Evaluating and optimizing bone health in children with chronic health conditions
The Canadian Paediatric Society gives permission to print single copies of this document from our website. For permission to reprint or reproduce multiple copies, please see our copyright policy.
Principal author(s)
Celia Rodd, Nicole Kirouac, Julia Orkin, Ruth Grimes; Canadian Paediatric Society,
Community Paediatrics Committee
Paediatr Child Health 2022 27(4):232–236.
Abstract
Paediatric health care providers (HCPs) play an important role in optimizing bone health. Early intervention is essential to maximize accrual of peak bone mass in adolescence and young adulthood and to reduce osteoporosis and fracture risk later in life. Children and adolescents with chronic health conditions may have several risk factors for poor bone health, including underlying inflammatory conditions, reduced weight-bearing activity, delayed puberty, and inadequate intake of calcium and vitamin D. Some medications—particularly glucocorticoids—can compromise bone mass and place a child at risk for fragility fractures. This practice point describes a targeted approach to identifying bone health risk factors in children and youth with chronic health conditions, highlights office initiatives aimed at optimizing bone mass accrual, and links HCPs to useful web-based tools and medical references. Indications for referral to a bone health specialist and bone-specific pharmacotherapeutic interventions are also reviewed.
Keywords: Bone mass accrual; Fragility fractures; Preventive bone care
BACKGROUND
Paediatric health care providers (HCPs) play an important role in optimizing bone health. Childhood accrual of bone mass accelerates in adolescence, with peak lifetime bone mass typically achieved between 20 and 25 years of age [1]-[3]. Thus, addressing modifiable risk factors throughout childhood is essential. Critical factors include a healthy lifestyle, adequate vitamin D and calcium intake, good health, and normally timed puberty. Conversely, chronic health conditions can create multiple risks for blunted bone accrual and reduced adult bone mass, increasing lifelong risk of fractures [2][3]. This practice point reviews a targeted approach to evaluating bone health, focusing on modifiable factors, and provides management recommendations. Primary osteoporosis, such as osteogenesis imperfecta, requires specialist care that is beyond the scope of this practice point.
RISK FACTORS FOR REDUCED BONE MASS
Recognition of risk factors for reduced bone mass is an essential step toward promoting bone mass accrual (Table 1) [1][4]-[12].
Table 1. Risk factors
|
Risk factors |
Examples |
Chronic inflammation |
Rheumatic disorders
Malignancies |
Reduced physical activity or low muscle mass |
Duchenne muscular dystrophy
Cerebral palsy
Immobilization |
Pubertal delay |
Turner syndrome |
Poor nutritional status: inadequate intake, inadequate absorption |
Anorexia nervosa
Malabsorption
Renal tubulopathies |
Medications |
Chronic glucocorticoids |
Examples drawn from references 1,4-12
Note: For more information on medications, see Table 4
|
HISTORY
A targeted history explores risk factors (Table 1) and elicits personal and family fracture history, including the number of fractures, location, and etiology. Inquire about back pain, which could be a symptom of a vertebral fracture [13][14]. Table 2 defines paediatric osteoporosis, which must be considered in any child with low-energy or multiple fractures. Low-energy fractures are associated with a fall from standing height or lower [15].
Table 2. International Society for Clinical Densitometry (ISCD) definition of paediatric osteoporosis
|
One or more vertebral fractures in the absence of local disease or high-energy trauma is indicative of osteoporosis. No BMD threshold is required.
|
A clinically significant fracture history (two or more long bone fractures by 10 years old OR three or more at any age up to 19 years) AND a reduced BMD Z-score ≤-2.0 indicates osteoporosis. |
Based on reference 16
BMD bone mineral density
|
The next step is to review diet and lifestyle, using validated tools (Table 3). Consider sharing parent notes [17] from the Canadian Paediatric Society’s CaringforKids website to start conversations with families about calcium and vitamin D intake, physical activity, sun exposure, and use of sunscreen. Note that in Table 3, the Dietary Reference Intakes (DRIs) are population-based, while the Recommended Dietary Allowance (RDA) is an individual’s usual Intake Goal [18]. The Tolerable Upper Intake Level (UL) is defined as the highest average daily intake that likely poses no risk of adverse health effects for almost all individuals. Moreover, consumption of caffeine, carbonated beverages, cigarettes, and alcohol should be reviewed, as all are associated with reduced bone mass [19].
Sun protection (e.g., sunscreen use and sun avoidance) is important for reducing skin cancer risk [20]. Although most Canadians have replete vitamin D status during the synthesizing months (April to October), a sunscreen with an SPF >8 reduces cutaneous vitamin D synthesis [19][21]-[23].
Table 3. Daily Dietary Reference Intakes (DRIs) from food and supplements for calcium and vitamin D for a healthy North American population
|
Age (years) |
Calcium (mg) |
Vitamin D (international units)
|
|
RDA |
UL |
RDA |
UL |
1 to 3 |
700 |
2500 |
600 |
2500 |
4 to 8 |
1000 |
2500 |
600 |
3000 |
9 to 18 |
1300 |
3000 |
600 |
4000 |
Data drawn from references 18,23
RDA Recommended Dietary Allowance; UL Tolerable Upper Intake Level
|
Also, review the onset of puberty and its completion, and take a detailed menstrual history. Sex hormones play a critical role in bone mass accrual, and even physiologically delayed puberty contributes to symptomatic, adult-onset osteoporosis [24].
Lastly, review the use of osteotoxic medications (Table 4). Glucocorticoids are most commonly associated with increased susceptibility to fragility fractures, particularly vertebral fractures, which are often asymptomatic [13][14]. The dose, duration, and route of glucocorticoids that increase fracture risk are not clear. Despite the risk for bone harm posed by some osteotoxic medications, control of the underlying disease can improve bone mass over the longer term compared to inadequately treated disorders [5].
Table 4. Medications associated with suboptimal bone mass or fractures
|
Medication |
Mechanism |
Impact |
Glucocorticoids |
Reduced intestinal calcium absorption
Increased urinary calcium excretion |
Fragility fractures, vertebral fractures, impaired mineralization
|
Traditional anticonvulsants (phenytoin, phenobarbital, carbamazepine, sodium valproate) |
Vitamin D deficiency |
Reduced intestinal absorption of minerals and mineralization |
GnRH agonists
Medroxyprogesterone |
Suppression of sex hormones |
Blunted pubertal bone mass gains |
Calcineurin inhibitors (e.g., cyclosporine, tacrolimus), antiretrovirals, anticoagulants, loop diuretics, and high dose methotrexate |
Reduced bone mass via several mechanisms |
Fragility fractures, impaired mineralization |
Examples drawn from references 4,12,25-28 |
PHYSICAL EXAMINATION
Growth charts provide important information regarding pubertal and nutritional status. A pubertal growth spurt denotes the presence of sex hormones. Both an under- and overweight body mass index are risk factors for reduced bone mass [29]. In children younger than 7 years, other signs of nutritional deficiency should be sought, such as rachitic signs, with widened metaphyses, limb pain, or deformities (e.g., genu valgus or varum). A clinical assessment for vertebral fracture is performed by asking the child to localize any pain and palpating thoracic and lumbar vertebrae for tenderness [13][14][30].
Pubertal assessment includes Tanner staging for breast development in girls (onset 10 years – range 6.5 to 13 years) or testicular enlargement in boys (11 to 12 years – range 9 to 14 years) [31].
Finally, a physical examination can detect less common findings suggestive of primary osteoporosis (e.g., blue gray sclera in osteogenesis imperfecta or joint laxity in collagen disorders, such as Ehlers-Danlos syndromes) [4][32].
POTENTIAL INVESTIGATIONS
Without a diagnosis of primary or paediatric osteoporosis (Table 2), most children do not require any investigations [16]. Obtaining a 25-hydroxyvitamin D (25-OH-D) measurement is typically indicated only when evaluating rickets or recurrent low-trauma fractures, although additional bone-specific investigations may be warranted after discussion with a bone health expert. Opinions differ in the absence of strong evidence for other testing indications for 25-OH-D [19][23][33]. An expert committee of the National Academies of Sciences, Engineering, and Medicine (NASEM) concluded in 2011 that almost all people are sufficient at levels ≥50 nmol/L [23]. Because 25-OH-D is a negative acute phase reactant, its suppression with acute illness limits its utility [34].
According to the 2019 International Society for Clinical Densitometry (ISCD) guidelines, a dual-energy X-ray absorptiometry (DXA) scan may be indicated when a child is being considered for an intervention to decrease fracture risk (e.g., bisphosphonate treatment) because imaging may influence follow-up and management (Table 5) [16]. DXA locations are posterior-anterior spine and total body (less head), bone mineral content (BMC) and BMD. Results from individuals with short stature need adjustment for height based on appropriate reference data [16]. Alternative sites are used for children with mobility issues [16].
Table 5. Radiographic investigations beyond initial diagnostic workup
|
Clinical suspicion |
Consider |
Caveat |
Fragility fractures
|
DXA |
Only if child is being considered for intervention |
Vertebral fractures |
Lateral thoracolumbar (T4 to L5) radiograph
Alternatively, and after discussion with a bone health expert, use DXA for vertebral fracture assessment
|
X-ray to be read by an experienced radiologist using a modified Genant score
Less radiation than a lateral radiograph
|
Rickets |
Wrist radiograph |
|
References 35-38
DXA dual-energy X-ray absorptiometry
|
OFFICE INITIATIVES
Encouraging families to be aware of and meet RDAs for calcium and vitamin D through their regular diet is more likely to ensure long-term adherence than prescribing supplements [19][23]. Supplementation may be required at times to ensure adequate intake or to manage vitamin D deficiency [19][23][33][39]. Consensus guidelines suggest that a supplement of 2000 international units (IU) per day of vitamin D for 3 months treats deficiency, though the data remain controversial [19][40][41]. Long-term intakes of calcium or vitamin D above the UL increase the risk of adverse health effects, including nephrolithiasis, hypercalcemia, and cardiovascular events, without enhancing bone mass [42]-[46]. Individuals with specific dietary requirements (e.g., due to a restrictive diet or malabsorption disorders), or whose diet is limited by poverty may need targeted guidance or specialized advice from a dietitian [47].
Encouraging child and family participation in weight-bearing activities such as daily walks can activate the muscle-bone units and augment bone mass [48]-[51]. Recommending a standing frame for the non-ambulatory child or passive physical movement for infants born prematurely may help mitigate bone loss, although evidence for both practices is mixed [52][53].
Some institutions use bone health algorithms to identify children at high risk for fractures. Special fragility stickers on hospital charts and posters at the bedside can alert HCPs to the need for extra care during procedures, such as bed transfer or phlebotomy [54][55].
BONE HEALTH TEAM AND PHARMACOTHERAPY
A child who meets ISCD criteria for paediatric osteoporosis or who is suspected to have primary osteoporosis should be referred to a bone health expert, typically a paediatric endocrinologist [4][16]. Specialized assessments such as a DNA analysis may be required, as may bone anti-resorption drugs [56][57] or sex steroid replacement. For youth with anorexia nervosa, the mainstays of therapy remain psychotherapy and nutritional rehabilitation, which should restore menses. Sex steroid use does not address the underlying causes of amenorrhea [58]-[60].
KEY POINTS FOR PRACTICE
- Essential office initiatives include the early identification of problems and anticipatory guidance on diet, exercise, and puberty using helpful tools developed by the CPS (e.g., Healthy Bones in Children and Youth, Healthy Active Living, and Sun Safety) [17][20][50].
- Few children need laboratory investigations, though a conversation with a bone health expert may guide specific investigations. Formal consultation is essential for children with evidence of osteoporosis.
Acknowledgements
This practice point has been reviewed by the Adolescent Health and Nutrition and Gastroenterology Committees of the Canadian Paediatric Society.
CANADIAN PAEDIATRIC SOCIETY COMMUNITY PAEDIATRICS COMMITTEE (2020-2021)
Members: Tara Chobotuk MD, Carl Cummings MD (past Chair), Michael Hill MD, Audrey Lafontaine MD, Alisa Lipson MD, Marianne McKenna MD (Board Representative), Julia Orkin MD (Chair)
Liaison: Peter Wong MD (CPS Community Paediatrics Section)
Principal authors: Celia Rodd MD, Nicole Kirouac RN, BN, Julia Orkin MD, Ruth Grimes MD
References
- Grover M, Bachrach LK. Osteoporosis in children with chronic illnesses: Diagnosis, monitoring, and treatment. Curr Osteoporos Rep 2017;15(4):271–82.
- Rizzoli R, Bianchi ML, Garabédian M, McKay HA, Moreno LA. Maximizing bone mineral mass gain during growth for the prevention of fractures in adolescents and the elderly. Bone 2010;46(10):294–305.
- Weaver CM, Gordon CM, Janz KF, et al. The National Osteoporosis Foundation’s position statement on peak bone mass development and lifestyle factors: A systematic review and implementation recommendations. Osteoporos Int 2016;27(4):1281–386.
- Harrington J, Sochett E. The child with multiple fractures, What next? Pediatr Clin North Am 2015;62(4):841–55.
- Mäkitie O. Causes, mechanisms and management of paediatric osteoporosis. Nat Rev Rheumatol 2013;9(8):465–75.
- Yaşar E, Adigüzel E, Arslan M, Matthews DJ. Basics of bone metabolism and osteoporosis in common pediatric neuromuscular disabilities. Eur J Paediatr Neurol 2018;22(1):17–26.
- Chidiac CW. An update on the medical consequences of anorexia nervosa. Curr Opin Pediatr 2019;31(4):448–53.
- Ozel S, Switzer L, Macintosh A, Fehlings D. Informing evidence-based clinical practice guidelines for children with cerebral palsy at risk of osteoporosis: An update. Dev Med Child Neurol 2016;58(9):918–23.
- Mailhot G, Perrone V, Alos N, et al. Cow’s milk allergy and bone mineral density in prepubertal children. Pediatrics 2016;137(5):e20151742.
- Meyer R. Nutritional disorders resulting from food allergy in children. Pediatr Allergy Immunol 2018;29(7):689–704.
- von Scheven E, Corbin KJ, Stagi S, Stefano S, Cimaz R. Glucocorticoid-associated osteoporosis in chronic inflammatory diseases: Epidemiology, mechanisms, diagnosis, and treatment. Curr Osteoporos Rep 2014;12:289–99.
- Hansen KE, Kleker B, Safdar N, Bartels CM. A systematic review and meta-analysis of glucocorticoid-induced osteoporosis in children. Semin Arthritis Rheum 2014;44(1):47–54.
- Nakhla M, Scuccimarri R, Watanabe Duffy KN, et al. Prevalence of vertebral fractures in children with chronic rheumatic diseases at risk for osteopenia. J Pediatr 2009;154(3):438–43.
- Ward LM, Ma J, Lang B, et al. Bone morbidity and recovery in children with acute lymphoblastic leukemia: Results of a six-year prospective cohort study. J Bone Miner Res 2018;33(8):1435–43.
- Huh SY, Gordon CM. Fractures in hospitalized children. Metabolism 2013;62(3):315–25.
- International Society for Clinical Densitometry. 2019 Official Positions Pediatric.pdf (Accessed November 3, 2021).
- Canadian Paediatric Society. Healthy bones in children and youth
- Health Canada. Vitamin D and Calcium: Updated Dietary Reference Intakes. 2008, modified July 28, 2020 (Accessed November 3, 2021).
- Golden NH, Abrams SA; Committee on Nutrition. Optimizing bone health in children and adolescents. Pediatrics 2014;134(4):e1229-43.
- Canadian Paediatric Society. Sun safety
- Brooks SPJ, Greene-Finestone L, Whiting S, Fioletov VE, Laffey P, Petronella N. An analysis of factors associated with 25-hydroxyvitamin D levels in White and Non-White Canadians. J AOAC Int 2017;100(5):1345–54.
- Linos E, Keiser E, Kanzler M, et al. Sun protective behaviors and vitamin D levels in the US population: NHANES 2003-2006. Cancer Causes Control 2012;23(1):133–40.
- Ross AC, Taylor CL, Yaktine AL, Del Valle HB; Institute of Medicine (US) Committee to Review Dietary Reference Intakes for Vitamin D and Calcium. Dietary Reference Intakes for Calcium and Vitamin D (Accessed November 3, 2021).
- Zhu J, Chan Y-M. Adult consequences of self-limited delayed puberty. Pediatrics 2017;139(6):e20163177.
- Albertazzi P, Bottazzi M, Steel SA. Bone mineral density and depot medroxyprogesterone acetate. Contraception 2006;73(6):577–83.
- Lange HLH, Manos BE, Gothard MD, Rogers LK, Bonny AE. Bone mineral density and weight changes in adolescents randomized to 3 doses of depot medroxyprogesterone acetate. J Pediatr Adolesc Gynecol 2017;30(2):169–75.
- Bozkaya G, Nart A, Uslu A, et al. Impact of calcineurin inhibitors on bone metabolism in primary kidney transplant patients. Transplant Proc 2008;40(1):151–5.
- Korula S, Titmuss AT, Biggin A, Munns CF. A practical approach to children with recurrent fractures. Endocr Dev 2015;28:210–25.
- Bialo SR, Gordon CM. Underweight, overweight, and pediatric bone fragility: Impact and management. Curr Osteoporos Rep 2014;12(3):319–28.
- LeBlanc CMA, Ma J, Taljaard M, et al. Incident vertebral fractures and risk factors in the first three years following glucocorticoid initiation among pediatric patients with rheumatic disorders. J Bone Miner Res 2015;30(9):1667–75.
- Lee PA, Guo SS, Kulin HE. Age of puberty: Data from the United States of America. APMIS 2001;109(2):81–88.
- Yepes JF. Dental manifestations of pediatric bone disorders. Curr Osteoporos Rep 2017;15(6):588–92.
- Choosing Wisely Canada. Vitamin D Tests: When you need them and when you don’t.. 2017 (Accessed November 3, 2021).
- Silva MC, Furlanetto TW. Does serum 25-hydroxyvitamin D decrease during acute-phase response? A systematic review. Nutr Res 2015;35(2):91–6.
- Alqahtani FF, Offiah AC. Diagnosis of osteoporotic vertebral fractures in children. Pediatr Radiol 2019;49(3):283–96.
- Genant HK, Wu CY, van Kuijk C, Nevitt MC. Vertebral fracture assessment using a semiquantitative technique. J Bone Miner Res 1993;8(9):1137–48.
- Saraff V, Högler W. Endocrinology and Adolescence: Osteoporosis in children: Diagnosis and management. Eur J Endocrinol 2015;173(6):R185-97.
- Weber DR, Boyce A, Gordon C, et al. The utility of DXA assessment at the forearm, proximal femur, and lateral distal femur, and vertebral fracture assessment in the pediatric population: 2019 ISCD official position. J Clin Densitom 2019;22(4):567–89.
- Whiting SJ, Langlois KA, Vatanparast H, Greene-Finestone LS. The vitamin D status of Canadians relative to the 2011 Dietary Reference Intakes: An examination in children and adults with and without supplement use. Am J Clin Nutr 2011;94(1):128–35.
- Munns CF, Shaw N, Kiely M, et al. Global consensus recommendations on prevention and management of nutritional rickets. J Clin Endocrinol Metab 2016;101(2):394–415.
- Saggese G, Vierucci F, Prodam F, et al. Vitamin D in pediatric age: Consensus of the Italian Pediatric Society and the Italian Society of Preventive and Social Pediatrics, jointly with the Italian Federation of Pediatricians. Ital J Pediatr 2018;44(1):51.
- Taylor PN, Davies JS. A review of the growing risk of vitamin D toxicity from inappropriate practice. Br J Clin Pharmacol 2018;84(6):1121–27.
- Galior K, Grebe S, Singh R. Development of vitamin D toxicity from overcorrection of vitamin D deficiency: A review of case reports. Nutrients 2018;10(8):953.
- Cohen JE, Wakefield CE, Cohn RJ. Nutritional interventions for survivors of childhood cancer. Cochrane Database Syst Rev 2016;2016(8):CD009678.
- Bolland MJ, Barber PA, Doughty RN, et al. Vascular events in healthy older women receiving calcium supplementation: Randomised controlled trial. BMJ 2008;336(7638):262–6.
- Epling JW, Mader EM, Roseamelia CA, Morley CP. Emerging practice concerning vitamin D in primary care. Qual Health Res 2015;25(7):1005–12.
- Health Canada. What are Canada’s Dietary Guidelines? Canada's Food Guide. 2020 (Accessed November 3, 2021).
- Behringer M, Gruetzner S, McCourt M, Mester J. Effects of weight-bearing activities on bone mineral content and density in children and adolescents: A meta-analysis. J Bone Miner Res 2014;29(2):467–78.
- Farr JN, Laddu DR, Going SB. Exercise, hormones and skeletal adaptations during childhood and adolescence. Pediatr Exerc Sci 2014;26(4):384–91.
- Lipnowski S, LeBlanc CMA; Canadian Paediatric Society, Health Active Living Committee. Healthy active living: Physical activity guidelines for children and adolescents. Paediatr Child Health 2012;17(4)209-10.
- Specker B, Thiex NW, Sudhagoni RG. Does exercise influence pediatric bone? A systematic review. Clin Orthop Relat Res 2015;473(11):3658–72.
- Whittaker S, Tomlinson R. Question 2: Do standing frames and other related physical therapies reduce the risk of fractures in children with cerebral palsy? Arch Dis Child 2015;100(12):1181–83.
- Vignochi CM, Miura E, Canani LH. Effects of motor physical therapy on bone mineralization in premature infants: A randomized controlled study. J Perinatol 2008;28(9):624–31.
- Winnipeg Regional Health Authority; Kirouac N. Osteoporosis in Children: A Family and Caregiver Guide. 2010 (Accessed November 3, 2021).
- Kirouac N, Taback S, Miller K, et al. Childhood osteoporosis: screening, prevention, treatment, and safe handling practices in a tertiary care pediatric hospital. J Pediat Nurs 2012;27(3):e7.
- Kraus E, Bachrach LK, Grover M. Team approach: Bone health in children and adolescents. JBJS Rev 2018;6(10):e6.
- Wood CL, Ahmed SF. Bone protective agents in children. Arch Dis Child 2018;103(5):503–08.
- Misra M, Katzman D, Miller KK, et al. Physiologic estrogen replacement increases bone density in adolescent girls with anorexia nervosa. J Bone Miner Res 2011;26(10):2430–38.
- Golden NH, Jacobson MS, Schebendach J, Solanto MV, Hertz SM, Shenker IR. Resumption of menses in anorexia nervosa. Arch Pediatr Adolesc Med 1997;151(1):16–21.
- Mairs R, Nicholls D. Assessment and treatment of eating disorders in children and adolescents. Arch Dis Child 2016;101(12):1168–75.
Disclaimer: The recommendations in this position statement do not indicate an exclusive course of treatment or procedure to be followed. Variations, taking into account individual circumstances, may be appropriate. Internet addresses are current at time of publication.