Bone Health: A Review

Many clinicians do not screen/counsel children and adolescents regarding factors that could positively or negatively impact their bone health, missing an important opportunity to reduce adult osteoporosis risk.After completing this article, readers should be able to:Explain why bone health is an essential consideration in pediatric care.Explain why meeting the recommended dietary allowance for calcium and vitamin D intake is important.Identify who is at higher risk for negative bone health outcomes.Bone health is an important, yet often underappreciated, pediatric concern. Bones are necessary for body structure and movement, protection of organs, and housing of marrow, and as a biological bank for minerals essential for muscle and nerve function. In addition, adult osteoporosis is a multitrillion dollar worldwide health problem, with significant prevention potential in the pediatric years. (1)(2)(3) Incorporating bone health considerations into routine pediatric clinical practice is important.Bone comprises collagen, proteins, minerals, and cells. Osteoblasts secrete osteoid, which is chiefly composed of type 1 collagen. Bone mineral, primarily calcium and phosphate, is deposited on the osteoid. Osteoclasts resorb the bone to free up mineral for bodily use. In addition, together, osteoblasts and osteoclasts remodel bone for it to grow and change shape. Osteocytes, derived from osteoblasts, live in the bone matrix and are connected to one another by dendritic processes, responding to stimuli to modulate the formation of osteoblasts and osteoclasts. (4)There are intrinsic and extrinsic factors influencing bone health. (2)(5)(6) One’s peak bone mass (PBM) is achieved in adulthood and is heavily influenced by genetics (60%–80%), a nonmodifiable factor. The remaining 20% to 40% of one’s PBM is impacted by nutrition, physical activity, hormonal milieu, disease processes, and medication and/or toxic exposures. Healthy bone possesses the intrinsic ability to model and remodel, which allows for growth and for the repair of microtraumas experienced on a near-daily basis in active individuals. Such repair requires adequate substrate (eg, calcium, vitamin D, hormones), an environment without toxins that can impair repair (eg, corticosteroids), and time. These modifiable factors can be incorporated into pediatric screening, counseling, and clinical management. The goal is to minimize patient exposure to known toxins when possible, treat illness that can negatively impact bone, optimize dietary intake to meet the recommended dietary allowance (RDA) for all macronutrients and micronutrients, ensure that overall energy intake meets the individual’s daily needs, and encourage physical activity that is safe and appropriate. Young growing bodies also need enough rest. If young people are not getting enough restorative rest and time away from repetitive bone trauma, they are at increased risk for stress injuries and/or fracture. This consideration is particularly relevant to adolescent athletes who may be engaging in excess repetitive exercise with inadequate energy intake and who are experiencing sleep deprivation given academic and athletic demands. (7) Ones’ mental health also may impact bone health, given the biochemical effects of psychological stress. (8) Therefore, thinking about the whole person to address their physical and psychological needs has the potential to positively impact bone health.Although several nutritional factors influence optimal bone health, bone is primarily composed of calcium and phosphate. (2)(5)(9) Given the physiologic importance of these minerals for bodily function, parathyroid hormone (PTH), vitamin D, and fibroblast growth factor-23 exert effects on bone, kidneys, and the intestine to maintain normal serum calcium and phosphorus levels. Should enteral intake be inadequate or urinary and fecal losses excessive, this well-calibrated system chooses to deplete bone of calcium and phosphorus at the expense of skeletal health to maintain normal serum calcium and phosphorus levels for bodily function. This means that if children and adolescents do not meet the RDA for calcium, phosphorus, and vitamin D, their bone mass accrual and bone integrity will be compromised (Table 1). A normal serum calcium level does not mean that enteral intake is adequate. Rather, it means that the body is doing what it needs for calcium homeostasis.Phosphorus is found in many foods and beverages, making adequate intake relatively easy to achieve. (10) Dietary calcium and vitamin D deficiencies are more common. (13) The RDA for calcium varies during the pediatric years, reaching 1,300 mg/d for 9- to 18-year-olds, the equivalent of 4 high-calcium foods or beverages each day. (11) Calcium enteral absorption is highest in infancy and declines with age. Spacing out calcium intake over the day into 3 to 4 or more servings optimizes absorption. This can be a challenge for busy, active youth or for individuals taking medication for which absorption is impaired by concurrent calcium intake, such as iron or thyroid medication. Taking a dietary recall to assess daily calcium intake will inform whether calcium supplements are needed. The most common calcium supplements include calcium citrate and carbonate. Calcium carbonate requires gastric acid for optimal absorption, meaning that such supplements should be taken with food and are less well absorbed with concurrent use of antacid therapy. Calcium citrate does not require gastric acid for absorption and so can be taken on an empty stomach or with concomitant use of antacids. Although it is ideal for the calcium RDA to be met through diet, this is not always feasible, making supplements very important.Vitamin D deficiency contributes to rickets in growing children and to osteomalacia in youth who are done growing. (14) Vitamin D, or calciferol, is a fat-soluble prohormone that can be endogenously produced by the skin when exposed to UV light. However, given the carcinogenic effects of UV radiation and the negative impact that sunscreen has on endogenous vitamin D production, ingested vitamin D is often necessary. Although some foods and beverages have naturally occurring or fortified vitamin D, few individuals have a diet meeting the RDA for vitamin D, necessitating supplementation. (12) Being fat soluble means that vitamin D is best absorbed when taken with a fat-containing meal, but, unlike calcium, vitamin D is well absorbed in large doses, so its intake need not be divided over the day. Vitamin D supplements are sold as cholecalciferol, the animal derivative, and as ergocalciferol, the plant derivative. Studies show that cholecalciferol is better absorbed, although either formulation is recommended for use depending on availability and patient preference. (15) The adequacy of vitamin D intake can be assessed with serum 25-hydroxycholecalciferol (25[OH]D or calcidiol), the storage form of vitamin D in the body after hepatic hydroxylation. It is not recommended that 25(OH)D be checked routinely in the general population. Rather, clinicians should conduct a dietary assessment and recommend increased dietary intake or supplementation as needed to meet the RDA. Evaluating 25(OH)D status is warranted in individuals with known or suspected primary or secondary bone disease. 1,25-Dihydroxycholecalciferol (1,25[OH]2D or calcitriol) is the active form of vitamin D after both hepatic and renal hydroxylation. Its half-life is short, and the body’s regulatory systems will attempt to maintain normal 1,25(OH)2D levels at the expense of 25(OH)D storage. Therefore, 1,25(OH)2D is not a recommended routine screening laboratory test unless someone has chronic renal failure.Physical activity has many health benefits, including bone health. Bone adapts to the mechanical loads placed on it. When muscle pulls on bone, that bone is strengthened. Activities with the greatest effect on bone mass include jumping activities and exercises with periods of rest between repeated loading cycles (eg, gymnastics, jumping rope). (16) However, repetitive and excess mechanical loading without adequate substrate to support healthy bone (ie, the proper nutritional and hormonal milieu) puts bone at risk for microtrauma or macrotrauma, resulting in stress injuries or fracture. (17) This is a concern for young athletes. For nonathletes without impaired mobility, any weightbearing physical activity is better for bone health than no activity at all. Therefore, counseling such youth to engage in any physical activity that appeals to them, such as going for walks or dancing to music, will help bone. Youth with physical and/or neurologic limitations are at risk for bone fragility because they do not experience the mechanical benefits of weightbearing activities. (18) Such individuals may benefit from physical therapy and use of a stander, an assistive device providing support to an individual to allow for standing, although the data regarding the actual weightbearing experienced varies by each individual and by the type of stander used. (19)Pediatric clinicians understand that normal child/adolescent growth and pubertal development reflect overall health, including bone health. The reason approximately 50% of one’s adult PBM is accrued in adolescence is, in part, due to the importance of sex hormones and growth factors made after pubertal onset. Therefore, anything that affects hormonal function (ie, primary or secondary endocrinopathies) will negatively impact bone health, with potential permanent repercussions depending on the duration of the insult.Disease processes, malnutrition, and medication impact the carefully orchestrated hormonal milieu needed for optimal bone health. Reviewing the many hormonal actions on bone is beyond the scope of this review, but some overarching principles are helpful to understand. In both sexes, estrogen promotes osteoblast survival and osteoclast apoptosis, thereby promoting bone mass formation. (4) Estrogen also promotes epiphyseal closure, eventually ending linear growth. Androgens stimulate bone formation on the outer bone surface, resulting in overall larger bones in individuals producing more testosterone. Growth hormone and insulinlike growth factor-1 are anabolic agents, essential for normal skeletal growth. In excess, cortisol induces dysfunction and apoptosis of osteoblasts and reduces intestinal absorption of calcium, with an overall negative effect on bone. Calcitonin, made by the C cells of the thyroid gland, inhibits osteoclast function to decrease serum calcium levels. (20) The parathyroid gland secrets PTH, which acts on bone, intestine, and the kidneys to increase serum calcium levels.The goal of bone health assessment is identifying primary bone disease (ie, connective tissue disorders such as osteogenesis imperfecta, Marfan syndrome, and Ehlers-Danlos syndrome) and determining risk factors for secondary bone disease (Table 2). Management follows, using therapeutics targeting the underlying connective tissue disorder and/or reducing/mitigating the factors contributing secondarily to impaired bone mass accrual. In some cases, such as with primary bone disease and neuromuscular disorders, the threat to bone health cannot be avoided, so the focus becomes optimizing any and all modifiable factors.A bone health history includes an assessment of an individual’s physical activity and diet, pubertal development and growth, dental health, current and previous medication use, chronic illness, and fracture history. Children who are nonambulatory, have deficient diets, have pubertal delay, are taking medications known to negatively impact bone (including glucocorticoids), or who have connective tissue disorders are at higher risk for negative bone health outcomes. Chronic illness can directly impact bone through inflammation or can secondarily impact bone through nutritional malabsorption, pubertal suppression, inactivity, or the need for bone toxic radiation or medication. A dental history of delayed or early tooth eruption/loss, enamel concerns, or frequent cavities can provide a clue to a connective tissue disorder impacting bone. Family history includes history of fractures, osteoporosis, nephrolithiasis, connective tissue disorders, pubertal history, and chronic illness. Fracture history should include the bones involved, the mechanism of injury and significance of the impact (mild, moderate, severe), the need for surgical intervention, and the healing process. It is important to remember that traumatic fractures in youth are common. (21)The physical examination to assess bone health is similar to a comprehensive annual examination. It is important to note standard growth parameters, discolored sclera (gray or blue in the setting of connective tissue disorders, iron deficiency, or autoimmune diseases such as myasthenia gravis; with certain medications, such as amiodarone or minocycline; or with excessive exposure to silver), dental appearance, thyromegaly, bone tenderness on palpation, limitations in or pain with bodily movement, shortened limbs, café-au-lait spots, striae of skin, bruising, general skin elasticity, laxity of joints, arachnodactyly, chest wall deformities, and pubertal status. A Beighton score can be used to quantify joint laxity. (22)(23) The spine should be assessed from behind with the patient in the standing position to look for asymmetry of the ribs and scapula, and from the side to assess for lordosis and kyphosis. In addition, the Adam’s forward bend test should be performed using a scoliometer to quantify the angle of any trunk rotation. (24) Radiography is recommended for a scoliometer reading of 7° or more.Further evaluation will be driven by the history and physical examination findings. Laboratory testing could include a complete blood cell count to evaluate for chronic illness, a basic metabolic panel to evaluate renal function, an alkaline phosphatase level (a marker of bone turnover), calcium and phosphorus levels, 25(OH)D level, and PTH level, as well as a random or 24-hour urine calcium-to-creatinine ratio to evaluate for hypercalciuria. Bone-specific alkaline phosphatase level is elevated when osteoblast activity is high (peak growth, rickets/osteomalacia, after fractures), and is low with hypophosphatasia, a rare genetic disorder characterized by defective bone mineralization. In the absence of known or suspected liver disease, initial evaluation with total alkaline phosphatase is appropriate and most cost-effective. Depending on the clinical picture, thyroid function testing, evaluation of the hypothalamic-pituitary-gonadal axis, screening for celiac disease, or evaluation of inflammatory markers may be warranted. 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