By Dr. Steven A. Abrams

Critical public health problems in adults, including cardiovascular disease, have strong roots both in genetic predisposition and in nutrition during childhood and adolescence. In the last 20 years, osteoporosis has been recognized as such a disease. Primary prevention of osteoporosis in otherwise healthy adults begins with appropriate diet and health care in childhood. An estimated 25 percent of adult bone mass is accrued during just two years of peak skeletal growth during early adolescence.⁽¹⁾

Patterns of bone development
We have been interested in both the genetic and the dietary aspects of understanding peak bone mass during childhood and adolescence. Peak bone mass, the maximum level of lifetime bone mineral, is achieved by most adults in their mid-20s, but 90 percent to 95 percent of this level is reached by age 16 in girls and slightly later in boys. Peak levels of calcium absorption and bone formation occur in early- to mid-puberty with a rapid decrease after menarche in girls such that by two years after menarche, bone formation rate is not much greater than it is in adults.⁽²⁾

Genetic factors attributed to reaching a high peak bone mass include ethnicity, gender, and age at puberty. More recently, certain genetic polymorphisms have been putatively associated with higher bone mineral levels. More than 50 such genetic variations have been reported, mostly involving action of vitamin D and the vitamin D receptor. However, very few studies have been done in children, and data are inconsistent and do not allow for identification of a high-risk genetic profile for osteoporosis.

Genetic factors
We evaluated the relationship between polymorphisms of one vitamin D receptor (VDR) gene, Fok1, and calcium metabolism.⁽³⁾  We measured bone mineralization and calcium metabolic parameters longitudinally in a group of 99 adolescents. We found a significant relationship between calcium absorption and skeletal calcium accretion and Fok1, but not with other VDR or related genetic polymorphisms. It appears that the Fok1 gene directly affects bone mineralization during pubertal growth, at least in part via an effect on calcium absorption.

Dietary factors
Short-term studies in adolescents have generally shown an enhancement of calcium absorption by inulin-type fructans (prebiotics). Results have been inconsistent, however, and previously there were no studies to determine if this effect persists with long-term use. We assessed the effects of one year of supplementation with a prebiotic on calcium absorption and bone mineral accretion.⁽⁴⁾  We found that adolescents who received the prebiotic had significantly greater calcium absorption than those who did not. Additionally, subjects who received the prebiotic had a greater increment than non-supplemented subjects both in whole body bone mineral content and in whole body bone mineral density. We are currently evaluating the mechanism by which prebiotics enhance mineral absorption.

Calcium supplementation and public policy
A large series of research studies has demonstrated that optimal calcium intake, defined as the intake needed to maximize bone mineralization during puberty, is between 1200 and 1500 mg per day. A level of 1300 mg per day was set in 1997 by the Dietary Reference Intake (DRI) panel as the “Adequate Intake” (AI) of calcium for males and females ages 9 through 18.⁽⁵⁾ In the case of extremely low daily calcium intakes (such as less than 500 to 600 mg per day) during puberty, a very large gap between maximal retention and actual retention can exist.⁽⁶⁾ Although low calcium intakes may lead to immediate problems, including increased fracture risk, the intake level needed to substantially increase this risk is unknown.

The problem is that, despite considerable and widespread public health campaigns, calcium intake in adolescents, especially girls, remains far below the target AI.^(7,8) Recent data, consistent with large amounts of previous data over the past 20 years, suggest that during puberty mean calcium intakes are about 800 to 900 mg per day in girls and 950 to 1050 mg per day in boys, with median intakes as much as 100 mg lower than the means and as many as 20 percent to 30 percent of adolescent girls with extremely low intakes (less than 500 mg per day).⁽⁵⁾

Pediatricians and bone health
At present the question is, what do we advise those whose dietary intakes do not reach the AI, especially most U.S. adolescents whose calcium intake is between about 700 to 1200 mg per day. It is important that pediatricians and other caregivers discuss and at least attempt to assess calcium intake in their pediatric populations.⁽⁹⁾ Very low intakes (especially less than 500 to 600 mg per day), health issues that affect bone metabolism, a strong family history of osteoporosis, or lack of adequate exercise should trigger a multifaceted response, including dietary counseling and, if dietary approaches are unsuccessful, use of supplements or other appropriate health interventions.

There is less evidence for the use of pill supplements for those with intakes closer to the recommendation (for example 700 to1200 mg per day in adolescents).⁽⁸⁾ Some catch-up may be possible in later adolescence and early adulthood, and it is reasonable to emphasize overall good dietary habits and exercise rather than advocating pill-type calcium supplements.⁽¹⁰⁾ Low-fat yogurts, fortified orange juice, and other fortified foods such as cereals may be appealing to adolescents who do not choose substantial amounts of fluid milk. The American Academy of Pediatrics (AAP) recently emphasized that pediatricians should provide counseling to families related to both calcium intake and exercise to enhance bone health.⁽⁹⁾ Ensuring adequate vitamin D status also is important. This counseling may best be provided during early childhood and adolescent visits.

In conclusion, osteoporosis, like many other chronic illnesses, can be seen as an often genetically determined disorder that can be exacerbated by a lifetime of poor diet or inadequate exercise, beginning in childhood. Eventually, risk profiles may be generated and specific individualized monitoring programs may be devised based on identified risk factors.

References

1. McKay HA, Bailey DA, Mirwald RL, Davison KS, Faulkner RA. Peak bone mineral accrual and age at menarche in adolescent girls: a 6-year longitudinal study. J Pediatr 1998;133:682–687.
2. Abrams SA, Copeland KC, Gunn SK, Gundberg CM, Klein KO, Ellis KJ. Calcium absorption, bone mass accumulation, and kinetics increase during early pubertal development in girls. J Clin Endocrinol Metab 2000;85:1805–1809.
3. Abrams SA, Griffin IJ, Hawthorne KM, Chen Z, Gunn SK, Wilde M, Darlington G, Shypailo R, Ellis K. Vitamin D receptor Fok1 polymorphisms affect calcium absorption, kinetics, and bone mineralization rates during puberty. J Bone Miner Res 2005;20:945–953.
4. Abrams SA, Griffin IJ, Hawthorne KM, Liang L, Gunn SK, Darlington G, Ellis KJ. A combination of prebiotic short-and long-chain inulin-type fructans enhances calcium absorption and bone mineralization in young adolescents. Am J Clin Nutr 2005:82;471–476.
5. Institute of Medicine (U.S.). Standing Committee on the Scientific Evaluation of Dietary Reference Intakes. DRI, Dietary reference intakes: for calcium, phosphorus, magnesium, vitamin D, and fluoride. Washington, DC: National Academy Press; 1997.
6. Abrams SA, Griffin IJ, Hicks PD, Gunn SK. Pubertal girls only partially adapt to low dietary calcium intakes. J Bone Miner Res 2004;19:759–763.
7. Lloyd T, Petit MA, Lin HM, Beck TJ. Lifestyle factors and the development of bone mass and bone strength in young women. J Pediatr 2004;144:776–782.
8. Abrams SA. Calcium supplementation during childhood: long-term affects on bone mineralization. Nutr Rev 2005;63:251–255.
9. Greer FR, Krebs NF, American Academy of Pediatrics, Committee on Nutrition. Optimizing bone health and calcium intakes of infants, children, and adolescents. Pediatrics 2006;117:578–585.
10. MacKelvie KJ, Khan KM, Petit MA, Janssen PA, McKay HA. A school-based exercise intervention elicits substantial bone health benefits: a 2-year randomized controlled trial in girls. Pediatrics 2003;112:e447.

Steven A. Abrams, M.D., is an attending physician in Neonatology at Texas Children’s Hospital and a professor of Pediatrics at Baylor College of Medicine.

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