1.

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MUSCULOSKELETAL GROWTH
AND DEVELOPMENT
Steven E. Koop

At birth the muscles and bones of a child with cerebral palsy are like those of any child
without a condition that intrinsically alters the formation of those tissues. Alterations of brain
function characteristic of cerebral palsy include loss of selective motor control, abnormal
muscle tone, imbalance of power between muscle agonists and antagonists, and impaired
body balance mechanisms. When altered tone, power and control are imposed on the
growing child’s muscles and bones, the results may include reduced muscle elasticity,
reduced joint range of motion, and disturbed bone and joint development. The previous
chapter has described basic features of the brain and the means by which it controls
locomotion. This chapter will review basic features of muscle and bone development
and point to features relevant to children with cerebral palsy. When we discuss the
pathophysiology of neuromuscular control in the next section, a fundamental concept will
emerge: altered brain function leads to altered muscle activity and motor function which,
in turn, influence the growth and development of the skeleton (Fig. 1.2.1).

Muscle
The basic element of skeletal muscle is the muscle fiber. Each muscle fiber is a mass of
cytoplasm containing several nuclei enclosed in a membrane with no internal cell
boundaries. Muscle fibers are supported by endomysium or supporting connective tissue.
Groups or bundles of muscle fibers make up muscle fascicles, each surrounded by
perimysium. Multiple groups of muscle fascicles, enclosed by enveloping epimysium,
constitute a whole muscle (Fig. 1.2.2). The geometric arrangement of muscle fascicles is
key to the contractile (and thus functional) properties of a muscle. Muscles may be formed
by fascicles grouped in parallel, oblique (pennate), or tapering (fusiform or spindle)
architecture.
One or more motor nerves control each skeletal muscle. Ultimately each muscle fiber
receives innervation at a single point. A motor unit includes a single alpha motor neuron
axon and all the muscle fibers it innervates. The muscle fibers of a motor unit may not be
adjacent, and the number of muscle fibers in a motor unit and the number of motor units in
a muscle are quite variable. A motor unit is activated (or stimulated to contract) by an
electrical impulse that originates at the anterior horn cell and travels the length of the axon
to the motor endplate or final point of contact with a muscle fiber. A Schwann cell specialized
to facilitate the release of acetylcholine that is stored in vesicles at the nerve end covers the

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Fig. 1.2.1 The basic sequence of consequences of altered brain function in cerebral palsy.

end of the axon. The junctional area consists of closely interdigitated folds of axon and
muscle fiber membranes. When the electrical impulse arrives at the terminal axon it permits
the flow of calcium ions into the nerve cell and the increased calcium concentration prompts
vesicles to fuse into the terminal membrane and release acetylcholine into the synaptic
space. Acetylcholine binds to the muscle membrane and triggers depolarization of
the membrane that spreads the length of the muscle fi ber (known as an action potential)
(Fig. 1.2.3).
The depolarization of muscle membrane reaches the interior of the fiber by a system of
internal membranes. Calcium is stored along those membranes in sacs (sarcoplasmic
reticula). Depolarization causes release of calcium into the muscle fiber cytoplasm and the
calcium prompts chemical reactions between structural proteins that result in muscle
shortening and force generation. The proteins are organized in repeating units of light and
dark bands known as sarcomeres. The primary protein of the light or I-band is actin and the
primary protein of the dark or A-band is myosin. The chemical reactions (which involve
several other proteins) result in cross-bridges between actin and myosin that cause the thick
filaments of the dark bands to slide past the thin filaments of the light bands. The sequence
of muscle activation provides many points of intervention for a child with increased tone,
particularly spasticity. Those interventions are described in subsequent chapters.
The immediate energy source for muscle contraction comes from the hydrolysis of
adenosine triphosphate (ATP). ATP can be replenished through several mechanisms but the
most efficient is the Krebs cycle. By this pathway one glucose molecule yields 38 ATP. If
the intensity and duration of activity allows oxidative, or aerobic, processes to meet the
energy requirements of the muscle then fatigue will be delayed. When activity is very intense
or lengthy, muscle relies upon anaerobic chemical reactions to yield ATP. For example,
glucose can be converted to lactic acid while yielding a small amount of energy (one glucose
molecule yields two ATP). The lactic acid is later fully metabolized as energy sources
are replenished at the end of exercise. The role of lactic acid as a muscle irritant that causes
the soreness associated with sustained activity is debated. It is simplistic to assume muscle

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Fig. 1.2.2 The hierarchical structure of skeletal muscle. Muscle fascicles are composed of many
muscle fibers. The motor unit consists of the motor neuron, the motor endplate and the muscle fibers
innervated by the motor neuron. Each muscle fiber is composed of interdigitating contractile proteins,
actin and myosin, structured as sarcomeres that are arranged in a series.

Fig. 1.2.3 An electromicrograph of the motor endplate and neuromuscular junction showing
acetylcholine (Ach) vesicles fused with presynaptic membrane.

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activity is sequential: utilization of available ATP comes first, followed by aerobic
mechanisms, with anaerobic mechanisms last. Like any household that utilizes cash,
savings, and short and long-term debt, muscle finds energy for activity by using all pathways
according to circumstances.
Inappropriate muscle activation increases the use of energy resources. This is most
commonly measured through quantification of oxygen utilization. Examples of inappro-
priate muscle activation include the increased tone of spasticity (and other tone disorders)
and the increased activity of muscles coping with disturbed skeletal structures (such as
joint contractures, bone torsions, and bad foot shapes). Oxygen utilization may serve
as a marker of the effects of interventions in those areas.
There are different fiber types but all fibers of a single motor unit are of the same type.
Fiber types have distinguishing structural and physiological features. Variations in the
percentage of fiber types within a muscle are common and they are linked to the tasks
of that muscle. Motor units and fiber types are recruited by the central nervous system
according to size with the smallest motor units recruited first.
Muscle tension can occur passively or as the result of muscle activation. Passive muscle
tension is increased as a muscle is stretched. Initial stretching yields little tension but as
stretch increases the tension increases exponentially and can be many times greater than
tension created by muscle activity. Excessive stretch causes muscle failure. Each muscle
has an ideal length at which neurological stimulation results in maximum active muscle
tension. As ideal length is approached and then passed the muscle tension or force that
results from activation increases and then diminishes. Movement in the limbs of humans
results from the application of tension or force to a point of muscle insertion on a bone on
the opposite side of one or more joints crossed by the muscle. Torque equals the muscle
force multiplied by the perpendicular distance from the line or vector of force application
and the axis of rotation. Variations in torque are tied to variations in muscle force (amount
activated, length at activation etc.) and variations in the moment arm or the perpendicular
distance of force application.
Muscles increase in length during growth through increased tendon and muscle fiber
length. While muscle lacks the discreet and specialized growth plate of immature long bones
it appears that sarcomeres are added at the muscle-tendon junction. Growth in bone length
and the stretching effects of everyday physical activity encourage the addition of sarcomeres
and muscle length. It appears that an increase in the number of nuclei in the fibers, an
increase in the number of satellite cells adjacent to muscle fibers, and hypertrophy of muscle
fibers during infancy and childhood are all affected by stress that is transduced by a number
of signaling molecules. Insulin-like growth factor (IGF) I and II are two of several important
signaling molecules (Christ and Brand-Saberi 2002, Grefte et al. 2007).

Bone
The basic make-up of bone is 65% mineral and 35% organic. The organic component is 95%
collagen (by dry weight) and 5% other proteins and proteoglycans. There are several types
of collagen, but type I is the most common in bone. It is organized in fibrils with a periodicity
of 64 nanometers in a quarter-stagger arrangement. Junctional areas represent sites for

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the deposition of hydroxyapatite crystals. The cells of bone include osteoblasts, osteocytes,
and osteoclasts. Osteoblasts are cells of mesenchymal origin and are responsible for the
majority of bone formation. Osteocytes are mature bone cells resident in bone lacunae and
responsible for mineral homeostasis. Osteoclasts are multinucleated giant cells specialized
in the breakdown of mineralized tissue.
Bone has important metabolic and mechanical functions. It serves as a calcium bank
and is crucial to mineral homeostasis. Hematopoietic cells are resident within bone. Bone
provides support for body segments and protection for vulnerable tissues (such as the brain,
and the heart and lungs). In addition, bones serve as levers for body movement and pro-
vide origins and insertion points for muscles. Much of the content of later chapters in this
book will address this bone function.
Bone formation and growth begin early in embryogenesis and continue until skeletal
maturity. Bone formation continues after maturation as part of continuous remodeling of
bone or as part of fracture healing. Intramembranous bone formation is the most primitive
form of osteogenesis: bone trabeculae form directly with condensations of mesenchymal
cells. Examples include the skull, maxilla, mandible, clavicle and scapula. Endochondral
ossification is the most common bone formation of growth and development.
Condensations of mesenchymal cells act as a model for the future bone and are replaced
by cartilage cells. Aging cartilage is vascularized and undergoes a primary mineralization.
Osteoblasts form osteoid (unmineralized bone matrix) along the mineralized cartilage. Early
mineralization of osteoid yields woven bone, immature bone that has not been organized
in response to stress application. Remodeling yields lamellar bone, mature bone that has
been formed and remodeled into stress-responsive layers.
Cortical bone is lamellar bone organized into osteons, cylindrical structures of layered
bone organized around a central canal. The appearance of a saguaro cactus is an apt visual
analogy. Cortical bone makes up the tubular walls of long bone and the outer shell of other
bones. It comprises approximately 80% of skeletal mass. Cancellous, or trabecular, bone is
organized into scaffold-like lattices. It makes up the ends of long bone and much of the inner
structure of flat and cuboidal bones. It is often lamellar but lattices can be made of immature
woven bone. Factors that affect the mechanical properties of bone include the geometry of
bone (tubular, flat, cuboid), type of bone (woven or lamellar, cortical or cancellous, child
or adult), and status of mineralization. Other factors include the rate and type of load
application (compression, tension, bending and twisting).
Centers of ongoing bone formation by endochondral ossification exist in the bones of
children. These are located near the ends of long bones as plate-like cartilage structures
(physes or ‘growth plates’) or along the edges of flat bones (such as the apophyseal cartilage
of the ilium). Articular cartilage in children may also be considered a type of ‘growth plate’.
Through ongoing endochondral bone formation at these sites, and intramembranous bone
formation along bone surfaces, the skeleton of a child grows in size.
The growth of the body is commonly described by graphs that portray the progressive
acquisition of stature and mass. A more pertinent graph for considering skeletal growth and
the impact of stress application on bone portrays growth velocity. Such a graph demonstrates
both speed of growth at a given age and growth potential (represented by the area remaining

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under the curve before skeletal maturity). Growth occurs in three phases. Between birth and
approximately 3 years of age the speed of growth is extraordinary but it is steadily decelerat-
ing. From age 3 years to the onset of puberty, growth occurs at a slowly decelerating linear
rate. At puberty (18 months later for males) growth velocity increases for 18–24 months,
achieves a peak velocity, and then decreases until the skeleton is mature (Fig. 1.2.4).
Bone is affected by its mechanical environment, created by passive and active muscle
tension, weight-bearing, and other forces. The mature skeleton responds according to
Wolff’s law, by which bone changes in response to mechanical stresses (Wolff 1896). The
cellular and molecular means of this response remain poorly understood. The response of
the immature skeleton to stress is even more complicated but key to understanding the
skeletal problems of children with cerebral palsy. Three features of the immature skeleton
are important: the presence of growth cartilage within bone, the relatively large amounts of
cartilage tissue in epiphyses and periarticular areas (such as the acetabulum), and the
structural characteristics of immature bone tissue. The contribution of these features is
strongly affected by the growth potential that remains for a child. Examples of the
consequences of these factors in children without cerebral palsy can be seen in fracture
patterns (torus and greenstick fractures and growth plate injuries) and problems such as
infantile hip instability and secondary dysplasia.
The Heuter–Volkmann principle states that (within physiological limits) compressive
forces stimulate the growth of articular, epiphyseal, and/or physeal cartilage (Heuter 1862,
Volkmann 1862). Atypical forces have different effects. Excessive compression forces
suppress growth cartilage activity. Reduction of usual compressive forces has the opposite
effect. Arkin and Katz (1956) showed that immature rabbit long bones subjected to bending
or rotational stress will develop an angular or torsional deformity. These observations are
fundamental to understanding the effects of delayed motor skills or the effects of increased
and unbalanced muscle tone on a child’s growing bones. Dr James Gage describes these
bone growth principles in the following fashion for the orthopaedic residents who work at
Gillette: ‘What they are saying is that if you put a twist on a growing bone, it takes the twist,
which is why the growing bone follows the Star Wars principle, “May the force be with
you!” However, if you prefer the older literature, the words of Alexander Pope also apply:
“Just as the twig is bent, the tree’s inclin’d.”’
An example of the immature skeleton’s response to normal stress application is the
resolution of fetal femoral anteversion. Anteversion is the term used to describe the shape
of the femur in the coronal plane. If an anatomic specimen is placed on a tabletop, resting
on the three points of the greater trochanter and the posterior aspect of the femoral condyles,
the line segment representing the femoral neck is inclined above the plane of the table.
At birth an infant has approximately 45º of anteversion. As the central nervous system
matures a child progresses through the developmental milestones of crawling, standing,
and walking. The growth-responsive proximal femur is subjected to stresses applied by the
anterior hip capsule and the stresses of weight bearing and muscle activity during walking.
Anteversion decreases rapidly in the first three to four years of life and shows further
resolution until puberty. This pattern of torsion resolution follows the growth potential
described by the three phases of the growth-velocity graph.

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cm
yr
23
Longitudinal whole-year centiles
22 BOYS Height velocity when peak 97
velocity occurs 50
at average age 3
21 when peak velocity 97
occurs at early and
20 late limits of age 50
(entire curves fall
within shaded limits) 3
19
18
17
16
15
14
13
12
11
10
9
8
7
6
5
4
3
2 97
90
1 Age, years 75
50
3 10 25
0
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19

Fig. 1.2.4 The phases of skeletal development of a child as portrayed by the growth velocity of
increasing stature.

The pertinence of the relationship between muscle activity and skeletal growth potential
is found in the musculoskeletal problems of cerebral palsy. Altered central nervous system
function, often resulting in increased and unbalanced muscle tone, sets off a cascade of bone
and muscle responses leading to problems familiar to every clinician. Muscle architecture
can change with alterations in muscle use associated with spasticity. Muscle cells in children
with cerebral palsy demonstrate decreased resting sarcomere length and nearly a doubling
of the modulus of elasticity when compared to other children. The resulting loss of elasticity
or ‘stiffness’ combines with altered spontaneous limb movement (part of disturbed motor

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milestones) to reduce muscle length and limit joint motion (contracture) (Lieber and Friden
2000, Christ and Brand-Saberi 2002, Friden and Lieber 2003, Tidball 2005). The bones to
which the muscles are attached change their growth. Infantile bone shapes, which would be
expected to change with the emergence of normal motor skills, fail to resolve. The femur is
an example of this. Infantile femoral anteversion fails to resolve and may increase in the
presence of persistent medial hip rotation. Some bones develop torsions under the persistent
influence of increased muscle tone or torsional stresses. The tibia is an example of this, often
developing internal or external torsion (see Chapter 5.6). Other examples include tarsal bones,
particularly the calcaneus (see Chapter 3.2). Lastly, the joints bridged by the altered muscles
are affected. Persistent imbalance of muscle activity can lead to bone dysplasia, subluxation
and dislocation. Altered bone shapes change the effect of muscles, leading to lever arm
dysfunction, which will be discussed more completely in Chapter 2.3 (Fig. 1.2.5).
Because the hip joint (femur and pelvis and associated muscles) has such a prominent
place in the musculoskeletal problems of cerebral palsy it will be described in more detail.
At birth an infant’s hip range of motion reflects its position in utero. The hip is flexed,
abducted, and externally rotated. The femur has anteversion of approximately 40 o. With
typical brain function the infant moves through motor milestones that reflect increasingly
sophisticated muscle control. Crawling and walking promote extension and internal rotation
of the hip and the stresses of muscle activity and body mass are applied to the femur. The
infantile hip flexion contracture disappears and internal rotation increases. Anteversion

Fig. 1.2.5 The cascade of muscle and bone consequences that follow altered brain function in cerebral
palsy.

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decreases in response to stresses applied to the proximal femur by the anterior hip capsule
during extension (Somerville 1957). Muscles, ligaments, ground reaction forces and limb
segment masses combine to create the net joint reaction force that, during growth and
development, is the key factor in the ultimate structure of the hip joint.
Altered motor function in cerebral palsy leads to a different outcome for the hip.
Increased muscle tone and altered milestones lead to reduced muscle elasticity, decreased
muscle growth, and failure to resolve the normal infant hip flexion contracture. Because
spasticity seems to affect hip adductors and flexors more than abductors and extensors the
muscle changes of cerebral palsy result in atypical, unbalanced application of stress to the
femoral head and acetabulum. Infantile anteversion fails to resolve or actually increases.
Anteversion is associated with coxa valga, which further reduces the mechanical effect of
the hip abductors. The lateral portion of the acetabulum experiences increased compression
stress and displays reduced growth (seen as an increased acetabular angle in radiographs).
Simultaneously the medial portion of the femoral head experiences compression stresses
that inhibit growth and lead to a loss of sphericity. The femoral begins to lose contact
with the medial wall of the acetabulum, which thickens because of a loss of compression
stresses. Ultimately the femoral head may dislocate and its articular surface deteriorate
(Figs 1.2.6, 7).

Fig. 1.2.6 The cascade of musculoskeletal consequences for the hip in cerebral palsy.

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Fig. 1.2.7 The evolution
of hip dysplasia in
cerebral palsy.

Understanding this cascade and accurately placing a child in the sequence of events will
assist in formulating a treatment plan. Tone reduction has a primary place in all treatment
strategies because of the impact of increased tone (particularly spasticity) on bone growth.
The method of tone reduction will vary with the nature of the central nervous system
problems and the age of the child. Systemic medications, intramuscular and intrathecal
medications, and selective dorsal lumbar rhizotomy, all have a role in the right circumstance.
Early spasticity reduction will minimize bone and joint problems. Spasticity that persists
into the juvenile years may require simultaneous plans to reduce the spasticity and address
the bone and joint dysplasias that have evolved (and which will not improve spontaneously
due to reduced remaining growth potential). Bone interventions to restore joints and the lever
functions of the skeleton are key to the best functional outcomes. But we have learned that
persistent tone in the presence of growth will be followed by recurrent bone deformity
that will erode early functional gains after skeletal procedures and, perhaps, necessitate
secondary bone surgeries.

REFERENCES

Arkin AM, Katz JF (1956) The effects of pressure on epiphyseal growth; the mechanism of plasticity of growing
bone. J Bone Joint Surg 38A: 1056–76.
Christ B, Brand-Saberi B (2002) Limb muscle development. Int J Dev Biol 46: 905–14.
Friden J, Lieber RL (2003) Spastic muscle cells are shorter and stiffer than normal cells. Muscle Nerve
27: 157–64.
Grefte S, Kuijpers-Jagtman MM, Torensma R, Von den Hoff JW (2007) Skeletal muscle development and
regeneration. Stem Cells Dev 16: 857–68.
Heuter C (1862) Anatomische Studien an den extremitatengelenken Neugeborener und Erwachsener. Virchows
Archiv 25: 572–99.
Lieber RL, Friden J (2000) Functional and clinical significance of skeletal muscle Architecture. Muscle Nerve
23: 1647–66.
Somerville EW (1957) Persistent foetal alignment of the hip.J Bone Joint Surg 39B: 106–13.
Tidball JG (2005) Mechanical signal transduction in skeletal muscle growth and adaptation. J App Physiol
98: 1900–8.
Volkmann R (1862) Chirurgische Erfahrungen uber Knochenverbiegungen und Knochenwachsthum. Arch
Pathol Anat 24: 512–40.
Wolff J (1896) The Law of Bone Remodeling. Berlin, Heidelberg, New York: Springer. (Translation of 1892
German edn.)

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