Position StatementSkeletal Sites for Osteoporosis Diagnosis: The 2005 ISCD Official Positions
Introduction
Bone mineral density (BMD) assessed by dual-energy X-ray absorptiometry (DXA) is used to diagnose osteoporosis, assess fracture risk, and monitor changes in BMD over time. The World Health Organization (WHO) has proposed a set of operational criteria to define osteoporosis in postmenopausal Caucasian women (1). The BMD value of an individual is expressed in terms of the number of standard deviations from the mean of a healthy young-adult reference population, commonly referred to as the T-score (1). Osteoporosis has been defined by a T-score that is equal to or less than -2.5. This classification was established based on reference values of BMD measured at the lumbar spine, hip∗ (also referred to as proximal femur), or forearm. The socio-economical emphasis on hip fractures, however, together with studies showing that BMD measured at the proximal femur has the strongest association with hip fracture (2), have focused some clinical guidelines for the assessment of individual patients on BMD measurements made by DXA at the hip 3, 4, 5. Furthermore, the WHO working group did not specify how many skeletal sites to measure, or which region(s) of interest (ROI) within a skeletal site should be used for diagnosis.
To help healthcare providers adequately utilize the multiplicity of skeletal sites measurable by DXA, the ISCD has recommended that BMD should be measured for the purpose of diagnosing osteoporosis at two preferred skeletal sites, the hip and lumbar spine. A third site (33% or one-third radius of the non-dominant forearm) should be investigated if technical problems arise at any of these two primary sites (6). The ISCD recommended that osteoporosis be diagnosed on the basis of the lowest T-score for BMD found at the spine, total hip, femoral neck, and trochanter, and the distal one-third of the radius, if measured (6). This position differs from that of the International Osteoporosis Foundation (IOF), which recommended the use of WHO criteria only at the hip, stating that in all situations this skeletal site would predict osteoporotic fractures as well as for any other skeletal sites (3). While divergence exists in handling discordances among skeletal sites, technical improvements in DXA open new perspectives in the interpretation of DXA scans. The improvement in resolution of the DXA scan renders the search for artifacts more reliable, enabling the exclusion of a single vertebra, for example. Awareness of technical differences among manufacturers, coupled with an increase in patient mobility (e.g., moving from one city to another), has resulted in manufacturers recognizing the importance of finding equivalency links in order to convert BMD values measured on one DXA system into a value that is comparable to another. However, even with progress in this area, problems arise. For example, it is common to observe physicians applying the operational WHO definition of osteoporosis to any skeletal region of interest (ROI), or to convert densitometric GE data to Hologic data without careful consideration, although this is not recommended by any medical society. Potential consequences of such approaches include an important change in the prevalence of osteoporosis according to the choice of the skeletal sites chosen, and an obvious misdiagnosis of the patient (7), possibly leading to a decrease in the credibility of the field of bone densitometry (3). It is therefore crucial that along with advances in DXA technology, practitioners be given updated recommendations to ensure correct use of DXA in clinical patient management.
The following questions regarding skeletal site selection and reference databases were addressed at the 2005 ISCD Position Development Conference, held in Vancouver, British Columbia, Canada, the results of which are presented here.
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Should the lowest T-score of the total proximal femur, femoral neck, trochanter, and spine continue to be used for diagnosis?
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Should the ISCD endorse use of the National Health and Nutrition Examination Survey (NHANES) database for proximal femur T-score derivation?
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Can the WHO classification be applied to a single vertebral body T-score?
Section snippets
Methodology
The methods used to develop, and the grading system applied to these ISCD Official Positions is presented in detail in the Executive Summary that accompanies this paper. Briefly, all Positions were graded on quality of evidence (good, fair, poor), strength of the recommendation (A, B, or C, where A is a strong recommendation supported by the evidence, B is a recommendation supported by the evidence, and C is a recommendation supported primarily by expert opinion), and applicability (worldwide
ISCD Official Positions:
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The WHO international reference standard for osteoporosis diagnosis is a T-score of -2.5 or less at the femoral neck:
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The reference standard from which the T-score is calculated is the female, white, age 20–29 years NHANES III database.
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Grade: Good-A-1
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Osteoporosis may be diagnosed in postmenopausal women and in men age 50 and older if the T-score of the lumbar spine, total hip, or femoral neck is -2.5 or less∗:
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In certain circumstances the 33% radius (also called 1/3 radius) may be utilized.
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Grade:
Rationale
In the past, the ISCD Official Position was to use the lowest T-score of the total proximal femur, femoral neck, trochanter, and posterior/anterior spine for the diagnosis of osteoporosis. In light of current data, the ISCD Official Position has been updated.
Although most studies have treated hip fractures as a homogeneous condition 2, 8, 9, they can be separated into fractures of the cervical region (femoral neck fractures, intracapsular fractures), and fractures of the trochanteric region
Discussion
When extrapolating these data for use in clinical practice, differences in recommendations have arisen concerning the hip ROI to be used (femoral neck, trochanter, or total hip) between the IOF (3) and the ISCD (28). On the technical aspect, one could argue that the lack of complete ROI agreement amongst manufacturers may impact the choice of hip sub-regions in the diagnosis of osteoporosis. Indeed, at this stage, the total hip ROI is one of the most consistent amongst manufacturers; however,
Additional Questions for Future Research
The following suggestions for additional research are listed below, stated in the form of questions, most of which could be investigated with retrospective analyses:
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From meta-analyses comprised of prospective studies, does using the lowest T-score amongst femoral sites improve the fracture prediction?
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Which one of the hip sub-regions better responds to current treatment?
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Due to the heterogeneous nature of their size and placement, is there a difference in rates of response of all sub-regions
ISCD Official Position
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The NHANES III database should be used for T-score derivation at the hip regions.
Grade: Poor C-1
Rationale
Differences in the measurement of BMD and T-scores amongst manufacturers are multifactorial. While technical diversities and differences in ROI exist, the selection of standardized reference databases for the calculation of T-scores could ameliorate some of the differences (7). Unfortunately, different manufacturers use the same names for the hip ROI, when the actual ROI placements and sizes are different. Until standardized ROIs are created by all manufacturers, the role of standardized BMD
Discussion
It has been suggested that the NHANES III database, obtained in the United States, is not necessarily valid in other countries. Furthermore, if one took a BMD value for the total hip that equalled −2.5 on a Hologic machine and converted it to sBMD, then took a value on a Norland or GE Healthcare machine that also equalled −2.5 and converted it to sBMD, the values would not be equal; therefore the NHANES derivation based on sBMD may not be a valid approach. More specifically, Binkley et al
Additional Questions for Future Research
A series of questions should be investigated, mostly in retrospective analyses:
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Should we use a different approach based on the percentage of the young normal mean that would be more appropriate if NHANES cannot be used?
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Would a standardized set of ROI definitions and anatomic positioning (set internal rotation and abduction angles) between manufacturers improve BMD concordance at the femur?
ISCD Official Position
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BMD based diagnostic classifications should not be made using a single vertebra.
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If only one evaluable vertebra remains after excluding other vertebrae, diagnosis should be based on a different valid skeletal site.
Grade: Fair-C-1.
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Anatomically abnormal vertebrae may be excluded from analysis if:
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They are clearly abnormal and non-assessable within the resolution of the system; or
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There is more than a 1.0 T-score difference between the vertebra in question and adjacent vertebrae.
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When vertebrae are
Rationale
In premenopausal women, where hip fracture risk is low, spinal BMD predicts the risk of any fracture as well as, or better than, hip BMD 2, 3. However, in later life, spine BMD measurements are often confounded by osteoarthrosis (39), whereas the hip is much less affected by these changes 40, 41, 42. The latest guidelines published by the ISCD clearly state that when measuring the lumbar spine by DXA one should use all evaluable vertebrae (L1-L4), and only exclude vertebral bodies (VB) that are
Discussion
One should also be cautious not to introduce bias by a systematic selection of the single lowest-density vertebral body, with the assumption that the BMD of all other vertebral bodies is over-estimated due to artefacts. Indeed, it may well be that the lowest vertebral body BMD is the consequence of a metastasis or other structural problems that reduce the apparent BMD. In such a case, the specific vertebra with low apparent BMD should be excluded. The exclusion of anatomically abnormal,
Additional questions for future research
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Do prospective fracture data suggest that the lowest VB has a different RR/SD than the total?
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Does the vertebral body with the lowest T-score fracture first?
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Does L1 increase in BMD faster on current therapies than L4?
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Can any of the medications currently available increase BMD in the spine by more than the LSC of a single vertebral body?
Summary
The ISCD Official Positions provided here address issues with respect to the application of the WHO classifications to specific skeletal sites and regions of interest. While they are made in consideration of best available evidence, they raise several questions that require further research. As knowledge in the field of bone densitometry expands, the Official Positions can be periodically re-evaluated.
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