Pancreas fat quantification with quantitative CT: an MRI correlation analysis.

AIM: To assess the fat content of the pancreas using quantitative computed tomography (QCT) and to correlate the results with chemical-shift-encoded magnetic resonance imaging (CSE-MRI) measurements of proton density fat fraction (PDFF). MATERIAL AND METHODS: Institutional review board approval for this research was obtained and 52 participants (25 men, 27 women; mean age 35.1 years; age range 22-50 years), who were enrolled in the Prospective Urban Rural Epidemiology (PURE) Study, underwent QCT and CSE-MRI for quantification of fat content in the pancreas. Two observers placed regions of interest (area of 100-130 mm2) in the head, body, and tail of the pancreas as closely matched as possible on the two scans. Pearson correlation and Bland-Altman analysis were performed to evaluate the correlation between the QCT and CSE-MRI measurements and the systematic difference between the two techniques. RESULTS: The QCT and CSE-MRI measurements of pancreatic fat content were well correlated (r=0.805, p<0.0001), although Bland-Altman analysis showed that the QCT measurements were systematically lower by 6.3% compared to CSE-MRI PDFF. CONCLUSION: In conclusion, the results of this study suggest good correlation between QCT and CSE-MRI measurements of pancreatic fat content. Further studies are required to improve the numerical agreement of QCT measurements with PDFF.

Differences in regional bone metabolism at the spine and hip: a quantitative study using (18)F-fluoride positron emission tomography.

SUMMARY: This study showed that regional bone blood flow and (18)F-fluoride bone plasma clearance measured by positron emission tomography are three times lower at the hip than the lumbar spine. INTRODUCTION: Measurements of effective bone plasma flow (K (1)), bone plasma clearance (K ( i )) and standardised uptake values (SUV) using (18)F-fluoride positron emission tomography ((18)F-PET) provide a useful means of studying regional bone metabolism at different sites in the skeleton. This study compares the regional (18)F-fluoride kinetics and SUV at the hip and lumbar spine (LS). METHODS: Twelve healthy postmenopausal women with no history of metabolic bone disease apart from two with untreated osteoporosis were recruited. Each subject underwent 60-min dynamic (18)F-PET scans at the LS and proximal femur two weeks apart. K (1), K ( i ) and SUV were measured at the LS (mean of L(1)-L(4)), femoral neck (FN), total hip (TH) and femoral shaft (FS). Differences between sites were assessed using the nonparametric Kruskal-Wallis test with a Bonferroni correction for multiple comparisons. RESULTS: Values of K (1), K ( i ) and SUV at the FN, TH and FS were three times lower than at the LS (p = 0.003). Amongst the proximal femur sites, K ( i ) and SUV were lower at the FS compared with the FN and TH, and SUV was lower at the TH compared with the FN (all p < 0.05). The volume of distribution was lower at the TH and FS compared with the LS (p < 0.05). CONCLUSION: The lower values of K (1), K ( i ) and SUV at the hip suggest that lower bone blood flow in the proximal femur is an important factor explaining the principal reason for the differences in bone fluoride kinetics between the LS and hip sites.

Precision of ¹8F-fluoride PET skeletal kinetic studies in the assessment of bone metabolism.

UNLABELLED: We assessed the precision of lumbar spine (18)F-PET measurements based on 58 scans performed on 20 postmenopausal women. The percentage coefficient of variation (%CV) (95% confidence interval) was 9.2% (7.5-11.8) for standardised uptake values, 11.7% (9.5-14.9) for plasma clearance measurements using the Patlak method and 14.5% (11.7-18.5) for plasma clearance measurements using the Hawkins three-compartment model. INTRODUCTION: (18)F-Fluoride positron emission tomography ((18)F-PET) is a non-invasive technique that allows the assessment of regional bone turnover in patients with metabolic bone disease. Knowledge of the precision errors of (18)F-PET measurements is important for planning the number of subjects required for research studies. METHODS: Twenty osteoporotic postmenopausal women had (18)F-PET scans of the lumbar spine at 0, 6 and 12 months after stopping long-term bisphosphonate treatment. No significant changes in the PET measurements were seen over the 12-month period, and the data were deemed suitable for a precision study. Precision errors were evaluated for standardised uptake values (SUVs) and for the fluoride plasma clearance to bone mineral (K (i)) determined using the Patlak and Hawkins methods. Precision errors were expressed as the %CV and were calculated for the mean L1-L4 region and for individual vertebrae. RESULTS: %CV (95% confidence interval) for the L1-L4 region was 9.2% (7.5-11.8) for SUV, 11.7% (9.5-14.9) for K (i) measured using the Patlak method and 14.5% (11.7-18.5) for K (i) measured using the Hawkins method. There was no significant difference between precision errors obtained for the L1-L4 region and those obtained for a single vertebra. CONCLUSIONS: SUV measurements showed the smallest precision error followed by the Patlak method, while the Hawkins method gave the largest error. Measuring a smaller region of interest did not increase the precision error, suggesting that the factor determining the errors may be scanner calibration.

Regional bone metabolism at the lumbar spine and hip following discontinuation of alendronate and risedronate treatment in postmenopausal women.

UNLABELLED: The aim of this study was to examine the effects of bisphosphonate discontinuation on bone metabolism at the spine and hip measured using (18) F-fluoride PET. Bone metabolism at the spine remained stable following discontinuation of alendronate and risedronate at 1 year but increased in the hip in the alendronate group only. INTRODUCTION: Bisphosphonates such as alendronate (ALN) or risedronate (RIS) have persistent effects on spine BMD following discontinuation. METHODS: Positron emission tomography (PET) was used to examine regional bone metabolism in 20 postmenopausal women treated with ALN (n = 11) or RIS (n = 9) for a minimum of 3 years at screening (range 3-9 years, mean 5 years for both groups). Subjects underwent a dynamic scan of the lumbar spine and a static scan of both hips at baseline and 6 and 12 months following treatment discontinuation. (18) F-fluoride plasma clearance (K(i)) at the spine was calculated using a three-compartment model. Standardised uptake values (SUV) were calculated for the spine, total hip, femoral neck and femoral shaft. Measurements of BMD and biochemical markers of bone turnover were also performed. RESULTS: With the exception of a significant decrease in spine BMD in the ALN group, BMD remained stable. Bone turnover markers increased significantly from baseline by 12 months for both study groups. Measurements of K(i) and SUV at the spine and femoral neck did not change significantly in either group. SUV at the femoral shaft and total hip increased significantly but in the ALN group only, increasing by 33.8% (p = 0.028) and 24.0% (p = 0.013), respectively. CONCLUSIONS: Bone metabolism at the spine remained suppressed following treatment discontinuation. A significant increase in SUV at the femoral shaft and total hip after 12 months was observed but for the ALN group only. This study was small, and further clinical studies are required to fully evaluate the persistence of BP treatment.

The effect of weight and weight change on the long-term precision of spine and hip DXA measurements.

SUMMARY: We examined the effect of weight and weight change on the long-term precision of spine and hip bone mineral density (BMD) in a group of 64 postmenopausal women studied over a 10-year period. Long-term precision errors were 50% larger than short-term errors. Over the range 50-90-kg weight was associated with a statistically significantly larger precision error when precision was expressed in BMD units, but not when expressed as the coefficient of variation (CV). Weight changes up to 5 kg had little effect on precision. INTRODUCTION: Reliable knowledge of the precision of bone mineral density (BMD) measurements is important for the interpretation of follow-up dual-energy X-ray absorptiometry (DXA) scans. In this study, we examined the effect of body weight and change in weight on the long-term precision of spine and hip BMD. METHODS: The study population was a group of 64 postmenopausal women enrolled in a 16-year trial of tibolone. We analyzed the spine, femoral neck, and total hip BMD data acquired over a 10-year period on a Hologic QDR4500A densitometer using linear regression to examine the trend of BMD with time for each subject. Precision was expressed in BMD units (g cm(-2)) (standard error of the estimate, SEE) and also as the coefficient of variation (CV). RESULTS: The long-term precision errors were in BMD (CV) units: 0.018 g cm(-2) (1.9%) for spine, 0.017 g cm(-2) (2.3%) for femoral neck, and 0.016 g cm(-2) (1.7%) for total hip BMD. An inverse relationship between CV and BMD was found for the spine (P = 0.003) and total hip (P = 0.043) sites, but none between SEE and BMD. For spine BMD, there were statistically significant correlations between SEE and weight (P = 0.025) and body thickness (P = 0.027). For femoral neck BMD, there were correlations between SEE and weight (P = 0.030), body mass index (BMI) (P = 0.023) and thickness (P = 0.021), but no correlations for total hip BMD or when precision was expressed as the CV. When study subjects were grouped in quartiles according to weight, the spine BMD SEE increased from 0.014 g cm(-2) for women in the lowest quartile (46-62 kg) to 0.018 g cm(-2) for women in the highest quartile (80-105 kg) (P = 0.008). There was a trend for SEE to be greater in individuals with larger weight changes, although these tended to be the heavier subjects. CONCLUSIONS: From the study, we were able to come up with the following conclusions: (1) long-term precision errors were 50% larger than short-term errors, (2) over the range 50 to 90 kg (BMI: 20-35 kg m(-2)), body weight had a small but statistically significant effect on precision expressed in BMD units, but not when expressed as the CV, and (3) weight changes up to 5 kg had little effect on precision. More studies of individuals >100 kg are required to fully investigate the dependence of DXA scan precision on weight.

Significant differences in UK and US female bone density reference ranges.

UNLABELLED: In the United Kingdom (UK), T- and Z-scores are usually calculated using reference ranges derived from United States (US) populations. In the UK arm of a recent randomised trial (International Breast Cancer Intervention Study II (IBIS-II)), substantially, fewer women than expected were recruited into the osteopenic (-2.545 years with a typical body mass index of 28 kg m(-2) have spine and hip bone mineral density (BMD) 0.6 standard deviation higher than their US counterparts. INTRODUCTION: Dual energy X-ray absorptiometry (DXA) is widely used for the diagnosis of osteoporosis and to investigate the effect of pharmacological treatments on BMD. In both routine and research settings, it is important that DXA results are correctly interpreted. METHODS: T- and Z-scores for the first 650 UK Caucasian women enrolled in the IBIS-II study were compared with data from two independent studies of unrelated, unselected UK Caucasian women: (1) 2,382 women aged 18 to 79 recruited to the Twins UK Adult Twin Registry; (2) 431 women aged 21 to 84 with no risk factors for osteoporosis recruited at Guy's Hospital. All DXA measurements were performed on Hologic densitometers. Subjects were divided into six age bands, and T- and Z-scores were calculated using the manufacturer's US reference range for the spine and the National Health and Nutrition Examination Survey III reference range for the femoral neck and total hip. RESULTS: The overall mean Z-scores for the IBIS-II, Twin, and Guy's groups were: spine: +0.61, +0.29, +0.33; femoral neck: +0.42, +0.36, +0.45; total hip: +0.65, +0.38, +0.39 (all p<0.001 compared with the expected value of 0). The mean body weight of subjects in the three studies was 74.4, 65.5, and 65.4 kg, respectively. Analysis revealed a highly significant relationship between Z-score and weight at each BMD site with a slope of 0.03 kg(-1). CONCLUSIONS: In general, US spine and hip reference ranges are not suitable for the calculation of Z-scores in UK women. For some research study designs, the differences may significantly influence the pattern of subject recruitment.

Genetic and environmental determinants on bone loss in postmenopausal Caucasian women: a 14-year longitudinal twin study.

SUMMARY: This longitudinal twin study documented that genetic factors explain 44-56% of the between-individual variance in bone loss at femoral neck, lumbar spine, and forearm in postmenopausal Caucasian women, providing a rationale for identifying the specific genes involved. INTRODUCTION: Although there is a significant genetic effect on peak BMD, until recently, no substantive studies on heritability of bone loss in human were available. The aim of the study was to estimate the heritability of the bone loss at multiple sites in postmenopausal Caucasian women. METHODS: Postmenopausal female monozygotic (MZ) and dizygotic (DZ) twins aged 40 or above at baseline were selected from the TwinsUK registry and followed up for an average of 8 years (range 5-14 years). All twins were noncurrent hormone replacement therapy users and not on any osteoporosis treatment. They had dual-energy X-ray absorptiometry (DXA) scans of their hip, lumbar spine, and forearm several times (range 2-9) during the follow-up period. Individual bone losses at femoral neck, lumbar spine, and forearm were estimated by linear regression modeling. Structural equation modeling was utilized to estimate the heritability of the bone loss. RESULTS: A total of 712 postmenopausal Caucasian female twins (152 MZ and 204 DZ pairs) were included. MZ twins were older and had slightly lower BMD at all sites than DZ twins. DZ twins had slightly higher bone loss at lumbar spine, but similar at femoral neck and forearm compared to MZ twins. Intraclass correlation coefficients (ICC) for the bone loss at all sites were significantly higher in MZ than DZ twin pairs (p = 0.0045, 0.0003, and 0.0007 for femoral neck, lumbar spine, and forearm, respectively), indicating a significant genetic influence on bone loss at these sites. After adjustment for age at baseline and weight change during the follow-up, the heritability estimate was 47% (95% CI 27-63%) for bone loss at femoral neck, 44% (95% CI 27-58%) for lumbar spine, and 56% (95% CI 44-65%) for forearm. CONCLUSIONS: Our data suggest that up to 56% of the between-individual variance in bone loss is due to genes, providing a rationale to identify specific genetic factors for bone loss.

Frequencies of null alleles at enzyme Loci in natural populations of ponderosa and red pine.

Pinus ponderosa and P. resinosa population samples have mean frequencies of enzymatically inactive alleles of 0.0031 and 0.0028 at 29 and 27 enzyme loci, respectively. Such alleles are rare and are apparently maintained by selection-mutation balance. Ponderosa pine have much higher amounts of allozymic and polygenic phenotypic variation than red pine, yet both species have similar frequencies of null alleles. Thus, null alleles apparently do not contribute to polygenic variation, as has been suggested. The concordance between allozymic and polygenic variation adds support to the view that allozyme studies may be valuable in predicting the relative amount of polygenic variation in populations.

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.

Differences in skeletal kinetics between vertebral and humeral bone measured by 18F-fluoride positron emission tomography in postmenopausal women.

We have sought to investigate regional differences in skeletal kinetics between lumbar vertebrae and the humerus of postmenopausal women with 18F-fluoride positron emission tomography (PET). Twenty-six women, mean age 62 years, had dynamic PET scans of the lumbar spine and lower humerus after the injection of 180 MBq 18F-fluoride ion. Plasma arterial input functions (IFs) were calculated from a mean IF measured arterially from 10 women and scaled according to late individual venous activity. Vertebral and humeral time activity curves were measured by placing regions of interest (ROI) over lumbar vertebrae and the humeral shaft. Using a three-compartmental model and nonlinear regression analysis the macroconstant Ki, representing plasma clearance of fluoride to bone mineral, and the individual rate constants K1 (related to regional skeletal blood flow) and k2 to k4 describing transport between plasma, an extracellular fluid compartment and a bone mineral compartment, were measured. Mean vertebral Ki (3.47x10(-2) ml x min(-1) x ml(-1)) and K1 (1.08x10(-1) ml x min(-1) x ml(-1)) were found to be significantly greater than humeral Ki (1.64x10(-2) ml min(-1) ml(-1); P<0.0001) and K1 (3.90x10(-2) ml x min(-1) x ml(-1); P<0.0001) but no significant differences were found in k2, k3, and k4. These findings confirm differences in regional skeletal kinetics between lumbar vertebrae and the lower humerus. These observations may help increase our understanding of the regional differences in pathophysiology and response to treatment that have been observed in sites consisting predominantly of either trabecular or cortical bone. 18F-fluoride PET may prove to be a valuable technique in the noninvasive measurement of regional skeletal metabolism.

Quantification of skeletal kinetic indices in Paget's disease using dynamic 18F-fluoride positron emission tomography.

The purpose of this study was to quantify indices of regional bone metabolism in Paget's disease and to compare these indices with normal bone using dynamic 18F-fluoride positron emission tomography (PET). Seven patients with vertebral Paget's disease had 1 h dynamic 18F-fluoride PET scans performed. The scans included a diseased vertebra and an adjacent normal vertebra. Arterial plasma input functions were also measured. A three-compartment, four-parameter model was used with nonlinear regression analysis to estimate bone kinetic variables. Compared with normal bone, pagetic bone demonstrated higher values of plasma clearance to bone mineral (Ki; 1.03 x 10(-1) vs. 0.36 x 10(-1) ml/min per milliliter; p = 0.018) and clearance to total bone tissue (K1; 2.38 x 10(-1) vs. 1.25 x 10(-1) ml/min per milliliter; p = 0.018), reflecting increased mineralization and blood flow, respectively. Release of 18F-fluoride from bone mineral (k4) was lower in pagetic bone (p = 0.022), suggesting tighter binding of 18F-fluoride to bone mineral. The notional volume of the extravascular bone compartment (K1/k2) was greater in pagetic bone (p = 0.018). Although the unidirectional extraction efficiency from the extravascular space to bone mineral (Ki/K1) was greater in pagetic bone (p = 0.018), a lower pagetic value of k2 (p = 0.028), describing the rate of transfer from the bone extravascular compartment to plasma, suggests that the 18F-fluoride that enters the relatively fibrotic marrow space of pagetic bone may be less accessible for return to plasma. These findings confirm some of the known pathophysiology of Paget's disease, introduce some new observations, and show how dynamic 18F-fluoride PET may be of value in the measurement of regional metabolic parameters in focal bone disorders.

Morphometric X-ray absorptiometry: reference data for vertebral dimensions.

Vertebral fractures are a common and important consequence of osteoporosis and are often identified via morphometric analysis of conventional lateral spine radiographs (morphometric radiography or MRX). A new method of performing vertebral morphometry using images acquired on dual-energy X-ray absorptiometry (DXA) scanners (morphometric X-ray absorptiometry or MXA) has recently been developed. In this study, we derive reference data for vertebral heights and height ratios using MXA scans as the data source and compare the results with previously published MRX studies. One thousand and nineteen Caucasian women (mean age 63 years, range 33-86) were recruited. An MXA scan, covering 13 vertebrae from L4 to T4, was acquired for each subject on one of four DXA systems located at three centers in the U.K. Analysis of variance found statistically significant but relatively small differences among centers, machines, and scan modes, and therefore data were pooled for reference range calculations. Three vertebral heights (anterior, mid, and posterior) were measured and four ratios (wedge, mid-wedge, and two crush) calculated. These data sets were trimmed using an iterative algorithm to remove extreme values assumed to represent deformed vertebrae, then mean and SD values were calculated using the remaining data. When the data were split by age, a small but statistically significant decrease in vertebral height between the sixth and eighth decades was found, but this was not replicated for the vertebral height ratios. Marked differences were observed between MXA data and MRX, but were comparable to those between different MRX studies. These may result from differences in image quality and point placement protocols, population differences, differences in radiographic technique, and differences in the derivation of a group of "normal" vertebrae. This study suggests that reference data of vertebral dimensions should be specific to the technique which uses those data as a reference, i.e., MXA.

Morphometric X-ray absorptiometry and morphometric radiography of the spine: a comparison of prevalent vertebral deformity identification.

Prevalent vertebral deformities are associated with a substantially increased risk of subsequent vertebral and nonvertebral fractures. Knowledge of vertebral fracture status is an important component in the prediction of further fractures in patients with osteoporosis. This study reports a comparison of the quantitative identification of vertebral deformities on morphometric X-ray absorptiometry (MXA) scans and conventional radiographs (MRX) in 161 postmenopausal women (mean age +/- SD, 64 +/- 7.1 years) recruited from patients referred by their family doctor for bone density measurement (n = 119) and osteoporotic subjects with known vertebral deformities attending an osteoporosis clinic (n = 42). Each subject had MXA scans and MRXs of the thoracolumbar spine, to image the vertebrae from T4-L4, at a single visit. The scans and radiographs were analyzed by two trained observers using six points to quantify the shape of each vertebral body. From these points, three vertebral heights were measured: anterior, middle, and posterior. Vertebral deformities were identified using the algorithms proposed by Eastell and by McCloskey. Generally good to excellent agreement (per vertebra, kappa = 0.87-0.93; per subject, kappa = 0.81-0.91) was observed between the two algorithms used for quantitative vertebral deformity identification using MXA or MRX. More moderate agreement (per vertebra, kappa = 0.70-0.79; per subject, kappa = 0.67-0.75) was seen when comparing the same algorithm between MXA and MRX. Agreement between MXA and MRX for the McCloskey algorithm was better than for the Eastell algorithm, largely because of the lower number of false positives produced by the McCloskey methodology. Deformity identification by MXA was limited because of poor image quality, primarily in the upper thoracic spine. One in six MRX deformities were missed by MXA as they occurred in vertebrae not visualized sufficiently for analysis on the MXA scans. Deformity identification was poorer in the upper thoracic spine in analyzable vertebrae with a sensitivity of 50.0% for MXA in terms of MRX using the Eastell algorithm for the vertebral levels T4-T7, compared with 80.6% for L1-L4A. MXA proved to be more effective at identifying moderate to severe MRX deformities producing a sensitivity of 22.0% for MXA in terms of identifying MRX grade 1 deformities using the Eastell algorithm, compared with 81.6% for grade 2 deformities. Although MXA image quality is inferior to that of conventional radiographs, MXA has distinct advantages such as a substantially reduced effective dose to the patient and acquisition of a single image of the spine. MXA is a potentially useful, relatively fast, low-radiation technique to identify prevalent vertebral deformities, particularly moderate to severe deformities in the middle/lower thoracic and lumbar spine, in conjunction with morphometric radiography in some patients.

The role of bone density measurements in the evaluation of new treatments for osteoporosis.

During the past ten years the range of treatments available for patients with osteoporosis has increased greatly. A decade ago the only proven therapy was oestrogen, while today the choice includes bisphosphonates, selective oestrogen receptor modulators, calcitonin, calcium and vitamin D supplementation and, in the near future, parathyroid hormone. Clinical trials involving bone mineral density (BMD) scans of the spine and femur have had an important role in the evaluation of these new therapies. Supplementary information about treatments has been provided by BMD scans of the total body and distal radius as well as by measurements of biochemical markers of bone turnover in serum and urine. Most important of all, the efficacy of treatments has been verified in large trials powered to show reductions in fracture risk. In routine clinical use, BMD scanning has an important role in identifying individual patients with osteoporosis and helping to make decisions about their treatment. However, in contrast to the use of BMD scans in clinical trials, their value for monitoring response to therapy in individual patients is less certain because in many cases the increases in BMD are too small to reliably distinguish between true changes and measurement error. However, experience with well established therapies such as oestrogen and bisphosphonates suggests that these treatments have a beneficial effect on bone in the large majority of patients and individual monitoring of BMD is probably not necessary.

The prevention of early postmenopausal bone loss by cyclical etidronate therapy: a 2-year, double-blind, placebo-controlled study.

PURPOSE: To determine whether intermittent cyclical etidronate therapy can prevent early postmenopausal bone loss. PATIENTS AND METHOD: This was a 2-year outpatient, randomized, double-blind, placebo-controlled clinical trial. The subjects were 152 women within 1 to 10 years of the onset of menopause and bone mineral density (BMD) between 0 and -2 SD of normal values for a 50 year old woman. The women were stratified according to years since the menopause (1 to 3 years: n = 43; 4 to 6 years: n = 53; 7 to 10 years: n = 56). Measurements of lumbar spine, proximal femur and total body BMD were performed at baseline, 12 and 24 months by dual x-ray absorptiometry. Biochemical markers of bone resorption and bone formation were measured on the same visits. RESULTS: One hundred thirty-five subjects completed the study. Mean percentage change in lumbar spine BMD (and SEM) at 2 years was +2.14 (0.47)% in the etidronate group and -1.72 (0.41)% in the placebo group. Results for lumbar spine BMD in the treated and control groups stratified according to years since the menopause were: 1 to 3 years: +1.73 (0.84)% and -3.30 (0.70)%; 4 to 6 years: +1.37 (0.88)% and -1.80 (0.61)%; 7 to 10 years: +3.42 (0.61)% and -0.38 (0.70)%. The effect of both treatment group and menopausal stratum were highly statistically significant for lumbar spine and total body BMD. Treatment group, but not stratum, was significant for BMD in the proximal femur. Markers of bone resorption and bone formation were significantly decreased by etidronate therapy. CONCLUSIONS: Cyclical etidronate prevents bone loss in the total skeleton and at the clinically relevant sites (spine and proximal femur) even in the early postmenopausal years. Hence, it appears to be an effective and safe nonhormonal therapy in postmenopausal women with normal or low BMD.

Applications of bone densitometry for osteoporosis.

Over the past decade, growing awareness of the impact of osteoporosis on the elderly population and the availability of new treatments to prevent fractures have stimulated the rapid development of new radiologic techniques to assist in diagnosis. With the ability to perform high precision measurements of bone mineral density (BMD) in the spine and hip, dual X-ray absorptiometry (DXA) is well suited to meet this latter need. However, there is continuing interest in smaller, cheaper systems for assessing the peripheral skeleton that include DXA scanning of the distal forearm and a variety of devices for performing quantitative ultrasound (QUS) measurements on bone. Alongside the new equipment, new guidelines have been developed to assist in the interpretation of bone densitometry studies and, following a report by a World Health Organization working group, osteoporosis is increasingly diagnosed on the basis of the patient's T-score value (difference of BMD from young adult mean normalized to the population SD). For the future, wider provision of bone densitometry services is required to properly target the new treatments now becoming available. Since it is unlikely that conventional DXA can meet these needs, QUS is an attractive alternative, especially because this technique is now proven in its ability to predict fracture risk in the elderly and FDA approval is imminent.

Different approaches to bone densitometry.

From 1990 to 2000, several effective new treatments were introduced for the prevention of osteoporotic fractures; these treatments were proven effective in large, international, clinical trials. At the same time, there was rapid technologic innovation, with the introduction of new radiologic methods for the noninvasive assessment of patients' bone density status. These developments led to the publication of guidelines for the clinical use of bone densitometry that include criteria for the referral of patients for investigation as well as recommendations for intervention thresholds for the initiation of preventive treatment of osteoporosis. Dual-energy x-ray absorptiometry scanning of the spine and hip remains the technique of choice for bone densitometry studies, although there is now a wider appreciation of the need for smaller, cheaper devices for scanning the peripheral skeleton if the millions of women most at risk of a fragility fracture are to be identified and treated. This article reviews these developments, concentrating in particular on the advantages and disadvantages of the different types of equipment available for performing bone densitometry investigations, the guidelines for the referral of patients, and the principles for the interpretation of the scan findings.

Strontium-89 therapy: measurement of absorbed dose to skeletal metastases.

We report measurements of absorbed dose to vertebral metastases in ten patients referred for 89Sr therapy for disseminated prostatic carcinoma. Patients received a tracer dose of 85Sr at the time of 89Sr treatment and metastatic strontium retention was monitored scintigraphically for 6 mo. Metastatic 85Sr activity corrected for tissue attenuation was measured using the conjugate view principle, with special care taken to eliminate errors due to the selection of the metastatic region of interest. Metastatic volume was determined from high resolution CT images, and density inferred from Hounsfield number using the QCT bone mineral calibration of Genant and Cann. The mean absorbed dose was 850 rad/mCi (23 cGy/MBq) with a range from 220-2260 rad/mCi (6 to 61 cGy/MBq). The wide range found was consistent with the variation expected to arise due to differences in strontium renal plasma clearance (range 0.1-11.81/day) and extent of skeletal metastatic disease (varying from two small metastases to a superscan on [99mTc]MDP images) among the patients studied.

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.