Bone Mineral Density and Type 1 Diabetes in Children and Adolescents: A Meta-analysis

BACKGROUND There is substantial evidence that adults with type 1 diabetes have reduced bone mineral density (BMD); however, findings in youth are inconsistent. PURPOSE To perform a systematic review and meta-analysis of BMD in youth with type 1 diabetes using multiple modalities: DXA, peripheral quantitative computed tomography (pQCT), and/or quantitative ultrasound (QUS). DATA SOURCES PubMed, Embase, Scopus, and Web of Science from 1 January 1990 to 31 December 2020, limited to humans, without language restriction. STUDY SELECTION Inclusion criteria were as follows: cross-sectional or cohort studies that included BMD measured by DXA, pQCT, or QUS in youth (aged <20 years) with type 1 diabetes and matched control subjects. DATA EXTRACTION We collected data for total body, lumbar spine, and femoral BMD (DXA); tibia, radius, and lumbar spine (pQCT); and phalanx and calcaneum (QUS). Weighted mean difference (WMD) or standardized mean difference was estimated and meta-regression was performed with age, diabetes duration, and HbA1c as covariates. DATA SYNTHESIS We identified 1,300 nonduplicate studies; 46 met the inclusion criteria, including 2,617 case and 3,851 control subjects. Mean ± SD age was 12.6 ± 2.3 years. Youth with type 1 diabetes had lower BMD: total body (WMD −0.04 g/cm2, 95% CI −0.06 to −0.02; P = 0.0006), lumbar spine (−0.02 g/cm2, −0.03 to −0.0; P = 0.01), femur (−0.04 g/cm2, −0.05 to −0.03; P < 0.00001), tibial trabecular (−11.32 g/cm3, −17.33 to −5.30; P = 0.0002), radial trabecular (−0.91 g/cm3, −1.55 to −0.27; P = 0.005); phalangeal (−0.32 g/cm3, −0.38 to −0.25; P < 0.00001), and calcaneal (standardized mean difference −0.69 g/cm3, −1.11 to −0.26; P = 0.001). With use of meta-regression, total body BMD was associated with older age (coefficient −0.0063, −0.0095 to −0.0031; P = 0.002) but not with longer diabetes duration or HbA1c. LIMITATIONS Meta-analysis was limited by the small number of studies with use of QUS and pQCT and by lack of use of BMD z scores in all studies. CONCLUSIONS Bone development is abnormal in youth with type 1 diabetes, assessed by multiple modalities. Routine assessment of BMD should be considered in all youth with type 1 diabetes.