Volume 12 · Number 2 · June 2020
- Methodology to improve the efficiency in the migration and detection of mesenchymal stem cells in murine models [37-39]
- A sensitive method for monitoring the migration of mesenchymal stem cells from bone marrow in murine models [40-44]
- Can 3D measurements obtained by lumbar DXA predict fractures in the dorsal vertebrae? [45-52]
- Impact of vascular calcification on bone health and mortality in kidney transplant patients [53-61]
- Relative fragility of osteoporotic femurs assessed with DXA and simulation of finite element falls guided by emergency X-rays [62-70]
Methodology to improve the efficiency in the migration and detection of mesenchymal stem cells in murine models
Osteoporosis is a generalised disease of the skeletal system characterised by an imbalance between the bone formation and resorption that leads to bone mass loss and to the deterioration of the microarchitecture of the bone tissue, compromising bone resistance and therefore resulting in a higher bone fragility and an increased susceptibility to fractures .
Two stem cells coexist in the bone cavity (bone marrow): the hematopoietic stem cell, which generates all the blood and immune system cells, and the mesenchymal stem cell, responsible for the formation of the skeleton. Osteoblasts or bone-forming cells originate from the differentiation of mesenchymal stem cells. These pluripotent cells can create a wide variety of cell types such as osteoblasts, adipocytes, or chondrocytes [2-4]. This characteristic makes them highly interesting candidates for regenerative medicine given their ability to migrate to injured areas to promote the de novo generation of bone .
A sensitive method for monitoring the migration of mesenchymal stem cells from bone marrow in murine models
Osteoporosis is the most frequent bone disease, characterized by low bone mass and alteration of the microstructure. This is due to an imbalance between bone formation and bone resorption that causes loss of connections among the different bone trabeculae, a greater thinning and cortical bone porosity. Consequently, there is greater bone fragility and an increased risk of fractures (Fx) [1,2].
Osteoblasts, cells specialized in bone formation, originate from the differentiation of mesenchymal stem cells (MSCs) . These cells are multipotent and can differentiate into a wide variety of mesoderm cell types, such as osteoblasts, adipocytes, or chondrocytes. MSCs are highly interesting candidates for regenerative medicine, because they migrate to skeletal lesions where they have the capacity to form new bone . The many relevant published studies show the importance of MSCs in tissue engineering and regenerative medicine [5,6]. In addition, there are currently more than 250 clinical trials with MSCs, as reflected in the clinical trial database (clinicaltrials.gov).
Every year 8.9 million osteoporosis-related fractures occur worldwide, representing one fracture every 3 seconds , with vertebral being the most common osteoporotic fractures .
Dual-energy X-ray absorptiometry (DXA) is the standard test for diagnosing osteoporosis and evaluating fracture risk [3,4], as it is a low-radiation, inexpensive technique. The DXA provides two-dimensional (2D) images that measure the bone mineral density of the area (aBMD) projected along the anteroposterior (AP) direction. Various studies show that a low aBMD value, measured in AP DXA explorations, is among the highest fracture risks [3-5]. The decrease of the aBMD standard deviation leads to an increase from 1.5 up to 3.0 times the risk of fracture, depending on its location and its measurement’s location . Nevertheless, a low BMD value is not enough to explain every fracture. Recent studies suggest that the risk of fracture is high when the BMD value is low, but this does not mean that fracture risk is negligible when the BMD value is normal [3-8].
Most osteoporosis-related vertebral fractures are located in the vertebral body . In AP DXA images of the spinal column, the vertebral body overlaps the posterior vertebral elements, so the BMD in the vertebral body cannot be estimated separately. On the other hand, the risk of fracture depends on the architecture of the trabecular bone and the thickness of the cortical bone . However, the trabecular and cortical bone compartments are difficult to assess separately on AP DXA scans.
Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD), was defined in 2009 as a set of systemic disorders of the bone and mineral metabolism due to chronic kidney disease, resulting in a combination of the following manifestations [1,2]:
I) Abnormalities of the metabolism of calcium, phosphorus, paratohormone or vitamin D.
II) Anomalies of bone remodeling, mineralization, volume, linear growth or resistance.
III) Vascular and other soft tissue calcifications.
This recently updated definition , and the consensus documents of various scientific societies , have highlighted the importance of the role of vascular calcification in the morbidity and mortality of patients with chronic kidney disease.
Relative fragility of osteoporotic femurs assessed with DXA and simulation of finite element falls guided by emergency X-rays
The increase in the elderly population and the growing concern about the consequences of fractures, together with insufficient rates of detection of situations of bone fragility [1,2], has increased the indication of the assessment of fracture risk in people of both sexes older than 64 years . The dual-energy X-ray absorptiometry (DXA) technique is currently the clinical standard for this type of bone measurement.
Nowadays, when evaluating the risk of fracture, different methods are applied, although the most widely used include the presence of clinical risk factors and the measurement of areal bone mineral density (BMD). Bone measurements are made in the proximal femur and lumbar spine using DXA. However, BMD only allows a limited assessment of the mechanical determinants of bone fracture [4,5].
Finite element analysis (FE) has been applied to assess bone resistance in volumetric bone models, based on computed tomography (CT) scans, precisely identifying the subject-specific mechanical determinants of fracture. This type of analysis includes the three-dimensional geometry of the bone, the quantity and distribution of bone tissue, and the loads to which the bone is subjected . With this process, the limitations of the BMDa are overcome. CT-based models of FE have been extensively validated ex vivo [7-12], and have shown better performance compared to a BMD in predicting proximal femur resistance in vitro [6,13]. A significant association between bone fractures and estimated resistance with FE has also been reported in an in vivo study .
Transient hypocalcaemia due to hypoparathyroidism is the most common complication of cervical surgery (thyroid and parathyroid) and also of reoperations. The deficiency of parathyroid hormone (PTH) secretion causes postoperative hypocalcemia due to an inhibition of bone resorption, a decrease in the synthesis of 1-25-dihydroxy vitamin D by the kidney and reduced intestinal calcium absorption. Some associated comorbidities, such as malabsorption, gastric bypass, and bisphosphonate therapy, may promote parathyroid failure. When PTH secretion is insufficient, hypocalcemia develops. Hypocalcaemia due to hypoparathyroidism is associated with few symptoms, if the hypocalcaemia is mild. In severe cases, symptoms include seizures, heart failure, or laryngospasm. In addition to the magnitude of hypocalcemia, the speed of establishment determines its clinical expression .
The removal or inadvertent damage of the parathyroids or the alteration of their blood supply are the responsible causes. Both transient and permanent hypoparathyroidism can have important repercussions on patients’ health and establishing appropriate protocols for their prevention, evaluation and treatment are needed .