Human skeleton compromising of 213 of total bones, separating the sesamoid bones (1). The human skeleton system classified into; appendicular skeleton, axial skeleton, auditory ossicles. The appendicular skeleton contains 126 bones, the axial skeleton has 74 bones, and the auditory ossicles compromising 6 bones. Each bone continuously experience modeling during lifetime, this remodeling aims at helping the bone to suit biomechanical force changing, as well as remodeling to take out old bones, there are a micro-damaged happen to the bones this remodeling function help in replacing damaged bones by a new bones that have long lifespan, and functioning well (2).
Bones categorized into four groups, long bones, short bones, flat bones, and irregular bones. Long bones contain many bones that seems to give the body its shape these bones are the clavicles, the two humeri, the two radii, the two ulnae, metacarpals, the two femurs, the two tibiae, the two fibulae, metatarsals, and phalanges. Short bones contain the carpal and tarsal bones, patellae, and sesamoid bones. Flat bones compromised the skull, mandible, scapulae, sternum, and ribs. Irregular bones that have many surfaces include the vertebral bones, sacrum, coccyx, and hyoid bone. Membranous bone formation forming the flat bones, in contrast, the long bones formed by a mixing of endochondral and membranous bone formation (3).
The skeleton has many different functions. The skeleton bones providing support for the rest of the body, giving movement and locomotion by providing a bar like for the muscles, protecting the entire bodily organs, storing the mineral to aids in the bodily homeostasis also it has big role in the acid-base balance, serve as a source of growth factors and cytokines, and it’s the main source of hematopoiesis inside the bones (2).
In analyzing the types of bones. Long bones are composed of a long part which is the diaphysis, the cone-shaped metaphyses are situated underneath the growth plates, and the rounded epiphyses situated on top of the growth plates. The diaphysis is composed of dense cortical bone, in contrast to the metaphysis and epiphysis are formed by a trabecular meshwork of bone surrounded by a relatively light shell of dense cortical bone (3).
The human skeleton is composed of cortical bones that have a percentage of 80% and the remaining 20 percentage is for the trabecular bone overall (4). Different bones and skeletal have different ratios of cortical to trabecular bone. The vertebral bones are containing a cortical and trabecular bone in a ratio of 25:75. Whereas the femoral head has a ratio of 50:50 and the radial diaphysis has a ratio of 95:5 (3).
Cortical bone is thick and solid and enclosing the bone marrow, whereas trabecular meshwork bone is containing a honeycomb-like network of trabecular plates and rods interspersed in the bone marrow compartment. Both cortical and trabecular bone are a collection of osteons (3).
The cortical osteons are called Haversian systems. Haversian systems define as a fundamental functional unit of the compact bone, cylindrical structural shape, it’s height is 400 mm long and 200 mm wide at their base, and form a branching network within the compact bone (4). The Haversian systems wall are formed by concentric lamellae. Compact bones have less metabolic function than trabecular meshwork. There are approximately 21 x 106 cortical osteons in healthy human skeleton system, with a total Haversian remodeling parts of nearly 3.5 m2 (3). Cortical remodeling causing cortical porosity and as result, there will be a decrease in cortical bone mass (3). Healthy aging adults normally experience thinning of the cortex and increased cortical porosity (3).
Cortical bone and Cancellous bone are normally formed in by a collagen fibrils (4). Lamellar bone can be seen throughout microscopic examination with polarized light, during which the lamellar pattern is present due to the effect of birefringence (3). The mechanism of osteoblasts which lay down collagen fibrils in a fibrous pattern is not known, but fibrous bone has significant strength as a result of the different orientations of collagen fibrils, like the plywood (3). Woven bone have absent of lamellar pattern, the collagen in the woven bone is in a disorganized manner, as a result, the woven bone is weaker than the lamellar bone (3). Woven bone is normally produced during formation of primary bone (3).
The periosteum is a fibrous connective tissue sheath that covering the outer surface of the cortical bone, excluding the bone with joints where is lined by articular cartilage, which contains blood vessels, nerve fibers, and osteoblasts and osteoclasts (3). The periosteum is strongly attached to the outer surface of the cortical bone by thick collagenous fibers, called Sharpey’s fibers, which extend into underlying bone tissue. (3) The endosteum is a membranous structure enclose the inner surface of cortical bone, trabecular bone, and the blood vessel canals (Volkman’s canals) present in bone. The endosteum is in contact with the bone marrow space, trabecular bone, and blood vessel canals and contains blood vessels, osteoblasts, and osteoclasts. (3)
Bone Growth, Modeling, and Remodeling
Bone has the capacity to grow longitudinally and radially, modeling, and remodeling within the life (3). Childhood and adolescent age group have the most longitudinal and radial growth of the bone (3). The growth plate has the role of the longitudinal growth, where there is a proliferation specifically in the epiphyseal and metaphyseal parts of long bones, before subsequently undergoing mineralization to fuse and forming a primary new bone. (3)
Bones modeling defined as the process in which a specific change occurs in the bone in its shape and its reaction to the physiological influences or mechanical power, leading to progressive adjustment of the human skeleton to the impact that it encounters (3). Bones may accompany changes in their shape due to the mechanical forces that causing it to widen or change axis, and by modeling removal or addition of bone take place to make appropriate surfaces by the independent behavior of anabolic and catabolic cells the osteoblasts and osteoclasts in response to biomechanical forces (3). Bones as a result of increased age and in response to periosteal apposition of new bone and consequential resorption of old bone undergoes widening (3). By observing the long bones Wolff’s law describes that change in the shape to adapt to the stressors (3). During bone modeling, bones are formed and reabsorbed and these two mechanisms are not happening equally (3). In adults, bones are less frequently modeling than remodeling (5). There are adrenal factors has a role in increasing the modeling like in hypoparathyroidism (6), nephrological causes like renal osteodystrophy (7), and there are different types of treatments that contain anabolic agents (8). Bone remodeling defined as the process in which a new bone take a place of old bone to conserve the strength of the bone, and mineral homeostasis of the bones (3). Remodeling has a controlled removal of old bone, and replacement of these removed old bones by a newly synthesized matrix, and following a mineralization of the formed matrix to form new healthy bone (3). The remodeling has two discrete roles one by resorbing the old bone and the second one is forming a new bone to prevent accumulation of bones (3). Remodeling starts before birth and proceeds until death (3). The bone remodeling unit is composed of a strong paired osteoclasts and osteoblasts that take resorption of old bone and formation of new bone (3). Bone remodeling increased and decreased in such situations, in peri-menopausal and early postmenopausal women the bone remodeling increased and then it slows and decreased with aging, but continues at a quick rate than in premenopausal women. Men Bone remodeling is thought to increase mildly in aging. (3)
The remodeling cycle is composed of certain sequential phases (3). Activation phase resorption phase, reversal phase, formation phase, and the activation precedes the reabsorption and reabsorption precedes the reversal phase and the reversal phase proceeds the formation phase (3). Remodeling are not in organized manner it may develop randomly but also are targeted to areas that need repair (9,10).
Activation phase involves recruitment and activation of a specific cell which is mononuclear monocyte-macrophage osteoclast precursors from the blood stream (11), increasing of the endosteum that contains the lining cells of the bone surface, and the mononuclear cells fused to form multi-nucleated preosteoclasts. Preosteoclasts bind to bone matrix via interactions between integrin receptors in their cell membranes and RGD (arginine, glycine, and asparagine)-containing peptides in matrix proteins, to form annular sealing areas around bone-resorbing compartments beneath the formed multi-nucleated osteoclasts (3).
Osteoclast-mediated bone resorption takes only around 2 to 4 weeks during each remodeling cycle. Osteoclast undergoes a a complex phases in its formation, activation, and resorption and is controlled by the ratio of receptor activator of NF- B ligand (RANKL) to osteoprotegerin (OPG; Figure 1), also interleukins has an important role in this regulation, such as IL-1 and IL-6, colony-stimulating factor (CSF), parathyroid hormone, 1,25-dihydroxyvitamin D, and calcitonin (12,13). Resorbing osteoclasts produce hydrogen ions via H-ATPase proton pumps and chloride channels in their cell membranes into the resorbing compartment to lower the pH within the bone-resorbing compartment to as low as 4.5, which aids in mobilizing bone mineral (14). Resorbing osteoclasts produce tartrate-resistant acid phosphatase, cathepsin K, matrix metalloproteinase 9, and gelatinase from cytoplasmic lysosomes (15) to breakdown the organic matrix, resulting in formation of saucer-shaped Howship’s lacunae on the surface of trabecular bone (Figure 2) and Haversian canals in compact bone (3). The resorption phase is ended with mononuclear cells after the multinucleated osteoclasts undergo a programmed damage cells “apoptosis” (16,17).