Nicolas Vilayphiou

Finite element analysis performed on radius and tibia HR-pQCT images and fragility fractures at all sites in postmenopausal women

Assessment of bone strength at the radius by micro-finite element analysis (muFEA) has already been associated with wrist fractures. In this study, the analysis has been extended to the distal tibia, and to a larger group of subjects to examine the association with several types of fragility fractures. We have compared muFEA based on in vivo HR-pQCT measurements of BMD and microarchitecture at the radius and tibia, in a case-control study involving 101 women with prevalent fragility fracture and 101 age-matched controls, from the OFELY cohort. Areal BMD was measured by DXA at the radius and the hip. All parameters were analyzed in a principal component (PC) analysis (PCA), and associations between PCs and fractures were computed as odds ratios (OR [95% CI]) per SD change. Radius (tibia) PCA revealed three independent components explaining 76% (77%) of the total variability of bone characteristics. The first PC describing bone strength and quantity, explained 50% (46%) of variance with an OR=1.84 [1.27-2.67] (2.92 [1.73-4.93]). The second PC including trabecular microarchitecture, explained 16% (10%) of variance, with OR=1.29 [0.90-1.87] (1.11 [0.82-1.52]). The third PC related to load distribution explained 10% (20%) of variance, with OR=1.54 [1.06-2.24] (1.32 [0.89-1.96]). Moreover, at the radius, vertebral fractures were associated with trabecular microarchitecture PC with OR=1.86 [1.14-3.03], whereas nonvertebral fractures were associated with bone strength and quantity PC with OR=2.03 [1.36-3.02]. At the tibia, both vertebral (OR=2.92 [1.61-5.28]) and nonvertebral fracture (2.64 [1.63-4.27]) were associated to bone strength and quantity PC. In conclusion, muFEA parameters at the radius and tibia were associated with all types of fragility fractures. We have also shown that muFEA parameters obtained with distal tibia data were associated with prevalent fractures with a similar magnitude that with parameters obtained at the radius.

Cross‐sectional analysis of the association between fragility fractures and bone microarchitecture in older men: The STRAMBO study

Areal bone mineral density (aBMD) measured by dual‐energy X‐ray absorptiometry (DXA) identifies 20% of men who will sustain fragility fractures. Thus we need better fracture predictors in men. We assessed the association between the low‐trauma prevalent fractures and bone microarchitecture assessed at the distal radius and tibia by high‐resolution peripheral quantitative computed tomography (HR‐pQCT) in 920 men aged 50 years of older. Ninety‐eight men had vertebral fractures identified on the vertebral fracture assessment software of the Hologic Discovery A device using the semiquantitative criteria, whereas 100 men reported low‐trauma peripheral fractures. Men with vertebral fractures had poor bone microarchitecture. However, in the men with vertebral fractures, only cortical volumetric density (D.cort) and cortical thickness (C.Th) remained significantly lower at both the radius and tibia after adjustment for aBMD of ultradistal radius and hip, respectively. Low D.cort and C.Th were associated with higher prevalence of vertebral fractures regardless of aBMD. Severe vertebral fractures also were associated with poor trabecular microarchitecture regardless of aBMD. Men with peripheral fractures had poor bone microarchitecture. However, after adjustment for aBMD, all microarchitectural parameters became nonsignificant. In 15 men with multiple peripheral fractures, trabecular spacing and distribution remained increased after adjustment for aBMD. Thus, in men, vertebral fractures and their severity are associated with impaired cortical bone, even after adjustment for aBMD. The association between peripheral fractures and bone microarchitecture was weaker and nonsignificant after adjustment for aBMD. Thus bone microarchitecture may be a determinant of bone fragility in men, which should be investigated in prospective studies.

Assessment of hand bone loss in rheumatoid arthritis by high-resolution peripheral quantitative CT

Objectives A new high-resolution peripheral quantitative CT (HR-pQCT) system allows for in vivo assessment of bone microarchitecture and volumetric bone mineral density (vBMD) with an 82 µm isotropic resolution. With this device, the microarchitecture impairment was evaluated in patients with rheumatoid arthritis (RA) in comparison with healthy controls and measured the erosion volume at metacarpal heads (MCPs). Methods In this cross-sectional study, the reproducibility was first assessed by 3 HR-pQCT exams with repositioning in 14 patients with late RA and 14 healthy subjects. Then, HR-pQCT parameters were measured in a group of 93 patients with RA and 31 healthy controls. Two RA subgroups were distinguished: early RA (disease duration ≤2 years) (n=36) and late RA (n=57) and compared them to healthy controls. Results The precision of the HR-pQCT volumetric measurements as assessed with coefficient of variation ranged from 0.7% to 1.8% in patients with late RA and from 0.6% to 1.4% in healthy subjects at MCPs. Total and trabecular vBMD and trabecular thickness were significantly decreased in patients with RA compared to healthy subjects and were significantly correlated to disease activity. The erosion volume was highly correlated to a semiquantitative assessment using the Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) scoring system applied to the HR-pQCT slices. Conclusions This study demonstrated the good reproducibility of the HR-pQCT volumetric measurements at MCPs and confirmed the involvement of trabecular compartment in periarticular osteopoenia. Thus, HR-pQCT appears interesting to simultaneously assess differences in bone volumetric density, microarchitecture and erosions.

Role of Trabecular Microarchitecture and Its Heterogeneity Parameters in the Mechanical Behavior of Ex Vivo Human L3 Vertebrae

Low bone mineral density (BMD) is a strong risk factor for vertebral fracture risk in osteoporosis. However, many fractures occur in people with moderately decreased or normal BMD. Our aim was to assess the contributions of trabecular microarchitecture and its heterogeneity to the mechanical behavior of human lumbar vertebrae. Twenty‐one human L3 vertebrae were analyzed for BMD by dual‐energy X‐ray absorptiometry (DXA) and microarchitecture by high‐resolution peripheral quantitative computed tomography (HR‐pQCT) and then tested in axial compression. Microarchitecture heterogeneity was assessed using two vertically oriented virtual biopsies—one anterior (Ant) and one posterior (Post)—each divided into three zones (superior, middle, and inferior) and using the whole vertebral trabecular volume for the intraindividual distribution of trabecular separation (Tb.Sp*SD). Heterogeneity parameters were defined as (1) ratios of anterior to posterior microarchitectural parameters and (2) the coefficient of variation of microarchitectural parameters from the superior, middle, and inferior zones. BMD alone explained up to 44% of the variability in vertebral mechanical behavior, bone volume fraction (BV/TV) up to 53%, and trabecular architecture up to 66%. Importantly, bone mass (BMD or BV/TV) in combination with microarchitecture and its heterogeneity improved the prediction of vertebral mechanical behavior, together explaining up to 86% of the variability in vertebral failure load. In conclusion, our data indicate that regional variation of microarchitecture assessment expressed by heterogeneity parameters may enhance prediction of vertebral fracture risk.

In obese postmenopausal women, bone microarchitecture and strength are not commensurate to greater body weight: the Os des Femmes de Lyon (OFELY) study.

Obesity is associated with higher areal bone density (aBMD) but its protective effect on the risk of fracture is controversial. We aimed to analyze bone microarchitecture and biomechanical properties in obese (OB) postmenopausal French women compared with normal weight (NW) women. A matched case‐control study from the Os des Femmes de Lyon (OFELY) cohort was conducted in 63 OB women (body mass index [BMI] > 30, mean age 69 ± 8 years) age‐matched with 126 NW women (19 ≤ BMI ≤ 25). Bone architecture was measured with high‐resolution pQCT at the distal radius and tibia and bone strength was assessed by micro–finite element analysis (µFEA). aBMD, total body fat mass (FM) and lean mass (LM) were measured by dual‐energy X‐ray absorptiometry (DXA). aBMD was 15% higher at the total hip in OB compared with NW women. At the radius, OB had 13% and 14% higher volumetric total and trabecular bone densities, 11% higher cortical thickness, 13% greater trabecular number, and 22% lower distribution of trabecular separation compared with NW (p adjusted for height, physical activity, and medication use, <0.01 for all). Differences of a similar magnitude were found at the distal tibia. At both sites, µFEA showed significant higher values of bone strength in OB compared to controls. After normalizing values for individual body weight, we observed that all the parameters were relatively lower in OB compared to NW women. The increase of FM was fourfold greater than the increase of LM in OB. The effect of FM on bone parameters was more pronounced at the tibia compared to the non–weight‐bearing site. Nevertheless, the coefficients of correlation were about one‐half of those of LM for the biomechanical parameters. We conclude that higher absolute values of bone densities, cortical and trabecular architecture, and strength indices were not in proportion to the excess of BMI and particularly of FM in obese postmenopausal French women.

Impaired bone microarchitecture at the distal radius in older men with low muscle mass and grip strength: the STRAMBO study.

The aim was to study the association between bone microarchitecture and muscle mass and strength in older men. Volumetric bone mineral density (vBMD) and bone microarchitecture were assessed in 810 men aged ≥60 years at the distal radius by high‐resolution peripheral computed tomography (HR‐pQCT). Areal bone mineral density (aBMD) and appendicular muscle mass (ASM) were assessed by dual‐energy X‐ray absorptiometry (DXA). Relative ASM of the upper limbs (RASM‐u.l.) was calculated as ASM of the upper limbs/(height)2. Grip strength was measured by dynanometry. In multivariable models, men in the lowest RASM‐u.l. quartile had lower cross‐sectional area (CSA), cortical area (Ct.Ar), cortical thickness (Ct.Th), and trabecular area (Tb.Ar) at distal radius compared with men in the highest quartile. The trends remained significant after adjustment for grip strength. Men in the lowest quartile of the normalized grip strength (grip strength/[height]2) had lower aBMD, total vBMD, Ct.Ar, Ct.Th, Tb.vBMD, and Tb.N, and higher Tb.Sp and Tb.Sp.SD. The associations for Ct.Ar, total vBMD, Ct.Th, Tb.vBMD, and Tb.Sp remained significant after adjustment for RASM‐u.l. In the models including RASM‐u.l. and normalized grip strength, CSA and Tb.Ar were associated with RASM‐u.l. but not with the strength. Lower Ct.Th, Tb.vBMD, and Tb.N were associated with lower grip strength but not with RASM‐u.l. Lower Ct.Ar was associated with lower grip strength and with lower RASM‐u.l. In conclusion, in older men, low RASM‐u.l. and low grip strength are associated with poor cortical and trabecular microarchitecture partly independently of each other, after adjustment for confounders.

Association of bone microarchitecture with parathyroid hormone concentration and calcium intake in men: the STRAMBO study

UNLABELLED OBJECTVIE: In the elderly, vitamin D deficit, low calcium intake, and impaired bone microarchitecture are associated with higher risk of hip fracture. We assessed the association of bone microarchitecture with calcium intake and serum concentrations of 25-hydroxycholecalciferol (25OHD) and parathyroid hormone (PTH) in men. DESIGN Cross-sectional analysis was performed in 1064 men aged 20-87 years not taking vitamin D or calcium supplements. METHODS Daily calcium intake was assessed using a food frequency questionnaire. Bone microarchitecture was assessed at distal radius and tibia by high-resolution peripheral quantitative computed tomography. We measured serum and urinary levels of biochemical bone turnover markers (BTMs). Statistical models were adjusted for age, weight, height, and glomerular filtration rate. RESULTS In 500 men aged <65 years, lower 25OHD levels and low calcium intake were associated with lower trabecular volumetric bone mineral density (Dtrab) at the distal tibia, due to lower trabecular number (Tb.N). Low calcium intake was associated with lower cortical thickness (Ct.Th). Higher PTH level was associated with higher BTM levels. In 563 men aged ≥65 years, the highest PTH quartile was associated with lower Ct.Th (tibia), lower Dtrab (both sites), and lower Tb.N (radius) compared with the lowest quartile. Low calcium intake was associated with lower Tb.N and more heterogenous trabecular distribution. BTM positively correlated with the PTH concentration. CONCLUSION In older men, elevated PTH concentration is associated with high bone turnover, poor trabecular microarchitecture (radius and tibia), and, at the distal tibia, lower Ct.Th. Low calcium intake is associated with lower Tb.N and more heterogenous trabecular distribution.

Age-related changes in bone strength from HR-pQCT derived microarchitectural parameters with an emphasis on the role of cortical porosity

The high resolution peripheral computed tomography (HR-pQCT) technique has seen recent developments with regard to the assessment of cortical porosity. In this study, we investigated the role of cortical porosity on bone strength in a large cohort of women. The distal radius and distal tibia were scanned by HR-pQCT. We assessed bone strength by estimating the failure load by microfinite element analysis (μFEA), with isotropic and homogeneous material properties. We built a multivariate model to predict it, using a few microarchitecture variables including cortical porosity. Among 857 Caucasian women analyzed with μFEA, we found that cortical and trabecular properties, along with the failure load, impaired slightly with advancing age in premenopausal women, the correlations with age being modest, with |rage| ranging from 0.14 to 0.38. After the onset of the menopause, those relationships with age were stronger for most parameters at both sites, with |rage| ranging from 0.10 to 0.64, notably for cortical porosity and failure load, which were markedly deteriorated with increasing age. Our multivariate model using microarchitecture parameters revealed that cortical porosity played a significant role in bone strength prediction, with semipartial r(2)=0.22 only at the tibia in postmenopausal women. In conclusion, in our large cohort of women, we observed a small decline of bone strength at the tibia before the onset of menopause. We also found an age-related increase of cortical porosity at both scanned sites in premenopausal women. In postmenopausal women, the relatively high increase of cortical porosity accounted for the decline in bone strength only at the tibia.

Determinants of the Mechanical Behavior of Human Lumbar Vertebrae After Simulated Mild Fracture

The ability of a vertebra to carry load after an initial deformation and the determinants of this postfracture load‐bearing capacity are critical but poorly understood. This study aimed to determine the mechanical behavior of vertebrae after simulated mild fracture and to identify the determinants of this postfracture behavior. Twenty‐one human L3 vertebrae were analyzed for bone mineral density (BMD) by dual‐energy X‐ray absorptiometry (DXA) and for microarchitecture by micro–computed tomography (µCT). Mechanical testing was performed in two phases: initial compression of vertebra to 25% deformity, followed, after 30 minutes of relaxation, by a similar test to failure to determine postfracture behavior. We assessed (1) initial and postfracture mechanical parameters, (2) changes in mechanical parameters, (3) postfracture elastic behavior by recovery of vertebral height after relaxation, and (4) postfracture plastic behavior by residual strength and stiffness. Postfracture failure load and stiffness were 11% ± 19% and 53% ± 18% lower than initial values (p = .021 and p < .0001, respectively), with 29% to 69% of the variation in the postfracture mechanical behavior explained by the initial values. Both initial and postfracture mechanical behaviors were significantly correlated with bone mass and microarchitecture. Vertebral deformation recovery averaged 31% ± 7% and was associated with trabecular and cortical thickness (r = 0.47 and r = 0.64; p = .03 and p = .002, respectively). Residual strength and stiffness were independent of bone mass and initial mechanical behavior but were related to trabecular and cortical microarchitecture (|r| = 0.50 to 0.58; p = .02 to .006). In summary, we found marked variation in the postfracture load‐bearing capacity following simulated mild vertebral fractures. Bone microarchitecture, but not bone mass, was associated with postfracture mechanical behavior of vertebrae.

Assessment of hand trabecular bone texture with high resolution direct digital radiograph in rheumatoid arthritis: A case control study

OBJECTIVES Rheumatoid arthritis is characterized by an early inflammatory related periarticular osteopenia. A new high resolution direct digital X-ray device has been recently developed to provide bone texture analysis which is designed to assess changes in trabecular bone architecture. For the first time, we have evaluated trabecular bone texture impairment in rheumatoid arthritis patients compared to healthy controls. METHODS In this cross-sectional study, the reproducibility was assessed by three separate digital X-rays of the right hand, with repositioning in 14 late rheumatoid arthritis patients and 14 healthy subjects. Then, trabecular bone texture of the MCP2 and MCP3 from patients enrolled in a prospective cohort of 78 rheumatoid arthritis patients was compared with that of 50 healthy subjects, using three texture parameters: Hmean, co-occurrence and run-length. RESULTS The coefficients of variation of the high resolution direct digital X-ray measurements ranged from 0.5 to 1.8%. Only the Hmean parameter was significantly decreased in rheumatoid arthritis patients compared to healthy subjects at MCP2 (0.637±0.040 vs. 0.654±0.032, P<0.05) and at MCP3 (0.646±0.044 vs. 0.665±0.037, P<0.05). This reduction was significantly correlated to disease activity. CONCLUSIONS This study demonstrated both the good reproducibility of the high resolution digital X-ray measurements and the trabecular bone texture impairment at MCP joints in rheumatoid arthritis patients. In addition to provide a high resolution hand radiograph, this technique may represent an interesting tool to easily quantify periarticular osteopenia with a low radiation dose.