An increase in calcium absorptive efficiency (fractional absorption of dietary calcium) during adolescence is associated with a rapid increase in total body bone mineral mass (BMM) accumulation. This increase occurs across a range of calcium intakes. It appears to be principally mediated by hormonal changes of puberty including increases in insulin-like growth factor-1 (IGF-1), luteinizing hormone (LH) and estrogen. Calcium supplementation during adolescence has led to short-term increases in measures of BMM, but has not had a consistent long-term benefit. This is likely due to the efficient nature of catch-up of mineralization throughout adolescence and early adulthood as long as calcium intake is not severely deficient and other dietary factors are adequate. Vitamin D is needed for active (transcellular) calcium absorption of calcium. However, in contrast to adults, no close relationship between serum 25-hydroxyvitamin D (25-OHD) concentration and calcium absorption in non-vitamin D-deficient adolescents has been demonstrated. No data are available to identify an optimal 25-OHD concentration in adolescents, although avoidance of very low levels is necessary. The routine supplementation of adolescents with high dose vitamin D (e.g., more than about 400 IU/d) is not justified based on currently available data unless specific risk factors for low vitamin D status or malabsorption of vitamin D exist. Other interventions that may enhance the absorption of calcium require further evaluation but may be of importance. For example, prebiotics have been demonstrated to enhance calcium absorption and BMM acquisition, but longer-term studies are needed. For most adolescents, a combination of avoiding a very low calcium intake (< 600-800 mg/d), and maintaining a diet with adequate amounts of other essential bone nutrients will lead to adequate calcium absorption and BMM accumulation during adolescence. Revision of dietary guidelines for calcium and vitamin D to create a full range of recommendations is urgently needed.
Adolescence is a critical time for the accumulation of bone mineral mass (BMM). Close
to half of all total body bone mineral content (BMC) acquisition occurs in girls
over a narrow window of 4 to 5 years beginning with the onset of pubertal
development (
The optimal method for achieving the genetically determined peak bone mass for an
individual is uncertain. The most obvious approach, increasing calcium intake during
adolescence, has not been convincingly shown to increase long-term BMM accumulation.
Over a dozen well-conducted, blinded, controlled intervention trials have
demonstrated a short-term increase in some measure of BMM or density, usually
total body bone mineral content (BMC) or bone mineral density (BMD). However,
several of these trials included a follow-up period after supplementation or a
long-term supplementation. These studies have shown little if any maintenance of a
benefit to BMM or density after calcium supplementation was stopped. In the longest
supplementation study in adolescents, very little benefit was demonstrated for 7
years of supplementation (
Therefore, efforts have centered on a variety of strategies other than promoting high
calcium intakes or calcium supplementation to support BMM accumulation. Further
physiological data have focused on the interaction of hormones, genes, exercise and
diet in promoting BMM accrual (
To consider these, we will initially note genetic and hormonal effects on peak BMM and then consider intervention strategies and the status of these interventions on supporting BMM accumulation. Finally, we will try to summarize these factors into a current perspective on this issue.
It is clear that the single largest determinant of peak bone mass and BMM
accumulation during adolescence is genetic. Traditionally recognized genetic factors
are gender and race. More recently, a series of genetic polymorphisms associated
with the vitamin D receptor have been recognized as affecting BMM. Data, however,
are minimal in adolescents compared to adults. We found a relationship between
calcium absorption and Fok1 polymorphisms of the vitamin D receptor gene.
Other polymorphisms associated with bone mineral density in adults are less clearly
associated with BMM in adolescents (
An additional genetic factor that has been identified in determining BMM is stature.
In both adolescents and adults, there is a small but significant relationship
between height and calcium absorption (
A difficult factor to assess has been the effects of reproductive and growth hormones
on the pattern and accumulation of BMM. Bone calcium deposition peaks 6-12 months
prior to puberty (
Studies of hormone administration in normal subjects and disease states are
consistent with important effects of sex steroids on calcium absorption.
Administration of testosterone to prepubertal boys induced large changes in calcium
absorption (
The adolescent growth spurt itself depends on both growth hormone and estradiol in
normal girls and boys. Several lines of evidence support the primacy of estradiol in
the control of the growth spurt. Hypopituitary patients deficient in both growth
hormone and gonadotropins do not have an adolescent growth spurt when growth hormone
alone is replaced (
How would sex steroids or growth hormones effect a substantial increase in calcium
absorption during puberty? One possibility is that they may directly increase the
efficiency of intestinal calcium absorption. Calcium absorption takes place by a
passive paracellular route and an active transcellular transport mechanism (
An estrogen- or growth hormone-responsive increase in the number of calcium
transporters would be predicted to increase the efficiency of calcium transport at
any given level of calcium intake and vitamin D, and such a change could in theory
account for much of the increase in calcium absorption that is required to support
rapid bone growth in the peripubertal period. Bone calcium deposition falls off
after menarche, however, in the face of continued high estradiol levels (
The increased rate of calcium accretion into bone during the pubertal growth spurt,
by reducing serum calcium, could induce an increase in intestinal calcium absorption
via PTH and vitamin D. In cross-sectional studies, the serum 1,25-dihydroxyvitamin D
concentration increases in the peripubertal period, but the changes are relatively
small (
To unravel further these hormonal effects, simultaneous determinations of the
associations of serum estrogen, IGF-1, PTH and serum 1,25-dihydroxyvitamin D
concentrations with calcium absorption and bone formation in longitudinal studies of
puberty would be useful. If calciotropic hormones couple the demands of bone growth
to intestinal calcium absorption, it might be predicted that adult height, as a
surrogate of the extent of bone growth, is a predictor of the PTH and serum
1,25-dihydroxyvitamin D concentrations during puberty. Absent the stimulatory effect
of estrogen on calcium absorption, growth hormone therapy of growth
hormone-deficient prepubertal children might be expected to cause larger increases
in PTH and 1,25-dihydroxyvitamin D than normal puberty; some evidence to suggest
this has been reported (
Intervention strategies to increase the total amount of absorbed calcium and thus
total body BMM have generally focused on the following; increases in calcium intake,
increase in vitamin D intake (or sun exposure), and increasing the bioavailability
of dietary calcium using other dietary factors such as prebiotics or by providing
more soluble salts of calcium (
Strategies to promote increased calcium intake among adolescents have been largely
ineffective, and supplementation studies have had minimal effect on BMM over a long
period of time (
The accuracy of both this calcium intake value and of the concept of a fixed asymptotic value for maximal calcium retention are uncertain. Rather, it is likely that there is no absolute value above which no or negligible further calcium can be absorbed or if there is such an intake, it is much higher than 1300 mg/d. On the other hand, the long-term catch-up of BMM suggests that reaching a “near asymptote” may be unnecessary. This has led to suggestions that excessive public health emphasis on achieving calcium intakes of 1300 mg/d, a level far beyond usual adolescent intakes and not achieved by > 80% of adolescent girls, may be somewhat misplaced. Rather, emphasis on overall healthy diets and lifestyle to support bone growth and mineralization should be provided.
This does not mean that adequate calcium intake should not be encouraged, however.
Very low calcium intakes, especially those < 600-800 mg/d, are unlikely to be
associated with maximal or near maximal total calcium absorption or BMM accretion
(
One potential approach to increasing calcium absorption at lower calcium intakes is
to increase vitamin D status and thus increase transcellular calcium absorption. In
studies in adults, a combination of calcium and vitamin D supplementation leads to
important increases in BMD and fewer fractures (
Of physiological importance is that there appears to be a difference in the
relationship between vitamin D status and calcium absorption in children and
adolescents compared to adults. The available data in adults indicate a relatively
linear increase in calcium absorption with serum 25-OHD concentration up to about 35
ng/mL (
In children and adolescents, however, the data are less clear regarding this
relationship. Low maternal vitamin D status has been linked to low BMM in infants
and children, although confirmatory and safety data, especially in an American
cohort, are needed before recommendations can be made regarding maternal high dose
supplementation for this purpose (
The relationship between serum 25-OHD concentrations and calcium absorption in
children remains somewhat puzzling. The inverse relationship between 25-OHD levels
and parathyroid hormone levels seen in adults is also seen in adolescents in
multiple studies (
Furthermore, it appears that adolescents adapt to lower 25-OHD concentrations and
increased serum PTH by increasing 1,25 dihydroxyvitamin D concentrations and
maintaining calcium absorption (
The current dietary recommendation for vitamin D, as with calcium, is an “adequate intake” (200 IU/d). The use of an adequate intake, a single, poorly-defined reference value, for both calcium and vitamin D intakes is highly inappropriate as current data are more than adequate to develop both an estimated adequate requirement (EAR) and a recommended dietary requirement (RDA). Many other nutrients about which far less scientific data exist have these guidelines in place. These values would greatly enhance dietary planning for both individuals and populations and should be developed as soon as possible as a matter of highest priority.
It is possible that a higher value than the current adequate vitamin D intake of 200 IU/d for adolescents would be determined to be an appropriate estimated average requirement or RDA. However, dietary recommendations well above this level, e.g., intakes above 400-500 IU/d, must be tested in controlled trials in adolescents before being advocated. Outcomes that must be tested would include calcium absorption, BMM accumulation and safety parameters including serum and urinary calcium concentrations. Such trials should be conducted in both northern and southern parts of the United States. They should be multi-ethnic and be conducted across multiple seasons. Long-term outcomes, including overall fracture rates during adolescence and BMM in adulthood after adolescent supplementation, would be ideal outcomes, although more difficult to assess within a reasonable time period.
Other dietary factors may also enhance calcium absorption and BMM accumulation (
Other dietary factors are increasingly being considered in enhancing peak BMM. These
include a possible role for long-chain polyunsaturated fatty acid supplementation.
Current data are limited, however, and principally derived from animal models (
In summary, a programmed large increase in fractional absorption of calcium occurs during early adolescence. This increase appears to be mediated by hormonal changes of puberty and does not appear to be associated with serum 25-OHD concentrations as long as overt vitamin D deficiency is avoided. From an evolutionary perspective, these conclusions are consistent with the speculation that adolescent bone growth, like pregnancy and lactation, has evolved to achieve success with minimal reliance on calcium and vitamin D intake. Interventions to enhance the total absorption of calcium using dietary strategies or supplements to increase calcium intake have had minimal long-term success in the United States and have not been widely accepted by adolescents.
Ultimately, it is necessary to further define the factors needed to approximate the maximal (peak) BMM. Increasing the bioavailability of calcium in the diet, enhanced exercise and increased vitamin D intake are all possibilities that have been explored minimally in adolescents compared to adults. Long-term efficacy data are especially weak. It is likely in the future that further genetic studies will increase the confidence in any approach as being likely to benefit an individual or subset of the population. Pending such data, avoidance of very low calcium intakes (< 600-800 mg/d), provision of adequate dietary vitamin D, and appropriate lifestyle habits including exercise may be recommended in adolescents as well as children. Urgent revision of dietary requirements for calcium and vitamin D to provide both an estimated average requirement and an RDA is needed.
This work is a publication of the U.S. Department of Agriculture (USDA)/Agricultural Research Service (ARS) Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine and Texas Children's Hospital, Houston, TX. This project has been funded in part with federal funds from the USDA/ARS under Cooperative Agreement number 58-6250-6-001. Contents of this publication do not necessarily reflect the views or policies of the USDA, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government.