Bone health and calcium requirements in adolescents

INTRODUCTION — Bone size and bone mineral content increase rapidly during late childhood and adolescence, continuing to the beginning of the third decade of life. This is a time of opportunity and vulnerability for accumulating the bone mineral content that is essential for bone health throughout the lifespan.

Adequate calcium intake and weightbearing physical activity are necessary to maximize peak bone mineral content and to minimize the risk of fractures in adolescence and the development of osteoporosis in adulthood, as discussed below. Adequate vitamin D is also important to bone health and is discussed separately. (See "Vitamin D insufficiency and deficiency in children and adolescents".)

DEFINITIONS RELATED TO BONE HEALTH

●Bone mineral content (BMC) and bone mineral density (BMD) – Dual-energy x-ray absorptiometry (DXA) measures BMC (in grams) and bone area (in cm²), then calculates "areal" BMD (in g/cm²). For children and adolescents, the results are presented as a Z-score value, which compares the individual's results with an age-matched population. A Z-score more than 2 standard deviations (SD) below the mean indicates increased fracture risk, although the clinical relevance of these definitions is less certain for children than for adults. (See "Overview of dual-energy x-ray absorptiometry", section on 'Children'.)

The term "bone mass" is sometimes used to refer to the whole weight of bone (reflecting BMD and bone size). However, BMC and BMD are more specific and clinically useful terms.

●Osteoporosis – In children and adolescents, osteoporosis is defined by [1]:

•One or more vertebral (crush) fractures (in the absence of local disease or high-energy trauma), or

•BMD Z-score more than 2 SD below the mean plus a clinically significant fracture history. Abnormal BMD is not sufficient to diagnose osteoporosis.

●Bone strength and quality – Bone strength is determined by BMD and other properties of bone that are collectively called "bone quality." (See "Overview of dual-energy x-ray absorptiometry", section on 'Bone quality'.)

BONE GROWTH DURING ADOLESCENCE

Time course — The rapid bone growth during the second decade of life is characterized by:

●Cumulative bone mineral content (BMC) – Approximately one-half of total body calcium is laid down during puberty in females and one-half to two-thirds in males [2,3]; by the end of puberty, males have nearly 30 percent more total body calcium than do females.

●Phases of bone growth – Pubertal changes start with an increase in bone width (bone area), followed by increases in BMC, then bone mineral density (BMD) [4]. The changes occurred earlier in females than in males, with most of the changes in females beginning in the two years before menarche and being completed approximately two to three years after menarche.

●Relation to peak height velocity – Peak BMC occurs approximately six years after peak height velocity [4]. During the pubertal growth spurt, bone growth outpaces bone mineralization, leading to a relative reduction in BMD for approximately one year after peak height velocity [2,3]. In a longitudinal study, the nadir of BMD coincided with peak height velocity in both males and females [5]. The same study reported that the incidence of distal radius fractures coincided with the same time point. (See 'Fractures during childhood' below.)

Although several resources report differences in average BMC and BMD by race/ethnic groups, this factor predicts a small component of the overall variance within the population and is not considered a relevant factor in determining recommended calcium intakes [6,7]. (See "Measurement of body composition in children", section on 'Dual-energy x-ray absorptiometry'.)

Clinical importance

Attainment of peak bone mass — Peak bone mass is a key determinant of long-term skeletal health and osteoporosis risk in adulthood (figure 1) [3,4,8]. Bone mass (bone size and BMD) increase dramatically between birth and early adulthood. Later in life (and particularly after menopause in females), BMD decreases, which can lead to osteoporosis or bone fragility. Even a modest increase in peak BMD can delay postmenopausal osteoporosis and greatly reduce fracture risk. Genetic factors influence skeletal structure and bone turnover and account for 60 to 80 percent of the differences in peak bone mass [2,3]. Environmental factors, particularly adequate dietary calcium and weightbearing activity, account for 20 to 40 percent of the variance in peak bone mass [3]. Thus, optimizing these factors during adolescence helps to maximize peak bone mass [9]. (See "Pathogenesis of osteoporosis".)

Fractures during childhood — Several epidemiologic studies suggest a link between bone mass or BMD and fractures in children [10-13]. For example, in a case-control study in females aged 3 to 15 years, those with distal forearm fractures had reduced BMD throughout the skeleton compared with age-matched controls [10]. In addition, after adjusting for weight, BMD was more common in cases than in controls (20 versus 12 percent).

Although physical activity increases BMD, certain types of physical activity also increase fracture frequency due to risk of falls (see 'Physical activity' below). Limited evidence suggests that high dietary calcium intake may be protective; this was found in a series of adolescents in which those with high calcium intake had a lower risk of fractures (adjusted odds ratio 0.28 [95% CI 0.09-0.92]) [14]. However, high calcium (and vitamin D) intake has minimal effect on the usual trauma-related fractures of childhood and adolescence.

OVERVIEW OF CALCIUM HOMEOSTASIS — Calcium homeostasis is a function of:

●Dietary intake

●Intestinal absorption

●Skeletal accretion and resorption

●Urinary excretion

The large demand for bone minerals during adolescence is accompanied by an increase in the efficiency of absorption and utilization of dietary calcium during early puberty in children [15,16]. In females, calcium absorption subsequently decreases approximately two to three years after menarche [16-18].

During adolescence, increased absorption and decreased excretion of calcium may partially compensate for low dietary intake [19]. The increase in calcium absorption during adolescence is thought to be mediated by calcitriol (1,25-dihydroxyvitamin D, the primary active metabolite of vitamin D), which also increases in concentration during the pubertal growth spurt [20]. Vitamin D fortification of calcium-containing foods enhances the efficiency of intestinal absorption of calcium, whereas dietary oxalate and phytate diminish it. These factors affect the absorbable calcium in foods, as shown by the examples in the table (table 1) [21]. (See "Overview of vitamin D", section on 'Metabolism'.)

Most of the body calcium and much of the phosphate exist as hydroxyapatite, Ca₁₀(PO₄)₆(OH)₂, the main mineral component of bone. Within the plasma, both calcium and phosphate circulate in different forms. Of the plasma calcium, for example, roughly 40 percent is bound to albumin; 10 percent is complexed with citrate, bicarbonate, or phosphate; and 50 percent exists as the physiologically important ionized (or free) calcium [22].

Although only a small fraction of the total body calcium and phosphate is located in the plasma, the plasma concentrations of ionized calcium and inorganic phosphate are regulated primarily by parathyroid hormone and vitamin D metabolites, both of which affect intestinal absorption, bone formation and resorption, and urinary excretion [22-24]. Urinary calcium excretion is increased by dietary salt and protein [21,25-27]. Diuretics also affect calcium excretion, which is increased by loop diuretics and reduced by thiazide diuretics. (See "Diuretics and calcium balance".)

KEY DETERMINANTS OF BONE HEALTH IN ADOLESCENTS

Genetics — Genetic factors are responsible for approximately 60 to 80 percent of osteoporosis risk, and familial patterns are expressed prior to puberty [3]. (See "Pathogenesis of osteoporosis", section on 'Genetics'.)

Key modifiable factors — Environmental factors, particularly calcium intake and physical activity, are responsible for 20 to 40 percent of peak bone mass.

Calcium intake — Epidemiologic studies have related bone mineral density (BMD) in adolescents and adults to calcium intake during childhood and adolescence, although this relationship is affected by many other factors such as vitamin D intake. Recommendations for calcium intake for adolescents are designed to maximize peak bone mass and thus reduce the ultimate risk of fractures and osteoporosis [9]. The recommendations are based on studies of calcium balance (net retention) and typical calcium accumulation (bone density studies), which are discussed in detail in the guidance documents [2,7].

●Recommended dietary allowance (RDA) – The RDA for calcium is 1300 mg (referring to elemental calcium) daily for males and females 9 to 18 years of age [2,7]. This RDA was set by the Food and Nutrition Board of the National Academy of Sciences, which estimated that maximum positive calcium balance is achieved at intakes between 1200 and 1500 mg/day, based on the results of calcium balance studies. This guideline is set to meet the needs of 95 percent of healthy children. A fact sheet summarizing the recommendations for calcium intake and calcium content of foods is available from the National Institutes of Health [28].

There is limited information to determine the effects of intakes that are moderately above or below the RDA target. The failure of the short-term supplementation studies to show a substantial long-term benefit in bone mineralization suggests that the higher calcium balance achieved with high calcium intakes may have limited or no long-term benefits [29-31]. However, calcium intakes of 1200 to 1500 mg/day in children is safe [32].

The calcium content on food labels usually is indicated as a percentage of the "Daily Value" in each serving. The Daily Value for calcium is 1300 mg/day. The Daily Value for calcium is a useful tool to compare different foods for calcium content but may not be the same as the RDA in all age groups. (See "Dietary history and recommended dietary intake in children", section on 'Terminology for dietary standards'.)

●Typical intake – A substantial gap exists between recommended calcium intake and the typical intake of children between the ages of 9 and 18 years. Calcium intake remains an important nutritional concern in most populations and is an important target for improvement in the Dietary Guidelines for Americans [33]. Most studies in this age group indicate that the usual intake is between 500 and 1000 mg/day [16,18,20,34,35]. Median intake is approximately 900 mg/day in adolescent females and approximately 1200 mg/day in adolescent males [2,36].

●Risk assessment – These general approximations can be used to guide risk assessment and counseling:

•Levels of calcium intake that are somewhat below the RDA (eg, 800 to 1000 mg of elemental calcium daily) but taken consistently throughout growth seem to be adequate because of catch-up bone mineralization in later adolescence.

•Extremely low calcium intakes, such as <600 mg/day, may pose more substantial risks of inadequate mineralization [19]. In particular, intakes <400 mg/day, especially when combined with low vitamin D status, pose a risk of rickets and fractures. This clinical picture may be seen in patients with strict dairy avoidance without adequate substitute sources of calcium and vitamin D, including those with anorexia nervosa or other forms of malnutrition. Children with very low calcium intakes often have dietary deficiency of vitamin D and magnesium and may require supplementation for those nutrients. (See "Vitamin D insufficiency and deficiency in children and adolescents".)

The key dietary risk factor is low intake of dairy products (or similar calcium-fortified foods or beverages). Some children avoid dairy products because of the misconception that these foods might promote weight gain. Many children and adolescents are unaware that low-fat milk has at least as much calcium as does whole milk [9]. Children who consume strict vegetarian diets often have very low calcium intakes if they avoid milk and dairy products (see "Vegetarian diets for children"). In one study, transgender/gender diverse youth (who were not on puberty-suppressing treatment) were found to have low BMD in early puberty compared with a standard reference population, which may have been related to suboptimal intake of dietary calcium [37]. (See "Management of transgender and gender-diverse children and adolescents", section on 'Monitoring during pubertal suppression'.)

●Approaches to increase dietary calcium intake – Assessment of calcium intake and risk factors for osteoporosis can be achieved in the office setting by asking several questions related to dietary intake, activity, and medical history (table 2) [9].

Calcium intake can be increased to achieve the recommended level through foods that are naturally rich in calcium (table 1), calcium-fortified foods, and calcium supplements:

•Dairy – Most of the calcium needs of children and adolescents can be met by consuming milk and dairy products, which provide approximately 75 percent of the calcium in the average American diet [21]. For children with lactose intolerance, low-lactose and lactose-free milks or lactase enzyme supplements are available. (See "Lactose intolerance and malabsorption: Clinical manifestations, diagnosis, and management", section on 'Dietary management'.)

•Calcium-fortified foods – Numerous calcium-fortified foods are available, including soy milk, soy yogurt, and soy cheese, as well as calcium-precipitated tofu and calcium-fortified cereals, breakfast bars, pastas, waffles, and juices [38]. Calcium bioavailability in most of these sources is equivalent to that of milk, although bioavailability of calcium from some soy milks has been shown to be somewhat lower [39]. As an example, one 8-ounce (240 mL) glass of calcium-fortified orange juice provides 300 mg of calcium, equivalent to an 8-ounce glass of milk. The fractional absorption of calcium from calcium-fortified breakfast cereal was equivalent to that of milk in a double-blind, randomized trial [40]. Neither iron absorption nor fractional absorption of calcium from milk were affected by ingestion of the calcium-fortified cereal. In contrast, the bioavailability of calcium in soy milk is only 75 percent of that in cow's milk [39].

•Other foods – Most vegetables contain calcium, although at low density. Thus, relatively large servings are needed to equal the total intake achieved with typical servings of dairy products. The bioavailability of calcium from vegetables generally is high [21]. An exception is spinach, which is high in oxalate, rendering the calcium virtually nonbioavailable. Some high-phytate foods, such as whole-bran cereals, also may have calcium that is poorly bioavailable.

•Calcium supplements – Although foods that are rich in or fortified with calcium are generally preferred because they provide additional nutrients that are important for growth and development, calcium supplements can be considered for children and adolescents who have very low intakes of dietary calcium (table 3). The use of supplements should be individualized based on the dietary habits of the adolescent, risk factors for osteoporosis, and likelihood of adherence. The dose of a supplement can be selected based primarily on the content of elemental calcium (table 4). The bioavailability of calcium citrate and calcium citrate malate is somewhat higher than calcium carbonate. However, these differences are relatively small for supplements that are well solubilized and are generally not a reason to choose more expensive supplements in otherwise healthy individuals [41].

Available evidence does not provide strong support for calcium supplementation for healthy females whose usual calcium intake is similar to that of most of the United States population, even if that intake is well below the RDA.

More than 40 randomized trials have examined whether increasing calcium intake with supplements improves bone density in healthy children, adolescents, and young adults. A meta-analysis found a modest effect of calcium supplementation on bone mineralization (standardized mean difference for total body BMD 0.413, 95% CI 0.261-0.565), with greater effects for supplementation during young adulthood compared with younger age groups [42]. However, most such trials investigated relatively short-term supplementation (one to two years). The few longer-term studies reported that treatment effect tended to wane after several years of supplementation [43] or disappeared after cessation of therapy [29,30]. Taken as a whole, these data do not support routine supplementation in the United States for individuals whose usual calcium intake is near the United States average (eg, approximately 900 mg/day in adolescent females and 1200 mg/day in adolescent males, as summarized above).

●Adverse effects – Higher calcium intake reduces the risk of calcium kidney stones in adults [44,45]. This association is counterintuitive but may be because dietary calcium binds dietary oxalate in the gut, leading to decreased oxalate absorption and excretion. (See "Kidney stones in adults: Epidemiology and risk factors", section on 'Calcium'.)

Physical activity — Regular weightbearing exercise produces modest benefits for skeletal health, provided that calcium intake is sufficient [2]. A meta-analysis of 27 randomized and nonrandomized studies found a small but significant effect of weightbearing activity on bone mineral content (BMC; effect size 0.17, 95% CI 0.02-0.32) and BMD (effect size 0.26, 95% CI 0.02-0.49) [46]. A substantial portion of the variance in BMC was explained by baseline calcium intake and maturational stage (with greater effects for prepubertal children). Longitudinal studies reach disparate conclusions regarding whether the osteogenic effect depends on continuing physical activity into adulthood [47-50].

Paradoxically, an excess of physical endurance training may interrupt menstrual function in females and have a detrimental effect on bone, known as the "female athlete triad" (see "Functional hypothalamic amenorrhea: Pathophysiology and clinical manifestations"). Similarly, male athletes engaged in excessive endurance training or weight restriction (eg, for weight-class sports) can develop functional hypothalamic hypogonadism and low BMD, known as the "male athlete triad" [51].

Although physical activity increases bone mass, it can also increase fracture frequency due to risk of falls [3,52].

Vitamin D — In a generally well-nourished population, vitamin D intake is not an important limiting factor on bone mass accrual [53]. Nonetheless, adequate vitamin D intake is recommended for optimal bone health [54]; recommendations are discussed separately. (See "Vitamin D insufficiency and deficiency in children and adolescents", section on 'Recommended vitamin D intake'.)

Other factors

●Lifestyle factors – Counseling to adolescents and their families should also include discussion of the following lifestyle factors that impact bone density:

•Carbonated beverages – Limited evidence suggests that consumption of carbonated beverages may be associated with adverse effects on bone health. However, modest consumption of these beverages by healthy adolescents, consistent with overall dietary guidelines and the primary use of low-calorie beverages, probably does not pose a substantial risk to bone health [55].

Evidence for a possible adverse effect of carbonated beverages on bone health includes a study of 460 9^th and 10^th grade females in Australia, in which carbonated beverage consumption was associated with an increased risk for fractures; the odds ratio was 3.14 (95% CI 1.45-6.78) overall and 4.94 (95% CI 1.79-13.62) among physically active females [56]. Compatible findings were seen in a study of South Korean adolescents and young adults, in which those who consumed cola had 4 to 5 percent lower BMD compared with those who did not consume cola [57]. The physiologic basis for this is unclear and may be more related to very low mineral intake than an actual effect of any cola beverages. However, one prospective study showed that carbonated beverage intake was negatively associated with an index of bone strength even after adjusting for milk intake [58]. Furthermore, these data have not been confirmed in prospective studies.

•Caffeine – Moderate amounts of caffeine probably do not have adverse effects on BMD in adolescents or young adults, provided that calcium intake is adequate [59,60]. Although caffeine consumption promotes renal excretion of calcium [61,62], this effect is at least partially offset by decreased renal excretion of calcium during the night [63]. Data in adolescents and young adults are limited [64], but two studies suggest that caffeine consumption (mean intake <100 mg/day, approximately two cans of caffeine-containing soda) is not a significant predictor of BMD in White females [65,66]. These data are supported by a review of available data in multiple age groups [67]. Other studies in adults reach variable conclusions, which may depend on other risk factors including dietary calcium intake. (See "Benefits and risks of caffeine and caffeinated beverages", section on 'Osteoporosis'.)

•Magnesium – Magnesium is a critical component of bone health, with some data in both children and adults suggesting that adequate dietary magnesium is a limiting factor for bone mineralization [68,69]. Magnesium is found in a variety of vegetables as well as in dairy products. Still, intake in adolescents is often suboptimal.

•Tobacco and alcohol – Cigarette smoking and heavy alcohol intake have been associated with reduced bone mass in adults [70,71]. The evidence for this association in adolescents and young adults is less robust [3]. Cigarette smoking and excess alcohol intake should be discouraged [72]. (See "Overview of the management of low bone mass and osteoporosis in postmenopausal women", section on 'Lifestyle measures to reduce bone loss' and "Overview of the risks and benefits of alcohol consumption", section on 'Osteoporosis'.)

●Medications – Medications that may have clinically important effects on bone health include glucocorticoids, certain anticonvulsants and antiretroviral drugs used to treat human immunodeficiency virus (HIV) infection, certain antifungal agents including ketoconazole, gonadotropin-releasing hormone agonists (for pubertal suppression), proton pump inhibitors, vitamin A, and statins. (See "Drugs that affect bone metabolism", section on 'Drugs that may have adverse effects'.)

Depot medroxyprogesterone acetate (DMPA) used for contraception also may have negative effects on bone density [73]. Adolescent females treated with DMPA should be counseled to ensure recommended intake of calcium (1300 mg daily) and vitamin D (15 mcg [600 international units] daily). Decisions regarding the use and duration of DMPA contraception and monitoring of bone density are discussed separately. (See "Drugs that affect bone metabolism", section on 'Medroxyprogesterone acetate' and "Contraception: Issues specific to adolescents", section on 'Depot medroxyprogesterone acetate'.)

●Medical conditions – Medical conditions that have adverse effects on bone mass include:

•Hypogonadism – Any condition associated with hypogonadism during childhood or delayed puberty is a risk factor for decreased bone density. This includes a variety of congenital and genetic conditions, as well as diseases associated with inflammation and/or undernutrition, such as inflammatory bowel disease. (See "Approach to the patient with delayed puberty".)

•Skeletal dysplasias – Certain skeletal dysplasias (osteogenesis imperfecta and hypophosphatasia) are associated with low bone density. (See "Skeletal dysplasias: Specific disorders", section on 'Low bone density'.)

•Malnutrition – Malnutrition or extreme weight loss (eg, anorexia nervosa) are associated with diminished bone density and increased risk of fractures [74]. The effects of anorexia nervosa on BMD are discussed in detail elsewhere. (See "Anorexia nervosa: Endocrine complications and their management".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Pediatric bone health" and "Society guideline links: Healthy diet in children and adolescents".)

SUMMARY AND RECOMMENDATIONS

●Clinical importance – Adolescence is a time of opportunity and vulnerability for accumulating the bone mass that is essential for bone health throughout the lifespan. In healthy individuals, one-half to two-thirds of bone mass is accumulated during puberty. Bone mass is inversely associated with fractures during childhood, and peak bone mass during young adulthood is inversely associated with osteoporosis. (See 'Clinical importance' above.)

●Genetics – Genetic factors are responsible for approximately 60 to 80 percent of osteoporosis risk, and familial patterns are expressed prior to puberty. (See 'Genetics' above.)

●Calcium – Calcium intake is an important modifiable factor that affects peak bone mass. (See 'Calcium intake' above.)

•Recommended intake – For children 9 to 18 years of age, the recommended dietary allowance (RDA) for calcium is 1300 mg/day. If this target intake is not possible, an intake of 1000 mg, representing the estimated average requirement, can be followed. Very low calcium intakes, such as <600 mg/day, likely have significant adverse effects on bone health.

•Counseling – The target calcium intake is ideally supplied by calcium-rich or calcium-fortified foods (table 1) because foods provide multiple nutrients that are important for bone health in addition to calcium, including zinc, protein, phosphorus, and magnesium. For adolescents whose calcium intake is very low (eg, <600 mg/day) despite dietary counseling to increase the intake with foods and fortified beverages, we suggest calcium supplementation (Grade 2C) (table 3). Such children usually also have dietary deficiency of vitamin D and magnesium and may require supplementation for those nutrients.

For children with typical calcium intakes (eg, 600 to 1200 mg/day), intervention trials show only a small effect of calcium supplementation on bone mineralization and there is no evidence that there is any long-term benefit on bone health, which would lead to the recommendation for routine supplementation. Nevertheless, a diet targeting intakes at the higher RDA levels is safe and may yield beneficial long-term effects that are not detectable through the methods of these studies.

●Vitamin D – In a generally well-nourished population, vitamin D intake is not an important limiting factor on bone mass accrual. Nonetheless, adequate vitamin D intake is recommended for optimal bone health. The RDA for vitamin D is 15 mg (600 international units) daily for children and adolescents. (See 'Vitamin D' above and "Vitamin D insufficiency and deficiency in children and adolescents".)

●Physical activity – Weightbearing activity should be encouraged for its multiple benefits on health, which include a small but significant effect on peak bone mass. For females, avoid extreme activity that may lead to pubertal delay or amenorrhea, which has adverse effects on bone health. This pattern can also occur in young male athletes involved in endurance and weight-class sports. (See 'Physical activity' above.)

●Other – Other lifestyle factors that appear to have adverse effects on bone health include high intake of carbonated beverages (perhaps because they replace milk and thus reduce calcium intake), alcohol, and smoking. (See 'Other factors' above.)