Accounting for Surgical Confounding Factors Affecting Dual-Energy X-ray Absorptiometry in a Large Clinical Trial.

Joint replacements are among the most common orthopedic procedures performed in the U.S. and will continue to increase with the aging population. It is therefore necessary to account for these and other confounding factors, such as breast implants, when performing dual-energy X-ray absorptiometry (DXA) measurements. Whole-body DXA scans were performed in 771 participants (men ≥50 yr and women ≥55 yr) to assess bone mineral density (BMD) and body composition (fat and lean mass). In the DXA scan analyses of participants with internal metal, these affected regions of interest were replaced with measures from the unaffected, contralateral side, consistent with recommendations of the International Society for Clinical Densitometry. T-scores and Z-scores were recalculated using default sex and ethnicity-matched databases. We also explored effects of breast implants on bone density and body composition analyses. Approximately 13.1% of participants had internal metal artifacts at baseline. Replacing metal artifacts with the unaffected, contralateral side decreased the whole-body BMD by an average of 8.1% (SEM 0.84%; n = 67). In participants with unilateral hip (n = 17) and knee replacements (n = 20), BMD was decreased by an average of 14.1% (SEM 1.7%) and 11.2% (SEM 1.1%), respectively. Fat and lean mass were not significantly affected by metal artifacts, as differences between values with and without metal were within 1%. Two participants had bilateral breast implants, and in a separate trial, one participant had a unilateral breast implant. Bone mineral content (BMC) in the region with the breast implant was 5.8 times higher than the contralateral side, and whole-body BMC was increased by 4.7%. Metal artifacts and breast implants can confound DXA whole-body bone but not fat and lean results. It is therefore important in clinical studies to account for these factors to detect physiologically relevant differences in bone measures.

Effects of Supplemental Vitamin D on Bone Health Outcomes in Women and Men in the VITamin D and OmegA-3 TriaL (VITAL).

Although supplemental vitamin D is used to promote bone health in the general population, data from randomized controlled trials (RCTs) have been inconsistent. We determined whether daily, vitamin D3 supplementation improves bone mineral density (BMD) and/or structure. VITamin D and OmegA-3 TriaL (VITAL) is a double-blind, placebo-controlled RCT of supplemental vitamin D3 (2000 IU/d) and/or omega-3 fatty acids (1 g/d) in 25,871 adults nationwide. This ancillary study included a subcohort of 771 participants (men ≥50 and women ≥55 years; not taking bone active medications) evaluated at baseline and at 2-year follow-up (89% retention). Total 25(OH)D levels were measured by liquid chromatography tandem mass spectrometry (Quest Diagnostics, San Juan Capistrano, CA, USA). Free 25(OH)D (FVD) levels were measured using the ELISA assay by Future Diagnostics Solutions BV (Wijchen, Netherlands). Primary endpoints were 2-year changes in areal (a) BMD at the spine, hip, and whole body determined by dual-energy X-ray absorptiometry (DXA). Secondary endpoints were 2-year changes in volumetric (v) BMD and cortical thickness at the radius and tibia assessed by peripheral quantitative computed tomography. Supplemental vitamin D3 versus placebo had no effect on 2-year changes in aBMD at the spine (0.33% versus 0.17%; p = 0.55), femoral neck (-0.27% versus -0.68%; p = 0.16), total hip (-0.76% versus -0.95%; p = 0.23), or whole body (-0.22% versus -0.15%; p = 0.60), or on measures of bone structure. Effects did not vary by sex, race/ethnicity, body mass index, or 25(OH)D levels. Among participants with baseline FVD levels below the median (<14.2 pmol/L), there was a slight increase in spine aBMD (0.75% versus 0%; p = 0.043) and attenuation in loss of total hip aBMD (-0.42% versus -0.98%; p = 0.044) with vitamin D3 . Whether baseline FVD levels help to identify those more likely to benefit from supplementation warrants further study. Supplemental vitamin D3 versus placebo for 2 years in general healthy adults not selected for vitamin D insufficiency did not improve BMD or structure. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.

Baseline characteristics of participants in the VITamin D and OmegA-3 TriaL (VITAL): Effects on Bone Structure and Architecture.

Vitamin D supplements are often used to benefit skeletal health, although data on effects of daily high-dose vitamin D alone on bone density and structure are lacking. The ongoing VITamin D and OmegA-3 TriaL (VITAL) is a double-blind, randomized, placebo-controlled trial testing effects of high-dose supplemental vitamin D3 (cholecalciferol; 2000 IU/day) and/or omega-3 fatty acids (FAs; 1 g/day) for the primary prevention of cancer and cardiovascular disease. The study has a mean treatment period of 5 years among 25,874 U.S. men ≥50 years and women ≥55 years old from all 50 states. The ancillary study, VITAL: Effects on Bone Structure and Architecture, is testing effects of vitamin D3 and/or omega-3 FAs on musculoskeletal outcomes and body composition in a subcohort of 771 participants. At in-person visits at the Harvard Catalyst Clinical and Translational Science Center (CTSC), participants completed bone density/architecture, body composition, and physical performance assessments at baseline and two-year follow-up. Baseline characteristics were evenly distributed among treatment groups, suggesting that any uninvestigated confounders will be evenly distributed; sex differences were also analyzed. Future analyses of the two-year follow-up visits will elucidate whether daily high-dose, supplemental vitamin D3 and/or omega-3 FAs improve musculoskeletal outcomes, helping to advance clinical and public health recommendations. CLINICAL TRIAL REGISTRATION NUMBER: NCT01747447.