Sex- and Site-Specific Normative Data Curves for HR-pQCT

Burt, Lauren A; Liang, Zhiying; Sajobi, Tolulope T.; Hanley, David A.; Boyd, Steven K.

doi:10.1002/jbmr.2873

Cited by 100 publications

(130 citation statements)

References 42 publications

(93 reference statements)

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“…Predicted change derived from our previously published cross‐sectional data accurately forecasts rate of change for males’ and females’ total density and cortical thickness at the radius and cortical density at the tibia, in the participants older than 50 years. There are some parameters, including cortical porosity and trabecular area that are not consistent with the cross‐sectional predictions.…”

Section: Discussionmentioning

confidence: 82%

Cross-sectional Versus Longitudinal Change in a Prospective HR-pQCT Study

Burt

Hanley

Boyd

2017

Journal of Bone and Mineral Research

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Longitudinal studies assessing age-related changes using high-resolution peripheral quantitative computed tomography (HR-pQCT) provide novel insight compared with cross-sectional analyses. The purpose of this cohort study was 1) to determine individuals' change in HR-pQCT parameters over 5 years relative to least significant change (LSC), and 2) to evaluate if predicted rate of change from cross-sectional data is comparable to actual change from longitudinal investigation. A cohort of 466 (162 male, 304 female) participants completed two HR-pQCT scans with 5 years between assessments. After image registration, standard and cortical morphological analyses were conducted. Rate of bone microarchitectural change was compared between cross-sectional models and actual change calculated from longitudinal analyses. At the young end of the life span, we observed gains in total bone density of +0.2% to +2.9% per year, whereas the older participants (aged >50 years) lost total bone density at a rate of -0.3% to -1.3% per year. Declines in total bone density begin at age 40 years in females and 60 years in males, and significant adaptation was found at both ends of the age spectrum with respect to the LSC. Models predicting rate of change from cross-sectional data were similar to the actual change reported in this longitudinal study for total density and cortical thickness at the radius and cortical density at the tibia, but we found that changes in comparison to our 5-year longitudinal results were often overestimated from cross-sectional data. Studies aimed at observing age-related changes in a normative cohort, especially in a follow-up period of less than 5 years, are better to focus on the tibia rather than the radius because of the increased sensitivity to change at the tibia. © 2017 American Society for Bone and Mineral Research.

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Section: Discussionmentioning

confidence: 82%

Cross-sectional Versus Longitudinal Change in a Prospective HR-pQCT Study

Burt

Hanley

Boyd

2017

Journal of Bone and Mineral Research

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“…(F) HR‐pQCT scans of the distal tibia of patient A1. (G) Bone microstructure parameters of the distal tibia of patients A1, B1, and B2 (carrying heterozygous ENPP1 mutations) obtained by HR‐pQCT in comparison to a healthy sex‐ and age‐matched control group …”

Section: Resultsmentioning

confidence: 99%

“…4D and Supplemental Table S7). Biomechanical findings at 23 weeks continued to exhibit reduced bone (35) stiffness and maximum load but also demonstrated increased ductility, suggesting that the accumulation of unmineralized matrix over time has altered the material properties of bone (Fig. 4E).…”

Section: Murine Phenotype Of Enpp1 Deficiencymentioning

confidence: 97%

Human Heterozygous ENPP1 Deficiency Is Associated With Early Onset Osteoporosis, a Phenotype Recapitulated in a Mouse Model of Enpp1 Deficiency

Oheim

Zimmerman

Maulding

et al. 2019

Journal of Bone and Mineral Research

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Biallelic ENPP1 deficiency in humans induces generalized arterial calcification of infancy (GACI) and/or autosomal recessive hypophosphatemic rickets type 2 (ARHR2). The latter is characterized by markedly increased circulating FGF23 levels and renal phosphate wasting, but aberrant skeletal manifestations associated with heterozygous ENPP1 deficiency are unknown. Here, we report three adult men with early onset osteoporosis who presented with fractures in the thoracic spine and/or left radius, mildly elevated circulating FGF23, and hypophosphatemia. Total hip bone mineral density scans demonstrated osteoporosis (Z‐score < −2.5) and HRpQCT demonstrated microarchitectural defects in trabecular and cortical bone. Next‐generation sequencing revealed heterozygous loss‐of‐function mutations in ENPP1 previously observed as biallelic mutations in infants with GACI. In addition, we present bone mass and structure data as well as plasma pyrophosphate (PPi) data of two siblings suffering from ARHR2 in comparison to their heterozygous and wild‐type family members indicative of an ENPP1 gene dose effect. The skeletal phenotype in murine Enpp1 deficiency yielded nearly identical findings. Ten‐week‐old male Enpp1 asj/asj mice exhibited mild elevations in plasma FGF23 and hypophosphatemia, and micro‐CT analysis revealed microarchitectural defects in trabecular and cortical bone of similar magnitude to HRpQCT defects observed in humans. Histomorphometry revealed mild osteomalacia and osteopenia at both 10 and 23 weeks. The biomechanical relevance of these findings was demonstrated by increased bone fragility and ductility in Enpp1 asj/asj mice. In summary, ENPP1 exerts a gene dose effect such that humans with heterozygous ENPP1 deficiency exhibit intermediate levels of plasma analytes associated with bone mineralization disturbance resulting in early onset osteoporosis. © 2019 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.

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“…To further emphasize the clinical significance of these findings, we used differences in T-score between fixed and %-of-length measurements to relate the observed measurement bias to biological variability. While it has been suggested that centile curves, rather than T- or Z-scores, are more appropriate for the clinical application of HR-pQCT [7], our observations suggest that meaningful interpretation of an individual HR-pQCT score will require anatomically standardized measurements, regardless of the score formulation applied. For example, on average the fixed offset measurement of Ct.BMD deviated by 1.0 SD from what would be measured at a standard anatomic %-of-length position.…”

Section: Discussionmentioning

confidence: 71%

“…gender and race comparison studies) and potentially diminishes the statistical power in discriminant analyses. Furthermore the dependence on bone length significantly limits the clinical utility of HR-pQCT for individual assessment of bone quality in patients with body sizes that differ from the mean of the reference population [7–11]. Adapting scan localization protocols to account for subject-specific limb length would therefore remove an important source of measurement variability, thereby improving the power of this technology in musculoskeletal research and relevance for clinical practice.…”

Section: Introductionmentioning

confidence: 99%

The comparability of HR-pQCT bone measurements is improved by scanning anatomically standardized regions

et al. 2017

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Introduction High-resolution peripheral quantitative computed tomography (HR-pQCT) measures of bone do not account for anatomic variability in bone length: a 1-cm volume is acquired at a fixed offset from an anatomic landmark. Our goal was to evaluate HR-pQCT measurement variability introduced by imaging fixed vs. proportional volumes and to propose a standard protocol for relative anatomic positioning. Methods Double-length (2-cm) scans were acquired in 30 adults. We compared measurements from 1-cm subvolumes located at the default fixed offset, and the average %-of-length offset. The average position corresponded to 4.0% ± 1.1 mm for radius, and 7.2% ± 2.2 mm for tibia. We calculated the RMS difference in bone parameters and T-Scores to determine the measurement variability related to differences in limb length. We used anthropometric ratios to estimate the mean limb length for published HR-pQCT reference data, and then calculated mean %-of-length offsets. Results Variability between fixed vs. relative scan positions was highest in the radius, and for cortical bone in general (RMS difference Ct.Th = 19.5%), while individuals had T-score differentials as high as +3.0 SD (radius Ct.BMD). We estimated that average scan position for published HR-pQCT reference data corresponded to 4.0% at the radius, and 7.3% at tibia. Conclusion Variability in limb length introduces significant bias to HR-pQCT measures, confounding cross-sectional analyses and limiting the clinical application for individual assessment of skeletal status. We propose to standardize scan positioning using 4.0% and 7.3% of total bone length for the distal radius and tibia, respectively.

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Sex- and Site-Specific Normative Data Curves for HR-pQCT

Cited by 100 publications

References 42 publications

Cross-sectional Versus Longitudinal Change in a Prospective HR-pQCT Study

Cross-sectional Versus Longitudinal Change in a Prospective HR-pQCT Study

Human Heterozygous ENPP1 Deficiency Is Associated With Early Onset Osteoporosis, a Phenotype Recapitulated in a Mouse Model of Enpp1 Deficiency

The comparability of HR-pQCT bone measurements is improved by scanning anatomically standardized regions

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