Lumbosacral Transitional Vertebra-Related Low Back Pain: Resolving the Controversy

Study Design Case control study. Purpose The association of lumbosacral transitional vertebra (LSTV) with low back pain (LBP) is controversial, as is the role of occupational physical activity and radiological spinal abnormalities suggestive of other spinal disorders (OSDs) such as spinal degeneration and instability. This study aimed to determine if any association of LSTV with LBP exists. If so, the association of the level of physical activity and presence of OSD with LSTV-related LBP was determined. Overview of Literature The cause of LBP has been linked to proximal level disc degeneration, arthritic pseudoarticulation between LSTV and the sacral ala, facet joint degeneration, and nerve root compression due to a broadened transverse process. LSTV associated with LBP is present among individuals who are involved in high-level physical activity, including military recruits and athletes. Methods This was an unmatched study comprising 372 cases and 224 controls consecutively recruited with clinical and radiographic documentation. The relationship between LSTV and LBP was analyzed, and the effects of LSTV and OSD on this relationship were also assessed and statistically controlled. Results The presence of LSTV (p =0.039) was significantly associated with LBP, and the presence of OSD was associated with LTSV-related LBP, after statistically controlling for the level of physical activity (p =0.024). The level of physical activity was not associated with LBP. Demographic analysis revealed female predominance with an advanced age (>45 years) among those with LSTV-related LBP who have OSD. Conclusions The presence of LSTV was associated with an increased prevalence of LBP. This association was probably due to the confounding effect of OSD. The level of occupational physical activity was not associated with LSTV-related LBP. We speculate that advanced age and female sex caused the spurious association of LSTV with LBP in our study, rendering LSTV-related LBP controversial in published literature

Developing focal construct technology for in vivo diagnosis of osteoporosis

Osteoporosis is a prevalent bone disease around the world, characterised by low bone mineral density and increased fracture risk. Currently, the gold standard for identifying osteoporosis and increased fracture risk is through quantification of bone mineral density (BMD), using dual energy X-ray absorption (DEXA). However, the use of BMD to diagnose osteoporosis is not without limitation and arguably the risk of osteoporotic fracture should be determined collectively by bone mass, architecture and physicochemistry of the mineral composite building blocks. Rather than depending exclusively on the 'mass' of bone, our previous research investigated predicting the risk of fracture using 'bone quality'. The work highlighted that the material properties of OP tissue differ significantly to that of 'normal' bone and for the first time reported the clinical value of new biomarkers (obtained from X-ray scatter signatures) for fracture risk prediction. Thus, in order to improve fracture prediction models, diagnostic tools need to be developed which not only measure bone mineral density, but also bone quality. This pilot study builds on our previous work and aims to develop a new technology, Focal Construct Technology (FCT), which is hoped can measure XRD signatures in vivo. Our previous work was performed entirely with interrogating probes applied in transmission mode. This has some disadvantages that would be overcome were reflection mode employed. This study involves the creation of unique, high impact data with the potential to form the basis of a new generation of medical diagnostic instrumentation. A systematic series of conventional reflection mode ex vivo experiments were performed in which bone specimens were examined through increasing thicknesses of overlaying muscle/fat/skin. Further, we applied FCT to these geometries. This had not previously been attempted and required some initial modelling to ensure correct topologies of the hollow beams. The results from this study suggest it may be possible to obtain the parameters in vivo with the same precision as those obtained within the laboratory when using FCT

Mineral maturity and crystallinity index are distinct characteristics of bone mineral

The purpose of this study was to test the hypothesis that mineral maturity and crystallinity index are two different characteristics of bone mineral. To this end, Fourier transform infrared microspectroscopy (FTIRM) was used. To test our hypothesis, synthetic apatites and human bone samples were used for the validation of the two parameters using FTIRM. Iliac crest samples from seven human controls and two with skeletal fluorosis were analyzed at the bone structural unit (BSU) level by FTIRM on sections 2–4 lm thick. Mineral maturity and crystallinity index were highly correlated in synthetic apatites but poorly correlated in normal human bone. In skeletal fluorosis, crystallinity index was increased and maturity decreased, supporting the fact of separate measurement of these two parameters. Moreover, results obtained in fluorosis suggested that mineral characteristics can be modified independently of bone remodeling. In conclusion, mineral maturity and crystallinity index are two different parameters measured separately by FTIRM and offering new perspectives to assess bone mineral traits in osteoporosis

A novel underuse model shows that inactivity but not ovariectomy determines the deteriorated material properties and geometry of cortical bone in the tibia of adult rats

Our goal in this study was to determine to what extent the physiologic consequences of ovariectomy (OVX) in bones are exacerbated by a lack of daily activity such as walking. We forced 14-week-old female rats to be inactive for 15 weeks with a unique experimental system that prevents standing and walking while allowing other movements. Tibiae, femora, and 4th lumbar vertebrae were analyzed by peripheral quantitative computed tomography (pQCT), microfocused X-ray computed tomography (micro-CT), histology, histomorphometry, Raman spectroscopy, and the three-point bending test. Contrary to our expectation, the exacerbation was very much limited to the cancellous bone parameters. Parameters of femur and tibia cortical bone were affected by the forced inactivity but not by OVX: (1) cross-sectional moment of inertia was significantly smaller in Sham-Inactive rat bones than that of their walking counterparts; (2) the number of sclerostin-positive osteocytes per unit cross-sectional area was larger in Sham-Inactive rat bones than in Sham-Walking rat bones; and (3) material properties such as ultimate stress of inactive rat tibia was lower than that of their walking counterparts. Of note, the additive effect of inactivity and OVX was seen only in a few parameters, such as the cancellous bone mineral density of the lumbar vertebrae and the structural parameters of cancellous bone in the lumbar vertebrae/tibiae. It is concluded that the lack of daily activity is detrimental to the strength and quality of cortical bone in the femur and tibia of rats, while lack of estrogen is not. Our inactive rat model, with the older rats, will aid the study of postmenopausal osteoporosis, the etiology of which may be both hormonal and mechanical

Towards new material biomarkers for fracture risk

Osteoporosis is a prevalent bone condition, characterised by low bone mass and increased fracture risk. Currently, the gold standard for identifying osteoporosis and increased fracture risk is through quantification of bone mineral density (BMD) using dual energy X-ray absorption (DEXA). However, the risk of osteoporotic fracture is determined collectively by bone mass, architecture and physicochemistry of the mineral composite building blocks. Thus DEXA scans alone inevitably fail to fully discriminate individuals who will suffer a fragility fracture. This study examines trabecular bone at both ultrastructure and microarchitectural levels to provide a detailed material view of bone, and therefore provides a more comprehensive explanation of osteoporotic fracture risk. Physicochemical characterisation obtained through X-ray diffraction and infrared analysis indicated significant differences in apatite crystal chemistry and nanostructure between fracture and non-fracture groups. Further, this study, through considering the potential correlations between the chemical biomarkers and microarchitectural properties of trabecular bone, has investigated the relationship between bone mechanical properties (e.g. fragility) and physicochemical material features

Mineral Composition is Altered by Osteoblast Expression of an Engineered Gs-Coupled Receptor

Activation of the Gs G protein–coupled receptor Rs1 in osteoblasts increases bone mineral density by 5- to 15-fold in mice and recapitulates histologic aspects of fibrous dysplasia of the bone. However, the effects of constitutive Gs signaling on bone tissue quality are not known. The goal of this study was to determine bone tissue quality in mice resulting from osteoblast-specific constitutive Gs activation, by the complementary techniques of FTIR spectroscopy and synchrotron radiation micro-computed tomography (SRμCT). Col1(2.3)-tTA/TetO-Rs1 double transgenic (DT) mice, which showed osteoblast-specific constitutive Gs signaling activity by the Rs1 receptor, were created. Femora and calvariae of DT and wild-type (WT) mice (6 and 15 weeks old) were analyzed by FTIR spectroscopy. WT and DT femora (3 and 9 weeks old) were imaged by SRμCT. Mineral-to-matrix ratio was 25% lower (P = 0.010), carbonate-to-phosphate ratio was 20% higher (P = 0.025), crystallinity was 4% lower (P = 0.004), and cross-link ratio was 11% lower (P = 0.025) in 6-week DT bone. Differences persisted in 15-week animals. Quantitative SRμCT analysis revealed substantial differences in mean values and heterogeneity of tissue mineral density (TMD). TMD values were 1,156 ± 100 and 711 ± 251 mg/cm3 (mean ± SD) in WT and DT femoral diaphyses, respectively, at 3 weeks. Similar differences were found in 9-week animals. These results demonstrate that continuous Gs activation in murine osteoblasts leads to deposition of immature bone tissue with reduced mineralization. Our findings suggest that bone tissue quality may be an important contributor to increased fracture risk in fibrous dysplasia patients

Machining-induced thermal damage in cortical bone: necrosis and micro-mechanical integrity

In bone cutting, the tissue is exposed to necrosis due to temperature elevation, which can significantly influence postoperative results in orthopaedic surgeries. This damage is usually revealed through histological analysis to show the necrotic extent; however, this technique does not capture mechanical damage, which is essential for a full material integrity assessment. Here, with micro-mechanics, it is demonstrated that machining-induced damage in bone extends beyond the necrotic region. Drilling with different conditions was performed on ex-vivo bovine cortical bone, inducing different damage degrees. Micro-pillar compression tests were performed in the machined sub-surface to identify changes in properties and failure modes caused by drilling. It was revealed that at high cutting temperatures, the bone near the machined surface suffers from lower modulus (−42%), strength (−41%) and brittle behaviour, whereas the bulk bone remains undamaged with pristine properties and ductile behaviour. Histology was also performed to evaluate necrosis and, surprisingly, it was found that the brittle and weaker bone layer is more than three times larger when compared to the necrotic layer, clearly showing that the drilling thermo-mechanical effect could affect not only biologically, but also micro-mechanically. Consequently, these results reveal another kind of bone damage that has so far been neglected

Digital tomosynthesis (DTS) for quantitative assessment of trabecular microstructure in human vertebral bone.

Digital tomosynthesis (DTS) provides slice images of an object using conventional radiographic methods with high in-plane resolution. The objective of this study was to explore the potential of DTS for describing microstructural, stiffness and stress distribution properties of vertebral cancellous bone. Forty vertebrae (T6, T8, T11, and L3) from 10 cadavers (63-90 years) were scanned using microCT and DTS. Anisotropy (μCT.DA), and the specimen-average and standard deviation of trabecular bone volume fraction (BV/TV), thickness (Tb.Th), number (Tb.N) and separation (Tb.Sp) were obtained using stereology. Apparent modulus (EFEM), and the magnitude (VMExp/σapp) and variability (VMCV) of trabecular stresses were calculated using microCT-based finite element modeling. Mean intercept length, line fraction deviation and fractal parameters were obtained from coronal DTS slices, then correlated with stereological and finite element parameters using linear regression models. Twenty-one DTS parameters (out of 27) correlated to BV/TV, Tb.Th, Tb.N, Tb.Sp and/or μCT.DA (p\u3c0.0001-p\u3c0.05). DTS parameters increased the explained variability in EFEM and VMCV (by 9-11% and 13-19%, respectively; p\u3c0.0001-p\u3c0.04) over that explained by BV/TV. In conclusion, DTS has potential for quantitative assessment of cancellous bone and may be used as a modality complementary to those measuring bone mass for assessing spinal fracture risk