Physis for the FRCS Orth

Courtesy: Quen Tang, FRCS Orth, UK

 

PHYSIS: STRUCTURE & RELATED DISORDERS
• STRUCTURE OF LONG BONE
– Diaphysis
– Epiphysis
– Metaphysis
– Articular Cartilage
– Periosteum
– Medullary Canal
– Endosteum

• OSSIFICATION
– The natural process of bone formation
– In human embryo bone appears after 6-7th week
– Typically two distinct pathways in which bone forms

1. INTRAMEMBRANOUS (cartilaginous intermediary absent)
2. ENDOCHONDRAL (cartilage model is first formed and which ossifies in latter process)

– Non-physiological : not involving the skeletal development.
– Physiological : Callus formation and regenerate development
– Pathological : ectopic ossification and myositis ossificans

A. INTRAMEMBRANOUS OSSIFICATION
– A cartilage anlage forms, and gets completely resorbed.
– On the preformed scaffold of cartilage the osteoprogenitor cells aggregates (preosseous condensation) and differentiate into osteoblasts.
– Osteoblasts lay bone successively on this scaffold in layers – Apposition (deposition upon prior bone).
– Ossification centers develop within the bone.
– The surrounding mesenchyme condense into periosteum
– The bones take on a lamellar character gradually.
– Eg: The flat bones of skull, face and clavicle

B. ENDOCHONDRAL OSSIFICATION
– Cartilage anlage forms from aggregated mesenchymal cells .

Five Stages.

– 1st stage – mesenchymal stem cells differentiates to cartilage progenitors.
– 2nd stage (the precartilaginous state) – condensation of mesenchymal stem cells to form compact nodules and differentiate into chondrocytes.
– 3rd stage – chondrocytes proliferation to form cartilage model (pre-cartilage condensation) and secrete cartilage-specific extracellular matrix.
– 4th stage – chondrocytes hypertrophy and produce collagen type X and fibronectin, so that mineralization can proceed by calcium carbonate.
– 5th stage – vascular invasion of the cartilage model and apoptosis of hypertrophic chondrocytes.

– Eg: The appendicular skeleton, vertebral column and pelvis.

– Ossification occurs first at the region forming future diaphysis of long bone – Primary center of ossification.
– The endochondral ossification spreads vertically along the axis of the developing bone in both directions.
– Secondary centers of ossification form at the ends of each bone (the epiphysis)

• GROWTH PLATE / PHYSIS
– The remaining hyaline cartilage layer between the metaphysis and the epiphysis.
– At skeletal maturity – replaced with bone to form the epiphyseal scar
– Two growth plates exist at each end of immature long bones
– Regulates, helps and determines the length and shape of mature bone
– Last portion of the bone to ossify – vulnerable to fractures.
– Composed of cartilage cells arranged in well ordered long parallel columns

• VASCULAR SUPPLY OF PHYSIS
1. Epiphyseal arteries : supply blood via multiple branches , providing vascularisation of the proliferative zone
2. Perichondrial arteries : supplies to the fibrous structure of growth plate.
3. Nutrient artery : provides four – fifth of the metaphyseal blood supply
4. Metaphyseal artery: the terminal branches of these vessels end in small vascular loops or capillary tufts below the last intact row of chondrocyte lacunae of growth plate

• PHYSIS – THREE STRUCTURAL COMPONENTS
1. CARTILAGE COMPONENT
2. BONY COMPONENT (METAPHYSIS)
3. FIBROUS PERICHONDRIAL RING AND OSSIFICATION GROOVE

A. CARTILAGE COMPONENT
1. Reserve Zone (Germinal / Resting Cartilage)
2. Zone of Chondrocyte Proliferation
3. Zone of Chondrocyte Hypertrophy
a. Maturation Zone
b. Degenerative Zone
c. Zone of Provisional Calcification

1. RESERVE ZONE (RESTING/ GERMINAL ZONE)–
– Contains spherical, single or paired chondrocytes involved in matrix production.
– Lies immediate adjacent to epiphysis.
– Cells are not organized into columns.
– two main roles: matrix production and storage
– Ratio of extracellular matrix to cell volume is high.
– The epiphyseal arteries pass through this layer on their way to the proliferative zone
– Injury to this layer leads to cessation of growth.

2. ZONE OF CHONDROCYTE PROLIFERATION –
– Three purposes—matrix production, cellular proliferation and longitudinal growth.
– It has flattened chondrocytes arranged in distinct columns – only cells of growth plate that divide (proliferate).
– The epiphyseal arteries form terminating capillaries here
– The cells have a local feedback loop (PTHrP, TGF-b, IHH).
– Growth hormone exerts its effect here.

3. ZONE OF CHONDROCYTE HYPERTROPHY –
– Cells increase in size
– Weakest zone of the physis
– The function of this zone is to prepare the matrix for calcification and to calcify the matrix.
– The lacunae that remain after apoptosis of hypertrophic chondrocytes are utilized by blood vessels.
– This zone has three discrete functional and histological zones
– Abnormalities in chondrocyte development or function can disrupt this organized sequence of physeal growth and maturation producing abnormal bones (stunted in growth and having crooked shape).

a) Maturation Zone

– Chief function is to prepare the matrix for calcification.
– Chondrocytes enlarge to five to ten times
– Matrix is mainly composed of type II collagen and proteoglycan (most common Aggrecan).
– Cell division ceases in this zone and calcium is accumulated in mitochondria

b) Degenerative Zone

– Role is further preparation of the matrix for calcification.
– Programmed cell death (apoptosis) of the chondrocytes (non inflammatory).

c) Zone of Provisional Calcification.

– Matrix vesicles, previously deposited into the extracellular matrix, release calcium into the zone of provisional calcification.
B. BONY COMPONENT (METAPHYSIS)
– It is involved in vascular invasion of transverse
– The other functions are new bone formation and bone remodeling.
– The external or anatomic remodeling gives funnel shape to metaphysis (funnelization).

– It has two components

1. The Primary Spongiosa – vascular invasion zone (Woven bone is formed)
2. The Secondary Spongiosa (remodelling of woven bone into lamaellar bone)

C. FIBROUS PERICHONDRIAL RING AND OSSIFICATION GROOVE
– A fibrous sheath surrounds the growth plate at periphery, comprises of

1. Perichondrial Ring Of Lacroix –

• provides mechanical support bone-cartilage junction of the growth plate.
• It is a dense fibrous band that encircles the growth plate at the bone-cartilage junction and in which collagen fibers run vertically, obliquely and circumferentially

2. The Ossification Groove Of Ranvier.

• contributes chondrocytes to the physis for the growth in diameter (appositional growth or latitudinal growth) of the plate.
• Three distinct cell groups:
  a) Progenitor cells for osteoblasts : this is a group of densely packed cells that forms the bony band in the perichondrial ring.
  b) Undifferentiated cells : contribute to appositional chondrogenesis and are responsible for diametrical growth of physis.
  c) Fibroblasts : cover the groove and serve to firmly anchor the perichondrium of hyaline cartilage to growth plate.

PHYSIS ASSOCIATED DISORDERS
• DISORDERS OF RESERVE ZONE
1. Gaucher’s disease – Lysosomal storage dysfunction
2. Diastrophic dwarphism – Defective type 2 collagen syntheses
3. Pseudoachondroplasia – Defective processing and transport of proteoglycans
4. Kniest’s syndrome – Defective processing of proteoglycans

• GAUCHER’S DISEASE

• Most prevalent Lysosomal storage diseases
• Autosomal recessive
• Deficiency in glucocerebrosidase
• Accumulation of glucosylceramide in lysosomes.
• Gaucher cells” in the bone marrow
• Orthopaedic Manifestations – bone pain (fracture, osteomyelitis), joint pain or contracture, bone crisis (osteonecrosis), diffuse osteopenia
• 80% will develop deformities of the distal femur or proximal tibia – “Erlenmeyer Flask” appearance

TREATMENT :

• multidisciplinary approach (orthopedic , hematologic, and neurological abnormalities)

• DIASTROPHIC DWARPHISM (DIASTROPHIC DYSPLASIA)

• Rare congenital disorder (autosomal recessive).
• Mutations in the SLC26A2 gene.
• Defective type 2 collagen synthesis
• Normal development of cartilage and its conversion to bone lost.

CLINICAL FEATURES :

• Short stature (“twisted dwarf”)
• Relatively normal trunk height
• Cleft palate (60%)
• Cauliflower ears (80%)
• Hitchhikers thumb
• Thoracolumbar scoliosis
• Severe cervical kyphosis
• Hip and knee contractures
• Genu valgum
• Skewfoot (serpentine or Z foot)
• Tarsometatarsal adductus and valgus hindfoot
• Rigid clubfeet (equinocavovarus)

TREATMENT :

• multidisciplinary approach to improve and maintain function.
• Surgical spinal instrumentation and fusion (atlantoaxial instability, cervical myelopathy, or progressive scoliosis)

PSEUDOACHONDROPLASIA

• Autosomal dominant.
• Similar to achondroplasia but without characteristic facial features
• Mutations in the cartilage oligomeric matrix protein (COMP) gene
• Defective processing and transport of proteoglycans results in abnormal protein build-up within the chondrocytes.
• Early cell death of the chondrocytes
• short limb dwarfism.

CLINICAL FEATURES:

• Short trunk
• Rhizomelic or mesomelic shortness
• Waddling gait
• Ligamentous laxity
• Odontoid hypoplasia
• Scoliosis
• Platyspondyly
• Hip subluxation
• Varus or valgus knee (commonly windswept deformity).

TREATMENT :

• Surgery if symptomatic atlantoaxial instability.
• Scoliosis is managed by bracing for curves between 25° and 45°
• Spinal fusion is indicated for larger curves.
• Femoral and iliac osteotomies often are needed for hip subluxation.
• Windswept knees are corrected with femoral and tibial osteotomies.

• KNIEST’S SYNDROME / DYSPLASIA

• Autosomal dominant.
• Mutations in the COL2A1 gene, resulting in defective processing of proteoglycans

CLINICAL FEATURES:

• Short stature
• Disproportionate short-trunk dwarfism
• Joint stiffness / contractures
• Dumbell-shaped femur
• Hypoplastic pelvis and spine
• Scoliosis & kyphosis
• Early osteoarthritis
• Osteopenia
• Coxa vara
• Genu valgum

TREATMENT :

• Multidisciplinary (Orthopedic, Facial and Ocular abnormalities).

• DISORDERS OF PROLIFERATIVE ZONE
1. Gigantism – Growth hormone driven increased cell proliferation
2. Achondroplasia – Deficiency of cell proliferation
3. Hypochondroplasia – Less severe deficiency of cell proliferation
4. Malnutrition – Decreased cell proliferation
5. Irradiation – Decreased cell proliferation

• HYPERPITUTARISM
– Due to Hypersecretion of GH due to acidophil adenoma.
– Causes excessive growth of entire skeleton in children & adolescents.

1. GIGANTISM : when GH hypersecretion occurs before the fusion of the long bone epiphysis and is characterized by tall stature.

2. ACROMEGALY : when GH hypersecretion occurs after the fusion of the epiphysis leading to large extremities and characteristic facies

– Patient may develop deformity of hip due to epiphyseal displacement(epiphysiolysis)
– Mental retardation, sexual immaturity
– TREATMENT
• Early surgical resection of tumour.
• Somatostatin analogs
• Radiation therapy

ACHONDROPLASIA

• The commonest form of abnormal short stature.About 1 in 25,000 births.
• Severe, disproportionate shortening of limb bones may be diagnosed by x-ray before birth.
• The main pathology lies in the abnormal endochondral longitudinal growth.
• Autosomal dominant : Point mutation in the gene coding for FGF receptor 3 (key role in endochondral cartilage growth).
• Adult height is usually around 125 cm in females and 132 cm in males

CLINICAL FEATURES

• Rhizomelic dwarfism
• Proximal part of limb is shorter
• Macrocephaly
• Frontal bossing (broad forehead)
• Midface hypoplasia
• Bradydactyly (short digits)
• Trident hands
• Genu varum
• Thoracolumbar kyphosis
• Foramen magnum stenosis
• Champagne Glass Pelvis
• Inverted V In Distal Femur Physis

HYPOCHONDROPLASIA

• Very mild form of achondroplasia.
• per 100,000 live births
• Short stature and noticeable lumbar lordosis.
• Head and face – not affected.
• Autosomal dominant
• X-RAY – slight pelvic flattening and thickening of long bones

TREATMENT

• Lower-limb lengthening surgery can be done in few cases with considerable chance of success.

MALNUTRITION

• Malnutrition or food restriction results in decreased cell proliferation in this proliferative zone of the physis.
• Deleterious effect of shorter bone length.
• Histological of physis: reduced chondrocytes per column in the proliferative zone.

IRRADIATION

• Irradiation in animal studies has been found to suppress cellular proliferation and cause disarray of cartilage cell
• The proliferative zone is sensitive.
• Radiotherapy to treat childhood cancers can damage the proliferative zone

DISORDERS OF HYPERTROPHIC ZONE

1. Trauma – Reduction in proportion of strengthening Extracellular matrix
2. Multiple hereditary exostosis – Hamartomatous proliferation
3. Mucopolysaccharidoses – Derangement of glycosaminoglycan metabolism
4. Rickets – Failure of calcification of chondrocytes
5. SCFE – Reduction in proportion of strengthening Extracellular matrix

• TRAUMATIC INJURY
– Ligaments in children are functionally stronger than physis
– The physis is relatively weaker part of bone
– In children, over 30% of fractures may involve injury to the growth plate – most heal without any long term complication.
– May result in pre-mature ossification of the injured part & serious deformity of bone growth.

Salter-Harris Classification (Mainly 5 Types)

• Type 1 : occurs through physis only +/- displacement. GOOD prognosis
• Type 2 : have metaphyseal spike attached to the seperated epiphysis +/- displacement. MOST COMMON
• Type 3: occurs through physis and epiphysis into the joint with joint inconguity (if displaced). POOR prognosis
•  Type 4 : occurs in metaphysis and pass through physis and epiphysis into joint. Joint inconguity(if displaced). POOR prognosis
• Type 5 : usually diagnosed retrospect. Compression or crush fractures of physis. Cause permanent damage and growth arrest. WORST prognosis

TREATMENT:
– Displaced fractures should be reduced as soon as possible.
– Types 1 & 2 : usually be done closed (non- operatively) immobilization (cast/slab) for 3-6 weeks.
– Type 3 & 4 : ORIF, require perfect anatomical reduction as they may result in premature fusion/asymmetrical growth of bone end.
– Type 5 : ORIF, causes premature fusion and retardation of growth.

• GROWTH ARREST

– Injury to the growth plate can result in a bridge of bone (or bar) forming across the cartilaginous physis.
– Premature growth arrest – lead to angular deformity of a limb or LLD.
– Bars may be peripheral, central or linear.
– Complete growth arrest – shortening .
– Partial arrest – angular deformity.

TREATMENT:
– Bony bridge is mapped out with MRI or CT scanning to ascertain the precise size and location.

– I) Resection of the bar with the interposition of fat
– II) Epiphysiodesis to complete the arrest of the physis.

If there is limb length discrepancy – further treatment

– I) To manage the length discrepancy conservatively
– II) Contralateral epiphysiodesis
– III) Ipsilateral lengthening of the affected bone.

• A bar of over 50% is not suitable for resection.
• If bar is less than 50%, resection can be considered with the Lagenskiold technique.
• This involves the removal of the bar via a tunnel through a metaphyseal window and the interposition of fat
• The fat is to prevent reformation of the bony bridge.

HEREDITARY MULTIPLE EXOSTOSIS (DISPHYSEAL ACLASIS)

• The most common and least disfiguring of all the skeletal dysplasias.
• The underlying fault is unrestrained transverse growth of the physeal plate.
• Autosomal dominant disorder.
• Mutations are seen on the chromosomes 8, 11 and 19.
• Results in benign chondrogenic bone tumours growing from the metaphysis towards the diaphysis

X-RAY

• Poorly modelled, broadened metaphysis, with sessile or pedunculated exostoses arising from the cortices.
• Bony mottled appearance around a bony excrescence indicates calcification in the cartilage cap
• The distal end of ulna is sometimes tapered or carrot shaped and reduced in length
• The radius is usually bowed and this discrepancy may lead to sub- laxation of radiohumeral joint.
• TREATMENT:
  – Conservative Management if no symptoms
  – If the deformities of forearms or legs is so severe and functionally limiting : Osteotomy
  – it should be postponed till late adolescence.

MUCOPOLYSACCHARIDOSES

• Proteoglycan’s – major component in bone matrix, cartilage, Inter-vertebral discs and synovium.
• Defective proteoglycan’s are degraded by lysosomal enzymes.
• If these enzymes deficient – accumulation of PG’S & irregular bone matrix.
  Mainly 8 types :
  – MPS type I (Hurler syndrome. Hurler-Scheie syndrome. Scheie syndrome)
  – MPS type II (Hunter syndrome)
  – MPS type III (Sanfilippo syndrome)
  – MPS type IV (Morquio syndrome)
  – MPS type VI (Maroteaux-Lamy syndrome)
  – MPS type VII (Sly syndrome)
  – MPS type IX (Hyaluronidase deficiency)
  All except Hunter’s syndrome (an X-linked recessive disorder) are transmitted as autosomal recessive.

Orthopaedic Manifestations:

• Hip dysplasia
• Carpal tunnel syndrome
• Trigger finger
• Coarse facies
• Craniocervical pathology
• Genu valgum
• X-RAY : Bone dysplasia affecting the vertebral bodies, epiphyses and metaphysis, typically bones have a spatulate pattern.

RICKETS

• Characterized by softening and weaking of bones with defective mineralization of bone matrix which is seen histologically as excessive unmineralized osteoid.
• it occurs before closure of growth plate so that abnormalities of skeletal growth are super-imposed.

AETIOLOGY-
o Deficiency of vitamin D, calcium and phosphate
o Malabsorption
o Renal diseases (renal losses, distal RTA, CRF etc).

TYPES OF RICKETS
a) Nutritional rickets or vitamin D deficiency rickets.
b) Vitamin D dependent rickets: type 1 & type 2
c) Vitamin D resistant rickets (Familial hypophosphataemia).
d) Secondary rickets : CLD, End stage renal diseases (CKD) etc.

CLINICAL FEATURES

• Large head, open fontanelles and craniotabes (frontal bossing)
• Narrow chest / Pigeon chest
• Beaded ribs- the rickety rosary
• Prominent abdomen.
• Bowing of long bones with genu valgum / varum
• Delayed dentition with irregular, soft decaying teeth
• Pale skin, flabby subcutaneous tissue, typical wizened look.

RADIOLOGICAL APPEARANCES

• “CUPPING, SPLAYING, FRAYING”
• Acute Stage – Normal rounded appearance of epiphysis is replaced by a cloudy area containing one or more indistinct centres of ossification.
• Second Stage – Epiphysis appears as a mottled irregular, ill- defined shadow and broadened. The metaphysis is ragged but is now broader than normal.
• Third Stage – The shadow becomes denser and at the end of metaphysis a dense line appears.
• Fourth stage – The characteristic increase in breadth of metaphysis is still present, but the bone is now clearly defined & shows normal content of calcium salts.

TREATMENT

• Medical : Diet and supplementation
  Prevention of deformity – child’s movements should be controlled.
  o In difficult children it is often advisable to fit ‘rickets’ splints.
  o Treatment of existing deformity- Deformity is usually corrected by splints or by osteotomy.

 

DISORDERS OF THE METAPHYSIS
1. Metaphyseal chondroplasia – Cells of hypertrophic layer extend into metaphysis
2. Acute haematogenous osteomyelitis – Low PO2 and sluggish circulation
3. Osteopetrosis – Defective osteoclastic activity
4. Osteogenesis imperfecta – Reduced normal type 1 collagen
5. Scurvy – Inadequate formation of collagen

METAPHYSEAL CHONDRODYSPLASIAS (PYLE’S DISEASE)

• Rare genetic skeletal dysplasia
• Consisting of Jansen and Schmid types in which cells of the hypertrophic zone extend into the metaphysis

OSTEOMYELITIS

• An acute or chronic inflammatory process involving the bone and its structures secondary to infection with pyogenic organisms, including bacteria, fungi, and mycobacteria.
• Common in children – Acute hematogenous
• Organisms usually settle in metaphysis
• Most often in proximal tibia or at proximal/distal femur.
• Most common organism : Staphylococcus aureus(70 %)
• Under 4 years : Haemophilus influenza

Why Metaphysis?

• Near the transverse septa separating metaphyseal from cartilage component there is low oxygen tension
• high degree of rouleaux formation of RBCs due to vascular stasis.
• High levels of phosphoglucoisomerase (enzyme compatible with anaerobic metabolism)
• The low oxygen tension inhibits WBC activity which is highly oxygen dependent – favorable for pathogens.

CLINICAL FEATURES:

• Severe pain (throbbing)
• Fever
• Malaise
• Loss of function
• Toxaemia in neglected cases.
• Metaphyseal tenderness
• Resistance to joint movement
•  Soft tissue abscess

DIAGNOSIS

•  X RAY : Faint extra-cortical outline due to periosteal new bone formation (classical sign of pyogenic OM).
• USG-may detect a sub-periosteal collection of fluid in the early stages of osteomyelitis.
• Radioscintigraphy with 99Tc-HDP.
• MRI can distinguish soft tissue infection from osteomyelitis
• Typical feature is a reduced intensity signal in T2- weighted images.
• Aspiration of pus from the metaphyseal sub-periosteal abscess or adjacent joint.

TREATMENT

• Supportive treatment for pain and hydration
• Splintage of affected part
• Antibiotic therapy
• Surgical drainage.

COMPLICATIONS

• Altered bone growth in infants, physeal damage may lead to arrest of growth and shortening of bone.
• In older children – the bone occasionally grows too long because metaphyseal hyperaemia stimuate the growth disc.

OSTEOPETROSIS (ALBERS-SHONBERT DISEASE)

• Rare metabolic disease due to abnormal resorption of immature bone
• defective osteoclastic activity.
• The result is dense bone which is prone to fracture.
• Osteopetrosis – ‘stone bone’ , marble bone disease.
• X-rays : loss of the medullary canals and dense bone.
  Rugger jersey spine
  Bone-in-bone appearance

OSTEOGENESIS IMPERFECTA (BRITTLE BONE DISEASE)
– There are multiple forms, with variable clinical pictures and differing modes of inheritance.
– Most common genetic mutations – COL 1A1 and COL 1A2 genes.
– Reduced type 1 collagen production
– Thus brittle bones – multiple fractures and deformities (such as tibial bowing).

SCURVY

• Vitamin C (ascorbic acid) deficiency.
• Vitamin C is needed for the hydroxylation of proline (vital step for the formation of collagen).
• Deficiency leads to fragile capillaries, bleeding gums and bone pain.
• The secondary spongiosa of the metaphysis is most affected.

CLINICAL FEATURES AND X RAY FINDINGS

• Bone pain
• Myalgia
• Generalized osteopenia
• Cortical thinning: “pencil-point” cortex
• Periosteal reaction due to subperiosteal hemorrhage
• Scorbutic rosary: expansion of the costochondral junctions
• Hemarthrosis
• Wimberger ring sign: circular, opaque radiologic shadow surrounding epiphyseal centers of ossification, which may result from bleeding
• Frankel line: dense zone of provisional calcification
• Trummerfeld zone: lucent metaphyseal band underlying frankel line
• Pelkin spur: metaphyseal spurs that result in cupping of the metaphysis
• Pelkin fracture: metaphyseal corner fracture

• LAWS OF THE PHYSIS
o Hueter-Volkmann law: ‘Increased compression at the growth plate slows longitudinal growth.’
o Delpeche’s law: ‘Increasing tension on the growth plate speeds growth.
o Wolff’s law: ‘Bone adapts according to loads under which it is placed.’