Diseases of the Musculoskeletal Disease Flashcards
NORMAL JOINT STRUCTURE AND CLASSIFICATION
A joint consists of the ends of contiguous bones together with their surrounding soft tissue components, ligaments, tendons, and synovium.
Joints can be classified according to the type of tissue present at the articulating interface as follows: (These are all SOLID joints)
1. Bony joints (skull sutures) (synostosis)
2. Fibrous joints (pubis symphysis) (syndesmosis)
3. Cartilaginous joints - most joints in our body, hip bone, knee, etc. (symphsis)
There is a CAVITATED joint that is synovial
- i.e. the knee
- synovial cells make fluid, allowing the joint to move fluidly and also provides nutrients
- Normal synovium has a few layers of synovial lining cells at the top and then blood vessels below
- the synovium also has adipocyte, mast cells, fibroblasts, and macrophages
Cartilage in joints
Cartilage is firm yet pliable and changes shape under increasing loads such that the surfaces of the joint come into increasing contact thereby distributing the load more equitably.
Cartilage is also elastic by virtue of its abundant extracellular matrix which retains water.
When forces are transmitted from one bone to the adjacent bone, the cartilage of the joint is compressed and extracellular water is extruded.
- Upon removal of the force, the extracellular matrix draws the water back in and the cartilage recovers its original shape.
Cartilage is avascular and therefore receives all nourishment from synovial fluid.
Because joints are not perfectly congruous, during compression, flow of synovial fluid occurs.
Like bone, the articular surfaces (cartilage and subchondral bone) are dynamic and are constantly undergoing remodeling in order to optimize load distribution.
Normal functioning of a joint
The normal functioning of a joint is dependent on three features:
1) the maintenance of stability during use
2) freedom of opposed articular surfaces to move painlessly over one another within a normal range of motion
3) correct distribution of load across joint tissues in order to avoid damage.
These aspects of joint function are governed by the shape of the articulating surfaces of the joint, the integrity of the supporting tissues of the joint, and the biologic cellular control of the mechanical properties of the tissues forming the joint.
Disturbances of any one of these may lead to joint disease.
Diseases of the joint
Diseases of the joint can essentially be grouped into 3 categories:
a) ARTHRITIS - most common (inflammation/degradation) (arthritides)
b) INFECTIONS (septic arthritis)
c) TUMOURS - least common
CLASSIFICATION OF ARTHRITIS
- Non-inflammatory arthritis
a. Osteoarthritis - Inflammatory arthritis
a. Infectious
b. Non-Infectious
i. Rheumatoid arthritis
ii. Seronegative arthropathies
iii. Crystal induced arthritis
Distinction of the arthritides requires good clinical information, by the time a joint has been affected many of the morphological and histological changes are the same for the various entities.
In the majority of cases, the etiology is at best unclear.
Osteoarthritis (Degenerative Joint Disease) - clinical features
Osteoarthritis (OA) is the most common form of arthritis in the Western world affecting nearly 10% of individuals greater than 60 years of age.
Typically the disease is limited to a single or only a few, large, weight-bearing joints, usually the knee or hip.
- single, asymmetrical
Patients with OA usually complain of decreased mobility of the affected joint(s), stiffness, and pain that worsens with use and is relieved with rest.
Key features
- very common
- one/few large joints, asymmetric
- narrowing of joint space (x ray)
- increased bone production (osteophytes)
- no inflammation
- not systemic
- interfere with function
- treatment - symptomatic
Osteoarthritis (Degenerative Joint Disease) - radiographic features
Radiologically, there is loss of the joint space, osteophyte formation, increased density of the bone immediately beneath the articular cartilage (subchondral bone sclerosis), and subchondral cyst formation.
Osteoarthritis (Degenerative Joint Disease) - gross pathologic features
The articular surface and bone are misshapen with the formation of peripherally located bone spurs (osteophytes).
Rather than being smooth, pearly-blue, and shiny, the articular cartilage will show areas of thinning, roughening (fibrillation), red-brown discoloration, and often areas of complete loss of articular cartilage with exposure of the underlying bone which becomes quite smooth resembling polished marble (eburnation).
After cross-sectioning the articular surface and bone, subchondral bone sclerosis and subchondral cysts may be identified.
Despite the loss of cartilage, regenerative changes at the periphery exceed loss such that the joint is actually larger than the normal joint.
Osteoarthritis (Degenerative Joint Disease) - microscopic pathologic features
These include duplication and irregularity of the tidemark (the line where cartilage begins to undergo endochondral ossification), chondrocyte clones (large clusters of chondrocytes trying to replace the lost articular cartilage), synovial cell hyperplasia/hypertrophy, villous change of the synovium, and nil to minimal chronic inflammation.
If present, the inflammation is negligible in comparison to that present in the inflammatory arthritides.
Osteoarthritis (Degenerative Joint Disease) - pathophysiology
The sequence of events (pathophysiology) leading to OA is as follows:
i) The earliest change in the articular cartilage is loss of proteoglycans from the extracellular matrix.
- This can only be appreciated histologically by the use of special stains.
- This alteration is indicative of abnormal biochemical functioning of the chondrocytes.
ii) Small numbers of chondrocytes die and groups of enlarged chondrocytes (chondrocyte clones) develop in an attempt to replace the damaged cartilage.
iii) As the cartilage weakens, superficial cracks develop (fibrillation).
- With time, these cracks become quite deep (fissures).
- These cracks may be vertical or horizontal and may result in the breaking off of fragments of the articular cartilage which may float freely within the joint space (joint mice, loose bodies).
- The chondrocytes within the loose bodies remain viable as they get sufficient nutrition from the synovial fluid.
- The lost hyaline cartilage is often replaced to some extent by fibrocartilage.
- End-stage degenerative changes
— loss of lots of articular cartilage
— will try to make new cartilage, but it is not very good at doing so
— when it DOES eventually make cartilage, it tends to be a different type. It tends to be fibrocartilage and hyaline cartilage. So it doesn’t do as well as a job compared to the normal cartilage.
iv) Loss of articular cartilage exceeds replacement resulting in exposure of the underlying (subchondral) bone.
- This bone remodels, becoming thickened (sclerotic) in an attempt to handle the transmitted forces and often becomes smooth and polished in appearance (eburnated).
v) The subchondral bone cracks (microfractures), allowing synovial fluid to enter into the bone marrow cavity and form subchondral cysts.
vi) The loss of articular cartilage and retransmission of forces results in osteophyte formation at the lateral portion of the joint.
- These are masses of bone and cartilage formed by the mesenchymal cells of the synovium.
- They are also called bone spurs.
- In the fingers they are called Heberden and Bouchard’s nodes.
Osteoarthritis (Degenerative Joint Disease) - etiology
Many underlying conditions may result in the development of OA (secondary OA) including congenital hip dysplasia, fracture, infection, avascular necrosis, metabolic diseases, etc.
More commonly, however, the exact etiology is unknown (primary OA).
While OA increases with increasing age, OA is not an inevitability of aging.
On the contrary, many joints remain essentially normal even into extreme old age.
OA is not simply a result of wear and tear, although this may play a significant role.
OA may result from any condition that affects the articular surfaces of the joint, the bones of the joint, or the tissues supporting the joint (ligaments, tendons, capsule).
It is an end stage of multiple processes
Rheumatoid Arthritis (RA) - clinical features
RA is the most common of the inflammatory arthritides.
RA is a chronic, systemic disease of unknown etiology that primarily attacks the synovial lining of the peripheral joints.
- The synovitis results in the secondary destruction of the articular cartilage.
- chronic meaning that it occurs over years
RA is characterized by bouts of remission and exacerbation and affects women more than men (3-5:1).
Peak incidence is 20-40 years old
Affects all races
Extra-articular features are common and include arteritis, neuropathy, pericarditis, pleuritis, lymphadenopathy, and rheumatoid nodules.
Patients complain of malaise, and pain and stiffness of the joints which is typically worse in the morning and improves throughout the day.
RA usually involves multiple joints, bilaterally and symmetrically.
- Although any joint may be involved, the small joints of the hands and feet are most commonly affected.
The joints are usually swollen, painful, hot, and red.
Synovial fluid analysis of an acute joint frequently reveals neutrophils however, no organisms grow on culture.
Advanced RA:
- in hands, the fingers will point towards ulnar side aka away from the thumb
Rheumatoid Arthritis (RA) - radiographic features
The typical findings are: periarticular loss of bone (osteopenia), bone erosion, narrowing of the joint space,
subluxations, dislocations, and soft tissue swelling.
Rheumatoid Arthritis (RA) - gross pathologic features
One sees joint destruction but, unlike OA, there is little reparative activity, and osteophytes and new bone formation are not prominent.
The synovium is hyperplastic and thickened and extends over the articular surface (pannus).
Rheumatoid Arthritis (RA) - Microscopic pathologic features
The synovial lining cells increase in number (hyperplasia) and size (hypertrophy).
The synovium is expanded by edema, increased numbers of blood vessels (angiogenesis), and chronic inflammatory cells (lymphocytes and plasma cells – not neutrophils) which frequently form lymphoid follicles with germinal centres.
This expansion causes the synovium to form finger-like extensions (papilla/villi) that extend into the joint space and over the surface of the articular cartilage (pannus).
Rheumatoid Arthritis (RA) - Pathophysiology
After the initial injury, there is attack of the synovial lining. This results in:
- leaky vessels causing edema and makes tissues expand, and also causes large components (like fibrin) to cross, possibly causing fibrin deposition leaking out and causing grains in the synovial space within the joints
- influx of lymphocytes, histiocytes, and plasma cells, NOT neutrophils.
- inflammatory mediators cause synovial lining cells to undergo hypertrophy and hyperplasia
- neovascularization
- synovial hyperplasia
Lymphocytes will be arranges in many prominent lymphoid nodules
Fibrin will coat the surface
Synovium is thick due to hyperplasia, forming finger-like extensions that form over the articular cartilage.
- called pannus
Pannus
- associated with fibrin, so there will be white deposition on it
- pannus gets trapped in joint space and sheared by bones in the articular cartilage and that causes tearing and bleeding; and this breakdown of blood leads to iron deposition, giving it a brown-red color
Inflammation will form lymphoid follicles with germinal centres
The pannus grows in joint space, burrows into bone, and destroys the underlying cartilage by several mechanisms:
1) The pannus physically covers the cartilage thereby preventing it from receiving adequate nutrition from the synovial fluid,
2) The pannus releases enzymes that directly destroy cartilage and,
3) The pannus releases inflammatory mediators that activate osteoclasts which destroy bone and cartilage.
Pannus may cause joint to fuse and be unable to move properly
- fusion is termed ankylosis
- if the pannus is ossified or turned into a bone, it is called bony ankylosis
there is loss of articular cartilage and periarticular bone at the joint
The end result is destruction of the articular surface and loss of bone with joint subluxation and instability.
There is PMN leukocytes in synovial fluid
Joint findings: rice bodies
- fibrin bodies floating around in space
- fibrin bodies contains neutrophils; but neutrophils are not within the pannus; neutrophils do not destroy the joint
Rheumatoid Arthritis (RA) - etiology
- Autoimmunity (cellular - CD4+, humoral - RF)
RA is believed to be an immune mediated disease.
Most patients have rheumatoid factor (auto-antibodies to autologous IgG).
Rheumatoid factor complexes with IgG and deposits in the synovium where an immune reaction takes place inciting damage via released enzymes and pro-inflammatory mediators.
Inflammation causes pleuritis that can deposit in tissues and organs to make things called rheumatoid nodules. Rheumatoid nodules:
- it is necrosis in tissue and inflammation around necrosis, creating large circular nodules around the joint
- firm, non tender
- round, oval nodule
- micro: central fibrinoid necrosis surrounded by histiocytes, lymphocytes, and plasma cells
- Microbial agents acting synovial lining
- EBV
- parvovirus
- retrovirus
- mycobacteria - Genetic susceptibility
- familial
- twin studies
- HLA-D
Bone function
Locomotion
Protection
- heart
- lungs
- brain (skull)
Hematopoiesis
- RBC, WBC, platelets
Metabolic (bone is made of these components and also stores them)
- Ca2+
- PO4
Energy (inside of bone has fat tissue)
- fat
Morphological classification of bones
206 bones
axial/appendicular
Tubular
- long
- short
Flat
Cuboidal
Bone anatomy - long tubular bones
Middle is diaphysis
Ends are epiphysis
Order: epiphysis, growth plate, metaphysis, diaphysis
Cortex of bone
Function is to maintain structure
Periosteum on the outside
- attached to cortex
- has cells that lie dormant
- periosteum can wake up and cause cell production, such as cells that become chondrocytes to replace lost bone cells (such as during injury)
- made of fibrous CT
Endosteum
Lacuna
Osteon
- bone forms around blood vessels
- has haversian canal in the middle, which is blood vessels
Outer lamella
Trabeculae
Spongy bone
Osteocytes distributed around
Black lines are canaliculi
Medullary cavity is the inner area of bone
Compact bone on outer layers of bone, then trabecular bone on the inner layers
Compact bone aka cortical bone
To make sure bone is not crushed under forces
Circumferential lamellae
Haversian system (osteon)
- haversian canal
- lacuna
Osteocytes all around
Black lines are canaliculi
- allows communication between different cells
Trabecular bone aka spongy bone
Is where bone marrow is housed
It is medullary bone
Is where all the biological processes take place
- maintenance of calcium and phosphate levels
Formed of sheets of bone that cross together
Bone trabeculae surrounding yellow bone (fatty) marrow (adipose tissue)
- As we age, bone marrow has more fat
- Strands of bone are called trabeculae
Lamellar bone vs Woven bone
Lamellar bone
- very organized bone
- both bone in cortex and trabecullar bone have this
- lines aka layers on top of one another: organized
Woven bone
- precursor before lamellar bone
- not as organized
- more cellular
- has collagen fiber type I
- it will eventually organize to become lamellar bone
- present in developing fetus
- in adult is 1-2% of woven bone
Bone growth
Cells
Matrix
Minerals
Physical
Hormonal
Cytokines
Growth factors
- Cells need to make appropriate matrix (cartilage, bone, etc.)
- organic phase of bone then becomes mineralized, so need to make sure there is calcium, phosphate, and hydroxy ions
- the bone also responds to physical forces. the more force, the more bone is created
- there are also hormones and cytokines and growth factors that circulate around to facilitate bone formation
Bone development types
Endochondral ossification
Intramembranous ossification
Endochondral ossification
There is initial cartilaginous precursor model that gets replaced by bone
Growth plates at ends of bones are examples of endochondral ossification
- cartilage is at the top
- bottom has dying cartilage cells because there is ingrowth blood vessels. Then, the cartilage matrix becomes mineralized.
- the trabecular mineralized cartilage will serve as a calcified scaffolding that allows for bone cells to grow in from the periphery, and then there will be new bone laid down on top
- now there is new bone
Most bone in the body are formed this way
Intramembranous ossification
Bone is laid down directly and on top of itself, and then expands
Done by bones of skull and jaw (the gnathic bones collectively)
Immature mesenchyme will be called upon to differentiate and the cells will become osteoblasts
- osteoblasts are the cells that produce bone, which will make matrix
- when cells are surrounded by matrix, the cells are now called osteocytes
- now, the matrix will be mineralized or calcified, which makes hard bone
- it grows via deposition of new bone on the surface. The left hand or right hand side will expand
Cartilage cells - chondrocytes
Cartilage is made by chondroblasts
When chondoblasts are encased by cartilage matrix, they are now called chondrocytes
Chondrocytes sit in spaces called lacunae
Bone cells - osteoblasts
Cells that make bone when things are dead
When osteoblasts are surrounded by matrix, then the cells are called osteocytes
Bone cells - osteoclasts
Is a larger cell with multiple nuclei
Derived from a hematopoietic precursor
Does resorption or removal of bone
There is resorption bay next to osteoclasts
Osteoclasts will remove weak bone areas by forming a border with the bone and a tight seal
- then they release hydrogen ions, which is acid, into the border. This caused demineralization of the bone, which removes the mineral component. The organic component remains
- the osteoclast releases enzymes that can degrade the bone
Basic multicellular unit
The osteoclasts and osteoblasts work in unison to make sure weak bone areas are replaced by strong bone
Takes 2-2.5 years to replace bone
Remodelling cycle: the process of removing weak bone and replacing it with stronger bone
- constantly occurs
BONE COMPOSITION AND FUNCTION
Bone consists of two components:
1) an organic component (collagen, bone-forming and bone-related proteins)
2) an inorganic (mineral) component (calcium phosphate = hydroxyapatite)
Besides the obvious locomotor role bones play, they also protect internal organs, are key in the regulation of serum calcium and phosphate, and house the marrow, from which hematopoietic cells (red blood cells, white blood cells, platelets) originate.
MORPHOLOGICAL CLASSIFICATION OF BONES
Bones can be categorized based on their gross appearances into several forms:
- Tubular bones
- a) long tubular - femur, tibia, fibula, humerus, ulna, radius
- b) short tubular - phalanges, metacarpals, metatarsals).
- The tubular bones can be divided into 3 regions: epiphysis (above the growth plate also known as the physis), metaphysis (directly below the growth plate), diaphysis (area between
metaphyses at either end of the bone) - Flat bones - ribs, sternum, scapula
- Short (epiphysioid) bones – carpals in hands, tarsals in feet
- Irregular bones - pelvis, vertebrae, skull
Despite the different gross morphological appearances of bones within the human body, they all essentially have a similar design with a thick outer rim of dense cortical bone and a less dense, spongy or honeycomb- like interior called medullary or cancellous bone.
- The cortex resists bending and provides structural integrity whereas the medullary bone is where metabolic processes take place – blood cell production, calcium and phosphate homeostasis.
HISTOLOGICAL CLASSIFICATION OF BONES
Under the microscope, bone can have different appearances depending on how well organized the collagen fibres are and whether or not the organic component of bone is mineralized or not.
- Lamellar bone - collagen fibres arranged in parallel layers or sheets (lamellae), 98% of bone is lamellar from infancy to adulthood
- Woven (non-lamellar) bone - randomly oriented coarse collagen fibres, seen in fetuses, initial new bone formation in disease states (for instance: fracture, bone tumours,etc). Lamellar and woven bone are readily distinguished by viewing bone under polarized light.
- Mineralized vs non-mineralized bone (osteoid) - new bone typically forms on pre-existing bone (appositional growth). When it is laid down there is a mineralization lag time of about 10 days. The presence of increased osteoid may signal disease of mineralization (rickets/osteomalacia).
- Cortical bone - consists of concentrically arranged lamellar bone around a vascular core (haversian canal) to form an osteon, it is dense and resists bending
- Cancellous bone - spongy bone which is made up of a series of interconnecting plates of bone perforated by holes providing greater surface area for metabolic activity
BONE CELLS
- Osteoblasts - flat to round cells produce organic component of bone, lie on surface of bone, mesenchymal derivation
- Osteocyte - osteoblast embedded within bone, connected to other osteocytes/cells and interstitial fluid via long processes within numerous canaliculi
- Osteoclasts - multinucleated giant cells which resorb bone, hematopoietic stem cell derivation (blood- borne monocyte)
- Chondroblasts/chondrocytes - round cells that produce cartilage matrix, analogous to osteoblasts/osteocytes
- Periosteal cells - firmly adherent thin tough fibrous membrane which covers bone surface except at articular surface and insertion of tendons and ligaments; inner layer (layer closest to bone) forms bone, allowing for growth in width
BONE DEVELOPMENT AND GROWTH
Embryologically, an initial precursor skeleton made of immature uncommitted mesenchyme is formed which then forms bone via two mechanisms:
- Endochondral ossification
- Intramembranous ossification
Bone is not static and is continuously undergoing changes in its microscopic structure (remodeling) in response to various stresses.
Remodeling is achieved by the actions of the osteoblasts and osteoclasts which are so closely co-ordinated that they are often referred to as the bone structural unit or the bone remodeling unit.
If a bone has been sufficiently remodeled that changes are visible by the unaided eye, the bone is said to have undergone modeling.
Under normal conditions bone formation equals bone resorption and equilibrium is maintained.
- This phenomenon is referred to as coupling.
Factors promoting net bone formation include estrogen, testosterone, growth hormone, and weight bearing activity.
Factors promoting net bone resorption include corticosteroids, excess thyroid hormone, parathyroid hormone, and lack of weight bearing activity.
Endochondral ossification
All bones in the body except the craniofacial bones form by this mechanism. An initial primitive cartilage bone model is made that eventually undergoes calcification killing the chondrocytes. Blood vessels grow in from the periosteum and bone is deposited on the remaining cartilage matrix. This process normally occurs in the mid-diaphysis and extends in both directions (primary ossification centre). Eventually a secondary centre of ossification forms in the epiphyses by the in-growth of additional blood vessels, leaving behind the growth plate (physis) which allows for continued vertical growth, until adolescence at which point it also is invaded by vessels and undergoes ossification leaving an epiphyseal scar and stopping further growth.
Intramembranous ossification
The craniofacial bones form by this mechanism.
Primitive mesenchymal cells directly lay down bone.
There is no pre-existing cartilage model
DISEASES OF BONE - CLASSIFICATION
- Abnormal synthesis of organic matrix components
a. Disturbances in collagen synthesis - osteogenesis imperfecta
b. Disturbances in proteoglycan synthesis - mucopolysaccharidoses
c. Chondrodysplasias - Achondroplastic Dwarfism - Abnormal formation of inorganic matrix components (mineralization)
a. Hyperparathyroidism
b. Osteomalacia/Rickets - Abnormal cell linkage
a. Osteosclerotic-conditions - osteopetrosis, Paget disease of bone
b. Osteopenic-conditions - osteoporosis - Accumulation of abnormal metabolic products
- Infectious bone disease
- Bone tumours
BONE DISEASES RESULTING FROM ABNORMAL SYNTHESIS OF ORGANIC MATRIX COMPONENTS
As the formation of normal collagen molecules is complex, it can be affected at various stages of its production.
- Interestingly, the various collagen defects manifest clinically quite differently but have in common that tissues in which collagen is prevalent are affected.
OSTEOGENESIS IMPERFECTA (OI)
OSTEOGENESIS IMPERFECTA (OI)
Name given to a heterogeneous group of conditions which have in common the production of abnormal type I collagen.
Different presentation depending on where defect in collagen synthesis occurs
Can be inherited in autosomal dominant autosomal recessive, or spontaneous mutations and present at birth (congenita) or later in childhood (tarda)
OI - is classified into 4 categories based on specific phenotypes, biochemical data, and hereditary
patterns:
1. neonatal lethal (10%)
2. severe nonlethal (20%)
3. moderate and deforming
4. mild nondeforming
Defects in collagen result in weak, brittle bone, and abnormalities of other tissues in which collagen is a significant component: sclerae, teeth, ligaments
Results: osteopenia, bone fractures with deformities, blue sclerae, lax joints, deafness, malformed teeth (dentinogenesis imperfecta) in 25% of patients
Microscopically the bone is hypercellular and predominantly woven.
- The cortices are thinned, the trabeculae are short, thin widely spaced and disorganized.
Depending on severity of disease patients may die shortly after birth or may live relatively normal life.
Treatment - no therapy currently exists to alter the course of the disease. Correction of deformation and fracture prevention is all that can be attempted.
BONE DISEASES RESULTING FROM DISTURBANCES IN MINERAL HOMEOSTASIS
Calcium and phosphate play a crucial role in human biologic processes.
- About 99% and 85% are contained within the skeleton respectively as hydroxyapatite.
Calcium homeostasis is regulated by several endocrine hormones including parathyroid hormone, vitamin D, and calcitonin.
- Its regulation is also dependent upon the normal functioning of target organs (kidney, gut, bone).
A major bone disease resulting from disordered mineralization is rickets/osteomalacia.
Rickets/Osteomalacia
Rickets/osteomalacia result from failure of normal mineralization of bone due to vitamin D, calcium, or phosphate deficiency, ingredients essential for normal bone mineralization. Deficiencies may result from numerous causes: inadequate diet or sun exposure, liver disease, kidney disease, and genetic enzyme defects. The disease is referred to as rickets in children and osteomalacia in adults. Children present with skeletal deformities including beading of the costochondral junctions of the ribs (rachitic rosary), a chicken- breasted appearance, enlarged wrists, knees, and ankles, and curvature of the long bones (anterior bowing of the legs). In adults bone pain is the most common symptom secondary to microfractures. Radiography reveals generalized osteopenia and fractures. Macroscopically there is a marked increase in the amount of nonmineralized matrix (osteoid) on the surfaces of the cortical bone, frequent microfractures, and resorptive changes typical of secondary hyperparathyroidism. Treatment is aimed at replenishing the missing ingredient(s) necessary for mineralization.
Paget Disease of Bone - BONE DISEASES RESULTING FROM ABNORMAL CELL LINKAGE
Paget disease of bone is a disease in which, initially, there is a wave of resorption by osteoclasts that is followed by a wave of osteoblastic deposition of new bone.
- Ultimately, the result is thick, disorganized, sclerotic bones.
This disease typically affects northern Europeans.
Most often the disease is monostotic (affects one bone) and asymptomatic and is detected incidentally.
Patients with polyostotic disease come to clinical attention due to bone pain, fractures, deformities, arthritis, or nerve impingement.
- In these patients, the axial bones (skull, vertebrae, pelvis) are more commonly affected.
Occasionally the disease can be generalized.
- The disease is felt related to a slow-virus infection of osteoclasts leading to their activation.
- Osteoblasts react in turn by laying down new bone which however is disorganized.
Microscopically, increased numbers of resorbing osteoclasts are seen initially along with fibrovascular changes of the marrow.
- This is followed by osteoblastic proliferation and osteoid deposition leading to the classic mosaic pattern.
A rare complication of Paget’s disease is the development of malignancy in one of the affected bones.
Osteoporosis - BONE DISEASES RESULTING FROM ABNORMAL CELL LINKAGE
Osteoporosis refers to decreased density of normally mineralized bone.
This disease has a high prevalence and associated morbidity.
Females are affected more often (3:1).
Normal bone density peaks at about age 35.
- Thereafter net bone loss is a normal consequence of aging.
If this loss is excessive and fractures ensue, the condition is pathological.
- Most cases (95%) are of unknown etiology.
- The remaining cases result from increased bone resorption.
The most common presentation is major and minor fractures.
- Microfractures result in vertebral crush fractures leading to loss of vertebral height, kyphosis & Dowager’s hump.
Mineralization is normal but the cancellous bones are thin, elongated, and disconnected from one another.
Numerous microfractures are identifiable.
Osteoporosis may be slowed or prevented by exercise, good diet, calcium supplementation, and hormone replacement therapy.
Osteoporosis - Risk factors
Race/genetics/sex
- poorly understood, more common in Caucasians, females more than males, probably due to decreased peak bone mass
Age
- net bone loss progresses with age
Estrogen
- bone loss is accelerated postmenopausally as estrogen normally inhibits osteoclast activity.
- Other causes of decreased estrogen include anorexia nervosa, exercise-induced amenorrhea, Turner’s syndrome, hypopituitarism, oophorectomy
Hypercortisolism, endogenous, Cushing=s syndrome, exogenous, corticosteroid therapy
Hyperparathyroidism
Immobilization
- weight-bearing exercises supplies mechanical stresses necessary for maintenance of bone integrity
Nutritional deficiency
Others
- alcohol, smoking, malignancy
BONE TUMOURS
Malignant - Osteosarcoma
Malignant – Chondrosarcoma
Osteosarcoma
Aggressive bone producing tumour with predilection for young
Usually arises in long bones at sites of increased growth (metaphysis)
Associated with pain, rapidly enlarging mass, fractures, destruction of involved bone, early metastasis.
- histologically categorized into osteoblastic, chondroblastic, fibroblastic subtypes, but all have similar behaviour
- other variants exist and are separated based on behaviour, location, and associated underlying conditions (ie. familial predisposition).
Almost uniformly fatal 20 years ago, current combined chemotherapy and surgery achieves ~85% 5 yr survival
Limb salvage therapy is used increasingly resulting in improved patient functioning
Chondrosarcoma
Occurs in older, skeletally mature patients
Involves pelvic bones, proximal long tubular bones – not bones of acral sites (hands and feet)
Large destructive lesions with characteristic arc and ring-like calcifications on radiographs
Consist of atypical cartilage cells in hyaline cartilage
Locally aggressive, higher grade tumours will metastasize
Treatment is surgery; chemo and radiotherapy have little effect
Morphological variants exist including clear cell chondrosarcoma, mesenchymal chondrosarcoma,
dedifferentiated chondrosarcoma (the last two behave more aggressively)
