method is judged based on the healing time, the quality of the regenerated bone, and the efficacy of acceptance of the bone graft/biomaterial in the body. Some of the important considerations are to test patients who have given their informed consent and to determine that the variables that will interfere with the treatment options are constant. Different lengths and periods of time are tested to analyze the best form of therapy administration. When designing clinical trials, it is also important to consider the ethical policies of each country. For example, the policies on the use of human embryos and stem cells derived from them are very different in the United States compared to the European Union (EU). For studies dealing with bone regeneration clinical trials, the period for assessing the immune acceptance of the graft/biomaterial is between six and 12 weeks. The efficacy of the bone regeneration is tested by analyzing the bone density and constitution of the fresh bone. Of course, healing of the fractures is the main goal. Another factor is assessing the formation of scar tissue that might get in the way of function restoration. This is important in dealing with therapies for regeneration of the hip and joints. And, last but not least, infections during the procedure need to be prevented, in addition to targeting a therapy with a reduced pain factor.
Some of the future technologies and patents include use of porous metals that form the basic structure on which the stem cells form the regeneration. The metal provides support and structure to the developing cells.
Sharanya Kumar
Independent Scholar
See Also: Bone: Cell Types Composing the Tissue; Bone: Current Research on Isolation or Production of Therapeutic Cells; Bone: Development and Regeneration Potential; Bone: Major Pathologies; Bone: Stem and Progenitor Cells in Adults; Bone Marrow Transplants.
Further Readings
Dimitriou, R., E. Jones, D. McGonagle, and P. V. Giannoudi. “Bone Regeneration: Current Concepts and Future Directions.” BMC Medicine, v.9/66 (2011).
La, W. G., et al. “Delivery of Bone Morphogenetic Protein-2 and Substance P Using Graphene Oxide for Bone Regeneration.” International Journal of Nanomedicine, v.9/Supp. 1 (2014).
Bone: Major Pathologies
Bone: Major Pathologies
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Bone: Major Pathologies
The bones are multifunctional organs of the body that are a part of the endoskeleton. They are composed of cortical (compact) bone and cancellous (spongy) bone. Cortical bone is the outer hard covering, which gives bones the characteristic white color. Cancellous bone is the inner part of the bone, which is composed of a porous network in which the blood vessels and bone marrow are located. The bones have many essential functions. They act as a protective barrier for vital organs such as the brain and heart. They are required for structure and movement of the human body. The major function of the bone is hematopoiesis, which is the production of red blood cells (RBC) and white blood cells (WBC). Therefore, disorders of the bones can have highly detrimental effects in the body and can lead to death. Stem cells have great potential in the recovery of normal function after treatment of a bone disease. During the course of disease, there is death of essential cells and a decrease in normal function. Hematopoietic stem cells can be implanted after chemotherapy to regain normal WBC and RBC production. This article explains some of the major pathologies affecting bone.
Osteoporosis
Osteoporosis is the most common bone disease. The incidence is much higher in females than in males. In this disease, there is a loss of bone density, resulting in weak bones that are highly susceptible to fractures. Osteoporosis is a disease of age, as it mostly affects elderly humans. This is due to progressive loss of bone composition with age due to decreased locomotion, inadequate nutrition, and decreased production of hormones such as estrogen in the case of postmenopausal women. It can be divided into two types. Primary osteoporosis can be characterized into postmenopausal, senile, and idiopathic. Secondary osteoporosis is associated with underlying disorders such as endocrine, gastrointestinal, use of certain chemotherapeutic drugs, and neoplasia. Pathophysiology includes five major factors. The peak bone mass is influenced by nutrition and physical activity. Individuals with decreased levels of dietary calcium, vitamin D, and increased levels of PTH are at a greater risk of developing osteoporosis. In addition, low levels of physical activity cause a loss of bone because the force associated with activity helps the essential process of bone remodeling. Genetic factors such as the inheritance of OPG, RANK, estrogen receptors are also important as 60 percent to 80 percent of the variation in bone density is genetically determined. Aging contributes to the development of osteoporosis by decreasing replicative activity of osteoprogenitor cells, decreasing the synthetic activity of osteoblasts, and decreasing the biological activity of matrix-bound growth factors. Females in menopause are more likely to develop this disease because this condition is associated with decreased serum estrogen, increased levels of IL-1, IL-6, and TNF levels, increased expression of RANK, RANKL, and increased osteoclastic activity. This disease can be relatively controlled if the patient is encouraged to exercise regularly as well as have a good diet rich in calcium and vitamin D. Smoking is also thought to have a major contributory effect, so cessation of smoking can also prevent aggravation of disease.
Paget’s Disease
Paget’s disease (osteitis deformans) is a primary disease caused by osteoclastic dysfunction. It usually begins in late adulthood and becomes progressively more common thereafter. It can be divided into three phases: (1) initial osteolytic stage, (2) a mixed osteoclastic-osteoblastic stage, and (3) a burnt-out quiescent osteosclerotic stage. The cause of Paget’s disease remains uncertain but evidence suggests both genetic and environmental factors being contributory. The risk of developing this disorder is approximately seven times greater in first-degree relatives of affected individuals. Mutations involving the SQSTM1 gene are found in approximately 40 to 50 percent of the cases of familial disease. The SQSTM1 mutations enhance NF-kB activation of RANK signaling, leading to increased osteoclast activity and an increased susceptibility to the disease. Mutations in the RANKL and RANK/OPG genes have also been linked to genetic conditions that resemble clinical features of Paget’s disease. The cases are usually mild and are discovered accidentally. The axial skeleton is involved in up to 80 percent of the cases, and although no bone is immune, involvement of the ribs, fibula, and small bones of the hands and feet is unusual.
Infection: Osteomyelitis
Osteomyelitis indicates inflammation of the bone and marrow and may arise as a complication of any systemic infection. Most of the time, it manifests as a primary solitary focus of disease with all types of organisms (viruses, bacteria, parasites, fungi) producing the disease. Pyogenic osteomyelitis is always caused by bacteria and the organism can reach the bone by hematogeneous spread, extension from a contiguous site, and by direct implantation. Staphylococcus aureus is responsible for the majority of the cases in which an organism is recovered.
Other organisms commonly associated are Escherichia coli, pseudomonas, and Klebisella in patients with genitourinary tract infections and IV drug abusers and Haemophilus influenzae and group B streptococci in neonatal patients. The location of the infection within the bone is influenced by the osseous vascular circulation, which varies with age. The metaphyseal vessels penetrate the growth plate in neonates and localization of the organism in the metaphysis in children is common. In adults, the organisms are commonly isolated from epiphysis and subchondral regions.
Tuberculous osteomyelitis
