Randomized Vitamin D Trials Outlining the Relation Between Vitamin D Metabolites and Bone Health Outcomes
| Article Intervention . | N . | Age Gender Race . | Relation to total 25(OH)D . | Relation to PTH . | Relation to calcium + BTM + BMD . | Assay . | Formula for calculated 25(OH)D . | Ranges of vitamin D level . |
|---|---|---|---|---|---|---|---|---|
| Sollid et al, 2016 (27) | 472 | Age 62 years on average | Measured free 25(OH)D | Total 25(OH)D | Total 25(OH) D by LC-MS | Vermeulen’s equation | Total 25(OH)D ~ 63 ± 22 nmol/L, 25.2 ± 8.8 ng/mLCalculated free 25(OH) D 20 ± 7.4 pmol/L, 8 ± 2.96 ng/L | |
| Intervention: 20,000 IU/week | Male/Female 293/179 | r = 0.73, S | r = −0.21* | Free 25(OH) D by ELISA | Measured free 25(OH)D 13.4 ± 4.2 pmol/L, 5.36 ± 1.68 ng/L | |||
| OR 2857 IU/day for 12 mos | Calculated free 25(OH)D | Measured Free 25(OH)D | Calculated bioavailable 25(OH)D 8.5 ± 3.1 nmol/L, 3.4 ± 1.24 μg/L | |||||
| * no r provided | r = −0.17* | After supplementation: | ||||||
| Total 25(OH)D ~ 109 ± 26.2 nmol/L, 43.6 ± 10.48 ng/mL | ||||||||
| Calculated free 25(OH)D 36.9 ± 9.4 pmol/l, 14.7 ± 3.7 ng/L | ||||||||
| Measured free 25(OH)D 21.9 ± 5.2 pmol/L, 8.7 ± 2.08 ng/L | ||||||||
| Yao et al, 2017 (45) | 448 | Age 30 years on average | Baseline bioavailable 25(OH)D | Supplementation Total 25(OH)D and Bioavailable 25(OH)D*, r not provided | Bioavailable 25(OH) D and Calcium, r = 0.11* | Total 25(OH) D by LC-MS | Vermeulen’s equation | Total 25(OH)D 32.8 nmol/L, 13.2 ± 3.52 ng/ mL |
| Intervention: 2000 IU/day for 20 weeks | Male/ Female 141/307 | NS | Bioavailable 25(OH)D 2.7 ± 0.8 nmol/L, 1.08 ± 0.32 μg/L | |||||
| Supplementation Bioavailable 25(OH)D*, no r provided | After supplementation: | |||||||
| Total 25(OH)D 67.3 ± 23.1 nmol/L, 26.92 ± 9.24 ng/mL | ||||||||
| Bioavailable 25(OH)D 3.0 ± 3 nmol/L, 1.2 ± 1.2 μg/L | ||||||||
| Smith et al, 2019 (38) | 358 | Older women: | Baseline free 25(OH) D, S, r = 0.73 | Total and measured free 25(OH)D* | Total 25OHD by LC-MS | Total 25 (OH)D ~ 50.9 ± 13.2 nmol/L, 20.36 ± 5.28 ng/mL | ||
| Intervention: 400 to 4800 IU/day for 12 mos | Age 66 years on average | Supplementation free 25(OH)D r = 0.86* | Free 25(OH) D measured by ELISA | Free 25 (OH)D ~ 9.21 ± 2.88 nmol/L, 3.68 ± 1.15 ng/L | ||||
| Caucasian 140 (62%) | ||||||||
| African American 88 (38%) | ||||||||
| Younger women: | ||||||||
| Age 37 years on average | ||||||||
| Caucasian 91(70%) | ||||||||
| African American 39 (30%) | ||||||||
| Meryl LeBoff et al, 2020 (48) | 771 | Age 63 years on average | pQCT percent change, NS | Total 25(OH) D by LC-MS | Total 25(OH)D 69.1 ± 22.7 nmol/L, 27.64 ± 9.08 ng/mL | |||
| Intervention: 2000 IU/ day for 2 years | Male/ Female: 411/360 | Free 25(OH) D by ELISA | Free 25(OH)D 14.6 ± 4.7 pmol/L, 5.9 ± 1.88 ng/L | |||||
| White 630, Black 67, Hispanic 26, Asian 15 | After supplementation: | |||||||
| Native American or Alaskan native 5 | Total 25(OH)D 98.6 nmol/L, 39.44 ng/mL | |||||||
| Free 25(OH)D 22.3 pmol/L, 8.92 ng/L | ||||||||
| Aspray et al, 2019 (47) | 379 | Age 74 years on average | Total and measured free 25(OH)D, S, no r | Change in BMD, NS | Total 25 (OH)D by LC-MS | Mathematical model | Total 25(OH)D 41.6 ± 19.9 nmol/L, 16.64 ± 7.96 ngl/mL | |
| Intervention: 12,000, 24,000, 48,000 IU/ mo for 12 mos, | Male/ Female: 260/112 | Free 25(OH)D 8.7 ± 4.2 pmol/L, 3.48 ± 1.68 ng/L | ||||||
| Equivalent to 400 IU/ day, 800 IU/day, 1600 IU/day | ||||||||
| After supplementation: | ||||||||
| Total 25(OH)D [55.0-79] nmol/L, [22-31.6] ng/mL | ||||||||
| Free 25(OH)D [11.7-16.8] pmol/L, [4.68-6.72] ng/L |
| Article Intervention . | N . | Age Gender Race . | Relation to total 25(OH)D . | Relation to PTH . | Relation to calcium + BTM + BMD . | Assay . | Formula for calculated 25(OH)D . | Ranges of vitamin D level . |
|---|---|---|---|---|---|---|---|---|
| Sollid et al, 2016 (27) | 472 | Age 62 years on average | Measured free 25(OH)D | Total 25(OH)D | Total 25(OH) D by LC-MS | Vermeulen’s equation | Total 25(OH)D ~ 63 ± 22 nmol/L, 25.2 ± 8.8 ng/mLCalculated free 25(OH) D 20 ± 7.4 pmol/L, 8 ± 2.96 ng/L | |
| Intervention: 20,000 IU/week | Male/Female 293/179 | r = 0.73, S | r = −0.21* | Free 25(OH) D by ELISA | Measured free 25(OH)D 13.4 ± 4.2 pmol/L, 5.36 ± 1.68 ng/L | |||
| OR 2857 IU/day for 12 mos | Calculated free 25(OH)D | Measured Free 25(OH)D | Calculated bioavailable 25(OH)D 8.5 ± 3.1 nmol/L, 3.4 ± 1.24 μg/L | |||||
| * no r provided | r = −0.17* | After supplementation: | ||||||
| Total 25(OH)D ~ 109 ± 26.2 nmol/L, 43.6 ± 10.48 ng/mL | ||||||||
| Calculated free 25(OH)D 36.9 ± 9.4 pmol/l, 14.7 ± 3.7 ng/L | ||||||||
| Measured free 25(OH)D 21.9 ± 5.2 pmol/L, 8.7 ± 2.08 ng/L | ||||||||
| Yao et al, 2017 (45) | 448 | Age 30 years on average | Baseline bioavailable 25(OH)D | Supplementation Total 25(OH)D and Bioavailable 25(OH)D*, r not provided | Bioavailable 25(OH) D and Calcium, r = 0.11* | Total 25(OH) D by LC-MS | Vermeulen’s equation | Total 25(OH)D 32.8 nmol/L, 13.2 ± 3.52 ng/ mL |
| Intervention: 2000 IU/day for 20 weeks | Male/ Female 141/307 | NS | Bioavailable 25(OH)D 2.7 ± 0.8 nmol/L, 1.08 ± 0.32 μg/L | |||||
| Supplementation Bioavailable 25(OH)D*, no r provided | After supplementation: | |||||||
| Total 25(OH)D 67.3 ± 23.1 nmol/L, 26.92 ± 9.24 ng/mL | ||||||||
| Bioavailable 25(OH)D 3.0 ± 3 nmol/L, 1.2 ± 1.2 μg/L | ||||||||
| Smith et al, 2019 (38) | 358 | Older women: | Baseline free 25(OH) D, S, r = 0.73 | Total and measured free 25(OH)D* | Total 25OHD by LC-MS | Total 25 (OH)D ~ 50.9 ± 13.2 nmol/L, 20.36 ± 5.28 ng/mL | ||
| Intervention: 400 to 4800 IU/day for 12 mos | Age 66 years on average | Supplementation free 25(OH)D r = 0.86* | Free 25(OH) D measured by ELISA | Free 25 (OH)D ~ 9.21 ± 2.88 nmol/L, 3.68 ± 1.15 ng/L | ||||
| Caucasian 140 (62%) | ||||||||
| African American 88 (38%) | ||||||||
| Younger women: | ||||||||
| Age 37 years on average | ||||||||
| Caucasian 91(70%) | ||||||||
| African American 39 (30%) | ||||||||
| Meryl LeBoff et al, 2020 (48) | 771 | Age 63 years on average | pQCT percent change, NS | Total 25(OH) D by LC-MS | Total 25(OH)D 69.1 ± 22.7 nmol/L, 27.64 ± 9.08 ng/mL | |||
| Intervention: 2000 IU/ day for 2 years | Male/ Female: 411/360 | Free 25(OH) D by ELISA | Free 25(OH)D 14.6 ± 4.7 pmol/L, 5.9 ± 1.88 ng/L | |||||
| White 630, Black 67, Hispanic 26, Asian 15 | After supplementation: | |||||||
| Native American or Alaskan native 5 | Total 25(OH)D 98.6 nmol/L, 39.44 ng/mL | |||||||
| Free 25(OH)D 22.3 pmol/L, 8.92 ng/L | ||||||||
| Aspray et al, 2019 (47) | 379 | Age 74 years on average | Total and measured free 25(OH)D, S, no r | Change in BMD, NS | Total 25 (OH)D by LC-MS | Mathematical model | Total 25(OH)D 41.6 ± 19.9 nmol/L, 16.64 ± 7.96 ngl/mL | |
| Intervention: 12,000, 24,000, 48,000 IU/ mo for 12 mos, | Male/ Female: 260/112 | Free 25(OH)D 8.7 ± 4.2 pmol/L, 3.48 ± 1.68 ng/L | ||||||
| Equivalent to 400 IU/ day, 800 IU/day, 1600 IU/day | ||||||||
| After supplementation: | ||||||||
| Total 25(OH)D [55.0-79] nmol/L, [22-31.6] ng/mL | ||||||||
| Free 25(OH)D [11.7-16.8] pmol/L, [4.68-6.72] ng/L |
Values for 25(OH) D levels in italics provide values using units similar to ones in our study for ease of comparability, values of vitamin D metabolites correspond to values at baseline unless specified otherwise.
* indicates significance
Abbreviations: 25(OH)D, 25-hydroxyvitamin D; BMD, bone mineral density; BTM, bone turnover marker; LC-MS, liquid chromatography–mass spectrometry; NA, not available; NS, not significant; pQCT, peripheral quantitative computed tomography.
Randomized Vitamin D Trials Outlining the Relation Between Vitamin D Metabolites and Bone Health Outcomes
| Article Intervention . | N . | Age Gender Race . | Relation to total 25(OH)D . | Relation to PTH . | Relation to calcium + BTM + BMD . | Assay . | Formula for calculated 25(OH)D . | Ranges of vitamin D level . |
|---|---|---|---|---|---|---|---|---|
| Sollid et al, 2016 (27) | 472 | Age 62 years on average | Measured free 25(OH)D | Total 25(OH)D | Total 25(OH) D by LC-MS | Vermeulen’s equation | Total 25(OH)D ~ 63 ± 22 nmol/L, 25.2 ± 8.8 ng/mLCalculated free 25(OH) D 20 ± 7.4 pmol/L, 8 ± 2.96 ng/L | |
| Intervention: 20,000 IU/week | Male/Female 293/179 | r = 0.73, S | r = −0.21* | Free 25(OH) D by ELISA | Measured free 25(OH)D 13.4 ± 4.2 pmol/L, 5.36 ± 1.68 ng/L | |||
| OR 2857 IU/day for 12 mos | Calculated free 25(OH)D | Measured Free 25(OH)D | Calculated bioavailable 25(OH)D 8.5 ± 3.1 nmol/L, 3.4 ± 1.24 μg/L | |||||
| * no r provided | r = −0.17* | After supplementation: | ||||||
| Total 25(OH)D ~ 109 ± 26.2 nmol/L, 43.6 ± 10.48 ng/mL | ||||||||
| Calculated free 25(OH)D 36.9 ± 9.4 pmol/l, 14.7 ± 3.7 ng/L | ||||||||
| Measured free 25(OH)D 21.9 ± 5.2 pmol/L, 8.7 ± 2.08 ng/L | ||||||||
| Yao et al, 2017 (45) | 448 | Age 30 years on average | Baseline bioavailable 25(OH)D | Supplementation Total 25(OH)D and Bioavailable 25(OH)D*, r not provided | Bioavailable 25(OH) D and Calcium, r = 0.11* | Total 25(OH) D by LC-MS | Vermeulen’s equation | Total 25(OH)D 32.8 nmol/L, 13.2 ± 3.52 ng/ mL |
| Intervention: 2000 IU/day for 20 weeks | Male/ Female 141/307 | NS | Bioavailable 25(OH)D 2.7 ± 0.8 nmol/L, 1.08 ± 0.32 μg/L | |||||
| Supplementation Bioavailable 25(OH)D*, no r provided | After supplementation: | |||||||
| Total 25(OH)D 67.3 ± 23.1 nmol/L, 26.92 ± 9.24 ng/mL | ||||||||
| Bioavailable 25(OH)D 3.0 ± 3 nmol/L, 1.2 ± 1.2 μg/L | ||||||||
| Smith et al, 2019 (38) | 358 | Older women: | Baseline free 25(OH) D, S, r = 0.73 | Total and measured free 25(OH)D* | Total 25OHD by LC-MS | Total 25 (OH)D ~ 50.9 ± 13.2 nmol/L, 20.36 ± 5.28 ng/mL | ||
| Intervention: 400 to 4800 IU/day for 12 mos | Age 66 years on average | Supplementation free 25(OH)D r = 0.86* | Free 25(OH) D measured by ELISA | Free 25 (OH)D ~ 9.21 ± 2.88 nmol/L, 3.68 ± 1.15 ng/L | ||||
| Caucasian 140 (62%) | ||||||||
| African American 88 (38%) | ||||||||
| Younger women: | ||||||||
| Age 37 years on average | ||||||||
| Caucasian 91(70%) | ||||||||
| African American 39 (30%) | ||||||||
| Meryl LeBoff et al, 2020 (48) | 771 | Age 63 years on average | pQCT percent change, NS | Total 25(OH) D by LC-MS | Total 25(OH)D 69.1 ± 22.7 nmol/L, 27.64 ± 9.08 ng/mL | |||
| Intervention: 2000 IU/ day for 2 years | Male/ Female: 411/360 | Free 25(OH) D by ELISA | Free 25(OH)D 14.6 ± 4.7 pmol/L, 5.9 ± 1.88 ng/L | |||||
| White 630, Black 67, Hispanic 26, Asian 15 | After supplementation: | |||||||
| Native American or Alaskan native 5 | Total 25(OH)D 98.6 nmol/L, 39.44 ng/mL | |||||||
| Free 25(OH)D 22.3 pmol/L, 8.92 ng/L | ||||||||
| Aspray et al, 2019 (47) | 379 | Age 74 years on average | Total and measured free 25(OH)D, S, no r | Change in BMD, NS | Total 25 (OH)D by LC-MS | Mathematical model | Total 25(OH)D 41.6 ± 19.9 nmol/L, 16.64 ± 7.96 ngl/mL | |
| Intervention: 12,000, 24,000, 48,000 IU/ mo for 12 mos, | Male/ Female: 260/112 | Free 25(OH)D 8.7 ± 4.2 pmol/L, 3.48 ± 1.68 ng/L | ||||||
| Equivalent to 400 IU/ day, 800 IU/day, 1600 IU/day | ||||||||
| After supplementation: | ||||||||
| Total 25(OH)D [55.0-79] nmol/L, [22-31.6] ng/mL | ||||||||
| Free 25(OH)D [11.7-16.8] pmol/L, [4.68-6.72] ng/L |
| Article Intervention . | N . | Age Gender Race . | Relation to total 25(OH)D . | Relation to PTH . | Relation to calcium + BTM + BMD . | Assay . | Formula for calculated 25(OH)D . | Ranges of vitamin D level . |
|---|---|---|---|---|---|---|---|---|
| Sollid et al, 2016 (27) | 472 | Age 62 years on average | Measured free 25(OH)D | Total 25(OH)D | Total 25(OH) D by LC-MS | Vermeulen’s equation | Total 25(OH)D ~ 63 ± 22 nmol/L, 25.2 ± 8.8 ng/mLCalculated free 25(OH) D 20 ± 7.4 pmol/L, 8 ± 2.96 ng/L | |
| Intervention: 20,000 IU/week | Male/Female 293/179 | r = 0.73, S | r = −0.21* | Free 25(OH) D by ELISA | Measured free 25(OH)D 13.4 ± 4.2 pmol/L, 5.36 ± 1.68 ng/L | |||
| OR 2857 IU/day for 12 mos | Calculated free 25(OH)D | Measured Free 25(OH)D | Calculated bioavailable 25(OH)D 8.5 ± 3.1 nmol/L, 3.4 ± 1.24 μg/L | |||||
| * no r provided | r = −0.17* | After supplementation: | ||||||
| Total 25(OH)D ~ 109 ± 26.2 nmol/L, 43.6 ± 10.48 ng/mL | ||||||||
| Calculated free 25(OH)D 36.9 ± 9.4 pmol/l, 14.7 ± 3.7 ng/L | ||||||||
| Measured free 25(OH)D 21.9 ± 5.2 pmol/L, 8.7 ± 2.08 ng/L | ||||||||
| Yao et al, 2017 (45) | 448 | Age 30 years on average | Baseline bioavailable 25(OH)D | Supplementation Total 25(OH)D and Bioavailable 25(OH)D*, r not provided | Bioavailable 25(OH) D and Calcium, r = 0.11* | Total 25(OH) D by LC-MS | Vermeulen’s equation | Total 25(OH)D 32.8 nmol/L, 13.2 ± 3.52 ng/ mL |
| Intervention: 2000 IU/day for 20 weeks | Male/ Female 141/307 | NS | Bioavailable 25(OH)D 2.7 ± 0.8 nmol/L, 1.08 ± 0.32 μg/L | |||||
| Supplementation Bioavailable 25(OH)D*, no r provided | After supplementation: | |||||||
| Total 25(OH)D 67.3 ± 23.1 nmol/L, 26.92 ± 9.24 ng/mL | ||||||||
| Bioavailable 25(OH)D 3.0 ± 3 nmol/L, 1.2 ± 1.2 μg/L | ||||||||
| Smith et al, 2019 (38) | 358 | Older women: | Baseline free 25(OH) D, S, r = 0.73 | Total and measured free 25(OH)D* | Total 25OHD by LC-MS | Total 25 (OH)D ~ 50.9 ± 13.2 nmol/L, 20.36 ± 5.28 ng/mL | ||
| Intervention: 400 to 4800 IU/day for 12 mos | Age 66 years on average | Supplementation free 25(OH)D r = 0.86* | Free 25(OH) D measured by ELISA | Free 25 (OH)D ~ 9.21 ± 2.88 nmol/L, 3.68 ± 1.15 ng/L | ||||
| Caucasian 140 (62%) | ||||||||
| African American 88 (38%) | ||||||||
| Younger women: | ||||||||
| Age 37 years on average | ||||||||
| Caucasian 91(70%) | ||||||||
| African American 39 (30%) | ||||||||
| Meryl LeBoff et al, 2020 (48) | 771 | Age 63 years on average | pQCT percent change, NS | Total 25(OH) D by LC-MS | Total 25(OH)D 69.1 ± 22.7 nmol/L, 27.64 ± 9.08 ng/mL | |||
| Intervention: 2000 IU/ day for 2 years | Male/ Female: 411/360 | Free 25(OH) D by ELISA | Free 25(OH)D 14.6 ± 4.7 pmol/L, 5.9 ± 1.88 ng/L | |||||
| White 630, Black 67, Hispanic 26, Asian 15 | After supplementation: | |||||||
| Native American or Alaskan native 5 | Total 25(OH)D 98.6 nmol/L, 39.44 ng/mL | |||||||
| Free 25(OH)D 22.3 pmol/L, 8.92 ng/L | ||||||||
| Aspray et al, 2019 (47) | 379 | Age 74 years on average | Total and measured free 25(OH)D, S, no r | Change in BMD, NS | Total 25 (OH)D by LC-MS | Mathematical model | Total 25(OH)D 41.6 ± 19.9 nmol/L, 16.64 ± 7.96 ngl/mL | |
| Intervention: 12,000, 24,000, 48,000 IU/ mo for 12 mos, | Male/ Female: 260/112 | Free 25(OH)D 8.7 ± 4.2 pmol/L, 3.48 ± 1.68 ng/L | ||||||
| Equivalent to 400 IU/ day, 800 IU/day, 1600 IU/day | ||||||||
| After supplementation: | ||||||||
| Total 25(OH)D [55.0-79] nmol/L, [22-31.6] ng/mL | ||||||||
| Free 25(OH)D [11.7-16.8] pmol/L, [4.68-6.72] ng/L |
Values for 25(OH) D levels in italics provide values using units similar to ones in our study for ease of comparability, values of vitamin D metabolites correspond to values at baseline unless specified otherwise.
* indicates significance
Abbreviations: 25(OH)D, 25-hydroxyvitamin D; BMD, bone mineral density; BTM, bone turnover marker; LC-MS, liquid chromatography–mass spectrometry; NA, not available; NS, not significant; pQCT, peripheral quantitative computed tomography.
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