Expressive

rs10989692 - MTND3P4 - ARL2BPP7

Magnitude 4.5 · 1 study on file

Reported associations

  • Genetics of glucocorticoid-associated osteonecrosis in children with acute lymphoblastic leukemia. - Blood (2016) · Karol SE, Yang W, Van Driest SL, Chang TY, Kaste S, Bowton E, Basford M, Bastarache L, Roden DM, Denny JC, Larsen E, Winick N, Carroll WL, Cheng C, Pei D, Fernandez CA, Liu C, Smith C, Loh ML, Raetz EA, Hunger SP, Scheet P, Jeha S, Pui CH, Evans WE, Devidas M, Mattano LA, Relling MV · PubMed 26265699

    Glucocorticoids are important therapy for acute lymphoblastic leukemia (ALL) and their major adverse effect is osteonecrosis. Our goal was to identify genetic and nongenetic risk factors for osteonecrosis. We performed a genome-wide association study of single nucleotide polymorphisms (SNPs) in a discovery cohort comprising 2285 children with ALL, treated on the Children's Oncology Group AALL0232 protocol (NCT00075725), adjusting for covariates. The minor allele at SNP rs10989692 (near the glutamate receptor GRIN3A locus) was associated with osteonecrosis (hazard ratio = 2.03; P = 3.59 × 10(-7)). The association was supported by 2 replication cohorts, including 361 children with ALL on St. Jude's Total XV protocol (NCT00137111) and 309 non-ALL patients from Vanderbilt University's BioVU r

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Lifestyle context

Concrete actions anchored to the cited research. We do not prescribe, we describe.

Diet

  • adequate calcium and vitamin D intake Moderate

    glucocorticoid-induced bone loss and osteonecrosis risk; calcium and vitamin D support bone remodeling and resilience

    target 1000-1200 mg dietary calcium daily and 1000-2000 IU vitamin D3 daily; increase if on glucocorticoids long-term

Discuss with your doctor

  • genetic risk for glucocorticoid-induced osteonecrosis High

    carries risk allele for glucocorticoid-induced osteonecrosis near GRIN3A glutamate receptor gene; 2-fold increased hazard ratio

    inform all healthcare providers of this genetic predisposition, especially when glucocorticoids are being considered

Exercise

  • weight-bearing or resistance exercise for bone density maintenance Moderate

    weight-bearing and resistance exercise maintain bone mass and strength to counteract glucocorticoid-induced bone loss

    30 or more minutes of weight-bearing or resistance exercise 3 or more days per week, especially if on glucocorticoids

Screening

  • bone health surveillance if prescribed glucocorticoids High

    2-fold increased osteonecrosis risk when exposed to glucocorticoids; glutamate pathway also associated with vascular ischemic events

    baseline and periodic bone imaging (DXA or MRI) if initiating prolonged glucocorticoid therapy; monitor for bone pain, joint swelling, or mobility loss