CALCIUM, VITAMIN D AND BONE GROWTH
OBJECTIVE NUTRITION 72, (JUNE 2004)
by Prof. Jean-Philippe BONJOUR, Faculty of Medicine, University of Geneva, Geneva, Switzerland

In the majority of Western countries, calcium and vitamin D intake in childhood and adolescence are adequate to prevent the occurrence of overt bone disease during childhood. The increased interest in calcium and vitamin D intake in children and teenagers over the last 15 years, can be explained otherwise:  in fact, bone mineral mass reached at the end of the growing period is a major determinant of risk of osteoporosis, to the same extent as postmenopausal and/or age-related bone mass loss.

From a very young age up to the end of adolescence, calcium and vitamin D are essential to bone growth.  Calcium deficiency slows skeletal growth by decreasing bone tissue mass.  The trabecular bone microarchitecture deteriorates, which further decreases bone resistance to mechanical stress. Vitamin D deficiency slows the intestinal absorption of the calcium phosphate product in the extracellular compartment and that of inorganic phosphate (IP), with the subsequent decrease of the calcium-phosphate product in the extracellular compartment and mineral deposition in the organic bone matrix.  Such a deficiency causes rickets in children and osteomalacia in adults.

Epidemiological studies have demonstrated that a 10% increase (about one standard deviation) in the peak mineral bone mass (PBM)  (Figure 1) may reduce the risk of subsequent osteoporotic fractures by 50%. In this regard, nutritional factors, including most importantly calcium, have been studied especially in children and teenagers.

Epidemiological data

   ·  Calcium intake

Recent results indicate that in women 20 to 49 years of age, (the age category in which PBM is reached and bone mineral density (BMD) is almost constant), the bone mineral mass was that much higher when ingestion of milk in childhood and adolescence was high.  In women over 50 years of age, a relatively high ingestion of milk in childhood was associated not only with an increased BMD at the upper end of the femur but also with a lower risk of osteoporotic fractures.  These data agree with those of observational studies on populations of healthy children and teenagers, demonstrating a positive correlation between calcium intake (65-70 % of which comes from dairy products) and gain in bone mineral mass.  This relationship is especially marked before the start of pubertal maturation.
In pre-pubertal girls 7 to 9 years of age, we found a median level of spontaneous calcium intake from dairy products of about 850 mg/day. Subjects whose daily intake of calcium was about 1150 mg had a BMD in the lumbar vertebrae, neck of the femur, femoral and radial diaphysis of about 0.1-0.3 SD higher than that of girls who ingested about 650 mg of calcium a day.
An observational study in Finland over an 11-year period also suggests that, apart from physical activity, calcium intake above 800 mg a day in childhood and adolescence in female subjects, is associated with a higher bone mineral mass when the it is measured in the neck of the femur at age 27 to 28 years, i.e., after
PBM is reached.

   ·  Function of vitamin D

Even in the absence of an obvious deficiency, a correlation exists between vitamin D intake and gain in bone mineral mass during the growth period.  In 8-year old girls,    BMD measured at several sites of the skeleton was higher in girls who had received physiological doses of vitamin D (400 IU per day) during the first year of life. In a prospective Finnish study conducted on girls 9 to 15 years of age at time of enrolment, vitamin D status was positively correlated with increased BMD in the proximal femur, and even more so in the lumbar vertebrae.

Interventional studies

The effect of calcium supplementation during the growth period has been evaluated in several interventional, randomized, placebo-controlled trials. Overall, these studies have demonstrated a higher gain in children or teenagers who received a calcium supplement of 300 - 800 mg a day for 1 to 3 years, compared to placebo groups.
"The calcium effect” is more pronounced at skeletal sites mainly comprised of cortical bone such as the radial or femoral diaphysis.  The response to calcium supplementation is especially evident in subjects whose spontaneous intake of calcium is relatively low.

The differences observed from one study to another in the extent of bone response can be accounted for by age differences, pre-pubertal maturation, protein intake, and physical activity (Figure 2). The type of calcium salt tested could also affect the bone response.

Does the benefit persist after discontinuation
of calcium supplementation ?

The persistence or the disappearance of benefit after the end of the supplementation may also depend on the calcium salt ingested as well as age at time of enrolment in relation to start of pubertal maturation.  In an interventional randomized, double-blind, placebo-controlled trial, conducted on a homogeneous group of 144 pre-pubertal girls, mean age 7.9 years, the supplement was supplied for 12 months in food enriched with a calcium salt derived from milk extracts, thus as a phosphate salt. Subjects in the placebo group received the same food but not enriched with calcium.  Mean calcium intake which amounted to about 900 mg a day rose to 1700 mg in the calcium-supplemented group. The increase in calcium intake was reflected by a higher yearly gain in bone mineral mass, especially in the radius and femur. The gain obtained at the end of the supplementation had not disappeared 1.0 and  3.5 years after discontinuation of calcium supplementation. At a mean age of 16.4 years, i.e., 7.5 years after the end of the supplementation, the persistence of gain in BMD in the radius and femur was very significant, but only in the girls who had had their menarche at a relatively early age. This study with long-term follow-up suggests that  a supplementation using a calcium salt extracted from milk in prepubertal girls can have a positive effect on the BMD course and  probably increase PBM. Persistence of the effect seems to depend on factors which determine pubertal maturation.

At what age should calcium intake be increased ?

Skeletal response to increased calcium intake seems to be especially favorable before the start of pubertal maturation, which does not mean that the peripubertal period (during which bone growth is 2 to 4 times higher) should be neglected. This period lasts on average for 36 months, from age 11 to 14 in girls, and 48 months, from age 13 to 17, in boys. To satisfy this accelerated bone growth, it is estimated that net daily calcium allowances rise from 70-150mg before puberty to 250 mg in girls and 300 mg in boys.  Consequently, the recommendation is to increase calcium intake starting at age 10 from 900 to 1200 mg a day  (Table 1).

Effect of other nutrients

Two interventional studies have demonstrated that the intake of a supplement of milk or dairy products significantly increases the gain in bone mass during the peripubertal period.  These data suggest that milk and related products contain a combination of nutrients (in particular proteins and calcium salt in phosphate form) which promote bone growth, even during a period when endocrine factors play a dominant role.
IP is an essential component of bone crystal matrix. Its transport by bone-forming cells is activated by certain growth factors, such as insulin-like growth factor 1 (IGF-1), which also produces a positive effect on bone formation.  Elevation of plasma IP occurs during the phases of accelerated growth.  Hypophosphatemia is associated with slowed growth and bone mineralization. Therefore, IP is essential to physiological development of the skeleton.  It promotes the retention of calcium, and not the contrary, as sometimes stated.  Proteins, including casein, stimulate the production of IGF-1 in the liver, through the action of certain essential amino acids.  Thus, an increase in plasma IGF-1 levels has been observed after milk supplementation in teenagers. IGF-1 also acts on the kidney by stimulating the production of an active metabolite of vitamin D, i.e., 1,25 dihydroxy vitamin D (1, 25 D), which in turn increases the capacity of the intestinal epithelium to absorb calcium and IP. IGF-1 also stimulates the tubular reabsorption of IP, and consequently tends to increase serum phosphate concentrations.

Conclusion

The bone mineral acquisition at the end of the growth period is an important determining factor for the risk of subsequent osteoporosis. Optimizing the acquisition of bone mass during growth is a measure for primary osteoporosis prevention and its bone fracture complications.  Calcium and vitamin D have a positive effect on bone    stores reached at the end of the growth period.
Proteins and IP have a positive effect on bone growth. Due to their high calcium, IP and proteins content, dairy products represent a class of foods that are especially well-suited to optimum bone growth, in so far as the total amount of vitamin D intake through the skin and diet is sufficient.

Prof. Jean-Philippe BONJOUR
Faculty of Medicine, University of Geneva, Geneva,  Switzerland

Figure 1.
Changes of bone mass over a lifetime

Figure 2.
Main determining factors of peak bone mass (PBM)

Table 1.
Recommended dietary allowances (RDA) of calcium and vitamin D during growth period

From AFFSA-CNERNA-CNAS. Recommended dietary allowances for the French population  – 3rd edition –TEC Publisher and DOC 2001.
*1mg = 40 IU.
** A supplement of a 5 mg per day compensates for a dietary vitamin D deficiency in subjects with normal exposure to sunlight.. Some teenagers who do not receive adequate exposure to sunlight should receive a supplement during the wintertime.  A 10 mg per day supplement meets the requirements of subjects who do not receive exposure to sunlight.

Table 2.
Quantity of food to be ingested to obtain the required 300 mg of calcium.