- Email: [email protected]
Techniques for measuring bone mineral density
International Congress Series 1229 (2002) 63 – 68
Techniques for measuring bone mineral density Jan J. Stepan * 3rd Department of Internal Medicine, Charles University Faculty of Medicine 1, Prague, Czech Republic
Abstract Bone mineral density (BMD) is an accurate and reproducible, non-invasive way of measurement used to diagnose the low bone mass before the first fracture occurs, and as a surrogate for the bone strength to predict an individual’s future fracture risk. In addition, it assists in intervention decisions, and in monitoring the progression or regression of osteoporosis. Techniques for measuring BMD are based on the differential absorption of the ionising radiation, namely the dual energy X-ray absorptiometry (DXA), or modification of the sound waves, the quantitative ultrasonometry (QUS). A decrease in BMD occurring with age depends on a BMD measurement site, measurement technique and the patient’s gender. The WHO criteria are appropriate for assessment of BMD at the posterior – anterior spine, hip, and forearm of postmenopausal Caucasian women using the DXA techniques. Age-standardised risk equivalents to a T score (units of risk) are being developed. Newer techniques, such as QUS, offer the possibility of measuring indices relevant to the fracture risks other than BMD. D 2002 Elsevier Science B.V. All rights reserved. Keywords: Dual energy X-ray absorptiometry; Quantitative computed tomography; Radiographic absorptiometry; Quantitative ultrasonometry; Fracture risk
Evaluation of the bone status in the clinical environment requires that the accurate assessment of all the risk factors for fracture occurrence have been determined. The skeletal risk factors include clinical history and physical examination, bone densitometry, events of previous fractures in a patient’s medical history, and laboratory examination of biochemical and genetic markers. Namely, it is the age that is an important determinant of the fracture risk, which is, in part, independent of the bone mineral density (BMD), so that absolute values for BMD have a different significance at different ages [1]. Approximately
*
Tel.: +420-2-2496-2913; fax: +420-2-2492-2370. E-mail address: [email protected] (J.J. Stepan).
0531-5131/02 D 2002 Elsevier Science B.V. All rights reserved. PII: S 0 5 3 1 - 5 1 3 1 ( 0 1 ) 0 0 4 7 7 - 0
64
J.J. Stepan / International Congress Series 1229 (2002) 63–68
80% of the variance in the bone strength is explained by BMD, and a decrease in BMD for 1 standard deviation is associated with a 1.4- to 2.6-fold increase in the fracture risk for both women and men [2]. Clinical indications for bone densitometry include presence of strong risk factors of osteoporosis, radiological evidence of osteopenia and/or vertebral fracture, previous fragility fracture, and monitoring of the treatment [3]. The choice of an appropriate measurement site or sites for the assessment of the fracture risk may vary, depending on specific medical circumstances of the patient and should, in any given clinical situation, be based on an understanding of the strength and limitations of the different techniques. The majority of available techniques for measuring BMD is based upon the differential absorption of the ionising radiation. The dual energy X-ray absorptiometry (DXA) is based on the use of photons emitted at two different energies, which allows measurements on the sites with the uneven soft tissue composition to be performed. DXA yields a high precision and enables fast scanning. BMD (expressed in g/cm2) is generally measured at two different sites, which are, conventionally, the poster– anterior (PA) lumbar spine and proximal femur, but BMD can actually be measured regionally at any site. The major advances that have occurred over the past decade include: (i) third-generation densitometers permitting axial scans to be obtained in time intervals shorter than 30 s by the use of the fan-beam X-ray geometry with array detectors (the radiation dose being 10 – 50 higher than that of pencil-beam scanners); (ii) improved differentiation of the bone from the adjacent soft tissue; and (iii) an improved and highly automated identification of regions of interest (femur neck, trochanter), and incorporation of ‘‘operator assistance’’ in the software to help maintain ideal scan acquisition and better scan analysis. Of the recent innovations, the array detector based on cadmium zinc telluride allows rapid photon counting and permits scanning at high speeds but, more importantly, with a 5– 10 lower dose of irradiation than conventional fan-beam densitometers [4]. The total femur region has been accepted as a standard measurement site (less influenced by positioning, 1% precision better than for the femur neck). The diagnostic sensitivity of the total body BMD determination is comparable to that of the axial skeleton. This measurement is commonly used in paediatric medicine, endocrine and gastrointestinal disorders, and in clinical trials for antiosteoporotic agents. The capability of DXA instrumentation to evaluate the body composition is extremely desirable, not only from a clinical point of view, but also for research on growth hormone, steroids, etc. Lateral spine measurements avoid osteophytes and other posterior artefacts, frequently seen in patients over the age of 70. However, the lateral spine has not been established as a standard measurement site because it is less sensitive to the monitoring of bone changes compared to the PA spine BMD. The DEXA approach is utilised also for the appendicular skeleton (forearm, heel) measurements. Densitometers with area detectors and cone-beam X-ray geometry allow scanning of the appendicular skeleton within 5 – 10 s. In clinical practice, vertebral fractures may be neglected due to the inconvenience, expense and radiation concerns associated with the conventional radiography imaging and vertebral morphometry of the spine, especially in patients with no serious symptoms. Consequently, only one in three vertebral fractures is clinically recognised. The fast, highresolution fan-beam image obtained by third-generation densitometers does allow the clinician to visualise the entire spine using a low radiation dose which represents
J.J. Stepan / International Congress Series 1229 (2002) 63–68
65
approximately a mere 1% of the dose to which the patient is usually exposed during conventional X-rays. The Instant Vertebral Assessment (Hologic), or Lateral Vertebral Assessment (Lunar) [5], enables the fracture status to be determined during the same visit as the BMD test is done. This further improves the risk assessment, selection of candidates for intervention, patient’s understanding of the consequences of osteoporosis and patient’s long-term compliance and their adherence to the treatment. A negative study may essentially rule out vertebral fracture. Only a positive study needs confirmation using conventional rigid morphometric criteria to avoid overestimation of fracture occurrence. The combination of the data obtained from the low BMD measurement with those obtained from the fracture assessment represents a more powerful predictor for a prospective occurrence of future fractures than BMD alone. Independent of the low BMD, an existing vertebral fracture is associated with a 4 – 5-fold increase in additional spine fracture risk and yields the information representing a two-fold increase in the risk of a prospective subsequential hip fracture [6]. This is extremely important because it is the patient with the low BMD and previous vertebral fractures who would benefit the most from the therapy. Quantitative computed tomography (QCT) has an advantage over the other techniques in its ability to measure the true volumetric density (expressed in mg/cm3). Furthermore, the trabecular bone located in the lumbar spine (L1– L3) can be measured independently of the surrounding cortical bone. However, QCT scanning generally allows less precision with a longer scanning time and with a higher radiation dose than it does during DXA measurements. The major source of error in the single energy QCT systems is the presence of fat in the bone marrow. The spine QCT may be used as a primary diagnostic method in patients with severe degenerative disease of the spine, scoliosis, lumbar compression fractures, or obesity. However, diagnostic criteria are not well established and, using WHO criteria, is not appropriate. Of the most recent innovations, the automated scanning and analysis software and dual-energy modes improve precision and reduce the radiation dose. The femur software is currently being developed. Peripheral QCT allows selective measurement of the trabecular bone (direct visualisation of trabecular number and separation) and the true volumetric BMD of the forearm (minimum impact of degenerative changes). Low radiation dose and independence on bone size during the measurement may be valuable for the diagnosis of low bone mass in children [7]. High-resolution CT and high-resolution magnetic resonance image represent promising methods for a quantitative assessment of a microstructure of the trabecular bone in vivo. Radiographic absorptiometry (RA) compares the optical density of the region of interest using a standard X-ray of the hand and forearm (in some instruments one or three phalanges) with the calibration standard (aluminium wedge) that is included in the exposure field and calculates BMD [8]. Either film or digital images are acquired and analysed locally; films can also be sent to a processing centre for analysis. Quantitative ultrasonometry (QUS) uses sound waves (mechanical vibrations) that pass through the bone at a rate which is dependent on its structural characteristics. Modification of the waves (the frequency dependence of the broadband ultrasound attenuation, BUA, and speed of sound, SOS) are influenced not only by BMD but also by the bone microstructure (acoustic anisotropy). BUA has been related to trabecular separation, connectivity and orientation, and SOS to the elasticity of bone and trabecular separation.
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J.J. Stepan / International Congress Series 1229 (2002) 63–68
The correlation between QUS and BMD measurements at the same (calcaneal) site is in a range of 0.5– 0.8, suggesting that part of the variability of QUS and BMD measurements is unrelated. This is in turn consistent with the ultrasound assessment of other indices of the bone strength, such as the microarchitecture. Consequently, QUS parameters have been shown to be related to the risk of fracture independent of BMD. However, QUS devices vary with regard to technology, site (calcaneus, tibia, radius, phalanges), transducer coupling (gel or water), data acquisition (fixed single point or imaging), definitions of velocity and attenuation, sound frequencies and calibration methods [9]. The recent innovations include axial reflective SOS measurements, further analysis of the transmitted signal (ultrasonography) [10], and the measurement of the ultrasound backscatter and acoustic microscopy using high frequency ultrasound. QUS is less expensive than DXA or QCT, avoids ionising radiation, and is relatively portable. However, QUS has a generally poorer precision than DXA. As in the case of BMD, QUS measurement values have been shown to decrease with the age. Currently, there is no agreement on how results of QUS devices should be interpreted in order to diagnose osteoporosis. However, performance of several QUS devices to predict the risk of osteoporotic fractures equals that of the best DXA approaches. More data on the QUS ability to monitor the changes during the treatment need to be obtained. The association between BMD and the fracture risks is continuous and, consequently, there is no single cut-off point, below which a fracture will occur and above which it will not. The WHO classification describes a severity of the disease rather than an intervention threshold. BMD and risk of the fracture occurrence are used to stratify an individual according to the BMD values obtained from the measurements performed on the young population rather than that on age-matched subjects [3]. Using DXA of the hip, spine or forearm, T score < 2.5 identifies approximately 30% of postmenopausal women as having osteoporosis, and approximates an equivalent lifetime fracture risk for femur neck, spine or forearm fracture to be about 16 –18%. The femur neck BMD can be combined with other risk factors to give a 5-year, or even a lifetime, risk prediction for the hip fracture [11]. For global fracture risk assessment, any skeletal site provides useful information. Therefore, the first preference for fracture risk assessment for a specific skeletal site is the measurement directly at this site of interest. Although BMD is currently being considered as the best predictor for a prospective future fracture, the changes in BMD in response to different antiresorptive agents significantly underestimate the subsequently observed reduction in vertebral fractures. The diagnosis based on BMD alone is limited. A low BMD, considered in isolation, does not equate with osteoporosis and does not allow classification of osteoporosis into primary and secondary types. Some other limitations of BMD measurements have already been resolved. Different results obtained from measurements performed by the DXA devices, which were supplied by different manufacturers, have been caused by the different equipment design (e.g., edge detection, regions of interest) and have been corrected using standardised BMD (sBMD) based on regression equations for spine and total femur scans. A comparison of the sBMD values to a standardised reference database (NHANES III) enables the determination of standardised T scores and thereby the correction for differences in the reference populations studied by the different DXA manufacturers for determining their normal ranges (and hence means and SD) for the hip.
J.J. Stepan / International Congress Series 1229 (2002) 63–68
67
More importantly, decrease in BMD with age depends on a BMD measurement site, measurement technique and gender which causes serious limitations of diagnosis based on the BMD measurement [3]. The discrepancies between BMD measured at different skeletal sites are related to both accuracy errors of the measurements, and different rates of bone loss at sites with different proportions of the cortical and trabecular bone [12]. The problem is further confounded by the additional parameters measured by a variety of ultrasound devices. The WHO criteria are appropriate for assessment of BMD at the posterior –anterior spine, hip, and forearm of postmenopausal Caucasian women using the DXA techniques. The WHO criteria are unsuitable for men, premenopausal women, nonCaucasian populations, for skeletal sites other than PA spine, hip, and forearm (i.e., DXA of lateral spine, total body, heel, finger) and technologies other than DXA (i.e., QCT, RA and quantitative ultrasonometry). To correct this situation, age-standardised risk equivalents to a T score (units of risk) are being developed for measurements using different techniques. The absolute risk, i.e., the probability of fractures for a given value at a given age, might enable a more accurate estimation of the risk to be made as well as more interventions for individual patients [11]. Kanis and Gluer [3] have suggested that the probability of fractures be based over 10 years. This is a more realistic approach compared to the lifetime risk of fracture [13]. The clinical usefulness of this new approach has to be validated. It is important that no diagnostic thresholds are confused with intervention thresholds, which depend not only on the risk of fracture and life expectancy, but also on the benefits, side effects and costs of interventions [3]. In conclusion, the measurement of BMD remains the best method for diagnosing osteoporosis and for prospective fracture prediction, and, importantly, provides information that can affect the patient’s management. Newer techniques, such as ultrasound, appear to be promising tools which could be used for a measurement of the indices other than BMD that are relevant to fracture risk.
References [1] C.E. De Laet, B.A. Van Hout, H. Burger, A.E. Weel, A. Hofman, H.A. Pols, Hip fracture prediction in elderly men and women: validation in the Rotterdam study, J. Bone Miner. Res. 13 (1998) 1587 – 1593. [2] D. Marshall, O. Johnell, H. Wedel, Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures, Br. Med. J. 12 (1996) 1254 – 1259. [3] J.A. Kanis, C.C. Gluer, An update on the diagnosis and assessment of osteoporosis with densitometry, Osteoporosis Int. 11 (2000) 192 – 202. [4] R.B. Mazess, J.A. Hanson, R. Payne, R. Nord, M. Wilson, Axial and total-body bone densitometry using a narrow-angle fan-beam, Osteoporosis Int. 11 (2000) 158 – 166. [5] N. Crabtree, J. Wright, A. Walgrove, J. Rea, L. Hanratty, M. Lunt, I. Fogelman, R. Palmer, M. Vickers, J.E. Compston, J. Reeve, Vertebral morphometry: repeat scan precision using the Lunar Expert-XL and the Hologic 4500A, A study for the ‘WISDOM’ RCT of hormone replacement therapy, Osteoporosis Int. 11 (2000) 537 – 543. [6] C.M. Klotzbuecher, P.D. Ross, P.B. Landsman, T.A. Abbott III, M. Berger, Patients with prior fractures have an increased risk of future fractures: a summary of the literature and statistical synthesis, J. Bone Miner. Res. 15 (4) (2000) 721 – 727. [7] T.L. Binkley, B.L. Specker, pQCT measurement of bone parameters in young children: validation of technique, J. Clin. Densitom. 3 (2000) 9 – 14. [8] P.D. Ross, Radiographic absorptiometry for measuring bone mass, Osteoporosis Int. 7 (1997) S103 – S107.
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J.J. Stepan / International Congress Series 1229 (2002) 63–68
[9] C.C. Glu¨er for the International Quantitative Ultrasound Consensus Group, Quantitative ultrasound techniques for the assessment of osteoporosis: expert agreement on current status, J. Bone Miner. Res. 12 (1997) 1280 – 1288. [10] P. Hadji, O. Hars, M. Schuler, K. Bock, C. Wuster, G. Emons, K.D. Schulz, Assessment by quantitative ultrasonometry of the effects of hormone replacement therapy on bone mass, Am. J. Obstet. Gynecol. 182 (2000) 529 – 534. [11] J.A. Kanis, O. Johnell, A. Oden, B. Jonsson, A. Dawson, W. Dere, Risk of hip fracture derived from relative risks: an analysis applied to the population of Sweden, Osteoporosis Int. 11 (2000) 120 – 127. [12] M.E. Arlot, E. Sornay-Rendu, P. Garnero, B. Vey-Marty, P.D. Delmas, Apparent pre- and postmenopausal bone loss evaluated by DXA at different skeletal sites in women: the OFELY cohort, J. Bone Miner. Res. 12 (1997) 683 – 690. [13] T.A. Abbott, P.D. Ross, A simple clinical tool for estimating lifetime fracture risk from age, bone density and other risk factors, Calcif. Tissue Int. 64 (1999) S1 – S42.
Techniques for measuring bone mineral density Jan J. Stepan * 3rd Department of Internal Medicine, Charles University Faculty of Medicine 1, Prague, Czech Republic
Abstract Bone mineral density (BMD) is an accurate and reproducible, non-invasive way of measurement used to diagnose the low bone mass before the first fracture occurs, and as a surrogate for the bone strength to predict an individual’s future fracture risk. In addition, it assists in intervention decisions, and in monitoring the progression or regression of osteoporosis. Techniques for measuring BMD are based on the differential absorption of the ionising radiation, namely the dual energy X-ray absorptiometry (DXA), or modification of the sound waves, the quantitative ultrasonometry (QUS). A decrease in BMD occurring with age depends on a BMD measurement site, measurement technique and the patient’s gender. The WHO criteria are appropriate for assessment of BMD at the posterior – anterior spine, hip, and forearm of postmenopausal Caucasian women using the DXA techniques. Age-standardised risk equivalents to a T score (units of risk) are being developed. Newer techniques, such as QUS, offer the possibility of measuring indices relevant to the fracture risks other than BMD. D 2002 Elsevier Science B.V. All rights reserved. Keywords: Dual energy X-ray absorptiometry; Quantitative computed tomography; Radiographic absorptiometry; Quantitative ultrasonometry; Fracture risk
Evaluation of the bone status in the clinical environment requires that the accurate assessment of all the risk factors for fracture occurrence have been determined. The skeletal risk factors include clinical history and physical examination, bone densitometry, events of previous fractures in a patient’s medical history, and laboratory examination of biochemical and genetic markers. Namely, it is the age that is an important determinant of the fracture risk, which is, in part, independent of the bone mineral density (BMD), so that absolute values for BMD have a different significance at different ages [1]. Approximately
*
Tel.: +420-2-2496-2913; fax: +420-2-2492-2370. E-mail address: [email protected] (J.J. Stepan).
0531-5131/02 D 2002 Elsevier Science B.V. All rights reserved. PII: S 0 5 3 1 - 5 1 3 1 ( 0 1 ) 0 0 4 7 7 - 0
64
J.J. Stepan / International Congress Series 1229 (2002) 63–68
80% of the variance in the bone strength is explained by BMD, and a decrease in BMD for 1 standard deviation is associated with a 1.4- to 2.6-fold increase in the fracture risk for both women and men [2]. Clinical indications for bone densitometry include presence of strong risk factors of osteoporosis, radiological evidence of osteopenia and/or vertebral fracture, previous fragility fracture, and monitoring of the treatment [3]. The choice of an appropriate measurement site or sites for the assessment of the fracture risk may vary, depending on specific medical circumstances of the patient and should, in any given clinical situation, be based on an understanding of the strength and limitations of the different techniques. The majority of available techniques for measuring BMD is based upon the differential absorption of the ionising radiation. The dual energy X-ray absorptiometry (DXA) is based on the use of photons emitted at two different energies, which allows measurements on the sites with the uneven soft tissue composition to be performed. DXA yields a high precision and enables fast scanning. BMD (expressed in g/cm2) is generally measured at two different sites, which are, conventionally, the poster– anterior (PA) lumbar spine and proximal femur, but BMD can actually be measured regionally at any site. The major advances that have occurred over the past decade include: (i) third-generation densitometers permitting axial scans to be obtained in time intervals shorter than 30 s by the use of the fan-beam X-ray geometry with array detectors (the radiation dose being 10 – 50 higher than that of pencil-beam scanners); (ii) improved differentiation of the bone from the adjacent soft tissue; and (iii) an improved and highly automated identification of regions of interest (femur neck, trochanter), and incorporation of ‘‘operator assistance’’ in the software to help maintain ideal scan acquisition and better scan analysis. Of the recent innovations, the array detector based on cadmium zinc telluride allows rapid photon counting and permits scanning at high speeds but, more importantly, with a 5– 10 lower dose of irradiation than conventional fan-beam densitometers [4]. The total femur region has been accepted as a standard measurement site (less influenced by positioning, 1% precision better than for the femur neck). The diagnostic sensitivity of the total body BMD determination is comparable to that of the axial skeleton. This measurement is commonly used in paediatric medicine, endocrine and gastrointestinal disorders, and in clinical trials for antiosteoporotic agents. The capability of DXA instrumentation to evaluate the body composition is extremely desirable, not only from a clinical point of view, but also for research on growth hormone, steroids, etc. Lateral spine measurements avoid osteophytes and other posterior artefacts, frequently seen in patients over the age of 70. However, the lateral spine has not been established as a standard measurement site because it is less sensitive to the monitoring of bone changes compared to the PA spine BMD. The DEXA approach is utilised also for the appendicular skeleton (forearm, heel) measurements. Densitometers with area detectors and cone-beam X-ray geometry allow scanning of the appendicular skeleton within 5 – 10 s. In clinical practice, vertebral fractures may be neglected due to the inconvenience, expense and radiation concerns associated with the conventional radiography imaging and vertebral morphometry of the spine, especially in patients with no serious symptoms. Consequently, only one in three vertebral fractures is clinically recognised. The fast, highresolution fan-beam image obtained by third-generation densitometers does allow the clinician to visualise the entire spine using a low radiation dose which represents
J.J. Stepan / International Congress Series 1229 (2002) 63–68
65
approximately a mere 1% of the dose to which the patient is usually exposed during conventional X-rays. The Instant Vertebral Assessment (Hologic), or Lateral Vertebral Assessment (Lunar) [5], enables the fracture status to be determined during the same visit as the BMD test is done. This further improves the risk assessment, selection of candidates for intervention, patient’s understanding of the consequences of osteoporosis and patient’s long-term compliance and their adherence to the treatment. A negative study may essentially rule out vertebral fracture. Only a positive study needs confirmation using conventional rigid morphometric criteria to avoid overestimation of fracture occurrence. The combination of the data obtained from the low BMD measurement with those obtained from the fracture assessment represents a more powerful predictor for a prospective occurrence of future fractures than BMD alone. Independent of the low BMD, an existing vertebral fracture is associated with a 4 – 5-fold increase in additional spine fracture risk and yields the information representing a two-fold increase in the risk of a prospective subsequential hip fracture [6]. This is extremely important because it is the patient with the low BMD and previous vertebral fractures who would benefit the most from the therapy. Quantitative computed tomography (QCT) has an advantage over the other techniques in its ability to measure the true volumetric density (expressed in mg/cm3). Furthermore, the trabecular bone located in the lumbar spine (L1– L3) can be measured independently of the surrounding cortical bone. However, QCT scanning generally allows less precision with a longer scanning time and with a higher radiation dose than it does during DXA measurements. The major source of error in the single energy QCT systems is the presence of fat in the bone marrow. The spine QCT may be used as a primary diagnostic method in patients with severe degenerative disease of the spine, scoliosis, lumbar compression fractures, or obesity. However, diagnostic criteria are not well established and, using WHO criteria, is not appropriate. Of the most recent innovations, the automated scanning and analysis software and dual-energy modes improve precision and reduce the radiation dose. The femur software is currently being developed. Peripheral QCT allows selective measurement of the trabecular bone (direct visualisation of trabecular number and separation) and the true volumetric BMD of the forearm (minimum impact of degenerative changes). Low radiation dose and independence on bone size during the measurement may be valuable for the diagnosis of low bone mass in children [7]. High-resolution CT and high-resolution magnetic resonance image represent promising methods for a quantitative assessment of a microstructure of the trabecular bone in vivo. Radiographic absorptiometry (RA) compares the optical density of the region of interest using a standard X-ray of the hand and forearm (in some instruments one or three phalanges) with the calibration standard (aluminium wedge) that is included in the exposure field and calculates BMD [8]. Either film or digital images are acquired and analysed locally; films can also be sent to a processing centre for analysis. Quantitative ultrasonometry (QUS) uses sound waves (mechanical vibrations) that pass through the bone at a rate which is dependent on its structural characteristics. Modification of the waves (the frequency dependence of the broadband ultrasound attenuation, BUA, and speed of sound, SOS) are influenced not only by BMD but also by the bone microstructure (acoustic anisotropy). BUA has been related to trabecular separation, connectivity and orientation, and SOS to the elasticity of bone and trabecular separation.
66
J.J. Stepan / International Congress Series 1229 (2002) 63–68
The correlation between QUS and BMD measurements at the same (calcaneal) site is in a range of 0.5– 0.8, suggesting that part of the variability of QUS and BMD measurements is unrelated. This is in turn consistent with the ultrasound assessment of other indices of the bone strength, such as the microarchitecture. Consequently, QUS parameters have been shown to be related to the risk of fracture independent of BMD. However, QUS devices vary with regard to technology, site (calcaneus, tibia, radius, phalanges), transducer coupling (gel or water), data acquisition (fixed single point or imaging), definitions of velocity and attenuation, sound frequencies and calibration methods [9]. The recent innovations include axial reflective SOS measurements, further analysis of the transmitted signal (ultrasonography) [10], and the measurement of the ultrasound backscatter and acoustic microscopy using high frequency ultrasound. QUS is less expensive than DXA or QCT, avoids ionising radiation, and is relatively portable. However, QUS has a generally poorer precision than DXA. As in the case of BMD, QUS measurement values have been shown to decrease with the age. Currently, there is no agreement on how results of QUS devices should be interpreted in order to diagnose osteoporosis. However, performance of several QUS devices to predict the risk of osteoporotic fractures equals that of the best DXA approaches. More data on the QUS ability to monitor the changes during the treatment need to be obtained. The association between BMD and the fracture risks is continuous and, consequently, there is no single cut-off point, below which a fracture will occur and above which it will not. The WHO classification describes a severity of the disease rather than an intervention threshold. BMD and risk of the fracture occurrence are used to stratify an individual according to the BMD values obtained from the measurements performed on the young population rather than that on age-matched subjects [3]. Using DXA of the hip, spine or forearm, T score < 2.5 identifies approximately 30% of postmenopausal women as having osteoporosis, and approximates an equivalent lifetime fracture risk for femur neck, spine or forearm fracture to be about 16 –18%. The femur neck BMD can be combined with other risk factors to give a 5-year, or even a lifetime, risk prediction for the hip fracture [11]. For global fracture risk assessment, any skeletal site provides useful information. Therefore, the first preference for fracture risk assessment for a specific skeletal site is the measurement directly at this site of interest. Although BMD is currently being considered as the best predictor for a prospective future fracture, the changes in BMD in response to different antiresorptive agents significantly underestimate the subsequently observed reduction in vertebral fractures. The diagnosis based on BMD alone is limited. A low BMD, considered in isolation, does not equate with osteoporosis and does not allow classification of osteoporosis into primary and secondary types. Some other limitations of BMD measurements have already been resolved. Different results obtained from measurements performed by the DXA devices, which were supplied by different manufacturers, have been caused by the different equipment design (e.g., edge detection, regions of interest) and have been corrected using standardised BMD (sBMD) based on regression equations for spine and total femur scans. A comparison of the sBMD values to a standardised reference database (NHANES III) enables the determination of standardised T scores and thereby the correction for differences in the reference populations studied by the different DXA manufacturers for determining their normal ranges (and hence means and SD) for the hip.
J.J. Stepan / International Congress Series 1229 (2002) 63–68
67
More importantly, decrease in BMD with age depends on a BMD measurement site, measurement technique and gender which causes serious limitations of diagnosis based on the BMD measurement [3]. The discrepancies between BMD measured at different skeletal sites are related to both accuracy errors of the measurements, and different rates of bone loss at sites with different proportions of the cortical and trabecular bone [12]. The problem is further confounded by the additional parameters measured by a variety of ultrasound devices. The WHO criteria are appropriate for assessment of BMD at the posterior –anterior spine, hip, and forearm of postmenopausal Caucasian women using the DXA techniques. The WHO criteria are unsuitable for men, premenopausal women, nonCaucasian populations, for skeletal sites other than PA spine, hip, and forearm (i.e., DXA of lateral spine, total body, heel, finger) and technologies other than DXA (i.e., QCT, RA and quantitative ultrasonometry). To correct this situation, age-standardised risk equivalents to a T score (units of risk) are being developed for measurements using different techniques. The absolute risk, i.e., the probability of fractures for a given value at a given age, might enable a more accurate estimation of the risk to be made as well as more interventions for individual patients [11]. Kanis and Gluer [3] have suggested that the probability of fractures be based over 10 years. This is a more realistic approach compared to the lifetime risk of fracture [13]. The clinical usefulness of this new approach has to be validated. It is important that no diagnostic thresholds are confused with intervention thresholds, which depend not only on the risk of fracture and life expectancy, but also on the benefits, side effects and costs of interventions [3]. In conclusion, the measurement of BMD remains the best method for diagnosing osteoporosis and for prospective fracture prediction, and, importantly, provides information that can affect the patient’s management. Newer techniques, such as ultrasound, appear to be promising tools which could be used for a measurement of the indices other than BMD that are relevant to fracture risk.
References [1] C.E. De Laet, B.A. Van Hout, H. Burger, A.E. Weel, A. Hofman, H.A. Pols, Hip fracture prediction in elderly men and women: validation in the Rotterdam study, J. Bone Miner. Res. 13 (1998) 1587 – 1593. [2] D. Marshall, O. Johnell, H. Wedel, Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures, Br. Med. J. 12 (1996) 1254 – 1259. [3] J.A. Kanis, C.C. Gluer, An update on the diagnosis and assessment of osteoporosis with densitometry, Osteoporosis Int. 11 (2000) 192 – 202. [4] R.B. Mazess, J.A. Hanson, R. Payne, R. Nord, M. Wilson, Axial and total-body bone densitometry using a narrow-angle fan-beam, Osteoporosis Int. 11 (2000) 158 – 166. [5] N. Crabtree, J. Wright, A. Walgrove, J. Rea, L. Hanratty, M. Lunt, I. Fogelman, R. Palmer, M. Vickers, J.E. Compston, J. Reeve, Vertebral morphometry: repeat scan precision using the Lunar Expert-XL and the Hologic 4500A, A study for the ‘WISDOM’ RCT of hormone replacement therapy, Osteoporosis Int. 11 (2000) 537 – 543. [6] C.M. Klotzbuecher, P.D. Ross, P.B. Landsman, T.A. Abbott III, M. Berger, Patients with prior fractures have an increased risk of future fractures: a summary of the literature and statistical synthesis, J. Bone Miner. Res. 15 (4) (2000) 721 – 727. [7] T.L. Binkley, B.L. Specker, pQCT measurement of bone parameters in young children: validation of technique, J. Clin. Densitom. 3 (2000) 9 – 14. [8] P.D. Ross, Radiographic absorptiometry for measuring bone mass, Osteoporosis Int. 7 (1997) S103 – S107.
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