IntroductionIntroductionThe Skeleton 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 organised manner it may develop randomly but also are targeted to areas that require repair (9,10). Activation involves recruitment and activation of mononuclear monocyte-macrophage osteoclast precursors from the circulation (11), lifting of the endosteum that contains the lining cells off the bone surface, and fusion of multiple mononuclear cells to form multinucleated preosteoclasts.
Preosteoclasts bind to bone matrix via interactions between integrin receptors in their cell membranes and RGD (arginine, glycine, and asparag- ine)-containing peptides in matrix proteins, to form annular sealing zones around bone-resorbing compartments beneath multinucleated osteoclasts. Osteoclast-mediated bone resorption takes only approxi- mately 2 to 4 wk during each remodeling cycle. Osteoclast formation, activation, and resorption are regulated by the ratio of receptor activator of NF- B ligand (RANKL) to osteoprote- gerin (OPG; Figure 1), IL-1 and IL-6, colony-stimulating factor (CSF), parathyroid hormone, 1,25-dihydroxyvitamin D, and calcitonin (11,12). Resorbing osteoclasts secrete 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 helps mobilize bone mineral (13). Resorbing osteoclasts secrete tartrate-resistant acid phosphatase, cathepsin K, matrix metalloproteinase 9, and gelatinase from cytoplasmic lyso- somes (14) to digest the organic matrix, resulting in formation of saucer-shaped Howship’s lacunae on the surface of trabec- ular bone (Figure 2) and Haversian canals in cortical bone.
The resorption phase is completed by mononuclear cells after the multinucleated osteoclasts undergo apoptosis (15,16). During the reversal phase, bone resorption transitions to bone formation. At the completion of bone resorption, resorp- tion cavities contain a variety of mononuclear cells, including monocytes, osteocytes released from bone matrix, and preos- teoblasts recruited to begin new bone formation. The coupling signals linking the end of bone resorption to the beginning of bone formation are as yet unknown. Proposed coupling signal candidates include bone matrix—derived factors such as TGF- , IGF-1, IGF-2, bone morphogenetic proteins, PDGF, or fibroblast growth factor (17–19).
TGF- concentration in bone matrix correlates with histomorphometric indices of bone turn- over and with serum osteocalcin and bone-specific alkaline phosphatase. TGF- released from bone matrix decreases oste- oclast resorption by inhibiting RANKL production by osteo- blasts. The reversal phase has also been proposed to be medi- ated by the strain gradient in the lacunae (20,21). As osteoclasts resorb cortical bone in a cutting cone, strain is reduced in front and increased behind, and in Howship’s lacunae, strain is highest at the base and less in surrounding bone at the edges of the lacunae.
The strain gradient may lead to sequential activa- tion of osteoclasts and osteoblasts, with osteoclasts activated by reduced strain and osteoblasts by increased strain. The oste- oclast itself has also been proposed to play a role during rever- sal (22). Bone formation takes approximately 4 to 6 mo to complete. Osteoblasts synthesize new collagenous organic matrix (Figure 3) and regulate mineralization of matrix by releasing small, membrane-bound matrix vesicles that concentrate calcium and phosphate and enzymatically destroy mineralization inhibitors such as pyrophosphate or proteoglycans (23).
Osteoblasts sur- rounded by and buried within matrix become osteocytes with an extensive canalicular network connecting them to bone sur- face lining cells, osteoblasts, and other osteocytes, maintained by gap junctions between the cytoplasmic processes extending from the osteocytes (24). The osteocyte network within bone serves as a functional syncytium. At the completion of bone formation, approximately 50 to 70% of osteoblasts undergo apoptosis, with the balance becoming osteocytes or bone-lining cells. Bone-lining cells may regulate influx and efflux of mineral ions into and out of bone extracellular fluid, thereby serving as a blood-bone barrier, but retain the ability to redifferentiate into osteoblasts upon exposure to parathyroid hormone or mechan- ical forces (25). Bone-lining cells within the endosteum lift off he surface of bone before bone resorption to form discrete bone remodeling compartments with a specialized microenviron- ment (26).
In patients with multiple myeloma, lining cells may be induced to express tartrate-resistant acid phosphatase and other classical osteoclast markers. The end result of each bone remodeling cycle is production of a new osteon. The remodeling process is essentially the same in cortical and trabecular bone, with bone remodeling units in trabecular bone equivalent to cortical bone remodeling units divided in half longitudinally (27). Bone balance is the differ- ence between the old bone resorbed and new bone formed. Periosteal bone balance is mildly positive, whereas endosteal and trabecular bone balances are mildly negative, leading to cortical and trabecular thinning with aging. These relative changes occur with endosteal resorption outstripping perios- teal formation.
The main recognized functions of bone remodeling include preservation of bone mechanical strength by replacing older, microdamaged bone with newer, healthier bone and calcium and phosphate homeostasis. The relatively low adult cortical bone turnover rate of 2 to 3%/yr is adequate to maintain biomechanical strength of bone. The rate of trabecular bone turnover is higher, more than required for maintenance of mechanical strength, indicating that trabecular bone turnover is more important for mineral metabolism. Increased demand for calcium or phosphorus may require increased bone remodeling units, but, in many cases, this demand may be met by increased activity of existing osteoclasts. Increased demand for skeletal calcium and phosphorus is met partially by osteoclastic resorp- tion and partly by nonosteoclastic calcium influx and efflux.
Ongoing bone remodeling activity ensures a continuous supply of newly formed bone that has relatively low mineral content and is able to exchange ions more easily with the extracellular fluid. Bone remodeling units seem to be mostly randomly distributed throughout the skeleton but may be triggered by microcrack formation or osteocyte apoptosis. The bone remod- eling space represents the sum of all of the active bone remod- eling units in the skeleton at a given time.