Osteoporosis, Osteoarthritis and Rheumatoid Arthritis: An Agonizing Skeletal Triad

The liver is composed of hepatocytes, biliary epithelial cells, Kupffer cells, stellate cells, and hepatic sinusoidal endothelial cells. It also plays an important role in the digestive system and immune system at the same time. The different types of hepatitis, including viral liver diseases, autoimmune liver diseases, and metabolic liver diseases, are all closely related to osteoporosis. People with liver disease have a significantly higher risk of developing osteoporosis than people without hepatitis. Fibrosis is part of the wound-healing response that maintains organs after tissue injury, but excessive fibrosis may also contribute to a variety of human diseases. Hepatic stellate cells are the key to liver fibrosis. The apoptotic hepatocytes stimulate fibrosis in hepatic myofibroblasts, and activated hepatic stellate cells are the main source of myofibroblasts in the liver. Activated hepatic stellate cells possess many voltage-operated calcium channels. Changes in the concentration of calcium ions mediate hepatic stellate cell activation and fibrosis regression. The skeleton is one of the main regulatory mechanisms of calcium ions in the body. Therefore, chronic hepatitis leads to a disturbance of calcium homeostasis in vivo, which may be one of the factors causing bone loss.

Knee osteoarthritis (KOA) is a common degenerative joint disease that results in disability due to joint dysfunction and pain. Almost one-fifth of early KOA cases are missed during the routine practice resulting in the progression of the disease. This narrative review aimed to explore and analyze various literatures that proposed Convoluted Neural Network (CNN) model in detecting KOA and its severity based on Kellgren Lawrence grading classification. At first, 221 publications were retrieved using the search term “artificial intelligence” and Knee osteoarthritis”. Only studies that used CNN and radiographic images were included in this study in which only 14 studies fitted our inclusion criteria. Each paper was thoroughly investigated for the input data and CNN model adopted as well as the performance and limitation of that study. Lastly, the conclusion was made and discussed using these results. Object detection and Classification models were among the most popular techniques adopted. Our results showed that object detection models were overall superior regarding the accuracy in the detection of KOA and its severity. The application of CNN for the detection of KOA from radiographic images has shown great promise where each technique has its own advantage. In the foreseeable future, the combination of object detection and classification detection may provide excellent potential as a merit tool to help orthopedists and related physicians for the proper diagnosis and treatment of KOA.

Rheumatoid arthritis (RA) is a chronic, inflammatory, and destructive polyarthritis with numerous autoimmune features and the potential for extra-articular and systemic complications. Much progress has occurred in defining important mechanistic components of RA, leading to significant advances in its treatment. RA is a multifactorial and multistage disease, beginning with preclinical autoimmunity that arises in a genetically predisposed individual who encounters one or more environmental triggers, progressing to the clinical appearance of inflammation in joints and sometimes in other organs, and leading to destruction of the articular cartilage and adjacent bone. Regulatory role in inflammation, autoimmunity and articular destruction in the joints of rheumatoid arthritis patients is played primarily by chemokines and cytokines. Amongst many top players of inflammation in RA, tumour-necrosis factor-alpha (TNF-α) is counted as the chief culprit. It is produced by synovial macrophages, B lymphocytes, and NK-cells. Furthermore, TNF-α has exhibited to be of particular utility as a therapeutic target. IL-17A is synthesized by T helper 17 (Th17), which initiates the generation of inflammation causing cytokines like interleukin-6 (IL-6), IL-8 and GM-CSF by cells of endothelium, epithelium and fibroblasts and localization of neutrophils. Progression of inflammation in the synovial fluid is augmented by chemokines in the joints of rheumatoid patients. Elevated levels of CC chemokines (CCL2, CCL3, CCL4 and CCL5) and CXC chemokines (CXCL5, CXCL8, CXCL9 and CXCL10) have been reported in such patients. Moreover, these chemokines may control cell trafficking directly by interacting with their cognate receptors present on inflammatory cells and also by modulating angiogenesis. Several proinflammatory cytokines and chemokines participate in many biological pathways finally setting the loop of inflammation and exacerbation of the outcome and these serve as biomarkers for a number of autoimmune and inflammatory disorders. 

Recent studies have identified the involvement of the immune system in several bone complications like osteoporosis, rheumatoid arthritis (RA), periodontitis, osteoarthritis, etc. Immune cells have an indispensable role in the regulation of bone metabolism and explicitly influence the differentiation of bone cells by producing various cytokines. Fortunately, recent research has examined different immune-based therapeutics for the prevention of bone diseases in addition to revealing more information about the interaction of the bone and the immune system. Vitamin D maintains bone health by effectively absorbing calcium and thereby promoting bone mineralization. In addition, vitamin D has great immunomodulatory potential and can influence the effect of immune cells and cytokines on the pathogenesis of bone deformities. Therefore, it is plausible to suggest that the detrimental effect of vitamin D deficiency on bone is also linked to the immune system apart from its classic effect on bone mineralization. However, very few studies have enlightened on this aspect of vitamin D-mediated regulation of bone homeostasis which needs to be further unraveled. In the present chapter, we have compiled recent studies highlighting the effect of vitamin D on bone health via its effect on the host immune system. Further, we have also highlighted the role of the immune system in the maintenance of skeletal health and then have discussed the effect of vitamin D on various immune cells. In addition, we have reviewed vitamin D-facilitated immune-based approaches for the effective management of various bone pathologies such as osteoporosis, osteoarthritis and rheumatoid arthritis. This information will supposedly help in revealing further mechanistic insights into the immunological regulation of bone health by vitamin D.

Water is the most crucial nutrient that constitutes roughly 20% of the cortical bone by volume, yet most ignored in health and nutrition areas. Hydration significantly influences the mechanical properties and tissue quality of bone, whereas bone dehydration causes an increase in its elastic modulus. Moreover, the low water content in the trabecular skeleton changes its construction (shrinkage) and leads to a significant alteration in mechanical properties. Numerous internal (a lack of thirst sensation) or external (polypharmacy or chronic consumption of certain drugs) factors cause hypohydration. Unfortunately, frail elderly individuals are more vulnerable to developing dehydration particularly, due to a decrease in the fat-free mass, which contains 73% of total body water. Today, technical advancements have led to an emerging understanding of how bone water changes in various conditions including aging, diabetes, osteoporosis, and osteogenesis imperfecta. Drugs may also change the impression of hypohydration through the increase of water elimination causing diarrhoea, diuresis, or sweat; a decrease in thirst sensation or appetite; or affecting the central thermoregulation mechanism. However, research on the interaction between bone hydration status and drugs/excipients has been insufficient. In the present review, we evaluate studies that focus on the significance of bone hydration and the effects of drugs/excipients on hydration status. 

Rheumatoid arthritis (RA) is a systemic autoimmune inflammatory disease that impairs patients' capacity to engage in everyday activities and deteriorates their quality of life. The disease develops in genetically vulnerable individuals via an autoimmune inflammatory process triggered by environmental stimuli. Diet and nutrition are potential environmental variables influencing the start and progression of the disease. Traditionally, nutrition and disease research has examined the relationships between individual nutrients, foods, or dietary groupings and risk factors with health outcomes. By examining food consumption in terms of dietary patterns, it is possible to gain complete knowledge of the combined effects of nutrients and foods on chronic illnesses. The Mediterranean, DASH, and vegetarian diets are preventive dietary patterns, whereas the Western diet stimulates RA activity.

It has been suggested that South Asian patients with RA report increased levels of pain and demonstrated increased disease severity as compared to the British white population. This study assesses the self-perceived quality of life in South Asian RA patients compared to White British RA patients. 131 South Asian (SA) and 134 British White (BW) RA patients from the East Midlands participated in the study as a part of ongoing studies on RA pathogenesis by completing the qualitative lifestyle questionnaire. The SA patients developed RA significantly earlier than BW patients (χ2 = 21.01, P = 0.001, df = 5). Compared to the BW, a majority of SA perceived the disease to be severe (χ2 = 8.57, P < 0.05, df = 3). They also reported higher pain (χ2 = 26.12, P < 0.05, df = 3), reduced mobility (χ2 = 17.57, P < 0.004, df = 5) and reduced physical activity performed (χ2 = 17.94, P < 0.0005, df = 3). Reduced mobility and a decrease in physical activity may be associated with a higher perception of RA-related pain among South Asians. This may have important public health implications in terms of disease progression and treatment modalities.