Search

Recently, the bone strain index (BSI), a new index of bone strength based on a finite element model (FEA) from dual X-ray absorptiometry (DXA), has been developed. BSI represents the average equivalent strain inside the bone, assuming that a higher strain level (high BSI) indicates a condition of higher risk. Our study aimed to analyze the relationship between BSI and age, BMI and areal BMD in pre- and postmenopausal women and to prospectively investigate fracture prediction (Fx) by BSI in postmenopausal women. Methods. At the 14th annual follow-up of the OFELY study, BSI was measured at spine (Spine BSI) and femoral scans (Neck and Total Hip BSI), in addition to areal BMD with DXA (Hologic QDR 4500) in 846 women, mean (SD) age 60 yr (15). The FRAX® (fracture risk assessment tool) for major osteoporotic fractures (MOF) was calculated with FN areal BMD (aBMD) at baseline; incident fragility fractures were annually registered until January 2016. Results. In premenopausal women (n = 261), Neck and Total Hip BSI were slightly negatively correlated with age (Spearman r = -0.13 and -0.15 respectively, p = 0.03), whereas all BSIs were positively correlated with BMI (r = +0.20 to 0.37, p 0.01) and negatively with BMD (r = -0.69 to -0.37, p 0.0001). In postmenopausal women (n = 585), Neck and Total Hip BSI were positively correlated with age (Spearman r = +0.26 and +0.31 respectively, p 0.0001), whereas Spine BSI was positively correlated with BMI (r = +0.22, p 0.0001) and all BSIs were negatively correlated with BMD (r = -0.81 to -0.60, p 0.0001). During a median [IQ] 9.3 [1.0] years of follow-up, 133 postmenopausal women reported an incident fragility Fx, including 80 women with a major osteoporotic Fx (MOF) and 26 women with clinical vertebral Fx (VFx). Each SD increase of BSI value was associated with a significant increase of the risk of all fragility Fx with an age-adjusted HR of 1.23 for Neck BSI (p = 0.02); 1.27 for Total Hip BSI (p = 0.004) and 1.35 for Spine BSI (p 0.0001). After adjustment for FRAX®, the association remained statistically significant for Total Hip BSI (HR 1.24, p = 0.02 for all fragility Fx; 1.31, p = 0.01 for MOF) and Spine BSI (HR 1.33, p 0.0001 for all fragility Fx; 1.33, p = 0.005 for MOF; 1.67, p = 0.002 for clinical VFx). In conclusion, spine and femur BSI, an FEA DXA derived index, predict incident fragility fracture in postmenopausal women, regardless of FRAX®.

Many fractures occur in individuals with normal areal Bone Mineral Density (aBMD) measured by Dual X-ray Absorptiometry (DXA). High Resolution peripheral Quantitative Computed Tomography (HR-pQCT) allows for non-invasive evaluation of bone stiffness and strength through micro finite element (?FE) analysis at the tibia and radius. These ?FE outcomes are strongly associated with fragility fractures but do not provide clear enhancement compared with DXA measurements. The objective of this study was to establish whether a change in loading conditions in standard ?FE analysis assessed by HR-pQCT enhance the discrimination of low-trauma fractured radii (n = 11) from non-fractured radii (n = 16) obtained experimentally throughout a mechanical test reproducing a forward fall. Micro finite element models were created using HR-pQCT images, and linear analyses were performed using four different types of loading conditions (axial, non-axial with two orientations and torsion). No significant differences were found between the failure load assessed with the axial and non-axial models. The different loading conditions tested presented the same area under the receiver operating characteristic (ROC) curves of 0.79 when classifying radius fractures with an accuracy of 81.5%. In comparison, the area under the curve (AUC) is 0.77 from DXA-derived ultra-distal aBMD of the forearm with an accuracy of 85.2%. These results suggest that the restricted HR-pQCT scanned region seems not sensitive to loading conditions for the prediction of radius fracture risk based on ex vivo experiments (n = 27).

INTRODUCTION Recent technological advances with dual-energy quantitative computed tomography (DEQCT) allow to combine two images of different level of energy to obtain simulated mono-energetic images at 60 keV (SIM60KeV-QCT) with improved image contrast in clinical practice. This study includes three topics: (1) compare bone mineral content (BMC), areal and volumetric bone mineral density (aBMD, vBMD) obtained with SIM60KeV-QCT, single-energy QCT (SEQCT), and dual X-ray absorptiometry (DXA); (2) compare ash density and weight with respective vBMD and BMC assessed on SIM60KeV-QCT, SEQCT, and DXA; and (3) compare the influence of reconstruction kernels on the accuracy of vBMD and BMC using ash density and ash weight as the reference values. METHODS DXA, SEQCT, and DEQCT acquisitions were performed ex vivo on 42 human femurs. Standard kernel (SK) and bone kernel (BK) were applied to each stack of images. Ten diaphyses and 10 femoral necks were cut, scanned, and reconstructed using the techniques described above. Finally, the bone specimens were calcined to obtain the ash weight. RESULTS QCT analysis (SEQCT, SIM60KeV-QCT) underestimated BMC value compared to DXA. For femoral necks, all QCT analyses provided an unbiased estimate of ash weight but underestimated ash density regardless of the kernel used. For femoral diaphysis, SEQCT BK, SIM60KeV-QCT BK, and SK underestimated ash weight but not ash density. CONCLUSION BMC and vBMD quantifications with the SIM60KeV-QCT gave similar results as the SEQCT. Further studies are needed to optimize the use of SIM60KeV-QCT in clinical situations. SK should be used given the effect of kernels on QCT assessment.

Background Dual X-ray absorptiometry body composition measurements are widely used for clinical and research settings. It is well known that measurements vary across instruments, needing caution for longitudinal monitoring or multicentric studies. This study was to quantify intra- and inter-center variability of bone mineral content, bone mineral density, fat and lean body composition measurements between Hologic Discovery models in order to calculate the corrective factors to be applied for multicenter research projects. Materials and methods A whole body phantom composed of materials representing the thickness and percentage of bone, lean and fat mass in the human physiological range was analyzed ten times in three different centers using dual energy X-ray absorptiometry scanners (Two Hologic Discovery QDR A and one QDR W). In addition, we used a morphometric vertebral phantom to monitor stability and a three steps block phantom to check accuracy. Results We found a good long-term stability and accuracy for the three devices. Intra-center coefficients of variation were within the range of the manufacturer acceptable values (bone mineral density: 1.40%, bone mineral content: 1%, area: 1.50%, fat mass: 0.89%, lean mass: 0.76%, total mass: 0.12%). Whereas the inter-center coefficient of variation exceeded 8% (bone mineral density: 8.18%, bone mineral content: 3.03%, area: 8.63%: fat mass: 3,92%, lean mass: 7.89%, total mass: 2.85%). Conclusion Our study showed that the discrepancies across centers remain a major concern, particularly with regard to body composition results. Our study highlight the need of cross calibration between densitometers and proposes corrective factors evaluated from a whole body phantom to lead multicentric studies adjustment.

International audience; Lysphosphatidic acid (LPA) is a major natural bioactive lipid mediator whose biological functions affect multiple organs. These include bone as demonstrated by global Lpar1-knockout mice (Lpar1-/-) which present a bone growth defect. LPA acts on all bone cells including osteoblasts, that are responsible for bone formation, and osteoclasts, which are specialized cells that resorb bone. LPA appears as a potential new coupling molecule during bone remodeling. LPA1 is the most ubiquitous LPA receptor among the six LPA receptor family members (LPA1-6). To better understand the specific role of LPA via its receptor LPA1 in osteoblastic cell lineage we generated osteoblast-specific Lpar1 knockout mice (Lpar1-∆Ob) by crossing Lpar1flox/flox and Osx:Cre+ mouse lines. Lpar1-∆Ob mice do not recapitulate the bone defects of Lpar1-/- mice but revealed reduced bone mineralization and decreased cortical thickness, as well as increased bone porosity associated with an augmentation in the lacunae areas of osteocyte and their apoptotic yield. In vitro, primary Lpar1-∆Ob and immortalized cl1-Ob-Lpar1-/- osteoblasts revealed a remarkable premature expression of alkaline phosphatase, reduced cell proliferation associated with decreased YAP-P nuclear accumulation, and reduced mineralization activity. Osteocyte specification is markedly impaired as demonstrated by reduced expression of early (E11) and late (DMP1, DKK1, SOST) osteocyte markers ex vivo in enriched osteocytic fractions of Lpar1-∆Ob mouse bone explants. In addition, E11 expression and dendrite formation induced by FGF2 are markedly impaired in both primary Lpar1-∆Ob and immortalized cl1-Ob-Lpar1-/- osteoblasts. Taken together these results suggest a new role for LPA in bone mass control via bone mineralization and osteocyte function.

In humans, the middle ear contains a chain of three ossicles with a major highly specific mechanical property (transmission of vibrations) and modeling that stops rapidly after birth. Their bone quality has been rarely studied either in noninflammatory ossicles or in those from ears with chronic inflammation. Our primary goal was to assess bone microarchitecture, morphology and variables reflecting bone quality from incuses, in comparison with those from human femoral cortical bone as controls. Secondly, the impact of chronic inflammation on quality of ossicles was documented. The study was performed on 15 noninflammatory incuses from 15 patients (35±32 years, range: 2-91). Comparisons were performed with 13 inflammatory incuses from 13 patients (55±20 years, range: 1-79) with chronic inflammation of the middle ear, essentially cholesteatoma. Microarchitecture and bone mineral density (BMD) were assessed by microcomputed tomography. Microhardness was measured by microindentation. Mineral and organic characteristics were investigated by Fourier transform infrared microspectroscopy. Noninflammatory incuses were composed of a compact, well mineralized bone without bone marrow and with sparse vessels. Remodeling activity was rarely observed. Woven or lamellar textures and numerous osteocytes were observed. In inflammatory incuses, architecture was degraded, organic tissue was abundant and bone cavities contained fibrocellular tissue and adipocytes. BMD of noninflammatory incuses was significantly higher than BMD from both control bones (4 embedded cortical femoral bone samples; age: 72±15 years, range: 50-85) and inflammatory incuses. Noninflammatory incuses were less hard than both control bone (8 cortical femoral bone samples; age: 49±18 years, range: 24-74) and inflammatory incuses. All incuses were more mineralized and less mature than controls. In conclusion, bone quality of incuses (dense, well mineralized, hard) is well adapted to their function of sound transmission. In inflammatory condition, incuses were degraded, thus explaining the decline of hearing. Moreover, microhardness was found higher than in noninflammatory incuses. Compared to bone with remodeling, the mineralization index in incuses does not explain variation of microhardness. Interestingly, a linear multiple regression model indicated that a combination of two variables, i.e., crystallinity index (crystal size/perfection) and carbonation (incorporation of carbonate ions in apatite) explains 26% of the increase in microhardness variability. Because the low remodeling level of ossicles could not prevent the reversibility of their degradation which impacts audition quality, an early management of ear inflammation in chronic otitis is recommended.

Low bone mineral density (BMD) is a major determinant of fragility fractures (Fx), but its very long-term prediction is poorly documented.We analyzed the risk of Fx beyond 10 years in women.In a longitudinal cohort study (Os des Femmes de Lyon), we studied 867 women aged 40 years and older (mean age 59 ± 10 y) over 20 years.We assessed the risk of the first incident Fx according to the baseline BMD obtained by dual-energy X-ray absorptiometry, clinical risk factors, and the Fracture Risk Assessment Tool (FRAX).During a median (interquartile range) follow-up of 20 years (3), 245 women sustained one or more incident fragility Fx. Women who sustained a first Fx beyond 10 years (Fx 10-20, n = 109) were younger and had lower values of FRAX compared with those in the first 10 years (Fx 0-10, n = 136). After adjustment for age, they still had greater grip strength and BMD. Parental hip Fx was associated with an increased risk of Fx 10-20 but contrasting with Fx 0-10, the risk of Fx 10-20 was not associated with age, previous Fx, and FRAX except in women younger than 70 years. Each SD decrease of BMD at the spine, femoral neck, total hip, and ultradistal radius was associated with an increased risk of Fx 10-20 with adjusted odds ratios [95% confidence interval (CI)] of 1.43 (95% CI 1.12-1.82), 1.39 (95% CI 1.08-1.82), 1.47 (95% CI 1.14-1.89), and 2.00 (95% CI 1.47-2.7). Women with osteoporosis had an increased risk of both Fx 0-10 and Fx 10-20 compared with women with normal BMD, whereas osteopenia was not associated with a higher risk of Fx beyond 10 years.Low BMD in women is significantly associated with an increased risk of Fx over 20 years. Beyond 10 years, the prediction conferred by baseline BMD was better than that from clinical risk factors.

Clinical cone beam computed tomography (CBCT) was compared to high-resolution peripheral quantitative computed tomography (HR-pQCT) for the assessment of ex vivo radii. Strong correlations were found for geometry, volumetric density, and trabecular structure. Using CBCT, bone architecture assessment was feasible but compared to HR-pQCT, trabecular parameters were overestimated whereas cortical ones were underestimated. HR-pQCT is the most widely used technique to assess bone microarchitecture in vivo. Yet, this technology has been only applicable at peripheral sites, in only few research centers. Clinical CBCT is more widely available but quantitative assessment of the bone structure is usually not performed. We aimed to compare the assessment of bone structure with CBCT (NewTom 5G, QR, Verona, Italy) and HR-pQCT (XtremeCT, Scanco Medical AG, Bruttisellen, Switzerland). Twenty-four distal radius specimens were scanned with these two devices with a reconstructed voxel size of 75 μm for Newtom 5G and 82 μm for XtremeCT, respectively. A rescaling-registration scheme was used to define the common volume of interest. Cortical and trabecular compartments were separated using a semiautomated double contouring method. Density and microstructure were assessed with the HR-pQCT software on both modality images. Strong correlations were found for geometry parameters (r = 0.98–0.99), volumetric density (r = 0.91–0.99), and trabecular structure (r = 0.94–0.99), all p

The relationships between body composition and bone mineral density are well established but the contribution of body composition to the risk of fracture (Fx) has rarely been evaluated prospectively. We analyzed the risk of Fx by body composition in 595 postmenopausal women (mean age 66±8years) from a longitudinal cohort study (Os des Femmes de Lyon). We assessed the risk of the first incident fragility Fx according to body composition obtained from whole-body DXA: abdominal visceral (VFAT) and subcutaneous fat mass (SFAT), total body fat mass (FM), lean mass index (LMI) and appendicular skeletal muscle mass index (ASMI). During a median [IQ] follow-up of 13.1years [1.9], 138 women sustained a first incident Fx, including 85 women with a major osteoporotic Fx (MOP Fx: hip, clinical spine, humerus or wrist). After adjustment for age, women who sustained Fx had lower BMI (-4%, p=0.01), LMI (-6%, p=0.002) and ASMI (-3%, p=0.003), compared with women without Fx. After adjustment for age, prevalent Fx, physical activity, incident falls and FN BMD, each SD increase of baseline values of LMI and ASMI was associated with decreased Fx risk with adjusted hazard ratios of 0.76 for both of p≤0.02. Those associations were similar after accounting for the competing risk of death. VFAT and SFAT were associated with Fx risk in the multivariate model only for MOP Fx and the association did not persist after consideration of competing mortality. We conclude that lean mass and appendicular muscle mass indexes are associated with the risk of fracture in postmenopausal women independently of BMD and clinical risk factors.

Eighty one women with vertebral osteoporosis were treated for up to 2 years with fluoride administered either as monofluorophosphate (MFP, 200 mg/day, i.e., 26.4 mg fluoride-ion) or sodium fluoride (NaF, 50 mg/day, i.e., 22.6 mg fluoride-ion). All patients received calcium supplementation (1 g of Ca2+/day) taken apart from NaF and in the same tablet for MFP. Despite almost similar fluoride dosage of both regimens, the early increase in the bone mineral density (BMD) of the lumbar spine was higher with MFP than with NaF, reaching 11% and 4%, respectively, at 1 year (p = 0.007), and 21% and 6%, respectively, at 18 months (p less than 0.001). The incidence of lower extremity pain syndrome related to benign stress microfractures was also higher with MFP than with NaF (35% and 15%, respectively, p less than 0.01). Urinary fluoride levels were higher in the MFP than in the NaF group (9.6 +/- 3.5 vs. 6.8 +/- 3.4 at one year, p = 0.003), suggesting that this difference in efficacy and tolerance is related to a better bioavailability of fluoride provided by MFP than by NaF. The occurrence of a stress microfracture could not be predicted by any clinical, biochemical, or densitometric parameter before treatment, but patients presenting with a stress microfracture during the course of the treatment had a higher gain in bone mass than those without stress fractures (at 1 yr+11 vs. +5%, p = 0.03 and at 18 months +18 vs. +6.9%, p less than 0.02). In conclusion, there is a clear correlation between the efficacy and the occurrence of side effects of fluoride therapy in osteoporosis.(ABSTRACT TRUNCATED AT 250 WORDS)

We previously showed that circulating undercarboxylated osteocalcin (ucOC) is elevated in elderly women and is a powerful marker of the subsequent risk of hip fracture in elderly institutionalized women (J Clin Invest 1993; 91:1769). To investigate the relationship between bone mass and ucOC, we measured bone mineral density (BMD) of the hip with dual-energy x-ray absorptiometry in 98 elderly institutionalized women, 81.4 +/- 6.0 years old. ucOC was negatively correlated with BMD at all sites (r = -0.26 to -0.38, p0.001 to p0.0001), even after exclusion of the effect of age by partial correlation (for the femoral neck, r = -0.26, p0.01) and after controlling for serum parathyroid hormone. BMD was significantly lower at all sites of measurement in women with elevated ucOC (1.65 ng/ml, upper limit of the normal range in young women) than in those with normal ucOC (for the neck, 0.58 +/- 0.13 versus 0.43 +/- 0.13 g/cm2, p0.001). Similar results were obtained for ucOC expressed as the fraction of total OC (ucOC%). Multiple regression showed that ucOC has the highest predictive value for BMD when including age and body weight in the equation. In summary, our data indicate that serum ucOC is an independent determinant of BMD of the hip in elderly women. The mechanism by which serum ucOC is related to bone mass is unclear and should be addressed in further studies. However, our data suggest that ucOC level may be an interesting marker in the investigation of bone status in the elderly.

We measured the heels of 43 women who had recently sustained a hip fracture and 86 age matched controls, using an Achilles ultrasound device. Average BUA, SOS, and Stiffness were significantly lower in fractured patients (p < 0.0001). We also estimated ultrasound parameters for patients as a function of controls and found the mean BUA to be -1.09 SD compared with controls, the mean SOS -0.89 SD, and the mean Stiffness -0.98 SD. Femoral BMD measured at the neck, Ward's triangle, and the trochanter with a DPX Plus was also significantly lower in fractured patients (p < 0.0001). The increased risk of hip fracture associated with low ultrasound values was estimated with logistic regression analysis for each bone parameter, adjusted for height and weight. The adjusted regression coefficients associated with BUA, SOS, Stiffness, and BMD were all significant (p < 0.0001) demonstrating the influence of all ultrasound and DXA parameters on the risk of hip fracture. After adjusting the logistic regressions for BMD neck, BUA, SOS, and Stiffness were still significant independent predictors of hip fracture. Sensitivity and specificity of all measures were analyzed with the area under the ROC curve which were for BUA, 0.77 +/- 0.04; for SOS, 0.75 +/- 0.04; for Stiffness, 0.78 +/- 0.04; and for BMD, 0.74 +/- 0.04. We determined the range for the best compromise between sensitivity and specificity of BUA, 97-98 dB/MHz; SOS, 1482-1487 m/s; Stiffness 59-62% Young Adult; and of BMD, 0.64-0.69 g/cm2. The area under the ROC curves of BUA, SOS, Stiffness, and DXA were compared and no statistically significant difference was found.(ABSTRACT TRUNCATED AT 250 WORDS)

The risk of fragility fractures in elderly men is only partly explained by areal bone mineral density (aBMD) measured by dual X-ray absorptiometry (DXA). Several studies suggest the importance of bone morphology for the risk of fracture. The aim of this study was to assess the value of bone size and estimated structural parameters for the prediction of incident fractures in a large cohort of men. This study was made in 759 men aged 50-85 from the MINOS cohort. During a 90-month follow-up, 74 men sustained incident vertebral and peripheral fractures. Areal BMD was measured by DXA at femoral neck, distal radius and distal ulna. Estimates of structural bone parameters and volumetric BMD (vBMD) were derived from aBMD measured by DXA. Given the limited number of fractures, the predictive value of investigated parameters was assessed for peripheral and vertebral fractures jointly by using logistic regression. Men who sustained the fractures had, at baseline, lower aBMD (3.5-6.5%), lower bone mineral content (BMC 5.4-8.7%) and lower cortical thickness (3.5-6.9%) compared with the men without fracture. At all the three skeletal sites, aBMD, BMC, width, cortical area and thickness, cross-sectional moment of inertia (CSMI), and section modulus predicted incident fractures (O.R. = 1.28-1.92 per 1 SD decrease, P0.05-0.0001). Fracture risk was weakly associated with vBMD for ulna (O.R. = 1.25 per 1 SD decrease, P0.05) but not for femoral neck or radius. After adjustment for aBMD, bone width remained a significant predictor of fractures (O.R. = 1.37-1.48 per 1 SD decrease, P0.02-0.01). Men with osteopenia (BMD T score-1) and low bone width (T score-1) had the fracture incidence similar to that observed in men with BMD T score-2. Bone width and aBMD of the femoral neck and radius were predictive of fractures in 49 men with the incident peripheral fractures, whereas their O.R. did not attain the level of statistical significance in 25 men with the incident vertebral fractures. Men, who had both low aBMD and low CSMI ( both T scores-1), had the fracture risk 3.8 to 4.2 higher than the reference group (both T scoresor= -1). Men, who had both low aBMD and low section modulus (both T scores-1), had the fracture risk 2.1 to 4.1 higher than the reference group (both T scoresor= -1). In conclusion, men who sustained a fragility fracture during a 90-month follow-up had, at baseline, lower BMC because they had narrower bones but not necessarily less dense. In elderly men, small bone width, low BMC and poor resistance to bending may increase bone fragility. Low bone width seems to be associated with an increased fracture risk in elderly men regardless of aBMD.

Mechanical behavior of bone depends on its mass and architecture, and on the material properties of the matrix, which is composed of a mineral phase and an organic component mainly constituted of type I collagen. Mineral accounts largely for the stiffness of bone, whereas type I collagen provides bone its ductility and toughness, i.e., its ability to undergo deformation and absorb energy after it begins to yield. The molecular mechanisms underlying the effect of alterations in type I collagen on bone mechanical properties are unclear. We used an in vitro model of fetal bovine cortical bone specimens (n = 44), where the extent of type I collagen cross-linking was modified by incubation at 37 degrees C for 0, 60, 90 and 120 days, keeping constant the architecture and the mineral content. At each incubation time, the following parameters were determined: (1) the bone concentration of enzymatic (pyridinoline; PYD and deoxypyridinoline, DPD) and non-enzymatic (pentosidine) crosslinks by HPLC, (2) the extent of aspartic acid isomerization of the type I collagen C-telopeptide (CTX) by ELISA of native (alpha CTX) and isomerized (beta CTX) forms, (3) the mineral density by DXA, (4) the porosity by micro-computed tomography and (5) the bending and compressive mechanical properties. Incubation of bone specimens at 37 degrees C for 60 days increased the level (per molecule of collagen) of PYD (+98%, P = 0.005), DPD (+42%, P = 0.013), pentosidine (+55-fold, P = 0.005), and the degree of type I collagen C-telopeptide isomerization (+4.9-fold, P = 0.005). These biochemical changes of collagen were associated with a 30% decrease in bending and compressive yield stress and a 2.5-fold increase in compressive post-yield energy absorption (P0.02 for all), with no significant change of bone stiffness. In multivariate analyses, the level of collagen cross-linking was associated with yield stress and post-yield energy absorption independently of bone mineral density, explaining up to 25% of their variance. We conclude that the extent and nature of collagen cross-linking contribute to the mechanical properties of fetal bovine cortical bone independently of bone mineral density.

The International Society for Clinical Densitometry (ISCD) has developed Official Positions to assist healthcare providers in addressing some of the issues inherent with the use of bone mineral density (BMD) assessed by dual-energy X-ray absorptiometry (DXA) to diagnose osteoporosis, apply World Health Organization (WHO) T-score classifications, and monitor BMD changes over time. Differences exist, however, between the ISCD Official Position statement and that of the International Osteoporosis Foundation with respect to WHO criteria for skeletal sites. Consequently, a subcommittee of the ISCD was directed to address the application of the WHO classifications to specific skeletal sites and regions of interest. In 2005, the ISCD Position Development Conference reviewed the findings and prepared Official Positions, which address whether or not: (1) the lowest T-score of the total proximal femur, femoral neck, trochanter, and spine should continue to be used for diagnosis; (2) the WHO classification may be applied to a single vertebral body T-score; and (3) the ISCD should endorse the use of the National Health and Nutrition Examination Survey database for proximal femur T-score derivation. The resulting ISCD Official Positions, with their corresponding rationales and evidence are provided here, as well as questions that will need to be addressed in the future.

Rationale Hip fractures can be separated into cervical and trochanteric fractures. Trochanteric fractures have been associated with up to twice the short-term mortality of cervical fractures in the elderly. There is also evidence suggesting that the mechanisms are different. Evidence from the literature remains limited on the predictive power of bone mineral density (BMD) and quantitative ultrasounds (QUS) for both types of hip fractures. Methods 5703 elderly women aged 75 years or more, who were recruited from the voting lists in the EPIDOS study, and had baseline calcaneal ultrasounds (QUS) and DXA measurements at the hip and the whole body, were analyzed in this paper. Among those, 192 hip fractures occurred during an average follow-up of 4 years, 108 cervical and 84 trochanteric fractures. Results Femoral neck, trochanteric and whole body BMD were able to predict trochanteric hip fracture (RR’s and 95% CI were, respectively, 3.2 (2.4–4.2); 4.8 (3.5–6.6); and 2.8 (2.2–3.6)) more accurately than cervical fractures (respectively, 2.1 (1.7–2.7); 2.3 (1.8–3.0); 1.2 (1.0–1.6)). All ultrasound parameters, SOS, BUA, and stiffness index (SI) were significant predictors of trochanteric (RR’s respectively 3.0 (2.2–4.1), 2.5(2.0–3.1), and 3.5(2.6–4.7)) but not cervical fractures. After adjustment for femoral neck or trochanteric BMD ultrasound parameters were still significant predictors of trochanteric fracture, and stiffness tended to be a better predictor of trochanteric fractures than either BUA or SOS with a relative risk of 2.25 (1.6–3.1). Conclusions A significant decrease of all bone measurements, BMD and QUS, was highly predictive of trochanteric fractures, whereas a decrease of femoral neck and trochanteric BMD were only associated with a slight increase in cervical fracture risk and a low total body BMD or QUS parameters were not significant predictors of cervical fractures. In women who sustained a hip fracture, the decrease of BMD and QUS values increases the risk of trochanteric fracture as compared to cervical fracture. Trochanteric fractures were mostly a consequence of a generalized low BMD and QUS, whereas other parameters might be involved in cervical fractures.

Diagnosis of vertebral fracture is critical for management of osteoporosis, as existence of such deformities substantially increases the risk of subsequent fracture. Thus, accurate and precise techniques allowing detection of such deformities are essential to clinicians. So far, this detection has been performed by spinal lateral X-rays. More advanced techniques have recently been developed, based on dual energy X-ray absorptiometry (DXA). This review describes these different techniques and discusses the effectiveness of the DXA technique to assess vertebral deformities compared to X-ray. The use of DXA detection of vertebral fracture for clinical practice and clinical trials is discussed. Specifically, vertebral morphometry using DXA provides an excellent specificity, with moderate sensitivity. The major limitation of the DXA vertebral assessment is the poor quality of images of thoracic vertebrae. The clinical utility of vertebral morphometry using densitometry may help screening patients with vertebral fracture, but technological improvements are necessary to improve image quality.

Osteoporosis in men is becoming a public health problem in developed countries. Fracture incidence increases with age, and the number of fractures increases because of the ageing of the population. We assessed the predictive value of bone mineral density (BMD) for osteoporotic fractures evaluated prospectively in a large cohort of elderly men and assessed the sensitivity of the T-score =−2 to detect men who will sustain a fracture. Fracture incidence was evaluated for 90 months in 759 men from the MINOS cohort aged 50 and over at baseline. In 74 men, 77 incident vertebral and peripheral fractures occurred. BMD was measured at baseline at the lumbar spine, hip, whole body and distal forearm. The incidence of osteoporotic fractures increased with age and with decreasing body weight. In men with low BMD (T-score

Structural failure becomes increasingly likely as the load on bone approximates or exceeds the bone’s ability to withstand it. The vertebral fracture risk index (FRI) expresses the risk for structural failure as a ratio of compressive stress (load per unit area) to estimated failure stress, and so should be a more sensitive and specific predictor of vertebral fracture than spine areal BMD (aBMD) or volumetric BMD (vBMD), surrogates of bone strength alone. To address this issue, we analyzed the results of a case-control study of 89 postmenopausal women with vertebral fractures and 306 controls in Melbourne, Australia, and a 10-year community-based prospective study in which 30 postmenopausal women who had incident vertebral fractures were compared with 150 controls in Lyon, France. The FRI and vBMD of the third lumbar vertebral body and spine aBMD were derived using dual X-ray absorptiometry. In the cross-sectional analysis, each SD increase in FRI was associated with 2.1-fold (95% confidence interval [CI], 1.55–2.73) increased vertebral fracture risk, while each SD decrease in aBMD or vBMD was associated with 4.0-fold (95% CI, 2.69–6.18 and 2.65–6.94, respectively) increase in risk. Using receiver operating characteristic (ROC) analysis, the FRI was less sensitive and specific than aBMD in discriminating cases and controls (area under ROC, 0.76 vs 0.84, p

Hip fracture is the most disastrous osteoporotic fracture, characterized by high mortality, morbidity and institutionalization for the patient and by high economic costs for the health care system. The morphology of the upper part of the femur can influence the risk of hip fracture, e.g., a longer femoral neck is associated with a higher risk of cervical fractures, but not trochanteric ones. In this study, we evaluated the prediction of hip fracture risk by morphological parameters estimated from DXA measurements, and we compared their predictive value for cervical and trochanteric fractures in elderly women by reanalyzing previously published data (Duboeuf et al. J Bone Miner Res 1997 12 1895). This nested case-control study was performed in 232 elderly community-dwelling women from the EPIDOS cohort, including 65 women who sustained a hip fracture. After adjustment for confounding variables, women who sustained a cervical fracture had lower areal bone mineral density (aBMD), lower cortical thickness and a higher average buckling ratio (P0.005 for all) as well as longer femoral neck (P0.01) than controls. Women who sustained a trochanteric fracture had lower aBMD, lower cortical thickness and higher buckling ratio than controls (P0.0001) and than women who sustained a cervical fracture (P0.05). Their bending resistance (cross-sectional moment of inertia-CSMI, section modulus) was significantly lower in comparison with controls (P0.05-0.001). A decrease in aBMD, cortical thickness, CSMI and section modulus as well as an increase in buckling ratio were predictive of all hip fractures (OR -1.42-2.46 per 1 SD, P0.05-0.0001), but the ORs for all structural parameters were markedly higher for trochanteric than for cervical fractures. CSMI and section modulus were predictive of trochanteric, but not cervical fractures. However, aBMD was strongly correlated with the CSA, cortical thickness and buckling ratio (r20.74), which suggests that they convey the same information. CSMI and section modulus correlated with aBMD more weakly, but their OR lost statistical significance after adjustment for aBMD. In conclusion, low femoral neck aBMD, CSA and cortical thickness as well as a high buckling ratio are associated with the higher risk of hip fracture, especially trochanteric ones. These indices are highly correlated with aBMD and convey the same message. The calculated CSMI and section modulus predict trochanteric fractures, but not cervical fractures, and their statistical significance is lost after adjustment for aBMD, indicating that they reflect mainly aBMD, not mechanical properties. Thus, the independent contribution of the external diameter of the femoral neck to the risk of hip fracture cannot be reliably estimated by this technique.

In the skeleton of elderly men, two opposite activities occur: bone loss at the endosteal envelope, which increases bone fragility, and periosteal apposition, which improves bending strength of bone. Both may contribute to serum bone formation markers although they have an opposite effect on bone fragility. The aim of this study was to determine if circulating bone formation markers reflect periosteal bone formation and endosteal bone remodelling in 640 men aged 55-85 years belonging to the MINOS cohort. We measured biochemical markers of bone formation (osteocalcin, bone alkaline phosphatase, N-terminal extension propeptide of type I collagen) and bone resorption (urinary and serum beta-isomerised C-terminal telopeptide of collagen type I, total and free deoxypyridinoline). Parameters of bone size (cross-sectional surface of third lumbar vertebral body measured by X-ray, projected areas of total hip, femoral neck, radius and ulna measured by dual-energy X-ray absorptiometry) increased with age (r = 0.20-0.32, P0.0001). In contrast, parameters related to bone loss (areal bone mineral density [aBMD], volumetric bone mineral density [vBMD] and cortical thickness) and determined mainly by bone resorption, decreased with ageing (r = -0.14 to -0.23, P0.005-0.0001). Men in the highest quartile of bone resorption markers had lower aBMD (3.8-10.2%, P0.05-0.0001), lower vBMD (3.9-13.0%, P0.05-0.0001), and lower cortical thickness (1.5-9.6%, P0.05-0.0001) than men in the lowest quartile. Markers of bone resorption were not significantly associated with estimates of bone size at any skeletal site. Markers of bone formation were not associated with estimates of periosteal formation after adjustment for covariates. In contrast, men in the highest quartile of the bone formation markers had significantly lower aBMD (4.0-11.7%, P0.05-0.0001), lower vBMD (4.2-16.3, P0.05-0.0001) and lower cortical thickness (4.0-7.4%, P0.05-0.0001) than men in the lowest quartile. In summary, serum levels of bone formation markers are negatively correlated with the estimates of endosteal bone loss. In contrast, they disclose no association with parameters reflecting periosteal apposition. Thus, in elderly men, bone formation markers reflect endosteal bone remodelling, probably because of the coupling between resorption and formation activities. In contrast, they do not reflect the periosteal bone formation, probably because the periosteal surface is smaller and has a slower remodelling rate than the endosteal surface.

While the potential of quantitative ultrasound (QUS) in the management of osteoporosis has been accepted, its interaction with follow-up time has never been investigated. The aim of our study is to prospectively evaluate the influence of follow-up time on the prediction of hip fracture by ultrasound parameters in the elderly as compared to bone mineral density (BMD) and to establish a long-term fracture prediction model. In the multicenter prospective study EPIDOS, 5898 Caucasian healthy women, aged 75 and over, had femoral dual-energy X-ray absorptiometry (DXA) and heel ultrasound measurements at baseline. A survey of fracture occurrence was conducted every 4 months. Statistical analyses were performed for three different average lengths of follow-up, namely, 1.5, 2.5 and 3.5 years. Relative risks per standard deviation decrease (RR) and the area under the receiver operating characteristic (AUC) curves were given. Estimates of the long-term hip fracture prediction by DXA and QUS were extrapolated. During an average of 3.5 years follow-up, 227 women sustained their first non-traumatic hip fracture. For the three categories of follow-up, low values of both calcaneal ultrasound and hip BMD were associated with a significant increased risk of hip fracture [e.g. ultrasound Stiffness index RR = 2.8 (2.1-3.8), 2.1 (1.7-2.6) and 1.9 (1.7-2.3) for 1.5, 2.5 and 3.5 years of follow-up, respectively]. The combination of femoral neck BMD with the Stiffness showed an improvement of the hip fracture prediction model. Using extrapolation, the prediction of hip fracture by the Stiffness remained significant up to 7.5 years [RR = 1.2 (1.03-1.41)], whereas the limit of significance was reached at 10 years for the femoral neck BMD [RR = 1.25 (1.04-1.52)]. Our results indicate that the Stiffness tends to be the best short- and long-term predictor of hip fracture among ultrasound parameters. This paper provides additional information on the long-term prediction of hip fracture, which has always been an important issue in routine clinical practice as it influences the management of the disease. Our model should give a relatively good estimation of the fracture risk prediction at 5 years with the ultrasound and 10 years for the femoral neck BMD.

The beneficial effects of hormone replacement therapy (HRT) on bone mineral density (BMD) and bone turnover are well documented but whether HRT withdrawal is followed by an accelerated rate of bone loss is still controversial. We analyzed 26 women who have withdrawn HRT during a 6-year follow-up of the OFELY cohort. They were compared with three groups of women from the same cohort: one hundred four healthy postmenopausal women who continued HRT during the 6-year follow-up, 78 untreated postmenopausal women matched for age, and 31 untreated women within 5 years of menopause. Bone markers [serum osteocalcin (Intact OC), bone alkaline phosphatase (Bone ALP), and serum CTX] were performed annually during 4 years and bone mineral density (BMD) was measured at the forearm (DXA) during 6 years. Withdrawal of HRT was followed by a significant bone loss with an annual rate ranged from -0.7 to -1.6% at the radius according to the skeletal site and by a marked increase of bone markers after 6 months: +36 % for osteocalcin, +23% for bone alkaline phosphatase, and +120% for serum CTX (P < 0.05 to P < 0.001). In contrast, in the HRT continuing group, there was no bone loss and no substantial change of bone markers over 4 years. The rate of bone loss after withdrawal of HRT was significantly greater than in postmenopausal women matched for age who never received HRT (2.2 to 2.8 times higher according to the radius area) and not different as compared to the accelerated bone loss observed in untreated women within 5 years of menopause. We conclude that in postmenopausal women who have been on HRT for 6 years, cessation of treatment results in a rapid increase of bone turnover and a rate of bone loss similar to early postmenopausal women during the subsequent 4 years and greater than untreated women of the same age.

The purpose of this ex vivo study was to analyse two commonly established methods of mechanical bone property assessment for application in horses: Quantitative ultrasound (QUS), which depends on the bone's density and Young's modulus, and dual energy X-ray absorptiometry (DXA), which depends on the areal bone mineral density (BMD). The third metacarpal bone (MC III) of horses was selected as examination region for practical reasons. An interrelationship between QUS- and DXA-values was examined. Both MC III of eleven randomly selected equine cadavers were divided in nine regions of interest (ROI). A multi-site QUS device was used for axial transmission speed of sound (SOS) measurements and a DXA device was used for BMD evaluation. Full cortical thickness BMD (FcBMD), overall aspect BMD and 4 mm cortical border slice BMD (4 mmBMD) were evaluated. In addition, each ROI of one MC III was measured 10 times to determine QUS- and DXA-measurement precision. SOS values and BMD values obtained at different aspects of MC III were different (P < 0.001). FcBMD and overall BMD obtained at different levels were different (P < 0.001). SOS data correlated with FcBMD-, overall BMD- and 4 mmBMD-data at various ROI. FcBMD-, overall BMD- and 4 mmBMD-data were strongly correlated. The intra-operator coefficient of variation was 1.3% for SOS-measurements and ranged between 1.94 and 10.3% for BMD-measurements. Multi-site axial transmission QUS as well as DXA can be used to precisely measure bone characteristics of MC III in horses. However, both techniques do not measure the same bone properties. It is therefore concluded, that QUS and DXA techniques are complementary for application in horses.

Although the long-term outcomes of osteoporosis (Op) such as fracture, kyphosis, and pain are well known, the physical, psychological, and social consequences, beyond fracture and pain, are less clear. The Osteoporosis-targeted Quality-of-life (OPTQoL) questionnaire aimed at assessing the physical difficulty, fears, and adaptations to one's daily life was developed as a cross-sectional instrument to characterize the burden of Op within a community. The purpose of this study was to assess the impact of Op and related factors on community women participating in the OFELY study in France. Femoral neck bone mineral density (BMD) and OPTQoL questionnaire data were collected from women randomly selected from a large insurance company. Data were obtained for 756 women (mean age 59 years, range 36-92), most of whom were white. Women were classified into five groups based on the extent of physical manifestations and family history of Op. Women who had prior fractures, height loss, and/or kyphosis or both reported greater physical difficulty, more adaptations to their lives, and greater fears than women reporting no such changes. Scores on the Physical Difficulty domain, however, did not differ significantly based on BMD alone (BMD T score

Tobacco was found to be a risk factor for osteoporosis, mainly in postmenopausal women. We studied the effect of smoking on bone mineral density (BMD) and bone turnover in a cohort of 719 men, aged 51-85 yr, composed of 83 current smokers, 405 former smokers, and 231 men who never smoked. Most current and former smokers were moderate smokers (median, 10 cigarettes/d). Current smokers were younger, thinner, and drank more coffee and more alcoholic beverages. After adjustment for age, body weight, alcohol intake, and caffeine intake, current and former smokers had similar BMD, except at the forearm. Former smokers had lower BMD compared with never-smokers at most skeletal sites. Men who had smoked more than 7120 packs (third quartile) had lower BMD of total hip (P < 0.01) and distal forearm (P = 0.03) compared with men in the 2 lower tertiles. In the 3 groups, levels of bone formation markers did not differ. After adjustment for confounding variables, levels of urinary markers of bone resorption (beta-isomerized C-terminal telopeptide, free and total deoxypyridinoline) were higher in the current smokers than in former smokers and never-smokers. Concentrations of T, total 17beta-E2, and androstenedione were higher, whereas that of 25-hydroxyvitamin D was lower, in current smokers. When men were divided according to tertiles of body weight, increased bone resorption, decreased BMD and biochemical indexes of secondary hyperparathyroidism were observed in current smokers in the lowest tertile of body weight (

Children's bones are interesting from both the mechanical and the clinical point of view because they frequently show typical bone fractures (greenstick), which is obviously a different fracture mo...

The aims of this study performed in ewes were: (1) to confirm in this animal model the effects on bone of ovariectomy (OVX) alone or associated with Lentaron (L), a potent peripheral aromatase inhibitor, used to amplify the effects of OVX and (2) to evaluate the effects of a new selective estrogen receptor modulator (SERM; MDL 103,323) on bone remodeling. Thirty-nine old ewes were divided into five groups: sham (n = 7); OVX (n = 8); OVX + L (n = 8); OVX + L + MDL; 0.1 mg/kg per day (n = 8); and OVX + L + MDL 1 mg/kg per day (n = 8). The animals were treated for 6 months. Biochemical markers of bone turnover (urinary excretion of type 1 collagen C-telopeptide [CTX], serum osteocalcin [OC], and bone alkaline phosphatase [BAP]) were measured each month. Bone biopsy specimens were taken at the beginning and after death at the end of the experiment. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry (DXA) on the lumbar spine and femur. OVX induced a significant increase in biochemical markers. This effect was the highest after 3 months for CTX (+156% vs. sham) and after 4 months for OC and BAP (+74% and +53% vs. sham, respectively). L tended to amplify the effect of OVX on OC and BAP. OVX induced significant increases in the porosity, eroded, and osteoid surfaces in cortical bone but no effect was observed in cancellous bone. MDL treatment reduced the bone turnover as assessed by bone markers, which returned to sham levels as well as histomorphometry both in cortical and in cancellous bone. Cancellous osteoid thickness decreased by 27% (p < 0.05), mineralizing perimeter by 81% (p < 0.05), and activation frequency by 84% (p < 0.02) versus OVX + L. Femoral and spinal BMD were increased by MDL and tended to return to the sham values. The effects of OVX on bone turnover were different on cortical and cancellous bone. These effects on cortical bone were reflected by changes in biochemical markers. MDL markedly reduces bone turnover and increases BMD suggesting that this new agent may prevent postmenopausal bone loss.

There are few data on osteoporosis in men, but cross-sectional studies have shown that age-related bone loss in men is of lower magnitude than in women. To elucidate some controversies related partially to methodological aspects, we measured bone mineral density (BMD) by dual-energy X-ray absorptiometry (DEXA) at various skeletal sites (spine, hip, and whole body using a Hologic QDR-1500 device; forearm using an Osteometer DTX 100 device) in a large cohort of 1040 men, aged 19-85 years. The final investigation was performed on 934 men, aged 19-85 years, after exclusion of 106 men with disease or treatment known to affect bone metabolism. Peak BMD was achieved at 25 and 29 years at the lumbar spine and hip, respectively, but only at 40 and 37 years at the distal forearm and whole body, respectively. The magnitude of bone loss between peak bone mass and 80 years of age was linear at most sites and averaged 13%-18%; that is, SD of 1.1-1.8 from peak BMD, except for Ward's triangle, which showed a marked bone loss of 43% (i.e., 2.5 SD), and for the lumbar spine. In the entire cohort, increase of the average lumbar spine BMD after the age of 55 years was related to the development of osteoarthritis, because, in men without severe arthritis, lumbar spine BMD continued to decrease. Height-adjusted partial correlations indicate that both the mineral content and the area of long bones of the limbs increased with age up to 50 years, followed by a significant decrease of BMD without change of bone surface. SD of mean BMD increased significantly with age at most skeletal sites. In summary, age-related change of BMD varied according to skeletal site in men with peak bone mass achieved earlier at sites rich in trabecular bone than at those rich in cortical bone. Bone loss varied according to skeletal site from 14% to 43%. The variability of BMD increased with age, which may reflect interindividual variability of age-related bone loss.

We used an experimental software measuring the hip axis length (HAL) and bone mineral density (BMD) in specific regions of the lower and upper part of the femoral neck on dual-energy X-ray absorptiometry scans. To determine whether these parameters were significant predictors of the type of hip fracture, we measured 167 healthy women (controls), 24 women with trochanteric, and 42 women with cervical hip fractures within the EPIDOS prospective cohort. EPIDOS is a multicenter prospective study on risk factors for hip fracture performed in 7575 elderly women living at home, aged 75-95 and conducted in five French centers (Amiens, Lyon, Montpellier, Paris, Toulouse). Measurements were performed on data acquired at baseline before the occurrence of fracture. In the cervical fracture group, HAL was significantly longer than in controls (94.2 vs. 92.3, p = 0.03), and the associated odds ratio (OR) adjusted for age, weight, and total femoral neck BMD was significant (OR = 1.64, 95% confidence interval [CI] 1.06-2.55). In contrast, HAL was not significantly different from controls in the trochanteric fracture group. Femoral neck diameter was not a predictor of fracture. The upper and lower femoral neck BMD was lower in the trochanteric fracture group than in controls, and both measurements predicted trochanteric femoral neck fracture. In contrast, the prediction of cervical femoral neck fracture was enhanced by measuring only the upper part of the femoral neck (OR = 2.79 vs. 1.97 for the total femoral neck) while BMD of the lower part was not different from controls. Hip axis length is a predictor of femoral neck fracture. Femoral neck BMD distribution is different between cervical and trochanteric fractures. These results support the hypothesis of a different pathophysiological mechanism between the two types of hip fractures.

In an attempt to reduce patient positioning errors, the authors tested the use of a new hip-specific positioning tool, OsteoDyne's Hip Positioner System (HPS). The HPS is an "A" frame splint designed to abduct both legs approximately 15 degrees to hold them in full extension at the hips and knees and to lock the feet in a neutral position. Seventy volunteer women aged 35-82 years were randomly assigned in two age-matched groups (mean age 56 years). Each group underwent two consecutive femur dual X-ray absorptiometry (DXA) scans with intermediate repositioning using the HPS system and two others utilizing the standard hip positioner provided with Hologic and Lunar scanners. One technician performed all scans using a Hologic QDR 1000-Plus and Lunar DPX-Plus densitometer. One hundred and fifty volunteer women aged 50-84 years (mean age, 64 years) were recruited in a multicenter study for the assessment of precision. Each subject underwent three consecutive femur DXA scans with intermediate repositioning using the HPS system. The coefficient of variation (CV) was significantly improved at the femoral neck by the use of the HPS with 0.7 versus 1.2 with the Hologic densitometer but only moderately altered at other sites. Similar results were found with the Lunar densitometer with improvement of precision at the femoral neck, 0.8 versus 1.8 with a similar trend but no significant difference at the other regions. No statistical difference was noted between the femoral neck BMD measured with the HPS system and with the standard positioners in either group. The mean precision of data obtained on the QDR 1000+ was 0.8% (range 0.1-1.4) for the femoral neck BMD, 1.1% (range 0.1-3.0) for the trochanter BMD, 2.3% (range 0.2-5.2) for Ward's triangle BMD, and 0.8% (range 0.1-1.9) for the total femur BMD. The mean precision of data obtained on the QDR 2000 was 0.7% (range 0.1-2), 1% (range 0.1-4.9), 2.6% (range 0.3-5.7), and 0.7% (range 0.1-1.8), respectively. In conclusion, data obtained with the new OsteoDyne's HPS seem capable of reducing patient positioning errors for the hip measurement. Its use is likely to improve confidence in hip bone mineral density measurements.

Dual-energy X-ray absorptiometry (DXA) of the lumbar spine provides an estimation of the bone mineral content (BMC) corrected by the projected area of the spine and expressed in g/cm2. This two-dimensional estimate of the bone mineral density (BMD) is influenced by the skeletal size, assessed by the subject's height. In order to obtain an estimate of the volumetric BMD, we measured BMC with a new DXA device (Sophos L-XRA) equipped with 24 detectors and a rotating arm, thus allowing scanning of the lumbar spine in both an anteroposterior (AP) projection and a lateral (LAT) projection with the patient in a supine position. Comparison between the results obtained on the third (L3) and fourth (L4) lumbar vertebrae with automatic or manual analysis showed that the best precision was obtained with the lateral measurement of L3 alone with an automatic soft tissue baseline determination. Results were expressed in g/cm2 and in g/cm3 (by dividing the g/cm2 value by the width (AP area divided by the height of the vertebra) of L3), and were compared with those obtained by conventional AP scanning of L2–4 (g/cm2). The in vivo precision error evaluated by triplicate measurements on 10 controls was 17 mg/cm2 (1.96%) and 5.2 mg/cm3 (2.31%) for LAT L3 as compared with 13 mg/cm2 (1.15%) for AP L2–4. Volumetric BMD (g/cm3) measurement, assessed in vitro on a calibrated hydroxyapatite phantom, and the absolute values obtained in normal women were similar to those obtained by quantitative computed tomography (QCT). In 39 healthy adults (27±4 years) BMD expressed in g/cm2 was correlated with height (r=0.36 for AP L2–4 andr=0.39 for LAT L3;p

Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry (DEXA) in 133 normal females on five regions of the femoral site: neck, trochanteric, intertrochanteric, Ward's triangle, and total area of the proximal femur. One hundred and twenty-five women (56 older than 65, range 65-97, and 69 with an age range of 21-65) were also examined for spinal bone mineral density. The mean in vivo precision (CV%) of the measurements with repositioning assessed on five young and eight elderly patients was ranged from 0.7% to 1.7% but lower for Ward's triangle (CV = 2.95% and 3.87%). Between 30 and 90 years, a linear age-related bone mineral decrease was found at all sites with a similar magnitude of bone loss for the femoral neck, total or intertrochanteric regions (-33% to -39%). A greater decrease was found for the Ward's triangle region (-61%). In the subgroup of elderly women (65-97 years old), the lumbar BMD measured with an anteroposterior incidence did not decrease significantly with age, contrasting with an average 27% decrease of the BMD of the hip between 65 and 90 years of age. In addition, 31 patients suffering either from a cervical (n = 12) or pertrochanteric (n = 19) fracture were measured on their contralateral femur 15 to 30 days after the fracture event. The mean calculated BMD values were, depending on the measured area, from 14% to 21% lower than those reported for age-matched controls (z-score from -1.11 to -0.65). A fracture threshold was determined for each site from this population and the elderly controls.(ABSTRACT TRUNCATED AT 250 WORDS)

The amount of bone and the trabecular microarchitecture are two determinants of bone strength which can be quantified by bone histomorphometry. Among the parameters of bone microarchitecture, the Euler number developed in our laboratory (E strut.cavity ) and trabecular bone pattern factor (TBPf) evaluate the connectivity and complexity independently of the bone quantity, and the speed of sound (SOS) measured by quantitative ultrasound (QUS) corroborates E strut.cavity . The aim of the present study was to validate E strut.cavity , TBPf, and SOS as parameters of bone microarchitecture and their contribution to bone strength. We examined 20 right os calcis taken after necropsy in 11 males and 9 females, aged 52–95 years. At the same anatomic location, we measured SOS and broadband ultrasound attenuation (BUA) using a Hologic Sahara device and bone mineral density (BMD) using a Hologic QDR 1000W. At this site a transcortical cylinder was cut for both apparent density measurement (Ap.Dens) and biomechanical tests (maximum compressive stress (σmax) and Young’s modulus (E)), and histomorphometry was performed with an automatic image analyzer (Visiolab, Explora Nova, France). E and σmax were significantly correlated with the parameters of bone quantity, microarchitecture, and QUS. However, after adjustment for the bone quantity, E correlated only with E strut.cavity , TBPf, and SOS, and σmax with BUA. In conclusion, the bone connectivity and complexity evaluated by E strut.cavity and TBPf contribute to bone strength, independently of the bone quantity. The bone mechanical properties may be assessed, in os calcis, in the elastic domain by SOS and in the plastic domain by BUA.

Vertebral fracture is currently underdiagnosed, despite its common severity and its value to predict further osteoporotic fracture. Morphometry using dual X-ray absorptiometry (DXA) [vertebral fracture assessment (VFA)] is a new technique that may facilitate detection of many vertebral fractures, as images are obtained at the same time as bone mineral density (BMD) measurement, and would also allow avoiding spine radiographs.We conducted a cross-sectional study to assess the diagnostic value of Instant Vertebral Assessment (IVA), which is a morphometry scan using the Hologic Delphi densitometer, to detect prevalent vertebral fracture in postmenopausal women. Interobserver precision was assessed, then IVA scans were compared with lateral spine radiographs, considered the gold standard, to test diagnostic agreement between the two techniques. Sensitivity, specificity and predictive values were calculated, as well as the likelihood ratio of the positive test, using sensitivity and specificity at each vertebral level.Among 85 patients of whom 50% had at least one vertebral fracture identified with radiographs, we found that interobserver precision was moderate, with frequent difficulties in discerning upper thoracic vertebrae. On a per-vertebra basis, sensitivity was around 70% from L4 to T11 and lower above T11 whereas specificity was above 90% for all vertebrae, and the negative predictive value remained above 80% from L4 to T7 and decreased above T7. On a per-patient basis, sensitivity was 0.69, specificity 0.74, positive predictive value equalled 0.72 and negative predictive value 0.71. When only grades 2 and 3 fractures were considered, results were comparable, with slightly improved specificity. Then, with the likelihood ratios calculated in our sample, we obtained posttest probabilities using the prevalence of vertebral fracture at lumbar and thoracic levels in a large sample of postmenopausal women with osteopenia and osteoporosis with and without vertebral fracture [baseline data in women of the Multiple Outcomes on Raloxifene Evaluation (MORE) trial]. At levels where fractures were most common, likelihood ratios of the positive test were good or excellent, associated with sizeable posttest probabilities.IVA allowed diagnosis of vertebral fracture at levels where vertebral fracture were most common, i.e., the lumbar and mid and lower thoracic levels, but its value was weaker at the upper thoracic levels.

A 3-year, randomized, double-blind, placebo-controlled trial evaluated the effect of oral alendronate on the BMD of 64 adult patients with osteogenesis imperfecta. The mean increases in the lumbar spine BMD were 10.1 ± 9.8% (p < 0.001) and 0.7 ± 5.7% in the alendronate and placebo groups, respectively. Oral alendronate increases BMD in adult patients with osteogenesis imperfecta. Introduction: This study evaluated the effect of oral alendronate on the BMD of adult patients with osteogenesis imperfecta. Materials and Methods: We carried out a 3-year, randomized, double-blind, placebo-controlled trial of oral alendronate in 64 adult patients with osteogenesis imperfecta. The primary endpoint was the difference between the groups in the mean percent change in lumbar spine BMD at 3 years. Secondary outcomes included changes in BMD of total hip, vertebral and peripheral fracture incidence, pain, hearing loss, and bone turnover biochemical markers. Patients were treated daily with either placebo or 10 mg alendronate. All received 1 g of calcium and 800 IU of vitamin D daily. Results: The mean ± SD increases in the lumbar spine BMD were 10.1 ± 9.8% (p < 0.001) and 0.7 ± 5.7% in the alendronate and placebo groups, respectively. Hip BMD increased in the alendronate group by 3.3 ± 0.5% (p = 0.001) and decreased in the placebo group by 0.3 ± 0.6%. The sample size was not sufficient to determine an effect of alendronate on fracture rate. A significant increase of the pain score was noted in the alendronate group (p = 0.04) in the intent-to-treat analysis but not in the per protocol analysis. There was no change in hearing in either group. Bone resorption and formation biochemical markers were significantly decreased in the alendronate group (p < 0.001). There were no differences in severe adverse effects between the groups, but there was an increase in nonsevere upper gastrointestinal effects in the alendronate group (p = 0.003). Conclusions: Oral alendronate increases BMD and increase nonsevere gastrointestinal adverse effects but does not modify the hearing loss in adult patients with osteogenesis imperfecta. More studies are needed to evaluate an effect on the fracture rate.

In osteoporosis, bone fragility results from both bone loss and changes in trabecular microarchitecture, which can be quantified by bone histomorphometric parameters. Twenty human calcaneum were collected after necropsy. All measurements were performed at the same anatomical location. Bone histomorphometric parameters were measured on histological slides with an automatic image analyzer. The aims of our study were (1) to develop automatic measurements of four additional parameters reflecting trabecular network connectivity and complexity, i.e., trabecular bone pattern factor (TBPf), Euler number/tissue volume (Euler) according to the three definitions previously reported and to a fourth one established in the laboratory (Euler(strut.cavity)), marrow star volume, and interconnectivity index, and to determine their usefulness in microarchitecture characterization; and (2) to validate these parameters by evaluating their relationship with dual-energy X-ray absorptiometry and quantitative ultrasound (QUS) measurements performed on the same samples. The statistical analysis showed that TBPf and Euler(strut.cavity) appeared to be the most significant connectivity parameters, independently of bone quantity (bone mineral density, apparent density, cancellous bone volume). For QUS, after adjustment for bone quantity, only speed of sound (SOS) was significantly and negatively correlated to Euler(strut.cavity). Broadband ultrasound attenuation depends only on bone quantity. In conclusion, TBPf (a strut analysis parameter extrapolable in three dimensions) and Euler(strut.cavity) (the only bone connectivity parameter reflecting SOS) are two valid bone microarchitecture parameters. These new parameters were significantly correlated to the established trabecular structure parameters: trabecular thickness or trabecular spacing, being weakly correlated with SOS.

BMD is a major determinant of the risk of fragility fractures, but the role of the rate of postmenopausal bone loss is still unclear. In 671 postmenopausal women from the OFELY cohort, we found that the rate of bone loss was significantly associated with fracture risk independently of other well-known predictors including BMD and previous fractures. Introduction: The level of BMD is a major determinant of the risk of fragility fractures, but the role of the rate of postmenopausal bone loss is still unclear. Materials and Methods: In the OFELY study, we analyzed the risk of fracture in 671 postmenopausal women (mean age, 62.2 ± 9 years), according to the rate of bone loss. BMD was measured annually by DXA at the forearm, with a mean number of measurements of 10.3 ± 2.6. Peripheral fractures, all confirmed by radiographs, were prospectively registered, and vertebral fractures were evaluated with spine radiographs every 4 years. Results: During a median (interquartile range [IQ]) of 11.2 years (11–12.3 years) of follow-up, 183 incident fragility fractures including 53 vertebral and 130 nonvertebral fractures were recorded in 134 women. The annual median ± IQ rate of bone loss, calculated from the slope, was −0.30 ± 0.76% at the mid-radius, −0.55 ± 0.79% at the distal radius, and −0.40 ± 0.96% at the ultradistal radius. Women with incident fracture had a rate of bone loss (before fracture) higher by 38–53% than those without fracture (p = 0.0003–0.016). Using multivariate Cox regression models, we found that bone loss in the highest tertile at the mid-radius, distal radius, and ultradistal radius was associated with a significant increased risk of all fractures with an hazard ratio from 1.45 to 1.70 (p = 0.02 to p = 0.009 after adjusting for age, previous fractures, maternal history of fracture, physical activity, grip strength, falls, and baseline BMD). Conclusions: The rate of bone loss in postmenopausal women is significantly associated with fracture risk independently of other well-known predictors such as BMD and history of fractures.

Recent studies have demonstrated that bone is highly innervated and contains neuromediators that have functional receptors on bone cells. However, no data exist concerning the quantitative changes of innervation during bone loss associated with estrogen withdrawal. To study the involvement of nerve fibers in the regulation of bone remodeling, we have evaluated the modifications of innervation in a classical in vivo model of osteopenia in rats, ovariectomy (OVX). Skeletal innervation was studied by immunocytochemistry using antibodies directed against specific neuronal markers, neurofilament 200 and synaptophysin, and the neuromediator glutamate. Sciatic neurectomy, another model of bone loss due to limb denervation and paralysis, was used to validate our quantitative image analysis technique of immunostaining for nerve markers. Female Wistar rats at 12 wk of age were sham-operated (SHAM) or ovariectomized (OVX). Bone mineral density measurement and bone histomorphometry analysis of tibiae 14 d after surgery demonstrated a significant bone loss in OVX compared with SHAM. We observed an important reduction of nerve profile density in tibiae of OVX animals compared with SHAM animals, whereas innervation density in skin and muscles was similar for OVX and control rats. Quantitative image analysis of immunostainings demonstrated a significant decrease of the percentage of immunolabeling per total bone volume of neurofilament 200, synaptophysin, and glutamate in both the primary and secondary spongiosa of OVX rats compared with SHAM. These data indicate for the first time that OVX-induced bone loss in rat tibiae is associated with a reduction in nerve profile density, suggesting a functional link between the nervous system and the bone loss after ovariectomy.

We have analyzed the relationship between spine osteoarthritis and fractures in the OFELY cohort. Despite a higher BMD associated with spine OA, the risk of fragility fractures is not reduced. Disc space narrowing is associated with an increased risk of vertebral fracture. These data indicate that the risk of osteoporotic fracture should not be underestimated in women with spine OA. Introduction: Although osteoarthritis (OA) and osteoporosis both increase with age, their co-existence is uncommon. A higher BMD in OA is well documented, but a reduction of the fracture risk is still controversial. Our objective was to analyze the risk of fracture in postmenopausal women with spine OA. Materials and Methods: In a cross-sectional study, spine OA was evaluated by lateral radiographs according to the method of Lane, and BMD was measured by DXA in 559 postmenopausal women from the OFELY cohort (mean age, 68 ± 8 years; range, 58–94 years) 8 years after their inclusion into the study. Previous fragility fractures, all confirmed by radiographs, were prospectively registered during the annual follow-up for 8 years, and vertebral fractures were evaluated with spine radiographs. Severity of OA was assessed by scoring on osteophytes and disc narrowing on a four-point scale from 0 (normal) to 3 (severe) and graded as 0 (normal), 1 (mild osteophyte and/or narrowing), or 2 (moderate or severe osteophyte and/or narrowing). Results: Osteophytes and disc narrowing were present in 75% and 64%, respectively, of women at the lumbar spine and in 88% and 51%, respectively, at the thoracic spine, increasing with age. BMD of the spine, hip, and whole body increased with the severity of osteophytosis, whereas severity of narrowing was associated with a higher BMD only at the spine. Ninety-six fractures, including 48 vertebral fractures, occurred before OA assessment. No significant association was found between spine OA and all fragility fractures. In contrast, disc narrowing was associated with an increased risk of vertebral fracture with an odds ratio (95% CI) of 3.2 (1.1–9.3) after adjusting for age, body mass index, and BMD. The risk of vertebral fracture increased with the severity of disc narrowing. In comparison with the score 0, the odds ratio increased from 2.8 (0.9–8.7) to 4.6 (1.2–16.9) in women with mild to severe disc narrowing score. Conclusions: Despite a higher BMD, women with spine OA do not have a reduced risk of fracture. Disc narrowing is associated with a significant increased vertebral fracture risk.

Objective. The purpose of this study was to evaluate the potential use of dual energy x-ray absorptiometry for the assessment of bone mineral content and bone mineral density before implant placement. Material and Methods. The material examined consisted of 63 mandibular bone specimens cut from 21 fresh cadavers (11 men; 10 women). Three specimens were cut per cadaver in the incisal, premolar, and molar regions. Three regions of interest (G, R1, and R2) were delineated. The global bone specimen (G) consisted of the whole specimen (ie, both cortical and trabecular bone). R1 and R2 were delineated in the trabecular bone of the alveolar process. Results. In all subjects, the combined bone mineral content of the whole mandible specimens (global bone mineral content) was significantly correlated with age. The difference between the mean bone mineral densities of the male and female mandibles was found to be significant for G (P =.009). The mean bone mineral densities of dentate and edentulous specimens were also found to be significantly different for G and R1, respectively (P =.001 and P =.02), but not for R2. A positive correlation could be detected among the mean bone mineral density of G and R1, G and R2, and R1 and R2 of (1) male and female specimens, (2) dentate and edentulous specimens, and (3) incisal, premolar, and molar specimens. Conclusions. The intra-alveolar trabecular bone of these 21 mandibles is affected by the same local and systemic influences as cortical bone, whereas the infra-alveolar trabecular bone is mostly sensitive to dental status. The cortical and trabecular bone of the 10 mandibles from women is more sensitive to systemic influences, whereas that from men is more sensitive to local influences. This is somewhat in agreement with some studies that found an association between osteoporosis and oral bone loss, which is a metric measure. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2003;95:364-70)

The aim of our study was to describe cross-sectional and longitudinal bone mineral decrease in pre-, peri-, and postmenopausal healthy women using a monoenergy X-ray densitometer specifically designed for forearm assessement. Measurements were performed on the most distal part of the radius (ultradistal, 55% of trabecular bone and 45% of trabecular bone), and on the distal part (distal, 13% of trabecular bone and 87% of cortical bone). A specific trabecular-rich region of interest (nROI) comprising two trapezoids regions of interest located proximally to the endplates of the radius and ulna was also investigated. From a large prospective study (OFELY study), 455 women were measured once a year for 2 years (three measurements). The proportion of postmenopausal women classified as having osteoporosis (i.e., a T score

The aim of the present study on human vertebral cancellous bone was to validate structural parameters measured with high-resolution (150 microm) computed tomography (HRCT) by referring to histomorphometry and to try to predict mechanical properties of bone using HRCT. Two adjacent vertical cores were removed from the central part of human L2 vertebral body taken after necropsy in 22 subjects aged 47-95 years (10 women, 12 men; mean age 79 +/- 14 years). The right core was used for structural analysis performed by both HRCT and histomorphometry. Two cancellous bone specimens were extracted from the left core: a cube for HRCT and a compression test, and a cylinder for a shear test. Significant correlations were found between HRCT and histomorphometric measurements (BV/TV, trabecular thickness, separation and number, and node-strut analysis), but with higher values for most of the tomographic parameters (BV/TV and trabecular thickness determined by HRCT were overestimated by a factor 3.5 and 2.5 respectively, as compared with histomorphometry). The maximum compressive strength and Young's modulus were highly correlated (rho = 0.99, p0.0005). Significant correlation was obtained between bone mineral density (determined using dual-energy X-ray absorptiometry) and the maximum compressive strength (rho = 0. 64, p = 0.002). In addition the maximum compressive strength and architectural parameters determined by HRCT or histomorphometry showed significant correlations (e.g., for HRCT, BV/TV: rho = 0.88, p0.0005, N.Nd/TV: rho = 0.73, p0.001). The shear strength was significantly correlated with BV/TV (rho = 0.62, p = 0.002), Tb.Sp (rho = -0.58, p = 0.004) and TSL (rho = 0.55, p = 0.006) measured by HRCT. In conclusion, an HRCT system with 150 microm resolution is not sufficient to predict the true values of the structural parameters measured by histomorphometry, although high correlations were found between the two methods. However, we showed that a resolution of 150 microm allowed us to predict the mechanical properties of human cancellous bone. In vivo peripheral systems with such a resolution should be of interest and would deliver an acceptable radiation dose to the patient.

The ability of biochemical markers to predict the rate of postmenopausal bone loss is still controversial. To investigate this issue further, baseline levels of a panel of specific and sensitive biochemical bone markers were correlated to the rate of change of forearm bone mineral density (BMD) assessed by four measurements over a 4-year period using dual-energy X-ray absorptiometry in a large population-based prospective cohort of 305 women aged 50-88 years (mean 64 years), 1-38 years postmenopausal. In the whole population, higher baseline levels of bone formation (serum osteocalcin and serum type I collagen N-terminal propeptide) and bone resorption markers (urinary N-telopeptides; urinary and serum C-telopeptides) were significantly associated with faster BMD loss (r = -0.19 to -0.30, p < 0.001), independently of age. In women within 5 years of menopause that have the highest rate of bone loss, the predictive value of bone markers was increased with correlation coefficients reaching 0.53. Women with an abnormally high bone turnover, i.e., with levels of bone markers at baseline 2 SD above the mean of premenopausal women, had a rate of bone loss that was 2- to 6-fold higher than women with a low turnover (p = 0.01-0.0001) according to the marker. When the population was categorized according to quartiles of bone markers at baseline, a similar relationship between increased levels of bone markers and faster rate of bone loss was found (p = 0.008-0.0001). In the logistic regression model, the odds-ratio of fast bone loss, defined as the rate of bone loss in the upper tertile of the population, was increased by 1.8- to 3.2-fold for levels of biochemical markers in the high turnover group compared with levels within the premenopausal range, with, however, a limited value for identifying individual fast bone losers. We conclude that increased levels of some of the new biochemical markers of bone turnover are associated with greater radial bone loss. Because increased bone loss is associated with an increased risk of fracture, bone turnover markers may be useful to improve the prediction of the risk of osteoporosis in postmenopausal women.

The purpose of this investigation was to compare the ability of two different bone densitometry techniques (quantitative computed tomography and dual X-ray absorptiometry) to discriminate subjects without any vertebral fracture from those with definite vertebral fractures. Bone mineral density (BMD) was determined in 112 post-menopausal women. 83 women were classified free of vertebral fracture and 29 were considered to have definite vertebral fractures. Quantitative computed tomography (QCT) was performed using three different spinal regions of interest. Dual X-ray absorptiometry (DXA) was measured at the spine (both in posteroanterior (PA) and lateral (L-DXA) projection, and at hip (total, neck and Ward regions). An additional estimated volumetric BMD was derived from the PA and L-DXA spine scans. Individuals with definite vertebral fractures had lower bone mineral density for each of the methods and regions of interest (ROI). Spinal QCT results, total and Ward hip DXA results showed the greatest percentage decrement. Odds ratio estimates revealed a significant relationship between BMD and fracture with spinal QCT, hip, and volumetric spinal DXA. The greatest areas under the receiver operating characteristic (ROC) curves were found with results of spinal QCT, total and Ward hip DXA, and volumetric spinal DXA measurements. It is concluded that spinal QCT and femoral total DXA measurement may be preferred to PA and lateral L3 DXA measurements.

The two main determinants of hip fractures are falls and bone loss leading to an intrinsic femoral fragility. Substantial femoral bone loss continues throughout old age, with a continuous and exponential increase in the risk of hip fracture; thus any reduction or arrest of this loss will induce an important reduction in the incidence of hip fracture. Preventive measures may be achieved during childhood by increasing peak bone mass with calcium and exercise, by using long-term estrogen replacement therapy after menopause, but also by using vitamin D and calcium supplements for late prevention in the elderly. Vitamin D insufficiency and a deficit in calcium intake are very common in the elderly living either in institutions or at home and the cumulative response to these deficits is a negative calcium balance which stimulates parathyroid hormone secretion. This senile secondary hyperparathyroidism is one of the determinants of femoral bone loss and can be reversed by calcium and vitamin D supplements. We have shown in a 3-year controlled prospective study that the daily use of supplements (1.2 g calcium and 800 IU vitamin D3) given in a large population of 3270 elderly ambulatory women living in nursing homes reduced the number of hip fractures by 23% (intention-to-treat analysis). In parallel, serum parathyroid hormone concentrations were reduced by 28% and low baseline serum 25-hydroxy vitamin D concentration returned to normal values. After 18 months of treatment the bone density of the total proximal femoral region had increased by 2.7% in the vitamin D3-calcium group and decreased by 4.6% in the placebo group (p

Hypovitaminosis D and a low calcium intake contribute to increased parathyroid function in elderly persons. Calcium and vitamin D supplements reduce this secondary hyperparathyroidism, but whether such supplements reduce the risk of hip fractures among elderly people is not known.We studied the effects of supplementation with vitamin D3 (cholecalciferol) and calcium on the frequency of hip fractures and other nonvertebral fractures, identified radiologically, in 3270 healthy ambulatory women (mean [+/- SD] age, 84 +/- 6 years). Each day for 18 months, 1634 women received tricalcium phosphate (containing 1.2 g of elemental calcium) and 20 micrograms (800 IU) of vitamin D3, and 1636 women received a double placebo. We measured serial serum parathyroid hormone and 25-hydroxyvitamin D (25(OH)D) concentrations in 142 women and determined the femoral bone mineral density at base line and after 18 months in 56 women.Among the women who completed the 18-month study, the number of hip fractures was 43 percent lower (P = 0.043) and the total number of nonvertebral fractures was 32 percent lower (P = 0.015) among the women treated with vitamin D3 and calcium than among those who received placebo. The results of analyses according to active treatment and according to intention to treat were similar. In the vitamin D3-calcium group, the mean serum parathyroid hormone concentration had decreased by 44 percent from the base-line value at 18 months (P0.001) and the serum 25(OH)D concentration had increased by 162 percent over the base-line value (P0.001). The bone density of the proximal femur increased 2.7 percent in the vitamin D3-calcium group and decreased 4.6 percent in the placebo group (P0.001).Supplementation with vitamin D3 and calcium reduces the risk of hip fractures and other nonvertebral fractures among elderly women.

International audience; Bone sialoprotein (BSP) and osteopontin (OPN) are both highly expressed in bone, but their functional specificities are unknown. OPN knockout ((-/-)) mice do not lose bone in a model of hindlimb disuse (tail suspension), showing the importance of OPN in bone remodeling. We report that BSP(-/-) mice are viable and breed normally, but their weight and size are lower than wild-type (WT) mice. Bone is undermineralized in fetuses and young adults, but not in older (>/=12 mo) BSP(-/-) mice. At 4 mo, BSP(-/-) mice display thinner cortical bones than WT, but greater trabecular bone volume with very low bone formation rate, which indicates reduced resorption, as confirmed by lower osteoclast surfaces. Although the frequency of total colonies and committed osteoblast colonies is the same, fewer mineralized colonies expressing decreased levels of osteoblast markers form in BSP(-/-) versus WT bone marrow stromal cultures. BSP(-/-) hematopoietic progenitors form fewer osteoclasts, but their resorptive activity on dentin is normal. Tail-suspended BSP(-/-) mice lose bone in hindlimbs, as expected. In conclusion, BSP deficiency impairs bone growth and mineralization, concomitant with dramatically reduced bone formation. It does not, however, prevent the bone loss resulting from loss of mechanical stimulation, a phenotype that is clearly different from OPN(-/-) mice.

Bone mineral density (BMD) measured by single photon absorptiometry (SPA) with a Moolsgard 1100 device on the distal and proximal part of the radius was compared with histomorphometric parameters measured on iliac crest biopsies in 37 patients suffering from various bone disorders. In the whole population, a good correlation was observed between the cancellous bone volume (Cn-BV/TV) measured on iliac crest biopsies and BMD from both the proximal part of the radius (r = 0.76, p less than 0.001) and the distal part of the radius (r = 0.73, p less than 0.001). Significant, although weaker correlations, were also found between the cortical width and the BMD from the distal part (r = 0.37, p less than 0.001) and the proximal part (r = 0.44, p less than 0.001) of the radius. In the 14 untreated osteoporotic patients, only a significant Spearman correlation was observed between the iliac Cn-BV/TV and the proximal radial BMD (r' = 0.69, p less than 0.05). It is thus not clear, whether radial proximal BMD correctly indicates cortical bone density in osteoporotic patients or not. The large internal variability of each of the two investigated methods and the small group of osteoporotic patients might explain the lack of correlation between the two methods in this group.

Bone mineral density (BMD) measurement of the lumbar spine by dual-photon absorptiometry (DPA) using a radioactive source and more recently an x-ray tube (DEXA) is a useful noninvasive technique to assess bone loss in vertebral osteoporosis. Because an anteroposterior (AP) projection is used, DPA measures not only the mainly trabecular bone of the vertebral body but also the cortical bone of the posterior processes, which does not contribute to the development of crushed fractures. Using a DPA apparatus equipped with a 153 Gd source coupled with an 18-detector system that provides better collection efficiency for the narrow beam of 153 Gd radiation, we have developed a technique measuring the BMD of the vertebral body of L2, L3, and L4 on a lateral projection based on previous studies using radiographic photodensitometry for lateral spine. The precision of the method-1.7% in vivo and 0.88% in vitro-is similar to that obtained with the AP projection (respectively, 1.7 and 1.0%). Lateral BMD decreased with age in 143 normal women and was best accounted for by a cubic curve (r = -0.51, p less than 0.001). The age-related bone loss between 30 and 80 years of age was much higher with the lateral (-44%) than with the AP (-22%) projection, a pattern consistent with the greater trabecular than cortical age-related bone loss. When osteoporotics (OP) were compared to age-matched normal women, the decreased in BMD was larger with the lateral (-30%) than with the AP projection (-23%), but in terms of Z scores, no difference could be found between both projections.(ABSTRACT TRUNCATED AT 250 WORDS)