Development of the Musculoskeletal System
1. Describe the process of bone ossification and of the growth, development,
maturation and common development variations of the lower limb
2. Outline the progressive development of ossification centres with age
Ossification = osteogenesis = the process of bone formation
In embryos, ossification leads to formation of the bony skeleton. Later bone growth enables the body to
continue to increase in size, goes on until early adulthood.
Ossification in adults is mainly for remodeling and repair.
Formation of the bony skeleton
Before wk 8, the skeleton of the embryo is fibrous membrane and hyaline cartilage. Then after this,
bone tissue begins to develop. Bones that develops from fibrous membrane is involved in
transmembranous ossification and the bone is called membrane bone.
Bone development that replaces hyaline cartilage is called endochondral ossification.
Intramembranous ossification
Results in the formation of the skull and the clavicles. All bones become flat bones. This is a four step
process:
1.
2.
3.
4.
Ossification centre appears in the fibrous connective tissue membrane
Bone matrix (osteoid) secreted within the fibrous membrane
Woven bone and periosteum form
Bone collar of compact bone forms and red marrow appears
Endochondral Ossification
Except for the clavicles, all bones below the base of the skull form by endochondral ossification. The
process begins in the 2nd month of development. Uses the hyaline cartilage formed earlier as models or
patterns for bone construction.
It is a complex process (more than intramembranous ossification) because hyaline cartilage needs to be
broken down as ossification proceeds.
a. The formation of a long bone begins in the centre of the hyaline cartilage shaft at a region called
the primary ossification centre
b. The perichondrium covering the hyaline cartilage is infiltrated with blood vessels and converts it
to vascularised periosteum
c. Due to an increase in nutrients, the underlying mesenchymal cells specialize into osteoblasts.
Now ossification can begin.
Steps in Ossification:
1. Bone collar forms around the diaphysis of the hyaline cartilage model
a. Osteoblasts of the periosteum secrete osteoid against hyaline cartilage, encasing it in a
bone collar
2. Cartilage in the centre of the diaphysis calcifies then cavitates
a. Chondrocytes in the shaft enlarge and signal surrounding cartilage matrix to calcify.
Calcified matrix is impermeable to diffusing nutrients so chondrocytes die and the
matrix begins to deteriorate, opening up cavities. However the hyaline cartilage model is
still stabilsed by the bone collar. The cartilage continues to grow elsewhere because it is
still healthy so the bone continues to elongate.
3. The periosteal bud invades the internal cavities and spongy bone is formed
a. Happens in month 3. The cavities are invaded by periosteal bud consisting of nutrient
artery, vein, lymphatics, nerve fibres, red marrow elements, osteoblasts and osteoclasts.
Osteoclasts partially erode the calcified matrix and the osteoblasts secrete osteoid
around fragments of hyaline cartilage forming bone covered cartilage trabeculae.
4. The diaphysis elongates and a medullary cavity forms
a. The primary ossification centre enlarges, osteoclasts breakdown the newly formed
spongy bone and opens up a medullary cavity in the centre of the diaphysis
b. Throughout the foetal period the epiphyses are entirely cartilage. This enables the
hyaline cartilage model to continue to elongate by division of viable cartilage cells.
c. Cartilage is calcifying, being eroded and then replaced by bony spicules on the
epiphyseal surfaces facing the medullary cavity; ossification follows cartilage formation
along the length of the shaft.
5. Ossification of epiphyses
a. Shortly before or after birth secondary ossification centres appear in one or both
epiphyses and they gain bony tissue. The large long bones form secondary ossification
centres in both epiphyses, small long bones form only one secondary ossification centre.
b. The cartilage in the centre of the epiphyses calcifies and deteriorates, making cavities
where a perosteal bud can entre. Bony trabeculae appear.
c. Secondary ossification reproduce the same events as primary ossification except:
i. Spongy bone in interior is retained
ii. No medullary cavity forms
d. When secondary ossification is complete, hyaline cartilage exists only in 2 places: i)
epiphyseal surfaces (articular cartilages) ii) epiphyseal plates.
Postnatal Bone Growth
During infancy and youth, long bones lengthen by interstitial growth of the epiphyseal plates (growth
from within the bone)
All bones grow in thickness by appositional growth (growth from outside).
Most bones stop growing in adolescence however bones of the nose and lower jaw continue to grow
throughout life.
Growth in length of long bones – mimics endochondral ossification.
Epiphyseal plate side facing epiphysis, the cartilage is quiescent (inactive). Epiphyseal plate side facing
diaphysis, the cartilage is organized into a pattern that allows fast, efficient growth. Here the cartilage
cells form tall columns like a stack of coins. The cells at the top of the stack (facing epiphysis) divide
quickly, pushing the epiphysis away from the diaphysis, causing lengthening (growth zone).
The chondrocytes closer to the diaphysis (transformation zone) hypertrophy, lucanae erode and enlarge
therefore the surrounding cartilage matrix calcifies, these chondrocytes die and deteriorate. This leaves
long spicules of calcified cartilage at the epiphyseal-diaphyseal junction.
This now becomes part of the osteogenic zone which is invaded by marrow elements from the
medullary cavity.
The cartilage spicules are partly eroded by osteoclasts but quickly recovered by osteoblasts, forming
spongy bone.
During growth the epiphyseal plate maintains a constant thickness because the rate of cartilage growth
is balanced by replacement of bony tissue.
As adolescence ends, the chondroblasts of the epiphyseal plate divide less and less, the plate becomes
thinner until eventually they are replaced entirely by bone tissue.
Longitudinal bone growth ends when bone of the epiphysis and diaphysis fuse = epiphyseal plate
closure. Happens at 18yo for female, 21 yo for males.
Adult bones can still increase in diameter and thickness via apposition growth if stressed by excessive
muscle activity or weight.
Bone Homeostasis: Remodelling and Repair
Every week we recycle 5-7% of our bone mass and as much as ½ g of calcium may enter or leave the
adult skeleton each day.
Spongy bone is replaced every 3-4years. Compact bone is replaced every 10 years.
When bone remains in place for long periods, the calcium crystallizes and becomes brittle, easily leading
to fractures.
Bone remodeling
This is bone deposition and bone resorption at the surface of the periosteum and the surface of the
endosteum.
This is regulated by osteoblasts and osteoclasts. In healthy people (young adults in particular), total
bone mass remains constant, suggesting that bone deposition and resorption are equal.
Remodelling does not occur uniformally. E.g. distal part of the femur is replaced fully every 5-6mths
where as the shaft is replaced much more slowly.
Bone deposit occurs where bone is injured or added bone strength is required. Optimal bone deposit
requires a diet rich in proteins, Vit C, D, A and minerals (Calcium, phosphate, magnesium, manganese).
New bone matrix deposits by osteocytes is marked by the presence of osteoid seams – an unmineralised
band of bone matrix. Between the osteoid seam and the older mineralized bone there is an abrupt
transition called the calcification front. It appears that osteoid needs to mature for about 1wk before it
can calcify. It is unknown what triggers this calcification. However it is influenced by the local
concentration of calcium and phosphate ions. When these products reach a certain level, they catalyse
further crystallization of calcium salts in the area. Other factors include matrix proteins that bind and
concentrate calcium and the enzyme alkaline phosphatase (shed by osteoblasts) – essential for
mineralization.
Bone resorption involves osteoclasts which arise from the same haematopoietic stem cells that
differentiate into macrophages.
Osteoclasts move along a bone surface, digging grooves called resorption bays as they break down the
matrix.
The part of the osteoclast that touches the bone is highly folded to form a ruffled membrane enabling it
to cling to the bone tightly and also seals off the area of bone destruction. The ruffled membrane
secrets: i) lysosomal enzymes (digest organic matrix) ii) hydrochloric acid that converts calcium salts into
soluble forms that pass easily into solution. Osteoclasts may also phagocytise the demineralised matrix
and dead osteocytes.
The digested matrix end products and dissolved minerals are transported across the osteoclast and
released at the opposite side where they enter interstitial fluid and then the blood. How are osteoclasts
activated? It is unclear however T-cells are important.
Control of Remodelling
1. Negative feedback hormonal mechanism that maintains Ca²⁺ homeostasis in the blood
2. Responses to mechanical and gravitational forces acting on the skeleton.
Calcium is important for
 Transmission of nerve impulses
 Muscle contraction
 Blood coagulation
 Secretion by glands and nerve cells
 Cell division
More than 99% of the body’s calcium is present in bone minerals.
The hormonal loop maintains blood Ca²⁺ within the range of 9-11mg per 100ml of blood.
Calcium requirements:
 400-800mg from birth – 10 years old
 1200-1500mg from 11-24 years old.
Hypercalcemia can lead to undesirable deposits of calcium in the blood vessels, kidneys and other soft
organs, impairing their function.
Response to Mechanical Stress
The bone’s response to mechanical stress (muscle pull) and gravity keeps the bones strong where
stressors are acting.
Wolff’s law – a bone grows or remodels in response to the demands placed on it.
Bones have different stressors e.g. weight bearing, pulling, and compression.
This tension (load) usually bends it – compressing on one side, stretching on the other and these forces
cancel each other out at the centre, so that’s why bones can have a hollow centre.
 Bones are thickest midway along the diaphysis
 Curved bones are thickest where they are likely to buckle
 Trabeculae of spongy bone form trusses or struts along lines of compression
 Large bony projections occur where heavy, active muscles attach.
Bedridden people have atrophied bones due to disuse.
The mechanism of how bone responds to mechanical stimuli is largely unknown. Deforming a bone
produces as electrical current. Stretch regions are oppositely charged.
Hormonal loop determines whether and when remodeling occurs (in response to changing Ca²⁺ blood
levels). Mechanical stress determines where it occurs.
Common development variations of the lower limbs
 Bow legs (Genu Varum) – common up to 2yo. Bowing at the tibia, usually goes away. If there is
bowing in only one leg, should investigate.
 Knock knees (Genu Valgum or a Valgus deformity) – affects children between 2-7yo. Usually
corrects itself by 7yo. No treatment really necessary. Obese children over 12yo may require
treatment.
 Rolling in of the ankles – due to joint laxity. No treatment necessary as it usually corrects itself.
 Flat feet – normal for younger age because children have low arches and loose and flexible
joints. Common in preschoolers. Present in <10% of teenagers
 Accessory navicular bone – temporary discomfort, relived by wearing arch supports for a period
of a year or two. Rarely requires surgery to remove.
 Curly middle toe – third toe curls inwards under the 2nd toe. This is acceptable until 2 years of
age.
 In toe gait (pigeon toe) is common. Caused by inset hips, internal torsion of the tibia and
metatarsus adductus.