Bone loss. Quantitative imaging techniques for assessing bone mass in rheumatoid arthritis

Osteoporosis is associated with low bone mass and microarchitectural deterioration of bone tissue with clinical manifestation of low trauma fractures. Rheumatoid arthritis (RA) is a risk factor due to generalized and articular bone loss. This minireview presents past and current bone mass measurement techniques in RA. These techniques include: plain radiographs, absorptiometry, quantitative computed tomography (QCT) and ultrasound. The most widely used technique is dual x-ray absorptiometry (DXA). RA patients have lower bone mass as compared with normals and substantial bone loss may occur early after the onset of disease. Measurement of bone mineral density (BMD) at the hand using either DXA or ultrasound maybe a useful tool in the management of RA patients.     

Relationships between bone mass and micro-architecture at the mandible and iliac bone in edentulous subjects: a dual X-ray absorptiometry, computerised tomography and microcomputed tomography study

doi: 10.1111/j.1741‐2358.2011.00527.x Relationships between bone mass and micro‐architecture at the mandible and iliac bone in edentulous subjects: a dual X‐ray absorptiometry, computerised tomography and microcomputed tomography study Objectives: To compare bone volume, bone mineral density, cortical thickness and bone micro‐architecture in a series of paired mandibular and iliac bone samples analysed by various imagery techniques to see whether relationships exist between the various techniques and between mandibular and iliac bone. Materials and methods: Bone samples from the mandible and ilium were harvested in 20 cadavers and analysed by dual energy X‐ray absorptiometry (DXA), computerised tomography (CT) on a conventional hospital machine and microCT. Results: Significant correlations were found between Hounsfield density obtained by CT, and bone mass determined by microCT but not with DXA values. Cortical thickness measurements were well correlated between CT and microCT. No relationships were found between mandibular and iliac bone, when considering mineral density, cortical thickness, bone volume or micro‐architecture. Conclusion: In clinical practice, CT remains the most appropriate routine means for bone qualitative and quantitative evaluation at the mandible. In this ex vivo study, these results confirm that mandibular bone status does not reflect the axial skeletal one and assist in the placement of implants with dental prostheses in old or osteoporotic patients.     

Assessment of bone architecture with ultrasonometry: experimental and clinical experience

Over the last decade, ultrasound technology has been introduced as a method of analysing bone tissue in clinical practice, and several studies have compared various ultrasound devices with dual-energy X-ray absorptiometry (DXA). Unlike DXA, the ultrasound technique is not limited to the measurement of bone density - it also has the potential to provide information on the mechanical and architectural characteristics of bone. The first generation of ultrasound devices used the speed of sound and attenuation of the ultrasound signal to obtain information on bone mineral content. Second generation ultrasound devices, which analyse the ultrasound signal received, permit the study of bone structure and elasticity, in addition to its mineral content, in both experimental studies and clinical practice. This is accomplished by signal processing analysis, the study of backscattering and the application of Biot's theory. This approach to the study of bone tissue represents the future for the development of ultrasound technology for use in clinical practice.     

The D3-creatine dilution method non-invasively measures muscle mass in mice

Developing accurate methods to quantify age-related muscle loss (sarcopenia) could greatly accelerate development of therapies to treat muscle loss in the elderly, as current methods are inaccurate or expensive. The current gold standard method for quantifying sarcopenia is dual-energy X-ray absorptiometry (DXA) but does not measure muscle directly—it is a composite measure quantifying “lean mass” (muscle) excluding fat and bone. In humans, DXA overestimates muscle mass, which has led to erroneous conclusions about the importance of skeletal muscle in human health and disease. In animal models, DXA is a popular method for measuring lean mass. However, instrumentation is expensive and is potentially limited by anesthesia concerns. Recently, the D₃-creatine (D₃Cr) dilution method for quantifying muscle mass was developed in humans and rats. This method is faster, cheaper, and more accurate than DXA. Here, we demonstrate that the D₃Cr method is a specific assay for muscle mass in mice, and we test associations with DXA and body weight. We evaluated the D₃Cr method compared to DXA-determined lean body mass (LBM) in aged mice and reported that DXA consistently overestimates muscle mass with age. Overall, we provide evidence that the D₃Cr dilution method directly measures muscle mass in mice. Combined with its ease of use, accessibility, and non-invasive nature, the method may prove to more quickly advance development of preclinical therapies targeting sarcopenia.     

Non-invasive measure of body composition of snakes using dual-energy X-ray absorptiometry

Non-invasive techniques to measure body composition are critical for longitudinal studies of energetics and life histories and for investigating the link between body condition and physiology. Previous attempts to determine, non-invasively, the body composition of snakes have proven problematic. Therefore, we explored whether dual-energy X-ray absorptiometry (DXA) could be used to determine the body composition of snakes. We analyzed 20 adult diamondback water snakes (Nerodia rhombifer) with a DXA instrument and subsequently quantified their body composition by gravimetric and chemical extraction methods. Body composition components scaled with body mass with mass exponents between 0.88 and 1.53. DXA values for lean tissue mass, fat mass and total-body bone mineral mass were significantly correlated with observed masses of lean tissue, fat and ash from chemical analysis. Using regression models incorporating DXA values we predicted the fat-free tissue mass, lean tissue mass, fat mass, ash mass and total body water content for this sample of water snakes. A cross-validation procedure demonstrated that these models estimated fat-free tissue mass, lean tissue mass, fat mass, ash mass and total-body water content with respective errors of 2.2%, 2.3%, 16.0%, 6.6% and 3.5%. Compared to other non-invasive techniques, include body condition indices, total body electrical conductivity (TOBEC) and cyclopropane absorption, DXA can more easily and accurately be used to determine the body composition of snakes.     

Accuracy and precision of dual-energy X-ray absorptiometry for body composition measurements in rhesus monkeys

Accuracy of body composition measurements by dual-energy X-ray absorptiometry (DXA) was compared with direct chemical analysis in 10 adult rhesus monkeys. DXA was highly correlated (r-values > 0.95) with direct analyses of body fat mass (FM), lean mass (LM) and lumbar spine bone mineral content (BMC). DXA measurements of total body BMC were not as strongly correlated (r-value = 0.58) with total carcass ash content. DXA measurements of body FM, LM and lumbar spine BMC were not different from data obtained by direct analyses (P-values > 0.30). In contrast, DXA determinations of total BMC (TBMC) averaged 15%, less than total carcass ash measurements (P = 0.002). In conclusion, this study confirms the accurate measurement of fat and lean tissue mass by DXA in rhesus monkeys. DXA also accurately measured lumbar spine BMC but underestimated total body BMC as compared with carcass ash determinations.     

Bone densitometry: assessing the effects of growth hormone treatment in adults

Dual-energy X-ray absorptiometry (DXA) is the reference method for the measurement of bone mineral mass at different skeletal sites. It has been widely used in recent years to assess the effects of growth hormone (GH) treatment on bone metabolism. In normal individuals, bone mineral content (BMC) and density (BMD), as assessed using DXA, correlate with body size. Therefore, using DXA in patients with congenital GH deficiency (GHD), who have a smaller body frame, would be expected to result in lower bone mass. Thus, comparisons with reference data derived from populations of normal body size are invalid. The evaluation of the effects of GH administration should take into account the possible effects of GH on bone size, not only in children, but also in adults. The enlargement of bone, due to stimulation of the periosteal apposition, may partially mask an increase in BMC, resulting in little or no change in BMD. The ability of GH to affect bone area therefore requires analysis of the possible changes in bone area and BMC, as well as BMD. This issue has been poorly handled in the studies published to date. Lastly, the acceleration of bone turnover induced by GH leads to an increase in bone remodelling space, which in turn is associated with a reduction in BMC and BMD, independent of the net balance between breakdown and formation in each metabolic unit. This bone loss is completely reversible when the remodelling space returns to previous levels. This phenomenon must be taken into account when analysing the effects of GH treatment on bone mass, because a net gain in bone mass may be found in long-term GH treatment or after GH discontinuation, even if bone loss was evident during the first 6 months of treatment. In conclusion, the interpretation of bone density data in patients with GHD, and after GH administration, should take into account some of the methodological aspects of bone densitometry, as well as the specific actions of GH on bone metabolism and body composition.     

Precision and Accuracy of Dual‐Energy X‐ray Absorptiometry for Determining in Vivo Body Composition of Mice

Objective: To evaluate the precision and accuracy of dual‐energy X‐ray absorptiometry (DXA) for the measurement of total‐bone mineral density (TBMD), total‐body bone mineral (TBBM), fat mass (FM), and bone‐free lean tissue mass (LTM) in mice. Research Methods and Procedures: Twenty‐five male C57BL/6J mice (6 to 11 weeks old; 19 to 29 g) were anesthetized and scanned three times (with repositioning between scans) using a peripheral densitometer (Lunar PIXImus). Gravimetric and chemical extraction techniques (Soxhlet) were used as the criterion method for the determination of body composition; ash content was determined by burning at 600°C for 8 hours. Results: The mean intraindividual coefficients of variation (CV) for the repeated DXA analyses were: TBMD, 0.84%; TBBM, 1.60%; FM, 2.20%; and LTM, 0.86%. Accuracy was determined by comparing the DXA‐derived data from the first scan with the chemical carcass analysis data. DXA accurately measured bone ash content (p = 0.942), underestimated LTM (0.59 ± 0.05g, p < 0.001), and overestimated FM (2.19 ± 0.06g, p < 0.001). Thus, DXA estimated 100% of bone ash content, 97% of carcass LTM, and 209% of carcass FM. DXA‐derived values were then used to predict chemical values of FM and LTM. Chemically extracted FM was best predicted by DXA FM and DXA LTM [FM = ?0.50 + 1.09(DXA FM) ? 0.11(DXA LTM), model r² = 0.86, root mean square error (RMSE) = 0.233 g] and chemically determined LTM by DXA LTM [LTM = ?0.14 + 1.04(DXA LTM), r² = 0.99, RMSE = 0.238 g]. Discussion: These data show that the precision of DXA for measuring TBMD, TBBM, FM, and LTM in mice ranges from a low of 0.84% to a high of 2.20% (CV). DXA accurately measured bone ash content but overestimated carcass FM and underestimated LTM. However, because of the close relationship between DXA‐derived data and chemical carcass analysis for FM and LTM, prediction equations can be derived to more accurately predict body composition.     

Pregnancy-associated changes in bone density and bone turnover in the physiological state: prospective data on sixteen women.

Areal bone mineral density (BMD, g/cm 2) was measured for the total body, lumbar spine and hip with dual-energy x-ray absorptiometry (DXA) before pregnancy and after delivery in sixteen women aged 21 - 35 years. Additional measurements included quantitative ultrasound indices (broadband ultrasound attenuation, BUA, at the calcaneus at baseline and at 16, 26, and 36 weeks of pregnancy, and postpartum) as well as biochemical markers of bone formation and resorption (measured before pregnancy and during pregnancy at 16, 22, 26, 30, 34, and 36 weeks of pregnancy and postpartum). The results of measurements were as follows: 1. Postpartum BMD showed a significant reduction in the total body (- 13.4 %), in the spine (- 9.2 %) and in the hip (-7.8 % at the femoral neck and - 9.2 % at the Ward's triangle) compared to pre-pregnancy values. 2. Biochemical markers of bone resorption increased by 26 weeks. 3. Bone ultrasound measurements that provide information on bone density before delivery did not change throughout pregnancy. A significant reduction of BUA (- 14.5 % compared to baseline) was observed postpartum only. These data would suggest that pregnancy-induced bone loss develops rapidly after the 36 week of pregnancy, possibly via enhanced bone resorption.     

Non-invasive methods for the determination of body and carcass composition in livestock: dual-energy X-ray absorptiometry,computed tomography,magnetic resonance imaging and ultrasound: invited review

The ability to accurately measure body or carcass composition is important for performance testing, grading and finally selection or payment of meat-producing animals. Advances especially in non-invasive techniques are mainly based on the development of electronic and computer-driven methods in order to provide objective phenotypic data. The preference for a specific technique depends on the target animal species or carcass, combined with technical and practical aspects such as accuracy, reliability, cost, portability, speed, ease of use, safety and for in vivo measurements the need for fixation or sedation. The techniques rely on specific device-driven signals, which interact with tissues in the body or carcass at the atomic or molecular level, resulting in secondary or attenuated signals detected by the instruments and analyzed quantitatively. The electromagnetic signal produced by the instrument may originate from mechanical energy such as sound waves (ultrasound – US), ‘photon’ radiation (X-ray-computed tomography – CT, dual-energy X-ray absorptiometry – DXA) or radio frequency waves (magnetic resonance imaging – MRI). The signals detected by the corresponding instruments are processed to measure, for example, tissue depths, areas, volumes or distributions of fat, muscle (water, protein) and partly bone or bone mineral. Among the above techniques, CT is the most accurate one followed by MRI and DXA, whereas US can be used for all sizes of farm animal species even under field conditions. CT, MRI and US can provide volume data, whereas only DXA delivers immediate whole-body composition results without (2D) image manipulation. A combination of simple US and more expensive CT, MRI or DXA might be applied for farm animal selection programs in a stepwise approach.     

Dual-energy X-ray absorptiometry (DXA) can accurately and nondestructively measure the body composition of small, free-living rodents

Dual-energy x-ray absorptiometry (DXA) is a nondestructive technique that can potentially measure specific components of whole-body composition in free-living and lab-raised animals. Our aim was to test the ability of DXA to measure the composition of a common arvicoline rodent, the northern red-backed vole (Clethrionomys rutilus). We used a DXA apparatus to obtain measurements of fat mass (FM), lean mass (LM),bone mineral content, bone mineral density, and fat-free mass(FFM) in carcasses of free-living and lab-raised voles. We then used chemical carcass analysis to derive predictive algorithms for actual values of FM, total body water, total protein, total mineral, LM, and FFM. Unexplained error in the equations for all voles grouped collectively ranged from R(2) = 0.82 to R(2) = 0.98. The DXA FM measurement had the highest coefficient of variation, and it was higher for free-living voles than for lab-raised voles. However, FM can be determined by difference with excellent precision by using the FFM equation (R(2) = 0.98). We also derived corrective terms for passive integrated transponder-tagged animals. Thus, DXA is a nonlethal, nondestructive tool capable of precisely and accurately measuring many specific parameters of whole-body composition in small free-living and lab-raised rodents.     

Body Fat Loss Automatically Reduces Lean Mass by Changing the Fat‐Free Component of Adipose Tissue

Fat‐free mass or lean tissue mass includes nonskeletal muscle components such as the fat‐free component of adipose tissue fat cells. This fat‐free component of adipose tissue may need to be taken into consideration when large changes in body fat occur following a weight loss intervention. It is not uncommon to see a loss of lean mass with interventions designed to promote the loss of large amounts of fat mass. However, after eliminating the influence of the fat‐free component of adipose tissue on dual‐energy x‐ray absorptiometry (DXA)‐derived lean mass, the original loss of lean mass is no longer observed or is markedly reduced. This suggests that the majority of the lean mass lost with dieting may be the fat‐free component of adipose tissue. To accurately estimate the change in lean tissue, eliminating the fat‐free adipose tissue from DXA‐derived lean mass is needed when large changes in body fat occur following an intervention.     

Ovariectomy-induced bone loss occurs independently of B cells

Estrogen withdrawal is associated with a significant expansion in B cell precursor and mature B cell populations. However, despite significant circumstantial evidence the role of B lineage cells in ovariectomy-induced bone loss in vivo is unclear. In vitro studies have demonstrated that mature B cells have the potential to both positively and negatively impact osteoclastogenesis by virtue of their capacity to secrete pro-osteoclastogenic cytokines including receptor activator of NFkappaB ligand (RANKL), as well as anti-osteoclastogenic cytokines such as osteoprotegerin (OPG) and transforming growth factor beta (TGFbeta). Although several studies have suggested that expansion of the B lineage following ovariectomy may play a key role in the etiology of ovariectomy-induced bone loss, in vivo studies to directly test this notion have yet to be conducted. In this study, we performed ovariectomy on microMT(-/-) mice which are specifically deficient in mature B cells. Analysis of bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA) and micro-computed tomography (CT) demonstrate that mature B cell-deficient mice undergo an identical loss of bone mass relative to wild-type (WT) control mice. Our data demonstrate that mature B cells are not central mediators of ovariectomy-induced bone loss in vivo.     

The Lichfield bone study: the skeletal response to exercise in healthy young men

The skeletal response to short-term exercise training remains poorly described. We thus studied the lower limb skeletal response of 723 Caucasian male army recruits to a 12-wk training regime. Femoral bone volume was assessed using magnetic resonance imaging, bone ultrastructure by quantitative ultrasound (QUS), and bone mineral density (BMD) using dual-energy X-ray absorptiometry (DXA) of the hip. Left hip BMD increased with training (mean ± SD: 0.85 ± 3.24, 2.93 ± 4.85, and 1.89 ± 2.85% for femoral neck, Ward's area, and total hip, respectively; all P < 0.001). Left calcaneal broadband ultrasound attenuation rose 3.57 ± 0.5% (P < 0.001), and left and right femoral cortical volume by 1.09 ± 4.05 and 0.71 ± 4.05%, respectively (P = 0.0001 and 0.003), largely through the rise in periosteal volume (0.78 ± 3.14 and 0.59 ± 2.58% for right and left, respectively, P < 0.001) with endosteal volumes unchanged. Before training, DXA and QUS measures were independent of limb dominance. However, the dominant femur had higher periosteal (25,991.49 vs. 2,5572 mm(3), P < 0.001), endosteal (6,063.33 vs. 5,983.12 mm(3), P = 0.001), and cortical volumes (19,928 vs. 19,589.56 mm(3), P = 0.001). Changes in DXA, QUS, and magnetic resonance imaging measures were independent of limb dominance. We show, for the first time, that short-term exercise training in young men is associated not only with a rise in human femoral BMD, but also in femoral bone volume, the latter largely through a periosteal response.     

Hormone replacement therapy improves distal radius bone structure by endocortical mineral deposition

Hormone replacement therapy (HRT) produces a small increase in bone mineral density (BMD) when measured by dual energy X-ray absorptiometry (DXA). The corresponding decrease in fracture risk is more impressive, implying that other factors that contribute to bone strength are favourably modified by HRT. We investigated, using peripheral quantitated computed tomography (pQCT), the changes produced by HRT in both the distribution of mineral between cortical and trabecular bone and the changes produced by HRT in the apparent structure of trabecular bone, expressed as average hole area and apparent connectivity. Twenty-one postmenopausal women starting HRT and 32 control women were followed for 2 years, with distal radius pQCT measurements every 6 months. HRT prevented the loss of total bone mass seen in controls (p < 0.02). HRT also produced an apparent rapid loss of trabecular bone mass within the first 6 months of the study (p < 0.02), with an associated rapid loss in the apparent connectivity (p = 0.034). Average hole area also increased but not to a statistically significant extent. Exogenous estrogen apparently fills small marrow pores close to the endocortical surface, such that the pQCT-defined boundary between trabecular and cortical bone is shifted in favour of cortical bone. Trabecular bone structure indices are adversely affected, as the central, poorly interconnected trabecular bone with greater than average marrow spaces constitutes a greater fraction of the remaining trabecular bone. This study suggests that the improvements in fracture risk resulting from HRT are explained by a reversal of net endocortical resorption of bone.     

Combination of conjugated linoleic acid with fish oil prevents age-associated bone marrow adiposity in C57Bl/6J mice

The inverse relationship between fat in bone marrow and bone mass in the skeleton of aging subjects is well known. However, there is no precise therapy for the treatment of bone marrow adiposity. We investigated the ability of conjugated linoleic acid (CLA) and fish oil (FO), alone or in combination, to modulate bone loss using 12 months old C57Bl/6J mice fed 10% corn oil diet as control or supplemented with 0.5% CLA or 5% FO or 0.5% CLA+5% FO for 6 months. We found, CLA-fed mice exhibited reduced body weight, body fat mass (BFM) and enhanced hind leg lean mass (HLLM) and bone mineral density (BMD) in different regions measured by dual energy x-ray absorptiometry (DXA); however, associated with fatty liver and increased insulin resistance; whereas, FO fed mice exhibited enhanced BMD, improved insulin sensitivity, with no changes in BFM and HLLM. Interestingly, CLA+FO fed mice exhibited reduced body weight, BFM, peroxisome proliferator-activated receptor gamma and cathepsin K expression in bone marrow with enhanced BMD and HLLM. Moreover, CLA+FO supplementation reduced liver hypertrophy and improved insulin sensitivity with remarkable attenuation of bone marrow adiposity, inflammation and oxidative stress in aging mice. Therefore, CLA with FO combination might be a novel dietary supplement to reduce fat mass and improve BMD.     

Hormonal therapies and osteoporosis

Osteoporosis, now defined as a disease characterized by low bone mass and a microarchitectural deterioration of bone tissue leading to enhanced bone fragility and fracture risk, is a major public health problem. Classic hormonal therapies to prevent and treat osteoporosis associated with menopause have recently been questioned due to the risk/benefit ratio of prolonged treatment. There is a critical need for safe and effective alternative therapeutics for this disease. Nonhuman primates have been used as models to assess bone changes associated with estrogen deficiency because their trabecular and cortical bone remodeling processes, monthly menstrual cycles, and reproductive-hormone patterns are similar to those of humans. The ovariectomized nonhuman primate has become the preferred model in which to study effects on bone remodeling, particularly with regard to bone mass, architecture, and strength, in fulfillment of studies required by international guidelines for the development of antiosteoporotic drugs. The nonhuman primate is amenable to several methodologies that assess bone quantity and quality, including dual energy x-ray absorptiometry (DXA), quantitative computed tomography (QCT), histology, static and dynamic histomorphometry, and biomechanical testing, as well as assays developed for clinical use, which serve as biomarkers of bone metabolic processes. The use of the nonhuman primate model in the assessment of osteoporosis therapeutics, both hormonal (sex steroids and their analogues, parathyroid hormone) and nonhormonal (bisphosphonates), has provided valuable information on the safety and efficacy as well as the mechanisms of bone loss associated with estrogen deficiency that is directly applicable to the human situation.     

Evaluation of trabecular mechanical and microstructural properties in human calcaneal bone of advanced age using mechanical testing, microCT, and DXA

Early detection of fracture risk is important for initiating treatment and improving outcomes from both physiologic and pathologic causes of bone loss. While bone mineral density (a quantity measure) has traditionally been used for this purpose, alternative structural imaging parameters (quality measures) are proposed to better predict bone's true mechanical properties. To further elucidate this, trabecular bone from cadaveric human calcanei were used to evaluate the interrelationship of mechanical and structural parameters using mechanical testing, dual energy X-ray absorptiometry (DXA) scanning, and micro computed tomography (microCT) imaging. Directional specific structural properties were assessed in three-dimensional (3-D) and correlated to mechanical testing and DXA. The results demonstrated that microCT-derived indices of bone quality (i.e., volume fraction and structural model index) are better than DXA-derived bone mineral density for the prediction of the mechanical parameters of bone (i.e., elastic modulus, yield stress, and ultimate stress). Diagnostically, this implies that future work on the early prediction of fracture risk should focus as much on bone quality as on quantity. Furthermore, the results of this study show that a loss of bone primarily affects the connectedness and overall number of trabeculae. Ultimate stress, however, is better correlated with trabecular number than thickness. As such, primary prevention of osteoporosis may be more important than later countermeasures for bone loss.     

Validity and reliability of dual-energy X-ray absorptiometry for the assessment of abdominal adiposity.

A number of methods exist for the estimation of abdominal obesity, ranging from waist-to-hip ratio to computed tomography (CT). Although dual-energy X-ray absorptiometry (DXA) was originally used to measure bone density and total body composition, recent improvements in software allow it to determine abdominal fat mass. Sixty-five men and women aged 18-72 yr participated in a series of studies to examine the validity and reliability of the DXA to accurately measure abdominal fat. Total body fat and abdominal regional fat were measured by DXA using a Lunar DPX-IQ. Multislice CT scans were performed between L1 and L4 vertebral bodies (region of interest) using a Picker PQ5000 CT scanner, and volumetric analyses were carried out on a Voxel Q workstation. Both abdominal total tissue mass (P = 0.02) and abdominal fat mass (P < 0.0001) in the L1-L4 region of interest were significantly lower as measured by DXA compared with multislice CT. However, Bland-Altman analysis demonstrated good concordance between DXA and CT for abdominal total tissue mass (i.e., limits of agreement = -1.56-2.54 kg) and fat mass (i.e., limits of agreement = -0.40-1.94 kg). DXA also showed excellent reliability among three different operators to determine total, fat, and lean body mass in the L1-L4 region of interest (intraclass correlations, R = 0.94, 0.97, and 0.89, respectively). In conclusion, the DXA L1-L4 region of interest compared with CT proved to be both reliable and accurate method to determine abdominal obesity.     

Development and validation of the Osteoporosis Risk Assessment Instrument to facilitate selection of women for bone densitometry

BACKGROUND: Although mass screening for osteoporosis is not recommended among postmenopausal women, there is no consensus on which women should undergo testing for low bone mineral density. The objective of this study was to develop and validate a clinical tool to help clinicians identify which women are at increased risk for osteoporosis and should therefore undergo further testing with bone densitometry. METHODS: Using Ontario baseline data from the Canadian Multicentre Osteoporosis Study, we identified all cognitively normal women aged 45 years or more who had undergone testing with dual-energy x-ray absorptiometry (DXA) at both the femoral neck and the lumbar spine (L1-L4). Participants who had a previous diagnosis of osteoporosis or were taking bone active medication other than ovarian hormones were excluded. The main outcome measure was low bone mineral density (T score of 2 or more standard deviations below the mean for young Canadian women) at either the femoral neck or the lumbar spine. Logistic regression analysis and receiver operating characteristic (ROC) analysis were used to identify the simplest algorithm that would identify women at increased risk for low bone mineral density. RESULTS: The study population comprised 1376 women, of whom 926 were allocated to the development of the tool and 450 to its validation. A simple algorithm based on age, weight and current estrogen use (yes or no) was developed. Validation of this 3-item Osteoporosis Risk Assessment Instrument (ORAI) showed that the tool had a sensitivity of 93.3% (95% confidence interval [CI] 86.3%-97.0%) and a specificity of 46.4% (95% CI 41.0%-51.8%) for selecting women with low bone mineral density. The sensitivity of the instrument for selecting women with osteoporosis was 94.4% (95% CI 83.7%-98.6%). Use of the ORAI represented a 38.7% reduction in DXA testing compared with screening all women in our study. INTERPRETATION: The ORAI accurately identifies the vast majority of women likely to have low bone mineral density and is effective in substantially decreasing the need for all women to undergo DXA testing.