A silent skeletal condition called osteoporosis is characterized by weakening bones, which puts people at higher risk of breaking [1]. One in two women and one in five men over fifty have this metabolic bone disease, which is the most common in the West[1]. Osteoporosis was previously divided into two categories: primary osteoporosis, which results from age- and postmenopausal-related bone loss, and secondary osteoporosis, which is accelerated bone loss brought on by an underlying disease. Secondary osteoporosis occurs in up to 40% of cases in women and 60% of cases in men[2]. The illness is complicated, and there are a number of risk factors that have been shown to raise a person's chance of getting it[3].

Numerous risk factors are associated with osteoporotic fractures, including low peak bone mass, hormonal factors, drug use (e.g., glucocorticoids), smoking, low physical activity, low intake of calcium and vitamin D, race, small body size, and a personal or family history of fractures[4].Because fragility fractures, a result of osteoporosis, cause excess mortality, morbidity, chronic pain, hospital admissions, and financial costs [5,6] osteoporosis is a major health burden [7,8]. According to [9], They are responsible for 80% of all fractures in women over 50 going through menopause. According to [10[  there is a markedly elevated risk of death following hip or vertebral fractures in patients. According to [11] Approximately 24% of elderly patients with hip fractures die within a year. Deformities like kyphosis, loss of height, and protrusion of the abdomen are linked to vertebral fractures. If a person loses their independence and needs long-term care in a nursing home or in the community, this can have a significant financial impact [12]

Anatomy and Physiology of skeletal system

Human skeleton:

The Greek word for dried is where the word "skeleton" originates. The skeleton is thought of as being dry and lifeless, but in reality, it is made up of dynamic, living tissue that can grow, adapt to stress, and heal itself after damage.  The bones, joints, and the ligaments and cartilage that surround the joints make up the skeletal system [13]

According to [14] the skeletal system is separated into:.

1. The axial skeleton

 which is made up of the thoracic cage, the vertebral column, and 80 bones in the skull. 

2.The appendicular skeleton

is composed of 126 bones, which make up the limbs' upper and lower segments as well as the girdles connecting them to the axial skeleton. The skeletal system is involved in the following activities: sitting, standing, walking, and picking up a pencil. Thus, among the purposes of the skeletal system and bones are: 

1.The internal The bones protect the organs. The rib cage protects the heart and lungs, the vertebrae shield the spinal cord, and the skull shields the brain.

2. Assistance. In order to support the body's soft tissue and preserve its shape, bones offer a stiff framework. 

Bone: 

A unique type of connective tissue called bone is made up of a hard organic matrix that is significantly reinforced by calcium salt deposits. The weight of an average compact bone is approximately 70% salts and 30% matrix. According to [15] the percentage of matrix in newly formed bone may be significantly higher than that of salts.

Organic Matrix of Bone:

Ninety to ninety-five percent of the organic matrix in bone is made up of collagen fibers; the remaining material is a homogenous gelatinous medium known as ground substance. The strong tensile strength of bone is attributed to the collagen fibers, which mainly extend along the lines of tensional force. Extracellular fluid and proteoglycans, particularly chondroitin sulfate and hyaluronic acid, make up the ground substance. Although they do aid in regulating the deposition of calcium salts, it is unknown exactly what each of these does [15]

Bone Salts:

The main ingredients of the crystalline salts found in the organic matrix of bone are phosphate and calcium. Ca10(PO4)6(OH)2 is the formula for hydroxyapatite, the main crystalline salt [15]

 Bone is a highly intricate tissue that balances its mass and structure to fulfill two vital but conflicting functions: structural and metabolic. First of all, the skeleton gives the body an intricate framework that protects key organs and makes movement easier. Second, it acts as a mineral storehouse, holding 85% of the phosphorus and 99% of the total calcium in the body. In the catabolic and anabolic regulation of skeletal tissues, this dual responsibility generates competing stimuli and conflicting goals [16]

 Classification of the bones according to their shape:

Asymmetrical, flat, short, and long bones are the four different types of bones. The clavicles, humeri, radii, ulnae, metacarpals, femurs, tibiae, fibulae, metatarsals, and phalanges are examples of long bones. Short bones include the tarsal, carpal, patellae, and sesamoid bones. Among the flat bones are the ribs, scapulae, mandible, and sternum. Uneven bones include the sacrum, coccyx, hyoid bone, and vertebrae [17] 

Bone Structure:

The remaining 20% of bone in the body is made up of trabecular or spongy bones inside the cortical bone, while the remaining 80% of bone in the body is composed of compact or cortical bone, which makes up the outer layer of most bones. Both types of bone can be found in both children and adults [18]

Types of bone cells:

The bone is composed of three primary cell types [19].

osteoclast : One type of multinucleated cells with hemopoietic origin . They facilitate the reabsorption of calcium and phosphate into the bloodstream as well as the disintegration of bone.

2. Osteoblast: Mononuclear cells of mesenchymal origin that secrete a bone-specific matrix to aid in the formation of new bone.

3. Osteocyte: A developed bone cell that comes from an osteoblast. The osteoblasts in bone transform into osteocytes once they are encircled by matrix. It is assumed to be in charge of detecting and reacting to the skeleton's mechanical loading.

Peak bone mass (PBM): 

The maximum skeletal mass attained during growth following the fusion of the long bone epiphyses is known as bone mass. According to the majority of research, PBM is attained between the late 20s and the third decade of life [20]. Around the age of 20, the proximal femur reaches PBM, and six to ten years later, the remaining skeleton reaches PBM [21]. When PBM starts to decline is a topic of debate among researchers; some point to the third decade of life, while others suggest that it happens around the ages of 50 and 60 for men and women, respectively. Nonetheless, there is mounting proof that PBM plays a significant role in maintaining bone strength throughout life [20]. Studies that are cross-sectional and longitudinal reveal that although girls' volumetric bone density is higher, boys' mineral content is higher. On the other hand, boys' bones are larger. Volumetric density decreases in both axial and appendicular locations during puberty [22]. Genetics, exercise, calcium intake, hormones, and other environmental factors like smoking and medication can all have an impact on PBM. Certain studies indicate that PBM may be inherited [23]

Bone-remodeling: 

The majority of bone growth occurs in connection with puberty. During this period, more than 60% of the bone mass is synthesized. Following this time, the overall mass of bones is determined by the ratio of bone formation to bone breakdown. Osteoporosis can occur when there is more resorption of bone than new tissue growth in the skeleton over time. The trabecular tissue, which has a larger surface area and a lower bone density than the compact cortical tissue, is where bone loss begins. To preserve this homeostasis, both systemic and local regulatory systems are crucial [24]

The skeleton is constantly being modeled and altered during the course of life. In response to mechanical loading, modeling causes the formation of new bone mass and modifies the shape of bones without prior resorption. In remodeling, the morphology of the bone is preserved despite ongoing resorption and formation of new bone. This process is balanced in young individuals, meaning that all the bone that is resorbed during bone formation is replaced. However, as one ages, less bone tissue is created in relation to the mass that is reabsorbed, leading to an accumulation of bone loss. As women enter menopause, their loss of bone mass quickens. This is due to the absence of estrogen, which typically prevents bone remodeling and speeds up bone loss. This implies that there will be a rise in the frequency of remodeling cycles. [25]

Age and mechanical stress cause microfractures, which are repaired during the remodeling process. Calcium homeostasis also requires bone remodeling [24]

The large site is the initial point of attraction for peripheral blood osteoclast precursors, probably because the microdamaged area releases chemotactic factors locally. When bone marrow stromal cells express Receptor Activator of Nuclear Factor Kappa-light-chain-enhancer of activated B cells Ligand (RANKL), osteoclast precursors diverge into mature osteoclasts. Expressed on osteoclasts and precursors, the RANK receptor is activated by RANKL. Osteoprotegerin (OPG), a RANKL decoy receptor, blocks this. Mature osteoclasts surround the surface of the bone with a tight sealing zone that allows them to release proteolytic enzymes like cathepsin K and hydrochloric acid into the area underneath. Collagen is broken down by cathepsin K, while the acid dissolves the mineral. Osteoclasts undergo programmed cell death upon completion of resorption, and osteoblast precursors are drawn to the resorption site to initiate the formation of new bone. These develop into adult osteoblasts, which fill the resorption lacuna with new bone matrix until the hole is completely filled. Certain osteoblasts give rise to osteocytes after becoming stuck in the bone matrix. These function as biomechanical sensors and generate a number of molecules that affect phosphate metabolism and bone remodeling. Osteoblasts express lipoprotein-related receptor protein 5 (LRP5), which wnt proteins bind to and activate, thereby stimulating the formation of new bone. Sclerozin is one of the molecules that inhibits this process. An osteoid is a newly formed bone matrix that is initially uncalcified before mineralizing to form mature bone. Because it breaks down the inhibitor of mineralization pyrophosphate, alkaline phosphatase (ALP), which is generated by osteoblasts, is essential to the mineralization of bone. Circulating hormones like parathyroid hormone and estrogen, as well as locally produced substances like cytokines, control the remodeling of bones [19]

Systemic regulation of bone remodeling: 

Numerous systemic hormones influence the local expression of sclerosin, OPG, RANKL, and molecules in the Wnt/LRP5 pathway to influence bone turnover [19]

1.Vitamin D: 

A 10-minute sun exposure results in the body producing enough vitamin D3 from 7-dehydrocholesterol to support normal calcium homeostasis. In the liver, vitamin D3 is first hydroxylated to produce 25-hydroxy vitamin D; the kidney then hydroxylates this form of vitamin D. The active metabolite 1,25-dihydroxy vitamin D, also known as calcitriol, increases intestinal calcium absorption, providing the mineral required to build bone. Vitamin D inaction, as in vitamin D-resistant rickets brought on by vitamin D receptor mutations or in pseudovitamin D rickets caused by aberration of 1α-hydroxylase, results in hypocalcemia and severe rachitic bone disease [26] A deficiency in vitamin D or abnormalities in its metabolism are linked to decreased intestinal calcium absorption, increased secretion of parathyroid hormone (PTH), and increased bone resorption [27]. A sufficient amount of 1,25-dihydroxyvitamin D is needed to provide calcium for the development of bones[26]. It is commonly known that vitamin D and bone health are related.

2.PTH:

One of the key players in controlling the blood's levels of phosphate and calcium is PTH. PTH keeps serum phosphate and calcium concentrations above and below the normal physiological range, respectively. Ionized calcium's negative feedback level controls PTH secretion. PTH preserve calcium levels in the bloodstream by starting the release of calcium from the bone, maintaining calcium through the kidneys and enhancing calcium absorption in the intestines by activating vitamin D [28]. PTH causes bone resorption and osteoclast activity, which releases calcium from the bones. PTH membrane receptors on osteoblasts cause significant morphologic and metabolic alterations in these cells, which in turn cause changes in osteoclasts. PTH has distal effects through mobilizing cytosolic calcium ions and raising intracellular cyclic adenosine monophosphate (cAMP) levels. Osteoclasts are activated within minutes of osteoblast exposure to PTH, despite the possibility that these cells lack PTH receptors [26].

3.Sex steroid hormone: 

The quick decrease in skeletal mass following menopause highlights the critical control that sex steroids have over the metabolism of bone cells. Osteoblasts' expression of androgen and estrogen receptors indicates that bone cells are the intended recipients of these sex steroids. Increased osteoblast proliferation and a diminished osteoblast response to PTH are two effects of elevated estrogen levels. Furthermore, estrogens promote the expression of the osteoblastic collagen gene, insulin-like growth factor II synthesis, and they may even directly control the synthesis of the osteoclastic lysosomal enzymes [26]. Furthermore, it has been established that interleukin-6 (IL-6) is only effective in stimulating osteoclastic bone resorption when an individual is estrogen-deficient. It has been demonstrated that estrogen affects the RANKL-OPG equilibrium. While RANKL expression on osteoclast precursors remains unaltered, a lack of estrogen blunts the intracellular signaling triggered by RANKL binding, thereby reducing osteoclastogenesis. Furthermore, estrogen has been demonstrated to raise osteoprotegerin levels in the bloodstream, which reduces the impact of RANKL by blocking its ability to reach prospective osteoclasts [26]

4.Calcitonin:

The hormone calcitonin decreases blood calcium levels, whereas PTH raises them. The thyroid gland's parafollicular, or C, cells secrete calcitonin, also known as thyrocalcitonin. Calcitonin inhibits the release of calcium from bone into the extracellular fluid. It is assumed to function by suppressing osteoclast activity and causing calcium to be stored in bone cells. The decrease in serum calcium levels that occurs after pharmacologic doses of calcitonin are administered may be related to the fact that calcitonin also decreases the renal tubular reabsorption of calcium and phosphate [28]

Epidemiology of osteoporosis 

One in three postmenopausal women and one in five men over 65 are afflicted by the illness [29]. Low trauma or osteoporosis fractures are common; At age 50, the estimated lifetime risk of any fracture is 20% for men and more than 50% for women. The hip, wrist, and vertebrae are the most common sites for osteoporotic fractures; in fact, osteoporosis-related vertebral fractures make up almost half of all fracture presentations [30]. 200 million people worldwide suffer from osteoporosis, the most common metabolic bone disease[31] 28 million Americans either have osteoporosis or are at risk for developing it. Over 1.5 million osteoporotic fractures occur each year in the United States alone. Of them, there are 250,000 hip fractures, 500,000 wrist fractures, and 500,000 vertebral fractures. In the first year following a hip fracture, men have a mortality rate of 30% and women a rate of 12% to 24%. Furthermore, because they are unable to walk independently, half of the patients in nursing homes need long-term care [32]. Over 70 000 hip fracture cases and an estimated 260 000 osteoporotic fractures among women 50 years of age and older occur in the United Kingdom [33]

Diet, alcohol consumption, and level of activity are all considered modifiable risk factors [36]

2.4.2.1. Non modifiable risk factors:

1. Aging:

The oldest population in the world is growing at the fastest rate, and as people age, their risk of fractures increases and their bone mass declines[37]. Patients 65 years of age and above make up roughly 70% of all osteoporosis-related fractures[38]

2. Sex:

Women are more affected than men; four out of every five individuals with osteoporosis are female. Approximately 8 million (80%) of the 10 million Americans who have osteoporosis are women, and over 2 million (20%) are men. [39]. Of the 34 million Americans with low bone mass, about 22 million (65%) are women and 12 million (35%), are men [39] 

3. Menopause:

Rapid bone loss is generally linked to menopause, starting two to three years before and lasting up to four years after menopause. A notable drop in BMD is one way that this bone loss presents itself [40]

4. Race: 

While Asians appear to be equally susceptible to osteoporosis and osteoporotic fractures, Caucasian people are generally thought to be at a higher risk for developing osteoporosis [34,35]

5. Low BMI:

Low BMI and low weight are also associated with an increased risk of bone fractures [41]

6. Family history of fracture:

When evaluating a patient's risk, a family history of fragility fractures, especially hip fractures, can be helpful (WHO, 2003). The likelihood of hip fractures in women is roughly doubled compared to those without a family history of the condition[42]

. History of fragility fractures (low trauma fractures):7

According to [43], a fragility fracture is one that occurs at a site that is usually linked to low bone density, such as the hip, pelvis, wrist, or spine.

Risk factors for osteoporosis and fragility fractures in our population include smoking, low education, living in urban areas, women's gender, low body mass index, menopause, length of menopause, high parity number, advanced age, and inadequate education. Furthermore, individuals with hyperthyroidism, chronic rheumatological inflammatory diseases with elevated WBC and ESR levels, and those undergoing chemotherapy had extremely high incidences of osteoporosis. All of which could worsen the prognosis brought on by osteoporosis. Thus, it is important to treat this disorder seriously and to do so through a structured health services program at a clinic with specialized training. 

The authors declare that they have no conflict of interest

No funding sources

The study was approved by the university of Karbala, Karbala, Iraq

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