Osteoporosis 2016 | DXA and beyond: Dr Nicola Crabtree #osteo2016
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Dr Nicola Crabtree's presentation from Osteoporosis 2016: DXA and beyond. Find out more at: https://nos.org.uk/conference
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Osteoporosis 2016 | DXA and beyond: Dr Nicola Crabtree #osteo2016
- 1. Dr Nicola Crabtree Principal Clinical Scientist & NIHR Post Doctoral Research Fellow Birmingham Children’s Hospital / Queen Elizabeth Hospital Birmingham Fracture Risk Assessment - DXA and Beyond
- 2. Osteoporosis – Conceptual definition “a skeletal disease, characterised by low bone mass and micro-architectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture” Consensus development conference: diagnosis, prophylaxis and treatment of osteoporosis. Am J Med. 1993
- 3. Osteoporosis – Operational definition Operationally defined by dual-energy X-ray absorptiometry as 2.5 standard deviations or more below the young adult female mean (T-Score ≤ -2.5) measured at the femoral neck, total hip, or lumbar spine. World Health Organisation. Assessment of fracture risk and its application to screening for postmenopausal osteoporosis (1994)
- 4. Dual-Energy X-ray Absorptiometry DXA Widely available 2-D Projection modality Short scan times Good precision Reliable reference ranges Low radiation exposure Inversely related to fracture
- 6. 0 20 40 60 80 100 120 1 0,5 0 -0,5 -1 -1,5 -2 -2,5 -3 -3,5 -4 -4,5 -5 -5,5 Femoral neck BMD (T-score Nhanes) 0 20 40 60 80 100 120 140 160 EPISEM study; 6862 postmenopausal white women ≥70 years, randomly selected from population based listing - Mean f/u of 3.2 yrs. 678 OP fractures (hip, distal forearm, proximal humerus) BMD distribution No of women with fractures Fracture rate Fracturerateper1000Person-years Noofwomenwithfractures Courtesy of D Hans & MA Krieg – Adapted from the EPISEM Study BMD overlaps in women with & without fracture
- 7. Normal Bone Density BUT Vertebral Fracture
- 8. High Bone Density & Vertebral Fracture
- 9. Dual energy x-ray absorptiometry BMD as measured by DXA represents an amalgamation of volumetric bone density, bone size, microarchitecture and the material properties of bone. DXA = areal Bone mineral Density (g/cm2)
- 10. DXA Beyond BMD re-visit conceptual definition “a skeletal disease, characterised by low bone mass and micro-architectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture”
- 11. Bone Microarchitecture? Histomorphometry of trans illiac bone biopsy HRpQCT MRI Not easily assessed clinically
- 12. CAN WE ESTIMATE BONE MICRO-ARCHITECTURE IN-VIVO?
- 14. Trabecular Bone Score (TBS) Gray-level textural metric extracted from the two-dimensional lumbar spine dual-energy absorptiometry TBS is related to bone microarchitecture and provides skeletal information that is not captured from the standard bone density measurement Based on experimental variograms of the projected DXA image. TBS has the potential to discern differences between DXA scans that have similar BMD High TBS = Better skeletal micro structure Low TBS = Weaker micro structure
- 15. Trabecular Bone Score (TBS) Reproduced from Silva BC et al. JBMR 2014 [29], 3, 518-530
- 16. Can’t see the wood for the trees? High TBS Low TBS
- 17. Clinical Trabecular Bone Score (TBS) TBS is processed in the same region of interest as BMD. Bousson et al. Osteoporosis International 2011
- 18. TBS – Manitoba Study 29,407 women over 50 years of age BMD Hip & spine 4.7 years follow up TBS 1668 osteoporotic fractures BMD & TBS predicted fractures equally well Combining BMD & TBS improves the prediction Hans et al. JBMR 2011
- 19. TBS and Fracture Silva BC et al. 2013 JBMR Women Men Prospective suggest that the TBS predicts risk of fracture even after adjustment for BMD.
- 20. TBS FRAX Meta-Analysis: Gradients of Risks per SD change in risk score Age TBS only Clinical risk factors + BMD Clinical risk factors + BMD + TBS Hip fracture 50 1.51 (0.89 - 2.55) 4.03 (2.01 - 8.10) 5.09 (2.45 - 10.55) 60 1.46 (1.01 - 2.11) 3.46 (2.13 - 5.62) 4.90 (2.80 - 8.56) 70 1.41 (1.12 - 1.77) 2.97 (2.23 - 3.97) 4.72 (3.06 - 7.26) 80 1.36 (1.18 - 1.57) 2.55 (2.14 - 3.05) 4.54 (3.06 - 6.74) 90 1.31 (1.06 - 1.62) 2.19 (1.66 - 2.90) 4.37 (2.73 - 7.00) Other MOP fractures 50 1.54 (1.18 - 2.00) 1.56 (1.18 - 2.05) 1.62 (1.25 - 2.10) 60 1.51 (1.26 - 1.79) 1.52 (1.26 - 1.84) 1.58 (1.33 - 1.88) 70 1.47 (1.32 - 1.64) 1.49 (1.30 - 1.69) 1.54 (1.40 - 1.70) 80 1.44 (1.29 - 1.61) 1.45 (1.28 - 1.65) 1.50 (1.37 - 1.64) 90 1.41 (1.18 - 1.68) 1.42 (1.18 - 1.70) 1.46 (1.25 - 1.71) EV McCloskey et al. on behalf of the FRAX meta-analysis working group – 2015
- 21. Can TBS be usefully added to FRAX? TBS yields risk which is independent of BMD independent of CRFs amenable to intervention clinically meaningful Sufficient level of evidence (many studies) Validation cohort
- 22. TBS Meta analysis → FRAX TBS is predictor of fracture risk independent of FRAX and BMD
- 23. FRAX + NOGG
- 24. FRAX with added TBS High TBS reduces fracture risk Low TBS increases fracture risk
- 25. FRAX + NOGG + TBS Low TBS High TBS
- 26. Disease specific– Type II Diabetes Vestergaard et al OI 2007
- 27. TBS – Type II Diabetes 29,407 women ≥50 years with baseline DXA ANCOVA adjusted for age, BMI, glucocorticoids, prior major fracture, rheumatoid, arthritis, COPD, alcohol abuse and osteoporosis therapy. Diabetes – No diabetes Mean (95% CI) Lumbar spine BMD (g/cm2) +0.031 (0.024 : 0.038) Femoral neck BMD (g/cm2) +0.012 (0.007 : 0.016) Trochanter BMD (g/cm2) +0.008 (0.003 : 0.013) Total hip BMD (g/cm2) +0.019 (0.014 : 0.025) Lumbar spine TBS (unitless) -0.051 (-0.056 : -0.046) Leslie WD et al. JCEM 2013
- 28. TBS is More Sensitive Than BMD to Diabetes-Related Fracture Risk OR 0.66 OR 2.61 OR 0.68OR 0.80 0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 L14 BMD Fem Neck BMD Total Hip BMD L14 TBS AdjustedOR Odds ratios (95% CI bars) for lowest vs highest tertile according to presence of diabetes (adjusted for age, BMI, osteoporosis therapy, glucocorticoids, prior fracture, rheumatoid arthritis, COPD, alcohol abuse). Leslie WD et al. JCEM 2013
- 29. TBS and Osteoporosis Treatment Popp et al. 2012 JBMR Silva BC et al. 2013 JBMR
- 30. ISCD – PDC 2015 TBS is associated with vertebral, hip and major osteoporotic fracture risk in older women (hip and major osteoporotic fracture risk in older men) TBS should not be used alone to determine treatment TBS can be used in association with FRAX and BMD to adjust FRAX- probability in older women and men TBS is not useful for monitoring bisphosphonate TBS is associated with major osteoporotic fracture risk in postmenopausal women with type II diabetes Shepherd et al. JCD 2015
- 31. Hip Geometry
- 32. Hip Strength Analysis / Advanced Hip Analysis θ Beck et al. 1990
- 33. Bone Distribution 74 year old physically active lady 83 year old physically inactive lady
- 34. Faster & Stronger Slower & Weaker
- 35. Hip Geometry: Independent of FRAX and BMD Manitoba database, N=50,420 women >40, 1020 incident hip fractures HR per SD FRAX without BMD HR per SD FRAX with BMD CSA 1.79 (1.66-1.94) 1.11 (1.01-1.22) Section Modulus 1.47 (1.36-1.58) 1.04 (0.97-1.12) Buckling Ratio 1.21 (1.15-1.26) 1.21 (1.14-1.28) CSMI 1.25 (1.16-1.35) 1.05 (0.98) Neck Shaft Angle 1.23 (1.17-1.30) 1.23 (1.17-1.30) Hip Axis Length 1.30 (1.22-1.38) 1.30 (1.22-1.38) Leslie WD et al. 2015 JCEM
- 36. Hip Axis Length 67 year old woman T-scores: Total hip -1.6 FRAX: Major 11% Hip 2.7%
- 37. HAL predicts hip fracture independent of FRAX and BMD Leslie WD et al. JCD 2015 3.7%
- 38. Precision of Hip Geometry Parameters Precision % CV %LSC CSA 1.9 to 7.9 5.3 to 21.9 Section Modulus 3.3 to 10.1 9.1 to 28.0 Buckling Ratio 2.8 to 30.6 7.8 to 84.8 CSMI 3.2 to 11.7 8.9 to 32.4 Neck Shaft Angle 0.6 to 2.7 1.7 to 7.5 Hip Axis Length 0.4 to 1.8 1.2 to 5.0 Leslie 2015 ISCD
- 39. ISCD – PDC 2015 Hip axis length (HAL) derived from DXA is associated with hip fracture risk in postmenopausal women. Other hip geometry parameters derived from DXA should not be used to assess hip fracture risk. Hip geometry parameters derived from DXA should not be used to initiate treatment. Hip geometry parameters derived from DXA should not be used for monitoring. Shepherd et al. JCD 2015
- 41. Atypical Femoral Fractures Located in the sub trochanteric region and the diaphysis of the femur Reported in patients in bisphosphonates or denosumad treatment for osteoporosis But do occur in patients NOT taking these drugs Absolute risk of AFF in patients on bisphophonates is low ranging from 3.2 to 50 per 100,000 person-years Long-term use of bisphosphonates may be associated with higher risk approxiamtely 100 per 100,000 person-years First reported in 2005 (Odvina et al. JCEM) Shane et al. JBMR 2014
- 42. ASBMR Task Force 2013 -Revised Case Definition of AFFs The fracture must be located along the femoral diaphysis from just distal to the lesser trochanter to just proximal to the supracondylar flare. In addition, at least four of five Major Features must be present. None of the Minor Features is required but have sometimes been associated with these fractures. Major features 1. The fracture is associated with minimal or no trauma, as in a fall from a standing height or less 2. The fracture line originates at the lateral cortex and is substantially transverse in its orientation, although it may become oblique as it progresses medially across the femur 3. Complete fractures extend through both cortices and may be associated with a medial spike; incomplete fractures involve only the lateral cortex 4. The fracture is noncomminuted or minimally comminuted 5. Localized periosteal or endosteal thickening of the lateral cortex is present at the fracture site (“beaking” or “flaring”) Minor features 1. Generalized increase in cortical thickness of the femoral diaphyses 2. Unilateral or bilateral prodromal symptoms such as dull or aching pain in the groin or thigh 3. Bilateral incomplete or complete femoral diaphysis fractures 4. Delayed fracture healing Shane et al. JBMR 2014
- 43. ASBMR Task Force 2013 -Revised Case Definition of AFFs The fracture must be located along the femoral diaphysis from just distal to the lesser trochanter to just proximal to the supracondylar flare. In addition, at least four of five Major Features must be present. None of the Minor Features is required but have sometimes been associated with these fractures. Major features 1. The fracture is associated with minimal or no trauma, as in a fall from a standing height or less 2. The fracture line originates at the lateral cortex and is substantially transverse in its orientation, although it may become oblique as it progresses medially across the femur 3. Complete fractures extend through both cortices and may be associated with a medial spike; incomplete fractures involve only the lateral cortex 4. The fracture is noncomminuted or minimally comminuted 5. Localized periosteal or endosteal thickening of the lateral cortex is present at the fracture site (“beaking” or “flaring”) Minor features 1. Generalized increase in cortical thickness of the femoral diaphyses 2. Unilateral or bilateral prodromal symptoms such as dull or aching pain in the groin or thigh 3. Bilateral incomplete or complete femoral diaphysis fractures 4. Delayed fracture healing Shane et al. JBMR 2014
- 44. Example of Atypical Femoral fracture Shane et al. JBMR 2014
- 45. Bone Density and AFF
- 46. Whole Femur Imaging with DXA
- 47. Beaking – Quantification with DXA
Editor's Notes
- Good afternoon ladies and gentlemen, Over 20 years ago osteoporosis was conceptually defined as a skeletal disease characterised by low bone mass and micro-architectural deterioration of bone tissue with a consequent increase in bone fragility and susceptibility to fracture.
- A year later it was defined operationally by ……
- For many years DXA has provided the main diagnostic tool for clinicians to diagnose and treat patients with osteoporosis as it’s widely
- And we can see here in this clinical example of a 79 year lady with extremely low bone density at the lumbar spine who when having further imaging we can see the ultimate consequence of osteoporosis – a fracture indeed she has several vertebral fractures
- However, this is not always the case. We can see from data from the EPISEM study that fracture rate goes up exponentially as BMD declines but importantly many fractures occur in women who doe not have operational osteoporosis that is they have a T –score better than -2.5. In this cohort approximately one third of fractures occurred in this group.
- This can be seen in this clinical example of a 40 year old women with frankly normal bone density but again she has evidence of multiple vertebral fractures
- And one may be assured that this 70 year old lady has better than average bone strength on the basis for density, but as with the other 2 ladies she also has multiple vertebral fractures…..
- The problem with DXA is generates a 2-dimensional image of a 3-dimensional structure, amalgamating bone density, bone size, microarchitecture and material properties in to one all encompassing measure areal BMD!
- Can we get around this problem??? If we go back to the original conceptual definition we can see that DXA measures of areal bone density are only concentrating on the aspect of low bone mass, to understand a bones real fragility we must also consider the aspect of micro-architectural deterioration but can we measure this with DXA???
- It’s possible to measure bone micro-architecture with bone biopsy but this is a very invasive option, non-invasively we could use more sophisticated imaging techniques such as HRpQCT to MRI but these are not readily available in a clinical setting.
- Can we estimate bone micro-architecture in –vivo using clinically available technology?
- Well for the last 10 years a novel technique known as trabecular bone scoring has been testing this possibility…
- Trabecular bone scoring known as TBS is a gray…..
- Shown here pictorially is two ladies with the same bone density but vastly different TBS values. The gray-level textural analysis is demonstrated by the experimental variograms
- To try and explain this further, think of the tree analogy. If we take an areal view of the forest we can see the tops of many trees. If we quantify this image we get a metric that is proportional to the number and distribution of the trees. If there are the same number of trees are view as in the lower image then the overall density will be the same in the area measured but the number describing the distribution will be different in simple term TBS is a way of quantifying the aerial view!!!!
- One of the main advantage of TBS is it is processed in the same region of interest as BMD and can easily be performed either at the time of scanning or retrospectively
- He we can see data from the Canadian study of nearly 30,000 women over 50 years of age followed for just over 4.5 years. 1668 osteoporotic fractures were identified. The highest incidence of fracture occurred in women defined operationally as osteoporotic i.e. with a T-score less than 2.5 and with a TBS in the lowest tertile. However, within the same BMD group of either normal, osteopenic or osteoporotic, there is a varying incidence of fracture for the different tiles of TBS.
- From this data and several other large epidemiological studies we can see that independently of age, clinical risk factors and bone density, TBS predicts the risk of fracture at the spine, hip and other major osteoporotic sites – both in women and in men.
- And this risk is modified by age, with reduced TBS having a greater risk of fracture either on its own or when combined with BMD and or clinical risk factors. With all this information on risk it is the feasible to add TBS to our absolute fracture risk assessments. Well as Eugene has so eloquently reported this is indeed the case.
- We can do this because…. TBS yields a risk which is
- He is an example
- Do we treat? Major No – hip fracture yes????
- If we modifit the calclutation with TBS wither a high TBS of 1.5 or a low TBS of 1.1 we can see the effect
- If the lady had a low TBS her risk of fracture would go up and consequently treatment would be recommend for both hip and other fractures. However, if she had a high TBS she would no longer fall in to the treatment threshold for either hip or other major op fractures
- Much work had been done with disease specific groups. Diabetes being one example. In type 1 diabetes people tend to have lower BMD average BMI and an increase risk of fracture. Conversely in type 2 diabetes cases usually report higher than average BMD, have higher BMI’s so in theory their risk of fracture should be lower but what is actually seen is a 1.4 higher than average fracture rate.
- Again using the Canadian data, after adjusting for other clinical risk factors, those with type 2 diabetes had higher bone density at all sites but significantly lower TBS values
- Shown here graphically TBS had significantly higher odds for fracture compared to BMD alone
- Assessing TBS and treatment demonstrates less encouraging results. The graph highlights works from Popp and other on a cohort of women treated with either zoledronate or placebo. As you can see significant improvements were seen in BMD after only 6 months of treatment, where as TBS changed very little over time and if anything was comparable to the placebo treated group? Similar results were seen for other osteoporotic treatments.
- Due to increasing use and the large number of published studies last year the ISCD produced guidelines for its use stating…..
- Although TBS is gaining popularity and use there are other DXA add on which have been proposed to enhance fracture risk, for example assessing hip geometry from the routine DXA scan
- HSA or AHA as its called on the GE systems is not new. It has been an available add on for DXA for over 30 years. It works by estimating the distribution on bone in the femoral neck from the DXA bone profile. From this it can calculate parameters such as CSMI, CSA, bone lengths, bone angles and pseudo strength parameters such as section modulus, fall index and buckling ratio. It has been shown to be a good discriminator of fracture both retrospectively and prospectively
- Looking at it from an individual perspective her are bone density scans of two ladies one aged 74 and still relatively active and one a few years older and significantly less active. Although total BMD is the same, the BMD in the upper portion if the older lady is significantly lower…..
- When these values are included in the calculation we can see that the fall index is substantially lower in the less active lady who given her reduced mobility probably compound her low strength index with an increased propensity to fall – the outcome of which is most likely hip fracture.
- From the Canadian data we can see that although HSA parameters are related to fracture risk, this risk is significantly modified by BMD, with the exception shown in bold of NSA, buckling ratio and HAL
- Looking at HAL taking a 67 year old lady with a moderate risk of fracture
- If we include the fact that her HAL is 9mm above average her fracture risk increases from 2.7% to 3.7% of having a hip fracture in the next 10 years.
- Unfortunately one of the biggest problems with HSA is the poor precision. We can see here that with the exception if HAL and NSA none of the parameters are useful for looking a changes or even differences between groups. These issues and others were considered at the same position development conference as TBS but the outcome for HSA was less favourable….
- The guidelines state…
- Just to end this talk I would like to highlight the newest kid on the block for extended use of DXA
- AFF are….
- In 2010 and then again in 2013 the ASBMR produced a working definition of AFF’s highlighting 5 major features and 4 minor features.
- It is the first of the minor features which is has come to the attention of the DXA manufacturers Generalized increase in cortical thickness of the femoral diaphysis
- There want to be able to use DXA imaging to detect the early signs of cortical changes prevent the ultimate failure and of an AFF – two classic examples…
- Here’s a clinical example
- Hologic are prosing using an extended scan of the femur using their single energy imaging facility…
- And GE are proposing a method to quantify the cortical thickness to pick up the early changes. It’s still early days with both techniques but both look quite promising
- And on that note I would like to end and invite any questions from the audience. Thank you