Table 2.
Studies regarding the association between folate and bone health.
| Author Year |
Study characteristics Duration of follow-up (when applicable) Country Risk of bias |
Population characteristics: N (%men) Age (y) ± SD |
Folate status (nmol/L)* Mean ± SD |
Outcome | Association type | Results* | ||
|---|---|---|---|---|---|---|---|---|
| Gjesdal et al. 2007 [24] | Cohort (12.6 y) Norway Low risk |
4761 (45%) 65–67 at baseline |
♀ 6.0 ± 3.5 ♂ 5.2 ± 2.7 |
Hip fracture (verified by hospital discharge diagnoses) |
HR for hip fracture according to folate status 1: <2.9 2: 2.9–3.8 3: 3.9–6.5 4: ≥6.6 |
♀: 1: 2.40 (1.50–3.84) 2: 1.15 (0.68–1.94) 3: 1.02 (0.68–1.54) 4: 1.00 (reference)a |
♂: 1.00 (0.48–2.12) 0.80 (0.39–1.62) 0.81 (0.45–1.46) 1.00 (reference)a |
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| McLean et al. 2008 [25] | Cohort (16 y) USA Low risk |
960 (41%) 75.3 ± 4.9 |
Not shown | Hip fracture (verified by review medical records) |
HR for hip fracture according to folate status Normal: ≥11 Low: 7–10.9 Deficient: <7 |
Normal: 1.00 (reference) Low: 0.76 (0.43, 1.32) Deficient: 1.38 (0.91, 2.09)b |
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| Ravaglia et al. 2005 [26] | Cohort (4 y) Italy Moderate risk |
702 (47%) 73.0 ± 6.0 |
11.7 (9.0–12.2) mean (95% CI) |
Fracture (verified by review medical records) |
OR (95% CI) for risk of fracture at follow-up for each increment of 1 sd in the log-transformed serum folate value | 0.83 (0.59–1.19)c | ||
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| Baines et al. 2007 [41] | Cross-sectional Great Britain High risk |
328 (0%) 67.5 (40–85) mean (range) |
Osteoporosis: 8.1 ± 8.7# Osteopenia: 10.2 ± 4.6 Normal: 9.4 ± 6.3 |
BMD: os calcis/ heel bone [PIXI, GE Lunar] | ANOVA for difference between the normal, osteopenia and osteoporosis group |
FA status was significantly different between osteroporotic and osteopenic group (P = 0.049) |
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| Bozkurt et al. 2009 [32] | Cross-sectional Turkey High risk |
178 (0%) 53.5 ± 8.0 |
24.9 ± 7.9 |
BMD: FN, LS [DXA] |
Logistic regression for FN, LS and FN + LS combined. β (SE) + P value for assoc. BMD-folate status under the median value |
LS: −0.2 (0.2) P = 0.417 FN: −0.04 (0.2) P = 0.835 LS + FN: −0.03 (0.2) P = 0.896d |
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| Bucciarelli et al. 2010 [33] | Cross-sectional Italy Moderate risk |
446 (0%) 65.1 ± 9.4 |
(geometric mean ± SD) 3.8 ± 1.6 |
BMD: FN, LS, TH [DXA, Prodigy, GE, Lunar] | β for association folate-TH BMD β (SE) | 0.004 (0.018)e, 2 | ||
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| Cagnacci et al. 2008 [34] | Cohort (5 y) Italy Moderate risk |
117 (0%) 54.4 ± 0.5 |
(Mean ± SE) 20.6 ± 1.4 |
BMD: LS [DXA: Lunar DPX] |
Regression analysis for folate-BMD change β (SE) + P value | 1.602 (0.803) P = 0.048f | ||
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| Cagnacci et al. 2003 [8] | Cross-sectional Italy Moderate risk |
161 (0%) 53.3 ± 1.04 |
(Mean ± SE) 21.5 ± 4.3 |
BMD: LS [DXA: Lunar DPX] |
Regression analysis, r (P value) for association folate-BMD | r = 0.254 | (P < 0.002) | |
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| Gjesdal et al. 2006 [10] |
Cross-sectional Norway Moderate risk |
5329 (43%) middle aged: 47–50 Older: 71–75 |
♀ 8.9 ± 7.1 ♂ 7.3 ± 4.6 |
BMD: TH [DXA, Lunar EXPERT-XL] |
OR (95% CI) for low BMD per category folate status: 1: FA < 3.8 nmol/L 2: FA 3.8–4.9 nmol/L 3: FA 5.0–8.4 nmol/L 4: FA ≥ 8.5 nmol/L + P for trend Multivariate regression for folate-BMD β (SE) (per 50 nmol/L) |
♀: 1: 1.55 (1.07–2.23) 2: 1.18 (0.86–1.63) 3: 1.24 (0.99–1.56) 4: 1.00 (reference) P for trend = 0.02 |
♂: 0.81 (0.53–1.24) 0.96 (0.67–1.38) 1.15 (0.87–1.53) 1.00 (reference) P for trend = 0.26g |
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| Elderly women: β = 0.05 (0.02)g, 2 | ||||||||
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| Golbahar et al. 2004 [9] | Cross-sectional Iran Moderate risk |
271 (0%) 60.8 ± 6.8 |
(geometric mean ± SD) 11.6 ± 6.5 |
BMD: FN, LS [DXA, Lunar DPX-L] | β for association folate-BMD β (SE) |
FN: 0.008 (0.019)h, 2
LS: 0.010 (0.018)i, 2 |
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| Haliloglu et al. 2010 [36] | Cross-sectional Turkey Moderate risk |
120 (0%) 54.4 ± 1.1 |
Osteoporotic: 12.2 ± 6.3 Osteopenic: 15.4 ± 7.4 Normal: 15.8 ± 8.3 |
BMD: LS [DXA, Lunar DPX-L] |
ANOVA for difference in folate status per BMD group (osteoporotic, osteopenic, compared to normal BMD group) | No significant differences in folate status between BMD groups | ||
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| Krivosikova et al. 2010 [37] | Cross-sectional Slovakia High risk |
272 (0%) 41.3 ± 19.8 |
23.8 ± 9.6 | BMD: FN, LS, trochanter, TH [DXA, Lunar DPX-L] |
Stepwise multivariate linear regression, β for association folate-BMD. β (SE) P value |
FN: −0.028 (0.054) P = 0.606 j, 2
LS: −0.001 (0.067) P = 0.988 j, 2 TH: −0.032 (0.060) P = 0.595 j, 2 |
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| Morris et al. 2005 [7] | Cross-sectional USA Low risk |
1550 (47%) 68 |
Osteoporosis: 17.2 (15.4–19.2) Osteopenia: 17.2 (16.0–18.5) Normal: 16.7 (15.3–18.3) Geometric mean (95% CI) |
BMD: Trochanter, intertrochanter, FN, Ward's triangle, TH [DXA, Hologic QDR-1000] | OR (95% CI) for mean BMD in relation to quartile categories of folate status + P for trend Category median (nmol/L): Q1: 8.0 Q2: 12.4 Q3: 20.3 Q4: 38.9 |
Q1: 1.1 Q2: 1.1 Q3: 1.5 Q4: 1.0 P for trend |
(0.5–2.3) (0.0.5–2.9) (0.7–3.4) (reference) = 0.83k |
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| Naharci et al. 2012 [38] | Cross-sectional Turkey Moderate risk |
264 (100%) 77.0 ± 6.0 |
low (<7.0, group I): 0.0% borderline (7.0–10.9, group II): 9.2% normal (>10.9, group III): 90.8% |
BMD: FN, TH, trochanter, intertrochanter [DXA, hologic QDR-4500] |
Independent sample t-test for differences in FN BMD between group II and III of serum folate | No significant differences in BMD (all sites) between group II and III of folate status | ||
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| Ouzzif et al. 2012 [39] | Cross-sectional Morocco Moderate risk |
188 (0%) 57.8 ± 8.5 |
15.6 ± 6.8 | BMD: FN, LS, TH, trochanter [DXA, Lunar prodigy] | Multivariate regression, β for association folate-BMD β (SE) + P value |
LS: 0.007 (0.002) P = 0.808L
TH: 0.006 (0.001) P = 0.834L |
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| Rumbak et al. 2012 [40] | Cross-sectional Croatia Low risk |
131 (0%) 54.0 ± 4.9 |
22.4 ± 7.5 | BMD: FN, LS, TH, radius [DXA, Lunar-prodigy] |
Stepwise multivariate regression, β for association folate-BMD β + P value |
Premenopausal: LS: 3.31 (4.73) P = 0.490m, 2 FN: 1.32 (4.90) P = 0.791m, 2 TH: 2.87 (4.35) P = 0.516m, 2 Postmenopausal: LS: −3.75 (3.47) P = 0.284m, 2 FN: −1.32 (3.15) P = 0.679m, 2 TH: 0.66 (3.89) P = 0.862m, 2 |
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*Serum/plasma folate concentrations were converted to nmol/L if applicable, using the following equation: 1 ng/ml = 2.266 nmol/L. Subsequent outcomes were also converted. Where possible, subgroups were combined. BMD sites—LS: Lumbar Spine, FN: Femoral Neck, TH: Total Hip #data presented in article as μmol/L, this is presumably a typing error and should be nmol/L.
1 β (SE) as calculated from data provided by author; 2 β (SE) as calculated from presented data.
aadjusted for age, BMI, smoking, coffee intake, physical activity, vit D use, educational level, estrogen use in women; badjusted for sex, age, height, weight, estrogen use in women; cadjusted for age, gender, education, osteoporosis drug, serum creatinine, tHcy; dAdjusted for duration of menopause, smoking, BMI, B12, tHcy; eadjusted for age, BMI, logtHcy, logB12, creatinine clearance, smoking, alcohol intake;
fAdjusted for age, weight, weight change; gAdjusted for smoking, BMI, creatinin, coffee intake, physical activity, use of estrogen therapy; hadjusted for age, BMI, alkaline phosphatase; iadjusted for years since menopause, BMI, alkaline phosphatase, creatinine; jadjusted for age, B12, 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, B12; madjusted for Age, BMI, smoking, alcohol, physical activity, tHcy, B12.