ABSTRACT

BMD, bone microarchitecture, and bone mechanical properties assessed in vivo by finite element analysis were associated with wrist fracture in postmenopausal women.Introduction: Many fractures occur in individuals with normal BMD. Assessment of bone mechanical properties by finite element analysis (FEA) may improve identification of those at high risk for fracture. Materials and Methods: We used HR-pQCT to assess volumetric bone density, microarchitecture, and FEderived bone mechanical properties at the radius in 33 postmenopausal women with a prior history of fragility wrist fracture and 33 age-matched controls from the OFELY cohort. Radius areal BMD (aBMD) was also measured by DXA. Associations between density, microarchitecture, mechanical parameters and fracture status were evaluated by univariate logistic regression analysis and expressed as ORs (with 95% CIs) per SD change. We also conducted a principal components (PCs) analysis (PCA) to reduce the number of parameters and study their association (OR) with wrist fracture. Results: Areal and volumetric densities, cortical thickness, trabecular number, and mechanical parameters such as estimated failure load, stiffness, and the proportion of load carried by the trabecular bone at the distal and proximal sites were associated with wrist fracture (p < 0.05). The PCA revealed five independent components that jointly explained 86.2% of the total variability of bone characteristics. The first PC included FE-estimated failure load, areal and volumetric BMD, and cortical thickness, explaining 51% of the variance with an OR for wrist fracture ‫ס‬ 2.49 (95% CI, 1.32-4.72). Remaining PCs did not include any density parameters. The second PC included trabecular architecture, explaining 12% of the variance, with an OR ‫ס‬ 1.82 (95% CI, 0.94-3.52). The third PC included the proportion of the load carried by cortical versus trabecular bone, assessed by FEA, explaining 9% of the variance, and had an OR ‫ס‬ 1.61 (95% CI, 0.94-2.77). Thus, the proportion of load carried by cortical versus trabecular bone seems to be associated with wrist fracture independently of BMD and microarchitecture (included in the first and second PC, respectively). Conclusions: These results suggest that bone mechanical properties assessed by FE may provide information about skeletal fragility and fracture risk not assessed by BMD or architecture measurements alone and are therefore likely to enhance the prediction of wrist fracture risk.

ABSTRACT:We assessed the role of low aBMD and impaired architecture-assessed by an HR-pQCT system-in a case-control study of postmenopausal women with fractures. Vertebral and nonvertebral fractures are associated with low volumetric BMD and architectural alterations of trabecular and cortical bone, independent of aBMD assessed by DXA.Introduction: Alterations of bone architecture and low BMD both contribute to skeletal fragility, but the contribution of cortical and trabecular architecture, independently of areal BMD (aBMD), to the risk of fracture in postmenopausal women has not been thoroughly evaluated. We assessed the role of impaired architecture and low BMD in postmenopausal women with fractures. Materials and Methods: A matched case-control study in women from the OFELY cohort was performed after 13 years of follow-up. One hundred one women (mean, 73.7 ± 8 years) who sustained a fragility fracture during the follow-up of the study were age-matched with one control who never had a fracture. Density and architecture at the distal radius and tibia were measured with high-resolution pQCT (HR-pQCT) using an XTreme CT (Scanco Medical AG, Bassersdorf, Switzerland). aBMD at the total hip and ultradistal radius was measured by DXA. Results: There were 80 peripheral fractures in 72 women, 44 vertebral fractures in 34 women, and both types of fractures in 5 women over the 14 years of follow-up. At the distal radius, women with fractures had lower volumetric total (D tot) and trabecular (D trab) BMDs, BV/TV, cortical thickness (Cort Th), trabecular number (TbN), and trabecular thickness (TbTh) and higher trabecular separation (TbSp) and distribution of trabecular separation (TbSpSd) than controls without fractures. In a logistic model, each SD decrease of volumetric total and trabecular densities was associated with a significantly increased risk of fracture at both sites (ORs ranged from 2.00 to 2.47). After adjusting for aBMD measured by DXA at the ultradistal radius, differences between cases and controls remained significant for D trab, and there was a similar trend for TbN, TbSp, and TbSpSd, with adjusted ORs ranging from 1.32 to 1.50. At the distal tibia, before and after adjusting for total hip aBMD, differences between cases and controls remained significant for D tot, D trab, Cort Th, and TbTh, with adjusted ORs ranging from 1.80 to 2.09. Conclusions: In postmenopausal women, vertebral and nonvertebral fractures are associated with low volumetric BMD and architectural alterations of trabecular and cortical bone that can be assessed noninvasively and that are partially independent of aBMD assessed by DXA.

Trabecular bone score (TBS) is a gray-level textural index of bone microarchitecture derived from lumbar spine dual-energy X-ray absorptiometry (DXA) images. TBS is a bone mineral density (BMD)-independent predictor of fracture risk. The objective of this metaanalysis was to determine whether TBS predicted fracture risk independently of FRAX probability and to examine their combined performance by adjusting the FRAX probability for TBS. We utilized individual-level data from 17,809 men and women in 14 prospective population-based cohorts. Baseline evaluation included TBS and the FRAX risk variables, and outcomes during follow-up (mean 6.7 years) comprised major osteoporotic fractures. The association between TBS, FRAX probabilities, and the risk of fracture was examined using an extension of the Poisson regression model in each cohort and for each sex and expressed as the gradient of risk (GR; hazard ratio per 1 SD change in risk variable in direction of increased risk). FRAX probabilities were adjusted for TBS using an adjustment factor derived from an independent cohort (the Manitoba Bone Density Cohort). Overall, the GR of TBS for major osteoporotic fracture was 1.44 (95% confidence interval [CI] 1.35-1.53) when adjusted for age and time since baseline and was similar in men and women (p > 0.10). When additionally adjusted for FRAX 10-year probability of major osteoporotic fracture, TBS remained a significant, independent predictor for fracture (GR ¼ 1.32, 95% CI 1.24-1.41). The adjustment of FRAX probability for TBS resulted in a small increase in the GR (1.76, 95% CI 1.65-1.87 versus 1.70, 95% CI 1.60-1.81). A smaller change in GR for hip fracture was observed (FRAX hip fracture probability GR 2.25 vs. 2.22). TBS is a significant predictor of fracture risk independently of FRAX. The findings support the use of TBS as a potential adjustment for FRAX probability, though the impact of the adjustment remains to be determined in the context of clinical assessment guidelines.

Periosteal apposition does not increase after menopause to compensate for bone loss; it decreases. Bone fragility of osteoporosis is a consequence of reduced periosteal bone formation and increased endocortical resorption. Understanding the mechanisms of the age-related decline in periosteal apposition will identify new therapeutic targets. On the basis of our results, it may be speculated that the stimulation of periosteal apposition will increase bone width and improve skeletal strength.

About one-half of women with incident fractures have BMD above the WHO diagnostic threshold of osteoporosis. In the OFELY study, low BMD, increased markers of bone turnover, and prior fracture could be used to identify, within osteopenic women, those at high risk of fracture.Introduction: Recent data suggest that about one-half of women with incident fractures have BMD above the World Health Organization (WHO) diagnostic threshold of osteoporosis (T score Յ −2.5). We aimed to identify, within osteopenic women, those at high risk of fracture. Materials and Methods: In the 671 postmenopausal women (mean age: 62 years) belonging to the Os des Femmes de Lyon (OFELY) population-based prospective cohort, we measured at baseline BMD by DXA at the spine and total hip, bone turnover markers (BTM) and clinical risk factors for osteoporosis. All fragility vertebral or nonvertebral fractures, confirmed by radiographs, were assessed during a median follow-up of 9.1 years (IQ: 2.3). Results: 158 incident fractures were recorded in 116 women: 8% in normal, 48% in osteopenic, and 44% in osteoporotic women. Among osteopenic women, low BMD (−2.5 < T score Յ −2.0) was associated with an increased fracture risk with an age-adjusted hazard ratio (HR) of 2.5 (1.3-4.6). In addition, age, prior fracture, and high BTM-but not other risk factors-were independently associated with an increased fracture risk with an age-adjusted HR of 2.2 (1.2-4.3) for prior fractures and 2.2 (1.4-3.8) for bone alkaline phosphatase (BALP) in the highest quartile. In the whole group of osteopenic women, a large majority of incident fractures occurred in those with a low BMD, prior fractures, or BALP in the highest quartile, with an age-adjusted HR of 5.3 (2.3-11.8). The 10-year probability of fracture in osteopenic women was 26% if at least one predictor was present, contrasting with 6% in those without any of the three risk factors. Conclusions: In postmenopausal women with osteopenia, low BMD, increased BTM, and prior fracture are associated with an increased risk of fracture in the subsequent 10 years. Their assessment may play an important role in identifying women at high risk of fracture who could not be adequately detected by BMD measurement alone and who may benefit from a therapeutic intervention.

Background: Although dual-energy x-ray absorptiometry (DXA) assessed areal bone density (aBMD) is the clinical standard for determining fracture risk, the majority of older adults who sustain a fracture do not have osteoporosis (T-score < −2.5). Importantly, bone fragility results not only from low BMD, but also from deterioration in bone structure. We used high-resolution peripheral quantitative computed tomography (HR-pQCT) data from eight cohorts to evaluate whether HR-pQCT indices were associated with fracture risk independently of femoral neck (FN) aBMD and FRAX (Fracture Risk Assessment Tool) score. Methods: Participants included 7,254 individuals (66% women) from cohorts in the USA (Framingham, Mayo Clinic), France (QUALYOR, STRAMBO, OFELY), Switzerland (GERICO), Canada (CaMos), and Sweden (MrOS). We used Cox proportional hazards models to estimate hazards ratios (HRs) for the association between bone parameters (per standard deviation, SD, deficit) and incident fracture, adjusting for age, sex, height, weight and cohort. Findings: Mean baseline age was 69 (±9) years (range, 40 to 96). Cumulative incidence of fracture was 11% (n=765) over a mean follow-up time of 4.6 (± 2.4) years. The majority of participants (92%) had a femoral neck T-score >−2.5, and thus did not meet diagnostic criteria for osteoporosis. Failure load was the bone measure most strongly associated with risk of fracture: tibia HR=2.40 (1.98-2.91), radius HR=2.13 (1.77-2.56), per SD decrease in failure load. HRs for other bone indices ranged from HR=1.12 (1.03-1.23) per SD increase in tibia cortical porosity to HR=1.58 (1.45-1.72) per SD decrease in radius trabecular volumetric bone density (vBMD). After further adjustment for FN aBMD or FRAX, HRs were attenuated, but most bone parameters remained significantly associated with fracture. Cortical density, trabecular number, and trabecular thickness at the distal radius were the best set of predictors of fracture; while the same indices plus cortical area were identified for the tibia. These HR-pQCT indices and failure load improved prediction of fracture, beyond FN aBMD alone or FRAX. Interpretation: Results from this large international cohort of women and men confirm prior studies showing that deficits in trabecular and cortical bone density and structure contribute to fracture risk independently of aBMD and FRAX. Measurements of cortical and trabecular bone density and morphology at the peripheral skeleton may improve identification of those at highest risk for fracture. Funding: National Institutes of Health, National Institute of Arthritis Musculoskeletal and Skin Diseases, R01AR061445

We measured the bone mineral density (BMD) at various skeletal sites (total body, hip, anteroposterior [AP] and lateral [lat] spine, and forearm) in a large population-based cohort of women aged 31-89 years (the OFELY cohort), and results were analyzed according to age and postmenopausal years. A significant apparent bone loss was found before the menopause in cancellous bone, i.e., at the lat spine and Ward's triangle (؊10%; p < 0.05-0.001). Cross-sectional analysis indicated that, after the menopause, apparent bone loss was accelerated within the 10 years following menopause, continued thereafter at all sites except the AP spine, and was again accelerated in elderly menopausal for more than 25 years. Between 30 and 80 years, BMD decreased by 15 to 44% (T score ؊1.6 to ؊3.4) according to the site. The amount of apparent bone loss was highest at the Ward's triangle when expressed in percentage (44%) and at the mid-and distal radius when expressed in number of standard deviations from the peak bone mass (؊3.4). As a result, the percentage of women classified as osteoporotic according to the World Heath Organization, i.e., with a T score ؊2.5, varied substantially from site to site and was highest at the radius (37% and 46%) and lateral spine (25-31%), intermediate at the Ward's triangle, AP spine, and whole body BMD, and lowest at the whole body bone mineral content, femoral neck, and trochanter (10 -12%). In conclusion, this cross-sectional but large study suggests that there is a moderate apparent premenopausal bone loss that occurs only at cancellous bone sites and that apparent bone loss is accelerated at most skeletal sites after the age of 75 years. Because of the highly variable coefficient of variation of the peak bone mass at various skeletal sites, the percentage of postmenopausal women identified as being osteoporotic varies widely according to the site of measurement. (J Bone Miner Res 1997;12:683-690)