DISEASES OF BONES

Diseases Associated with Abnormal Bone Matrix

OSTEOGENESIS IMPERFECTA (TYPE I COLLAGEN DISEASE):

A group of mainly autosomal dominant genetic disorders resulting from defective synthesis of type I collagen due to mutations in the gene for type I collagen . Affected bones have thin bone cortices and trabeculae and are markedly fragile and easily broken. In addition to bone, other tissues rich in type I collagen are also affected e.g. sclerae, teeth ears, joints and skin

:OSTEOPOROSIS A condition in which the bone mass is reduced below the level necessary .for normal bone function

Pathogenesis: An excess of bone resorption over bone formation due to increased resorption, decreased .formation or both

:Causes Senility due to age-related decrease in osteoblastic. 1 (.activity (senile osteoporosis Estrogen deficiency, mainly due to increased. 2 osteoclastic activity (postmenopausal (.osteoporosis Excessive production or administration of adrenal. 3 cortical hormones, due to decreased osteoblastic .activity Local factors e.g poliomyelitis, paraplegia or. 4 immobilization of fractured bones, due to decreased mechanical stimulation of osteoblastic .activity

:Pathology Variable thinning of bone cortices and trabeculae with normal bone .mineralization

:Effects/Complications Bone pains. 1 Reduced height or even. 2 kyphosis, due to vertebral collapse Pathological fractures. 3 following minor trauma, mainly in neck of femur and pelvic bones

Diseases due to osteoclastic dysfunction

:OSTEOPETROSIS A goup of genetic disorders resulting from osteoclastic dysfunction leading . to diffuse bone sclerosis The sclerotic bones are, however, .fragile and easily fractured

:Pathology Defective bone remodeling with. 1 persistence of woven bone Marked thickening of bone cortices and. 2 trabeculae with marked narrowing of marrow spaces Narrowing of neural foramina with. 3 compression of exiting nerves

PAGET'S DISEASE OF BONE (OSTEITIS ):DEFORMANS A rare disease that probably results from osteoclastic dysfunction due to a slow . virus infection by a paramyxovirus The disease appears after the age of 40 . years and may be familial It is usually generalized affecting the leg bones, vertebrae and skull but may rarely .be localized affecting mainly the tibia

:Pathology Early in the disease, there is. 1 increased osteoclastic bone resorption with replacement of the affected bones by poorly mineralized osteoid and highly vascularized fibrous tissue leading to bone softening and deformity with kyphosis and bowing of leg bones (.(osteolytic phase

Later on, bone resorption gradually. 2 decreases and bone formation progressively increases leading eventually to thickening and hardening of the deformed bones and the skull (osteoblastic phase). Microscopic examination of bone at this stage shows thickened bone trabeculae with a characteristic .mosaic (jigsaw puzzle) appearance

:Effects/Complications (Bone deformity (see above. 1 Bone pains. 2 Pathological fractures. 3 Osteoarthritis due to abnormal stresses on the. 4 joints by the bone deformity Deafness due to compression of the 8th cranial. 5 nerve by narrowed exit foramina in the skull 6. Spinal cord compression by thickened vertebral bodies Osteosarcoma in 1% of cases. 7 High output cardiac failure due to increased. 8 venous return from the abnormal bones Increased serum alkaline phosphatase. 9

Disease associated with Abnormal Bone Mineralization

:RICKETS A bony disease of infants (6 months 2 years) resulting from vitamin D deficiency, most commonly due to lack of exposure to ultraviolet rays of the sun (which changes (.subcutaneous sterols to vitamin D

:Bony manifestations These result from failure of mineralization of bone with accumulation of excessive osteoid on the surface of bone trabeculae leading to abnormally soft bones. :They include

Thickening of frontal and parietal bones . 1 (of the skull (bossing Delayed closure of skull sutures and fontanelles Delayed eruption of teeth. 3 ( Thinning of occipital bones (craniotabes. 4 .2

Pigeon chest: The sternum is pushed .5 forwards with a longitudinal groove on each side Rickety rosary: The chest appears. 6 "beaded" on each side due to enlargement of the costochondral junctions Harrison's sulcus: A transverse groove on. 7 each side of the chest corresponding to the insertion of the diaphragm in the rib

Deformity of the lumbar vertebrae . 8 in the form of kyphosis, lordosis or scoliosis

Narrow pelvic inlet: The sacral promontory is pushed forwards . and the acetabula inwards

.9

In females, this may lead to difficult labor later on

Bowing of long bones (femur, tibia,. 10 (radius, ulna Swelling of wrists, ankles and knees due to widening of the epiphyseal plates . 11

:Microscopically there is. 12 a) Increased osteoid on surfaces of poorly mineralized bone trabeculae b) Irregular thickening of the epiphyseal plates due to failure of osteoclastic resorption of cartilage (consequent to failure of mineralization of the carilage ( matrix

:Extra-skeletal manifestations
Pot belly due to flabbiness of abdominal muscles. 1 Enlargement of spleen and lymph nodes. 2 Anemia. 3 Low serum calcium and phosphorus. 4

:Complications and causes of death

Gastroeneteritis. 1 Bronchopneumonia. 2

:OSTEOMALACIA A bony disease of adults resulting from . deficiency of vitamin D and calcium It usually occurs in females following repeated pregnancies and is characterized by deformities of long bones and vertebrae and narrow pelvic inlet, .consequent to bone softening

OSTEITIS FIBROSA CYSTICA (von ):RECKLINGHAUSEN'S DISEASE OF BONE A bony disease resulting from excessive secretion of parathyroid hormone by hyperplasia or adenoma of the parathyroid . glands Parathyroid hormone leads mobilization of calcium and phosphate from bone and increased resorption of calcium from the .bowel

:Pathology Generalized bone decalcification and resorption :associated with Increased osteoclasts. 1 Focal replacement of. 2 bone by fibrous tissue that commonly undergoes cystic degeneration Tumor-like masses composed of fibrous tissue, . 3 abundant hemosiderin and numerous (osteoclasts (brown tumors

:Effects/Complications Bone pains. 1 Bone swellings. 2 Pathological fractures. 3 Hypercalcemia, hypophosphatemia and. 4 increased serum alkaline phosphatase Renal calculi. 5

:RENAL OSTEODYSTROPHY Bony changes seen in patients with chronic renal failure particularly .those receiving dialysis

:Pathogenesis Mobilization of calcium from bone due to. 1 secondary hyperparathyroidism consequent to phosphate retention resulting from decreased glomerular filtration Inadequate production of active vitamin D. 2 metabolites by the failing kidneys :Deposition of aluminum in bone, derived from. 3 a) Dialysis solutions prepared from water with a high aluminum content b) Aluminum-containing oral phosphate binders

Pathology: The following changes may be seen :separately or in variable combinations Osteitis fibrosa cystica in 80 90% of patients. 1 Rickets/osteomalacia in 20 40% of patients. 2 Increased bone density (osteosclerosis) due to . 3 excessive formation of woven bone in 30% of patients Amyloid deposition in bone and periarticular tissues in some patients .4

Bone Infections )(Osteomyelitis

:ACUTE SUPPURATIVE OSTEOMYELITIS Acute suppurative inflammation of bone and its soft tissues, namely, periosteum, Haversian canals and bone marrow :Causative organisms Staph. aureus: The commonest. 1 Other organisms: Streptococci, E. coli, H.. 2 influenzae, Proteus, Pneumococci, typhoid bacilli

:Predisposing factors Trauma: This leads to a hematoma. 1 which provides a good medium for bacterial growth Age and sex: Male children and adolescents are most commonly affected .2

:Routes (modes) of infection

Blood borne infection from a septic focus. 1 elsewhere in the body e.g skin boil, tonsillitis. This is the commonest mode of infection leading to "acute "hematogenous osteomyelitis Local spread of infection from a nearby. 2 focus of suppuration e.g dental abscess, suppurative otitis media Direct infection of bone through a. 3 compound (open) fracture

:Bones affected In acute hematogenous osteomyelitis, the. 1 metaphyses of long bones are the .commonest site of affection In non-hematogenous osteomyelitis, any. 2 .bony site can be affected

Pathology of acute hematogenous :osteomyelitis A localized suppurative inflammation (abscess). 1 develops in the metaphysis from which infection rapidly spreads to the bone marrow cavity and . along the Haversian canals to the periosteum Infection of the periosteum is rapidly followed by. 2 accumulation of pus underneath the periosteum . i.e. formation of a subperiosteal abscess Thrombosis then occurs in the penetrating arteries. 3 leading to ischemic necrosis of a variable portion of the bone which becomes gradually separated from the surrounding viable bone by osteoclastic ". activity. The necrotic bone is called "sequestrum

As the infection becomes less acute, new. 4 bone is formed by the irritated osteoblasts, particularly subperosteally. The subperiosteal new bone forms a shell around the sequestrum, known as "involucrum". The involucrum is often interrupted by irregular openings known as "cloacae" through which pus is discharged and may dissect its way to .open through the skin by multiple sinuses

N.B. Infection does not usually spread to :nearby joints because a) The epiphyseal cartilage provides a mechanical barrier against spread of .infection from the metaphysis b) The periosteum is firmly attached to the margin of the epiphyseal cartilage preventing spread of infection from the .subperiosteal abscess

:Complcations Acute toxemia. 1 Septicemia which may lead to acute bacterial endocarditis Pyemia due to septic thrombophlebitis. 3 Pathological fracture. 4 Chronicity. 5 Sympathetic effusion in nearby joints. 6 Suppurative arthritis due to local spread of .7 infection to joints where the metaphysis is partly intra-articular e.g hip and shoulder joints .2

:NONSPECIFIC CHRONIC OSTEOMYELYTIS This follows acute suppurative osteomyelitis and is characterized by thickened deformed bones with .cloacae and skin sinuses discharging pus :Complications Pathological fracture. 1 Secondary amyloidosis. 2 Squamous cell carcinoma developing in a skin sinus .3

:BRODIE'S ABSCESS A localized chronic osteomyelitis that occurs most commonly in the upper tibial metaphysis. It appears as a small cavity filled with pus or serous fluid and surrouned by reactive .sclerotic bone

:TUBERCULOUS OSTEOMYELITIS This is always secondary and usually results from hematogenous dissemination of infection from a tuberculous focus in the . lungs, lymph nodes or urinary tract The tuberculous reaction leads to caseation and bone destruction with only little or NO new bone formation. Any bone can be affected but the commonest sites are the .vertebrae

Tuberculosis of the Spine (Pott's ):Disease

This develops most commonly in the lower dorsal (thoracic) and upper lumbar vertebrae. Infection usually starts in a single vertebral body leading to caseation and bone destruction, then : spreads a) through the inter-vertebral discs to involve other vertebral bodies, and b) to the nearby soft tissues leading to localized accumulations of caseous material known as cold .abscesses

:Complications Deformity of the spine due to vertebral collapse, in the form. 1 of kyphosis, lordosis or scoliosis Paraplegia due to compression of the spinal cord by caseous. 2 material and necrotic bone fragments derived from the diseased vertebral bodies :Cold abscess in. 3 a) Retropharyngeal space or posterior triangle of the neck ( (cervical vertebrae (b) Intercostal space along a rib (thoracic vertebrae c) Psoas sheath (psoas abscess), inguinal region or even ( popleteal fossa (lumbar vertebrae Miliary tuberculosis. 4 Secondary amyloidosis. 5

Bone Tumors and Tumor-like Conditions

:BONE FORMING TUMORS :These include Osteoma. 1 Osteoid osteoma. 2 Benign osteoblastoma. 3 Osteosarcoma. 4.

:Osteoma A benign tumor composed of woven or lamellar . bone It develops most commonly in cranial and facial . bones It appears grossly as a hemisphecal hard mass that bulges underneath the periosteum or endosteum. It is usually solitary but multiple osteomas occur in Gardner's syndrome (an autosomal dominant disorder characterized by multiple osteomas, intestinal adenomatous polyps, epidermal cysts (.and fibromatosis

):Osteosarcoma (osteogenic sarcoma A malignant mesenchymal tumor in which the neoplastic cells form osteoid or . calcified bone matrix It is the commonest primary malignant bone . tumor It occurs most commonly between the ages of 10 and 25 years, particularly in males. Cases occurring after the age of 40 years are usually preceded by Paget's disease of .bone or bone irradiation

:Gross appearance The commonest site of osteosarcoma is metaphysis of long bones, particularly around the knee joint, although any bone . can be affected It appears grossly as a fusiform mass that destroys and replaces the bone and often elevates and infiltrates the periosteum. It may also infiltrate the surrounding skeletal muscle. The consistency and color vary according to the microscopic (histologic) :type of the tumor

In the osteoblastic (osteosclerotic) type. 1 in which the neoplastic cells form excessive bone matrix, the consistency is firm to hard and the . color is grayish The neoplastic bone often forms spicules that run perpendicular to the long axis of the bone giving a characteristic "sun ray appearance" in X-ray . films Another characteristic X-ray finding is the "Codman's triangle" resulting from the deposition of reactive subperiosteal bone in the angle between the .bone and the elevated periosteum

In the osteolytic type. 2 in which there is only little or practically no new bone formation, the consistency is soft and the cut surface is pinkish-grayi with areas of .necrosis and hemorrhage

In the telangiectatic type. 3 which is highly vascular, the consistency is soft and the color is .purplish-red

:Microscopic appearance :Osteosarcoma consists of Malignant osteoblasts which may be polygonal, . 1 spindly or multinucleated and show variable nuclear pleomorphism and mitotic activity depending on the grade of the tumor A stroma containing variable amounts of osteoid,. 2 calcified bone matrix, cartilage, fibrous tissue and blood vessels depending on the histologic type of the tumor

:Spread Direct (local) spread to periosteum, .1 surrounding muscles and marrow cavity Blood (hematogenous) spread to lungs and other organs. This occurs early .2

Lymphatic spread. This is rare and late. 3

:CARTILAGE FORMING TUMORS :These include (Osteochondroma (exostosis. 1 Chondroma. 2 Benign chondroblastoma. 3 Condromyxoid fibroma. 4 Chondrosarcoma. 5

):Osteochondroma (exostosis
A benign developmental tumor-like lesion consisting . of bone and hyaline cartilage It arises most commonly from the metaphysis of long bones near the epiphyseal plate and appears grossly as a bony mass covered by a cap of cartilage and attached to the bone by a pedicle. It is usually solitary but multiple exostosis are inherited as an autosomal dominant disease. It may rarely undergo malignant transformation into a chondosarcoma, particularly when .multiple

:Chondroma A benign tumor composed of hyaline . cartilage It occurs most commonly in the short .tubular bones of the hands and feet It is usually solitary but multiple chondromas occur in Ollier's disease. It may rarely undergo malignant transformation into a chondrosarcoma, .particularly when multiple

:Chondrosarcoma . A malignant cartilaginous tumor It occurs most commonly in adults between the ages of 30 and 60 . years, particularly in males It usually arises do novo but may rarely arise from a pre-existing .exostosis or chondroma

:Gross appearance The commonest sites of chondrosarcoma are the pelvic bones, ribs, shoulder girdle and proximal . femur or humerus It appears grossly as a firm to hard, lobulated, translucent, bluish-gray mass that destroys and replaces the bone. Focal calcification is common and constitutes and important radiological sign. There may be also myxomatous degeneration and . necrosis The mass may be located within the medullary cavity (central or intramedullary chondrosarcoma) or on the surface of the bone (peripheral or juxtacortical (.chondosarcoma

:Microscopic appearance Chondrosarcoma consists of malignant cartilage cells . and a cartilaginous matrix Low grade chondrosarcomas may be so well diffrentiated and, hence, difficult to distinguish from benign chondromas. In such cases, clinical and radiological features may be more important . for differentiation than microscopic examination High grade chondrosarcomas, on the other hand, show marked nuclear pleomorphism, multinucleate tumor giant cells and frequent mitosis and may be difficult to differentiate from other high grade sarcomas. .Immunohistochemistry may help in such cases

:Spread .Local to surrounding tissue. 1 Blood spread to lungs and other .2 organs, mainly in high grade tumors

:FIBROUS AND FIBRO-OSSEOUS TUMORS :These include Fibrous cortical defect and non-ossifying fibroma Fibrous dysplasia. 2 Fibrosarcoma. 3 Malignant fibrous histiocytoma. 4

.1

:Fibrous dysplasia A benign tumor-like lesion of unknown etiology that may involve a single bone (monostotic type) or (. multiple bones (polyostotic type It occurs most commonly in children and usually . affects the ribs, jaw, femur and tibia Microscopically, it consists of fibrous tissue interspersed by thin, branching or curved trabeculae of woven bone that lack osteoblastic rimming. It may rarely change to a malignant .fibrous histiocytoma

:MISCELLANEOUS TUMORS :These include Ewings sarcoma. 1 Osteoclastoma. 2 Multiple myeloma. 3 Non-Hodgkins lymphoma. 4

:Ewing' s sarcoma . A highly malignant tumor of neuroectodermal origin Virtually all of these tumors have a reciprocal translocation between chromosomes 11 and 22 ([.[t(11;22 It occurs most commonly between the ages of 10 and 25 years .and usually affects the diaphyses of long bones

:Gross appearance A soft grayish mass that infiltrates and replaces the bone, surrounded by parallel layers of reactive subperiosteal bone that gives a characteristic "onion skin" .appearance in X-ray films

:Microscopic appearance Sheets of uniform small round cells with hyperchromatic nuclei and scanty cytoplasm containing .glycogen

:Clinical features Bone swelling and pain, sometimes accompanied by fever, leucocytosis and increased ESR, a picture that .may resemble osteomyelitis

:Spread Local to surrounding tissues. 1 Hematogenous to lung and other organs including other bones .2

Osteoclastoma (Giant Cell Tumor of ):Bone A bone tumor characterized by presence of numerous osteoclastic giant cells Its origin is not settled but it probably arises from the fibroblast or monocyte rather than the osteoclast It occurs most commonly between 20-40 years of age

:Gross appearance The commonest sites are the epipyhses of long bones, particularly the lower end of the femur, the upper end of the tibia, the upper end of the humerus and the lower end of the radius It appears grossly as a soft grayish mass ,that replaces & expands the epiphysis surrounded by a thin shell of cortical bone that gives a sensation of egg-shell crackling on palpation

:X-ray Appearance A characteristic soap bubble appearance due to persistence of variable amounts of thin bone trabeculae within the tumor

:Microscopic appearance Consists of Numerous osteoclasts appearing as. 1 large cells with many nuclei Plump, oval or spindly cells. 2

:Behavior (Most cases are benign (grade I tumors. 1 Some cases are locally malignant and frequently. 2 (recur after removal (grade II Rare cases are frankly malignant and may metastasize to the lungs. These show nuclear pleomorphism and frequent mitosis in the oval/spindly cells and a decreased number of (osteoclasts (grade III .3

:METASTATIC TUMORS Commoner than primary tumors and occur most commonly in sites rich in red bone marrow e.g. vertebrae, ribs and proximal .humerus and femur

Results most commonly from :hematogenous dissemination of Carcinomas, particularly thyroid, breast,. 1 lung, stomach, kidney, suprarenal and prostatic carcinomas Various sarcomas. 2 Childhood tumors e.g. neuroblastoma,. 3 Wilms tumor, rhabdomyosarcoma and Ewings sarcoma Choriocarcinoma and malignant melanoma. 4

:Effects Bone destruction leading to bone pains and tenderness, pathological fracture and hypercalcemia .1

Reactive new bone formation: This is rare . 2 and is typically seen in metastatic carcinoma of the prostate Anemia due to bone marrow replacement. 3