Elsevier

Bone

Volume 79, October 2015, Pages 259-266
Bone

TBS reflects trabecular microarchitecture in premenopausal women and men with idiopathic osteoporosis and low-traumatic fractures

https://doi.org/10.1016/j.bone.2015.06.007Get rights and content

Highlights

  • To test if trabecular bone score (TBS) may be useful as a surrogate for histomorphometric trabecular parameters of transiliac bone biopsies, areal bone mineral density (aBMD) and serum bone turnover markers (BTMs).

  • Participants: 80 female patients (median age, 39.9 years) and 43 male patients (median age, 42.7 years).

  • Multiple regression models including gender, aBMD and BTMs revealed TBS as an independent, discriminative variable with adjusted multiple R2 values ranging from 69.1% to 83.3% for trabecular bone μCT parameters. In univariate regression models, BTMs showed statistically significant results, whereas in the multiple models only P1NP and CTX were significant for trabecular number.

  • TBS is a practical, non-invasive, surrogate technique for the assessment of cancellous bone microarchitecture.

Abstract

Transiliac bone biopsies, while widely considered to be the standard for the analysis of bone microstructure, are typically restricted to specialized centers. The benefit of Trabecular Bone Score (TBS) in addition to areal bone mineral density (aBMD) for fracture risk assessment has been documented in cross-sectional and prospective studies. The aim of this study was to test if TBS may be useful as a surrogate to histomorphometric trabecular parameters of transiliac bone biopsies. Transiliac bone biopsies from 80 female patients (median age 39.9 years  interquartile range, IQR 34.7; 44.3) and 43 male patients (median age 42.7 years  IQR 38.9; 49.0) with idiopathic osteoporosis and low traumatic fractures were included. Micro-computed tomography values of bone volume fraction (BV/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N), trabecular separation (Tb.Sp), structural model index (SMI) as well as serum bone turnover markers (BTMs) sclerostin, intact N-terminal type 1 procollagen propeptide (P1NP) and cross-linked C-telopeptide (CTX) were investigated. TBS values were higher in females (1.282 vs 1.169, p <  0.0001) with no differences in spine aBMD, whereas sclerostin levels (45.5 vs 33.4 pmol/L) and aBMD values at the total hip (0.989 vs 0.971 g/cm2, p < 0.001 for all) were higher in males. Multiple regression models including: gender, aBMD and BTMs revealed TBS as an independent, discriminative variable with adjusted multiple R2 values of 69.1% for SMI, 79.5% for Tb.N, 68.4% for Tb.Sp, and 83.3% for BV/TV. In univariate regression models, BTMs showed statistically significant results, whereas in the multiple models only P1NP and CTX were significant for Tb.N. TBS is a practical, non-invasive, surrogate technique for the assessment of cancellous bone microarchitecture and should be implemented as an additional tool for the determination of trabecular bone properties.

Graphical abstract

Study design

Two-center cross-sectional study in premenopausal women and men with idiopathic osteoporosis and low-traumatic fractures

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Introduction

Osteoporosis is a skeletal disorder characterized by low bone strength and increased low-traumatic fracture risk. Areal bone mineral density (aBMD) measured by dual-energy X-ray absorptiometry (DXA) is considered the standard technique for the diagnosis of osteoporosis [1]. Patients who sustain osteoporosis-related low-traumatic fractures have reduced bone mass as well as alterations in bone microstructure. It is worth noting that most low-traumatic fractures occur in patients with osteopenia or normal aBMD, suggesting that aBMD is of limited benefit for fracture risk prediction. Furthermore, there is a considerable overlap in aBMD values of patients with and without fractures [2], [3]. As a result, aBMD alone is not a reliable indicator for fracture risk. Several factors are known to influence bone strength and fracture risk, including the anatomic dimensions of cortical bone, the microstructure of trabecular bone, microdamages, changes in material properties as well as bone mineralization and turnover [2]. To address these issues, advanced analytical methods have been established to assess cortical and trabecular microarchitecture individually. Transiliac bone biopsies, despite their invasiveness, are considered to be the current best method for microstructural analysis. In clinical practice, performing transiliac biopsies is limited and used only for exceptional and complicated patient cases. Beyond being invasive, transiliac bone biopsies are costly and time-intensive procedures [4]. Another factor worth considering is the ongoing discussion as to whether or not the iliac crest as a non–weight-bearing bone site is representative for microstructure elsewhere in the body. Among non-invasive techniques, high-resolution peripheral quantitative computed tomography (HR-pQCT) and magnetic resonance imaging (MRI) allow direct measurements of the bone microarchitecture. These methods remain impractical for routine screening due to high costs, the availability of devices and the lack of validation studies. In light of these difficulties, trabecular bone score (TBS), a greyscale textural analysis that estimates trabecular microarchitecture from the anterior/posterior (AP) lumbar spine DXA, has been established [5], [6]. The benefit of TBS in addition to aBMD for fracture risk assessment has been documented in several cross-sectional and prospective studies [6], [7], [8]. On the structural level of bone tissue, significant correlations have been identified between TBS and 3D parameters of bone microarchitecture independent of any correlation between TBS and aBMD. However, the analysis was performed in human cadaver vertebrae [9], [10].

The aim of the present study was to test whether or not a non-invasive 3D imaging technique, such as TBS assessed by spinal DXA, would be useful as a surrogate for morphometric trabecular parameters of transiliac bone biopsies.

The primary objective of this study was to evaluate associations between spine TBS and trabecular microarchitectural parameters of transiliac bone biopsies (SMI, Tb.N, Tb.Sp, BV/TV) in treatment-naïve premenopausal women and similarly aged men with low-traumatic fractures.

Secondary objectives were to evaluate the role of (i) TBS and serum bone turnover markers of osteocyte, osteoblast and osteoclast activity (sclerostin, P1NP, CTX) and (ii) gender-specific differences in this context in young patients with low-traumatic fractures.

Section snippets

Patients

In this two-center cross-sectional study, between January 2005 and December 2014, all eligible patients with idiopathic osteoporosis were recruited at the outpatient clinic of the Medical Department II for Rheumatology and Bone Diseases, St. Vincent Hospital Vienna (Austria) and the Department of Internal Medicine, Division of Endocrinology and Metabolism, the Medical University of Graz, Austria. The study was approved by the local ethics committee. All patients signed a written informed

Patient characteristics

Transiliac bone biopsies from 80 female patients with a median age of 39.9 years (interquartile range, IQR, 34.7; 44.3) and 43 male patients with a median age of 42.7 years (IQR, 38.9; 49.0) obtained between October 2004 and May 2014 were included in this analysis. Height, weight and body mass index (BMI) in females were significantly lower compared to males. Forty-nine percent of all patients had prevalent vertebral fractures, 61% had prevalent non-vertebral fractures and 7% had sustained a hip

Discussion

The aim of this cross-sectional study was to compare TBS assessed by spinal DXA with trabecular parameters of bone biopsies of the iliac crest, assessed by μCT, in a group of untreated young female and male patients with idiopathic osteoporosis and low traumatic fractures.

Bone microarchitecture is an important indicator of bone strength. Iliac crest biopsies allow both a quantitative and qualitative assessment of bone microarchitecture [15], [16]. Morphometric findings in osteoporotic bone

Conclusion

These findings suggest that for patients with idiopathic osteoporosis and low-traumatic fractures, TBS is a feasible, non-invasive surrogate technique for the assessment of cancellous bone microarchitecture texture from DXA scans in clinical routine that would not satisfy the definition of osteoporosis when based solely upon T-scores or aBMD values. BTMs provide limited information if TBS values are available. TBS should not replace aBMD, but rather be implemented as an additional tool for the

Authors’ roles

Study design: CM and HR. Study conduct: CM and RK. Data collection: CM, JH, AFP, GKM and RK. Data analysis: CM, HR, RK, JH, DP, AK, GKM, DH and AFP. Data interpretation: CM, HR, RK, JH, PP, AFP and DH. Drafting manuscript: CM, RK and JH. Revising manuscript content: CM, RK, JH, AK, PP, GKM, AFP and HR. Approving final version of manuscript and revised manuscript: CM, HR, RK, DP, DH, AK, JH, GKM, PP and AFP. CM and RK take responsibility for the integrity of the data analysis.

We cordially thank

Conflict of Interest

CM has received speaker honoraria from Amgen, Novartis, Servier, Eli Lilly, Nycomed Pharma/Takeda, Kwizda Pharma, Boehringer Ingelheim, Actavis, Daiichi-Sankyo. CM has received educational grants/research support from the Austrian Society for Bone and Mineral Research, Roche Austria, Eli Lilly Austria, Eli Lilly International and Amgen Austria. He has nothing to disclose concerning this manuscript.

HR has received speaker honoraria from Amgen, Novartis, Servier, Eli Lilly, Nycomed/Takeda, Merck

Competing interests

This study was not supported by any grant or pharmaceutical company.

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    CM and RK contributed equally to this manuscript.

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