Christian Mølgaard

Slide 1

Are early growth and nutrition related to bone health in adolescence?The Copenhagen Cohort Study of Infant Nutrition and Growth (CCS)

Christian Mølgaard

Anni Larnkjær

Alicja Budek

Kim Fleischer Michaelsen

Paediatric and International Nutrition

Department of Human Nutrition, LIFE

University of Copenhagen

The Power of Programming, EARNEST

Munich, Friday 7th of May 2010

Note: for non-commercial purposes only

Christian Mølgaard

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Is bone mineralization during childhood important?

Optimal peak bone mass (PBM) may be important for later fracture risk”The bone mass attained early in life is perhaps the most important determinant of lifelong bone health.” NIH Consensus Conference, JAMA February 14, 2001.

Optimal bone mineralization may be important for bone health and fracture risk in children with diseases

Cooper et a. JBMR 2004

http://www.singhealth.com.sg/HealthMatters/HealthGlossary/Osteoporosis.htm

Christian Mølgaard

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Gafni&Baron. Pediatrics 2007

Murray JF, Primer of the metabolic Bone diseases --, 1999 Lippincott Williams & Wilkins

Bone modelling: growth in Bone Width

Bone growth

Bone remodelling: Bone maintenance

Schoenau et al. 2004

Eriksen et al. 1994 Raven Press.

Endochondral ossification: growth in Bone Length

Christian Mølgaard

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BackgroundEarly growth and later bone mass

� It has earlier been shown that body size at one year was positively associated to BMC (but not BMD) in young adults (1) and elderly (2,3)

1. Cooper et al. J Bone Min Res 1995;10:940-947.

2. Cooper et al. Ann Rheumat Dis 1997;56:17-21.

3. Oliver et al. Bone 41 (2007) 400-405

� A study of prematurely born children (1) has shown a negative association between weight at 1 year and size adjusted BMC at 6-7 years (p=0.0053)

1. Kurl et al. Acta Paediatr 1998;87:650-653.

� Data from CCS has shown a a negative association between weight gain the first 9 mo and size adjusted BMC at 10 years (p=0.004)

1. Mølgaard et al. Osteoporosis Int Vol 11 Supplement 4 S9-S10 2000

Christian Mølgaard

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BackgroundEarly nutrition and later bone mass

1. Breastfeeding > 3 month in children born at term

• Higher BMD at 8 year of age (F: +0.26 SD, p=0.05; L:+0.34 SD, p=0.007;

WB: +0.41, p=0.0008)

• No effect in children born preterm

2. Children born preterm

• Lactation positive correlated to BMAD (L) at the age of 9-11 y in the mineral supplemented group (r=0.69, p=0.013, n=12)

3. Adults born preterm

• Early human milk intake associated with higher bone mass (WBBA, BMC)

1. Jones et al, Osteoporos Int (2000) 11:146-522. Backström et al, JPGN 29:575-82, 19993. Fewtrell et al. Bone 45 (2009) 142-149

Christian Mølgaard

Slide 7

The Copenhagen Cohort Study of Infant Nutrition and Growth

Prospective observational cohort study of a random sample of infants born at Hvidovre Hospital Denmark

Inclusion criteria:

• Parents of Danish origin

• Healthy singleton infants born from October 1987 to February 1988

• Term: Gestational age 37 – 42 weeks

• Normal birth weight: 10th to 90th percentile for gestational age

• Main group followed from birth to 12 mo (84 completed)• Control group only examined at 9 mo of age (59 completed)

• Follow up examination at 10 and 17 y of age

Christian Mølgaard

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The Copenhagen Cohort Study of Infant Nutrition and Growth

n=560

n=143

n=251 Fulfilled inclusion criteria

Full data collected

n=136

Infants, born 1987-88

n=140

n=106 Agreed

n=104 Completed

Contacted1997

Contacted2004 n=109

Agreed

n=109 Completed

Christian Mølgaard

Slide 9

Earlier publications on bones from CCS

1. Michaelsen KF, Johansen JS, Samuelson G, Price PA, Christiansen C. Serum bone gamma-carboxyglutamic acid protein in a longitudinal study of infants: lower values in formula-fed infants. Pediatr Res 1992;31:401-5.

2. Hoppe C, Molgaard C, Michaelsen KF. Bone size and bone mass in 10-year-old Danish children: Effect of current diet. Osteoporosis International 2000;11:1024-30.

• Size adjusted BMC positively associated to calcium intake (p=0.02)

• Size adjusted BA positive associated to dietary protein (p=0.003) and negatively associated to intakes of sodium (p=0.048) and phosphorous (p=0.01)

Christian Mølgaard

Slide 10

Earlier publications on bones from CCS

3. Budek AZ, Hoppe C, Ingstrup H, Michaelsen KF, Bugel S, Molgaard C. Dietary protein intake and bone mineral content in adolescents-The Copenhagen Cohort Study. Osteoporos Int2007;18:1661-7.

• Size adjusted WB BMC positively associated to total protein (p≤0.05) and milk protein intake (p=0.003)

4. Budek AZ, Mark T, Michaelsen KF, Molgaard C. Tracking of size-adjusted bone mineral content and bone area in boys and girls from 10 to 17 years of age. Osteoporos Int 2010;21:179-82.

• Size adjusted correlations between BMC at 10 and 17 years

(r=0.69-0.85, p<0.001) and significant higher correlations in girls (p<0.05)

Murray JF, Primer of the metabolic Bone diseases --, 1999 Lippincott Williams & Wilkins

Christian Mølgaard

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Christian Mølgaard

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Christian Mølgaard

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Objective

To examine if:

• Early growth is related to bone mass in adolescence

• Breast feeding is related to bone mass in adolescence

• Early bone turnover is related to bone mass in adolescence

Christian Mølgaard

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Selected examinations for this study, first year

� Birth: Weight and length (all)

� 2 and 6 mo of age: S-BGP (osteocalcin) by RIA (study group)

� 9 mo of age: S-BGP (osteocalcin), weight, length, (all)

� Breast-feeding was recorded monthly

Christian Mølgaard

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Statistics

� To estimate the relation between early nutrition, early growth, bone turnover and later bone mass, sex adjusted partial correlation analyses were used

� To estimate the relation between early nutrition, early growth, early bone turnover and later size and sex adjusted bone mass, multiple regression analyses were used as recommended by Prentice et al (AJCN 1994).

� Size adjusted BMC: After natural logarithm transformation BMC were controlled for BA, height, weight and sex.

� SPSS (version 18.0; SPSS Inc, Chicago, IL) was used for the statistical analyses

Christian Mølgaard

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Length/height and weight at birth and 17 y’s

73.2 ± 10.5 kg59.9 ± 10.7 kgWeight 17 y (kg)

183.3 ± 5.7 cm166.7 ± 5.9 cmHeight 17 y (cm)

52.1 ± 1.8 cm51.7 ± 2.0 cmBirth length (cm)

3522 ± 382 g3350 ± 348 gBirth weight (g)

BoysGirlsMean ± SD

Christian Mølgaard

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r = 0.23, p = 0.062S-BGP ng/ml 9 mo (n= 69)

r = 0.14, p = 0.36S-BGP ng/ml 6 mo (n=45)

r = -0.033, p = 0.82S-BGP ng/ml 2 mo (n=49)

S-osteocalcin ng/ml 17 y

Results

Sex adjusted correlations between s-osteocalcin at 17 y and s-BGP at 2, 6 and 9 mo

Christian Mølgaard

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Results

Sex adjusted correlations between bone mass at 17 y and early weight and weight gain

r = 0.004 p = 0.97

r = -0.01 p = 0.91

r = -0.007 p = 0.95

r = 0.13 p = 0.18

r = 0.33 p = 0.001

r = 0.26 p = 0.008

∆W9-b

r = -0.01 p = 0.92

r = 0.13 p = 0.21

r = 0.07 p = 0.49

r = 0.13 p = 0.2

r = 0.37 p <0.001

r = 0.28 p = 0.004

Weight 9mo

r = -0.036 p = 0.72

r = 0.35 p < 0.001

r = 0.20 p = 0.048

r = 0.000 p = 0.998

r = 0.14

p = 0.16

r = 0.073

p = 0.47

Birth W

LS-BMDLS-BALS-BMCT-BMDT-BAT-BMC

Christian Mølgaard

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r = 0.051 p = 0.61

r = 0.034 p = 0.73

r = 0.047 p = 0.64

r = 0.11

p = 0.27

r = 0.21

p = 0.035

r = 0.21

p = 0.035

∆L9-b

r = 0.029 p = 0.77

r = 0.26 p = 0.008

r = 0.18 p = 0.068

r = 0.15 p = 0.14

r = 0.39

p < 0.001

r = 0.30

p = 0.002

Length 9mo

r =-0.023 p = 0.82

r = 0.28 p = 0.004

r = 0.17 p = 0.09

r = 0.052 p = 0.60

r = 0.19 p = 0.06

r = 0.13 p = 0.19

Birth L

LS-BMDLS-BALS-BMCT-BMDT-BAT-BMC

Results

Sex adjusted correlations between bone mass at 17 y and early length and length gain

Christian Mølgaard

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r = 0.32

p = 0.032

r = 0.19

p = 0.21

r = 0.31

p = 0.034

r = 0.104 p = 0.49

r = 0.095 p = 0.53

r = 0.097 p = 0.52

S-BGP

6 mo

r = 0.12

p = 0.23

r = 0.17

p = 0.09

r = 0.15

p = 0.13

r = 0.004 p = 0.97

r = 0.034 p = 0.73

r = 0.001 p = 0.99

Any

BF (mo)

r = 0.23

p = 0.021

r = 0.22

p = 0.028

r = 0.26

p = 0.009

r = 0.09

p = 0.38

r = 0.11

p = 0.25

r = 0.10 p=0.3

Exclus.

BF (mo)

LS-BMDLS-BALS-BMCT-BMDT-BAT-BMC

Results

Sex adjusted correlations between bone mass at 17 y, breastfeeding and early s-BGP (osteocalcin)

S-BGP at 2 mo and 9 mo: No significant correlations

Christian Mølgaard

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Results

Sex adjusted association between size adjusted BMC at 17 y and early body size, growth, bone turnover and nutrition

No association between size adjusted (T or LS) BMC and body size and growth in infancy

Borderline positive association between size adjusted LS BMC and number of month with exclusive breastfeeding (p=0.075) but not any breastfeeding (p=0.38)

Significant positive association between size adjusted LS BMC and s-BGP at 6 month (p=0.047) but not 2 month (p=0.34) or 9 month (p=0.79)

Christian Mølgaard

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Limitations

Low number of participants especial in some of the analyses

Lumbar spine bone mass is from the whole body DXA scan and not from a regional lumbar DXA scan

Different methods for analyses of osteocalcin in infancy and adolescence

Strengths

Very detailed registrations in the first year of life with follow up at 10 and 17 years of age

Christian Mølgaard

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Conclusion

� As shown by others early body size and growth in infancy are related to later bone mass. Apparently mainly through tracking in body and bone size.

� Duration of exclusive breast feeding seems to be positively related to later spinal bone mass

� Early bone turnover seems to be related to later spinal bone mass

Christian Mølgaard

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Conclusion

� We speculate if the early influence of breastfeeding on later bone mass could be a programming effect through an early effect on bone turnover

� Another possibility is through an influence of breastfeeding on the IGF-1 axis (Larnkjær et al 2009)

Christian Mølgaard

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Christian Mølgaard

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Christian Mølgaard

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Thank you for the attention!