Based on emerging evidence and expert consensus, a panel assembled by the Osteogenesis Imperfecta and Childhood Osteoporosis Working Group of the Spanish Society of Pediatric Rheumatology (SERPE) released recommendations for the prevention, diagnosis, and treatment of secondary osteoporosis in pediatric patients. This report was published in Pediatric Rheumatology.

Investigators performed a systematic review of studies on strategies for managing secondary childhood osteoporosis. Quality of evidence was rated using the Oxford Centre for Evidence-based Medicine system. Recommendations were developed following a Delphi method by which the panel devised questions, elicited expert opinions, and reached consensus based on agreement ≥70%. 

General Recommendations

SERPE recommends that patients with chronic diseases (especially endocrinologic, nutritional, rheumatologic, renal, metabolic, hematologic, neurologic, and gastrointestinal diseases) be monitored for changes in bone mineral density (BMD) according to existing guidelines for their respective pathologies.

However, clinicians should pay special attention to patients with chronic diseases who receive treatments contributing to osteoporosis development, such as glucocorticoids, chemotherapy, or antiepileptic drugs.

Recommendations for Lifestyle and Dietary Habits

The panel recommends that clinicians identify children at risk for osteoporosis caused because of modifiable factors related to lifestyle and diet, long-term immobilization, anorexia, or adiposity, which are conditions associated with lower BMD and increased risk for fracture.

Since nutritional factors are known to affect bone health, SERPE recommends that healthy dietary habits, including optimal intake of calcium-rich foods and vitamin D, should be established in childhood. Children and adolescents should also be recommended to avoid caffeine, tobacco, and alcohol, as these factors are associated with decreased BMD and increased fracture risk.

To maintain appropriate levels of vitamin D, it is further recommended that clinicians encourage children and adolescents to receive daily exposure to sunlight on their hands, face, and arms for 6 to 8 minutes in the summer months (avoiding the hottest part of the day) and 30 minutes during the winter months.

Since regular physical activity is a key strategy for maximizing bone mass in childhood, SERPE recommends high-impact and low-frequency exercises, such as running, jumping, or resistance training, in healthy children and adolescents as these activities support increases in BMD. High-impact, low-frequency exercises may also be recommended for children with low BMD.

Recommendations for Diagnosis

Laboratory Tests

Children and adolescents with suspected or established secondary osteoporosis may receive complementary laboratory testing, including blood and urine chemistry, urine screening, and bone turnover markers. In pediatric patients, SERPE recommends measuring bone turnover markers in plasma vs urine since sample collection may be affected by age or concomitant disease.

SERPE further indicated that interpretation of biochemical parameters should be based on factors including age, sex, growth rate, nutritional status, pubertal stage, and other variables. Additional biochemical parameters, including immunoglobulins, antitransglutaminase IgA antibodies, cortisol, prolactin, follicle stimulating hormone, luteinizing hormone, testosterone, homocysteine, and genetic studies are only recommended in the event of clinical suspicion.

Imaging tests

Diagnosis of childhood osteoporosis is largely based on the presence of fragility fractures, and therefore, SERPE recommends dual-energy x-ray absorptiometry (DXA) to assess complete bone health in pediatric patients; DXA is recommended to be performed on the lumbar spine or total-body less head, since these sites are considered the most accurate and reproducible areas in children. In patients who are below the third percentile for size, SERPE recommends that Z-scores should be adjusted according to their height.

Among patients with suspected or confirmed bone fragility, or in the presence of vertebral fracture, a simple lateral full spine x-ray or DXA vertebral fracture assessment is recommended. In pediatric patients receiving glucocorticoids, if risk factors persist, or in the event of low bone mass, repeat bone density measurement after 1 year may be advised. Further, DXA may be used to assess treatment response after 6 months.

Other imaging techniques used to assess BMD in children include peripheral quantitative computed tomography and ultrasound; however, the use of these techniques is not recommended on a routine basis because of insufficient evidence from studies among pediatric populations.

Recommendations for Treatment

Calcium and Vitamin D Supplementation

SERPE recommends that children and adolescents with low BMD or confirmed osteoporosis have a proper daily calcium and vitamin D intake, and supplementation is advisable for this population, especially in patients with a low-calcium diet. Vitamin D supplementation should be prescribed to maintain plasmatic levels of 25-hydroxyvitamin D3 higher than 20 ng/dL, and 25-hydroxyvitamin D3, intact parathyroid hormone, and calciuria levels should be monitored every 6 to 12 months to enable modification of treatment.

Bisphosphonates

Treatment with bisphosphonates is typically prescribed after a first fracture occurs as a secondary prevention method; however, there is increasing evidence regarding the positive effect of bisphosphonates on BMD. The panel recommends that clinicians consider bisphosphonates for patients without osteoporosis but with low BMD in early puberty (demonstrated by Z-scores ≤-2 and declining trajectories).

Intravenous bisphosphonates are recommended for children with osteoporosis, and for pediatric patients with the presence of vertebral fractures; oral bisphosphonates are typically used only for mild forms of pediatric osteoporosis without vertebral fracture, if intravenous bisphosphonates are contraindicated, or during treatment de-escalation. SERPE recommends discontinuing or progressively reducing bisphosphonate dosage in patients without any fractures in the preceding year and who have achieved a Z-score >-2.

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Recommendations for Follow-Up

Follow-up is recommended for pediatric patients with persistent osteoporosis risk factors and with an established osteoporosis diagnosis, or during treatment with calcium and vitamin D supplementation, bisphosphonates, or other osteoporosis treatments.

SERPE recommends repeat DXA assessment after 1 year and then every 1 to 2 years based on the patient’s Z-score and trajectory. Radiologic assessment of vertebral fracture with lateral spine x-rays is also recommended as vertebral fractures are often asymptomatic and may appear in patients with a Z-score >-2; the proposed frequency is between 6 months and 2 years depending on the patient’s risk factors.

The panel recommends that patients receiving calcium and vitamin D supplementation be evaluated for calcium and phosphorus metabolism (according to calciuria and plasmatic levels of 25-hydroxyvitamin D3 and intact parathyroid hormone) every 6 to 12 months, or every 3 to 6 months following a dose change. Children receiving intravenous bisphosphonates should be assessed prior to each infusion, and those receiving oral bisphosphonates should be assessed every 6 months.

Recommendations for Corticosteroid-Induced Osteoporosis

Among patients treated with systemic glucocorticoids, monitoring BMD and occurrence of vertebral fracture is recommended. The panel suggests performing a DXA within the first 6 months of glucocorticoid treatment and every 9 to 12 months, if treatment is being continued. For vertebral fractures, which are frequently asymptomatic, it is advisable to obtain imaging at the beginning of treatment and annually thereafter as long as glucocorticoid therapy is maintained.

To prevent glucocorticoid-induced osteoporosis, SERPE recommends calcium (500-1000 mg/d) and vitamin D (400 IU/d) supplementation beginning at the same recommended dose for healthy children, particularly when glucocorticoids are prescribed for ≥3 months. In addition, SERPE recommends maintaining calcium and vitamin D supplementation for 3 months after discontinuing treatment with glucocorticoids.

Although the use of bisphosphonates as a preventative therapy has been proven among patients with pathologic fractures when glucocorticoid-induced osteoporosis has been established, it is not recommended in the absence of fragility fractures. Furthermore, routine procedures such as lateral spine x-rays or DXA are not recommended in patients receiving inhaled glucocorticoids at dosages under 800 mcg per day, unless other risk factors are present.

Reference

Galindo-Zavala R, Bou-Torrent R, Magallares-Lopez B, et al. Expert panel consensus recommendations for diagnosis and treatment of secondary osteoporosis in children. Pediatr Rheumatol. 2020;18(1):20.