The skeleton comprises cartilage and bone and is a support for
the insertion of muscles and tendons enabling movement, a shield
for soft tissue organs, a site for storage of bone marrow, and a reserve
pool of calcium, phosphate, and other ions. There are flat (eg,
cranium, scapula, pelvis) and long (eg, humerus, femur, phalanges)
bones. The outer surface of bone is enclosed in periosteum (a fibrous
network of osteoblasts that synthesizes peripheral compact bone);
endosteum lines its inner surface. The central portion of long bones
is a hollow shaft of dense cortical bone termed the diaphysis;
at both ends of many long bones are the metaphysis (composed of
cortical and cancellous or trabecular bone), cartilaginous growth
plate, and epiphysis.
Osteoblasts are bone-forming cells derived from
stromal mesenchymal stem cells that secrete collagen types I and
III and noncollagenous proteins that together form osteoid or bone
matrix into which calcium and phosphate are deposited. Osteoclasts are
bone resorbing cells that are derived from hematopoietic precursor
cells. Bone modeling is the process by which the shape and size
of a bone is determined and occurs only during intrauterine development and
postnatal growth. Bone remodeling is a process in which formed bone
is replaced by new bone and takes place throughout life.
Eighty percent of the skeleton is composed of cortical bone present
in the cranium, scapula, mandible, ilium, and shafts of the long
bones. Cancellous or trabecular bone is found in vertebrae, skull
base, pelvis, and ends of the long bones. Since only 15% to
25% of trabecular bone is calcified, it has a large surface
area and a high turnover rate and is particularly susceptible to
disorders that affect bone mineralization. Intramembranous ossification
is initiated by local condensation of mesenchymal stem cells that
differentiate directly into osteoblasts. When intracellular levels
of β-catenin are low, the mesenchymal stem cell
evolves into a chondroblast. Longitudinal growth of bone is the
result of chondrocyte proliferation in orderly columns within the
cartilaginous growth plate (see eFig. 543.1). Resting
or reserve cells at the most distal aspect of the growth plate differentiate
into proliferating chondrocytes under stimulation by bone morphogenetic
protein-6 and growth hormone. Locally synthesized insulin-like growth
factor I(generated in response to growth hormone, thyroid and sex
hormones) stimulates division of these chondrocytes and increase
in the length of the cartilage growth plate and of the long bone. Proliferating
chondrocytes mature into prehypertrophic chondrocytes, and these
become hypertrophic chondrocytes that secrete collagen type X prior
to their death. Endochondral bone develops as invading blood vessels
bring with them chondroclasts, osteoclasts, and osteoblasts; chondroclasts
reabsorb cartilage matrix and dying chondrocytes. Primary spongiosa
of bone is formed and then replaced by mature bone. In addition
to collagen type I, osteoblasts secrete many noncollagenous proteins
(eg, bone-specific alkaline phosphatase, osteocalcin) into a matrix
into which calcium and phosphate are deposited as hydroxyapatite.
Osteoblasts have a life span of 3 months.
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