1.

Osteology (Bone Anatomy)

Bones can be divided into 3 generic groups: long bones, short bones, and flat bones. [1, 2, 4] Long bones are formed
from a cartilage model precursor by endochondral ossification (see the image below) and can range in size from
a phalanx to a femur. They are typically tubular, have distinct anatomic zones, and are longer than they are wide.
[1, 2, 4]
Short bones arise from the same precursors but are not necessarily structurally similar to long bones, often
taking on unique shapes (eg, carpal bones). Flat bones are formed without a precursor by intramembranous
ossification [1] and can have unusual shapes (eg, skull or sternum).

Endochondral ossification of long bones through

cartilage precursor.
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Most bones have a thick, well-organized outer shell (cortex) and a less dense mesh of bony struts in the center
(trabecular bone) (see the image below). The ratio of cortical bone to trabecular bone varies widely; [5] in adults,
this ratio is typically 80:20. [4]

Trabecular and cancellous bone.

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The only bones that lack a true cortex are the vertebrae, which are covered by a compact condensation of
trabecular bone. [1] All bones are encased in a soft tissue envelope known as the periosteum, which is vital for
perfusion and nutrient supply to the outer third of the bone (see the image below). [1, 2] The remainder of the
blood supply is through nutrient vessels that pierce the cortex and supply the marrow cavity and the inner two
thirds of the cortical bone. [1, 2]

Anatomy of bone.

Long bones

Mature long bones have 3 distinct zones: epiphysis, metaphysis, and diaphysis (see the image below). [1] In
development, the epiphysis and metaphysis are separated by a fourth zone, known as the epiphyseal plate, or
physis. This segment of the bone is cartilaginous and is the region from which the bone grows longitudinally. By
adulthood, all epiphyseal plates have closed down, and a bony scar is all that remains of this important structure.
Long bones include the femur, tibia, fibula, humerus, radius, ulna, metacarpals, metatarsals, and phalanges.

Zones of mature long bone.

Epiphysis

The epiphysis is the region at the polar ends of long bones. Most commonly associated with joint surfaces, it
usually comprises a thin, compact bone shell with a large amount of bony struts (trabecular bone) for support of
the cortical shell. The network of bony struts below the compact shell is ideally suited for its job as a shock
absorber. [1]

The shell or covering of compact bone is thicker just below a joint and is known as the subchondral bone; it
supports the hyaline articular cartilage of the joint just above it. The subchondral bone is not true cortical bone,
in that it lacks some of the organization of cortical bone. [1]

The epiphysis also serves as an attachment region in many bones, allowing joint capsular attachments, many
ligamentous attachments, and some tendinous attachments as well. Like most sections of bone, it is strong, but it
lacks the rigidity of the diaphysis.

Epiphyseal plate (physis)

An extremely important zone in human development, the epiphyseal plate is responsible for longitudinal growth
of the skeleton and therefore one's height and stature. There are many diseases of the epiphyseal plate such as
achondroplasia that affect the plate’s ability to grow normally and this can lead to significant change in stature
and are often know as the skeletal dysplasias. The epiphyseal plate itself is broken down into distinct zones (see
the image below).

Zones of epiphyseal plate.

There is a layer of resting cartilage that is the precursor to the process. Cells are stimulated to replicate in the
zone of proliferation, and chondrocytes then hypertrophy in the zone of hypertrophy. They then undergo a
process of mineralization, and eventually death, in the zone of calcification. This forms the bone precursor that
will continuously be remodeled throughout life. Bones can also grow in width from direct bone formation
supported by the periosteum.

Metaphysis

The metaphysis is a transitional zone between the epiphysis and diaphysis. It is also characterized by thinner
cortical walls with dense trabecular bone. It is commonly the site of tendinous attachments to bone. It is a
metabolically active region and often supports a fair amount of bone marrow. The metaphysis is the region
where the bone made by the epiphyseal plate is fine-tuned into its diaphyseal shape.

Diaphysis

In the middle of long bones is the diaphysis, a segment of thick cortical bone with a minimal amount of
trabecular bone. It is often smaller in diameter than metaphyseal and epiphyseal bone; because its thick cortical
layer is extremely strong, it does not require a large diameter to distribute its load. The central portion is the
least dense area of the bone and is known as the intramedullary canal. The area of the bone inside the cortex is
continuous throughout an entire bone and is known as the endosteal area. [1]

Diaphyseal bone’s primary function is structural: it gives the skeleton much of its length and providing much of
the surface area for muscular and tendinous attachment.

Short bones

Short bones are also formed by the same cartilage precursor model as long bones; however, they tend to have
unique shapes and functions. They provide less overall height than long bones. Like long bones, they have a
cortical shell on the periphery and a trabecular inner portion. They vary in size and shape. Examples include the
carpal bones, vertebrae, patella, and sesamoid bones.

Flat bones

Although similar to the previously mentioned bones in some respects, flat bones differ completely in their
embryologic origin. Stemming from mesenchymal tissue sheets, flat bones never go through a cartilaginous
model. The mesenchymal sheets condense and organize and are eventually ossified. They grow from
membranous or periosteal growth. They consist of a cortical shell with a cancellous interior and are often broad
and flat. They provide protection (eg, skull) and also offer wide, flat surfaces for muscular attachment (eg,
scapula).

2. Normal Bone Anatomy and Physiology

Abstract

This review describes normal bone anatomy and physiology as an introduction to the subsequent articles in this
section that discuss clinical applications of iliac crest bone biopsy. The normal anatomy and functions of the
skeleton are reviewed first, followed by a general description of the processes of bone modeling and
remodeling. The bone remodeling process regulates the gain and loss of bone mineral density in the adult
skeleton and directly influences bone strength. Thorough understanding of the bone remodeling process is
critical to appreciation of the value of and interpretation of the results of iliac crest bone histomorphometry.
Osteoclast recruitment, activation, and bone resorption is discussed in some detail, followed by a review of
osteoblast recruitment and the process of new bone formation. Next, the collagenous and noncollagenous
protein components and function of bone extracellular matrix are summarized, followed by a description of the
process of mineralization of newly formed bone matrix. The actions of biomechanical forces on bone are sensed
by the osteocyte syncytium within bone via the canalicular network and intercellular gap junctions. Finally,
concepts regarding bone remodeling, osteoclast and osteoblast function, extracellular matrix, matrix
mineralization, and osteocyte function are synthesized in a summary of the currently understood functional
determinants of bone strength. This information lays the groundwork for understanding the utility and clinical
applications of iliac crest bone biopsy.

The Skeleton

The adult human skeleton has a total of 213 bones, excluding the sesamoid bones (1). The appendicular skeleton
has 126 bones, axial skeleton 74 bones, and auditory ossicles six bones. Each bone constantly undergoes
modeling during life to help it adapt to changing biomechanical forces, as well as remodeling to remove old,
microdamaged bone and replace it with new, mechanically stronger bone to help preserve bone strength.

The four general categories of bones are long bones, short bones, flat bones, and irregular bones. Long bones
include the clavicles, humeri, radii, ulnae, metacarpals, femurs, tibiae, fibulae, metatarsals, and phalanges. Short
bones include the carpal and tarsal bones, patellae, and sesamoid bones. Flat bones include the skull, mandible,
scapulae, sternum, and ribs. Irregular bones include the vertebrae, sacrum, coccyx, and hyoid bone. Flat bones
form by membranous bone formation, whereas long bones are formed by a combination of endochondral and
membranous bone formation.

The skeleton serves a variety of functions. The bones of the skeleton provide structural support for the rest of
the body, permit movement and locomotion by providing levers for the muscles, protect vital internal organs and
structures, provide maintenance of mineral homeostasis and acid-base balance, serve as a reservoir of growth
factors and cytokines, and provide the environment for hematopoiesis within the marrow spaces (2).

The long bones are composed of a hollow shaft, or diaphysis; flared, cone-shaped metaphyses below the growth
plates; and rounded epiphyses above the growth plates. The diaphysis is composed primarily of dense cortical
bone, whereas the metaphysis and epiphysis are composed of trabecular meshwork bone surrounded by a
relatively thin shell of dense cortical bone.

The adult human skeleton is composed of 80% cortical bone and 20% trabecular bone overall (3). Different
bones and skeletal sites within bones have different ratios of cortical to trabecular bone. The vertebra is
composed of cortical to trabecular bone in a ratio of 25:75. This ratio is 50:50 in the femoral head and 95:5 in
the radial diaphysis.

Cortical bone is dense and solid and surrounds the marrow space, whereas trabecular bone is composed of a
honeycomb-like network of trabecular plates and rods interspersed in the bone marrow compartment. Both
cortical and trabecular bone are composed of osteons.

Cortical osteons are called Haversian systems. Haversian systems are cylindrical in shape, are approximately
400 mm long and 200 mm wide at their base, and form a branching network within the cortical bone (3). The
walls of Haversian systems are formed of concentric lamellae. Cortical bone is typically less metabolically
active than trabecular bone, but this depends on the species. There are an estimated 21 × 106 cortical osteons in
healthy human adults, with a total Haversian remodeling area of approximately 3.5 m2. Cortical bone porosity is
usually <5%, but this depends on the proportion of actively remodeling Haversian systems to inactive cortical
osteons. Increased cortical remodeling causes an increase in cortical porosity and decrease in cortical bone mass.
Healthy aging adults normally experience thinning of the cortex and increased cortical porosity.

Cortical bone has an outer periosteal surface and inner endosteal surface. Periosteal surface activity is important
for appositional growth and fracture repair. Bone formation typically exceeds bone resorption on the periosteal
surface, so bones normally increase in diameter with aging. The endosteal surface has a total area of
approximately 0.5 m2, with higher remodeling activity than the periosteal surface, likely as a result of greater
biomechanical strain or greater cytokine exposure from the adjacent bone marrow compartment. Bone
resorption typically exceeds bone formation on the endosteal surface, so the marrow space normally expands
with aging.

Trabecular osteons are called packets. Trabecular bone is composed of plates and rods averaging 50 to 400 mm
in thickness (3). Trabecular osteons are semilunar in shape, normally approximately 35 mm thick, and composed
of concentric lamellae. It is estimated that there are 14 × 106 trabecular osteons in healthy human adults, with a
total trabecular area of approximately 7 m2.

Cortical bone and trabecular bone are normally formed in a lamellar pattern, in which collagen fibrils are laid
down in alternating orientations (3). Lamellar bone is best seen during microscopic examination with polarized
light, during which the lamellar pattern is evident as a result of birefringence. The mechanism by which
osteoblasts lay down collagen fibrils in a lamellar pattern is not known, but lamellar bone has significant
strength as a result of the alternating orientations of collagen fibrils, similar to plywood. The normal lamellar
pattern is absent in woven bone, in which the collagen fibrils are laid down in a disorganized manner. Woven
bone is weaker than lamellar bone. Woven bone is normally produced during formation of primary bone and
may also be seen in high bone turnover states such as osteitis fibrosa cystica, as a result of hyperparathyroidism,
and Paget's disease or during high bone formation during early treatment with fluoride.

The periosteum is a fibrous connective tissue sheath that surrounds the outer cortical surface of bone, except at
joints where bone is lined by articular cartilage, which contains blood vessels, nerve fibers, and osteoblasts and
osteoclasts. The periosteum is tightly attached to the outer cortical surface of bone by thick collagenous fibers,
called Sharpeys’ fibers, which extend into underlying bone tissue. The endosteum is a membranous structure
covering the inner surface of cortical bone, trabecular bone, and the blood vessel canals (Volkman's canals)
present in bone. The endosteum is in contact with the bone marrow space, trabecular bone, and blood vessel
canals and contains blood vessels, osteoblasts, and osteoclasts.

3. Bone tumor

Bone tumor A bone tumor is an abnormal growth of cells within a bone. A bone tumor may be cancerous
(malignant) or noncancerous (benign ). Causes The cause of bone tumors is unknown. They often occur in areas
of the bone that grow rapidly. Possible causes include: Genetic defects passed down through families Radiation
Injury In most cases, no specific cause is found. Osteochondromas are the most common noncancerous (benign)
bone tumors. They occur most often in young people between the ages of 10 and 20. Cancers that start in the
bones are called primary bone tumors. Cancers that start in another part of the body (such as the breast, lungs, or
colon) are called secondary or metastatic bone tumors. They behave very differently from primary bone tumors.
Cancerous primary bone tumors include: Chondrosarcoma Ewing sarcoma Fibrosarcoma Osteosarcomas
Cancers that most often spread to the bone are cancers of the: Breast Kidney Lung Prostate Thyroid These forms
of cancer usually affect older people. Bone cancer is more common in persons who have a family history of
cancers. Symptoms Symptoms of bone tumor may include any of the following: Bone fracture, especially from
slight injury (trauma) Bone pain , may be worse at night Occasionally a mass and swelling can be felt at the
tumor site Some benign tumors have no symptoms. Exams and Tests The health care provider will perform a
physical exam.

4. WHO Classification of Bone Tumours

5.
 6. How is bone cancer diagnosed?

A patient’s symptoms, physical exam, and results of imaging tests, and blood tests may suggest that bone cancer
is present. But in most cases, doctors must confirm this suspicion by examining a tissue or cell sample under a
microscope (a procedure known as a biopsy).

Other diseases, such as bone infections, can cause symptoms and imaging results that could be confused with
bone cancer. Accurate diagnosis of a bone tumor often depends on combining information about its location
(what bone is affected and even which part of the bone is involved), appearance on x-rays, and appearance
under a microscope.

Since a single bone metastasis can have the same signs and symptoms as a primary bone tumor, many doctors
require a biopsy to diagnose a patient’s first bone metastasis. After that, additional bone metastases can usually
be diagnosed based on x-rays and other imaging tests.

Imaging tests to detect bone cancer

X-rays

Most bone cancers show up on x-rays of the bone. The bone at the site of the cancer may appear “ragged”
instead of solid. The cancer can also appear as a hole in the bone. Sometimes doctors can see a tumor around the
defect in the bone that might extend into nearby tissues (such as muscle or fat). The radiologist (doctor who
specializes in reading x-rays) can often tell if a tumor is malignant by the way it appears on the x-ray, but only a
biopsy can absolutely determine that.

A chest x-ray is often done to see if bone cancer has spread to the lungs.
 8. Benign Tumors
If your tumor is benign, your doctor may recommend just monitoring it closely to see if it
changes. During this time, you may need periodic follow-up x-rays or other tests.

Some benign tumors can be treated effectively with medication. Some will disappear over
time. This is particularly true for certain benign tumors that occur in children, such as osteoid
osteoma.

Malignant Tumors
If you have bone cancer, treatment will include a team of doctors from different medical
specialties working together to provide care. Some will be oncologists—doctors who
specialize in cancer treatment. Your team may include an orthopaedic oncologist, medical
oncologist, radiation oncologist, radiologist, and pathologist. The goal of treatment is to cure
the cancer while maintaining function, as best as possible, in the part of the body affected by
the tumor.

Treatment depends upon several factors, including the stage of the cancer. If the cancer is
localized, cancer cells are contained to the tumor and the immediate surrounding area. When
the cancer has reached a metastatic stage, it has spread elsewhere in the body and may be
more serious and harder to cure.

Doctors often combine several methods to treat malignant bone tumors:

 Radiation therapy. Radiation therapy uses high-dose x-rays to kill cancer cells and shrink
tumors. This only treats the cancer in the area of the beam. It does not treat cancer elsewhere
in the body.
 Chemotherapy (systemic treatment). Chemotherapy is often used to kill tumor cells when
they have spread into the bloodstream but cannot yet be detected on tests and scans. It is
generally used when cancerous tumors have a very high chance of spreading. Chemotherapy
is usually given intravenously (injection into a vein) or in a pill or capsule that is swallowed.

Generally, malignant tumors are removed by surgery. Often, radiation therapy and
chemotherapy are used in combination with surgery.

9. MATERIALS AND METHODS:

Eighty patients (40 males and 40 females, ages 4-77 years) with 61 malignant and 19 benign
bone tumors were evaluated for local and distant complications after treatment. Two groups
of patients were studied: (1) 53 patients had resection without (43 patients) or with external
beam radiotherapy (RadRx) (10 patients) and (2) 27 patients underwent extracorporeal
irradiation and re-implantation without (22 patients) or with RadRx (5 patients). Patient
follow-up varied from 1 month to 13.63 years with mean follow-up of 4.7 years. Imaging
studies included bone and chest radiography, spin echo T1- and T2-weighted (or STIR)
magnetic resonance imaging (MRI), dynamic contrast-enhanced magnetic resonance imaging
(DCE-MRI), computed tomography (CT) for thoracic and abdominopelvic metastases and 3-
phase technetium-99m-labeled-methylene-diphosphonate (Tc99m MDP) scintigraphy for
bone metastases.
RESULTS:

DCE-MRI differentiated the rapidly enhancing recurrences, residual tumors and metastases
from the slowly enhancing inflammation, and the non-enhancing seromas and fibrosis.
Recurrences, metastases (mainly to lung and bone), and seromas were greater than twice as
frequent in patients after resection than after ECCRI. Although 11.3% of post-resection
patients had residual tumor, no ECRRI-treated patient had residual tumor. In contrast, after
ECRRI, infection was almost three times as frequent and aseptic loosening twice as frequent
as compared with the post-resection patients. Bones treated with RadRx and/or ECRRI
showed increased prevalence of fractures and osteoporosis. In addition, muscle inflammation
was more common in the externally irradiated patient as compared with the patient who did
not receive this therapy. However, another soft tissue complication, heterotopic ossification,
was rare in the patient after RadRx, but 25.6% of patients after resection and 40.9% after
ECRRI showed heterotopic ossification. Unusual complications after resection or ECRRI
involved adjacent nerves with partial denervation, amputation neuroma, or entrapment
(secondary to recurrence or fibrosis) after resection or ECRRI with or without RadRx. One
patient developed a posterior tibial artery pseudoaneurysm after ECRRI.

CONCLUSIONS:

Follow-up of patients with benign and malignant bone tumors demonstrated the efficacy of
DCE-MRI for distinguishing rapidly enhancing viable tumor from the slowly enhancing or
non-enhancing benign processes after different therapies. Although recurrences, residual
tumors, metastases and seromas were more common after resection, fractures, osteoporosis,
infection, and muscular atrophy predominated in the ECRRI-treated patient. RadRx further
predisposed post-resection and post-ECRRI patients to develop fractures, osteoporosis and
infection and was the major cause of persistent muscle inflammation at MRI. Because
complications can evolve and resolve years after treatment, the patients with bone tumors,
particularly sarcomas, must receive life-time multimodal imaging for maximal diagnosis and
treatment.

10. Outlook (Prognosis)

How well you do depends on the type of bone tumor.

Outcome is usually people with noncancerous (benign) tumors. But some benign bone tumors
can turn into cancer.

People with cancerous bone tumors that have not spread may be cured. The cure rate depends
on the type of cancer, location, size, and other factors. Talk to your doctor about your
particular cancer.