Erick Legrand

Trabecular Bone Microarchitecture, Bone Mineral Density, and Vertebral Fractures in Male Osteoporosis

Some studies have indicated that the risk of fragility fractures in men increases as bone mineral levels decrease, but there is an overlap in the bone mineral density (BMD) measurements between patients with or without fractures. Furthermore, it has been suggested that the biomechanical competence of trabecular bone is dependent not only on the absolute amount of bone present but also on the trabecular microarchitecture. In the present study, 108 men (mean age 52.1 years) with lumbar osteopenia (T score <−2.5) were recruited to examine the relationships between BMD, architectural changes in trabecular bone, and the presence of vertebral fractures. Lumbar BMD was assessed from L2 to L4 in the anteroposterior view with dual‐energy X‐ray absorptiometry. At the upper left femur, hip BMD was measured at the transcervical site. Spinal X‐ray films were analyzed independently by two trained investigators, and vertebral fracture was defined as a reduction of at least 20% in the anterior, middle, or posterior vertebral height. Transiliac bone biopsy specimens were obtained for all patients. Histomorphometric studies were performed on an image analyzer, and the following parameters were determined: trabecular bone volume (BV/TV), trabecular thickness (Tb.Th), number (Tb.N), and separation (Tb.Sp), interconnectivity index (ICI), characterization of the trabecular network (node count and strut analysis), and star volume of the marrow spaces. Spinal radiographs evidenced at least one vertebral crush fracture in 62 patients (group II) and none in 46 patients (group I). After adjusting for age, body mass index, and BMD, there were no significant differences between the two groups in BV/TV, Tb.Th, or star volume. In contrast, the mean values of ICI, free end–to–free end struts (FF/TSL), and Tb.Sp were significantly higher, whereas Tb.N and node‐to‐node struts (NN/TSL) were lower in patients with at least one vertebral fracture. Logistic regression analysis showed that only ICI, FF/TSL, NN/TSL, and Tb.N were significant predictors of the presence of vertebral fracture: odds ratios for an alteration of 1 SD ranged from 1.7 (1.0–3.2) for NN/TSL to 3.2 (1.1–10.1) for ICI. Patients with at least three vertebral fractures (n = 23) were categorized as “multiple fractures.” The results of logistic regression showed that spine BMD, BV/TV, and all architectural parameters were significant predictors of multiple vertebral fractures: odds ratios for an alteration of 1 SD ranged from 2.2 (1.1–4.6) for star volume to 3.7 (1.4–9.7) for ICI. These results strongly suggest that bone trabecular microarchitecture is a major and independent determinant of vertebral fractures in middle‐aged men with osteopenia.

Psychosocial risk factors for chronic low back pain in primary care—a systematic review

BACKGROUND Low back pain (LBP) is a major public health problem, often encountered in primary care. Guidelines recommend early identification of psychosocial factors that could prevent recovery from acute LBP. METHODS To review the evidence on the prognostic value of psychosocial factors on transition from acute to chronic non-specific LBP in the adult general population. Systematic review is the design of the study. A systematic search was undertaken for prospective studies dealing with psychosocial risk factors for poor outcome of LBP in primary care, screening PubMed, PsychInfo and Cochrane Library databases. The methodological quality of studies was assessed independently by two reviewers using standardized criteria before analysing their main results. RESULTS Twenty-three papers fulfilled the inclusion criteria, covering 18 different cohorts. Sixteen psychosocial factors were analysed in three domains: social and socio-occupational, psychological and cognitive and behavioural. Depression, psychological distress, passive coping strategies and fear-avoidance beliefs were sometimes found to be independently linked with poor outcome, whereas most social and socio-occupational factors were not. The predictive ability of a patients self-perceived general health at baseline was difficult to interpret because of biomedical confounding factors. The initial patients or care providers perceived risk of persistence of LBP was the factor that was most consistently linked with actual outcome. CONCLUSION Few independent psychosocial risk factors have been demonstrated to exist. Randomized clinical trials aimed at modifying these factors have shown little impact on patient prognosis. Qualitative research might be valuable to explore further the field of LBP and to define new management strategies.

Management of nontuberculous infectious discitis. treatments used in 110 patients admitted to 12 teaching hospitals in France.

The optimal management of pyogenic discitis is not agreed on. No randomized clinical trials of short-course or oral antibiotic regimens have been published to date. To shed light on this issue, we reviewed the management of patients admitted for pyogenic discitis to one of 12 networked rheumatology departments. In this cross-sectional observational study, each department included the first ten patients admitted starting in January 1997 for treatment of pyogenic discitis. One hundred ten patients met the inclusion criteria, 67 men and 43 women, with a mean age of 60.6 +/- 13.7 years (range, 17-86 years). Mean time from symptom onset to diagnosis was 39.6 +/- 39.8 days (range, 24 h-240 days). Blood cultures were positive in 47.3% of patients, and the percutaneous discal and vertebral biopsy in 63.6% of cases; these two investigations identified the causative organism in 79 cases (72.8%). Mean duration of the rheumatology department stay was 31.3 +/- 14.1 days (range, 4-78 days). Antibiotics were given intravenously to 103 (93.6%) patients, for a mean of 25.5 +/- 17.6 days (range, 4-124 days); duration of intravenous antibiotic therapy was longer than 4 weeks in 36.5% of patients. Only seven (6.4%) patients received primary oral antibiotics with no parenteral antibiotics. One hundred patients were given oral antibiotics at the same time as and after intravenous antibiotics, for a mean duration of 87.2 +/- 43.6 day (range, 20-278 days); Bracing was used in 98 (89.1%) patients. Although antibiotic selection was rational and in agreement with current recommendations, wide differences were noted across centers regarding intravenous treatment duration, hospital stay duration, and total treatment duration.

Bone Mineral Density and Vertebral Fractures in Men

Abstract: In women, many studies indicate that the risk of vertebral fragility fractures increases as bone mineral density (BMD) declines. In contrast, few studies are available for BMD and vertebral fractures in men. It is uncertain that the strength of the relationship between BMD and fractures is similar in magnitude in middle-aged men and in postmenopausal women. In the present study, 200 men (mean age 54.7 years) with lumbar osteopenia (T-score <−1.5) were recruited to examine the relationships between spine BMD and hip BMD and the associations of BMD with vertebral fractures. Lumbar BMD was assessed from L2 to L4, in the anteroposterior view, using dual-energy X-ray densitometry. At the upper left femur, hip BMD was measured at five regions of interest: femoral neck, trochanter, intertrochanter, Ward’s triangle and total hip. Spinal radiographs were analyzed independently by two trained investigators and vertebral fracture was defined as a reduction of at least 20% in the anterior, middle or posterior vertebral height. Spinal radiographs evidenced at least one vertebral crush fracture in 119 patients (59.5%). The results of logistic regression showed that age, femoral and spine BMDs were significant predictors of the presence of a vertebral fracture. Odds ratios for a decrease of 1 standard deviation ranged from 1.8 (1.3–2.8) for spine BMD to 2.3 (1.5–3.6) for total hip BMD. For multiple fractures odds ratios ranged from 1.7 (1.1–2.5) for spine BMD to 2.6 (1.7–4.3) for total hip BMD. In all models, odds ratios were higher for hip BMD than for spine BMD, particularly in younger men, under 50 years. A T-score <−2.5 in the femur (total femoral site) was associated with a 2.7-fold increase in the risk of vertebral fracture while a T-score <−2.5 in the spine was associated with only a 2-fold increase in risk. This study confirms the strong association of age and BMD with vertebral fractures in middle-aged men, shows that the femoral area is the best site of BMD measurement and suggests that a low femoral BMD could be considered as an index of severity in young men with lumbar osteopenia.

Comparison of eight histomorphometric methods for measuring trabecular bone architecture by image analysis on histological sections

Osteoporosis is defined as a disease characterized by low bone mass and microarchitectural deterioration of trabecular bone leading to enhanced bone fragility. Various histomorphometric methods have been described to measure bone architecture on histological sections. However, not all of the methods are strictly equivalent and some of them appear able to detect differences earlier in the course of the disease. We have compared 8 histomorphometric methods known to characterize the architecture of trabecular bone in 154 male osteoporotic patients. Measurements were done on transiliac bone biopsies: Trabecular number, thickness, and separation (Tb.N, Tb.Th, Tb.Sp); Trabecular Bone Pattern Factor (TBPf); Euler‐Poincarés number (E); Interconnectivity Index (ICI); strut analysis of the trabecular network with the ratio of nodes/free‐end (N/F); star volume of the bone marrow (V*m.space) and trabeculae (V*Tb) and the Kolmogorov fractal dimension of the trabecular boundaries (D). Relationships between the various architectural parameters were studied by hierarchical cluster analysis. Linear, hyperbolic, and exponential correlations were found between trabecular bone volume (BV/TV) and architectural parameters. Cluster analysis demonstrates the link between these architectural parameters. ICI, E, and TBPf, which reflect the amount of open/closed marrow cavities clustered together and appeared related to Tb.Sp, V*m.space which are indicators of the mean size of marrow cavities. Tb.Th, V*Tb and N/F flocked together as they reflect the trabecular size. Tb.N and D segregated together and seemed to best describe the trabecular network complexity. These histomorphometric techniques are correlated but correlations may be linear or nonlinear. Several histomorphometric techniques need to be used in parallel to appreciate the pathophysiological mechanisms of osteoporotic states. Microsc. Res. Tech. 45:303–312, 1999.

New laboratory tools in the assessment of bone quality

Bone quality is a complex set of intricated and interdependent factors that influence bone strength. A number of methods have emerged to measure bone quality, taking into account the organic or the mineral phase of the bone matrix, in the laboratory. Bone quality is a complex set of different factors that are interdependent. The bone matrix organization can be described at five different levels of anatomical organization: nature (organic and mineral), texture (woven or lamellar), structure (osteons in the cortices and arch-like packets in trabecular bone), microarchitecture, and macroarchitecture. Any change in one of these levels can alter bone quality. An altered bone remodeling can affect bone quality by influencing one or more of these factors. We have reviewed here the main methods that can be used in the laboratory to explore bone quality on bone samples. Bone remodeling can be evaluated by histomorphometry; microarchitecture is explored in 2D on histological sections and in 3D by microCT or synchrotron. Microradiography and scanning electron microscopy in the backscattered electron mode can measure the mineral distribution; Raman and Fourier-transformed infra-red spectroscopy and imaging can simultaneously explore the organic and mineral phase of the matrix on multispectral images; scanning acoustic microscopy and nanoindentation provide biomechanical information on individual trabeculae. Finally, some histological methods (polarization, surface staining, fluorescence, osteocyte staining) may also be of interest in the understanding of quality as a component of bone fragility. A growing number of laboratory techniques are now available. Some of them have been described many years ago and can find a new youth; others having benefited from improvements in physical and computer techniques are now available.

Fractal dimension of trabecular bone: comparison of three histomorphometric computed techniques for measuring the architectural two‐dimensional complexity

Trabecular bone has been reported as having two‐dimensional (2‐D) fractal characteristics at the histological level, a finding correlated with biomechanical properties. However, several fractal dimensions (D) are known and computational ways to obtain them vary considerably. This study compared three algorithms on the same series of bone biopsies, to obtain the Kolmogorov, Minkowski–Bouligand, and mass‐radius fractal dimensions. The relationships with histomorphometric descriptors of the 2‐D trabecular architecture were investigated. Bone biopsies were obtained from 148 osteoporotic male patients. Bone volume (BV/TV), trabecular characteristics (Tb.N, Tb.Sp, Tb.Th), strut analysis, star volumes (marrow spaces and trabeculae), inter‐connectivity index, and Euler–Poincaré number were computed. The box‐counting method was used to obtain the Kolmogorov dimension (Dk), the dilatation method for the Minkowski–Bouligand dimension (DMB), and the sandbox for the mass‐radius dimension (DMR) and lacunarity (L). Logarithmic relationships were observed between BV/TV and the fractal dimensions. The best correlation was obtained with DMR and the lowest with DMB. Lacunarity was correlated with descriptors of the marrow cavities (ICI, star volume, Tb.Sp). Linear relationships were observed among the three fractal techniques which appeared highly correlated. A cluster analysis of all histomorphometric parameters provided a tree with three groups of descriptors: for trabeculae (Tb.Th, strut); for marrow cavities (Euler, ICI, Tb.Sp, star volume, L); and for the complexity of the network (Tb.N and the three Ds). A sole fractal dimension cannot be used instead of the classic 2‐D descriptors of architecture; D rather reflects the complexity of branching trabeculae. Computation time is also an important determinant when choosing one of these methods. Copyright

Bone microarchitecture and bone fragility in men: DXA and histomorphometry in humans and in the orchidectomized rat model.

In men, the risk of fragility fractures increases as bone mineral declines but there is an overlap in the bone mineral density (BMD) measurements between patients with and those without fractures. Biomechanical competence of trabecular (Tb) bone depends on the amount of bone and on microarchitecture. We have developed new histomorphometric methods for evaluating microarchitecture on histological sections. These methods were used in the orchidectomized male rat (ORX--a model of hypogonadism-induced osteoporosis) and on transiliac bone biopsies performed in male osteoporotic patients. ORX rats were studied at 2, 4, 8, and 16 weeks post-ORX. Bone mineral content (BMC) was reduced at 16 weeks. Trabecular bone volume (BV/TV) was significantly decreased from the 4th week. Differences in the sensitivity of the methods were found. Fractal dimension was modified as early as 2 weeks and appeared the most potent descriptor of Tb disorganization. The architectural changes in this model mimic those observed in hypogonadic men. We examined the relationships among BMD, micro-architecture, and vertebral fracture in 108 men with lumbar osteopenia (T-score <-2.5). At least one vertebral fracture was observed in 62 patients and none in 46 patients. After adjusting for age, body mass index (BMI), and BMD, there was no significant difference between the two groups in BV/TV, Tb.Th, and Star volume. In contrast, the mean values of ICI and Tb.Sp were significantly higher whereas Tb.N and nodes were lower in patients with vertebral fracture. Logistic regression analysis showed that ICI, strut analysis, and Tb.N were significant predictors of the presence of vertebral fracture: odds ratios for an alteration of I SD ranged from 1.7 for nodes to 3.2 for ICI. These results strongly suggest that bone Tb microarchitecture is a major and independent determinant of vertebral fracture in men with osteoporosis.

Multidisciplinary Intensive Functional Restoration Versus Outpatient Active Physiotherapy in Chronic Low Back Pain A Randomized Controlled Trial

Study Design. Randomized parallel group comparative trial with a 1-year follow-up period. Objective. To compare in a population of patients with chronic low back pain, the effectiveness of a functional restoration program (FRP), including intensive physical training and a multidisciplinary approach, with an outpatient active physiotherapy program at 1-year follow-up. Summary of Background Data. Controlled studies conducted in the United States and in Northern Europe showed a benefit of FRPs, especially on return to work. Randomized studies have compared these programs with standard care. A previously reported study presented the effectiveness at 6 months of both functional restoration and active physiotherapy, with a significantly greater reduction of sick-leave days for functional restoration. Methods. A total of 132 patients with low back pain were randomized to either FRP (68 patients) or active individual therapy (64 patients). One patient did not complete the FRP; 19 patients were lost to follow-up (4 in the FRP group and 15 in the active individual treatment group). The number of sick-leave days in 2 years before the program was similar in both groups (180 ± 135.1 days in active individual treatment vs. 185 ± 149.8 days in FRP, P = 0.847). Results. In both groups, at 1-year follow-up, intensity of pain, flexibility, trunk muscle endurance, Dallas daily activities and work and leisure scores, and number of sick-leave days were significantly improved compared with baseline. The number of sick-leave days was significantly lower in the FRP group. Conclusion. Both programs are efficient in reducing disability and sick-leave days. The FRP is significantly more effective in reducing sick-leave days. Further analysis is required to determine if this overweighs the difference in costs of both programs.

Extraskeletal effects of vitamin D: Facts, uncertainties, and controversies

Vitamin D was long viewed as a hormone acting chiefly to regulate calcium-phosphate metabolism and bone mineralization. Over the last decade, however, basic science and clinical researchers have produced a bewildering amount of information on the extraskeletal effects of vitamin D. This article is a review of the clinical and biological actions of vitamin D including effects on the immune system, auto-immune diseases, infections, cancer, metabolic syndrome, fall risk, cognitive function, and muscle function.