Glen Blake

Accurate assessment of precision errors: how to measure the reproducibility of bone densitometry techniques.

Assessment of precision errors in bone mineral densitometry is important for characterization of a techniques ability to detect logitudinal skeletal changes. Short-term and long-term precision errors should be calculated as root-mean-square (RMS) averages of standard deviations of repeated measurements (SD) and standard errors of the estimate of changes in bone density with time (SEE), respectively. Inadequate adjustment for degrees of freedom and use of arithmetic means instead of RMS averages may cause underestimation of true imprecision by up to 41% and 25% (for duplicate measurements), respectively. Calculation of confidence intervals of precision errors based on the number of repeated measurements and the number of subjects assessed serves to characterize limitations of precision error assessments. Provided that precision error are comparable across subjects, examinations with a total of 27 degrees of freedom result in an upper 90% confidence limit of +30% of the mean precision error, a level considered sufficient for characterizing technique imprecision. We recommend three (or four) repeated measurements per individual in a subject group of at least 14 individuals to characterize short-term (or long-term) precision of a technique.

Sr-89 therapy: strontium kinetics in disseminated carcinoma of the prostate.

Strontium kinetics were investigated in a group of 14 patients receiving 89Sr palliation for metastatic bone disease secondary to prostatic carcinoma. Using 85Sr as a tracer, total body strontium retention R(t) was monitored for a 3 month period following 89Sr administration, and at 90 days was found to vary from 11% to 88% and to correlate closely with the fraction of the skeleton showing scintigraphic evidence of osteoblastic metastatic involvement. Strontium renal plasma clearance varied from 1.6 l/day to 11.6 l/day, and in nine patients was significantly reduced compared with values found in healthy adult men, probably due to increased renal tubular reabsorption associated with the disturbance of calcium homoeostasis. Renal clearance rate was the principal factor determining R(t) for t<6 days, and was an important secondary factor at later times. Over the interval 30 days t<90 days, R(t) was closely fitted by the power law function R(t)=R30 (t/30)-b, with R30 and b showing the close correlation expected from the effect of R(t) on strontium recycling. The correction of the data for this effect to determine the true skeletal release rate is described. Measurement of localized strontium turnover in individual metastatic deposits from whole body profiles and scintigraphic images gave retention curves that typically rose to a plateau by 10 days after therapy, and then decreased very slowly. In contrast, retention curves for adjacent normal trabecular bone showed more rapid turnover, peaking at 1 day and subsequently decreasing following a t-0.2 power law function. The changes in strontium kinetics found in metastatic bone disease are favourable to the objectives of 89Sr therapy.

Technical principles of dual energy X-ray absorptiometry

Since its introduction nearly ten years ago, dual-energy x-ray absorptiometry (DXA) has become the single most widely used technique for performing bone densitometry studies. One reason for its popularity is the ability of DXA systems to measure bone mineral density (BMD) in the spine and proximal femur, the two most common sites for osteoporotic fractures. Other advantages of DXA include the exceptionally low radiation dose to patients, short scan times, high resolution images, good precision and inherent stability of calibration. For these reasons DXA scans are widely used to diagnose osteoporosis, assist making decisions in treatment, and as a follow-up response to therapy. Another important application has been the use of DXA in many clinical trials of new treatments for osteoporosis. Since the first generation pencil beam DXA systems became available, the most significant technical innovation has been the introduction of fan beam systems with shorter scan times, increased patient throughput, and improved image quality. New clinical applications include the measurement of lateral spine and total body BMD, body composition, and vertebral morphometry. Despite these advances, posteroanterior (PA) spine and proximal femur scans remain the most widely used application because of their utility in treatment decisions and monitoring response to therapy.

Radiation exposure in bone mineral density assessment

Osteoporosis is a systematic skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue which leads to diminished biomechanical competence of the skeleton and low-trauma or atraumatic fractures. Due to increased awareness of the impact of osteoporosis on the elderly population, the use of bone densitometric techniques is becoming more widespread. Considerable progress has been made in the development of non-invasive methods for the assessment of the skeleton. While DXA and QCT are commonly used techniques, the popularity of other approaches such as RA, SXA and QUS is gaining grounds. QCT has an advantage over the other techniques in its ability to measure the true volumetric density of trabecular or cortical bone. We therefore present an overview of these current techniques for bone mineral density (BMD) measurements. In the second section we discuss the radiation doses incurred in BMD measurements by patients and methods for reducing patient and staff radiation exposure are given. Studies of radiation dose to patient from DXA confirms that patient dose is small (0.08-4.6 muSv) compared to that given by many other investigations involving ionizing radiation. Fan beam technology with increased resolution has resulted in increase patient dose radiation dose (6.7-31 muSv) but this is still relatively small. Carrying vertebral morphometry using DXA also incurs less radiation dose (< 60 muSv) than standard lateral radiographs QCT has radiation dose (25-360 muSv) comparable to simple radiological examination such as chest X-ray but lower than imaging CT. Radiation dose from other techniques such as RA and SXA are in the same order of magnitude as pencil beam DXA. For pencil beam DXA and SXA systems the time average dose to staff from scatter is very low even with the operator sitting as close as 1 m from the patient during measurement. However the scatter dose from fan beam DXA systems is considerable higher and approaches limits set by regulator bodies for occupational exposure.

The role of DXA bone density scans in the diagnosis and treatment of osteoporosis

Dual energy x ray absorptiometry (DXA) scans to measure bone mineral density (BMD) at the spine and hip have an important role in the evaluation of individuals at risk of osteoporosis, and in helping clinicians advise patients about the appropriate use of antifracture treatment. Compared with alternative bone densitometry techniques, hip and spine DXA examinations have a number of advantages that include a consensus that BMD results can be interpreted using the World Health Organization T-score definition of osteoporosis, a proven ability to predict fracture risk, proven effectiveness at targeting antifracture therapies, and the ability to monitor response to treatment. This review discusses the evidence for these and other clinical aspects of DXA scanning, including its role in the new WHO algorithm for treating patients on the basis of their individual fracture risk.

Patient dose in dual x-ray absorptiometry

Dual x-ray absorptiometry (DXA) provides a convenient, non-invasive method of assessing skeletal bone mineral which is widely used for clinical studies. This report describes a study to estimate the effective dose of radiation (ICRP-60(1990)) to a typical female patient from scans performed on three DXA scanners: the Hologic QDR-1000, QDR-1000/W and QDR-2000. The scans modes studied were: total body; anteroposterior (AP) lumbar spine; lateral lumbar spine; proximal femur; distal forearm. An ionization chamber and tissue-equivalent phantom were used to determine entrance surface dose and percentage depth-dose curves for each scan mode. Anatomical data from ICRP-23 (Reference Man) and a body section atlas were used to estimate the absorbed dose to each organ in the scan fields. Effective dose was estimated using the ICRP-60 tissue weighting factors and the fraction of each organ in the scan field. Results are summarized below. Figures for the effective dose are given both excluding and (in brackets) including the ovaries to cover the cases of postmenopausal and premenopausal women respectively.

Visual assessment of vertebral deformity by X-ray absorptiometry: A highly predictive method to exclude vertebral deformity

Abstract: The accurate identification of prevalent vertebral fractures is important in both the clinical and research setting as they are associated with increased risk of further fracture and irreversible clinical consequences. This study reports a direct comparison of prevalent vertebral deformity identification using X-ray absorptiometry (XA) scans, acquired on a dual-energy X-ray absorptiometry (DXA) machine, and conventional radiographs in a diverse group of 161 postmenopausal women, ranging from healthy subjects with normal bone mineral density (BMD) to osteoporotic subjects with multiple vertebral deformities. Deformities were identified by a trained operator by visual assessment of the XA scans (VXA) and semiquantitatively by an experienced radiologist on the conventional radiographs (XSQ). Subjects were recruited prospectively and were triaged according to their VXA results into normal, equivocal and definite deformity groups. VXA and XSQ demonstrated good agreement (96.3%, κ= 0.79) in classifying vertebrae as normal or deformed in the 1978 of 2093 vertebrae deemed analyzable on both the XA scans and conventional radiographs. VXA showed good sensitivity (91.9%) in the identification of moderate/severe XSQ deformities and an excellent negative predictive value (98.0%) was produced when VXA was used to distinguish subjects without vertebral deformities from those with possible or definite deformities on a per subject basis. The majority of disagreement between the two methods resulted from different classification of mild wedge and endplate deformities and the poor visualization of upper thoracic vertebrae on the XA scans. Agreement improved, particularly on a per subject basis, when analysis was restricted to the vertebral levels from L4 to T7. Visual triage of XA scans by a trained operator would seem to be swift, convenient and cost-effective method, with excellent negative predictive value, to distinguish subjects with very low risk of vertebral deformities from those with possible deformities. These ‘normal’ subjects can then be excluded prior to performing conventional radiographs and further time-consuming and costly methods of vertebral deformity assessment such as XSQ by an experienced radiologist and/or quantitative morphometry. VXA may prove useful in the clinical evaluation of patients at risk of osteoporosis as an adjunct to BMD scans or in the selection of subjects for osteoporosis-related clinical trials.

Can the WHO criteria for diagnosing osteoporosis be applied to calcaneal quantitative ultrasound

Abstract: With the increasing number of quantitative ultrasound (QUS) devices in use worldwide it is important to develop strategies for the clinical use of QUS. The aims of this study were to examine the age-dependence of T-scores and the prevalence of osteoporosis using the World Health Organization Study Group criteria for diagnosing osteoporosis and to examine the T-score threshold that would be appropriate to identify women at risk of osteoporosis using QUS. Two groups of women were studied: (i) 420 healthy women aged 20–79 years with no known risk factors associated with osteoporosis; (ii) 97 postmenopausal women with vertebral fractures. All subjects had dual-energy X-ray absorptiometry (DXA) measurements of the spine and hip and QUS measurements on three calcaneal ultrasound devices (Hologic Sahara, Hologic UBA575+, Osteometer DTUone). A subgroup of 102 (76 on the DTUone) healthy women aged 20–40 years was used to estimate the young adult mean and SD for each QUS and DXA measurement parameter to calculate T-scores. The age-related decline in T-scores for QUS measurement parameters was half the rate observed for the bone mineral density (BMD) measurements. The average T-score for a woman aged 65 years was –1.2 for QUS measurements and –1.75 for the BMD measurements. When osteoporosis was defined by a T-score ≤–2.5 the prevalence of osteoporosis in healthy postmenopausal women was 17%, 16% and 12% for lumbar spine, femoral neck and total hip BMD respectively. When the same definition was used for QUS measurements the prevalence of osteoporosis ranged from 2% to 8% depending on which ultrasound device and measurement parameter was used. Four different approaches, based on DXA-equivalent prevalence rates of osteoporosis, were utilized to examine which T-score threshold would be appropriate for identifying postmenopausal women at risk of osteoporosis using QUS measurements. These ranged from –1.05 to –2.12 depending upon the approach used to estimate the threshold and on which QUS device the measurements were performed, but all were significantly lower than the threshold of –2.5 used for BMD measurements. In conclusion, the WHO threshold of T=–2.5 for diagnosing osteoporosis requires modification when using QUS to assess skeletal status. For the three QUS devices used in this study, a T-score threshold of –1.80 would result in the same percentage of postmenopausal women classified as osteoporotic as the WHO threshold for BMD measurements. Corresponding T-score thresholds for individual measurement parameters on the two commercially available devices were –1.61, –1.94 and –1.90 for Sahara BUA, SOS and estimated heel BMD respectively and –1.45 and –2.10 for DTU BUA and SOS respectively Additional studies are needed to determine suitable T-score thresholds for other commercial QUS devices.

Quantitative ultrasound and bone mineral density are equally strongly associated with risk factors for osteoporosis

Because resources do not allow all women to be screened for osteoporosis, clinical risk factors are often used to identify those individuals at increased risk of fracture who are then assessed by bone densitometry. The aim of this study was to compare calcaneal quantitative ultrasound (QUS) and axial bone mineral density (BMD) T and Z scores in a large group of women, some with no clinical risk factors and others with one or more risk factors for osteoporosis. The study population consisted of 1115 pre‐ and postmenopausal women. A subgroup of 530 women was used to construct reference data for calculating T and Z scores. A total of 786 women was found to have one or more of the following risk factors: (i) atraumatic fracture since the age of 25 years, (ii) report of X‐ray osteopenia, (iii) predisposing medical condition or use of therapy known to affect bone metabolism, (iv) premature menopause before the age of 45 years or a history of amenorrhea of longer than 6 months duration, (v) family history of osteoporosis, (vi) body mass index (BMI) <20 kg/m2, and (vii) current smoking habit. Calcaneal broadband ultrasound attenuation (BUA) and speed of sound (SOS) measurements were performed on a Hologic Sahara and a DTUone and BMD was measured at the spine and hip using dual‐energy X‐ray absorptiometry (DXA). The Z score decrements associated with the seven risk factors calculated using multivariate regression analysis were similar for QUS and BMD measurements. Z score decrements (mean of BMD and QUS measurements combined) associated with a history of atraumatic fracture (−0.67), X‐ray osteopenia (−0.36), a family history of osteoporosis (−0.23), and a low BMI (−0.53) were all statistically significant compared with women with no risk factors. Z score decrements associated with a medical condition or use of therapy known to affect bone metabolism, a premature menopause or prolonged amenorrhea, or those who were current smokers were not significantly different from zero. As the number of risk factors present in each individual increased, the mean Z score decrements became more negative, increasing from −0.28 for women with one risk factor to −1.19 for those with four or more risk factors. QUS and BMD measurements yielded similar mean Z scores for women with one, two, three, or more than four risk factors. Using the World Health Organization (WHO) criteria to diagnose osteoporosis for BMD measurements and revised diagnostic criteria for QUS, approximately one‐third of postmenopausal women aged 50+ years with clinical risk factors were classified as osteoporotic compared with only 12% of women without clinical risk factors. Over two‐thirds of postmenopausal women with risk factors were classified as osteopenic or osteoporotic and approximately 28% were classified as normal. The proportion of women classified into each diagnostic category was similar for BMD and QUS. In conclusion, clinical risk factors for osteoporosis affected calcaneal BUA and SOS Z score measurements to the same extent as axial BMD Z score measurements. Provided revised diagnostic criteria are adopted for QUS, similar proportions of postmenopausal women are identified as osteopenic or osteoporotic as with BMD.

Screening for Osteopenia and Osteoporosis: Do the Accepted Normal Ranges Lead to Overdiagnosis?

Abstract: Osteoporosis is a common disease which causes significant morbidity and mortality and in many cases may be preventable. In the absence of fragility fractures the accepted method of identifying those at high risk is based upon bone mineral density (BMD) measurements with defined cut-off points. To correctly delineate normal from abnormal, reliable reference ranges appropriate to the observed population are required. We have studied the age-dependent changes in mean BMD and standard deviation at the lumbar spine and femoral neck in a normal population extracted from 4280 women screened for osteopenia and compared our findings with the manufacturers normal range (MNR). The recent World Health Organization criteria for the diagnosis of osteopenia and osteoporosis using the ‘manufacturers young normal’ (MYN) values and our ‘study young normal’ (SYN) values have been applied. The study normal population (SNP) included 2068 women (mixes social class; mean age 53 years, range 30–79 years). The distribution of mean lumbar spine BMD with age in SNP was generally similar to the MNR. In contrast mean femoral neck bone density from SNP was significantly different from the MNR, ranging from 3% to 12% lower in each 5-year group analysed (p < 0.05). Comparison of standard deviations in spine BMD in SNP against the fixed MNR standard deviation showed a statistically significant increase commencing at 45 years of age. The magnitude of this increase appeared to rise with age and remained significant in the 75-to-79-year group (p < 0.05). In contrast, standard deviation in femoral neck BMD in SNP appeared relatively constant with age except in the group of women at and around the time of the menopause. The SYN value for mean lumbar spine BMD was 0.994 g/cm2 (cf. MYN value 1.047, p < 0.0001) with a standard deviation of 0.122 g/cm2 (cf. MYN 0.11, p = 0.0005). Similarly our SYN value for femoral neck BMD was 0.787 (cf. MYN value 0.895, p < 0.0001) with a standard deviation of 0.109 (cf. MYN value 0.10, p = 0.0027). Using SYN values 36% (748) for the spine and 33% for the hip of our normal population are classified as osteopenic or osteoporotic. Using MYN values increases the proportion of women classified as osteopenic or osteoporotic to 52% (1078) for the spine and 68% (1409) for the femur. If both sites of measurement are considered simultaneously SYN classifies 46% (952) as either osteopenic or osteoporotic at one or other site, which is increased to 73% (1513) when the MYN values are used. We observe that manufacturers reference ranges may not be appropriate for the local population and may lead to an erroneously high diagnosis of osteopenia and osteoporosis, which would lead to unnecessary patient anxiety and perhaps errors regarding treatment.