Low bone mass content in children is due to low bone formation or an increase in bone loss. Factors that influence bone formation or modeling can place a child at a lower mineral density when compared with their age-matched peers-leaving bone with deficits that are subtle and unrecognized until a fragility fracture occurs. Others may not experience fracture but may be left with a decreased peak bone mass that subjects them to an increased lifelong risk of fracture.
There are internal influences on bone formation and bone loss in the pediatric population caused by underlying chronic disease states, inherited diseases, and hormonal imbalances. There has been a greater interest in pediatric and adolescent bone health due to the increased occurrence of osteoporosis-related fractures in this age group. Chronic childhood diseases can negatively impact bone acquisition. Galindo-Zavala et al. (2020) reported increased rates of fractures related to decreased bone acquisition that is believed to be related to improved survival rates in children with chronic diseases. Medical treatments such as chemotherapy and radiation can also lead to bone damage and bone loss (Galindo-Zavala et al., 2020). Other influences such as nutrition, supplementation, and exercise impact skeletal growth and development. Stress fractures or fragility fractures in pediatrics are usually caused by an underlying loss of bone mineral content (BMC) (Grover & Bachrach, 2017). The literature supports addressing bone quality in pediatric patients after a fragility fracture with prevention and treatment programs to minimize bone loss and optimize bone formation.
It is important to recognize that bone is a metabolically active living tissue that consists of bone cells, mineralized and unmineralized, connective tissue matrix, and bone marrow. Bone is dynamic in that it constantly changes and regenerates. In fact, the human skeleton is reported to completely regenerate itself over a period of 10 years through a process of bone formation and removal of older fatigued bone called bone resorption. It is the imbalance of bone formation and resorption that affect the strength of bone (Forewood, 2019). The purpose of this article is to review published literature that discusses the risk factors, evaluation, and treatment associated with a decreased BMC in children. The article also includes a public health planning model for pediatric low bone mass.
Influences on Bone Formation in Children
Calcium Intake
Bone experts agree that calcium is an important component for bone mineralization and cartilage matrix starting in infancy. Children require increased amounts of calcium for muscular growth and bone formation, with the highest recommendation during adolescents. Across the life span, the calcium recommendation during adolescents is the highest at 1,300 mg (Hospital for Special Surgery, 2021; National Osteoporosis Foundation, 2021).
One study examined BMC in preterm infants randomized to three treatment groups: (1) preterm unfortified human milk; (2) preterm fortified human milk with protein, calcium, and phosphorus; and (3) a prepared fortified formula (Greer & McCormick, 2001). Improvements in BMC and weight gains were noted at 6 weeks in the fortified human milk and fortified formula groups. The study suggested infants who received fortified human milk and formulas have increased BMC when compared with infants who received unfortified human milk (Greer & McCormick, 2001). This study points out that minerals, including calcium, are important for skeletal growth starting at infancy.
It is important to discuss dietary substitutes, such as vegetable- or soy-based products, which can achieve and sustain the necessary calcium requirements in children with certain medical conditions. For example, dairy may need to be avoided because of the inflammatory or mucous formation associated with these products. Some children may have a cow's milk allergy (CMA) and avoid dairy in their diet. Dairy avoidance requires children with CMA to substitute with alternative sources of calcium needed for the skeleton (Dupont et al., 2018). One classic study of 55 children aged 5-14 years old who had antibodies to cow's milk reported the effect of calcium intake on bone mineralization (Henderson & Hayes, 1994). The children were divided into four groups according to their varied dietary calcium intake for their condition, with 22% of the children receiving a calcium supplement. The average total intake of calcium ranged from 400 to 1,400 mg of calcium. Bone mineralization was measured by bone density testing using age-matched Z-scores in the child's lumbar spine and proximal femurs (Henderson & Hayes, 1994). The results concluded that bone mineralization increased across all groups in proportion to calcium intake (Henderson & Hayes, 1994). The findings support the recommendation of calcium intake in pediatric children with a growing skeleton, especially in children diagnosed with a CMA who are at risk for a weakened skeleton (Dupont et al., 2018).
Vitamin D Intake
Vitamin D is necessary for intestinal absorption of both calcium and phosphate, which are required for bone growth and mineralization. Vitamin D is absorbed through the small intestines when food or a vitamin D supplement is ingested. Deficiencies of vitamin D can occur with an inadequate intake or absorption of daily requirements, lack of sun exposure, obesity, and in individuals with darker skin pigmentation. Sources of vitamin D include oily fish (salmon, mackerel, sardines, and cod liver oil), organ meats (liver), and egg yolks. Children who follow vegan diets are also at a higher risk for vitamin D deficiency. Historically, it had been difficult to obtain vitamin D through one's diet; however, currently, manufacturers of cereals, juices, and other prepared foods are fortifying their products with vitamin D, which presents a viable option for children. Although there are various recommendations for vitamin D supplementation, the American Academy of Pediatrics currently supports vitamin D supplementation of 400 IU daily, especially in breastfed infants (Abrams & the Committee on Nutrition, 2013).
Beginning at infancy, the importance of breastfeeding is well recognized for its supply of nutrients and antibodies that support an infant's immunological system; however, breast milk contains low levels of vitamin D. Vitamin D deficiency is common among children who have been breastfed beyond 3-6 months, especially in children with a darker skin pigmentation (Henderson, 2005). One option may be to increase vitamin D levels in breastfeeding mothers. Vitamin D supplementation for mothers can increase the amount found in breast milk. Forty-four postpartum women were randomly assigned to three groups: (1) women who were given daily supplements of 1,000 IU; (2) women who were given daily supplements of 2,000 IU of vitamin D; and (3) a placebo group. Increases in vitamin D levels in breast milk samples were evident in women who were supplemented with 2,000 IU of vitamin D as compared with the 1,000 IU and placebo groups (Wall et al., 2015).
Small amounts of vitamin D can also be absorbed through sun exposure, optimally between the hours of 10 a.m. and 3 p.m., with absorption varying according to an individual's skin color and amount of pigmentation (Kumar et al., 2009). For example, sun exposure for the duration of 10-15 minutes is adequate in those populations with a lighter pigmentation as compared with Asians and to Indians who may require up to three times as much exposure. Also, very dark skin pigmentation in some African ancestry may require six to 10 times as much exposure to achieve equivalent vitamin D concentrations (Prentice, 2008). These findings highlight the importance of surveillance and monitoring of vitamin D levels in children with darker skin pigmentation. One study reported a 20 times greater risk of having a vitamin D concentration of less than 20 ng/ml in Black and Hispanic adolescents compared with White non-Hispanic adolescents. Females were also reported to be at higher risk than males in this same study (Kumar et al., 2009). Similarly, children who live in geographic locations with longer winter months, and typically located at higher latitudes, are known to absorb less sunlight from sun exposure and, consequently, are at a higher risk for developing vitamin D deficiencies (Kumar et al., 2009).
Certain disease states can alter the absorption of vitamins, which, in turn, can lead to a vitamin D deficiency. Children who have gluten sensitivity or who have a first- or second-degree relative with a history of celiac disease should be screened for celiac disease because many children are asymptomatic and go undiagnosed.
Exercise-Weight-Bearing Activities
Maintaining an adequate intake of calcium and vitamin D, complemented with routine weight-bearing physical activity, is important in enhancing bone mineral accrual and bone strength in children (Daly & Giangregorio, 2019). Studies also show a positive correlation of bone mass in adults who also engaged in weight-bearing activities during childhood. One prospective controlled trial involving school-age children who were assigned to an exercise regimen of hopping, skipping, and jumping for 10 minutes three times a week reported increased bone mineral density (BMD) in the hip (McKay et al., 2000).
Primary Causes of Low Bone Mass
Primary conditions affecting bone mass in children are caused by genetic musculoskeletal disorders such as osteogenesis imperfect (OI), juvenile idiopathic osteoporosis (JIO), and other neuromuscular disorders. These conditions are often referred to as primary osteoporosis. Primary osteoporosis in children causes a decrease in skeletal bone mass, resulting in brittle bones and fragility fractures.
Secondary Causes of Low Bone Mass
Chronic Diseases
Secondary osteoporosis in children is caused by systemic diseases that have a negative impact on bone mass. Gastrointestinal conditions such as celiac disease, Crohn's disease, pancreatic insufficiency, cystic fibrosis (CF), short gut syndrome, or cholestatic liver disease impair absorption of vitamins and minerals (Maas et al., 2017). Inflammatory causes of secondary osteoporosis can originate from rheumatological or hematological conditions that include juvenile chronic arthritis and immunoglobulin deficiency (Maas et al., 2017). Although this list of secondary causes of osteoporosis is not exhaustive, it highlights the most common of the diagnoses affecting bone health in children.
Delayed childhood growth patterns are reported in approximately one third of children prior to a diagnosis of Crohn's disease (Sanderson, 2014). Intestinal inflammation leads to a loss of appetite, malnutrition, and malabsorption of vitamins and minerals necessary for skeletal support. Gut inflammation can also suppress hormones necessary for growth and development such as insulin like growth factor (IGF-1) or other growth factors (Lev-Tzion et al., 2019). Glucocorticoids, which are the mainstay of treatment in many inflammatory conditions, can lead to further growth suppression and bone loss.
Cystic fibrosis is a genetic disease impacting the lungs and pancreas. Children with CF have a deficiency in pancreatic enzymes necessary to absorb fat-soluble vitamins such as A, D, E, and K. These children are treated with vitamin D supplementation from a young age to support bone and muscles, especially the important muscles necessary for respiration (Daley et al., 2019). Children with CF and vitamin D deficiency can also experience a decrease in calcium absorption, lowering bone mineralization that can lead to fractures (Daley et al., 2019).
Vitamin D Deficiency
Vitamin D deficiency, over time, can interfere with normal bone metabolism and cause low levels of calcium (hypocalcemia) and phosphorus (hypophosphatemia), leading to a condition of undermineralized bone such as osteomalacia and rickets (Winzenberg & Jones, 2019). Rickets is deficient growth plate bone mineralization causing an impairment in growth and development. Rickets is not commonly seen in the modern society, but it can exist in underserved remote areas of the world.
Childhood vitamin D deficiency has been associated with many other bone deformities and muscular conditions, including kyphoscoliosis and muscular myopathy (Misra et al., 2008). Infants and children with suspected vitamin D deficiency should also be examined for associated delayed closure of the anterior fontanelle, delayed tooth eruption, enamel breakdown, and dental decay (Misra et al., 2008).
The literature reports a varied and inconsistent range of recommendations regarding the amount of vitamin D supplementation required for children. A review of the literature examined different reported amounts of vitamin D given to healthy children and adolescents to determine whether recommended dosages varied by age, sex, or pubertal stage or whether there is a dose-dependent correlation with bone density (Winzenberg & Jones, 2019). Although there were no reported differences in the total body BMC and hip or forearm BMD, there was a small increase in the lumbar spine BMD in children who were vitamin D deficient and supplemented (Winzenberg & Jones, 2019). The authors concluded that even though insufficient evidence exists to support the use of vitamin D supplementation in healthy children, there is enough evidence to suggest vitamin D supplementation may be clinically useful in children with low vitamin D levels (Winzenberg & Jones, 2019).
Glucocorticoid Treatment
Glucocorticoid treatment is essential in many inflammatory diseases in children such as juvenile arthritis, Crohn's disease, and childhood asthma. Glucocorticoids inhibit bone formation and increase the breakdown of bone, leading to low bone mass or glucocorticoid-induced osteoporosis (GIO). The effects of glucocorticoids on bone depend upon the duration and dosage of commonly used steroids such as dexamethasone, prednisone, and hydrocortisone. Calcium levels often decrease with glucocorticoid therapy due to impaired absorption from the gut or urinary leak of calcium through the kidneys, which can lead to a deficient calcium level needed for bone mineralization (Bell et al., 2017). Glucocorticoids also interfere with the release of growth hormone, suppressing collagen formation and impairing growth in children. Growth inhibition has been reported at low corticosteroid doses of 3-5 mg per day (Bell et al., 2017). There is some evidence in human and animal models to support the use of growth hormone to increase collagen cross-links and bone strength to counteract the detrimental effects of corticosteroids on bone in children (Bell et al., 2017; Sun-Hee et al., 2019). Bell at al. (2017) reported a doubling in the baseline growth rate in children receiving corticosteroids with the use of growth hormone. However, the concurrent use of growth hormone in children receiving corticosteroid therapy is not the current standard of care.
The detrimental effects of steroids in children have also been reported with the use of inhaled steroids for asthma treatment. Maas et al. (2017) reported decreased bone mineral formation over 12 months in pediatric patients with asthma taking budesonide. The authors concluded that bone mineral formation markers should be monitored to assess the effects of inhaled glucocorticoid medications on bone (Maas et al., 2017).
Pediatric Bone Evaluation and Treatment
The increased incidence of fragility fractures in the pediatric population has expanded an awareness and interest in bone quality in children. Physical or behavioral risk factors that impact bone growth and development may require a formal evaluation. Pediatric providers are instrumental in identifying and evaluating children with delayed skeletal maturity or an increased risk of fracture. Additional diagnostic studies, for example, the radiographs of a child's wrist and hand when compared with standard references for the child's age and gender, may be helpful to identify disorders of deficient bone (Bachrach, 2014). Although diagnostic tools such as laboratory markers and bone densitometry are not commonly used in pediatrics, they can be used to identify and risk stratify children with disease processes that have the potential to decrease bone mass. Unlike adults, the measurement of bone mass in children is different and is based upon a volumetric measure. One assessment uses a size-adjusted BMC with the use of a total body-less head measurement, which is then adjusted for height and weight. The size-adjusted BMC is compared with children of the same height and weight in predicting fracture risk in children (Bogunovic et al., 2009).
In 2013, the International Society for Clinical Densitometry (ISCD) defined criteria for the diagnosis of osteoporosis in children with one of the following: one or more low-energy vertebral fractures; a bone density Z-score of -2 or less (compared with age-matched groups); or a history of two or more long bone fracture occurring by the age of 10 years or three or more long bone fractures at any age up to 19 years (Bachrach, 2014). The ISCD points out that a Z-score above -2 does not preclude the possibility of bone fragility, especially in individuals with disorders that can cause secondary osteoporosis (Bachrach, 2014). This recommendation supports the importance of an extensive history and evaluation in pediatric patients.
In addition to bone density testing, markers of bone formation and breakdown, commonly called bone biomarkers, can be detected in serum and urine. Although it is common practice to measure serum and urine bone biomarkers when evaluating low bone mineralization and fracture risk in adults, there are little data to support the use of bone biomarkers in children. Reference ranges are variable in children and have been difficult to establish as they are influenced by the age, gender, and pubertal stage.
Bone turnover markers have been used to monitor the effects of bisphosphonate therapy in children with primary osteoporosis. Studies in children with different types of primary osteoporosis (OI, JIO, GIO, or other neuromuscular diseases) treated with bisphosphonates have demonstrated favorable results. Consistent with adult findings, increases in lumbar spine Z-scores and improved bone biomarkers can be found in children treated with bisphosphonates (Bowden et al., 2014; Nasomyont et al., 2019). In fact, there is evidence that suggest changes in bone biomarkers are detected earlier than changes in bone density (Lev-Tzion et al., 2019). Furthermore, serum markers for bone formation may be a more immediate and sensitive test than delayed changes in BMD (Lev-Tzion et al., 2019). Although treatment with bisphosphonates for primary causes of osteoporosis can be used in children to improve bone mineralization, further studies are necessary to assess the use of bisphosphonates in children with secondary causes of osteoporosis (Nasomyont et al., 2019).
Public Health Planning and Awareness
According to the Health and Human Services' Healthy People 2020 initiative, certain public health influences can be modified to improve bone health, including one's behavior, physical environment, and social influences. This article highlights multiple reasons that pediatric bone mineralization should be a public health initiative. If left unrecognized, deficits in pediatric bone health can have a profound impact upon a child's current and future quality of life. The overall goal in improving bone health in children can be accomplished by targeting modifiable influences using a public health promotion planning model. Health promotion planning models are used as communication platforms for performance and change objectives that are specific, measurable, achievable, relevant, and time-bound. Performance objectives are necessary to accomplish change objectives. Table 1 includes examples of performance and change objectives that can be used to improve bone health in children.
A health promotion plan would also include evaluating environmental influences of culture and social determinants of health. Achieving health equity is necessary to eliminate health disparities in historically underserved populations and socially marginalized communities. The World Health Organization (WHO) outlined 10 behavioral and social risk factors that affect health. Many of the risk factors such as nutrition, exercise, and exposure to cigarette smoke are known to negatively impact bone health, especially in the earlier years of life. These risk factors can serve as an outline and platform when designing community health programs in pediatric bone health (WHO, 2002). Designing programs that are culturally sensitive with necessary social support structures provides a foundation for a change in early behaviors (WHO, 2002).
In response to this public health initiative of bone health in children, the Centers for Disease Control and Prevention has partnered with local and state agencies to guide and leverage private and public resources to develop programs that improve access and promote behavioral changes regarding healthy food choices. Community engagement through the establishment of a coalition consisting of members of the local community, public health officials, healthcare workers, teachers, funding agencies, and policy makers can assist in establishing bone health programs. The programs should be effective, reliable, and sustainable. To improve adoptability, programs should be comprehensive and respectful of the health beliefs, practices, and needs of diverse populations.
Logic models are often used by community and nonprofit groups for planning and implementation of programs. Logic models include inputs and activities with anticipated goals and outcomes. Visualizing the process can help outline the expected impact (W.K. Kellogg Foundation, 2004). Figure 1 is an example of a logic model that could be used to plan a program designed to improve bone health in children. The National Association of County and City Health Officials (2015) also has resources that facilitate the design of a road map to improve public health outcomes.
Conclusion
Osteopenia, osteoporosis, and fragility fractures later in life are well-known public health issues. This article reviews relevant literature related to pediatric bone health and highlights the importance of addressing skeletal health in children. Childhood is a critical time for bone, as it is the greatest period of bone formation and acquisition in the life span. Low bone acquisition is a well-recognized risk factor for osteoporosis and fractures later in life. Development of community-based public health programs is essential to address this growing public health concern.
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