Nutrition in Bone Health and Disease (2024) PDF

MyAin shams university Faculty of women for Arts, Science and Education Biochemistry and Nutrition department Diet Therapy Diploma (2024- 2025) Human Nutrition (BINU 526) Nutrition in Bone Health and Disease U...

MyAin shams university Faculty of women for Arts, Science and Education Biochemistry and Nutrition department Diet Therapy Diploma (2024- 2025) Human Nutrition (BINU 526) Nutrition in Bone Health and Disease Under supervision of: Prof.Dr/Fatma Abd-Elhamid (Year: October 2024) Prepared by Group(1): 1) Amira Abd-Elmohsen Mohamed 2) Aya Ebraheem Mohamed 3) Engy Fayez Bahnam 4) Mai Ahmed Essam 5) Manar Owise Mahmoud 6) Ola Ragab Mohamed 7) Sara Saeed El-Sayed 8) Shereen Nagi Younis 9) Zeinab Mohamed Mostafa 2|P ag e  List of Contents Page no. o Introduction…………………………………………………………………………..……………..5 o What is bone?...........................................................................................5 o Structures of bone ………………………………………………………………………………..7 o Bone cells ………………………………………………………………………..…………………..9 o Bone matrix ……………………………………………………………………..…………..……11 o Bone marrow…………………………………………………………………….…….………….12 o Bone functions ……………………………………………….…………………….………..….13 o Classification of bones ……………………………………………….……………..….…...15 - Classification according to shape ………………….…………………………….….15 - Classification according to structure …………………………………..……..…..18 - Classification according to maturation ……………………………..…………….20 o Bone modeling ………………….…………….…………….…………………………………….22 o Bone remodeling………………………………………………………………….………………23 o The regulating hormones with respect to bone health ………….….………….27 o Bone diseases ……………………………………………………………………….……………..31 1) Rickets ……………………………………………………………………………………………..…..31 2) Osteomalacia………………………………………………………………………………………..31 3) scoliosis…………………………………………………………………………….……………….….32 4) Paget disease………………………………………………………………………….…………....33 5) Gout disease ………….…………………………………………………………………….………33 6) Bone cancer ……………………………………………………………………….……..…………34 7) Osteoporosis and Osteopenia..………………………………………..……………..……35 - Definition ………………………………….…………………………..…………………….…35 - Symptoms ………………………………………………………………………………………36 - Causes …………………………………………………………………….………………………36 - Risk factor ……………………………………………………………….……………………..36 - Complications………………………………………………………….………………………37 - Diagnosis ………………………………………………………………….…………………….41 - Treatment…………………………………………………………………………………….…42 - Herbal treatment ……………………………………………………………………….…..43 - Prevention………………………………………………………………………………………44 - Nutritional treatment……………………………………………………………………..45 - Food to eat …………………………………………………………………………………….45 - Food to avoid ………………………………………………………………….………………47 8) Osteoarthritis………………………………………………………………………….…………...48 - causes………………………………………………………………………..…………………...49 - symptoms………………………………………………………………….……………………49 - diagnosis………………….………………….……………………….…………………………50 3|P ag e  - treatment…………………………………………………………….………………………….52 - Nutritional treatment…………………………………………….……………………….52 - Food to eat……………………………………………………………………………..……...53 - Food to avoid………………………………………………………………………..………..56 - The role of antioxidants……………………………………………………..……………57 - Nutrients have some benefits for managing osteoarthritis………………………………………………………………..…………………57 - Herbal treatment…………………………………………………………..………………..58 - Non-nutritional treatment………………………………….………………..…………59 - Medications…………………………………………………………………………..………..59 - Physical therapy…………………………………………………………………..………….60 9) Rheumatoid arthritis…………………………………………………………………….……...61 - Symptoms…………………………………………………………………..…………………..62 - Causes…………………………………………………………………………..………………..64 - Risk factors…………………………………………………………………..………………...65 - Complications………………………………………………………………………………….66 - Diagnosis……………………………………………………………………..………………….67 - Treatment……………………………………………………………………………………….69 - Medications…………………………………………………………………………………….69 - Nutritional treatment……………………………………………………………………..69 - Nutrients have some benefits for managing rheumatoid arthritis…………………..……………………………………………………………….………72 o Reference……………………………………………………………………………………………..74 4|P ag e Introduction: Bone is a living tissue and consequently requires all essential nutrients for growth and maintenance. Bone is comprised largely of protein, the main constituent of connective tissue, which occupies half of bone by volume and 20% by weight. Bone mineral is the other main component of bone. Healthy bone needs a balanced diet, regular weight-bearing exercise and the right levels of various hormones. Good nutrition is one of several important lifestyle choices to maintain good bone health.Nutrition provides the raw materials for bone structure. What is Bone? A bone is a rigid organ that constitutes part of the skeleton in most vertebrate animals. Bones protect the various other organs of the body, produce red and white blood cells, store minerals, provide structure and support for the body, and enable mobility. Bones come in a variety of shapes and sizes and have complex internal and external structures. Figure1: What is bone? 5|P ag e Bones provide the structure for our bodies. The adult human skeleton is made up of 206 bones.At birth, there are approximately 270 bones, with the final adult count decreasing as a portion of these bones fuse during phases of skeletal growth and maturation. Bones are made of connective tissue reinforced with calcium and specialized bone cells. Most bones also contain bone marrow, where blood cells are made. Bones contain most of our body’s calcium supply. The body is constantly building up and breaking down bone tissue as required. Figure2:Bone anatomy. 6|P ag e Structure of Bones: Bones are composed of two types of tissue:  Compact (cortical) bone: is a hard outer layer that is dense, strong, and durable. It makes up around 80% of adult bone mass and forms the outer layer of bone.  Cancellous ( spongy) bone: makes up the remaining 20% of bone and consists of a network of trabeculae, or rod-like, structures. It is lighter, less dense, and more flexible than compact bone. Figure3: Structure of bones. 7|P ag e  Spongy Bones Compact Bones Spongy Bones are also called cancellous Compact bones are also called cortical bones bones They are light, spongy and soft in nature They are heavy, tough and compact in nature They are made up of trabeculae They are made up of osteons They fill the inner layer of most bones They fill the outer layer of most bones It forms the ends or epiphyses of long It forms the shaft or diaphysis of long bones bones Bones also contain:  Osteoblasts and osteocytes, responsible for creating bone  Osteoclasts, or bone-resorbing cells  Osteoid, a mix of collagen and other proteins  Inorganic mineral salts within the matrix  Nerves and blood vessels  Bone marrow  Cartilage  Membranes 8|P ag e Bone cells: Bone consists of four types of cells: osteoblasts, osteoclasts, osteocytes, and osteoprogenitor (or osteogenic) cells. Figure4: Types of bone cells. Each cell type has a unique function and is found in different locations in bones. The osteoblast: the bone cell responsible for forming new bone, is found in the growing portions of bone, including the periosteum and endosteum. Osteoblasts, which do not divide, synthesize and secrete the collagen matrix and calcium salts. As the secreted matrix surrounding the osteoblast calcifies, the osteoblast becomes trapped within it. As a result, it changes in structure, becoming an osteocyte. The osteocyte: the primary cell of mature bone and the most common type of bone cell. Each osteocyte is located in a space (lacuna) surrounded by bone tissue. Osteocytes maintain the mineral 9|P ag e concentration of the matrix via the secretion of enzymes. As is the case with osteoblasts, osteocytes lack mitotic activity. They are able to communicate with each other and receive nutrients via long cytoplasmic processes that extend through canaliculi (singular = canaliculus), channels within the bone matrix. The osteoclast: The cell responsible for bone resorption, or breakdown, which is found on bone surfaces. It is multinucleated, and originates from monocytes and macrophages (two types of white blood cells) rather than from osteogenic cells. Osteoclasts continually break down old bone while osteoblasts continually form new bone. The osteogenic cell: These cells are undifferentiated with high mitotic activity; they are the only bone cells that divide. Immature osteogenic cells are found in the deep layers of the periosteum and the marrow. When they differentiate, they develop into osteoblasts. Bone matrix: Figure5: Bone matrix. 10 | P a g e The bone matrix is the intercellular substance of the bone that forms most of the mass of the bone. It consists of two types of material: organic and inorganic. The inorganic portion makes about half of the weight of the bone. It mostly consists of calcium hydroxyapatite, but there are also significant amounts of bicarbonate, citrate, magnesium, potassium, and sodium ions. The organic portion of the bone matrix consists of collagen fibers (type I), proteoglycans, and glycoproteins. The organic material is produced and secreted by the osteoblasts. When osteoblasts actively produce the bone matrix components they are cuboid in shape and their cytoplasm is basophilic. In contrast, when they are in an inactive state they flatten and their basophilic features reduce. The main function of the bone matrix is to provide mechanical support for the bones. Bone marrow: 11 | P a g e Bone marrow is present in almost all bones where cancellous, or spongy, bone is present. There are two types of bone marrow: red and yellow. Red bone marrow contains blood stem cells that can become red blood cells, white blood cells, or platelets. Yellow bone marrow is made mostly of fat and contains stem cells that can become cartilage, fat, or bone cells. Bone marrow produces blood cells, including:  Red blood cells, which deliver oxygen to cells  White blood cells, essential for the body’s immune system  Platelets, which the body uses for clotting The marrow produces around 2 million red blood cells every second. It also produces lymphocytes, or the white blood cells involved in the immune response. Bone Functions: Bone has many important jobs in the body:  The skeleton is made of bone to provide a strong framework to support and protect the soft organs (such as the brain, heart, and lungs) from injury.  Bone works with muscle to hold up the body when we stand and to move the body when we walk or run.  Bone houses the bone marrow, which makes blood cells.  Bone stores growth factors and minerals such as calcium.  Bone releases factors into the blood that are necessary for normal functioning of soft organs such as the kidney. Metabolic functions of bone:  Storage: Bones act as a reserve for minerals, particularly calcium and phosphorous. Bone marrow adipose tissue can also store fatty acids. 12 | P a g e  Endocrine function: Bones produce the precursors to various hormones, including those involved in growth, insulin production, and brain development. They release hormones that act on the kidneys and influence blood sugar regulation and fat deposition.  Calcium balance: Bones can raise or reduce calcium in the blood by forming bone, or breaking it down in a process called resorption.  pH balance: Some Source has suggested bones can release or absorb alkaline salts, helping blood to stay at the right pH level.  Detoxification: Bones can absorbheavy metals such as lead, mercury, and arsenic from the blood. Figure6: Bone functions 13 | P a g e Classifications of bones: Bones can be classified according to: 1) Shape 2) Structure 3) Development and Maturation  Classification according to shape: The 206 bones that compose the adult skeleton are divided into six categories based on their shapes. Figure7: Bones types according to shapes. 1) Long bones: A long bone is one that is cylindrical in shape, being longer than it is wide.Long bones are found in the armsand legs, as well as in the fingers and toes. Long bones function as levers; they move when muscles contract. Figure8:Longbones. 14 | P a g e 2) Short bones: A short boneis one that is cube-like in shape, being approximately equal in length, width, and thickness. The only short bones in the human skeleton are in the carpals of the wrists and the tarsals of the ankles. Short bones provide stability and support as well as some limited motion. Figure9: Short bones. 3) Flat bones: They are thin, flattened, and usually curved.The function of flat bones is to protect internal organs such as the brain, heart, and pelvic organs. Flat bones can provide protection, flat bones can also provide large areas of attachment for muscles. Figure10: Flat bones. 15 | P a g e 4) Irregular bones: vary in shape and structure and therefore do not fit into any other category. They often have a fairly complex shape, which helps protect internal organslike the vertebrae that support the spinal cord and protect it from compressive forces. Figure11: Irregular bones. 5) Sesamoid bones: shaped like a sesame seed.These are embedded in muscles and tendons near the surfaces of joints. These small, round bones are commonly found in the tendons of the hands, knees, and feet. Sesamoid bones function to protect tendons from stress and wear. Figure12: Sesamoid bones. 16 | P a g e  6) Sutural bones ( Wormian bones): Small irregular bones formed between the flat cranial bones. They vary in size and have irregular shape. Figure13: Sutural bones.  Classification according to structure: There are two types of bone tissue: compact and spongy. Figure14: Compact and spongy bones. Compact bone (or cortical bone): forms the hard external layer of all bones and surrounds the medullary cavity, or bone marrow. It provides protection and strength to bones. 17 | P a g e  Spongy bone or cancellous bone: forms the inner layer of all bones.Spongy bone reduces the density of bone and allows the ends of long bones to compress as the result of stresses applied to the bone. Figure15:Structural difference between spongy and compact bone  The difference between compact and spongy bones Compact Bone Spongy Bone Structure Dense, solid and compact Soft, Porous, and honeycomb-like structure Weight Heavier due to denser Lighter since it is porous structure Vascularity Highly vascularized Limited blood supply compared to which allow blood vessels and compact bone nerves to travel through them Function Provides strength, support, Facilitates shock absorption, reduces and protection weight, and enables the metabolic exchange Bone Marrow Contains Yellow bone marrow Contains Red marrow (contains stem (contains adipose tissue) cells for blood cell production) Location The outer layer of long bones The inner layer of flat and irregular bones 18 | P a g e  Classification according to development and maturation: Under the microscope, bone can be divided into two types: Woven bone (primary bone): Appears in embryonic development and fracture repair, as it can be laid down rapidly. It consists of osteoid with the collagen fibers arranged randomly. It is a temporary structure, soon replaced by mature lamellar bone. Lamellar bone (secondary bone): The bone of the adult skeleton. It consists of highly organized sheets of mineralized osteoid. This organized structure makes it much stronger than woven bone. Lamella bone itself can be divided into two types – compact and spongy. In both types of bone, the external surface is covered by a layer of connective tissue, known as the periosteum. Figure16:Lamellar and Woven bones. 19 | P a g e   The difference between Lamellar and Woven bones Figure 17:Woven and lamellar bone Woven bone (Immature bone) Lamellar bone (Mature bone) Formation and mineralization very Formation and mineralization slower rapid with high rate Disorganised tissue Highly organized Low mineral content High mineral content (stronger) High water content Low water content High osteocytes content Less osteocytes 20 | P a g e Bone Modeling and Remodeling: 1. Bone modeling: Definition: Bone modeling is the process by which bones are formed and shaped, primarily during childhood and adolescence. During this time, the skeletal structure develops, and bone mass and density increase. Mechanism: In this process, osteoblasts (bone-forming cells) create new bone tissue. Bones can change in size and shape in response to mechanical forces and growth. Purpose: This process allows bones to adapt to mechanical stresses and supports growth or changes in physical needs. Location & Timing: Bone modeling occurs mainly during growth until the skeleton reaches full maturity. Figure18: Bone modeling. 21 | P a g e  2. Bone remodeling: Definition: Bone remodeling is a continuous process that occurs throughout life, where old or damaged bone tissue is replaced with new bone tissue to maintain the overall health and strength of the bones. Mechanism: This process involves osteoclasts (bone-resorbing cells) that remove old or damaged bone, followed by osteoblasts that form new bone. Purpose: Bone remodeling helps repair micro-damage to bones from daily activities and maintains bone strength. It also plays a crucial role in regulating calcium and phosphate levels in the body. Location & Timing: It occurs in specific areas of the bone as needed and continues throughout life, especially in response to fractures, changes in physical activity, or hormonal fluctuations. Figure19: Bone modeling and remodeling. 22 | P a g e  Remodeling is characterized by four phases: 1) The activation phase: When the osteoclasts are recruited. 2) The resorption phase: When the osteoclasts resorb bone. 3) The reversal phase: Where the osteoclasts undergo apoptosis and the Osteoblasts are recruited. 4) The formation phase: Where the osteoblasts lay down new organic bone matrix that subsequently mineralizes. Figure20: Bone remodeling cycle. 23 | P a g e 24 | P a g e 25 | P a g e The most important regulating hormones with respect to bone health: Several hormones play important roles in regulating bone health by influencing bone formation and resorption. Here are the most important ones: 1) Parathyroid Hormone (PTH): Parathyroid hormone is secreted by the four parathyroid glands. Parathyroid hormone controls and regulates the levels of calcium in the blood and raises their levels when they are too low. This hormone performs its function through its actions on the bones, intestines, and kidneys. Effect on Bone Health: The parathyroid hormone (PTH) stimulates the release of calcium from stores of calcium present in the bones into the bloodstream.Chronic high levels of PTH can lead to bone loss (osteoporosis), while controlled levels help maintain a balance of calcium for bone strength. Intestine: PTH increases the calcium absorption in the intestine by food through its impacts and affects the metabolism of vitamin D. Kidneys: PTH minimizes the calcium loss in the urine and also stimulates active vitamin D formation in the kidneys. Figure21: Effect of PTH hormone. 26 | P a g e 2) Calcitonin: Calcitonin is a hormone that plays a role in regulating the level of calcium in blood by decreasing it. The C-cells in thyroid gland produce Calcitonin. Calcitonin main job is to lower calcium levels in the blood. It does this in two main ways:  Calcitonin inhibits (blocks) the activity of osteoclasts, which are cells that break down bone. When osteoclasts break down your bone, the calcium from your bone is released into your bloodstream. Therefore, the temporary blocking of osteoclasts by Calcitonin reduces the amount of calcium that enters blood.  Calcitonin can decrease the amount of calcium that your kidneys reabsorb and release back into your bloodstream, thus causing lower blood calcium levels. Figure22: Effect of Calcitonin hormone. 27 | P a g e 3) Calcitriol(Vitamin D): Synthesized in the skin (with sunlight exposure), and also obtained from food and supplements. It is the hormonally active metabolite of vitamin D. It plays a classical hormonal role in skeletal health to regulate calcium and phosphorus metabolism, by influencing intestinal absorption, bone resorption, and renal retention. A deficiency can lead to soft, weak bones (rickets in children, osteomalacia in adults). Figure23: Effect of Calcitriol hormone. 4) Estrogen hormone: Estrogen inhibits bone resorption by suppressing osteoclast activity and promoting the survival of osteoblasts. It also helps regulate bone remodeling and maintains bone density. Estrogen deficiency (e.g., after menopause) leads to increased bone resorption, reducing bone mass and increasing the risk of osteoporosis in women. 28 | P a g e 5) Growth Hormone (GH): Growth hormone stimulates bone growth by promoting the production of insulin-like growth factor 1 (IGF-1), which enhances osteoblast activity, leading to bone formation. GH is important for bone development during childhood and adolescence. In adults, it helps maintain bone mass, and deficiency can lead to reduced bone density and increased fracture risk. 6) Insulin-like Growth Factor 1 (IGF-1): IGF-1 promotes bone formation by stimulating osteoblast activity and increasing collagen production, which is essential for bone matrix development. It plays a critical role in bone growth during childhood and adolescence and helps maintain bone mass in adulthood. 7) Cortisol hormone: Cortisol regulates the body’s stress response and affects many metabolic processes, including bone turnover. It can reduce bone formation and increase bone resorption if present in high levels for extended periods. Chronic high levels of cortisol (e.g., in conditions like Cushing’s syndrome or long-term steroid use) can lead to bone loss and osteoporosis due to the suppression of osteoblast activity and promotion of osteoclast activity. 8) Thyroid hormones: Thyroid hormones regulate overall metabolism, including the turnover of bone cells. They stimulate both osteoclast and osteoblast activity, but excessive levels lead to more bone resorption than formation. Hyperthyroidism (excess thyroid hormone) can lead to increased bone turnover and bone loss, increasing the risk of fractures. 29 | P a g e Bone diseases: 1. Rickets: Rickets is the softening and weakening of bones in children, usually because of an extreme and prolonged vitamin D deficiency. Vitamin D helps your child's body absorb calcium and phosphorus from food. Not enough vitamin D makes it difficult to maintain proper calcium and phosphorus levels in bones, which can cause rickets. Children who don't get enough vitamin D from these two sources can develop a deficiency: Sunlight: Your child's skin produces vitamin D when it's exposed to sunlight. But children in developed countries tend to spend less time outdoors. They're also more likely to use sunscreen, which blocks the sun's rays that trigger the skin's production of vitamin D. Food: Fish oil, egg yolks and fatty fish such as salmon and mackerel contain vitamin D. Vitamin D has also been added to some foods and beverages, such as milk, cereal and some fruit juices. Problems with absorption: Some children are born with or develop medical conditions that affect the way their bodies absorb vitamin D. Some examples include: Celiac disease Inflammatory bowel disease Cystic fibrosis Kidney problems 30 | P a g e  2. Osteomalacia: Osteomalacia, a metabolic bone disorder commonly known as "soft bone disease," results from inadequate mineralization of bone tissue due to deficiencies in vitamin D, calcium, or phosphate. This deficiency leads to weakened, softened bones, manifesting in symptoms such as bone pain, muscle weakness, and an increased risk of fractures. Figure24:Osteomalacia disease. Prevention of osteomalacia rests on having an adequate intake of vitamin D and calcium, or other treatments if the osteomalacia hereditary (genetic). 31 | P a g e  3. Scoliosis: Scoliosis is an abnormal curving of the spine.The curve is usually S- or C- shaped over three dimensions. In some, the degree of curve is stable, while in others, it increases over time. Figure25: Scoliosis disease. 4. Paget's disease: Chronic condition in which both the breakdown and regrowth of bone are increased. Paget disease of bone occurs most frequently in the pelvic and leg bones, skull, and lower spine. It is most common in older individuals, and may lead to bone pain, deformities, and fractures. Figure26:Paget's disease. 32 | P a g e Management:  In general, patients with Paget's disease should receive 1000–1500 mg of calcium, adequate sunshine, and at least 400 units of vitamin D daily.  Exercise is very important in maintaining skeletal health, avoiding weight gain, and maintaining joint mobility. 5. Gout disease: Is due to elevated levels of uric acid in the blood (hyperuricemia). This occurs from a combination of diet, other health problems, and genetic factors. At high levels, uric acid crystallizes and the crystals deposit in joints, tendons, and surrounding tissues, resulting in an attack of gout. Gout occurs more commonly in those who regularly drink beer or sugar- sweetened beveragesor are overweight. Physical fitness, healthy weight, low-fat dairy products, and to a lesser extent, coffee and taking vitamin C, appear to decrease the risk of gout. complete abstinence from drinking alcoholic beverages, reducing the intake of fructose and purine-rich foods of animal origin, such as organ meats and seafood. Figure27: Gout disease. 33 | P a g e 6. Bone cancer: Is an abnormal growth of tissue in bone, traditionally classified as noncancerous (benign) or cancerous (malignant). Cancerous bone tumors usually originate from a cancer in another part of the body such as lung, breast, thyroid, kidney and prostate. There may be a lump, pain, or neurological signs from pressure. A bone tumor might present with a pathologic fracture. Other symptoms may include fatigue, fever, weight loss, anemia and nausea. Sometimes there are no symptoms and the tumor is found when investigating another problem. Figure28: Bone cancer. 7. Osteoporosis and Osteopenia: Figure29:Osteopenia and Osteoporosis.. 34 | P a g e Osteopenia known as "low bone mass" or "low bone density", is a condition in which bone mineral density is low. Because their bones are weaker, people with osteopenia may have a higher risk of fractures, and some people may go on to develop osteoporosis. Osteopenia is an early sign of osteoporosis. Their names sound so similar because they’re closely related.If it’s not treated, osteopenia can become osteoporosis. Osteoporosis is a bone disease that develops when bone mineral density and bone mass decreases, or when the structure and strength of bone changes. This can lead to a decrease in bone strength that can increase the risk of fractures (broken bones).Osteoporosis is the major cause of fractures in postmenopausal women and in older men. Figure30: Osteopenia and Osteoporosis. Symptoms: Osteoporosis is a “silent” disease because you typically do not have symptoms, and you may not even know you have the disease until you break a bone. But once your bones have been weakened by osteoporosis, you might have signs and symptoms that include:  Back pain, caused by a broken or collapsed bone in the spine.  Loss of height over time.  A stooped posture.  A bone that breaks much more easily than expected. 35 | P a g e  Figure31: Symptoms of osteoporosis. Causes: Osteoporosis occurs when too much bone mass is lost and changes occur in the structure of bone tissue.Osteoporosis happens as you get older and your bones lose their ability to regrow and reform themselves. Risk factors: Certain risk factors may lead to the development of osteoporosis.There are some risk factors that you cannot change, and others that you may be able to change. However, by understanding these factors, you may be able to prevent the disease and fractures. Factors that may increase your risk for osteoporosis include: 1. Unchangeable risks Some risk factors for osteoporosis are out of your control, including: Sex: Women are much more likely to develop osteoporosis than are men. Age: The older you get, the greater your risk of osteoporosis. Race: You're at greatest risk of osteoporosis if you're white or of Asian descent. Family history: Having a parent or sibling with osteoporosis puts you at greater risk, especially if your mother or father fractured a hip. 36 | P a g e Body frame size: Men and women who have small body frames tend to have a higher risk because they might have less bone mass to draw from as they age. Figure32: Osteoporosis risk factors. 2. Hormone levels: Osteoporosis is more common in people who have too much or too little of certain hormones in their bodies. Examples include: Sex hormones: Lowered sex hormone levels tend to weaken bone. The fall in estrogen levels in women at menopause is one of the strongest risk factors for developing osteoporosis. Treatments for prostate cancer that reduce testosterone levels in men and treatments for breast cancer that reduce estrogen levels in women are likely to accelerate bone loss. Thyroid problems: Too much thyroid hormone can cause bone loss. This can occur if your thyroid is overactive or if you take too much thyroid hormone medicine to treat an underactive thyroid. Other glands: Osteoporosis has also been associated with overactive parathyroid and adrenal glands. 37 | P a g e  3. Dietary factors:  Low calcium intake: A lifelong lack of calcium plays a role in the development of osteoporosis. Low calcium intake contributes to diminished bone density, early bone loss and an increased risk of fractures.  Eating disorders: Severely restricting food intake and being underweight weakens bone in both men and women.  Gastrointestinal surgery: Surgery to reduce the size of your stomach or to remove part of the intestine limits the amount of surface area available to absorb nutrients, including calcium. These surgeries include those to help you lose weight and for other gastrointestinal disorders. 4. Lifestyle choices: Some bad habits can increase your risk of osteoporosis. Examples include:  Sedentary lifestyle: People who spend a lot of time sitting have a higher risk of osteoporosis than do those who are more active. Any weight-bearing exercise and activities that promote balance and good posture are good for your bones.  Excessive alcohol consumption: Regular consumption of more than two alcoholic drinks a day increases the risk of osteoporosis.  Tobacco use: The exact role tobacco plays in osteoporosis isn't clear, but it has been shown that tobacco use contributes to weak bones. 5. Medications: Some medications or surgical procedures can increase your risk of osteoporosis:  Diuretics (medications that lower your blood pressure and clear extra fluid from your body.  Corticosteroids (medications that treat inflammation).  Medications used to treat seizures.  Bariatric (weight loss) surgery.  Hormone therapy for cancer (including to treat breast cancer or prostate cancer). 38 | P a g e   Anticoagulants.  Proton pump inhibitors (like those that treat acid reflux, which can affect your calcium absorption). 6. Thyroid disease: Thyroid hormone affects the rate of bone replacement so plays a crucial role in maintaining healthy bones. Too much thyroid hormone (i.e. thyroxin) in your body speeds the rate at which bone is lost. If this happens too fast the osteoblasts may not be able to replace the bone loss quickly enough. If the thyroxin level in your body stays too high for a long period or the Thyroid-Stimulating Hormone (TSH) level in your body stays too low for a long period, then there is a higher risk of developing osteoporosis. Figure33: Thyroid gland. Complications: Bone breaks, particularly in the spine or hip, are the most serious complications of osteoporosis. Hip fractures often are caused by a fall and can result in disability and even an increased risk of death within the first year after the injury. Figure34: Thyroid gland. 39 | P a g e In some cases, broken bones in the spine can occur even if you haven't fallen. The bones that make up your spine, called vertebrae, can weaken to the point of collapsing, which can result in back pain, lost height and a hunched-forward posture. Diagnosis: 1) dual-energy x-ray absorptiometry(DEXA or DXA): Dual-energy x-ray absorptiometry (DXA or DEXA) is a type of test that measures bone density, also known as bone mineral density (BMD). A central DXA scan evaluates bone density in areas that are prone to fracture. In most cases, a central DXA measures bone density in the spine and hip. A central DXA scan is both the most accurate and most common type of bone density test. It uses a low-dose x-ray to determine the amount of minerals in a specific area of bone. By examining the bones in at least two sites, a central DXA test can provide specific bone density scores:  A T-score compares your bone density to a healthy young adult.  A Z-score compares your bone density to an average person of your age. According to the World Health Organization, osteoporosis is defined based on the following bone density levels: Figure35: Bone density level.  A T-score within 1 SD (+1 or -1) of the young adult mean indicates normal bone density. 40 | P a g e   A T-score of 1 to 2.5 SD below the young adult mean (-1 to -2.5 SD) indicates low bone mass.  A T-score of 2.5 SD or more below the young adult mean (more than -2.5 SD) indicates the presence of osteoporosis. 2) Laboratory tests: After a diagnosis of osteoporosis, a doctor may recommend certain laboratory tests in order to check for underlying health conditions that could be affecting the bones. There are several kinds of blood tests that may be performed in people with osteoporosis or low bone density. Some of these tests examine levels of different vitamins and minerals such as:  Calcium  Vitamin D  Phosphorus  Electrolytes In addition, the following laboratory tests may be ordered to check for abnormalities in blood cells and specific hormones levels:  Complete blood count (CBC)  Thyroid-stimulating hormone (TSH)  Parathyroid hormone (PTH) Treatment: The most common osteoporosis treatments include: Exercise: Regular exercise can strengthen your bones (and all the tissue connected to them, like your muscles, tendons and ligaments). Your provider might suggest weight-bearing exercise to strengthen your muscles and train your balance. Exercises that make your body work against gravity like walking, yoga, Pilates and tai chi can improve your strength and balance without putting too much stress on your bones. Vitamin and mineral supplements: You might need over-the-counter or prescription calcium or vitamin D supplements. Your provider will tell you 41 | P a g e which type you need, how often you should take them and which dosage you’ll need. Medications for osteoporosis: Your provider will tell you which prescriptions will work best for you and your body. Some of the most common medications providers use to treat osteoporosis include hormone therapies like replacement estrogen or testosterone and bisphosphonates. Herbal treatment: Figure36:Herbs for osteoporosis. 1) Red sage:A review of 36 clinical trials found red sage treated and improved more than 80% of osteoporosis cases. have antioxidant properties that prevent inflammation and free radical production associated with the breakdown of bone. These compounds can also help bone growth. Red sage is also a good source of vitamin K, which is needed for healthy bones. 2) Red clover: it has been used as a complementary treatment for menopausal symptoms, such as hot flashes. Researchers found that bone mineral density was improved in the women who took red clover.However, other studies showed no change in bone health. 3) Thyme: Researchers found that regular consumption of thyme improved bone mineral density better than a calcium/vitamin D3 supplement. 42 | P a g e 4) Soy isoflavones: The isoflavones are considered phytoestrogens.With the loss of estrogen at menopause, the risk of bone loss in females is increased. Studies have demonstrated that soy isoflavones in the diet may improve bone health and slow bone loss associated with osteoporosis. 5) Turmeric: Curcumin, the active ingredient in turmeric, may help with low bone density. A preliminary study found taking a curcumin supplement for six months showed significant improvements in 57 people with low bone density. Prevention: Figure37: osteoporosis prevention. Prevention of low bone density can start early in life by maximizing peak bone density. Once a person loses bone density, the loss is usually irreversible, so preventing bone loss is important. Actions to maximize bone density and stabilize loss include :  Exercise, particularly weight-bearing exercise, resistance exercises and balance exercises promotes increased bone mass, and reduced fall risk.  Sufficient calcium in diet: older adults may have increased calcium needs, medical conditions such as Celiac and hyperthyroidism can affect absorption of calcium.  Sufficient Vitamin D in diet.  Estrogen replacement.  Avoidance of steroid medications.  Limit alcohol use and smoking. 43 | P a g e Nutritional treatment: A healthy balanced diet will help you build healthy bones from an early age and maintain them throughout your life.  Food to eat: Figure38:Food to eat. A) Calcium: Adults need 700mg of calcium a day. You should be able to get all the calcium you need by eating a varied and balanced diet. Good sources of calcium include:  milk, cheese and other dairy foods  green leafy vegetables, such as broccoli, cabbage and okra, but not spinach  soya beans  tofu  plant-based drinks (such as soya drink) with added calcium  nuts  bread and anything made with fortified flour  fish where you eat the bones, such as sardines and pilchards 44 | P a g e  B) Vitamin D: It's difficult to get all the vitamin D we need from our diet and we get most of our vitamin D from the action of the sun on our skin. Good food sources of vitamin D:  egg yolks  oily fish such as salmon, trout, mackerel, and tuna  beef liver  cheese  mushrooms that producers have treated with UV light  milk, margarine, orange juice, and cereals that manufacturers have fortified with vitamin D. C) Protein: Eating a diet with sufficient protein and calcium seems wise. Protein-rich foods include:  meat  fish  eggs  dairy products  beans, lentils, and legumes  soy products  seitan  nuts and seeds D) Micronutrients and antioxidants in fruits and vegetables: people with a higher fruit and vegetable intake had better BMD and less bone loss.The nutrients in fruits and vegetables that the study indicated are beneficial to bone health include:  vitamin C  vitamin K  magnesium  potassium  folate  carotenoids 45 | P a g e  E) Magnesium: Magnesium is an important nutrient that improves bone stiffness and increases osteoblasts (cells responsible for bone formation) and osteoclasts (cells responsible for removing old and damaged bones). It also helps maintain bone density and strength. Magnesium is essential for the absorption of Vitamin D. F) Vitamin C: A good amount of vitamin C can also go a long way in helping your bone health. Specifically, vitamin C helps with the synthesis of collagen, a protein that forms the structure of bones, cartilage and connective tissues. G) Vitamin K: Vitamin K is necessary for the synthesis of osteocalcin, a protein that helps strengthen bones. It helps activate a protein that binds with calcium to build strong bones and improve bone density. H) Omega-3 fatty acids: Omega-3 fatty acids have anti-inflammatory properties and may help reduce the risk of osteoporosis by promoting bone formation and preventing bone decay.  Foods to limit or avoid: In addition to eating a healthy diet to support bone health, people should be aware of some detrimental foods and drinks. A) Salt: Overconsumption of salt can cause the kidneys to excrete calcium. Therefore, people who have a low calcium intake should avoid adding salt to food or eating too many processed foods that can contain excess salt. 46 | P a g e  B) Alcohol: Excessive alcohol consumption can interfere with calcium absorption and disrupt the balance of hormones involved in bone health. Chronic heavy drinking can lead to decreased bone density and increase the risk of fractures. C) Caffeine: High intake of caffeine, found in coffee, tea, energy drinks and some sodas, may expel calcium quicker from your body, which can affect bone density. D) Sugar: A diet high in sugar has been shown to increase inflammation and insulin, reduce calcium intake, and increase urinary excretion of calcium and magnesium. Avoid sugar-sweetened beverages, specifically soda with phosphoric acid, which can produce an imbalance of phosphorus compared to calcium. Soda intake has been correlated with increased risk of bone fractures. 8. Osteoarthritis: Osteoarthritis is a degenerative joint disease, in which the tissues in the joint break down over time. It is the most common type of arthritis and is more common in older people. People with osteoarthritis usually have joint pain and, after rest or inactivity, stiffness for a short period of time. Figure39: Osteoarthritis. 47 | P a g e As the damage of soft tissues in the joint progresses, pain, swelling, and loss of joint motion develops. If you have joint pain, you may be less active, and this can lead to muscle weakness, which may cause more stress on the joint. Over time, the joint may lose its normal shape. Also, small bone growths, called osteophytes or bone spurs, may grow on the edges of the joint. The shape of the bone may also change. Causes: Factors that may contribute to the development of OA include:  Age: The risk of developing OA increases with age and symptoms generally, but not always, appear in people over 50.  Joint injury: A bone fracture or cartilage or ligament tear can lead to OA, sometimes more quickly than in cases where there is not an obvious injury.  Overuse: Using the same joints over and over in a job or sport can result in OA.  Obesity: Excess weight adds stress and pressure on a joint, plus fats cells promote inflammation.  Weak muscles: If muscles don’t provide adequate joint support, poor alignment can result, which can lead to OA.  Genetics: People with family members who have OA are more likely to develop it.  Gender: Women are more likely to develop OA than men.  Environmental Factors: Modifiable environmental risk factors include things like someone’s occupation, level of physical activity, presence or absence of prior joint injury, obesity, diet, sex hormones, and bone density. Symptoms: Common features of osteoarthritis include:  Pain and swelling in your joints.  Pain that increases after stressing your joint (such as by walking or lifting heavy objects).  A crunching sound or grinding sensation in affected joints.  Changes in the shape of your joints, including bone spurs (bony growths near joints). 48 | P a g e The location of the pain depends on the type of osteoarthritis: Primary osteoarthritis: is most common in the fingers, thumbs, spine, hips, knees and big toes. Secondary osteoarthritis: develops in joints that have been injured or damaged, such as from sports-related injuries or accidents. Secondary osteoarthritis can also develop in joints that have been damaged due to inflammatory diseases. Diagnosis: During the physical exam, your doctor will check your affected joint for tenderness, swelling, redness and flexibility. Figure40: Diagnosis of osteoarthritis. Imaging tests: To get pictures of the affected joint, your doctor might recommend:  X-rays: Cartilage doesn't show up on X-ray images, but cartilage loss is revealed by a narrowing of the space between the bones in your joint. An X-ray can also show bone spurs around a joint.  Magnetic resonance imaging (MRI):An Magnetic resonance imaging (MRI) uses radio waves and a strong magnetic field to produce detailed images of bone and soft tissues, including cartilage. An MRI isn't commonly needed to diagnose osteoarthritis but can help provide more information in complex cases. 49 | P a g e   Blood tests: Although there's no blood test for osteoarthritis, certain tests can help rule out other causes of joint pain, such as rheumatoid arthritis.  Lab tests: Analyzing your blood or joint fluid can help confirm the diagnosis.  Joint fluid analysis: Your doctor might use a needle to draw fluid from an affected joint. The fluid is then tested for inflammation and to determine whether your pain is caused by gout or an infection rather than osteoarthritis. Treatment: Osteoarthritis can't be reversed, but treatments can reduce pain and help you move better.  Lifestyle modification (such as weight loss and exercise) and pain  The diet must ensure optimal calcium and vitamin D intake and to take specific supplements if necessary. Nutritional treatment: Figure41: Food help with osteoarthritis. 50 | P a g e How can diet help with osteoarthritis? Changes to a person’s diet may help them manage osteoarthritis symptoms. Eating certain foods and avoiding or limiting others may help with managing inflammation associated with arthritis. Reducing inflammation and preventing damage: A balanced, nutritious eating plan that includes foods like fruits, vegetables, and lean protein, will give the body the nutrients it needs to prevent further damage to the joints, which is essential for people with osteoarthritis. Some foods are known to reduce inflammation in the body, and following an anti-inflammatory diet can improve symptoms. Eating enough antioxidants, including vitamins A, C, and E, may help prevent further damage to the joints.  Food to eat: A) Oily fish: Oily fish contain lots of healthful omega-3 fatty acids. These polyunsaturated fats have anti-inflammatory properties, so they may benefit people with osteoarthritis. Examples of oily fish include:  herring  mackerel  salmon  sardines B) Extra-virgin olive oil: In addition to oily fish, some other oils can reduce inflammation. Extra- virgin olive oil contains high levels of oleocanthal, which may have similar properties to nonsteroidal anti-inflammatory drugs (NSAIDs). Avocado oil and safflower oil may also help lower cholesterol. 51 | P a g e  C) Dairy: Dairy products such as milk, yogurt, and cheese are rich in calcium and vitamin D. These nutrients increase bone strength, which may improve painful symptoms. Dairy also contains proteins that can help build muscle. People who are aiming to manage their weight can choose low fat options. D) Dark leafy greens: Figure42: Dark leafy greens. Dark leafy greens are rich in vitamins A, C, and K and stress-fighting phytochemicals and antioxidants. They are also high in calcium, which makes up most of the structure of our bones. Examples of dark leafy greens include:  spinach  kale  Swiss chard  collard greens  Brussels sprouts  Broccoli 52 | P a g e  E) Broccoli: Broccoli contains a compound called sulforaphane, which researchers believe could slow the progression of osteoarthritis. This vegetable is also rich in vitamins K and C, as well as bone- strengthening calcium. F) Garlic: Scientists believe that a compound called diallyl disulfide that occurs in garlic may work against the enzymes in the body that damage cartilage. A 2010 study indicated that a diet rich in garlic and other alliums can help protect against hip osteoarthritis. While more research into the benefits of garlic for existing osteoarthritis is necessary, it may help a person manage symptoms. G) Nuts: Nuts are good for the heart and contain high levels of calcium, magnesium, zinc, vitamin E, and fiber. They also contain alpha-linolenic acid (ALA), which boosts the immune system. A person with osteoarthritis may consider adding the following nuts to their diet:  Almonds  Walnuts  Pine nuts  Pistachios 53 | P a g e  H) Green tea: Green tea contains high levels of polyphones. Polyphenols are antioxidants that experts believe may be able to reduce inflammation and slow the rate of cartilage damage. Figure43: Green tea.  Foods to avoid: When someone is living with osteoarthritis, their body is in an inflammatory state. While foods with anti-inflammatory properties may reduce symptoms, some foods contain substances that actively contribute to this inflammation. It is best to avoid or restrict these types of foods. Figure44: Food to avoid with osteoarthritis. 54 | P a g e  A) Sugar: Processed sugars can prompt the release of cytokines, which act as inflammatory messengers in the body.The sugars that manufacturers add to sweetened beverages largely contribute to the sugar intake in many people’s diets. This includes sugars added to:  Soda  sweet tea  flavored coffees  some juice drinks B) Saturated fat: Foods high in saturated fat can cause inflammation in the fat tissue. This speed up the progression of some types of osteoarthritis, such as knee osteoarthritis. Foods high in saturated fats include:  fatty meats and meat products  cream  cheese  butter  chocolate  cakes and pastries C) Refined carbohydrates Refined carbohydrates fuel the production of advanced glycation end (AGE) oxidants. These can stimulate inflammation in the body. Examples of refined carbohydrates include:  white bread  white rice  potato chips 55 | P a g e The role of antioxidants: An anti-inflammatory diet focuses on fresh fruits and vegetables, which are often good sources of antioxidants. Dietary antioxidants are molecules in food that help remove free radicals from the body. An anti-inflammatory diet may serve as a complementary therapy for many conditions that become worse with chronic inflammation, such as osteoarthritis. Nutrients have some benefits for managing osteoarthritis: 1) Vitamin K: Vitamin K plays a role in the health of cartilage and bone. It is best for a person with osteoarthritis to ensure they get enough vitamin K in their diet. Sources of vitamin K include:  turnip greens  spinach  kale  broccoli  soybeans 2) Vitamin D: Vitamin D is essential for bone and cartilage health. Studies have shown that it may have a positive effect on muscular strength and balance. Between Sunlight is the primary source of vitamin D. It can also be obtained from dietary sources. 3) Vitamin C: This vitamin is important for collagen synthesis, a key component of cartilage. Citrus fruits, strawberries, and bell peppers are good sources of vitamin C. 56 | P a g e 4) Calcium: Calcium plays a vital role in maintaining the health and integrity of cartilage, which cushions the joints. Adequate calcium intake supports the production and maintenance of healthy cartilage, reducing the risk of cartilage breakdown and the development of osteoarthritis. 5) Herbal treatment: Some herbs may provide anti-inflammatory properties that can help reduce osteoarthritis inflammation. Figure45: Herbal remedies for osteoarthritis.  Green tea: Green tea contains polyphones. These compounds may help lower inflammation and the need for medications.  Ginger: Oral ginger is also noted for reducing pain from osteoarthritis. Taking ginger long-term may even decrease the risk of osteoarthritis-related disability. Ginger and its beneficial role have been known for centuries but the anti- inflammatory properties and its active constituents in osteoarthritis gain attention. Ginger and its certain active constituents possess similar properties with synthetic drugs such as non-steroidal-anti-inflammatory drugs. 57 | P a g e Ginger is involved in inhibition of prostaglandin and leukotrienes by suppressing the stimulation of cyclooxygenase 1, cyclooxygenase 2, and 5-lipooxygenase. Ginger also plays a vital role in inhibition of several genes involved in the initiation of inflammatory response. These include cytokines, chemokines, and enzyme-encoding genes. Ginger possesses anti-inflammatory, antioxidant, and analgesic properties with the lack of gastrointestinal and renal side effects. In short, ginger and its anti-inflammatory and bioactive components have a beneficial effect on osteoarthritis.  Cinnamon bark from C. zeylanicum (verum) Cinnamon bark is one of the oldest traditional medicines used in India for inflammatory and pain-related disorders. It contains a lot of manganese, iron, dietary fiber, and calcium. Cinnamon contains derivatives, such as cinnamaldehyde, cinnamic acid, cinnamate, and numerous other components such as polyphenols and antioxidant, anti-inflammatory, antidiabetic, antimicrobial, anticancer effects. It exhibited an inhibitory effect on the production of nitric oxide, indicating that this substance can potentially be used as an anti- inflammatory agent.  Chamomilla recutita Chamomilla recutita extract restore the increased level of serum calcium level bone mineral content bone weight, bone strength indicating thus usefulness in osteoporosis. May be due to the effect of Chamomile recutita on pituitary gland leading to release of growth hormones, which produce increased weight of femur bone and also increased density of femur bone and may prove estrogen modulator like properties stimulating estrogen receptor and Increased absorption of intestinal calcium and inhibiting osteoclastic activity and enhancing the osteoblastic activity based on these result we concluded that Chamomilla recutita methanolic extract more potent in protecting the animal from osteoporosis than estrogen. Hence, Chamomile recutita is considered as an antiosteoporosis drug in treatment of postmenopausal and senile osteoporosis. 58 | P a g e   Turmeric and curcumin: Curcumin is the active compound in turmeric. It’s part of the ginger family but may help osteoarthritis in different ways.Curcumin may be able to slow disease progression and provide pain relief. Role of Curcumin in the Diseases Management Described as Following:  Anti-oxidant activity Antioxidant activity of herbs shows function in health management via its role in neutralization of free radical species. Finding based on in vitro showed that curcumin is an effective scavenger of ROS and reactive nitrogen species. and in other finding, the antioxidant activity was established by inhibition of controlled initiation of styrene oxidation. The effective anticancer property of curcumin is attributed to its antioxidant effect that control DNA damage and free radical–mediated lipid peroxidation.  Anti–inflammatory activity Nonsteroidal anti-inflammatory drugs are most commonly used drugs worldwide in the treatment of inflammation and are approved for orthopedic conditions and wound. However, such drugs show an adverse side effect and causes gastric ulcer. Curcumin have shown a vital effect in the prevention of inflammatory process via modulation or inhibition of various molecular pathways. A study based on animal model, curcumin, a chief ingredient of turmeric inhibited arachidonic acid metabolism and inflammation in skin epidermis through inhibition of cyclooxygenase-2 (COX-2) and 5-lipooxygenase, pro- inflammatory cytokine expression and suppression of nuclear factor kappa B (NF-κB) activation.  Anti-obesity effect Obesity is a major health problem worldwide, and it is also causes various types of pathogenesis. A study results demonstrated that curcumin improves insulin signaling, glucose disposal, as well as blocks obesity during high-fat diet consumption. 59 | P a g e Curcumin therapy ameliorates the inflammatory consequences of obesity in murine obesity models as compared to control obese animals. In addition, curcumin treated obese animals also showed decreased NF-κB activity in liver tissue. Oral curcumin supplementation was shown to prevent the development of obesity-associated inflammation, insulin resistance, and diabetes. Curcumin at cellular and whole organism levels shows potential health benefits for prevention of obesity and associated metabolic disorders through suppressing angiogenesis in adipose tissue, up-regulating adipocyte energy metabolism.  Immunomodulatory effect Immunomodulatory process plays an important role in the modulations of immune system either by enhance the immune response or suppressing the immune response. Curcumin, active compound of turmeric shows pivotal role in the modulation of immune system. A study was performed to check the effect of curcumin on T, B cells and macrophages and results showed that curcumin imparted immunosuppression by mainly down-regulating the expression of CD28 and CD80 and up-regulating cytotoxic T-lymphocyte antigen 4 (CTLA-4). Experiment results noticed that curcumin, chief ingredients of curcumin inhibits interleukin-2 production, NO generation, and lipopolysachharide- induced NF-κB and augments NK cell cytotoxicity. Numerous previous results have shown that curcumin role as immunomodulatory that shows an important effect in the modulation of activation of T cells, B cells, macrophages, dendritic cells, cell cycle protein, cell-mediated and humoral mediated immunity.  anti-osteoporotic effect of curcumin on osteoblasts CUR plays a role in bone formation by regulating the differentiation of osteoblasts. CUR promotes osteoblast proliferation and upregulates the expression of genes related to bone formation, including alkaline phosphatase (ALP). 60 | P a g e   Nigella sativa seeds (NS): Nigella sativa seeds (NS) has been used traditionally for various illnesses. The most abundant and active component of NS is thymoquinone (TQ). Osteoporotic patients were found to be under oxidative stress as their lipid peroxidation levels were elevated and antioxidant enzymes reduced. Most risk factors for osteoporosis were associated with oxidative stress such as hypertension, diabetes mellitus, and smoking. Exposure to oxidative stress would result in reduction of bone-mineral density. Free radicals have also been shown to activate nuclear factor- kappa B (NFκB) and raised the levels of bone-resorbing cytokines, interleukin-1(IL-1), and interleukin-6 (IL-6). It is interesting to find that the most significant property of TQ, the active compound of NS, is its antioxidative activities. It has been reported that the free radical scavenging capability of TQ is as effective as superoxide dismutase. It is most effective in scavenging superoxides, the reactive oxygen species which plays an important role in the activation of osteoclasts. Since TQ is a potent antioxidant, it is expected that it may be able to protect bone against osteoporosis due to oxidative stress. Inflammation is mediated by two enzymes, cyclooxygenase and lipoxygenase, which generates prostaglandins and leukotrienes from arachidonic acid, respectively. Therefore, both prostaglandins and leukotrienes are the main mediators of inflammation. TQ was believed to exert anti-inflammatory effects by inhibiting the synthesis of prostaglandins and leukotrienes. TQ contributed significantly to the anti-inflammatory activities of NS and has potential to be used as an alternative to nonsteroidal anti- inflammatory drugs. Another possible anti-inflammatory mechanism of TQ might be suppression of nitric oxide production by macrophages. 61 | P a g e Nonnutritional treatment: Osteoarthritis can't be reversed, but treatments can reduce pain and help you move better. Medications: Medications that can help relieve osteoarthritis symptoms, primarily pain, include: Acetaminophen: Acetaminophen has been shown to help some people with osteoarthritis who have mild to moderate pain. Taking more than the recommended dose of acetaminophen can cause liver damage. Nonsteroidal anti-inflammatory drugs (NSAIDs): Over-the-counter nonsteroidal anti-inflammatory drugs (NSAIDs) taken at the recommended doses, typically relieve osteoarthritis pain. Stronger NSAIDs are available by prescription. 62 | P a g e NSAIDs as gels, applied to the skin over the affected joint, have fewer side effects and may relieve pain just as well. Duloxetine (Cymbalta): Normally used as an antidepressant, this medication is also approved to treat chronic pain, including osteoarthritis pain. Physical therapy: A physical therapist can show you exercises to strengthen the muscles around your joint, increase your flexibility and reduce pain. Regular gentle exercise that you do on your own, such as swimming or walking, can be equally effective. Cortisone injections: Injections of a corticosteroid into your joint might relieve pain for a few weeks. Your doctor numbs the area around your joint, then places a needle into the space within your joint and injects medication. The number of cortisone injections you can receive each year is generally limited to three or four, because the medication can worsen joint damage over time. Lubrication injections: Injections of hyaluronic acid might relieve pain by providing some cushioning in your knee. Hyaluronic acid is similar to a component normally found in your joint fluid. Joint replacement: In joint replacement surgery, your surgeon removes your damaged joint surfaces and replaces them with plastic and metal parts. Artificial joints can wear out or come loose and might eventually need to be replaced. 63 | P a g e  Figure46: Knee osteotomy. 9. Rheumatoid Arthritis: Figure47: Rheumatoid arthritis. Rheumatoid Arthritis (RA): is a chronic, inflammatory, systemic autoimmune disease,it is a joint disease that affecting the joints, that initially affects small joints, progressing to larger joints, and eventually the skin, eyes, heart, kidneys, and lungs. 64 | P a g e Often, the bone and cartilage of joints are destroyed, and tendons and ligaments weaken. It occurs when the immune system mistakenly attacks its own tissues. All this damage to the joints causes deformities and bone erosion, usually very painful for a patient. The inflammation associated with rheumatoid arthritis is what can damage other parts of the body as well. While new types of medications have improved treatment options dramatically, severe rheumatoid arthritis can still cause physical disabilities. Symptoms: Figure48: Rheumatoid arthritis symptoms. Rheumatoid arthritis affects different joints in different people, and the symptoms vary from person to person too. They will depend on whether the inflammation is mild or severe and how far the rheumatoid arthritis has progressed. 65 | P a g e Common symptoms of RA include :  Morning stiffness of the affected joint.  Joints that are tender, swollen and warm, and rheumatoid nodules under the skin.  Disrupted sleep.  Depression and mood changes.  Dry eyes and mouth.  fatigue, fever, weight loss. Rheumatoid arthritis is usually first noticed in the small joints in the middle of the fingers and at the base of the fingers and toes, and sometimes in the elbows, ankles, or knees as well. Joints close to the torso, such as the shoulder joints or collarbone, may also become inflamed. The late stages of rheumatoid arthritis can lead to major joint damage. Especially the joints in the hands can become very deformed, weak and stiff. The disease-related inflammation can also affect other things in the body, such as the blood vessels. Because of this, many people who have rheumatoid arthritis also have a somewhat higher risk of cardiovascular (heart and blood vessel) disease. But this risk mainly depends on other factors, like high blood pressure, diabetes, smoking and high cholesterol levels. The tear glands or salivary glands may become inflamed too, reducing the production of tears or saliva. In very rare cases, organs like the lungs, the liver or the kidneys may also be affected. The inflammation typically affects the same joints on both sides of the body. 66 | P a g e  Figure49: Rheumatoid arthritis symptoms. Causes: Figure50: Causes of rheumatoid arthritis. The exact cause of rheumatoid arthritis is unknown. Researchers think it’s caused by a combination of genetics, hormones and environmental factors. Normally, your immune system protects your body from disease. With rheumatoid arthritis, something triggers your immune system to attack your joints. An infection, smoking or physical or emotional stress may be triggering. 67 | P a g e Risk factors: Figure51: Risk factors of rheumatoid arthritis. There are several risk factors for developing rheumatoid arthritis. These include:  Family history: You’re more likely to develop RA if you have a close relative who also has it.  Sex: Women and people designated female at birth are two to three times more likely to develop rheumatoid arthritis.  Age: Rheumatoid arthritis can occur at any age, but it most commonly begins in middle age.  Smoking: Smoking increases a person’s risk of rheumatoid arthritis and makes the disease worse.  Obesity: Your chances of developing RA are higher if you have obesity. 68 | P a g e Complications: Having rheumatoid arthritis can lead to several other conditions that may cause additional symptoms and can sometimes be life threatening. Figure52: Risk factors of rheumatoid arthritis. Possible complications include:  Carpal tunnel syndrome  Inflammation of other areas of the body (such as the lungs, heart and eyes)  An increased risk of heart attack and stroke Making sure that rheumatoid arthritis is well controlled can help to reduce your risk of these complications. 69 | P a g e Rheumatoid arthritis increases your risk of developing:  Osteoporosis: Rheumatoid arthritis itself, along with some medications used for treating rheumatoid arthritis, can increase your risk of osteoporosis.  Dry eyes and mouth: People who have rheumatoid arthritis are much more likely to develop Sjogren's syndrome, a disorder that decreases the amount of moisture in the eyes and mouth.  Infections: Rheumatoid arthritis itself and many of the medications used to combat it can impair the immune system, leading to increased infections. Protect yourself with vaccinations to prevent diseases such as influenza, pneumonia, and COVID-19.  Abnormal body composition: The proportion of fat to lean mass is often higher in people who have rheumatoid arthritis, even in those who have a normal body mass index (BMI).  Heart problems: Rheumatoid arthritis can increase your risk of hardened and blocked arteries, as well as inflammation of the sac that encloses your heart.  Lung disease: People with rheumatoid arthritis have an increased risk of inflammation and scarring of the lung tissues, which can lead to progressive shortness of breath.  Lymphoma: Rheumatoid arthritis increases the risk of lymphoma, a group of blood cancers that develop in the lymph system. 70 | P a g e  Diagnosis: Figure53: Diagnosis of rheumatoid arthritis. Rheumatoid arthritis can be difficult to diagnose in its early stages because the early signs and symptoms mimic those of many other diseases. There is no one blood test or physical finding to confirm the diagnosis. During the physical exam, your doctor will check your joints for swelling, redness and warmth. He or she may also check your reflexes and muscle strength.  Blood tests: The blood tests look for inflammation and blood proteins (antibodies) that are signs of rheumatoid arthritis. These may include:  Erythrocytesedimentation rate (ESR) or “sed rate” confirms inflammation in your joints.  C-reactive protein (CRP).  Rheumatoid factor (RF): About 80% of people with RA test positive for rheumatoid factor (RF).  Cyclic citrullinated peptides (CCP):About 60% to 70% of people living with rheumatoid arthritis have antibodies to cyclic citrullinated peptides (CCP) (proteins). 71 | P a g e   Diagnostic imaging tests: Your rheumatologist may order imaging tests to look for signs that your joints are wearing away. Rheumatoid arthritis can cause the ends of the bones within your joints to wear down. The imaging tests may include:  X-rays.  Ultrasounds.  Magnetic resonance imaging (MRI) scans. Treatment of rheumatoid arthritis: There is no cure for rheumatoid arthritis. But clinical studies indicate that remission of symptoms is more likely when treatment begins early with medications known as disease-modifying antirheumatic drugs (DMARDs).  Medications: The types of medications recommended by doctor will depend on the severity of symptoms and how long patient had rheumatoid arthritis. Medications are an essential part of treatment for most people with RA. Your treatment plan will likely include some of the following: NSAIDs: In low doses, nonsteroidal anti-inflammatory drugs (NSAIDs) can be effective at relieving pain. At higher, prescription doses they can also help control inflammation. DMARDs: Conventional synthetic disease-modifying antirheumatic drugs (DMARDs), primarily methotrexate, may be the first medication you are prescribed to slow disease activity in RA. Biologics: Biologics are genetically engineered proteins that target specific parts of the immune system that fuel inflammation. They are typically used if your disease doesn’t respond to conventional DMARDs. 72 | P a g e Analgesics: The pain reliever acetaminophen can ease pain if you aren’t able to take NSAIDs. It won’t reduce inflammation. Corticosteroids: Similar to the cortisone your body makes naturally, corticosteroid medications are potent anti-inflammatories. Your doctor may prescribe oral corticosteroids to reduce inflammation that can damage joints and organs.  Nutritional treatment: research hasdiscovered several links between arthritis and diet, so it’s still worth thinking aboutwhat you eat. The two most importantthings to think about are: Your weight: if you’re overweight, losing some weight will reduce the strain on your joints, so you may find you don’t need to take painkillers quite so often. Whether your diet gives you the vitamins and minerals you need, a good diet can help to protect you against some possible side- effects of drugs and against heart disease. (1) Cut down on fat: There are four kinds of fats in foods: A. Saturatedfats are the most important kind of fat to reduce since they can increase inflammation and pain in the body. They come mostly from animals and are found in: full-fat dairy products processed foods like cakes, biscuits and pastry chips (if fried in animal fat) some vegetable oils, such as palm oil and coconut oil. 73 | P a g e B. Monounsaturated fats: Are neutral or even useful fats in that they don’t make inflammation worse. But they contain just as many calories as saturated fats, so limiting them is still important if you’re trying to lose weight. They can be found in olive and rapeseed oil. C. Trans fats: Are the worst kind of fat. They’re made from oil chemically processed to make it solid and increase its shelf life but have mostly been removed from processed food in recent years. They increase cholesterol and are damaging to circulation and perhaps your joints. They’re listed on food labels as ‘hydrogenated oil’. D. Polyunsaturated fats: Omega-6 polyunsaturated fatty acids can increase inflammation in the body, so you should aim to eat fewer softer fats and oils from corn or sunflower sources, which are high in omega-6. Omega-3 polyunsaturated fatty acids are useful in the diet and are found in rapeseed oil, walnuts, free-range eggs (depending on the chicken feed), oily fish and fish oil supplements. 74 | P a g e (2) Cut down on sugar: Sugar contains only calories and has no other food value (so-called ‘empty calories’), so you can cut down on it without losing any nutrients. Try to get used to food being less sweet by not adding sugar or sweeteners to hot drinks. (3) Eat more fruit and vegetables: This is to make sure your body gets the important nutrients – particularly vitamins, minerals and antioxidants – that it needs to stay in good health and to protect it during the stress of disease. Brightly colored vegetables and fruits are rich in antioxidants, as are leafy green vegetables. It’s been suggested that antioxidants may help to protect the joints by mopping up some of the chemicals, known as free radicals, which may cause inflammation. Choose more brightly colored vegetables or salad to help fill your plate but lower your calorie intake. (4) Exercise regularly: Not only does exercise burn calories that would otherwise end up as fat, but it also increases your strength and suppleness. Of course, arthritis can make exercise difficult and painful, so it’s important to find something you can manage and enjoy so that you do it regularly. Swimming is particularly good exercise if you have arthritis because being in water takes the weight off your joints and exercises just about all muscle groups and joints in the body. Cycling or walking are also good, and many people find Pilates and yoga are helpful as they help to stretch and strengthen the muscles. 75 | P a g e Nutrients have some benefits for managing rheumatoid arthritis: 1) Calcium: Calcium is an essential mineral that maintains strong bones and teeth; regulates muscle contractions; transmits nerve impulses; and helps release essential hormones and enzymes. It also helps prevent osteoporosis (loss of bone density) and fractures, which are higher risks among people with rheumatoid arthritis (RA) and those taking corticosteroids. 2) Iron: Iron helps prevent anemia by helping produce hemoglobin, the protein in red blood cells that carries oxygen throughout the body. Anemia – low red blood cell levels – is common in people with rheumatoid arthritis and may result from inflammation, which inhibits iron absorption, or from digestive tract bleeding caused by medications. Studies show that people who have both RA and anemia have more severe disease and joint damage than people who don’t have anemia. 3) Selenium: Selenium is an antioxidant and helps prevent damage from free-radicals, or toxic by-products of natural bodily processes. It is also essential for proper functioning of the thyroid gland and immune system. Selenium may help prevent rheumatoid arthritis, but it has not been shown to relieve pain or stiffness in people with established disease. 76 | P a g e 4) Zinc: Zinc is involved in wound healing, cell reproduction and tissue growth, sexual maturation, and taste and smell. It is also associated with more than 100 enzymatic reactions in the body. 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