factor reduced mean between-laboratory bias for laboratories B and D. CONCLUSIONS Measurement of 25(OH)D by clinical laboratories yields similar results. The use of even a single calibrator will improve, but not resolve, between-laboratory variability. Based upon these data, in combination with reported within-individual variability, we recommend that clinicians aim for values greater than 30 ng/ml in their patients.

Low vitamin K status is associated with low BMD and increased fracture risk. Additionally, a specific menaquinone, menatetrenone (MK4), may reduce fracture risk. However, whether vitamin K plays a role in the skeletal health of North American women remains unclear. Moreover, various K vitamers (e.g., phylloquinone and MK4) may have differing skeletal effects. The objective of this study was to evaluate the impact of phylloquinone or MK4 treatment on markers of skeletal turnover and BMD in nonosteoporotic, postmenopausal, North American women. In this double-blind, placebo-controlled study, 381 postmenopausal women received phylloquinone (1 mg daily), MK4 (45 mg daily), or placebo for 12 mo. All participants received daily calcium and vitamin D(3) supplementation. Serum bone-specific alkaline phosphatase (BSALP) and n-telopeptide of type 1 collagen (NTX) were measured at baseline and 1, 3, 6, and 12 mo. Lumbar spine and proximal femur BMD and proximal femur geometry were measured by DXA at baseline and 6 and 12 mo. At baseline, the three treatment groups did not differ in demographics or study endpoints. Compliance with calcium, phylloquinone, and MK4 treatment was 93%, 93%, and 87%, respectively. Phylloquinone and MK4 treatment reduced serum undercarboxylated osteocalcin but did not alter BSALP or NTX. No effect of phylloquinone or MK4 on lumbar spine or proximal femur BMD or proximal femur geometric parameters was observed. This study does not support a role for vitamin K supplementation in osteoporosis prevention among healthy, postmenopausal, North American women receiving calcium and vitamin D supplementation.