Bone Microarchitecture Assessed by Trabecular Bone Score Is Independent of Mobility Level or Height in Pediatric Patients with Cerebral Palsy

Trabecular bone score (TBS) derived from secondary analysis of lumbar spine dual‐energy X‐ray absorptiometry (DXA) scans improves fracture prediction independent of bone mineral density (BMD) in adults. The utility of TBS to assess fracture risk in younger patients has not been established because pediatric norms have been lacking. Robust TBS reference data from the Bone Mineral Density in Childhood Study (BMDCS) have been published. TBS values for the BMDCS study were derived using an algorithm that accounts for tissue thickness (TBSTH) rather than the commercially available algorithm that adjusts for body mass index (BMI; TBSBMI). We examined the magnitude of differences in TBSTH and TBSBMI in a cohort of 189 healthy youth. TBS values using both algorithms increased with age and pubertal development in a similar pattern. However, TBSBMI values were systematically and significantly higher than TBSTH (mean = 0.06, p < 0.0001). The difference between calculated TBSBMI and TBSTH was not uniform. Differences were greater at lower TBS values, in males, in older individuals, in those at later Tanner stages, and in those with a greater BMI Z‐score. These systematic differences preclude the development of a simple formula to allow conversion of TBSBMI to TBSTH “equivalents.” Because of these systematic differences in these two algorithms, using an individual's TBSBMI to calculate a Z‐score using the BMDCS TBSTH reference values results in a falsely higher TBS Z‐score (differences mean = 0.73, interquartile range [IQR] = 0.3 to 1.6). Until TBSTH software for Hologic DXA equipment becomes commercially available, BMDCS TBS reference norms should not be used. © 2023 American Society for Bone and Mineral Research (ASBMR).

Section: Discussionmentioning

confidence: 99%

“…( 23 ) Reduced mobility was not shown to affect TBS in a study of 472 youth with cerebral palsy; the mean TBS Z ‐score for the cohort was within 1 SD of the Del Rio normative data. ( 24 )…”

Section: Discussionmentioning

confidence: 99%

Trabecular Bone Score (TBS) Varies with Correction for Tissue Thickness Versus Body Mass Index: Implications When Using Pediatric Reference Norms

Riveros

Long

Bachrach

et al. 2020

“…We assessed aBMD of the lumbar spine, hip, and total body less head (TBLH) (Lunar iDXA, GE Healthcare, Madison, WI, USA) at initial presentation and follow‐up, and adjusted the data for height‐adjusted Z ‐score (HAZ). ( 26,27 ) All parameters were assessed both before and post‐initiation of conventional treatment, consisting of phosphate and calcitriol, as well as 25(OH)D‐supplementation.…”

Section: Methodsmentioning

confidence: 99%

Response of the ENPP1-Deficient Skeletal Phenotype to Oral Phosphate Supplementation and/or Enzyme Replacement Therapy: Comparative Studies in Humans and Mice

Ferreira

Kavanagh

Oheim

et al. 2020

Inactivating mutations in human ecto‐nucleotide pyrophosphatase/phosphodiesterase‐1 (ENPP1) may result in early‐onset osteoporosis (EOOP) in haploinsufficiency and autosomal recessive hypophosphatemic rickets (ARHR2) in homozygous deficiency. ARHR2 patients are frequently treated with phosphate supplementation to ameliorate the rachitic phenotype, but elevating plasma phosphorus concentrations in ARHR2 patients may increase the risk of ectopic calcification without increasing bone mass. To assess the risks and efficacy of conventional ARHR2 therapy, we performed comprehensive evaluations of ARHR2 patients at two academic medical centers and compared their skeletal and renal phenotypes with ENPP1‐deficient Enpp1asj/asj mice on an acceleration diet containing high phosphate treated with recombinant murine Enpp1‐Fc. ARHR2 patients treated with conventional therapy demonstrated improvements in rickets, but all adults and one adolescent analyzed continued to exhibit low bone mineral density (BMD). In addition, conventional therapy was associated with the development of medullary nephrocalcinosis in half of the treated patients. Similar to Enpp1asj/asj mice on normal chow and to patients with mono‐ and biallelic ENPP1 mutations, 5‐week‐old Enpp1asj/asj mice on the high‐phosphate diet exhibited lower trabecular bone mass, reduced cortical bone mass, and greater bone fragility. Treating the Enpp1asj/asj mice with recombinant Enpp1‐Fc protein between weeks 2 and 5 normalized trabecular bone mass, normalized or improved bone biomechanical properties, and prevented the development of nephrocalcinosis and renal failure. The data suggest that conventional ARHR2 therapy does not address low BMD inherent in ENPP1 deficiency, and that ENPP1 enzyme replacement may be effective for correcting low bone mass in ARHR2 patients without increasing the risk of nephrocalcinosis. © 2021 American Society for Bone and Mineral Research (ASBMR).

“…(2) TBS reference values from the US NHANES survey for adults, ages 20 to 80 years, by sex and race, are incorporated in the software. (3) TBS has recently been used in studies involving pediatric populations to examine disease effects, (4)(5)(6)(7)(8)(9) and there is broad interest in using TBS as a clinical tool to identify children and adolescents with poor bone health and skeletal fragility. TBS values in children and adolescents increase with age, especially in early adolescence, (10)(11)(12) thus using adult reference values is not appropriate.…”

Section: Introductionmentioning

confidence: 99%

Trabecular Bone Score Reference Values for Children and Adolescents According to Age, Sex, and Ancestry

Kalkwarf

Shepherd

Hans

et al. 2020

Trabecular bone score (TBS) is used for fracture prediction in adults, but its utility in children is limited by absence of appropriate reference values. We aimed to develop reference ranges for TBS by age, sex, and population ancestry for youth ages 5 to 20 years. We also investigated the association between height, body mass index (BMI), and TBS, agreement between TBS and lumbar spine areal bone mineral density (aBMD) and bone mineral apparent density (BMAD) Z‐scores, tracking of TBS Z‐scores over time, and precision of TBS measurements. We performed secondary analysis of spine dual‐energy X‐ray absorptiometry (DXA) scans from the Bone Mineral Density in Childhood Study (BMDCS), a mixed longitudinal cohort of healthy children (n = 2014) evaluated at five US centers. TBS was derived using a dedicated TBS algorithm accounting for tissue thickness rather than BMI. TBS increased only during ages corresponding to pubertal development with an earlier increase in females than males. There were no differences in TBS between African Americans and non‐African Americans. We provide sex‐specific TBS reference ranges and LMS values for calculation of TBS Z‐scores by age and means and SD for calculation of Z‐scores by pubertal stage. TBS Z‐scores were positively associated with height Z‐scores at some ages. TBS Z‐scores explained only 27% and 17% of the variance of spine aBMD and BMAD Z‐scores. Tracking of TBS Z‐scores over 6 years was lower (r = 0.47) than for aBMD or BMAD Z‐scores (r = 0.74 to 0.79), and precision error of TBS (2.87%) was greater than for aBMD (0.85%) and BMAD (1.22%). In sum, TBS Z‐scores provide information distinct from spine aBMD and BMAD Z‐scores. Our robust reference ranges for TBS in a well‐characterized pediatric cohort and precision error estimates provide essential tools for clinical assessment using TBS and determination of its value in predicting bone fragility in childhood and adolescence. © 2022 American Society for Bone and Mineral Research (ASBMR).