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
Slide 2
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
Slide 3
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
Slide 5
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
Slide 6
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
Slide 8
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
Slide 12
Christian Mølgaard
Slide 13
Christian Mølgaard
Slide 14
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
Slide 15
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
Slide 16
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
Slide 17
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
Slide 18
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
Slide 19
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
Slide 20
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
Slide 21
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
Slide 22
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
Slide 23
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
Slide 24
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
Slide 25
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
Slide 26
Christian Mølgaard
Slide 27
Christian Mølgaard
Slide 28
Thank you for the attention!
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