The human skeleton is arguably the most important organ system for providing body structure and support and serves multiple other roles in the body including the mineral reservoir, the location of marrow and protection of internal organs. The skeleton is dynamic: growing, remodeling, and gaining strength and mass throughout adolescence. Optimization of these processes is critical to ensuring long-term bone health. Because peak bone mass, an important determinant of an individual's future risk of osteoporosis, is attained in young adulthood , understanding factors that contribute to peak bone mass is crucial in helping adolescents and young adults reach optimal bone health.
Skeletal adaptation to the mechanical environment – mechanical loading of bones against gravity coupled with muscle contraction is the primary factor determining bone strength . Bone mineral accrual is at its maximum about 6–12 months following peak height velocity, which means that in the later stages of puberty, adolescents have reached much of their final adult height, but far less of their peak bone mass , underscoring the importance of the end of puberty, middle and late adolescence in attainment of optimal bone health.
Because of the vital role bone plays in overall health, it is important to understand the factors contributing to bone health and recognize special populations at risk for compromised bone health. Providers who treat adolescents should be well acquainted with each, especially if considering therapy that may impact bone health. There are both modifiable and nonmodifiable factors contributing to bone health (Table 1). Nonmodifiable factors comprise much of the impact on bone health and attainment of peak bone mass, thus, optimizing modifiable factors is of utmost importance in adolescents during their peak time of bone mass accrual.
Nonmodifiable factors (ethnicity, biological sex, family history, pubertal onset)
Up to 80% of a person's peak bone mass potential is determined by nonmodifiable factors including ethnicity, biological sex, family history, and pubertal progression . Repeatedly, studies have shown that bone mineral density (BMD) is higher in males than females and in African-American children than children of other ancestries [3,4]. A family history of osteoporosis is correlated with lower BMD in offspring and increased risk of osteoporosis in relatives [5▪▪]. In otherwise healthy adolescents, earlier age of pubertal onset is strongly associated with more robust BMD and bone mineral content (BMC) in both girls and boys . These are important considerations when evaluating the overall bone health and bone potential for an individual patient.
Modifiable factor: exercise
Engaging in regular, high-impact, weight-bearing exercise (especially activities that involve running and jumping) is one of the best methods to impact peak bone mass in adolescents . Unfortunately, there are no consistent guidelines for the recommended frequency, amount, and duration of this exercise to optimize bone health, but less than 50% of high school students achieve 60 min of vigorous activity five or more days per week . The benefits of exercise far exceed just that of bone health. However, if exercise is not accompanied by adequate nutrition and rest, the positive effects on bone health can be quickly negated.
Modifiable factor: body composition and nutrition
The role of nutrition is multifaceted in bone health. Sufficient body mass is important for maintaining adequate loading of the skeleton against gravity and adolescents who are underweight risk inadequate BMD. Obesity may have adverse effects on BMD , thus it seems to be the maintenance of sufficient weight in the normal range that optimizes bone health.
Nutritional content is also important. Sufficient dietary intake of calcium has the most robust research to support its role in adolescent bone health  and the Recommended Dietary Allowance (RDA) of calcium is 1300 mg in 9–18-year-olds and 1000 mg in 19-year-olds and above . With dietary intake alone, the majority of adolescents are unable to reach this amount of calcium intake and require supplementation . Supplemental calcium is available in the form of calcium carbonate and calcium citrate, with calcium carbonate supplements containing higher levels of elemental calcium, though require an acidic environment for absorption, therefore there are special cases where calcium citrate may be more appropriate such as patients who are taking acid suppressing medication or those who have undergone gastric bypass surgery or have absorptive disorders . Because almost all the body's calcium is stored in bone, serum calcium levels rarely reflect inadequate calcium intake.
Vitamin D sufficiency is another well established critical part of achieving optimal adolescent bone health as it enhances the absorption of calcium and is needed for bone growth and remodeling . For adolescents, the RDA for vitamin D is 600iU, an amount rarely achieved by dietary intake alone by adolescents in the United States . Furthermore, there is some research to suggest that for adolescents, in order to maintain sufficient levels of vitamin D, their intake needs to be higher than the RDA . Vitamin D absorption is best with concurrent intake of dietary fat, though it is unclear how much . Vitamin D status is best estimated by using the level of serum 25(OH)D, which is the primary form of circulating vitamin D. A 25(OH)D level less than 20 ng/dl in adolescents with accruing bone mass is considered deficient by many researchers [12,13], although more recent international guidelines suggest any level of more than 20 ng/dl will prevent rickets, levels between 12 and 20 ng/dl are insufficient and less than 12 ng/dl are deficient and supplementation can be done with either vitamin D2 or D3 .
Other minerals, trace minerals, and vitamins including phosphorus, magnesium, boron, copper, iron, manganese, zinc, vitamin A, and vitamin K are all known to play roles in bone metabolism and bone health, although neither measurement of levels nor empiric supplementation has been well studied and is not currently recommended. However, if there is concern for nutritional deficiency of any kind, close evaluation of RDA of each of these to ensure adequate dietary consumption is recommended.
Modifiable factor: medications
Although often not immediately modifiable due to acute medical necessity, long-term use of medications that impact bone health is an important factor in attainment of optimal bone health. There are many different classes of medications that have been implicated in poor bone health, with the most common highlighted here. Because of the direct impact on osteoblasts, long-term glucocorticoid use is associated with decreased bone density and increased fracture risk . Medications that impact the body's production of sex steroids such as depot medroxyprogesterone acetate (DMPA) and gonadotropin-releasing hormone agonists (GnRHa) also impact bone health and use considered carefully especially in adolescents with other risk factors for poor bone health [16▪▪,17,18]. Antiepileptic medications, through their impact on bone turnover and vitamin and mineral metabolism have deleterious impacts on bone health and because some of the effects seem to be related to nutritional intake, careful dietary history is important in these patients .
Modifiable factor: lifestyle
Use of substances including alcohol and cigarettes have both been linked to poor bone health, though research is variable. With alcohol, many studies have shown association with poor bone health, however, because of inconsistent methods and variable amounts of alcohol use, definite recommendations on the impact of alcohol in adolescent attainment of optimal bone health are not possible . A very recent cross-sectional study of college-age females did show that binge drinking was associated with decreased BMD at the lumbar spine even when controlling for other factors that can impact bone health [20▪▪]. There is more consistent research on the impact of tobacco smoking on bone health with multiple cross-sectional studies indicating effect with different amounts of smoking all linked to suboptimal bone health .
There are certain populations of adolescents where special attention should be given because of a variety of cumulative risk factors for suboptimal bone health (Table 2).
Special population: adolescents with eating disorders
Adolescents with eating disorders are at high risk for inadequate bone accrual and the detrimental effects, owing to a multitude of factors including low body weight, low sex steroid levels, elevated stress hormone levels, low levels of bone trophic hormones such as insulin growth factor-1 (IGF-1), have been well documented [21,22▪,23]. Much of this evidence comes from studies where subjects were underweight, such as in patients with anorexia nervosa, however emerging evidence also suggests that females with bulimia nervosa have lower bone density than health controls . Weight restoration, cessation of eating disorder behaviors, and resumption of normal menstrual pattern are the most important parts of a treatment plan for these adolescents, although unfortunately, peak bone mass may never be attained underscoring the role for early diagnosis and treatment of adolescents with eating disorders [21,24]. It is important to understand that because of the complex interplay of factors leading to low bone density in patients with anorexia nervosa, treatment with a combination oral contraceptive pill (COC) in attempt to improve bone health has not been shown to be effective [25,26]. Use of physiologic doses of transdermal estrogen, paired with monthly progesterone for uterine health, has been shown in one study to improve BMD at the hip and spine in comparison to control subjects .
Special population: athletes
As above, weight-bearing exercise, through direct skeletal loading, is an important piece of building and maintaining bone health and in general, athletes have higher BMD than nonathletes [12,28]. However, when exercise is not accompanied by sufficient nutrition, inadequate energy availability results in detrimental skeletal effects. The female athlete triad and the condition of relative energy deficiency in sport are both phenomena that occur in athletes with inadequate energy availability and because of direct and indirect effects on bone metabolism, these conditions result in suboptimal bone health [29▪,30]. The American College of Obstetricians and Gynecologists recently issued a position statement specifically addressing the potential for adverse health outcomes in patients with the female athlete triad [31▪]. A recent prospective study of adolescent athletes showed that over a 12-month period, ‘catch-up’ bone accrual does not occur in oligomenorrheic athletes, who had poorer baseline bone health, even when they resume normal monthly menses, a finding that points to the critical importance of identifying athletes with menstrual irregularity to prevent potentially irreversible impacts on long-term bone health [32▪▪]. Recognizing athletes at risk for low energy availability and ensuring that menstrual irregularity in female athletes is not considered ‘normal’ are potential ways to help optimize bone health in this at-risk population [29▪,30,31▪].
Special population: adolescents using hormonal contraception
Hormone-containing contraceptive methods such as COC, DMPA, subdermal etonogestrel-releasing implant (ETN), and levonorgestrel intrauterine system (LNG-IUS) are widely used in adolescents for contraceptive and noncontraceptive purposes. DMPA has the most recognized potential impact on bone health, with the United States Food and Drug Administration (FDA) issuing a black box warning regarding DMPA and its potential impact on BMD, primarily because of estrogen deficiency as the result of hypothalamic suppression . This impact on BMD may be partly or even fully reversible when the medication is discontinued , and weight gain associated with DMPA may mitigate some of the impact on BMD in adolescents . It is possible that lower doses of DMPA (75 or 104 mg) may have less impact on BMD in adolescents [16▪▪] and could be considered as a reasonable alternative especially in patients with already compromised bone health.
COC use has conflicting data with respect to bone health with some studies not finding any impact on achievement of peak bone mass, whereas others have determined that COC use does impact peak bone mass. There is concern about suppression of endogenous estradiol production with COCs, especially during the first three postmenarchal years and increasing awareness that COCs with 20 μg ethinylestradiol impact acquisition of peak BMD . The ENG implant has not been widely studied with respect to impact on BMD, though a small study in adult users found no significant changes in BMD compared to those with copper-IUD , although caution should be used when extrapolating these results to adolescents, as it is unknown how ETG impacts acquisition of peak bone mass. Similarly, there have been very few studies investigating the impact of LNG-IUS on BMD, although available data in adult users of this method indicate no adverse impact on BMD .
Special population: adolescents using gonadotropin-releasing hormone agonists therapy
The use of GnRHa therapy in children, adolescents, and young adults should be done with consideration of bone health because of its hypogonadal effects. In adolescents with endometriosis treated with GnRHa therapy, add-back hormonal therapy with both norethindrone acetate and conjugated equine estrogen appears superior to norethindrone acetate alone in preserving bone density in these patients . In transgender youth who are using GnRHa therapy to suppress endogenous puberty, attention must be given to bone density throughout treatment and addition of cross-sex hormone therapy in these patients does appear to attenuate any reduction in bone health seen with pubertal suppression, although long-term studies are needed in this particular population . Guidelines for treatment of transgender adolescents including monitoring bone density have been updated recently [39▪▪].
Special population: adolescents with immobility
Adolescents who are chronically immobile, such as those with cerebral palsy or other neuromuscular diseases, have inadequate mechanical loading to allow for bony stimulus that allows for bone mass accrual and acquisition of bone strength. These same adolescents may also have delayed puberty and hypogonadism, which further contribute to poorer bone health outcomes [40,41]. Addition of medications that could further compromise bone health in these patients should be done judiciously and any opportunity for use of an adaptive stander should be utilized.
Special population: adolescents with chronic health conditions
Adolescents with chronic illness are at risk for suboptimal bone health because of a variety of potential factors including chronic inflammation, need for medications with bone health effects, poor nutrition, underweight status, malabsorption of critical bone trophic vitamins and minerals, and limited ambulation . Specific conditions including celiac disease, cystic fibrosis, type 1 diabetes mellitus, inflammatory bowel disease, chronic kidney disease, hypogonadism, neuromuscular disorders, Rett syndrome, and primary bone disease such as osteogenesis imperfecta all have known risk for poor bone health in children and adolescents and specific screening guidelines for measuring BMD with dual-energy x-ray absorptiometry (DXA) and vitamin D levels in these patient exist and should be considered when caring for patients with these conditions .
Providers who care for children and adolescents should be aware of the factors that impact bone health. Optimizing modifiable factors at every opportunity is critical in aiding adolescents’ acquisition of peak bone mass and thus lifelong skeletal health. In special populations who are already at risk for suboptimal bone health, very careful consideration must be given prior to initiating other therapies that might further compromise bone health.
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Conflicts of interest
There are no conflicts of interest.
REFERENCES AND RECOMMENDED READING
Papers of particular interest, published within the annual period of review, have been highlighted as:
- ▪ of special interest
- ▪▪ of outstanding interest
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