Osteoporosis: Stewart A

Krieg MA, Barkmann R, Gonnelli S, Stewart A, Bauer DC, Del Rio Barquero L, Kaufman JJ, Lorenc R, Miller PD, Olszynski WP, Poiana C, Schott AM, Lewiecki EM, Hans D. · Lausanne University Hospital, Lausanne, Switzerland. <> · J Clin Densitom. · Pubmed #18442758 No free full text.

Abstract: Dual-energy X-ray absorptiometry (DXA) is commonly used in the care of patients for diagnostic classification of osteoporosis, low bone mass (osteopenia), or normal bone density; assessment of fracture risk; and monitoring changes in bone density over time. The development of other technologies for the evaluation of skeletal health has been associated with uncertainties regarding their applications in clinical practice. Quantitative ultrasound (QUS), a technology for measuring properties of bone at peripheral skeletal sites, is more portable and less expensive than DXA, without the use of ionizing radiation. The proliferation of QUS devices that are technologically diverse, measuring and reporting variable bone parameters in different ways, examining different skeletal sites, and having differing levels of validating data for association with DXA-measured bone density and fracture risk, has created many challenges in applying QUS for use in clinical practice. The International Society for Clinical Densitometry (ISCD) 2007 Position Development Conference (PDC) addressed clinical applications of QUS for fracture risk assessment, diagnosis of osteoporosis, treatment initiation, monitoring of treatment, and quality assurance/quality control. The ISCD Official Positions on QUS resulting from this PDC, the rationale for their establishment, and recommendations for further study are presented here.

Horwitz M, Stewart A, Greenspan SL. · No affiliation provided · J Clin Endocrinol Metab. · Pubmed #10852439 links to  free full text

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Stewart A, Reid DM. · Department of Medicine and Therapeutics, University of Aberdeen, Aberdeen, Scotland, UK. · Semin Musculoskelet Radiol. · Pubmed #12541200 No free full text.

Abstract: Quantitative ultrasound (QUS) has been applied to the assessment of bone for almost two decades. The physical interaction of ultrasound and bone is complex and not completely understood. However, it is considered that QUS provides information on bone mass and structure. Although dual-energy X-ray absorptiometry (DXA) is currently considered the "gold standard" for the diagnosis of osteoporosis, through the World Health Organisation definition, there is, in some parts of the world, limited availability to axial DXA. This has stimulated interest in smaller, more portable, and less expensive techniques to indentify those at risk of osteoporotic fracture. One such quantitative method is QUS, which has the added advantage over other photon absorptiometric bone density techniques of not using ionizing radiation. This article reviews the capabilities of QUS and indicates its appropriate application in clinical practice, based on current review of the scientific literature.

Stewart A, Black AJ. · Department of Medicine and Therapeutics, University of Aberdeen, Scotland, UK. · Curr Opin Rheumatol. · Pubmed #10990188 No free full text.

Abstract: The inverse relation between osteoporosis and osteoarthritis has long been considered in the literature. This review looks at current evidence to support this relation, concentrating on studies published since 1998. The review also summarizes previous large studies investigating this relation. Recent studies indicate higher bone mineral density as measured by dual energy x-ray absorptiometry in subjects with osteoarthritis at a distant site, but suggest less association with hand osteoarthritis. Genetic work has sought to explain this association and this too is discussed. There is some indication that a higher bone density may not protect against fracture in these subjects, due to the increased risk of falls.

Barr RJ, Stewart A, Torgerson DJ, Seymour DG, Reid DM. · Department of Medicine and Therapeutics, University of Aberdeen, Aberdeen, UK. · Calcif Tissue Int. · Pubmed #15812582 No free full text.

Abstract: We have assessed the acceptability of a method for screening for risk of future hip fracture in elderly women. After receipt of an initial response to a mailed risk-factor questionnaire sent out to 5,306 women, women were randomly assigned to active or control groups. The active group was invited to participate in a screening visit that comprised a life-style questionnaire and a quantitative ultrasound heel scan. General practitioners (GPs) of women who were found to be in the lowest quartile of broadband ultrasound attenuation and/or who had two or more risk factors for hip fracture were advised to prescribe a calcium and vitamin D supplement. A second mailed questionnaire was sent to both groups 1 to 3 years later. Compared with the control group, the active group had a 56% lower risk of fracture (odds ratio [OR], 0.44; 95% confidence interval [CI], 0.24-0.81 adjusted age, weight, and treatment status). At follow-up, the proportion of fallers in the active group (25.3%) was lower than that in the control group (29.6%) (P = 0.064). The control group was found to have a higher rate of falls at follow-up than the active group (95% CI, 0.02-0.22); no difference was found at baseline (95% CI, -0.08 to +0.14). The screening method used was found to be acceptable to the majority of elderly women in this study. Screening the elderly in this way together with simple advice on treatment appears to reduce the age-associated increase in fall rates and the number of subsequent fractures. This form of screening may provide a cost-effective method to reduce falls and fractures in free-living elderly women. However, no such cost-effectiveness analysis has been performed to date.

Glüer CC, Eastell R, Reid DM, Felsenberg D, Roux C, Barkmann R, Timm W, Blenk T, Armbrecht G, Stewart A, Clowes J, Thomasius FE, Kolta S. · Medical Physics, Department of Diagnostic Radiology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany. · J Bone Miner Res. · Pubmed #15068502 No free full text.

Abstract: We compared the performance of five QUS devices with DXA in a population-based sample of 2837 women. All QUS approaches discriminated women with and without osteoporotic vertebral fractures. QUS of the calcaneus performed as well as central DXA. INTRODUCTION: Quantitative ultrasound (QUS) methods have found widespread use for the assessment of bone status in osteoporosis, but their optimal use remains to be established. To determine QUS performance for current devices in direct comparison with central DXA, we initiated a large population-based investigation, the Osteoporosis and Ultrasound Study (OPUS). MATERIALS AND METHODS: A total of 463 women 20-39 years of age and 2374 women 55-79 years of age were measured on five different QUS devices along with DXA of the spine and the proximal femur. Their vertebral fracture status was evaluated radiographically. The association of QUS and DXA with vertebral fracture status was evaluated using logistic regression. RESULTS: All QUS approaches tested discriminated women with and without osteoporotic vertebral fractures (20% height reduction), with age-adjusted standardized odds ratios ranging 1.2-1.3 for amplitude-dependent speed of sound (AD-SOS) at the finger phalanges, 1.2-1.4 for broadband ultrasound attenuation (BUA) at the calcaneus, and 1.4-1.5 for speed of sound (SOS) at the calcaneus, 1.4-1.6 for DXA of the total femur, and 1.5-1.6 for DXA at the spine. For more severe fractures (40% height reduction), age-adjusted standardized odds ratios increased to up to 1.9 for DXA of the spine and 2.3 for SOS of the calcaneus. CONCLUSIONS: In conclusion, all five QUS devices tested showed significant age-adjusted differences between subjects with and without vertebral fracture. When selecting the strongest variable, QUS of the calcaneus worked as well as central DXA for identification of women at high risk for prevalent osteoporotic vertebral fractures. QUS-based case-finding strategies would allow halving the number of radiographs in high-risk populations, and this strategy works increasingly well for women with more severe vertebral fractures. It is likely that the good performance of QUS was in part achieved by rigorous quality assurance measures that should also be used in clinical practice.

McGuigan FE, Macdonald HM, Bassiti A, Farmer R, Bear S, Stewart A, Black A, Fraser WD, Welsh F, Reid DM, Ralston SH. · Department of Medicine and Therapeutics, University of Aberdeen, UK. · J Bone Miner Res. · Pubmed #17059371 No free full text.

Abstract: The TGFB1 gene is a strong functional candidate for regulating genetic susceptibility to osteoporosis. We studied five common polymorphisms of TGFB1 in relation to osteoporosis-related phenotypes in a population-based cohort of 2975 British women, but found no significant association with bone mass, bone loss, bone markers, or fracture. INTRODUCTION: The gene encoding TGFB1 is a strong functional candidate for genetic susceptibility to osteoporosis. Several polymorphisms have been identified in TGFB1, and previous work has suggested that allelic variants of TGFB1 may regulate BMD and susceptibility to osteoporotic fracture. MATERIALS AND METHODS: We studied the relationship between common polymorphisms of TGFB1 and several osteoporosis-related phenotypes including BMD at the lumbar spine and femoral neck, measured by DXA; bone loss over a 6-year period; biochemical markers of bone turnover (urinary free deoxypyridinoline and free pyridinoline/creatinine ratio and serum N-terminal propeptide of type 1 collagen), and fractures in a population-based study of 2975 women from the United Kingdom. Participants were genotyped for single nucleotide polymorphisms (SNPs) in the TGFB1 promoter (G-800A; rs1800468; C-509T; rs1800469), exon 1 (T29C; rs1982073 and G74C; rs1982073); and exon 5 (C788T; rs1800471) on PCR-generated fragments of genomic DNA. Haplotypes were constructed from genotype data using the PHASE software program, and genotypes and haplotypes were related to the phenotypes of interest using general linear model ANOVA, with correction for confounding factors including age, height, weight, menopausal status, hormone replacement therapy (HRT) use, physical activity score, and dietary calcium intake. RESULTS: The polymorphisms were in strong linkage disequilibrium, and four common haplotypes accounted for >95% of alleles at the locus. There was no association between individual SNPs and BMD, bone loss, or biochemical markers of bone turnover. Haplotype analysis showed a nominally significant association with femoral neck BMD (p = 0.042) and with incident osteoporotic fracture (p = 0.013), but these were not significant after correcting for multiple testing. CONCLUSIONS: Common polymorphic variants of the TGFB1 gene did not influence BMD or bone loss in this population.

Stewart A, Felsenberg D, Eastell R, Roux C, Glüer CC, Reid DM. · Osteoporosis Research Unit, Department of Medicine and Therapeutics, University of Aberdeen, Aberdeen, UK. · Bone. · Pubmed #16644296 No free full text.

Abstract: There are many risk factors associated with low bone mineral density. Quantitative ultrasound (QUS) is a generally accepted method for measurement of bone and has been shown to be strongly associated with future fracture risk. The Osteoporosis and Ultrasound Study (OPUS) is a multi-centre European wide study examining 5 different QUS scanners (4 calcaneal, 1 finger device). The aim of this paper was to examine the relationship between risk factors (as assessed by questionnaire) and QUS measurements. 449 younger women (aged 20 to 39 years) and 2283 older women (aged 55 to 79 years) were included in this analysis. As expected, those with a self-reported previous fracture had lower QUS measurements than those without (P < 0.001). However, no significant difference was seen between those reporting a maternal hip fracture and those who did not report such an event. Differences were found for smokers vs. non-smokers for SOS but not for BUA measurements. Weight was positively correlated with all BUA variables but only with some SOS variables. We determined which risk factors were most strongly associated with QUS measurements by using step-wise multiple regression. Models for each QUS measurement were calculated, and the R2 values ranged from 0.18 to 0.28 for SOS, 0.27 to 0.32 for BUA and 0.31 to 0.42 for the finger QUS device. The most common risk factors across all models were age, use of hormone replacement therapy, self-reported previous fracture, self-reported diagnosis of osteoporosis, current weight, pulse rate and self-reported estimated height at age 20 years. We analysed relationships across the 5 centres and detected some geographical differences in the prevalence of the risk factors. In conclusion, similar relationships are seen with QUS measurements as are found for bone mineral density. However, the strength of the association is dependent on the type of QUS device and variable measured.

Stewart A, Kumar V, Reid DM. · Osteoporosis Research Unit, Department of Medicine and Therapeutics, University of Aberdeen, Aberdeen, United Kingdom. · J Bone Miner Res. · Pubmed #16491289 No free full text.

Abstract: This study investigated the ability of DXA and QUS to predict fractures long term when measured around the time of the menopause. We found both DXA and QUS are able to predict both any fracture and "osteoporotic" fractures and that QUS can predict independently of BMD. INTRODUCTION: There are now many treatments available for prevention of osteoporotic fracture. To be cost-effective, we need to target those most at risk. This study examines the ability of DXA and QUS to predict fractures in an early postmenopausal population of women. MATERIALS AND METHODS: We prospectively measured 3883 women who had been randomly selected from a community-based register. At baseline, they were measured using DXA of spine and hip (Norland XR-26) and QUS of the heel (Walker Sonix UBA 575). Follow-up had a mean of 9.7 +/- 1.1 (SD) years. All incident fractures were identified and validated by examination of X-ray reports, and these were compared with those without fracture in a Cox-regression model to calculate hazard ratios (HRs). RESULTS: We found adjusted HRs for any fracture per 1 SD reduction in spine BMD to be 1.61 (1.42-1.83), whereas neck of femur BMD was 1.54 (1.34-1.75). Areas under the curve (AUC) for a receiver operator characteristic (ROC) analysis were 0.62 for spine BMD and 0.59 for neck BMD. In a subgroup where QUS was also measured, the HR for a 1 SD reduction in BMD was 1.69 (1.29-2.22) for spine BMD and 1.55 (1.17-2.06) for neck BMD. The HR for a 1 SD reduction in broadband ultrasound attenuation (BUA) was 1.53 (1.19-1.96), and 1.44 (1.12-1.86) when further adjusted for neck BMD. The AUCs were 0.63 for spine BMD, 0.59 for neck BMD, and 0.62 for BUA. When only osteoporotic fractures were examined, the HRs increased in all situations. BUA showed the highest HR of 2.25 (1.51-3.34), and when further adjusted for neck BMD was 2.12 (1.38-3.28). CONCLUSIONS: In conclusion, it may be possible to scan women around the time of the menopause to predict future fractures. It seems that, for "osteoporotic" fractures, BUA may be an improved predictor of fractures in comparison with DXA, because the relative risk is highest for BUA, and independent of BMD.

Macdonald HM, McGuigan FE, Stewart A, Black AJ, Fraser WD, Ralston S, Reid DM. · Department of Medicine and Therapeutics, University of Aberdeen, Medical School Buildings, Foresterhill, Aberdeen, United Kingdom. · J Bone Miner Res. · Pubmed #16355284 No free full text.

Abstract: The VDR is a candidate gene for osteoporosis. Here we studied five common polymorphisms of VDR in relation to calcium intake and vitamin D status in a population-based cohort of 3100 British women, but found no significant association with bone mass, bone loss, or fracture. INTRODUCTION: Population studies of vitamin D receptor (VDR) polymorphisms have produced conflicting results. We performed a comprehensive study dealing with all potential confounders in a large population to determine whether polymorphisms in the VDR gene influence bone health. MATERIALS AND METHODS: We studied 3100 women (50-63 years old) with bone markers, 25-hydroxyvitamin D, calcium, PTH, diet, and physical activity collected in 1998-2000. BMD was measured in 1990-1994 and 1998-2000. Fracture prevalence was assessed in 2002. Women were genotyped for five polymorphisms in the VDR gene: Cdx-2, Fok1, Bsm1, Apa1, and Taq1. The relationship between VDR and BMD, and interactions between VDR genotype, dietary calcium, and 25-hydroxyvitamin D, were examined using analysis of covariance. RESULTS: Compared with carriers of the G allele, homozygotes for the rare Cdx-2 A polymorphism (n = 136) had less bone loss (-0.5 +/- 1.2 versus -0.7 +/- 1.0%/year [SD]; p = 0.01) and lower PTH (3.0 +/- 1.6 versus 3.4 +/- 2.0 pM; p = 0.03) despite similar vitamin D status. The association was not significant after correction for multiple testing or adjustment for confounders. At low calcium intakes, AA homozygotes had greater femoral neck (FN) BMD compared with carriers of the G allele, but at higher calcium intakes, the association was reversed. At low calcium intake, homozygotes for the b allele of Bsm1 had greater BMD compared with carriers of the B allele, but at higher calcium intakes, there was no difference. Similar results were seen for the Taq1 polymorphism. There was no evidence of gene-nutrient interaction when adjusted for body weight. No interactions between genotypes and vitamin D status on BMD were observed. CONCLUSIONS: VDR does not seem to influence BMD or bone turnover in early postmenopausal white women with adequate calcium intake. Gene-nutrient interactions on BMD may be an indirect consequence of interactions between genotype and calcium intake on weight.

Jawaid WB, Crosbie D, Shotton J, Reid DM, Stewart A. · Department of Rheumatology, Aberdeen Royal Infirmary, UK. · Ann Rheum Dis. · Pubmed #16126795 links to  free full text

Abstract: OBJECTIVE: To compare digital x ray radiogrammetry (DXR) with manual radiography for assessing bone loss in RA and examine the relationship of the scores obtained with other disease indices. METHODS: 225 consecutive consenting subjects attending the RA clinic were enrolled. An x ray examination was carried out; demographic details recorded; a self assessment questionnaire completed; blood taken for ESR measurement; and an assessment made by a trained nurse. All x ray films were scored manually using the modified Sharp technique by a single observer; 20 films were rescored by three readers. Films were assessed with the Pronosco X-Posure system, version 2.0. Analysis included chi2 tests, independent t tests, multiple linear regression, and partial correlations, as appropriate. The smallest detectable difference (SDD), coefficient of variation (CV), and coefficient of repeatability (CR) were determined from Bland and Altman plots. RESULTS: The DXR precision varied: SDD = 0.002-0.9; CV = 0.09-5.9%; CR = 0.002-0.792, but was better than that of the intra- and interobserver Sharp scores: SDD = 73.9; CV = 27.8%; CR = 33.0-47.6. The DXR measurements, bone mineral density (R2 = 0.210), metacarpal index (R2 = 0.222), and cortical thickness (R2 = 0.215), significantly predicted Sharp scores. In women, DXR measurements significantly correlated with modified HAQ scores but with no other disease indices. Sharp scores significantly correlated with assessor's global assessment, swollen and tender joint counts, pain, HAQ, and DAS28. CONCLUSION: DXR measurements are more precise than Sharp scores; both are related to long term disease activity in RA. DXR is simple to use, does not require intensive training, and may identify subjects not responding to standard treatment.

Gregory JS, Stewart A, Undrill PE, Reid DM, Aspden RM. · Department of Orthopaedics, University of Aberdeen, Aberdeen, Scotland, U.K. · Invest Radiol. · Pubmed #16118552 No free full text.

Abstract: OBJECTIVES: This article compares and combines methods for examining the external shape and the internal structure of the proximal femur with bone mineral density (BMD) to provide a classifier for hip fracture. MATERIALS AND METHODS: Fifty standard pelvic radiographs were available from age-matched fracture and control groups of postmenopausal women. Femoral shape was measured using an active shape model, the trabecular structure by means of a Fourier transform. RESULTS: Both the shape and various structure measures were independent of BMD (P=0.16 and >0.50, respectively). Calculating the area under the receiver operator characteristic (ROC) curve (Az), each of shape (Az=0.81), the best structure measure (Az=0.79-0.93), and BMD (Az=0.79), could partially classify the fracture and control groups. However, the combination achieved almost perfect separation (Az=0.99). CONCLUSIONS: This pilot study shows how bone shape and structure can complement BMD measurements for investigations of fracture risk.

Stewart A, Kumar V, Torgerson DJ, Fraser WD, Gilbert FJ, Reid DM. · Osteoporosis Research Unit, Department of Medicine and Therapeutics, University of Aberdeen, Victoria Pavilion, Woolmanhill Hospital, Aberdeen, AB25 1LD, UK. · Osteoporos Int. · Pubmed #15782281 No free full text.

Abstract: Previous studies have indicated a relationship between bone mineral density and the incidence of breast cancer in middle-aged and elderly women, with women with higher BMD being at significant increased risk. We investigated whether there was such a relationship in younger women who were perimenopausal or in their early postmenopausal years. As part of a population-screening program for osteoporosis, 5,119 women aged between 45 and 54 years were scanned between 1990-1994 at the Osteoporosis Research Unit. In 1997-2001, 3,884 returned for follow-up scans and questionnaires, and 3,144 returned a postal questionnaire in 2002. All cases of incident breast cancer were noted. One hundred sixty-six women indicated that they had suffered from breast cancer, of which 87 were incident cases (59 had prevalent breast cancer at baseline and 20 had benign or unconfirmed diagnosis and were excluded because of the use of agents that may interfere with BMD, e.g., tamoxifen). We compared therefore the incident breast cancer group (BC group; n=87) with a control group (C group; n=3,013). There were no significant differences using a t-test between the BC group and C group for baseline DXA of the spine or femoral neck. Further changes in BMD over a mean period of 6.9 years demonstrated no significant hazard ratio for the lumbar spine or femoral neck. No relationship was seen between the bone turnover markers pyridinoline/creatinine or deoxypyridinoline/creatinine assessed at their second study visit and incidence of breast cancer. In conclusion, in perimenopausal or early postmenopausal women there is no relationship between the incidence of breast cancer and BMD, change in BMD or bone turnover.

Albagha OM, Pettersson U, Stewart A, McGuigan FE, MacDonald HM, Reid DM, Ralston SH. · The Bone Research Group, Department of Medicine and Therapeutics, University of Aberdeen, Aberdeen AB25 2ZD, UK. · J Med Genet. · Pubmed #15744038 links to  free full text

Abstract: BACKGROUND: The gene encoding oestrogen receptor alpha (ESR1) appears to regulate bone mineral density (BMD) and other determinants of osteoporotic fracture risk. OBJECTIVE: To investigate the relation between common polymorphisms and haplotypes of the ESR1 gene and osteoporosis related phenotypes in a population based cohort of 3054 Scottish women. RESULTS: There was a significant association between a common haplotype "px", defined by the PvuII and XbaI restriction fragment length polymorphisms within intron 1 of the ESR1 gene, and femoral neck bone loss in postmenopausal women who had not received hormone replacement therapy (n = 945; p = 0.009). Annual rates of femoral neck bone loss were approximately 14% higher in subjects who carried one copy of px and 22% higher in those who carried two copies, compared with those who did not carry the px haplotype. The px haplotype was associated with lower femoral neck BMD in the postmenopausal women (p = 0.02), and with reduced calcaneal broadband ultrasound attenuation (BUA) values in the whole study population (p = 0.005). There was no association between a TA repeat polymorphism in the ESR1 promoter and any phenotype studied, though on long range haplotype analysis subjects with a smaller number of TA repeats who also carried the px haplotype had reduced BUA values. CONCLUSIONS: The ESR1px haplotype is associated with reduced hip BMD values and increased rates of femoral neck bone loss in postmenopausal women. An association with BUA may explain the fact that ESR1 intron 1 alleles predict osteoporotic fractures by a mechanism partly independent of differences in BMD.

Barr RJ, Adebajo A, Fraser WD, Halsey JP, Kelsey C, Stewart A, Reid DM. · Osteoporosis Research Unit of the Department of Medicine and Therapeutics, University of Aberdeen Medical School, Foresterhill, Aberdeen AB25 2ZD, Scotland, UK. · Osteoporos Int. · Pubmed #15703863 No free full text.

Abstract: While axial dual energy X-ray absorptiometry (DXA) is the accepted "gold standard" method both for diagnosing osteoporosis and predicting fractures, appropriate equipment is not universally available. Peripheral bone mass measurements may have the potential to identify patients at risk of fracture and to be used to target appropriate treatment. We assessed the effectiveness of peripheral DXA (PIXI, GELunar) in the assessment of risk and targeting treatment to prevent future fracture in 7,604 women aged 60-80 from five centres across Britain. At enrolment women completed a lifestyle and risk factor questionnaire and had a PIXI DXA scan of the heel. Women were categorised by PIXI DXA bone mineral density (BMD) into high, medium or low risk of future osteoporotic fracture. Treatment was recommended to those at highest risk. Follow-up was by simple questionnaire 18-24 months after baseline assessment. Seventy-four percent returned the follow-up questionnaire. The area under the receiver operator characteristic (ROC) curves for any fracture and osteoporotic fracture were comparable to those published using other sites and technologies. A 1-SD decrease in PIXI BMD was associated with an 86% increase in risk of osteoporotic fracture. Of the women identified as high risk, 74% had started treatment following their heel scan and 84.7% continued to take treatment at follow-up. No significant difference was noted in fracture rates in those who started treatment after assessment compared to those who did not. While peripheral DXA is highly effective for predicting older women who are at increased risk of future fracture, it has yet to be established as an effective method for targeting bisphosphonate or other therapy.

Stewart A, Mackenzie LM, Black AJ, Reid DM. · Osteoporosis Research Unit, Victoria Pavilion, Woolmanhill Hospital, Aberdeen AB25 1LD, Scotland, UK. · Rheumatology (Oxford). · Pubmed #15328427 links to  free full text

Abstract: OBJECTIVE: Periarticular osteoporosis is one of the first radiological signs of rheumatoid arthritis (RA). Osteoporosis is now quantified using dual-energy X-ray absorptiometry (DXA), although it was originally assessed by radiogrammetry. A new updated system of radiogrammetry has been developed: digitized X-ray radiogrammetry (DXR). We used this DXR system to identify whether changes seen in hand X-rays of RA patients can predict those who subsequently develop erosions. METHODS: We enrolled 24 patients with early RA and they attended for hand radiographs at baseline, 12, 24 and 48 months. The hand radiographs were analysed using a Pronosco X-Posure system which measures bone mineral density, and other parameters using DXR. DXA of the hand was also performed to measure bone mineral density. Sharp and Larsen radiographic scores were calculated and other disease activity markers were measured. RESULTS: DXR bone mineral density fell significantly throughout the study. The group of RA subjects were divided according to the change in erosive status. Change in DXR bone mineral density after 1 yr was very specific (100%) and highly sensitive (63%) in predicting those who either became erosive or whose erosions significantly worsened. In contrast, of the other disease activity markers, only baseline ESR (sensitivity 67%, specificity 80%) significantly predicted the erosive status of subjects at 4 yr. CONCLUSION: Computerized radiogrammetry from digitized images can predict at 1 yr those patients with RA who will become erosive at 4 yr. A larger prospective study is required to confirm these findings; however, these results show some promise as a method of targeting those patients who require more aggressive, expensive therapy.

Gregory JS, Testi D, Stewart A, Undrill PE, Reid DM, Aspden RM. · Department of Orthopaedics, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen, AB25 2ZD, UK. · Osteoporos Int. · Pubmed #14605797 No free full text.

Abstract: The shape of the proximal femur has been demonstrated to be important in the occurrence of fractures of the femoral neck. Unfortunately, multiple geometric measurements frequently used to describe this shape are highly correlated. A new method, active shape modeling (ASM) has been developed to quantify the morphology of the femur. This describes the shape in terms of orthogonal modes of variation that, consequently, are all independent. To test this method, digitized standard pelvic radiographs were obtained from 26 women who had suffered a hip fracture and compared with images from 24 age-matched controls with no fracture. All subjects also had their bone mineral density (BMD) measured at five sites using dual-energy X-ray absorptiometry. An ASM was developed and principal components analysis used to identify the modes which best described the shape. Discriminant analysis was used to determine which variable, or combination of variables, was best able to discriminate between the groups. ASM alone correctly identified 74% of the individuals and placed them in the appropriate group. Only one of the BMD values (Ward's triangle) achieved a higher value (82%). A combination of Ward's triangle BMD and ASM improved the accuracy to 90%. Geometric variables used in this study were weaker, correctly classifying less than 60% of the study group. Logistic regression showed that after adjustment for age, body mass index, and BMD, the ASM data was still independently associated with hip fracture (odds ratio (OR)=1.83, 95% confidence interval 1.08 to 3.11). The odds ratio was calculated relative to a 10% increase in the probability of belonging to the fracture group. Though these initial results were obtained from a limited data set, this study shows that ASM may be a powerful method to help identify individuals at risk of a hip fracture in the future.

Stewart A, Reid DM. · Department of Medicine and Therapeutics, University of Aberdeen, UK. · Br J Radiol. · Pubmed #10884730 links to  free full text

Abstract: Dual energy X-ray absorptiometry (DXA) is the current technique of choice to assess risk of future fracture and to diagnose osteoporosis as defined by bone mineral density (BMD). Guidelines for bone densitometry referral have been published listing clinical risk factors that might be considered grounds for assessment. However, these factors are known to be poorly predictive of subsequent BMD measurement and, accordingly, new inexpensive methods of selecting subjects for assessment should be sought. Quantitative ultrasound (QUS) of bone may be such a technique. Women (n = 250) considered by their general practitioners to be at risk of osteoporosis and who had been referred for DXA measurements of the spine and hip were recruited into the study. All underwent a QUS scan of the heel using a McCue CUBA Clinical machine, which measures broadband ultrasound attenuation (BUA) and velocity of sound (VOS), a clinical risk factor questionnaire, and spine and hip BMD measurement by a Norland XR-26 bone densitometer. Patients were categorized according to published diagnostic criteria for BMD, and these were also applied to the QUS parameters. Risk factors were arbitrarily categorized into "low", "medium" and "high" risk groups. Kappa scores were calculated to analyse the agreement between different techniques. Receiver operator characteristic (ROC) analyses were undertaken to demonstrate the technique with the best sensitivity and specificity for the detection of low BMD at the spine and hip. Analysis of the bone mass data demonstrated only moderate agreement (kappa 0.33) between femoral neck and spine BMD with femoral neck BMD and BUA showing a very similar level of agreement (kappa 0.31). ROC analysis demonstrated that VOS followed by BUA was the best predictor of low BMD, with risk factors alone being significantly poorer; QUS parameters are better predictors than clinical risk factors for women with low BMD and could be used effectively at the primary care level to indicate those who should be considered for full osteoporosis assessment. However, further study into the cost effectiveness of this approach is required.

Stewart A, Reid DM. · Osteoporosis Research Unit, Department of Medicine and Therapeutics, University of Aberdeen, UK. · Bone. · Pubmed #10865221 No free full text.

Abstract: Quantitative ultrasound (QUS) measurements of bone have been shown to be independent predictors of osteoporotic fracture risk. Drawbacks of this technique have included the precision of the scanners, which is said to be poorer than in dual-energy X-ray absorptiometry (DXA), in part due to difficulty in repositioning of the foot in an os calcis system and difficulty in comparison across different technologies. A new type of QUS scanner has been introduced that produces an image of the area scanned and is believed to improve precision by aiding repositioning. In this study, we compare three scanners: a dry system (McCue CUBA Clinical); a nonimaging water-bath system (Lunar Achilles(+)); and an imaging water-bath system (Osteometer DTU-One). Short-term phantom precision was calculated by repeating measurements ten times in succession on the manufacturer-supplied phantom. Long-term phantom precision was calculated by examining the phantom measurements over a 6 month period. In vivo precision was calculated in 26 normal volunteers (19 women, 7 men) and 20 women with osteoporosis. Monitoring time intervals (MTIs) were also calculated using the manufacturer's normative database. The MTI is the period between scans required to show that a "true" change has occurred, and was between 0.5 year for stiffness (a derived index produced by the Lunar Achilles instrument) and >5 years for all other measurements. The imaging system did not seem to improve precision. Precision for the QUS phantom was similar to that of DXA with a coefficient of variation (CV) of around 1.5% for BUA and <1% for speed of sound (SOS). The precision was such that the technique may be considered for monitoring skeletal changes. However, the change of bone mass at the os calcis in response to treatment was slow, which made the time needed to wait before assessing change, on the whole, longer than that for DXA. An exception may be the Lunar Achilles "stiffness" parameter, but this can only be determined in a longitudinal, comparative treatment study.

Stewart A, Walker LG, Porter RW, Reid DM, Primrose WR. · Osteoporosis Research Unit, Department of Medicine and Therapeutics, University of Aberdeen, UK. · J Clin Densitom. · Pubmed #10677789 No free full text.

Abstract: In an attempt to identify a high-risk cohort of patients, who could be offered preventive therapy, we assessed patients who had suffered one hip fracture. A total of 394 patients were prospectively followed to determine those who had suffered a second fracture. Entry bone mass of the unfractured hip and total body was examined by dual X-ray absorptiometry (DXA) and of the os calcis, by quantitative ultrasound (QUS), along with various clinical parameters. The relative risks in the QUS parameters did not reach significance, except for broadband ultrasound attentuation as measured by the McCue CUBA Clinical, whereas femoral neck and total body bone mineral density also reached significance. Lowest quartile body weight was also a significant risk factor as were occurrence of a new fall and poor mobility score. Using Receiver Operator Characteristic curves, we found no significant differences between DXA trochanter or for the Mini Mental State Examination score in predicting those who sustained a second hip fracture. In this elderly group risk factors are almost as good as bone mass at predicting those who will sustain a second hip fracture. Low body weight and poor mobility could be used as triggers for the use of preventive therapy without the use of bone mass measurements and to target expensive preventive therapy to reduce fracture risk.

Stewart A, Black A, Robins SP, Reid DM. · Department of Medicine and Therapeutics, University of Aberdeen, UK. · J Rheumatol. · Pubmed #10090173 No free full text.

Abstract: OBJECTIVE: Osteoarthritis (OA) and osteoporosis (OP) are reported to be rare in the same patient. We examined bone mass, bone turnover, and radiological presence of OA in a group of patients with OA with previous hip fractures and age matched controls. METHODS: Bone mass was assessed by bone mineral density (BMD), using dual energy x-ray absorptiometry (DEXA) of the hip and total body, and quantitative ultrasound of the os calcis, measuring broadband ultrasound attenuation and velocity of sound. Bone turnover was assessed by measuring urinary pyridinium crosslinks and serum osteocalcin. RESULTS: There were differences in bone density, the patients with OP having lower bone density, while patients with OA had similar or increased bone density compared to controls, Serum osteocalcin showed no significant differences among the 3 groups of patients. Urinary pyridinium crosslinks excretion was significantly elevated in the OA group but not in the OP group compared with controls. CONCLUSION: Increased bone turnover was restricted to the OA group.