John G. Birch
Growth and development of the musculoskeletal system, in tandem with gross and fine motor development, are overshadowed perhaps only by intellectual development in terms of magnitude, complexity, and sophistication from conception to skeletal maturity. The pathway delineated by postnatal development defines infancy, childhood, and adolescence. In the simplest terms, the growth plates (or physes) of long bones are the “motors” of skeletal development. Their physical characteristics and function help separate the “child” from the “adult,” orthopedically speaking. In this chapter, we will briefly review musculoskeletal embryology, postnatal musculoskeletal development, and the structure and function of the growth plate.
MUSCULOSKELETAL EMBRYOLOGY
Embryologic development may be thought of as having two phases: an embryonic period during which organ systems evolve and organize, and the fetal period, from the 12th week of gestation, during which these organ systems grow and mature.
Embryologically, the musculoskeletal system develops from the dorsal (somatic) mesoderm. Approximately 26 days after fertilization, the upper limb “bud” appears on the ventrolateral body wall, consisting of mesenchymal cell swelling covered by ectoderm. The tip of this ectodermal layer thickens to become the apical ectodermal ridge (AER), under which an area of rapidly proliferating, undifferentiated mesenchymal cells forms (the progress zone). The lower limb bud appears about 2 days after the upper; this slight delay relative to the upper limb in appearance, organization, and maturation continues throughout limb development. With continued growth and development, a chondrogenic core forms, beginning proximally and progressing distally (characteristic of both upper and lower limb formation). This chondrogenic core evolves to the point that the upper limb skeletal elements, except for the distal phalanges, are present by the seventh week (eighth for the lower limb). Subsequent to the development of the chondrogenic skeletal structure, nerve invasion of the limb occurs, followed quickly by skeletal muscle tissue formation. Joints form by programmed chondrogenic cell death (apoptosis) producing clefts within the chondrogenic skeleton. Further healthy joint development is dependent on movement, which is in turn dependent on the development and maturation of innervated skeletal muscle. By the eighth week, major tissue differentiation in the limbs is complete, and the majority of the remaining fetal period is dedicated to growth. Excellent detailed reviews of musculoskeletal embryology are available.1-3
BONE DEVELOPMENT AND POSTNATAL GROWTH
Bone is a composite tissue, consisting of an organic component (osteoid) and inorganic matrix (primarily hydroxyapatite) that give bone its hardness. Bone is formed by one of two pathways: intramembranous and enchondral ossification. Intramembranous ossification is characterized by direct ossification of fibrous primitive connective tissue; the clavicle and bones of the skull form intramembranously. During intramembranous ossification, dense nodules of mesenchymal cells convert to capillaries and osteoblasts. These osteoblasts secrete osteoid that subsequently becomes mineralized. The exact mechanism that induces mesenchymal cells to convert into osteoblasts is not known.
All other appendicular and axial bones form by enchondral ossification—that is, by gradual ossification of a cartilaginous anlage. Instead of converting directly into osteoblasts, condensations of mesenchymal cells transform into cartilage matrix-secreting chondroblasts. Long bones are anatomically characterized by a central shaft (diaphysis) flaring to a broader metaphysis at either end, and they terminate in a typically bulbous, articular cartilage-capped, epiphysis (Fig. 210-1). In the central region of each cartilage anlage, capillary invasion results in the replacement of chondroblasts by osteo-blasts, and the formation of primary centers of ossification. Ossification of the cartilaginous anlage then continues centrifugally. The epiphyses at various stages of development, particular to the individual bone, experience vascular invasion as well, resulting in the formation of secondary centers of ossification.1,4 Once the secondary centers of ossification have appeared, the cartilaginous growth plate (physis) can be “visualized” radiographically as the radiolucent disk between the bony metaphysis and epiphysis. The appearance of the various secondary centers of ossification typically occurs within a relatively narrow age range, so that their absence or appearance may be used to estimate the age of the fetus and infant (eFig. 210.1 ). Similarly, the physes will disappear (“close”) at skeletal maturity; the timing of physeal closure is specific to the individual physes and is location and gender dependent (eFig. 210.2 ). At a more sophisticated level during later stages of growth, careful analysis of the maturation of the distal radial and ulnar epiphyses, carpals, metacar-pals, and phalanges forms the basis for the calculation of skeletal (or “bone”) age. These estimations may used to identify hormonal growth inhibition and allow a calculation of growth remaining in long bones and, to a lesser extent, the spine.
FIGURE 210-1. Scheme of anatomic regions of long bones. The central shaft (diaphysis) flares to the metaphyses, which are capped by the usually bulbous, joint-forming ends (epiphyses). In skeletally immature children, the physis or growth plate is sandwiched between the epiphysis and metaphysis. Earliest ossification is characterized by vascular invasion of the diaphysis and ossification of the “primary center of ossification.” Later, secondary centers of ossification form within the epiphyses by a similar process. After the appearance of the secondary centers of ossification, the physis is identifiable as the radiolucent zone between the metaphyseal and epiphyseal bone.
The process of enchondral ossification continues throughout skeletal growth in the epiphyses and particularly in the physes of long bones. The physis is a highly organized disk of replicating and subsequently ossifying cartilage located between the epiphysis and metaphysis. The physes are the primary source of longitudinal skeletal growth. Each long-bone physis will elongate a typical and known amount per year of skeletal growth. The major long bones of the upper and lower limbs have a physis at either end, whereas the metacarpals, metatarsals, and phalanges usually have only one. The “globular bones” (carpals and tarsals) are more “jelly-bean”-like in their cartilaginous-bony structure, with a central ossific nucleus embedded in an ever-thinning rind of growing cartilage. The physes are highly complex cartilaginous structures microscopically divided into four layers or “zones” (Fig. 210-2): germinal (or “resting”), proliferative, hypertrophic, and zone of provisional calcification. The germinal layer, adjacent to the secondary ossific nucleus once the latter has appeared, is characterized by a relatively large amount of extracellular matrix with apparently randomly located chondroblasts. The proliferative layer has proportionately more cells and less extracellular matrix. The chondroblasts are strikingly arranged into longitudinal columns. Toward the metaphyseal region, these cells become larger in size, with even less extracellular matrix between them. This extracellular matrix becomes calcified, with chondroblast apoptosis, in the zone of provisional calcification. The zones of hypertrophy and provisional calcification are the structurally weakest layers, and it is here that fractures of the physes are most typically propagated. At the metaphyseal base of the zone of provisional calcification, vascular invasion and early ossification of the matrix occur.4
FIGURE 210-2. Scheme of the microscopic organization of the physis or growth plate. Traditionally, the physis is separated into four contiguous layers from epiphysis to metaphysis: resting (or germinal), proliferative, hypertrophic, and zone of provisional calcification.
The modulation of growth through the physis is subject to many hormonal and mechanical influences that are not, as yet, thoroughly understood. Insulinlike growth factors, growth hormone, thyroid hormone, and the estrogens all influence physeal activity during prenatal, postnatal, and preadolescent growth. The absence of certain vitamins and minerals (most notably vitamin D, vitamin C, and calcium) also adversely affect physeal growth and ossification in the provisional calcification zone of the physis (Fig. 210-2). In addition, the physis responds favorably and unfavorably, respectively, to physiologic and nonphysiologic loading, referred to as Delpech or Hueter-Volkmann principles. In general, excessive compressive forces decelerate normal physeal growth, whereas modest traction or distraction forces may result in accelerated physeal growth.4
It is important to recognize that even in long bones, growth does not occur exclusively at the physes. Appositional growth of the diaphysis and metaphysis occurs, primarily under the periosteum, by intramembranous ossification. The epiphyses expand in a centrifugal manner, resulting in enlargement of the ends of long bones and contributing to the overall increase in the total length of a long bone. Simultaneous with growth at all of these locations, reshaping (or “remodeling”) occurs, under both genetic and physical influences. The metaphyses tapers and condenses into the diaphysis, and the overall long bone remodels, so that there is three-dimensional growth through space of the limbs, not just a simple elongation of the ends (eFig. 210.3 ).
Each physis contributes a known amount to a long bone’s length during each year of skeletal maturation, both in percentage and actual amounts.5 Thus, injury, inadvertent or deliberate via surgery, can have a calculable effect on the ultimate length of a limb. This information is important because physeal injuries are common in children. Physes can be damaged physically by direct trauma, infection, or encroachment by both benign and malignant tumors. Physeal growth disturbances are, fortunately, not common, but significant deformities may result when they occur, and extensive orthopedic reconstruction treatment may be required. Similarly, pathological angular deformities or limb length inequality may be corrected by harnessing physeal growth using appropriately timed surgical tethering procedures (eFig. 210.4 ).
Table 210-1. Age (and Range) of Appearance of Certain Gross Motor Milestonesa
GROSS MOTOR DEVELOPMENT
Maturation of the neurological system after birth, particularly the peripheral nervous system, is integral to musculoskeletal growth. Gross motor milestones cannot be met without a complex interaction of central and peripheral nervous system development, as well as musculoskeletal growth and maturation. The average age and range of achievement of gross and fine motor milestones (discussed in Chapters 11and 82) should be well understood by all physicians and allied health care workers involved in the care of children. The major gross motor milestones and their average age of attainment are summarized in Table 210-1. Briefly, the average healthy infant begins rolling over from front to back at age 4 to 5 months and from back to front at 5 to 6 months, sits unsupported at 7 months, crawls at 8 to 9 months, pulls to stand at 9 to 10 months, “cruises” (walks holding on) at 11 months, walks independently at 12 months, and runs well by 24 months.6,7