Table 7.
Micronutrient | Reference | Study description | Population description | Number of subjects | End points | Results | |||||
---|---|---|---|---|---|---|---|---|---|---|---|
RCTs | |||||||||||
Magnesium | Carpenter et al. 2006 [185] | 1-year placebo-controlled, double-blind RCT of 300 mg/day supplementation of MgO | Sex: female Age: 8–14 years Race: white Location: New Haven, CT |
44 | BMC of total hip, femoral neck, Ward’s area, and lumbar spine | Combined overall hip | |||||
Treatment | Placebo | ||||||||||
1.05 % | 0.97 %, P = 0.0534 | ||||||||||
Prospective studies | |||||||||||
Fluoride | Levy et al. 2009 [187] | Lifetime associations of average daily fluoride intake and DXA bone outcomes at age 11 years | Sex: male and female Age: birth to 11 years for fluoride assessments; mean age 11.2 years for DXA assessment Race: 97 % white Location: Iowa Year(s): recruitment took place from 1992 to 1995 (fluoride study) and from 1998 to 2000 (bone development study) |
481 | BMC | Hip | Spine | Total body less head | |||
Girls | |||||||||||
0–11 years | 0.07, NS | 0.17, NS | 0.10, NS | ||||||||
0–8.5 years | 0.04, NS | 0.13, NS | 0.08, NS | ||||||||
0–3 years | 0.03, NS | 0.06, NS | 0.05, NS | ||||||||
3–6 years | −0.01, NS | 0.05, NS | 0.02, NS | ||||||||
6–8.5 years | 0.11, NS | 0.19, 0.01 | 0.16, NS | ||||||||
85.5–11 years | 0.18, 0.01 | 0.24, <0.01 | 0.19, NS | ||||||||
Boys | |||||||||||
0–11 years | 0.21, 0.01 | 0.23, 0.01 | 0.23, 0.01 | ||||||||
0–8.5 years | 0.21, 0.01 | 0.23, 0.01 | 0.24, 0.01 | ||||||||
0–3 years | 0.22, 0.01 | 0.22, 0.01 | 0.23, 0.01 | ||||||||
3–6 years | 0.14, NS | 0.18, NS | 0.19, 0.01 | ||||||||
6–8.5 years | 0.09, NS | 0.12, NS | 0.10, NS | ||||||||
85.5–11 years | 0.14, NS | 0.14, NS | 0.15, NS | ||||||||
• Data are from unadjusted bivariate associations (r) with fluoride intake and bone outcomes and corresponding P value. • No statistically significant relationships between daily fluoride intake and bone measures were found in adjusted models (for age, height, weight, and Tanner stage). | |||||||||||
Fluoride | Levy et al. 2014 [188] | Lifetime associations of average daily fluoride intake and DXA bone outcomes at age 15 years | Sex: male and female Age: birth to 15 years for fluoride assessments; mean age 15.3 years for DXA assessments Race: 98 % white Location: Iowa Year(s): recruitment took place from 1992 to 1995 (fluoride study) and from 1998 to 2000 (bone development study) |
358 | BMC | Females | Males | ||||
ß | R 2 | Partial R 2 | ß | R 2 | Partial R 2 | ||||||
Total body less head | 234, 0.02 | 0.03 | 0.03 | 182, NS | 0.02 | 0.02 | |||||
Spine | 7.32, 0.04 | 0.03 | 0.03 | 5.24, NS | 0.02 | 0.02 | |||||
Hip | 2.92, NS | 0.01 | 0.01 | 1.79, NS | <0.01 | <0.01 | |||||
• Data are from unadjusted bivariate associations (β) with fluoride intake and bone outcomes and corresponding P value. • With adjustment for height, weight, time since PHV, Tanner stage, calcium intake, and physical activity, none of the associations remained statistically significant. • No significant differences were observed between fluoride intake and bone measures across tertiles of fluoride intake from birth to 15 years. | |||||||||||
Observational studies | |||||||||||
Vitamin K | O’Connor et al. 2007 [191] | Cross-sectional associations of undercarboxylated osteocalcin (%ucOC) as an index of vitamin K status and BMC | Sex: female Age: 11–12 years Race: presumed white Location: Denmark |
223 | Serum %ucOC and total body BMC | β = −0.045, P = 0.016 | |||||
Lumbar BMC | β = −0.055, P = 0.037 | ||||||||||
Sodium | Hoppe et al. 2000 [149] | Cross-sectional analysis of nutrient intakes determined by 7-day diet records and bone | Sex: half were female, half were male Age: 10 years Race: presumed white Location: Denmark Year(s): 1997–1998 |
105 | Total body BMC | r = −0.206, P < 0.05 | |||||
Anterior–posterior projected bone area (cm2) | r = −0.215, P < 0.05 | ||||||||||
Phosphorous | Hoppe et al. 2000 [149] | Cross-sectional analysis of nutrient intakes determined by 7-day diet records and bone | Sex: half were female and half were male Age: 10 years Race: presumed white Location: Denmark Year(s): 1997–1998 |
105 | Total body BMC | r = −0.297, P < 0.01 | |||||
Anterior–posterior projected bone area (cm2) | r = −0.284, P < 0.01 | ||||||||||
Vitamin C | Prynne et al. 2006 [189] | Cross-sectional Cambridge Bone Studies to relate fruit and vegetable and nutrient intake from 7-day food diaries in 5 age and sex cohorts | Sex: female and male, nearly half of each Age: 16–19 years Race: presumed white Location: UK |
257 | Percent change with doubling in vitamin C intake from univariate analysis, in 4th-grade girls only | ||||||
Boys | Girls | ||||||||||
Total body BMC | 5.5, P < 0.01 | 1.4, NS | |||||||||
Spine BMC | 5.6, P < 0.05 | 2.1, NS | |||||||||
Total hip BMC | 5.7, P < 0.05 | −0.05, NS | |||||||||
Femoral neck BMC | 5.4, P < 0.01 | 5.2, NS | |||||||||
Trochanter BMC | 5.8, P < 0.05 | 2.5, NS | |||||||||
Vitamin C, zinc, and iron | Laudermilk et al. 2012 [190] | Cross-sectional analysis of nutrient intakes determined by the Harvard Youth/Adolescent Food frequency Questionnaire | Sex: female Age: 8–12 years, 4th- and 6th-grade students Race: ~87 % white, 7 % Asian, 3 % black, 2 % Latino and 1 % Native Hawaiian Location: Tucson, Arizona |
453 (n = 184 4th graders, n = 179 6th graders) |
pQCT | Vitamin C | Zinc | ||||
Femur 20 % site | |||||||||||
Cortical density | NS | 0.16, P < 0.05 | |||||||||
Periosteal circumference | 0.17, P < 0.05 | NS | |||||||||
Endosteal circumference | 0.17, P < 0.05 | NS | |||||||||
SSI | 0.18, P < 0.05 | NS | |||||||||
Tibia 4 % site | |||||||||||
Trabecular area | 0.18, P < 0.05 | NS | |||||||||
Periosteal circumference | 0.19, P < 0.01 | NS | |||||||||
Tibia 66 % site | |||||||||||
Cortical density | NS | 0.15, P < 0.05 | |||||||||
Cortical area | 0.15, P < 0.05 | NS | |||||||||
SSI | 0.18, P < 0.05 | NS | |||||||||
In regression modeling, iron was negatively associated with femoral cortical area and tibia SSI. | |||||||||||
Fluoride | Grobler 2009 [186] | This field study included the whole population of children aged 10–15 years living in areas of high and low fluoride in the drinking water. | Sex: male and female Age: 10–15 years Race: not specified, but of mixed ethnicity (i.e., from Khoi, Caucasian, and Negroid roots that developed into a homogenous ethnic group over many years) Location: South Africa Year(s): not specified |
166 (n = 77 from a 0.19 mg/L F area; n = 89 from a 3.00 mg/L F area) |
High fluoride | Low fluoride | P | ||||
Girls | Boys | Girls | Boys | ||||||||
Radius BMC (g) | |||||||||||
10–11 years | 1.29 | 1.29 | 1.26 | 1.32 | NS | ||||||
12–13 years | 1.56 | 1.41 | 1.33 | 1.29 | <0.05a | ||||||
14–15 years | 1.80 | 1.80 | 1.18 | 1.52 | <0.05a | ||||||
Radius bone width (cm) | |||||||||||
10–11 years | 0.97 | 0.98 | 0.98 | 1.01 | NS | ||||||
12–13 years | 1.09 | 1.08 | 1.04 | 1.15 | NS | ||||||
14–15 years | 1.10 | 1.14 | 1.18 | 1.21 | NS |
%ucOC percentage of undercarboxylated osteocalcin, BMC bone mineral content, DXA dual-energy x-ray absorptiometry, NS not significant, PHV peak height velocity, pQCT peripheral quantitative computed tomography, RCT randomized controlled trial, SSI stress–strain index
aSignificant differences in BMC in the 12- to 13-year-olds and the 14- to 15-year-olds were found among boys from the high fluoride area and girls from the low fluoride area