Miscellaneous Affections of Bone
- 1. Dr. Anshu Sharma Assistant Prof. Dept. of Orthopaediscs, GMC&H.
- 2. ACHONDROPLASIA Autosomal dominant disturbance in epiphyseal chondroblastic growth and maturation. The major abnormality is failure of normal enchondral cartilage growth at the physis. Its prevalence is approx 1 in 25,000 to 50,000 births with males more frequently affected. It is most common type of disproportionate dwarfism.
- 3. Pathophysiology:- Achondroplasia is essentially an abnormality of endochondral longitudinal growth (longitudinal growth occurs at epiphyseal plate) resulting in diminished length of the tubular bones . Membrane bone formation is unaffected , hence the normal growth of the skull vault and the periosteal contribution to bone width . In achondroplasia, the extremity involvement is rhizomelic( proximal ), with the arms and thighs more severely involved than the forearms, legs, hands, and feet.
- 4. Genetic basis : A single gene mapped to the short arm of chromosome 4 (band 4p16.3) is responsible for achondroplasia and is transmitted as an autosomal dominant trait. When one parent has achondroplasia, the chance of transmitting this gene to each child is 50%. When both parents have achondroplasia, 50% of their offspring are heterozygous and affected, 25% are homozygous, which is ordinarily fatal in the first few months of life, and 25% are unaffected. Over 80% of cases are sporadic , because few achondroplastic people have children .
- 5. Clinical Features Delayed motor milestones Normal cognitive function. Upper limbs: shortening of the upper limbs Flexed elbow short fingers and toes
- 7. Skull: A large head with prominent forehead Small mid face with a flattened nasal bridge Hydrocephalus Recurrent otitis media(due to Eustachian tube blockages) Sleep apnea (which can be central or obstructive) Spine: Dorsal spine kyphosis Lumbar spine lordosis
- 8. ANTENATAL ULTRASOUND • Antenatal detectable sonographic features include: Short femur length measurement: often well below 5th centile. The femur length (FL) to biparietal diameter (BPD) is taken as a useful measurement. Trident hand: 2nd ,3rd and 4th fingers appears similar in length. Protruding forehead: frontal bossing.
- 9. Imaging Studies Radiography Radiographs of the skull, spine, and extremities reveal the characteristic features. Lateral skull radiograph demonstrates: 1. Midface hypoplasia 2. Frontal prominence 3. Shortening of the base of the skull.
- 10. Note the increased disc height and bullet-nosed vertebrae.
- 11. • Note the posterior scalloping of the vertebral bodies. • The pedicles are short and thick and contribute to the development of lumbar spinal stenosis
- 12. Typical features of lower limbs in person with achondroplasia, including: 1. Horizontal acetabular roofs 2. Small sacrosciatic notches. 3. Inverted V-shaped distal femoral physis. 4. Genu varum and ankle varum with relative overgrowth of fibula.
- 13. Characteristic trident hand, with separation of the 3rd and 4th digits(divergent digits). The fingers are all the same in length. Short and thick tubular bones of Metacarpels and metatarsals.
- 14. Computed tomography The size of the foramen magnum can be measured most accurately by means of CT. The spinal canal is narrowed developmentally, particularly in the lower lumbar segments. CT can be used to develop a 3D image of the rib cage, which can be used to calculate lung volumes and can substantiate a successful surgical chest expansion.
- 15. Magnetic Resonance Imaging:- For the incidence and potential severity of neurologic symptoms associated with foramen magnum stenosis, a baseline MRI is strongly recommended in infancy. MRI showing cervicomedullary compression at foramen magnum.
- 16. Other Tests:- Somatosensory evoked potential (SSEP) abnormalities have been reported for 44% of neurologically intact persons with achondroplasia and are probably related to brainstem compression at the level of the foramen magnum. Pulmonary function tests are useful for preoperative evaluation when respiratory symptoms are present.
- 17. Prognosis • The standardized mortality ratio is increased for all age groups by a factor of 2.27 over that of the general population. • In children below 04 years , death most commonly occurs as a consequence of brainstem compression. • In individuals aged 5-24 years, CNS and respiratory abnormalities. • Aged 25-54 years, cardiovascular problems.
- 18. Morbidity associated with achondroplasia may include: • Otitis media • Neurologic complications • Obstructive and restrictive respiratory complications • Hydrocephalus • Spinal deformities (eg, kyphosis, lordosis, scoliosis) • Spinal canal stenosis • Genu varum • Cardiovascular complications.
- 19. • Treatment:- Currently, there is no way to prevent or treat Achondroplasia, since the majority of cases result from unexpected new mutations. • Medical Care:- • The availability of somatotropin (recombinant human growth hormone) has revolutionized the treatment of short stature. • For maximum benefit, it is recommended that therapy be initiated at a young age (1-6 years).
- 20. Surgical Care:- • All treatments are supportive. • Most of the orthopedic problems encountered in patients with achondroplasia are related to the spine. • Craniocervical stenosis, thoracolumbar kyphosis, spinal stenosis, angular deformities of the lower extremities, so treat of all associated abnormality .
- 21. Osteopetrosis Albers-Schönberg Disease = Marble Bone Disease Rare hereditary disorder There is defective osteoclast function and overgrowth of bone: which become thick, dense and sclerotic. However, their increased size does not improve their strength. Instead, their disordered architecture, results in weak and brittle bones that results in multiple fractures with poor healing. There are two separate sub types of osteopetrosis: • Infantile autosomal recessive osteopetrosis • Benign adult autosomal dominant osteopetrosis
- 22. Autosomal Recessive Osteopetrosis Infantile autosomal recessive osteopetrosis is the more severe form that tends to present earlier. Hence, it is referred to as "infantile" and "malignant“, compared to the autosomal dominant osteopetrosis. Epidemiology The natural history of the condition means that by age 6, 70% of the affected will die. Most of the remainder have a very poor quality of life with death resulting by the age of ≈ 10.
- 23. Those who survive childbirth present with : • failure to thrive • Cranial nerve entrapment • Snuffling (nasal sinus architecture abnormalities) • Pancytopaenia (anaemia, leukopaenia and thrombocytopaenia) • Hepatosplenomegaly (extramedullary haemopoesis) • Intracerebral haemorrhage (thrombocytopaenia) • Lymphadenopathy One of the commonest presentations is with ocular disturbance: failure to establish fixation, nystagmus or strabismus. The cause of these symptoms is compression of the cranial nerve roots because of foraminal overgrowth.
- 24. MRI showing Severe bilateral optic canal narrowing (arrows) in a 4-yr-old patient.
- 25. Autosomal Dominant Osteopetrosis The autosomal dominant type is less severe than its autosomal recessive type. Hence, it is also given the name "benign" or "adult" since patients survive into adulthood. • 50% patients are asymptomatic • Recurrent fractures • Mild anemia • Rarely cranial nerve palsy.
- 26. X-Ray Findings • Diffuse osteosclerosis, • Cortical thickening with medullary encroachment, • Erlenmeyer flask deformity = clublike long bones due to lack of tubulization + flaring of ends. • Bone-within-bone appearance • "Sandwich" vertebrae due to thickening and sclerosis of the vertebral endplates, and of the bone adjacent to the endplates. • Longitudinal metaphyseal striations Poorly pneumatized paranasal sinuses.
- 27. Spine radiographs reveal the classic sandwich vertebrae of osteopetrosis (red arrows). There is also marked thickening of the posterior vertebrae (yellow arrows), especially in the vertebral arch.
- 28. Generalized increased density of the bones and alternating areas of increased and decreased density in the metaphyses (bone within- bone appearance).
- 29. Densely sclerotic bone with Erlenmeyer flask deformity of the femurs with under tubulularization (lack of trabeculation) of femoral meatphyses.
- 30. Chest radiograph obtained in an infant demonstrates overall increased density of the osseous structures due to the accumulation of immature bone.
- 31. OSTEOGENESIS IMPERFECTA • Osteogenesis imperfecta is a genetic disorder of connective tissue with the clinical feature of bone fragility, multiple long-bone fractures, skeletal deformity, blue sclerae, hearing loss, and fragile, opalescent teeth (dentinogenesis imperfecta). • Less severe manifestations may include generalized ligamentous laxity, hernias, easy bruisability, and excessive sweating.
- 33. PATHOPHYSIOLOGY • Defect in the genes responsible for encoding type I collagen. • Leading to absolute reduction in the amount of normal type I collagen in bone or its replacement with a poorly functioning mutant collagen. • The formation of both enchondral and intramembranous bone is disturbed. • The bone trabeculae are thin and lack an organized trabecular pattern and intracellular matrix is reduced. • Osseous tissue almost always of the woven variety. • The secondary centers of ossification in the epiphysis are delayed in maturation
- 34. CLASSIFICATION SHAPIRO'S CLASSIFICATION:- • Osteogenesis imperfecta congenita (also known as Vrolik disease): -In utero or birth fractures; short, broad, crumpled femora and ribs -Deaths---15/16 (94%) -One survivor wheelchair bound. • Osteogenesis imperfecta tarda (also known as Ekman- Lobstein disease): -Fractures after birth but before walking -Death--0/21 (0%) -33% in wheelchair; 67% ambulatory.
- 35. SILLENCE CLASSIFICATION •Type IA:- • AD • Teeth-- N • Long bone deformity--Moderate • Hearing loss—40% • Prognosis--Fair • Eyes--Distinctly blue throughout life • Scoliosis and kyphosis in 20%.
- 36. • Type IB:- • AD • Dentinogenesis imperfecta • Long bone deformity--Moderate • Hearing loss—40% • Prognosis--Fair • Distinctly blue throughout life • Scoliosis and kyphosis in 20%.
- 38. • Type II:- • AR • Teeth--Unknown (because of Perinatal death) • Crumbled bone (accordion femora) marked • Perinatal death • Blue sclera • Marked absence of ossification.
- 39. • Type III:- • AR • Dentinogenesis imperfecta • Progressive bowing of the long bones and spine • Severe—smallest of all patients with OI • Nonambulatory, wheelchair bound • Bluish at birth, become less blue with age • Kyphoscoliosis • May die in third decade.
- 40. • Type IV:- • AD • Teeth-- N • Moderate Short stature • Low frequency hearing loss • Fair prognosis • Kyphoscoliosis.
- 41. CLINICAL FEATURES • In the severe congenital form (Sillence's type II) multiple fractures from minimal trauma during delivery or in utero cause the limbs to be deformed and short. Crepitation by palpation at fracture sites. The skull is soft and membranous. Almost always fatal, with death secondary to intracranial hemorrhage or respiratory insufficiency caused by incompetency of the rib cage; the infant is stillborn or lives only a short time.
- 42. • In the Non-lethal forms (Sillence's types I, III, and IV) fractures can occur after the minor trauma or fall. The femur is more commonly fractured than the tibia. Fractures heal at a normal rate; nonunion is relatively rare. Growth may be arrested by multiple microfractures at the epiphyseal ends. Typically, an anterolateral bow or proximal varus deformity of the femur develops; An anterior or anteromedial bow of the tibia may develop. Acetabular protrusion may be present.
- 43. • The faciocranial disproportion gives the face a triangular, elfin shape. • The ears are displaced downward and outward. The configuration of the skull is similar to soldier's helmet and is called “helmet head.” • Spinal deformity---Scoliosis or kyphosis, or both may be present. The most common type of curve is thoracic scoliosis. • Short stature. • Hypermobility of joints. • Adults may be predisposed to rupture of the patellar ligament or Achilles tendon.
- 44. • Muscles are hypotonic. • Blue sclera-opacity in the periphery of the cornea, and Retinal detachment may occur. • Deafness usually beginning in adolescence or adulthood.
- 46. Radiographic Findings •The long bones of the limbs are short and wide with thin cortices. Diaphyses are as wide as the metaphyses. Numerous fractures in various stages of healing. Multiple rib fractures and atrophy of the thoracic cage.
- 47. The skull has a mushroom appearance with very thin calvaria with marked paucity and delay in ossification.
- 48. Fracture union with hyperplastic callus formation.
- 49. PRE-NATAL ULTRASOUND Often useful in the diagnosis of type II and type III forms. • May show decreased calvarial ossification – this may result over visualisation of fetal brain detail – the skull may deform / compress with transducer pressure • May show evidence of fractures – long bones may appear shortened and/or angulated – rib may have a beaded appearance. • There may be presence of Polyhydramnios.
- 50. TREATMENT • The ideal treatment of osteogenesis imperfecta would be to correct the basic genetic defect by replacing the defective COL1A1 or COL1A2 gene with a normal one. That capability, of course, does not yet exist. • MEDICAL TREATMENT--- • Bisphosphonates • Bone marrow transplantation
- 51. BISPHOSPHONATES • Pamidronate-- is administered I/V in dosages ranging from 15 mg given every 20 days to 7 mg/kg/yr given every 4 to 6 months. • Improvement in generalized bone pain and a reduced incidence of fractures • Delayed healing of fractures or osteotomies has been reported in children treated with pamidronate. • Alendronate (orally) given over a period of 4 years was associated with reduced frequency of fracture and improved ambulatory or mobility status and improved Bone mineral density.
- 52. ORTHOPAEDIC TREATMENT • The goal of orthopaedic treatment is--- • to maximize the affected patient's function, • prevent deformity and disability resulting from fractures, • correct deformities that have developed, • watch for potential complicating conditions associated with osteogenesis imperfecta.
- 53. • Infants with birth fractures usually need only careful, supportive handling to prevent further injury. • If long-bone fractures are unstable, minimal external splinting may be used to stabilize the affected limb-- heal within a week or two. • Avoid excessive or prolonged immobilization at any age --aggravate the osteopenia and induce joint stiffness, either of which in turn increases the risk for fracture. Encourage to return judiciously to their usual level of activity as soon as feasible. • Protective bracing to prevent fractures and aid in ambulation is a mainstay in the conservative management of patients with osteogenesis imperfecta. • Nonambulatory patients-- use of motorized wheelchairs.
- 54. • General principle, intramedullary fixation is preferable to plates and screws whenever possible because of the stress risers produced by the latter. • Nonunion is an uncommon sequela of fracture or surgery, but it does occur--most commonly in the femur and humerus >> the radius, ulna, and pubis. Most important indication for surgical intervention is correction of long-bone deformity due to repeated fractures.
- 55. • Long-bone deformity in infants and children can be corrected by– • Closed osteoclasis without intramedullary fixation, • Closed osteoclasis with percutaneous intramedullary fixation, and • Open osteotomy with internal fixation (Telescopic Nails) Seekh-kabab osteotomy. • External fixation by the Ilizarov circular fixator with wire fixation and osteotomy-- to correct long-bone deformity in young adult patients.
- 57. Paget’s Disease of Bone • The English surgeon Sir James Paget first described chronic inflammation of bone as “Osteitis deformans” in 1877. • Paget's disease of bone is a chronic disease of the skeleton. • It is a common disease in older people, occurring in about 3 to 4% of the population over age 50 years. • It is slightly more common in men than women.
- 58. • Appear in families, 25 % to 40 % of the relatives of someone with the disease. • Common in people of Anglo-Saxon descent and those who live in certain geographic areas, such as England, the United States, Australia, New Zealand, and Western Europe. • It is not common in Scandinavia, China, Japan, or India.
- 59. • Paget's disease can affect any bone in the skeleton. • It appears most often in the spine, pelvis, long bones of the limbs, and skull. • It can be present in just one bone or in several bones. • It can affect the entire bone or just part of it.
- 60. Etiology • About 40-50% of people with the inherited version of Paget's disease have a mutation in the gene SQSTM1, which encodes a protein involved in regulating osteoclasts functioning, called p62. On electron microscopy of bone biopsies has demonstrated nuclear inclusions, similar to those found in viral diseases (Paramyxoviridae family) are found in the highly nucleated osteoclasts.
- 61. Pathophysiology • Begins with the Lytic phase, in which normal bone is resorbed by osteoclasts that are more numerous, are larger, and have many more nuclei (up to 100) than normal osteoclasts (5-10 nuclei). -Bone turnover rates increase to as much as 20 times of normal.
- 62. Second phase:-In Mixed phase, there is rapid increases in bone formation from numerous osteoblasts. Although increased in number, the osteoblasts remain morphologically normal. • The newly made bone is abnormal, because collagen fibers deposited in a haphazard fashion rather than linearly, as with normal bone formation. • As the osteoclastic and osteoblastic activities of bone destruction and formation repeat, a high degree of bone turnover occurs.
- 63. Final phase:- In the Final phase of Paget disease, the sclerotic phase, bone formation dominates and the bone that is formed has a disorganized pattern and is weaker than normal adult bone. • This woven bone pattern allows the bone marrow to be infiltrated by excessive fibrous connective tissue and blood vessels, leading to a hypervascular bone state.
- 64. Histology
- 65. Diagnosis • Pagetic bone has a characteristic appearance on Xrays. • ↑level of Alkaline Phosphatase in the blood. • Normal calcium, phosphate, & aminotransferase. • ↑- Markers of bone turnover in urine eg. deoxypyridinoline, C-telopeptide, N-telopeptide. • ↑ - Levels of serum & urinary hydroxyproline. • Bone scans are useful for extent and activity of the condition.
- 66. Radiological Findings Long bones X-ray:- Bowing Thickening of cortex, narrowing of medulla. Honey combed or spongy, large dense bone. Looser’s zone of transformation.
- 67. Brim Sign:- Thickening of the right pelvic brim (ileopectineal line) as compared to the left.
- 68. Osteitis circumscripta or cotton wool exudates
- 69. Tam o'shanter sign:- widening of the diploic space and an overall enlargement of the cranium
- 70. Pagets Spine:- Picture frame sign Ivory Vertebra
- 71. Blade of Grass or Candle flame sign:- Begins as a subchondral area of lucency with advancing tip of V-shape osteolysis, extending towards the diaphysis
- 72. Looser’s Zone
- 73. TREATMENT Inactive lesions doesn’t require any intervention Goals of treatment:- Suppression of Active disease Relief of Pain Prevention of Deformity, fractures and High output cardiac dysfunction Reducing the Sarcomatous transformation
- 74. Suppressive Agents BISPHOSPHONATES 2nd generation bisphosphonates like Tiludronate, Alendronate, risendronate produces longer remission at lower doses. Pamidronate – 30mg IV/day over 3 hours for 3 days Zolidronic Acid- 5mg IV over 5 mins First choice where rapid mineralization is required, in neurological symptoms, severe bone pain, risk of fracture prior to elective surgery. Vitamin D and calcium supplements. It normalizes the ALP in 6 months. Bisphosphonates should not be used in patients with renal impairment.
- 75. Calcitonin:- Dosage – 100 IU / day SC/IM for 6-18 months reduced to 50 IU / day x 3/week. Calcitonin therapy can temporarily arrest active disease. ALP, urine Hydroxyproline is reduced. Positive Calcium balance. High output heart failure is improved. Bone pain relieved. Surgical treatment is reserved for fractures, correction of bone deformity, THR, Spinal surgery. Preoperatively and postoperatively calcitonin therapy gives good results and reduces bleeding
- 76. Complications • Complications of Paget disease include the following:- • Fractures (abnormal bone) • Osteogenic Sarcoma • Neurological symptoms (compression palsy) • Joint disease (degenerative) • Cardiovascular abnormalities (hyper-dynamic circulation)
- 77. Thank you…!!!