Bone Disease  

Hereditary bone disease	Metabolic bone disease
Infectious bone disease	Bone tumors

                                         
              Hereditary bone disease 
                 Diseases of abnormal growth plate maturation (osteochondrodysplasia).
     

Achondroplasia
          Most common (1/3000) inherited form of dwarfism.  Condition is inherited
          both as autosomal dominant and recessive trait.  The recessive form is
          invariably lethal due to severe distortion of chest cavity with respiratory
          dyfunction.  Proliferative growth plate cartilage is absent or diminished
          leading to attenuated endochondral bone growth.

          Clinical: Bones of extremities short & thick.
                    Axial skeleton normal.
                    Organ development normal.
                    Av. hgt 4'3"-M   4'-F
          Prognosis:     Normal life span.

Osteogenesis Imperfecta (OI)

          This condition represents a group of inheritable disorders caused by
          abnormal type I collage synthesis.  Aberrant collagen deposition in osteoid
          synthesis leads to "brittle bones".  This condition may confuse social and
          health care workers in cases of potential child abuse.

          Clinical: Type I (A.D.)
                              Multiple fractures in infancy.
                              Blue sclera
                              Poor dentition
                              Hearing loss
                              Kyphoscoliosis

                         Type II (A.R.)
                              Perinatal death

Osteopetrosis (Marble bone disease of Albers-Schonberg).
          Rare disease inheritable as either dominant or recessive trait.  Recessive
          form is fatal during neonatal/infant stage.

          Clinical:      Cortical overgrowth
                         Pathologic fractures
                         Anemia
                         Cranial nerve entrapment
          Prognosis:     Variable with bone marrow transplant.

Metabolic Disease 

     Osteoporosis
          The primary manifestation of osteoporosis is loss of bone mass
          (osteopenia) that leads to bone fragility and pathologic fracture.  Bone
          loss is a feature of a number of disorders.  One of the major secondary
          causes of both localized and general osteoporosis is immobility.  Typically
          the term osteoporosis refers to its primary forms which include
          postmenopausal and senile disease.

     Factors affecting total bone mass:

     1.   Genetic:  
               Racial background
               VDR polymorphism
     2.   Age:
               Max. bone density age 30's
               Av. rate bone loss 0.7%/yr
               Loss greatest in spine/femoral neck.
     3.   Hormones:
               Loss of estrogen promotes synthesis of Il-1 that stimulates
               osteoblasts to release Il-6 that stimulates osteoclasts (resorption).
               Estrogen loss may also decrease potency of growth factors that
               stimulate osteoblasts.
     4.   Mechanical:
               Weight bearing exercise through Wolff's law stimulates bone
               deposition.
     5.   Diet:
               The role of both calcium and vitamin D with regard to bone loss
               prevention appears to be most important in adolescent females. 
               These nutrients have also been shown to slow the rate of bone loss
               in older patients.

     Clinical: Early - asymptomatic
               Late - fractures, deformity, pain
               Sites - vertebral bodies, femoral head, distal radius (Colle's fract.)
                    Severe kyphosis (Dowager's hump)

     Course:   Type I (P.M.) Complications about 10-15 yrs post menopause.
                    Type II (senile) Complications at age > 65.
                    Age 90   1/3 Fem.  1/6 Male have hip fractures.
                    30-50,000 deaths per year primarily from pneumonia and/or
                    pulmonary embolism.

Rickets/Osteomalacia
     This disease results from a deficiency of vitamin D which in turn leads to
     inadequate calcium absorption.  The primary impact of the disease is on the
     skeleton.  In children (rickets) it leads to skeletal deformity and in adults
     (ostemalacia) it is primarily asymptomatic but can lead to pathologic fractures.
     Routes of deficiency:
          1.   Dietary
          2.   Low solar exposure
          3.   Decreased absorption
          4.   Increased degradation (P-450)
          5.   Impaired synthesis of 25-hydroxylase
          6.   Impaired synthese of 1-hydroxylase
                    Vit. D dependent rickets type I
          7.   Target organ resistance
                    Vit. D dependent rickets type II
          8.   Phosphate depletion
                    Antacids
                    Increased tubular excretion
     Clinical: Soft bones
                    Craniotabes
                    Frontal bossing
                    Rachitic rosary
                    Pidgeon breast
                    Leg bowing
                    Lumbar lordosis
                    Pathologic fractures
                    Osteopenia

Hyperparathyroidism
     This condition results from excessive PTH release.  The primary form results
     from hyperplastic parathyroid tissue.  The secondary form is typically a
     consequence of renal failure.
     Unchecked PTH release stimulates osteoclasts to resorb bone.  Patients suffer
     from changes ocurring in bone and from the hypercalcemia that develops.
     Clinical: Osteitis fibrosa cystica
               Brown tumor
               Hypercalcemia
               Pathologic fractures

Osteomyelitis 
     Infectious inflammation of bone and marrow cavity.  Infection typically
     originates from:
          1.   Hematogenous spread
          2.   Contiguous extension
          3.   Direct implantation

     Most common organisms include:
          1.   Staphylococcus aureus
          2.   Group A Hemolytic Streptococcus
          3.   Mycobacterium tuberculosis

     Sites for infection:
          1.   Children - Metaphysis
          2.   Adults - Any area

     Age of patient has a bearing on how the infection proceeds.  In infants, vessels
     that penetrate the epiphyseal plate spread the bacteria to the epiphysis and joint
     tissue.  In children and neonates, subperiosteal spread is rapid.  In adults
     subperiosteal abscess formation is common but spread is inhibited.
     Clinical:
          Acute Osteomyelitis
               Neutrophilic infiltrate
               Bone necrosis
               Fever, pain, edema, erythema
          Chronic Osteomyelitis
               Brodie's abscess
               Sequestrum
               Involucrum
               Draining sinus
     Complications:
          Bacteremia
          Endocarditis
          Pathologic fractures
          Septic arthritis
          Squamous cell carcinoma

     Tuberculous Osteomyelitis
          Infection of vertebral body - Pott's Diseae
          Soft tissue infection - cold abscess

Paget's Disease (Osteitis Deformans)
     This unusual disorder (3% over 50) may be caused by infection with an as yet
     unidentified (paramyxovirus?) slow virus.  Osteoblast release of Il-6 results in
     periodic excessive osteoclast bone resorption with overall increase in bone
     deposition.  Although excessive bone is formed, it is structurally unsound leading
     to pathologic fractures.
     Stages of Paget's disease:
          1.   Osteolytic stage
          2.   Mixed stage
          3.   Sclerotic stage
     Disease can be monostotic (15%) or polyostotic (85%).  Primary sites include
     spine, skull, and pelvis.

     Clinical: Primarily asymptomatic
               High-output heart failure
               Back pain/cranial nerve entrapment
               Deformities/pathologic fractures
               Osteosarcoma

Bone Tumors 
     Metastatic tumors
          The most common type of bone cancer is metastatic from the following
          sites:
               1.   Prostate       2.   Breast
               3.   Lung           4.   Kidney
               5.   GI Tract       6.   Thyroid
          Metastatic lesions present as either bone forming, osteolytic, or mixed.

     Primary Bone Tumors
          Bone Forming - Benign
               Osteoma:  Exophytic lesions commonly seen in the paranasal
                         sinuses, head, and neck.
               Osteoid osteoma:    
                    Painful lesions (< 2 cm.) found in proximal femur/tibia.  Age
                    20-30.
               Osteoblastoma:
                    Similar lesion (>2 cm.) found on axial skeleton.  Age 20-30.

     Bone Forming Tumors - Malignant

          Osteosarcoma (Osteogenic sarcoma)
               Most common primary malignant tumor excluding multiple
               myeloma.  Age 10-20.  Common site is distal femur/proximal tibia. 
               Aggressive tumors often show mutations in the p53 gene (tumor
               suppressor).  Another group with relative high incidence are those
               with other primary lesions (Paget's disease, irradiation, bone
               infarcts, multiple osteochondromatosis, and Ollier's disease.)

               Clinical:      Bone pain
                              Pathologic fracture
                              Codman's triangle
                              Starburst X-ray
                              Pulmonary metastases

Cartilaginous Tumors - Benign

     Osteochondroma
          These lesions (exostoses) occur primarily on the long bones of the
          extremities.  Usually found as solitary lesions, a rare hereditary form
          (Multiple osteochondromatosis /multiple hereditary exostosis)
          presents with many lesions and a risk for malignant transformation.
          The primary site is the metaphysis of long bones.  They are continuous
          with the bone they extend from and are capped by rudimentary cartilage. 
          Growth usually stops with epiphyseal closure. Age 10-30.

     Chondroma (Enchondroma)
          Lesions of the small tubular bones of hands and feet.  Multiple forms
          (Ollier's disease) increases the risk for malignant transformation.

Cartilaginous Tumors - Malignant
     Chondrosarcoma
          This cartilage producing tumor is the second most common
          (nonhematopoietic) primary bone cancer.  Unlike osteosarcoma, this
          tumor is seen in patients age 40-60 with a preference for the axial
          skeleton.  Major sites are the medullary cavities of the pelvis, vertebral
          bodies, proximal femur, and ribs.  Major site for metastatic spread is the
          lungs.

Miscellaneous Tumors of Bone
     Giant Cell Tumor (Osteoclastoma)
          These benign tumors are seen in the epiphysis of young adults (age 20-40).  The lytic tumor can be a source of joint pain.  Giant cells resembling
          osteoclasts are products of macrophage fusion.  An outstanding feature of
          these common tumors (20% of all benign bone tumors) is the high rate of
          recurrence after surgical curretage (60%).

Ewing's Sarcoma
     Third most common primary bone malignancy.  This tumor is seen in patients
     age 10-20 and is the second most common cancer in this age group.  Major sites
     include the diaphysis of the tibia and femur.  A translocation of the sarcoma
     gene (Chr. 22) is a common finding.  Progressive growth within the diaphysis
     results in repeated periosteal injury with subsequent bone deposition.  This
     pattern is called onion skinning.

Fibrous Dysplasia
     This is a benign condition seen in children and young adults.  Trabecular bone is
     replaced by collagenous material and woven bone.  Three forms of disease
     include:
          1.   Monostotic (70%) ribs, jaw, calvaria, femur, tibia.
          2.   Polyostotic (25%) craniofacial, pelvis, femur, shoulder girdle.
          3.   McCune-Albright syndrome (3%) polyostotic plus endocrine
               disorders.

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