Bernard Cortet

Trabecular bone score (TBS): available knowledge, clinical relevance, and future prospects

The diagnosis of osteoporosis rests on areal bone mineral density (BMD) measurement using DXA. Cancellous bone microarchitecture is a key determinant of bone strength but cannot be measured using DXA. To meet the need for a clinical tool capable of assessing bone microarchitecture, the TBS was developed. The TBS is a texture parameter that evaluates pixel gray-level variations in DXA images of the lumbar spine. The TBS variations may reflect bone microarchitecture. We explain the general principles used to compute the TBS, and we report the correlations between TBS and microarchitectural parameters. Several limitations of the TBS as it is used now are pointed out. We discuss data from currently available clinical studies on the ability of the TBS to identify patients with fractures and to evaluate the fracture risk. We conclude that this new index emphasizes the failure of the BMD T-score to fully capture the fragility fracture risk. However, although microarchitecture may influence the TBS, today, to the best of our understanding, there is no sufficient evidence that a TBS measurement provides reliable information on the status of the bone microarchitecture for a given patient. The TBS depends on gray-level variations and in a projectional image obtained in vivo, these variations can have many causes. Nevertheless, as clinical studies suggest that the TBS predicts the risk of fracture even after adjustment for BMD, we are encouraged to learn more about this score. Additional studies will have to be performed to assess the advantages and limitations of the TBS, in order to ensure that it is used appropriately in clinical practice.

Spinal curvatures and quality of life in women with vertebral fractures secondary to osteoporosis.

STUDY DESIGN A prospective cross-sectional case-control study. OBJECTIVES To compare spinal curvatures in women with osteoporosis and control subjects with a new instrument, the curviscope. SUMMARY OF BACKGROUND DATA Few instruments are available for measuring spinal curvatures in the sagittal plane. Most of them have poor reproducibility, and they have been poorly investigated in osteoporosis. METHODS Ninety-eight postmenopausal women were evaluated. They were divided into two groups, according to their bone status: women with osteoporosis with at least one vertebral fracture (n = 51) and control subjects (n = 47). Women with osteoporosis were divided into two subgroups, according to the delay since the last vertebral fracture had occurred (i.e., more or less than 3 months). Quality of life was assessed by using a generic instrument, the Nottingham Health Profile, in patients with osteoporosis only. RESULTS Reproducibility of the curviscope was satisfactory. For kyphosis measurements, the coefficients of variation were 2.8% and 2.4% in control subjects and women with osteoporosis, respectively. Kyphosis values were significantly higher in women with osteoporosis than in age-matched control subjects (63 degrees +/- 13 degrees vs. 52 degrees +/- 11 degrees, respectively; P < 0.005). Nottingham Health Profile scores were significantly different (P < 0.05) in women with osteoporosis with a recently diagnosed vertebral fracture, compared with other women with osteoporosis in two aspects, physical mobility and energy. Kyphosis measurements were significantly correlated with age in the whole group (r = 0.26; P < 0.05). In the Nottingham Health Profile, physical mobility was significantly correlated with kyphosis (r = 0.35; P < 0.05). CONCLUSIONS The curviscope is a reliable tool, particularly useful in the assessment of osteoporosis. Moreover, kyphosis angles measured with the curviscope are markedly increased in women with osteoporosis, compared with control subjects. Finally, an increase of kyphosis angles is associated with decreased physical mobility.

Evaluation of spinal curvatures after a recent osteoporotic vertebral fracture.

OBJECTIVES To evaluate spinal curvature changes over a 3-year period in postmenopausal women who had had an osteoporotic vertebral fracture within the last 3 months. METHODS Thoracic kyphosis and lumbar lordosis were measured using a curviscope at baseline and after 1, 3, 6, 12, and 36 months. Anteroposterior and lateral radiographs of the thoracolumbar spine were obtained after 1 and 3 years. RESULTS Sixty-one patients were included. At baseline, a significant increase in thoracic curvature was found in the subgroup with thoracic fractures as compared to the subgroups with thoracolumbar or lumbar fractures (64 degrees +/- 9 degrees, 56 degrees +/- 10, and 56 degrees +/- 13, respectively; P < 0.05). No lumbar curvature differences were found. Thoracic curvature was significantly correlated with age (r = -0.48, P < 0.001) and with the vertebral deformity index (r = 0.6, P < 0.001). A significant increase in thoracic curvature was apparent 3 months into the study; after 3 years, the increase was 5.6 degrees +/- 0.7 (P < 0.01). A moderate increase in lumbar curvature was found after 3 years (P < 0.01). Five of 13 patients and five of 10 patients had at least one incident fracture after 1 and 3 years, respectively. Mean thoracic curvature was greater among the patients with than without incident fractures after 1 and 3 years, although the difference was not statistically significant. CONCLUSION Thoracic compression fractures significantly increase thoracic kyphosis as compared to dorsolumbar and lumbar fractures. Thoracic kyphosis worsens overtime in patients with prevalent vertebral fractures. These data invite an evaluation of techniques capable of providing early correction of alignment disorders, such as widespread use of bracing or kyphoplasty.

Does Quantitative Ultrasound of Bone Reflect More Bone Mineral Density Than Bone Microarchitecture

Relationships among quantitative ultrasound of bone (QUS), bone mineral density (BMD) and bone microarchitecture have been poorly investigated in human calcaneus. .Twenty-four specimens, from 12 men and 12 women (mean age 78 ± 10 years; range 53–93), removed from cadavers were studied. The feet were axially sectioned above the ankle. Two variables were measured for QUS (Achilles®, Lunar): broadband ultrasound attenuation (BUA) and speed of sound (SOS). A third variable, the stiffness index (SI), which is a combination of both BUA and SOS, was also calculated. BMD (a lateral view) was measured on a QDR 2000 densitometer (Hologic). Bone microarchitecture was assessed by computed tomography (CT) using a conventional CT-system. Fifteen sagittal sections (1 mm in width and 2 mm apart) were selected for CT. Methods used for characterizing bone microarchitecture consisted in structural (trabecular network characterization) and a fractal analyses. The relationships between QUS and bone microarchitecture were assessed by simple linear regression analysis with and without adjustment for BMD (partial correlation) and by backward stepwise regression analysis. Strong relationships were found between BMD and QUS. Adjusted r2 values were 0.545 for SOS and 0.717 for SI. Two microarchitectural variables were also significantly correlated with both SOS and SI: apparent trabecular separation (App Tr Sp) and trabecular bone pattern factor (App TBPF). After adjustment for BMD few correlations between QUS and microarchitectural variables were always significant. Adjusted squared semipartial coefficients of correlation (rsp2) values between SOS and bone microarchitecture were 6%, 6.8%, 13.2% and 4.6% for App BV/TV, App Tr Sp, App TBPF and fractal dimension (FD), respectively. For SI, corresponding figures were 3.7%, 4.1%, 5.2% and 3.2%. Backward stepwise regression analysis using BMD and microarchitecture showed a slight increase of r2 values that varied from 8.4% for SI to 17.8% for SOS, compared with BMD alone. The current study suggests that although BMD is a major determinant of acoustic properties of human calcaneus, significant density independent relationships with bone microarchitecture should also be taken into account.

Should percutaneous vertebroplasty be used to treat osteoporotic fractures? An update.

Acrylic cement vertebroplasty is being increasingly used to treat osteoporotic vertebral compression fractures (VCFs), although no controlled studies supporting this trend have been published. Vertebroplasty remains controversial as a treatment for osteoporotic fractures because it is a local response to a systemic disease and because the pain caused by osteoporotic fractures usually subsides within a few days or weeks. Current data suggest that pain severity may decrease by half, on average, in 90-100% of patients. Although vertebroplasty is usually well tolerated, serious neurological complications have been reported in a few patients. The most common adverse event is nerve root pain, usually caused by leakage of the cement into the intervertebral foramen. Whether vertebroplasty is followed by an increased risk of osteoporotic fractures in the adjacent vertebras remains unclear. Resorbable cements are being developed and may provide better results than the acrylic cements used today. At present, acrylic cement vertebroplasty to treat osteoporotic VCFs is appropriate in only a minority of patients selected carefully by a multidisciplinary team including a rheumatologist.

Bone microarchitecture and mechanical resistance

Abstract Although bone mass is the main determinant of bone mechanical resistance, it explains only 30 to 40% of the variability of this characteristic, indicating that other factors are involved. Among these factors is bone tissue quality, which depends on bone mineralization, bone turnover, and bone microarchitecture. Several parameters for characterizing bone microarchitecture have been developed over the last 15 years. The simplest (Parfitt’s parameters) are trabecular count, width, and separation. A binary image (two levels of gray) of bone tissue can be expanded and used to determine the trabecular bone pattern factor. This method tends to overestimate the number of convex surfaces, which are characteristic of trabecular network disruption. The binary image can be further simplified (skeletonized) and used to count the number of nodes (anastomoses between trabeculae) or free ends (segments disconnected from the network). The bone marrow star volume, the marrow interconnectivity index, and the Euler-Poincare number are useful for characterizing the bone marrow. These parameters can be measured on bone specimens or on computed tomography (CT) or magnetic resonance imaging (MRI) scans, although in-plane resolution is far lower with scans than with specimens. Two-dimensional analysis is widely used, although three-dimensional studies are more satisfactory. Finally, fractal analysis is an original approach in which fractal dimension measurement, which is fairly simple, is used to determine the degree of network disruption. Ex vivo histomorphometric data suggest that microarchitecture-related factors may explain 10 to 30% of the variability in bone mechanical resistance beyond the proportion explained by bone mass. Similar results have been obtained in microimaging, CT, and MRI studies. Discrepancies across studies exist, however, in the strength of the relationship between bone mass and bone mechanical resistance; they are probably ascribable to differences in measurement sites and to errors in the measurement of variables characterizing bone mechanical resistance. The finite element method may be a means of sidestepping these problems. It can be used, in particular, to calculate Young’s modulus of elasticity from three-dimensional bone segment reconstructions. The results of the few studies of the finite element method are promising but require confirmation. Finally, a more clinical approach consists in comparing bone architecture in patients with osteoporotic fractures and in controls matched on bone mass. A few cross-sectional studies have used this approach. Bone architecture was evaluated using histomorphometry, CT, or MRI. The results indicate that trabecular network disruption is more severe in patients with than without fractures.

Bone marrow fat.

Bone marrow fat (BMF) results from an accumulation of fat cells within the bone marrow. Fat is not a simple filling tissue but is now considered as an actor within bone microenvironment. BMF is not comparable to other fat depots, as in subcutaneous or visceral tissues. Recent studies on bone marrow adipocytes have shown that they do not appear only as storage cells, but also as cells secreting adipokines, like leptin and adiponectin. Moreover bone marrow adipocytes share the same precursor with osteoblasts, the mesenchymal stem cell. It is now well established that high BMF is associated with weak bone mass in osteoporosis, especially during aging and anorexia nervosa. But numerous questions remain discussed: what is the precise phenotype of bone marrow adipocytes? What is the real function of BMF, and how does bone marrow adipocyte act on its environment? Is the increase of BMF during osteoporosis responsible for bone loss? Is BMF involved in other diseases? How to measure BMF in humans? A better understanding of BMF could allow to obtain new diagnostic tools for osteoporosis management, and could open major therapeutic perspectives.

Bone loss in patients with HIV infection

The prognosis of HIV infection has been considerably improved by the introduction of antiretroviral drugs. However, the longer survival times are associated with the emergence of new complications including decreased bone mineral density (BMD) values and/or bone insufficiency fractures. A meta-analysis of studies published between 1966 and 2005 showed bone absorptiometry results indicating osteoporosis in 15% of HIV patients and osteopenia in 52%. Longitudinal studies found no evidence that antiretroviral drug therapy contributed to the occurrence of bone loss. Available data indicate uncoupling with increases in bone resorption markers and decreases in bone formation markers. In addition to conventional risk factors for osteoporotic fractures, factors in HIV-infected patients may include malnutrition (wasting syndrome), hypogonadism, disorders in calcium and phosphate metabolism, and HIV infection per se. In patients with established bone insufficiency, bisphosphonate therapy should be considered. Alendronate in combination with vitamin D and calcium supplementation has been found effective in improving BMD values.

Male osteoporosis: Diagnosis and fracture risk evaluation

Male osteoporosis is challenging to diagnose and to treat. Underestimation of the risk of male osteoporosis, the combined presence of several interwoven causative factors in many patients, and uncertainty regarding the absorptiometry cutoffs associated with fractures are major obstacles to the diagnosis of male osteoporosis and to the identification of men at risk for fractures. The lifetime risk of osteoporotic fracture is estimated at 15% among men older than 50 years. One-third of proximal femoral fractures occur in men, and the associated mortality rate is 2- to 3-fold that in women. In men, nearly half the cases of osteoporosis are related to disease, medications, or risk factors. Although the criteria for diagnosing male osteoporosis are not agreed on, the definitions developed by the World Health Organization can be used provided the reference population is composed of young males. An absorptiometry T-score < or = -2.5 is useful for diagnosing osteoporosis but fails to adequately predict the fracture risk. The identification of men at high risk for fractures requires a combined evaluation of bone mineral density data, clinical risk factors, and risk factors for falls.

New Method for Raman Investigation of the Orientation of Collagen Fibrils and Crystallites in the Haversian System of Bone

Knowledge of the organization of the components of bone is of primary importance in understanding how this tissue responds to stresses and provides a starting point for the design and development of biomaterials. Bone structure has been the subject of numerous studies. The mineralized fiber arrangement in cortical bone is either a twisted or orthogonal plywood structure. Both mineral models coexist in compact bone. Raman polarized spectroscopy offers definite advantages in the study of biological samples, enabling the simultaneous analysis of mineral and organic components and the determination of molecular orientation through the polarization properties of the Raman scattering. In this study, we used the Raman polarization approach to simultaneously investigate the orientation of collagen fibrils and apatite crystals in human cortical bone. Raman bands ratios were monitored as a function of sample orientation. Specific ratios were chosen—such as ν3 PO4/ν1 PO4, amide III (1271 cm−1)/amide III (1243 cm−1), and amide I/amide III (1243 cm−1)—due to their sensitivity to apatite-crystal and collagen-fibril orientation. Based on this original approach, spatial changes were monitored as a function of distance from the Haversian canal. The results revealed simultaneous tilting in intra-lamellar collagen-fibril and mineral crystal orientations. These results are consistent with a twisted plywood organization in the Haversian bone structure at the lamellar level. But at molecular level, the co-alignment of the collagen fibrils and the apatite crystal is observed in the innermost lamellae and becomes gradually less ordered as the distance from the Haversian canal increases. This work highlights the interest of Raman spectroscopy for the multiscale investigation of bone structure.