A Andry’s Tree

A knowledge of normal and abnormal growth and development is vital to an understanding of pediatric orthopedics [B]. This knowledge increases our comprehension of the musculoskeletal system, improves our understanding of the causes of disease, and makes us better able to manage the varied orthopedic problems of childhood.

Dividing the period of growth into six stages provides a convenient framework to review both normal and abnormal growth and development [C]. During the first stage, reproductive cells or gametes are formed.

Normal Growth

During normal development, cells proliferate, undergo differentiation, move, and even in some cases die in order to produce a normal, mature individual.

Gamete

Gamete is a collective term for ovum and sperm. During gametogenesis, meiotic division halves the chromosome number. Genetic material, which may include defective genes, is shuffled, and mature ova and sperm are formed [D].

Early Embryo

This early embryonic phase encompasses the 2-week period from fertilization to the implantation of the embryo.

First week

During the first week following fertilization, the zygote repeatedly divides as it moves through the fallopian tubes to the uterus. The zygote becomes a morula, then a blastocyst. The blastocyst implants itself on the posterior uterine wall.

Second week

During this week, the amniotic cavity and trilaminar embryonic disc are formed [A]. The early embryo is usually aborted if a lethal or serious genetic defect is present. During these first two weeks, the early embryo is less susceptible to teratogens than during the following embryonic period.

Embryo

The embryonic period is characterized by rapid cell activity and organ formation. Cells differentiate and mature, often through induction, a process by which surrounding cells act on other cells to produce entirely new cells or tissue.

Third week

This is the first week of organogenesis. During this week, the trilaminar embryonic disc develops, somites begin to form, and the neural plate closes to form a neural tube.

Fourth week

During this week, the limb buds become recognizable [B]. Somites differentiate into three segments. The dermatome becomes skin, the myotome becomes muscle, and the sclerotome becomes cartilage and bone. The apical ectodermal ridge develops in the distal end of each limb bud. The ridge has an inductive influence on limb mesenchyme, which promotes growth and development of the limb. Serious defects in limb development may originate at this time.

Fifth week

The hand plate forms and mesenchymal condensations occur in the limbs.

Sixth week

The rays of the digits become evident and chondrification of mesenchymal condensations occurs.

Seventh week

The notches appear between the digit rays. This process, responsible for joint formation, results from cell death. Failure of the separation of rays results in syndactylism. During this week, the upper and lower limbs rotate in opposite directions [C, previous page]. The lower limb rotates medially to bring the great toes to the midline, whereas the upper limb rotates about 90° laterally to position the thumb on the lateral side of the limb.

Eighth week

The fingers separate completely, the embryo assumes a human appearance, and the basic organ systems are completed.

Fetus

The fetal period is characterized by rapid growth and changes in body proportions.

Ninth to twelfth weeks

The first bone, the clavicle, ossifies by a process of intramembranous deposition of calcium. The skeleton develops in a cranial to caudad sequence, with the upper extremities developing before the lower limbs. This results in the upper limbs becoming proportionate compared to the rest of the body, but the lower limbs remaining short.

Thirteenth to twentieth weeks

Growth continues to be rapid. The lower limbs become proportionate, and most bones ossify. The fetal period is characterized by rapid growth and changes in body proportions

Twentieth to fortieth weeks

Growth continues and body proportions become more infant-like.

Connective Tissue

During early fetal life, the basic structure of connective tissue is formed largely of two families of macromolecules: collagens and proteoglycans.

Collagen

Collagen is a family of proteins containing a triple helix of peptide chains [A]. Although at least fifteen different types of collagen are known, five types are most common [B].

The biosynthesis of collagen

starts in the endoplasmic reticulum, where the basic molecule is assembled. In the extracellular space, procollagen is formed. It is arranged into fibrils and reinforced by cross-linkages to become collagen. Collagen is the major component of connective tissue.

Disorders of collagen are common

They may be minor, producing only increased joint laxity [C], or severe, causing considerable disability. The major collagen disorders are classified according to the site of the defect in the pathway of collagen biosynthesis.

Proteoglycans (mucopolysaccharides)

Proteoglycans are macromolecules that form the intracellular matrix of hyaline cartilage and the other connective tissues. Polypeptides or proteins attach to glycosaminoglycan to become proteoglycans [D]. Proteoglycans attach to a hyaluronic acid by a link protein to become an aggregate with a molecular weight in excess of one million. Proteoglycans are highly hydrophilic, and in water they combine with many times their weight of water to create an elastic matrix that is ideal for joint lining. Hyaline cartilage is composed of about equal amounts of proteoglycans and collagen, and it combines with about three times its weight of water, providing a resilient tissue with excellent shock absorbing characteristics. Defects in the formation of these complex molecules produce a variety of diseases.

Mucopolysaccharide (MPS) storage diseases result from a deficiency of specific lysosomal enzymes necessary for the degradation of glycosaminoglycans. These diseases are caused by excessive intracellular accumulation of partially degraded molecules that result in conditions such as avascular necrosis or spinal cord compression.

Joints

Synovial joints develop first as a cleft in the mesenchyme, which then chondrifies and cavitates [A]. Cavitation is completed by about the fourteenth gestational week, with the inner mesenchyme becoming synovium and the outer mesenchyme becoming the joint capsule. Normal joint development requires motion, and motion requires a functioning neuromuscular system. Thus, defective joints are often seen in infants with neuromuscular disorders such as myelodysplasia or amyoplasia.

Bone

Bones are formed by osteogenesis. The mandible and clavicle are first formed starting in the seventh gestational week by intramembranous ossification.

Intramembranous Ossification

Osteoblasts differentiate from mesenchyme to form bone directly without a cartilaginous stage. Further growth occurs by appositional bone formation.

Endochondral Ossification

During the sixth gestational week, mesenchymal cells differentiate, condense, and transform into chondrocytes to form a model of the future skeleton. In the center of this model, chondrocytes hypertrophy and begin to calcify. During the next week, a periosteal sleeve of bone is formed, and by the eighth week, vascularization is under way [B].

During the fetal period, primary ossification centers develop in long bones within the diaphysis [C]. Ossification first occurs under the perichondrium. Within the cartilage, hypertrophied cells degenerate. Next, vascular ingrowth occurs, and then the core of the cartilage model is ossified to form the primary ossification center. Endochondral ossification proceeds at the cartilage–bone interphase. Later, secondary ossification centers develop at the ends of the bones, and the cartilage interposed between the primary and secondary ossification centers becomes the growth plate.

Except for the clavicle, all bones of the axial and appendicular skeleton are preformed in cartilage and converted to bone by enchondral ossification. This process begins in the scapula, humerus, radius, and ulna. Ossification continues in an orderly fashion, with centers appearing at different ages. Ossification is earlier in girls than boys [D].

Periosteum

The periosteum seems to develop from the perichondrium. The periosteum is osteogenic, allowing appositional bone growth, and provides a thick sleeve adding resilience and strength to the growing skeleton. This osteogenic capability results in rapid fracture healing and bone regeneration.

Bone Types

Growing bone possesses special characteristics, providing the infant and child with greater flexibility and resilience than that of the adult.

Woven bone

is formed during the fetal period. This bone has less structure, a relatively higher collagen content, and more flexibility than lamellar bone. Woven bone makes up the metaphysis of growing bones, and the type of bone making up the callus following fracture. This flexibility becomes essential during the traverse of the birth canal.

Lamellar bone

Once the need for this high degree of flexibility has passed, woven bone is gradually replaced by lamellar bone starting soon after birth. By four years of age, most woven bone has been converted to lamellar bone.

Ossification Centers

Primary ossification centers

for long bones usually develop before birth [C, previous page], whereas primary ossification centers for smaller bones, such as the patella and most carpal and tarsal bones, develop during infancy [A].

Secondary ossification centers

develop during infancy and early childhood. They fuse with the primary centers during late childhood, adolescence, and early adult life. Because osseous maturation continues throughout childhood and adolescence in a reasonably orderly fashion, the extent of ossification, as radiographically documented, has become the standard for assessing maturation.

Bone Growth

Cortical thickness increases throughout childhood. For example, the diameter of the diaphysis of the femur increases faster than does the diameter of the medullary canal. This produces an increasing diaphyseal thickness with advancing age. This increasing thickness, lamellar structure, and proportion of calcium give mature bone great tensile strength but little flexibility. These changes are important factors in producing the varying patterns of skeletal injury seen during infancy, childhood, and adult life.

Growth Plate

The growth plate of long bones develops between the primary and secondary ossification centers [A]. The growth plate is responsible for the longitudinal growth of long bones. Growth plate chondrocytes go through an orderly process of proliferation and differentiation followed by terminal differentiation and the formation of new bone. Growth plates with more limited growth potential develop at other sites. These include the periphery of round bones, such as the tarsal bones or vertebral bodies, and the sites of muscle attachments, such as the margins of the ilium. Such sites are referred to as apophyses.

The typical long bone epiphysis is divided into zones that reflect morphological, metabolic, and functional differences.

The Reserve Zone (RZ)

This zone is adjacent to the secondary ossification centers and is a zone of relative inactivity. The RZ does not participate in the longitudinal growth of the bone, but it does provide some matrix production and storage functions. This zone contains proteins and genes important in specifying the chondrocyte phenotype, such as SOX–9.

The Proliferative Zone (PZ)

This is the zone of cartilage cell replication and growth. A high metabolic rate and abundant blood supply, oxygen, glycogen, ATP, and collagen make this rapid growth possible. Signaling pathways, important in regulating cell proliferation, are found in this zone. These include insulin-like growth factors and fibroblastic growth factors; both factors are active in this zone.

The Hypertrophic Zone (HZ)

This zone consists of three sub-zones: maturation, degeneration, and provisional calcification segments. In the HZ, the cartilage cells increase in size and the matrix is prepared for calcification. This is associated with a decline in blood supply, oxygenation, and glycogen stores, and with a disintegration of aggregated mucopolysaccharides and chondrocytes. In the sub-zone of provisional calcification, a unique collagen X that accepts calcium deposition is synthesized.

The Metaphysis

This zone is the site of vascularization, bone formation, and remodeling. The calcified matrix is removed, and fiber bone is formed and replaced by lamellar bone.

The Periphery

This zone includes the growth plate and metaphysis, which are the primary sites for infections, neoplasms, fractures, and metabolic and endocrine disorders. Problems in the growth plate constitute a significant portion of diseases of the musculoskeletal system in childhood.

Perichondral Ring

The perichondral ring of LaCroix and the ossification groove of the Ranvier ring surround the growth plate [B]. These structures support and expand the width of the growth plate.

The perichondral ring

of LaCroix is continuous with the metaphyseal periosteum, increasing the strength of the metaphyseal–physeal interphase.

The ossification groove

of Ranvier is an accumulation of chondrocytes, providing the reserve cells necessary for appositional growth of the growth plate.

Growth Plate Types

Growth plates form in a number of patterns, depending upon the shape of the bone [C]. These include:

Epiphyseal plate

forms at the end of long bones, providing longitudinal growth.

Ring epiphyses

surround round bones such as the tarsals or metatarsals. The bones grow circumferentially.

Apophyses

are growth plates applied to the surface of a bone such as the iliac crest.

Traction apophyses

are growth plates to which a muscle is attached. Examples include the tibial tubercle and greater trochanter.

Bone Growth

Bone growth rate is precisely regulated with each growth center contributing a prescribed percentage of the final growth. These values are important to know due to their clinical significance [D].

Growth rates from various epiphyses vary. In the upper limb, growth is most rapid at the shoulder and wrist, in contrast to the lower limb where most growth occurs just above and below the knee. To help remember the different growth rates in extremities, a commonly used memory aid is imaging a child in a bathtub. The growth plates that would be above water are the most fast growing [E]. Alterations in the general health of the child are often recorded by growth arrest lines [A]. These are linear calcifications from slowing of growth.

Growth and Development

Infancy extends from birth to 2 years of age. It encompasses the period of most rapid growth and development after birth.

Growth Rates

The growth rate varies with age and is greatest in early infancy, declines during childhood, and briefly increases again during the adolescent growth spurt. A child is about half his or her adult height at 2 years of age and about three-fourths by 9 years of age [A].

Predicting Adult Height

Estimating adult height is valuable in managing certain deformities, particularly anisomelia (limb length inequality). A variety of methods for predicting adult height are available.

The simplest method is to double the child’s height at two years [A].

Another way involves establishing the percentile of height by plotting the child’s height on the growth chart by bone age rather than by chronological age. This percentile is projected out to skeletal maturity to provide an estimate of adult height [B].

The most commonly used method [C] is to add the mother’s and father’s heights in either inches or centimeters. Add 5 in. (13 cm) for boys and subtract 5 in. (13 cm) for girls. Then divide in two. Using this method, most children will reach an adult height within 4 in. (10 cm) of this estimation.

Growth of Different Tissues

The growth rate of tissues varies with age. Subcutaneous fat, which provides nutritional reserve and protection from cold and injury, develops during the first year. The fat obscures the longitudinal arch of the foot, giving the infant a flatfooted appearance [D]. The percentage of muscle increases with age, but the percentage of neural tissue declines with advancing age.

Body Proportions

Growth of various body parts are different from one another. Upper limb growth occurs earlier than lower limb growth, and the foot grows earlier than the rest of the lower limb. In childhood, the trunk grows most rapidly; in adolescence, the lower limbs grow the fastest. Throughout growth, body proportions gradually assume adult form [A].

Determining Maturation Level

Knowing the amount of growth remaining is important to the timing of physeal fusion and thus in correcting leg length inequality [B] and in managing patients with scoliosis.

Hand–wrist radiographs

Use the Greulich–Pyle atlas to estimate the bone age.

Risser sign

is based on the extent of ossification of the iliac crest as assessed on the AP radiograph [C]. This sign has been commonly used in assessing maturity when managing scoliosis.

Tanner stages

The level of maturation is based on physical examination. Because this assessment requires an assessment of breast and genital development [D] in a sensitive age group, its use is limited.

Other signs,

such as the velocity of height gain and the status of the triradiate cartilage (acetabulum), are becoming useful maturational indices.

Extremes in Growth

Wide ranges of normal exist in normal individuals [A]. However, orthopedic problems are more likely to occur in excessively heavy or short children. We define excessive as being either above the 95th percentile in weight or below the 5th percentile in height [B].

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