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

Abstract

<u>Background</u> <p>There is substantial evidence that adults with type 1 diabetes have reduced bone mineral density (BMD), however findings in youth are inconsistent.</p> <p><u>Purpose</u></p> <p>Systematic review and meta-analysis of BMD in youth with type 1 diabetes using multiple modalities: dual energy X-ray absorptiometry (DXA), peripheral quantitative computed tomography (pQCT) and/or quantitative ultrasound (QUS).</p> <p><u>Data Sources</u></p> <p>PubMed, Embase, Scopus and Web of Science from 01/01/1990 to 31/12/2020, limited to humans, without language restriction.</p> <p><u>Study Selection</u></p> <p>Inclusion criteria: cross sectional or cohort studies that included BMD measured either by DXA, pQCT and/or QUS in youth (age <20 years) with type 1 diabetes and matched controls. </p> <p><u>Data extraction</u></p> <p>Total body (TB), lumbar spine (LS) and femoral BMD (DXA); tibia, radius and lumbar spine (pQCT); and phalanx and calcaneum (QUS). Weighted mean difference (WMD) or standardized mean difference (SMD) were estimated and meta-regression was performed using age, diabetes duration and HbA1c as covariates.</p> <p><u>Data Synthesis </u></p> <p>We identified 1300 non-duplicate studies; 46 met the inclusion criteria, including 2617 cases and 3851 controls. Mean age was 12.6 ± 2.3 years. Youth with type 1 diabetes had lower BMD: TB (WMD -0.04 g/cm<sup>2</sup>, 95% CI -0.06 to -0.02, <i>P</i>=0.0006); LS (-0.02 g/cm<sup>2</sup>, -0.03 to -0.0, <i>P = 0.01</i>); femur (-0.04 g/cm<sup>2</sup>, -0.05 to -0.03, <i>P</i><0.00001); tibial trabecular (-11.32 g/cm<sup>3</sup>,-17.33 to -5.30, <i>P</i>=0.0002), radial trabecular (-0.91, -1.55 to -0.27, <i>P=0.005</i>); phalangeal (-0.32, -0.38 to -0.25, <i>P</i><0.00001) and calcaneal (SMD -0.69, -1.11 to -0.26, <i>P</i>=0.001). Using meta-regression TB BMD was associated with older age (coefficient -0.0063, -0.0095 to -0.0031, <i>P</i>=0.002), but not longer diabetes duration or HbA1c.</p> <p><u>Limitations</u></p> <p>Meta-analysis was limited by the small number of studies using QUS and pQCT and lack of use BMD z-scores in all studies. </p> <p><u>Conclusions</u></p> <p>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.</p>

Childhood type 1 diabetes is associated with abnormal bone development

“…Multiple studies have examined bone parameters in children with T1D by DXA and have reported normal 22–26 or low lumbar spine BMD, 10,12–17,19,20 but these studies had heterogeneous study populations, limiting direct comparison between them, as highlighted in our recent systematic review 2 . Our study cohort had lower right femoral neck BMD similar to previous studies in young adults 15,23,25 .…”

Impact of Type 1 Diabetes Mellitus on Bone Health in Children

“…The literature on DXA measurements to assess bone mass in children and adolescents with T1DM is conflicting. The most recent, comprehensive meta-analysis including 2,617 children with T1DM showed significantly lower mean total body BMD, lumbar spine BMD, and femur neck BMD (−0.04 kg/cm 2 , −0.02 g/cm 2 and −0.04 g/cm 2 , respectively) compared to 3,851 healthy controls [27]. Some smaller cross-sectional studies in children with T1DM revealed lower total body BMD Z -scores compared to controls [34], lower total body less head (TBLH) BMC and aBMC at the femoral neck, lower tibial cortical vBMD [35], lower total body, and lumbar spine BMC [36] when compared to age-matched reference data.…”

“…Further evidence for the impact of overall health on bone health is provided by a study by Pham-Short et al [24], which showed lower BMC at the radius measured by pQCT in children with T1DM and well-controlled celiac disease compared to children with T1DM without celiac disease. Finally, a recent comprehensive meta-analysis showed that the mean differences in tibial trabecular vBMD and radial trabecular vBMD (−11.32 kg/cm 3 and −0.91 g/cm 3 , respectively) were significantly lower in youth with T1DM compared to controls [27].…”

“…Beyond pQCT, high-resolution pQCT (HRpQCT) further enables the measurement of bone microarchitecture and bone strength, calculated via micro-finite element analysis [21]. During the last 15 years, studies investigating pQCT [22][23][24][25][26] and HRpQCT [26][27][28] in children with T1DM have been published and provided results for biomechanically relevant determinants of bone quality including vBMD, bone microarchitecture and bone strength. Another reason for conflicting study results based on DXA measures may be sample size.…”

“…Another reason for conflicting study results based on DXA measures may be sample size. However, a very recent, comprehensive meta-analysis including 46 studies with 2,617 cases and 3,851 controls showed that BMD measured with DXA (total body, lumbar spine, femur), pQCT (radius and tibia) and quantitative ultrasound of the calcaneus and phalanx was substantially lower in children with T1DM compared to controls [27].…”