No abstract

Compact bone makes up approximately 80% of the human skeleton by mass; but there are little data available on the effects of increased bone turnover on compact bone mechanical and material properties. This study addresses this question by measuring intracortical remodeling, resorption cavity number, and porosity in an ovariectomized (OVX) sheep model, and measures changes in biomechanical properties. Thirty-eight sheep were divided into two groups. Group 1 were controls (n ¼ 19), and Group 2 were ovariectomized (OVX; n ¼ 19). Fluorochrome dyes were administered intravenously to both groups at five time points over 12 months post-OVX to label sites of bone turnover. At 12 months post-OVX all animals were euthanized. Samples were harvested from the left metatarsal and were analyzed for intracortical bone turnover at five time points, the number of resorption cavities, and the level of intracortical porosity. The effects of these parameters on bone biomechanical properties were then measured. Bone turnover was increased in the OVX group at 6, 9, and 12 months (p < 0.05). Resorption was also higher in the OVX group at 12 months (p < 0.05). Furthermore, porosity was significantly increased in the OVX group at 12 months (p < 0.05). Stiffness and yield strength were reduced in the OVX group compared to controls (p ¼ 0.05). Ultimate compressive strength and work to fracture did not differ between groups. These findings provide new insights into the mechanisms and effects of increased bone turnover on bone material and microstructural properties. Keywords: bone turnover; porosity; ovariectomy; ovine animal model Bone turnover is an important determinant of the structural integrity of bone. It is a crucial process of tissue renewal that normally occurs at an optimal physiological rate for maximum bone strength in a healthy individual. 1 Any change to the optimal bone turnover rate, such as the increase that occurs following ovariectomy (OVX) or menopause, has the potential to dramatically change the bone at microstructural and material levels. High bone turnover can have the effect of increasing remodeling spaces, accelerating bone loss, increasing stress concentrations, and increasing cortical porosity, each of which can undermine bone mechanical properties. A precise definition of bone quality remains elusive, however; bone turnover and microarchitecture are considered to be two important contributors to this phenomenon along with mineralization, microdamage, and collagen content. Thus, these parameters are important considerations in the pathophysiology of skeletal diseases such as osteoporosis and the mechanisms that underlie fracture. 2 Previous studies have shown that bone turnover has a direct influence on fracture risk. 3 It is thought that compact bone is affected by accelerated turnover in two ways. First, more mineralized bone is removed and replaced with younger, less mineralized bone, which reduces the material's local stiffness. Second, the presence of more resorption cavities creates stress concen...

Gunnlaugsson and co-workers have undertaken the synthesis and physical study of luminescent nanoagents for use in imaging of damaged bone structures. These agents are based on europium macrocyclic complexes that are tethered to the surface of nanometer-sized gold nanoparticles through covalent spacers. These nanoagents can selectively bind to exposed calcium sites, also called microcracks, within a damaged bone surface. Using a sensitizing antennae and two-photon microscopy, the authors have achieved 3D mapping of the damaged bone area by observing the long-wavelength lanthanide-centered emission.

Microcrack accumulation in cortical bone has been implicated in skeletal fragility and stress fractures. These cracks have also been shown to affect the mechanical and material properties of cortical bone. Their growth has been linked to osteocyte apoptosis and the initiation of the remodeling process, which also has a role in their repair. Clinically, osteoporosis is diagnosed using dual energy x-ray absorptiometry. However, evidence now indicates that bone mass alone is insufficient to satisfactorily explain the skeletal fragility of osteoporosis and consideration needs to be given to bone quality in the diagnosis and treatment of the disease. Bone quality includes parameters such as trabecular and cortical microarchitecture, morphology, bone turnover, degree of mineralization of the bone matrix, and significantly, the amount of microdamage present in the bone. Current clinical treatments concentrate on the inhibition of osteoclast activity to maintain bone mass in osteoporotic patients. However, these cells have a major role in removing existing microcracks from the bone matrix, and hence the use of bone resorption- inhibiting drugs may lead to insufficient bone repair and therefore an increase in microdamage accumulation and loss of bone quality.

Ovariectomized (OVX) sheep are now considered to be useful models for a variety of metabolic bone disorders. The specific aim of this study was to determine the effects of ovariectomy on the structural parameters and material density of the subchondral bone of the ovine tibial plateau as measured by microcomputed tomography (MicroCT). Twenty-three sheep were examined in this study; 10 of the sheep underwent ovariectomy (OVX), and the remainder (n = 13) were kept as controls (CON). These animals were then sacrificed at 12 months post-operatively. Three-dimensional analyses were performed of osteochondral samples (15 mm deep) which were obtained from the medial tibial plateau using MicroCT. Bone volume fraction of the subchondral trabecular bone was reduced in the ovariectomized sheep as compared to control animals (0.439 vs. 0.483, P = 0.038). Trabeculae were also significantly thinner in the OVX group (0.220 vs. 0.252 mm, P = 0.010), with reduced connectivity density (7.947 vs. 11.524 mm )3, P = 0.014). There was a trend towards lower numbers of individual trabeculae present in the OVX group as compared to controls, but this did not reach significance (2.817 vs. 3.288 mm )1 , P = 0.1). There was also increased trabecular separation in the OVX group, which again fell short of significance (0.426 vs. 0.387 mm, P = 0.251). There was no difference in hydroxyapatite concentration (HA) between the two groups (929 vs. 932 mgHA cm )3, P = 0.687). In conclusion, significant alterations of the trabecular architecture under the tibial plateau were observed following 12 months of oestrogen-deficiency in this ovine model. Despite these marked morphological and structural density differences, the material densities were equal in the two groups.

No abstract

Background Clinical complexity is increasingly prevalent among patients with atrial fibrillation (AF). The ‘Atrial fibrillation Better Care’ (ABC) pathway approach has been proposed to streamline a more holistic and integrated approach to AF care; however, there are limited data on its usefulness among clinically complex patients. We aim to determine the impact of ABC pathway in a contemporary cohort of clinically complex AF patients. Methods From the ESC-EHRA EORP-AF General Long-Term Registry, we analysed clinically complex AF patients, defined as the presence of frailty, multimorbidity and/or polypharmacy. A K-medoids cluster analysis was performed to identify different groups of clinical complexity. The impact of an ABC-adherent approach on major outcomes was analysed through Cox-regression analyses and delay of event (DoE) analyses. Results Among 9966 AF patients included, 8289 (83.1%) were clinically complex. Adherence to the ABC pathway in the clinically complex group reduced the risk of all-cause death (adjusted HR [aHR]: 0.72, 95%CI 0.58–0.91), major adverse cardiovascular events (MACEs; aHR: 0.68, 95%CI 0.52–0.87) and composite outcome (aHR: 0.70, 95%CI: 0.58–0.85). Adherence to the ABC pathway was associated with a significant reduction in the risk of death (aHR: 0.74, 95%CI 0.56–0.98) and composite outcome (aHR: 0.76, 95%CI 0.60–0.96) also in the high-complexity cluster; similar trends were observed for MACEs. In DoE analyses, an ABC-adherent approach resulted in significant gains in event-free survival for all the outcomes investigated in clinically complex patients. Based on absolute risk reduction at 1 year of follow-up, the number needed to treat for ABC pathway adherence was 24 for all-cause death, 31 for MACEs and 20 for the composite outcome. Conclusions An ABC-adherent approach reduces the risk of major outcomes in clinically complex AF patients. Ensuring adherence to the ABC pathway is essential to improve clinical outcomes among clinically complex AF patients.

Osteoporosis is a common disease characterised by reduced bone mass and an increased risk of fragility fractures. Low bone mineral density is known to significantly increase the risk of osteoporotic fractures, however, the majority of non-traumatic fractures occur in individuals with a bone mineral density too high to be classified as osteoporotic. Therefore, there is an urgent need to investigate aspects of bone health, other than bone mass, that can predict the risk of fracture. Here, we successfully predicted association between bone collagen and nail keratin in relation to bone loss due to oestrogen deficiency using Raman spectroscopy. Raman signal signature successfully discriminated between ovariectomised rats and their sham controls with a high degree of accuracy for the bone (sensitivity 89%, specificity 91%) and claw tissue (sensitivity 89%, specificity 82%). When tested in an independent set of claw samples the classifier gave 92% sensitivity and 85% specificity. Comparison of the spectral changes occurring in the bone tissue with the changes occurring in the keratin showed a number of common features that could be attributed to common changes in the structure of bone collagen and claw keratin. This study established that systemic oestrogen deficiency mediates parallel structural changes in both the claw (primarily keratin) and bone proteins (primarily collagen). This strengthens the hypothesis that nail keratin can act as a surrogate marker of bone protein status where systemic processes induce changes.