Incident Vertebral Fractures and Risk Factors in the First Three Years Following Glucocorticoid Initiation Among Pediatric Patients With Rheumatic Disorders

Abstract

Vertebral fractures are an important yet underrecognized manifestation of osteoporosis in children with chronic, glucocorticoidtreated illnesses. Our goal was to determine the incidence and clinical predictors of vertebral fractures in the 3 years following glucocorticoid initiation among pediatric patients with rheumatic disorders. Incident vertebral fractures were evaluated according to the Genant semiquantitative method on lateral radiographs at baseline and then annually in the 3 years following glucocorticoid initiation. Extended Cox models were used to assess the association between vertebral fractures and clinical risk predictors. A total of 134 children with rheumatic disorders were enrolled in the study (mean AE standard deviation (SD) age 9.9 AE 4.4 years; 65% girls). The unadjusted vertebral fracture incidence rate was 4.4 per 100 person-years, with a 3-year incidence proportion of 12.4%. The highest annual incidence occurred in the first year (6.0%; 95% confidence interval (CI) 2.9% to 11.7%). Almost one-half of the patients with fractures were asymptomatic. Every 0.5 mg/kg increase in average daily glucocorticoid (prednisone equivalents) dose was associated with a twofold increased fracture risk (hazard ratio (HR) 2.0; 95% CI 1.1 to 3.5). Other predictors of increased vertebral fracture risk included: (1) increases in disease severity scores between baseline and 12 months; (2) increases in body mass index Z-scores in the first 6 months of each 12-month period preceding the annual fracture assessment; and (3) decreases in lumbar spine bone mineral density Z-scores in the first 6 months of glucocorticoid therapy. As such, we observed that a clinically significant number of children with rheumatic disorders developed incident vertebral fractures in the 3 years following glucocorticoid initiation. Almost one-half of the children were asymptomatic and thereby would have been undiagnosed in the absence of radiographic monitoring. In addition, discrete clinical predictors of incident vertebral fractures were evident early in the course of glucocorticoid therapy.

Bone histomorphometric changes in children with rheumatic disorders on chronic glucocorticoids

“…This association between increased BMI and greater bone fragility has also been demonstrated in a prospective study of children with rheumatic conditions which assessed determinants of vertebral fractures [13]. Combined, these findings would support that clinicians should have heightened vigilance around bone health screening in those rheumatological patients with systemic glucocorticoid effects.…”

“…Given higher rates of vitamin D deficiency in children with rheumatic conditions [45, 46], ensuring adequate vitamin D and calcium intake to maintain bone mineralization is an important first line therapy, although may not be sufficient to help prevent fragility fractures [13]. The use of biologic agents in JIA, has been demonstrated to help facilitate new bone formation after discontinuation of glucocorticoids [47].…”

“…Children with rheumatic diseases including SLE and JIA have been shown to have reduced BMD compared to healthy age-matched controls [1, 10–12]. Decreased lumbar spine BMD Z score in the first 6 months of initiation of glucocorticoid treatment has been demonstrated to be an important predictor for increased vertebral fracture risk [13]. DXA has, however, limitations in the assessment of bone health in pediatric cohorts given that the results are influenced by bone size [14].…”

Diagnosis and management of Duchenne muscular dystrophy, part 2: respiratory, cardiac, bone health, and orthopaedic management

“…73,84 As noted, some individuals with vertebral fractures are relatively asymptomatic, even in more advanced stages of collapse. 71 Therefore, to detect vertebral fractures, spine imaging should not be prompted solely by back pain or deformity; rather, people with known risk factors for vertebral fractures, including motor disorders 85 or glucocorticoid therapy, 72,84 should receive regular spine imaging. The fact that vertebral fractures at any time point in a patient’s clinical course are predictive of future spine fractures even when the initial vertebral fractures are mild or asymptomatic 71 —a phenomenon known as the vertebral fracture cascade 86 — underscores the need for early identification.…”

Review of American College of Rheumatology (Acr) Clinical Guidelines for the Prevention and Treatment of Glucocorticoid-Induced Osteoporosis

“…У детей прием ГК приводит к нарушению процессов формирования, рос-та и прочности кости, что не дает возможности достичь пи-ка костной массы во взрослом возрасте. Увеличение сред-ней ежедневной дозы ГК на каждые 0,5 мг/кг ассоциирова-лось с двукратным увеличением риска переломов позвон-ков [15,16].…”