I Definition

Osteogenesis imperfecta (OI) is a group of genetic disorders that mainly affect the bones. The term "osteogenesis imperfecta" means imperfect bone formation. People with this condition have bones that break easily, often from mild trauma or with no apparent cause. Multiple fractures are common, and in severe cases, can occur even before birth. OI is usually inherited as an autosomal dominant condition. In autosomal dominant inheritance, a single abnormal gene on one of the autosomal chromosomes (one of the first 22 non-sex chromosomes) from either parent can cause the disease.

II History
The current four type system began with Sillence in 1979An older system deemed less severe types"Osteogenesis Imperfecta Tarda" while more severe forms were deemed "Osteogenesis Imperfecta Congenita." As this did not differentiate well, and all forms are congenital, this has since fallen out of favour. The condition has been found in an Ancient Egyptian mummy from 1000 BC. TheNorse king Ivar the Boneless may have had this condition as well. The earliest studies of it began in 1788 with the Swede Olof Jakob Ekman. He described the condition in his doctoral thesis and mentioned cases of it going back to 1678. In 1831, Edmund Axmann described it in himself and two brothers. Jean Lobstein dealt with it in adults in 1833. Willem Vrolik did work on thecondition in the 1850s. The idea that the adult and newborn forms were the same came in 1897with Martin Benno Schmidt Alternative Names Brittle Bone Disease Ekman-Lobstein syndrome Glass-bone disease

III Prevalence

Possibly affected in the United States has the best estimate of a minimum of 20,000 and possibly as many as 50,000. It is believed to be that there are 6-7 persons per 100,000 affected with osteogenesis imperfecta worldwide. In the Philippines, there are 5,174 cases according to extrapolated statistics

IV Etiology
Osteogenesis is an inherited disorder caused by genetics

V Diagnostic Exams

Physical Examination assessment of patients body parts for signs of disease. Ultrasound can identify bone abnormalities. Chronic Villi sampling via amniocentesis- for analysis of genetic mutation. Collagen test via skin biopsy skin biopsy for quantity and quality of collagen protein. DNA Analysis - allows identification of a specific mutation of type 1 collagen genes that causes OI. Radiography reveals osteopenia, fracture, bowing of long bones, vertebral compressions, and wormian bones of the skull. Dual Energy X-ray Absorptiometry (DEXA) a type of bone mineral density test. ENT/Dental To identify dentinogenesis imperfecta(treatment for this condition usually involves placement of crowns on the teeth).

VI Signs and Symptoms

Short stature Weak tissues, fragile skin, muscle weakness and loose joints Bleeding, easy bruising, frequent and in a small number of people heavy bleeding from injuries Hearing loss may begin in childhood and affects approximately 50% of adults Breathing problems, higher incidence of asthma plus risk for other lung problems Curvature of the spine.

Classifications of Osteogenesis Imperfecta Type I Most common and mildest type of OI. Bones fracture easily. Most fractures occur before puberty. Normal or near-normal stature. Loose joints and muscle weakness. Sclera (whites of the eyes) usually have a blue, purple, or gray tint. Triangular face. Tendency toward spinal curvature. Bone deformity absent or minimal. Brittle teeth possible. Hearing loss possible, often beginning in early 20s or 30s. Collagen structure is normal, but the amount is less than normal. Type II Most severe form. Frequently lethal at or shortly after birth, often due to respiratory problems. Numerous fractures and severe bone deformity. Small stature with underdeveloped lungs. Tinted sclera. Collagen improperly formed. Type III Bones fracture easily. Fractures often present at birth, and x-rays may reveal healed fractures that occurred before birth. Short stature. Sclera have a blue, purple, or gray tint. Loose joints and poor muscle development in arms and legs. Barrel-shaped rib cage. Triangular face. Spinal curvature. Respiratory problems possible. Bone deformity, often severe. Brittle teeth possible. Hearing loss possible. Collagen improperly formed. Type IV Between Type I and Type III in severity. Bones fracture easily. Most fractures occur before puberty.

Shorter than average stature. Sclera are white or near-white (i.e. normal in color). Mild to moderate bone deformity. Tendency toward spinal curvature. Barrel-shaped rib cage. Triangular face. Brittle teeth possible. Hearing loss possible. Collagen improperly formed. By studying the appearance of OI bone under the microscope, investigators noticed that some people who are clinically within the Type IV group had a distinct pattern to their bone. When they reviewed the full medical history of these people, they found that groups had other features in common. They named these groups Types V and VI OI. The mutations causing these forms of OI have not been identified, but people in these two groups do not have mutations in the type I collagen genes. Type V Clinically similar to Type IV in appearance and symptoms of OI. A dense band seen on x-rays adjacent to the growth plate of the long bones. Unusually large calluses (hypertrophic calluses) at the sites of fractures or surgical procedures. (A callus is an area of new bone that is laid down at the fracture site as part of the healing process.) Calcification of the membrane between the radius and ulna (the bones of the forearm). This leads to restriction of forearm rotation. White sclera. Normal teeth. Bone has a mesh-like appearance when viewed under the microscope. Dominant inheritance pattern

Type VI Clinically similar to Type IV in appearance and symptoms of OI. The alkaline phosphatase (an enzyme linked to bone formation) activity level is slightly elevated in OI Type VI. This can be determined by a blood test. Bone has a distinctive fish-scale appearance when viewed under the microscope. Diagnosed by bone biopsy. Whether this form is inherited in a dominant or recessive manner is unknown, but researchers believe the mode of inheritance is most likely recessive. Eight people with this type of OI have been identified. Recessive Forms of OI after years of research, two forms of OI that are inherited in a recessive manner were discovered in 2006. Both types are caused by genes that affect collagen formation. These forms provide information

for people who have severe or moderately severe OI but who do not have a primary collagen mutation. Type VII The first described cases resemble Type IV OI in many aspects of appearance and symptoms. In other instances the appearance and symptoms are similar to Type II lethal OI, except infants had white sclera, a small head and a round face. Short stature. Short humerus (arm bone) and short femur (upper leg bone) Coxa vera is common (the acutely angled femur head affects the hip socket). Results from recessive inheritance of a mutation to the CRTAP (cartilage-associated protein) gene. Partial function of CRTAP leads to moderate symptoms while total absence of CRTAP was lethal in all 4 identified cases. Type VIII Resembles lethal Type II or Type III OI in appearance and symptoms except that infants have white sclera. Severe growth deficiency. Extreme skeletal under mineralization. Caused by a deficiency of P3H1 (Prolyl 3-hydroxylase 1) due to a mutation to the LEPRE1 gene.

VII Anatomy and Physiology of the Skeletal System

Axial skeleton
The axial skeleton (80 bones) is formed by the HYPERLINK "http://en.wikipedia.org/wiki/Vertebral_column" \o "Vertebral column" vertebral column (26), the HYPERLINK "http://en.wikipedia.org/wiki/Thoracic_cage" \o "Thoracic cage" thoracic cage (12 pairs of HYPERLINK "http://en.wikipedia.org/wiki/Rib" \o "Rib" ribs and the HYPERLINK "http://en.wikipedia.org/wiki/Sternum" \o "Sternum" sternum), and the HYPERLINK "http://en.wikipedia.org/wiki/Human_skull" \o "Human skull" skull (22 bones and 7 associated bones). The axial skeleton transmits the weight from the head, the trunk, and the upper extremities down to the lower extremities at the HYPERLINK "http://en.wikipedia.org/wiki/Hip_joint" \o "Hip joint" hip joints, and is therefore responsible for the upright position of the human body. Most of the body weight is located in back of the spinal columns which therefore have the HYPERLINK "http://en.wikipedia.org/w/index.php?title=Erectors_spinae&action=edit&redlink=1" \o "Erectors spinae (page does not exist)" erectors spinae muscles and a large amount of HYPERLINK "http://en.wikipedia.org/wiki/Ligament" \o "Ligament" ligaments attached to it resulting in the curved shape of the spine. The 366 skeletal muscles acting on the axial skeleton position the spine, allowing for big movements in the thoracic cage for HYPERLINK "http://en.wikipedia.org/wiki/Breathing" \o "Breathing" breathing, and the head. Conclusive research cited by the American Society for Bone Mineral Research (ASBMR) demonstrates that weight-bearing exercise stimulates bone growth. Only the parts of the skeleton that are directly affected by the exercise will benefit. Non weight-bearing activity, including swimming and cycling, has no effect on bone growth.

Appendicular skeleton
The appendicular skeleton (126 bones) is formed by the pectoral girdles (4), the upper limbs (60), the pelvic girdle (2), and the lower limbs (60). Their functions are to make locomotion possible and to

protect the major organs of locomotion, digestion, excretion, and reproduction. The skeletal system provides four basic functions: Support for tissues and muscle Protection for vital organs Movement through bones and attached muscles Storage for minerals and immature blood cells Protection These structures protect some of the vital tissues and functional organs of the body. Typical examples are: Skull - protects the brain Vertebrae - protects the spinal cord Thoracic cage - protects the heart and lungs Movement Bones act as levers during movement and provide solid structures to which muscles are attached. The joints allow movement between bones and these movements are directly related to the type of joint and range of motion. Joints fall into one of three categories: Fixed fibrous or Synarthroses (e.g. bones of the skull), slightly moveable or Amphiarthroses (e.g. symphysis pubis) and freely movable or Diarthroses. Freely Movable joints comprises of four main groups: Ball and Socket (e.g. hip), Hinge (e.g. elbow), Pivot (e.g. radius and ulna) and Gliding (e.g. carpal joint of the wrist) Component parts of a synovial joint A fibrous capsule surrounds the joint and is strengthened by ligaments. The stability of these joints is dictated by the shape of articulating surfaces, their surrounding ligaments and muscles. For example, the knee is given great strength from 2 cruciate and 2 collateral ligaments. One of the hardest joints to dislocate is the hip. It is formed with the head of femur fitting neatly into the socket or acetabulum in the pelvis. Ligaments are tough fibrous bands of tissue which connect bone to bone and help stabilise a joint, the strongest ligament in the body being situated at the front of the hip capsule, preventing excessive backward movement of the legs. Ligaments, although stronger than muscle tissue, have fewer nerve endings and less blood supply, and therefore take longer to repair when damaged. Whilst these strong fibrous bands offer great stability to a joint in preventing excessive movement, if they are stretched or torn through injury, they do not necessarily return to their former length and therefore may remain stretched, therefore offering reduced stability to that particular joint. A bursa is a small sac formed in connective tissue lined by a synovial membrane and containing a small amount of synovial fluid. It is situated between moving parts, often between tendon and bone, to prevent rubbing. Storage In some bones, there is red marrow which produces red blood cells, some white cells and platelets. Minerals, especially calcium and phosphorous are also stored in bones and can be distributed to other

parts of the body.

VIII Pathophysiology

IX. Management

Management focuses on supportive therapy to minimize fracture and maximize function, minimize disability, foster independence and maintain overall health.

Non-surgical

Biophosphonates Drug that prevent the loss of bone mass. It inhibits digestion of bone by osteoclasts. Braces & Splints To correct and prevent deformity Provide walking aids, specialized wheelchairs, and home adaptation devices to help improve the patient's mobility and function. Physical Therapy Minimizing fracture, maximizing mobility and strengthen muscles.

Surgical

Rodding Surgery Rodding surgery involves inserting a metal rod into the bone to give it support, the rod acts as an internal splint.

Nursing Responsibility

Assessment of patients level of consciousness Give parents instructions in handling their children Promotion of appropriate physical activity Be gentle and cautious during transfers; avoid sudden pulling of limbs, neck, or spine. Never twist, bend, apply pressure to, or try to straighten limbs. Some limbs cannot be straightened because of deformity. Make sure that blankets and sheets are not too tight, and be careful when removing them to avoid getting fingers, toes, etc., caught in the folds, which could cause a fracture. Always remember the goal is focused on supportive therapy to minimize fracture and maximize function and minimize disability

X Discharge Planning
Medicine bisphosphonates (also called diphosphonates) are a class of drugs that prevent the loss of bone mass, used to treat osteoporosis and similar diseases. They are called biohosphonates because they have two phosphate (PO3) groups. Exercise - Swimming and water therapy, prolonged immobilization can further weaken bones and can lead to muscle weakness and fractured cycles. Treatment Use Braces and Splints to correct deformity. Focus on minimizing fracture and maximizing mobility. Health Teaching All movement should be slow, methodical and gentle Infants with OI should not be picked up under the axillae or around the Rib cage Never push, pull twist, bend, apply pressure, or try to straighten arms or legs Obesity Should be avoided to reduce the amount of weight on the compromised bone Out patient - Attend scheduled checkup and comply with the treatments. Diet should be advised to eat a balanced diet which includes a variety of vitamins and minerals and is low fat & sugar

Adequate calcium & vitamin D is necessary to optimize bone mass and prevent bone loss Excessive weight gain should be avoided to reduce stress or compromised bones, lungs and heart. Spiritual - Encouraged to pray more to God and strengthen their faith in Him.

Precipitating Factors Teratogens Trauma

Predisposing Factors Genetics Hereditary Age Gender

Autosomal Dominant Defect (1 mutated copy of the gene)

Defect in Type 1 collagen

Decreased Quantity of Collagen

Abnormal development of Collagen

Poorly developed bones that breaks easily

Signs & Symptoms -short stature -bones that fracture easily -skeletal deformities of limb chest & skull -hearing loss -Blue sclera etc..

OSTEOGENESIS IMPERFECTA

Preventive measures: -Rehabilitation -Minimize fracture and maximize mobility

Untreated: Complications -heart failure -respiratory infection