I am an Endocrinologist and PhD student at Monash University, Australia
Using new technology to assess bone microstructure non-invasively
Coeliac disease is a condition characterised by an immune reaction to gluten, and causes damage to the lining of the small intestine. Coeliac disease affects at least 1% of the population and serious repercussions of this disease includes malabsorption of nutrients, leading to loss of bone mass and an increased risk of fracture.
Trabecular bone score (TBS) is a textural metric derived from two-dimensional bone mineral density scans. This provides us with an indirect measure of bone texture, which correlates with bone microarchitecture. While bone mineral density measures bone mass, it does not provide information on bone microstructure, an important determinant of bone quality. Bone microstructure is similar to the foundations of a house, where one might expect a house with better foundations to be more sturdy and table.
TBS is widely available, relatively cheap and does not involve further radiation to a patient who would otherwise have a routine scan for bone mineral density assessment.
There are only a few studies evaluating the effects of coeliac disease on bone microarchitecture presently, and these have demonstrated that bone microarchitecture is indeed compromised. The use of TBS can enhance our understanding of bone microstructural changes specific to coeliac disease, and may be a useful adjunct to bone mineral density to better predict fracture risk in this cohort.
Abstract: In the milder form of primary hyperparathyroidism (PHPT), cancellous bone, represented by areal bone mineral density at the lumbar spine by dual-energy x-ray absorptiometry (DXA), is preserved. This finding is in contrast to high-resolution peripheral quantitative computed tomography (HRpQCT) results of abnormal trabecular microstructure and epidemiological evidence for increased overall fracture risk in PHPT. Because DXA does not directly measure trabecular bone and HRpQCT is not widely available, we used trabecular bone score (TBS), a novel gray-level textural analysis applied to spine DXA images, to estimate indirectly trabecular microarchitecture.The purpose of this study was to assess TBS from spine DXA images in relation to HRpQCT indices and bone stiffness in radius and tibia in PHPT.This was a cross-sectional study conducted in a referral center.Participants were 22 postmenopausal women with PHPT.Outcomes measured were areal bone mineral density by DXA, TBS indices derived from DXA images, HRpQCT standard measures, and bone stiffness assessed by finite element analysis at distal radius and tibia.TBS in PHPT was low at 1.24, representing abnormal trabecular microstructure (normal ≥1.35). TBS was correlated with whole bone stiffness and all HRpQCT indices, except for trabecular thickness and trabecular stiffness at the radius. At the tibia, correlations were observed between TBS and volumetric densities, cortical thickness, trabecular bone volume, and whole bone stiffness. TBS correlated with all indices of trabecular microarchitecture, except trabecular thickness, after adjustment for body weight.TBS, a measurement technology readily available by DXA, shows promise in the clinical assessment of trabecular microstructure in PHPT.
Pub.: 26 Mar '13, Pinned: 25 Aug '17
Abstract: The trabecular bone score (TBS) is a gray-level textural metric that can be extracted from the two-dimensional lumbar spine dual-energy X-ray absorptiometry (DXA) image. TBS is related to bone microarchitecture and provides skeletal information that is not captured from the standard bone mineral density (BMD) measurement. Based on experimental variograms of the projected DXA image, TBS has the potential to discern differences between DXA scans that show similar BMD measurements. An elevated TBS value correlates with better skeletal microstructure; a low TBS value correlates with weaker skeletal microstructure. Lumbar spine TBS has been evaluated in cross-sectional and longitudinal studies. The following conclusions are based upon publications reviewed in this article: 1) TBS gives lower values in postmenopausal women and in men with previous fragility fractures than their nonfractured counterparts; 2) TBS is complementary to data available by lumbar spine DXA measurements; 3) TBS results are lower in women who have sustained a fragility fracture but in whom DXA does not indicate osteoporosis or even osteopenia; 4) TBS predicts fracture risk as well as lumbar spine BMD measurements in postmenopausal women; 5) efficacious therapies for osteoporosis differ in the extent to which they influence the TBS; 6) TBS is associated with fracture risk in individuals with conditions related to reduced bone mass or bone quality. Based on these data, lumbar spine TBS holds promise as an emerging technology that could well become a valuable clinical tool in the diagnosis of osteoporosis and in fracture risk assessment.
Pub.: 21 Jan '14, Pinned: 25 Aug '17
Abstract: Altered bone micro-architecture is an important factor in accounting for fragility fractures. Until recently, it has not been possible to gain information about skeletal microstructure in a way that is clinically feasible. Bone biopsy is essentially a research tool. High-resolution peripheral Quantitative Computed Tomography, while non-invasive, is available only sparsely throughout the world. The trabecular bone score (TBS) is an imaging technology adapted directly from the Dual Energy X-Ray Absorptiometry (DXA) image of the lumbar spine. Thus, it is potentially readily and widely available. In recent years, a large number of studies have demonstrated that TBS is significantly associated with direct measurements of bone micro-architecture, predicts current and future fragility fractures in primary osteoporosis, and may be a useful adjunct to BMD for fracture detection and prediction. In this review, we summarize its potential utility in secondary causes of osteoporosis. In some situations, like glucocorticoid-induced osteoporosis and in diabetes mellitus, the TBS appears to out-perform DXA. It also has apparent value in numerous other disorders associated with diminished bone health, including primary hyperparathyroidism, androgen-deficiency, hormone-receptor positive breast cancer treatment, chronic kidney disease, hemochromatosis, and autoimmune disorders like rheumatoid arthritis. Further research is both needed and warranted to more clearly establish the role of TBS in these and other disorders that adversely affect bone.
Pub.: 24 May '14, Pinned: 25 Aug '17
Abstract: Trabecular bone score (TBS) is a novel method that assesses skeletal texture from spine dual-energy X-ray absorptiometry (DXA) images. TBS improves fracture-risk prediction beyond that provided by DXA bone mineral density (BMD) and clinical risk factors, and can be incorporated to the Word Health Organization Fracture Risk Assessment tool (FRAX®) to enhance fracture prediction. There is insufficient evidence that TBS can be used to monitor treatment with bisphosphonates. TBS may be particularly helpful to assess fracture risk in diabetes. This article reviews technical and clinical aspects of TBS and its potential utility as a clinical tool to predict fracture risk.
Pub.: 31 Jan '17, Pinned: 25 Aug '17
Abstract: Trabecular bone score (TBS) is a recently-developed analytical tool that performs novel grey-level texture measurements on lumbar spine dual X-ray absorptiometry (DXA) images, and thereby captures information relating to trabecular microarchitecture. In order for TBS to usefully add to bone mineral density (BMD) and clinical risk factors in osteoporosis risk stratification, it must be independently associated with fracture risk, readily obtainable, and ideally, present a risk which is amenable to osteoporosis treatment. This paper summarizes a review of the scientific literature performed by a Working Group of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis. Low TBS is consistently associated with an increase in both prevalent and incident fractures that is partly independent of both clinical risk factors and areal BMD (aBMD) at the lumbar spine and proximal femur. More recently, TBS has been shown to have predictive value for fracture independent of fracture probabilities using the FRAX® algorithm. Although TBS changes with osteoporosis treatment, the magnitude is less than that of aBMD of the spine, and it is not clear how change in TBS relates to fracture risk reduction. TBS may also have a role in the assessment of fracture risk in some causes of secondary osteoporosis (e.g., diabetes, hyperparathyroidism and glucocorticoid-induced osteoporosis). In conclusion, there is a role for TBS in fracture risk assessment in combination with both aBMD and FRAX.
Pub.: 20 May '15, Pinned: 25 Aug '17
Abstract: The impact of celiac disease autoimmunity on bone health is unclear. We investigated the associations of seropositivity for tissue transglutaminase antibodies (tTGA) and endomysial antibodies (EMA) with incident hip fractures using data from a prospective cohort study, Mini-Finland Health Survey. Baseline serum samples, taken in 1978-80, were tested for tTGA and EMA. Incident hip fractures up to the year 2011 were ascertained from a national hospitalization register. Associations between seropositivity and hip fractures were modeled using Cox proportional hazards regression adjusted for age, sex, body mass index, vitamin D, gamma-glutamyl transferase, smoking, and self-rated health. Our analyses were based on 6919 men and women who had no record of celiac disease or hip fracture before the study baseline. A total of 382 individuals had a hip fracture during a median follow-up of 30 years. Compared with the tTGA-negative individuals (n = 6350), tTGA-positive participants (n = 569; with hip fracture, n = 51) had a higher risk of hip fractures (hazard ratio [HR] = 1.59, 95% confidence interval [CI] 1.17, 2.14). The findings were similar for another tTGA test (n 200; with hip fracture, n = 26; HR = 2.23, 95% CI 1.49, 3.34). We found no evidence for an association between EMA positivity and hip fracture risk (HR = 0.92, 95% CI 0.34, 2.47; n = 74; with hip fracture, n = 4). In our prospective population-based study of Finnish adults, seropositivity for tTGA was associated with an increased hip fracture risk.
Pub.: 02 Oct '14, Pinned: 25 Aug '17
Abstract: Patients with celiac disease (CD) have low bone mineral density. Evidence of increased fracture risk in these patients is conflicting, and the indication for bone mineral density screening of all adult CD patients is debated. Our aim was to review current published data on fractures in CD. Cross-sectional cohort studies and one case study were identified by searching Medline and Embase. Although the identified studies are heterogeneous and difficult to compare, the overall findings indicate a positive association between CD and risk of fracture. Adult patients with CD should be considered for bone densitometry in order to estimate fracture risk.
Pub.: 03 Apr '14, Pinned: 25 Aug '17
Abstract: Celiac disease (CD) is associated with an increased fracture risk, an increase that persists after diagnosis. A significant proportion of patients with CD have persistent villous atrophy (VA) on follow-up biopsy.The objective of the study was to determine whether persistent VA impacts long-term fracture risk.This was a cohort study.We identified all patients in Sweden with histological evidence of CD who underwent a follow-up biopsy and compared patients with persistent VA with those with mucosal healing.The following were measured: 1) any fracture; 2) likely osteoporotic fracture (defined as fractures of the hip, distal forearm, thoracic and lumbar spine, or proximal humerus); and 3) hip fracture.Of 7146 patients, VA was present on follow-up biopsy in 43%. There was no significant association between persistent VA and overall fractures [hazard ratio (HR) of persistent VA compared with those with healing 0.93, 95% confidence interval (CI) 0.82-1.06] or with likely osteoporotic fractures (HR 1.11, 95% CI 0.84-1.46). Persistent VA was associated with an increased risk of hip fracture (HR 1.67, 95% CI 1.05-2.66). Hip fracture risk increased, depending on the degree of VA (HR for partial VA compared with those with healing 1.70, 95% CI 0.82-3.49, HR for subtotal/total VA compared with those with healing 2.16, 95% CI 1.06-4.41).Persistent VA on follow-up biopsy is predictive of hip fracture risk. The association between persistent VA and hip fractures, but not fractures overall, implies that thinner sc tissue and fall or trauma may be mechanisms by which persistent VA confers an increased fracture risk.
Pub.: 18 Jan '14, Pinned: 25 Aug '17
Abstract: We investigated the association between celiac disease (CD) and bone mass density (BMD) and risk of osteoporotic fractures in the general US population. In children and men ≥18 years, CD was associated with reduced BMD, and in men ≥40 years, CD was associated with increased risk of osteoporotic fractures.Celiac disease (CD) is an autoimmune condition, characterized by inflammation of the small intestine. CD has an increasing prevalence, and if unrecognized or untreated, CD can lead to complications from malabsorption and micronutrient deficiencies. We aimed to study whether CD is an independent predictor of reduced bone mineral density (BMD) and FRAX scores in the general US population.We used data from the National Health and Nutrition Examination Survey, 2009-2010 and 2013-2014. CD was defined by positive tissue transglutaminase IgA antibody test. Multivariable models of BMD and FRAX scores were adjusted for BMI, serum 25-hydroxyvitamin D, vitamin D and calcium supplements, milk intake, serum calcium, and smoking status, when available.In children, aged 8-17 years, CD was associated with decreased Z-scores, by 0.85 for hip and 0.46 for spine (both P < 0.001). In men aged ≥ 18 years, CD was associated with 0.06 g/cm(2) decrease in BMD in hip and with 0.11 g/cm(2) decrease in BMD in spine (P = 0.08 and P < 0.001, respectively). In women, there were no statistically significant differences in the multiple-adjusted model. In men aged ≥ 40 years, CD predicted FRAX scores, resulting in increased scores by 2.25 % (P = 0.006) for hip fracture and by 2.43 % (P = 0.05) for major osteoporotic fracture. CD did not predict FRAX scores in women aged ≥40 years.CD is independently associated with reduced BMD in children and adults aged ≥18 years and is an independent risk factor of osteoporotic fractures in men aged ≥40 years.
Pub.: 08 Oct '16, Pinned: 25 Aug '17
Abstract: We have recently identified a significant deterioration of bone microarchitecture in premenopausal women with newly diagnosed celiac disease (CD) using high-resolution peripheral quantitative computed tomography (HRpQCT). The aim of this work was to assess changes in bone microarchitecture after 1 year on a gluten-free diet (GFD) in a cohort of premenopausal women. We prospectively enrolled 31 consecutive females at diagnosis of CD; 26 of them were reassessed 1 year after GFD. They all underwent HRpQCT scans of distal radius and tibia, areal BMD by DXA, and biochemical tests (bone-specific parameters and CD serology) at both time points. Secondary, we compared 1-year results with those of a control group of healthy premenopausal women of similar age and BMI in order to assess whether the microarchitectural parameters of treated CD patients had reached the values expected for their age. Compared with baseline, the trabecular compartment in the distal radius and tibia improved significantly (trabecular density, trabecular/bone volume fraction [BV/TV] [p < 0.0001], and trabecular thickness [p = 0.0004]). Trabecular number remained stable in both regions. Cortical density increased only in the tibia (p = 0.0004). Cortical thickness decreased significantly in both sites (radius: p = 0.03; tibia: p = 0.05). DXA increased in all regions (lumbar spine [LS], p = 0.01; femoral neck [FN], p = 0.009; ultradistal [UD] radius, p = 0.001). Most parameters continued to be significantly lower than those of healthy controls. This prospective HRpQCT study showed that most trabecular parameters altered at CD diagnosis improved significantly by specific treatment (GFD) and calcium and vitamin D supplementation. However, there were still significant differences with a control group of women of similar age and BMI. In the prospective follow-up of this group of patients we expect to be able to assess whether bone microarchitecture attains levels expected for their age. © 2016 American Society for Bone and Mineral Research.
Pub.: 01 Sep '16, Pinned: 25 Aug '17