Jinhui Ma

Incident vertebral fractures and risk factors in the first three years following glucocorticoid initiation among pediatric patients with rheumatic disorders

Vertebral fractures are an important yet underrecognized manifestation of osteoporosis in children with chronic, glucocorticoid‐treated 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 ± standard deviation (SD) age 9.9 ± 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.

Incident Vertebral Fractures in Children With Leukemia During the Four Years Following Diagnosis

OBJECTIVES The purpose of this article was to determine the incidence and predictors of vertebral fractures (VF) during the 4 years after diagnosis in pediatric acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS Children were enrolled within 30 days of chemotherapy initiation, with incident VF assessed annually on lateral spine radiographs according to the Genant method. Extended Cox models were used to assess the association between incident VF and clinical predictors. RESULTS A total of 186 children with ALL completed the baseline evaluation (median age, 5.3 years; interquartile range, 3.4-9.7 years; 58% boys). The VF incidence rate was 8.7 per 100 person-years, with a 4-year cumulative incidence of 26.4%. The highest annual incidence occurred at 12 months (16.1%; 95% confidence interval [CI], 11.2-22.7), falling to 2.9% at 4 years (95% CI, 1.1-7.3). Half of the children with incident VF had a moderate or severe VF, and 39% of those with incident VF were asymptomatic. Every 10 mg/m(2) increase in average daily glucocorticoid dose (prednisone equivalents) was associated with a 5.9-fold increased VF risk (95% CI, 3.0-11.8; P < .01). Other predictors of increased VF risk included VF at diagnosis, younger age, and lower spine bone mineral density Z-scores at baseline and each annual assessment. CONCLUSIONS One quarter of children with ALL developed incident VF in the 4 years after diagnosis; most of the VF burden was in the first year. Over one third of children with incident VF were asymptomatic. Discrete clinical predictors of a VF were evident early in the patients clinical course, including a VF at diagnosis.

The management of osteoporosis in children.

SummaryThis article reviews the manifestations and risk factors associated with osteoporosis in childhood, the definition of osteoporosis and recommendations for monitoring and prevention. As well, this article discusses when a child should be considered a candidate for osteoporosis therapy, which agents should be prescribed, duration of therapy and side effects.AbstractThere has been significant progress in our understanding of risk factors and the natural history of osteoporosis in children over the past number of years. This knowledge has fostered the development of logical approaches to the diagnosis, monitoring, and optimal timing of osteoporosis intervention in this setting. Current management strategies are predicated upon monitoring at-risk children to identify and then treat earlier rather than later signs of osteoporosis in those with limited potential for spontaneous recovery. On the other hand, trials addressing the prevention of the first-ever fracture are still needed for children who have both a high likelihood of developing fractures and less potential for recovery. This review focuses on the evidence that shapes the current approach to diagnosis, monitoring, and treatment of osteoporosis in childhood, with emphasis on the key pediatric-specific biological principles that are pivotal to the overall approach and on the main questions with which clinicians struggle on a daily basis. The scope of this article is to review the manifestations of and risk factors for primary and secondary osteoporosis in children, to discuss the definition of pediatric osteoporosis, and to summarize recommendations for monitoring and prevention of bone fragility. As well, this article reviews when a child is a candidate for osteoporosis therapy, which agents and doses should be prescribed, the duration of therapy, how the response to therapy is adjudicated, and the short- and long-term side effects. With this information, the bone health clinician will be poised to diagnose osteoporosis in children and to identify when children need osteoporosis therapy and the clinical outcomes that gauge efficacy and safety of treatment.

The Radiology of Vertebral Fractures in Childhood Osteoporosis Related to Glucocorticoid Administration

A number of unusual conditions cause decreased bone mass and density in children and these may be associated with low-trauma fractures. However, a series of reports have more recently identified that children with chronic disease sustain vertebral fractures (VFs) much more often than had been suspected. The common denominator involved is glucocorticoid (GC) administration, although other factors such as disease activity come into play. This review will focus on the imaging findings in this form of secondary osteoporosis. Spinal fractures in children have been found to correlate with back pain. At the same time, up to 2/3 of children with VFs in the GC-treated setting are asymptomatic, underscoring the importance of routine surveillance in at-risk children. Other predictors of prevalent and incident VFs include GC exposure (average daily and cumulative dose), declines in lumbar spine bone mineral density Z-scores and increases in body mass index Z-scores, as well as increases in disease activity scores. The imaging diagnosis of osteoporotic VFs in children is made differently from that in adults because immature vertebral bodies continue to ossify during growth. Thus, it is not possible to assess the vertebral end plates or periphery until late, as enchondral ossification extends centripetally within the centrum. Diagnosis, therefore, is much more dependent upon changes in shape than on loss of structural integrity, which may have a more prominent diagnostic role in adults. However, children have a unique ability to model (a growth-dependent process) and thereby reshape previously fractured vertebral bodies. If the underlying disease is successfully treated and the child has sufficient residual growth potential, this means that, on one hand, treatment of the bone disease may be of more limited duration, and, as a last recourse, the diagnosis may be apparent retrospectively.

Increased bone matrix mineralization in treatment-naïve children with inflammatory bowel disease

Inflammatory bowel disease (IBD) affects many organ systems including the skeleton. In children with IBD, bone mineral density (BMD) and bone turnover are frequently low. Disturbances in bone mineralization density distribution (BMDD) are linked to alterations in bone material strength; however, BMDD has not previously been reported in children with chronic inflammatory disorders. The aim of this study was to characterize BMDD based on quantitative backscatter electron imaging in cancellous (Cn.) and cortical (Ct.) compartments from trans-iliac biopsy samples from a cohort of 20 treatment-naïve children at the time of their IBD diagnosis (12 males, mean age 14.5±2.3years). The outcomes were compared to pediatric reference BMDD data and correlation with revisited biochemical and histomorphometric outcomes was analyzed. BMDD in treatment-naïve children with IBD was shifted toward higher calcium concentrations compared to reference: (i) In cancellous bone, the most frequent calcium concentration (Cn.CaPeak+2.8%, p=0.004) and the portion of highly mineralized bone (Cn.CaHigh+52%, p=0.009) were increased. (ii) In cortical bone, the mineralization heterogeneity (Ct.CaWidth+17.0%, p=0.001) and Ct.CaHigh (+30.4%, p=0.006) were increased. (iii) Furthermore, significant correlations with serum alkaline phosphatase (ALP), bone-specific alkaline phosphatase (bsALP), and urinary crosslinked N-telopeptide of type I collagen (uNTX) were observed: the higher CaMean (the average calcium concentration), CaPeak and CaHigh, the lower were ALP, bsALP, and uNTX (p-value from <0.001 to 0.05). Children with treatment-naïve IBD have decreased bone turnover leading to a higher bone matrix mineralization density, findings which may contribute to compromised bone strength.

Osteoporosis: Diagnosis and Management

Bone health is now recognized as an important facet of child health with sufficient evidence to support standardized approaches to diagnosis, monitoring, treatment, and prevention. Current management strategies are based on monitoring at-risk children to identify and then treat earlier rather than later signs of osteoporosis in those with limited potential for spontaneous recovery. Research studies addressing prevention of the first-ever fracture are still needed for children who have both a high likelihood of developing fractures and less potential for recovery.