Table 1.
Studies regarding the association between vitamin B12 and bone health.
| Author Year |
Study characteristics Duration of follow-up (when applicable) Country Risk of bias |
Population characteristics: N (% men) Age (y) ± SD |
Vitamin B12 status pmol/L* Mean ± SD |
Outcome | Association type | Results* | ||
|---|---|---|---|---|---|---|---|---|
| Dhonukshe-Rutten et al. 2005 [3] |
Cohort (3 y) The Netherlands High risk |
1253 (48%) 75.5 ± 6.6 |
♀: 289 ± 99 ♂: 268 ± 89 |
Fracture (verified by physician or radiograph) |
β (SE) for association vitB12-fracture (per 50 pmol/L) |
♀: −0.09 (0.06)a, 1
♂: 0.02 (0.08)a, 1 |
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| Gjesdal et al. 2007 [24] | Cohort (12.6 y) Norway Low risk |
4761 (45%) 65–67 at baseline |
♀: 386.4 ± 372.0 ♂: 359.3 ± 276.2 |
Hip fracture (verified by hospital discharge diagnoses) |
β (SE) for association vitB12-hip fracture (per 50 pmol/L) |
♀: −0.03 (0.03)b, 2
♂: −0.06 (0.05)b, 2 |
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| McLean et al. 2008 [25] | Cohort (16 y) USA Low risk |
823 (41%) 75.3 ± 4.9 |
Deficient (<148): ♀ 9%/♂14.0% Low (148–257.9): ♀ 24.3%/♂32.5% Normal (≥258): ♀ 66.7%/♂53.5% |
Hip fracture (verified by review medical records) |
β (SE) for association vitB12-hip fracture (per 50 pmol/L) |
♀: −0.09 (0.06)c, 1
♂: −0.09 (0.11)c, 1 |
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| Ravaglia et al. 2005 [26] | Cohort (4 y) Italy Moderate risk |
702 (47%) 73.0 ± 6.0 |
Geometric mean (95% CI) 249.1 (203–272) |
Fracture (verified by review medical records) |
β (SE) for association vitB12-fracture (per 50 pmol/L) | 0.04 (0.08)d, 2 | ||
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| Bozkurt et al. 2009 [32] | Cross-sectional Turkey High risk |
178 (0%) 53.5 ± 8.0 |
247.7 ± 85.4 | BMD: LS, FN [DXA] |
Logistic regression for FN, LS and FN + LS combined for vitB12 status under the quintile value. β (SE) + P value |
LS: −2.3 (0.9) P = 0.017 FN: −0.4 (0.9) P = 0.669 LS + FN: 1.8 (0.8) P = 0.045e |
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| Bucciarelli et al. 2010 [33] | Cross-sectional Italy Moderate risk |
446 (0%) 65.1 ± 9.4 |
(geometric mean ± SD) 399.1 ± 1.6 |
BMD: FN, LS, TH [DXA, Prodigy, GE, Lunar] | β for association vitB12-TH BMD β (SE) (per 50 pmol/L) | −0.00105 (0.939)f, 2 | ||
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| Cagnacci et al. 2008 [34] | Cohort (5 y) Italy Moderate risk |
117 (0%) 54.4 ± 0.5 |
(Mean ± SE) 548.5 ± 40.5 |
BMD: LS [DXA: Lunar DPX] |
Regression for vitB12-BMD change β (SE) P value | −0.003 (0.012) P = 0.784g | ||
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| Dhonukshe-Rutten et al. 2003 [35] |
Cross-sectional The Netherlands Moderate risk |
194 (26%) 78.3 ± 5.5 |
♀ 288 ± 131 ♂ 238 ± 95 |
BMD: whole body [DXA, Lunar DPX-L] |
Multivariate regression, β for association vitB12-BMD β (95% CI) in women | ♀: 12.3·10−5 (0.2·10−5–2.4·10−4)h | ||
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| Gjesdal et al. 2006 [10] | Cross-sectional Norway Moderate risk |
5329 (43%) middle aged: 47–50 Older: 71–75 |
♀ 393.4 ± 235.8 ♂ 374.6 ± 230.7 |
BMD: TH [DXA, Lunar EXPERT-XL] |
OR (95% CI) for low BMD per category vitB12 status 1: <230 pmol/L 2: 230.0–279.9 pmol/L 3: 280.0–414.9 pmol/L 4: ≥415.0 pmol/L + P for trend |
♀: 1: 0.97 (0.68–1.37) 2: 0.87 (0.63–1.21) 3: 1.02 (0.82–1.27) 4: 1.00 (reference) P for trend = 0.61 |
♂: 1.22 (0.82–1.81) 1.14 (0.80–1.62) 0.97 (0.74–1.28) 1.00 (reference) P for trend = 0.25i |
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| Golbahar et al. 2004 [9] | Cross-sectional Iran Moderate risk |
271 (0%) 60.8 ± 6.8 |
(geometric mean ± SD) 339.5 ± 247.6 |
BMD: FN, LS [DXA, Lunar DPX-L] |
β (SE) for association vitB12-BMD (per 50 pmol/L) |
FN: 0.0002 (0.07)2
LS: 0.0114 (0.14)2 |
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| Haliloglu et al. 2010 [36] | Cross-sectional Turkey Moderate risk |
120 (0%) 54.4 ± 1.1 |
Osteoporotic: 216.0 ± 135.1 Osteopenic: 190.8 ± 97.4 Normal BMD: 251.0 ± 205.8 |
BMD: LS [DXA, Lunar DPX-L] |
ANOVA for difference in vitB12 status per BMD group compared to normal BMD group | No sign differences in vitB12 status between BMD groups | ||
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| Krivosikova et al. 2010 [37] | Cross-sectional Slovakia High risk |
272 (0%) 41.3 ± 19.8 |
273.2 ± 152.7 | BMD: FN, LS, trochanter, TH [DXA, Lunar DPX-L] |
Stepwise multivariate linear regression, β for association vitB12-BMD. β (SE) P value (per 50 pmol/L) |
FN: −2.0 (2.73) j, 2
LS: −1.15 (1.42) j, 2 TH: −0.5 (3.03) j, 2 |
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| Morris et al. 2005 [7] |
Cross-sectional USA Low risk |
1550 (48%) 68 |
Geometric mean (95% CI) Osteoporosis: 271 (243–302) Osteopenia: 309 (293–325) Normal: 310 (297–323) Serum MMA (nmol/L) Osteoporosis: 305 (276–337) Osteopenia: 251 (234–269) Normal: 241 (212–274) |
BMD: Trochanter, intertrochanter, FN, Ward's triangle, TH [DXA, Hologic QDR-1000] | OR (95% CI) for mean BMD in relation to quartile categories of vitB12 and MMA status + P for trend. Category medians: | Vit B12: Q1: 2.0 (1.0–3.9) Q2: 1.3 (0.6–2.7) Q3: 1.7 (0.8–3.3) Q4: 1.0 (reference) P for trend = 0.09 |
MMA: 1.0 (reference) 3.5 (1.4–8.5) 5.2 (2.0–13.1) 7.2 (3.4–15.2) P for trend <0.001k |
|
| B12 (pmol/L): Q1: 182 Q2: 268 Q3: 349 Q4: 495 |
MMA (nmol/L): 157 206 272 415 |
Among subjects with vitB12 <220 pmol/L mean BMD increased sign with increasing vitB12 (P = 0.01) | ||||||
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| Naharci et al. 2012 [38] | Cross-sectional Turkey Moderate risk |
264 (100%) 77.0 ± 6.0 |
26.7% low (<148, group I) 39.1% borderline (148–221, group II) 34.2% normal (>221, group III) |
BMD: FN, TH, trochanter, inter-trochanter [DXA, hologic QDR-4500] | Anova for differences in FN BMD between groups of serum vitB12 |
Sign differences FN BMD group I and II (P = 0.013) group I and III (P < 0.001) group II and III (P = 0.003) FN BMD was positively correlated with serum vitB12 (r = 0.362, P < 0.001) |
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| Ouzzif et al. 2012 [39] | Cross-sectional Morocco Moderate risk |
188 (0%) 57.8 ± 8.5 |
360.4 ± 149.2 |
BMD: FN, LS, TH, trochanter [DXA, Lunar prodigy] | Multivariate regression, β for association vitB12-BMD β (SE) (per 50 pmol/L) P value | LS: −7.85 (0.25) TH: −11.65 (0.02) |
P = 0.160L, 2
P = 0.007L, 2 |
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| Rumbak et al. 2012 [40] | Cross-sectional Croatia Low risk |
131 (0%) 54.0 ± 4.9 |
239.6 ± 97.0 | BMD: FN, LS, TH, radius [DXA, Lunar-prodigy] |
Stepwise multivariate regression, β for association vitB12-BMD for pre- and postmenopausal women β (SE) P value (per 50 pmol/L) |
Premenopausal: LS: −3.39 (8.91) P = 0.709m, 2 FN: 7.45 (10.07) P = 0.467m, 2 TH: −1.36 (7.53) P = 0.862m, 2 Postmenopausal: LS: 7.45 (8.98) P = 0.411m, 2 FN: 12.20 (8.97) P = 0.180m, 2 TH: 8.81 (8.63) P = 0.314m, 2 |
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| Stone et al. 2004 [11] | Cohort (5.9 y) USA Low risk |
83 (0%) 71.1 ± 4.4 |
352 ± 174 |
BMD: TH, FN (change) [DXA, Hologic QDR-1000] | t-test for difference in BMD change between low and normal vitB12 status | Participants with low vitB12 (≤207 pmol/L) had a more rapid decline in BMD (−1.91%/year) than part. with normal vitB12 (−0.10%/year), P < 0.05 | ||
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| Tucker et al. 2005 [6] | Cross-sectional USA Low risk |
2576 (44%) 58.8 ± 9.5 |
Distribution per category of plasma vitB12 status 1: ♀ 4.4%/♂4.7% ≤148 2: ♀ 6.9%/♂7.8% >148–185 3: ♀ 25.4%/♂28.2% >185–259 4: ♀ 63.3%/♂ 59.3% >259 |
BMD: FN, LS, TH, Trochanter, Ward [DXA, Lunar DPX-L] |
Differences in BMD per category of plasma vitB12 level, relative to category 1 |
♀: FN: no differences ♀: LS: vitB12 in cat 2 (P < 0.10), 3, 4 (P < 0.05) was assoc. with better BMD ♀: TH: vitB12 in cat 3, 4 (P < 0.10) was assoc. with better BMD ♂: FN: vitB12 in cat 2, 3, 4 was assoc. with better BMD (P < 0.05) ♂ LS: no differences ♂ TH: vitB12 in cat 2 (P < 0.10), 3, 4 (P < 0.05) was assoc. with better BMDn |
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*Serum/plasma vitamin B12 concentrations were converted to pmol/L if applicable, using the following equation: 1 pg/mL = 1 ng/L = 0.738 pmol/L. subsequent outcomes were also converted. Where possible, subgroups were combined. BMD sites: LS: Lumbar Spine, FN: Femoral Neck, TH: Total Hip.
1 β(SE) as calculated from data provided by author; 2 β (SE) as calculated from presented data.
aadjusted for age, BMI, smoking, recurrent falling; badjusted for age, BMI, smoking, coffee intake, physical activity, vit D use, educational level, estrogen use in women; cadjusted for sex, age, height, weight, estrogen use in women; dadjusted for age, sex, education, osteoporosis drugs, creatinine, tHcy; eadjusted for duration of menopause, smoking, BMI, folic acid levels, tHcy levels; fadjusted for age, BMI, logtHcy, logFolate, creatinine clearance, smoking, alcohol intake; gAdjusted for age, weight, weight change; hadjusted for weight, height, energy intake; iadjusted for smoking, BMI, creatinin, coffee intake, physical activity, use of estrogen therapy; jadjusted for age, folate, tHcy, PTH, CTx, Ca, Cr; kAdjusted for age, sex, ethnicity, BMI, smoking, physical activity, creatinin, alcohol, coffee, energy, calcium, vitamin D zinc intake; Ladjusted for age, BMI, tHcy and folate; madjusted for Age, BMI, smoking, alcohol, physical activity, tHcy, Folate; nadjusted for energy, calcium, vitamin D intake, BMI, height, smoking, age, physical activity, calcium supplement, vitamin D supplement, alcohol, osteoporosis medication, season of measurement.