Skeletal Outcomes in Children and Young Adults with Glomerular Disease
Authors: Goodwin Davies Amy J. , Xiao Rui , Razzaghi Hanieh , Bailey L. Charles , Utidjian Levon , Gluck Caroline , Eckrich Daniel , Dixon Bradley P. , Deakyne Davies Sara J. , Flynn Joseph T. , Ranade Daksha , Smoyer William E. , Kitzmiller Melody , Dharnidharka Vikas R. , Magnusen Brianna , Mitsnefes Mark , Somers Michael , Claes Donna J. , Burrows Evanette K. , Luna Ingrid Y. , Furth Susan L. , Forrest Christopher B. , Denburg Michelle R. 
Published: September 2022

Significance Statement
Children and young adults with glomerular disease have unique risk factors for compromised bone health, but data on skeletal complications are lacking. We leveraged the PEDSnet pediatric health system population of more than 6.5 million children to compare incidence rates of adverse skeletal outcomes in patients with glomerular disease to a general pediatric reference cohort. Children and young adults with glomerular disease had greater risk of vertebral and hip/femur fractures, avascular necrosis/osteonecrosis, and slipped capital femoral epiphysis than those in the reference cohort. For fractures at any body site, girls with glomerular disease were at increased risk compared with peers in the general pediatric population, an effect that CKD does not appear to drive entirely.

Background
Children with glomerular disease have unique risk factors for compromised bone health. Studies addressing skeletal complications in this population are lacking.

Methods
This retrospective cohort study utilized data from PEDSnet, a national network of pediatric health systems with standardized electronic health record data for more than 6.5 million patients from 2009 to 2021. Incidence rates (per 10,000 person-years) of fracture, slipped capital femoral epiphysis (SCFE), and avascular necrosis/osteonecrosis (AVN) in 4598 children and young adults with glomerular disease were compared with those among 553,624 general pediatric patients using Poisson regression analysis. The glomerular disease cohort was identified using a published computable phenotype. Inclusion criteria for the general pediatric cohort were two or more primary care visits 1 year or more apart between 1 and 21 years of age, one visit or more every 18 months if followed >3 years, and no chronic progressive conditions defined by the Pediatric Medical Complexity Algorithm. Fracture, SCFE, and AVN were identified using SNOMED-CT diagnosis codes; fracture required an associated x-ray or splinting/casting procedure within 48 hours.

Results
We found a higher risk of fracture for the glomerular disease cohort compared with the general pediatric cohort in girls only (incidence rate ratio [IRR], 1.6; 95% CI, 1.3 to 1.9). Hip/femur and vertebral fracture risk were increased in the glomerular disease cohort: adjusted IRR was 2.2 (95% CI, 1.3 to 3.7) and 5 (95% CI, 3.2 to 7.6), respectively. For SCFE, the adjusted IRR was 3.4 (95% CI, 1.9 to 5.9). For AVN, the adjusted IRR was 56.2 (95% CI, 40.7 to 77.5).

Conclusions
Children and young adults with glomerular disease have significantly higher burden of skeletal complications than the general pediatric population.