orthopedic speciality

1. Presented by dr lauay hassan PGY5
Supervised by assistant prof dr omer barawi
10/3/2016
Shar hospital

2.  Understand the pathology and the
management of paget disease,eiosinophilic
granuloma and heterotopic ossification in
relation to orthopedic specialty

3. Introduction
 First Described in 1877 by James Paget
 Chronic, non-metabolic bone disorder
 Characterized by aggressive bone resorption,
and abnormal formation and remodeling ⇒an
unbalanced derangement of normal
processes
 Results in bone deformity, structural
weakness, altered joint biomechanics

4.  Epidemiology
◦ A disease of middle to advanced age Rare below age
40
 Prevalence in US~1% over age 40
 1.5-3% over age 60
◦ Incidence doubles every decade after age 50
 Men>Women (1.6 : 1)
◦ Geographic variation Highest prevalence in
Britain, Australia, New Zealand, North America and
Western Europe

5.  Etiology
 Unknown
 Proposed Theories Viral Paramyxovirus, measles virus, RSV,
canine distemper virus
 Viral particles seen in pagetic osteoclasts
 Genetic5-40% have 1st degree relative with Paget’s
 Genetics
◦ inheritance
 most cases are spontaneous
 hereditary
 familial clusters have been described with ~40% autosomal dominant
transmission
◦ mutations
 at least 4 genes have associated with Paget's disease (& other
disorders of bone turnover)
 most important is SQSTM1 (p62/Sequestosome)
 tend to have severe Paget disease
 Environmental Arsenic
 Animals: cattle, dogs

6.  Pathophysiology
◦ Abnormal osteoclasts↑quantity
◦ ↑size
◦ ↑activity
◦ ↑# of nuclei
 Aggressive, focal bone resorption makes large
cavities in bone
 Leads to osteoblast recruitment and overactive
osteoblastic activity
 Rapid, disorganized bone formation
 New bone isCoarse, disorganized, irregular,
woven
 Less resistant to forces
 ∴Prone to deformity and fracture

7.  3 Phases of Disease
◦ 1.) Osteoclastic/ResorptivePhase
◦ Bursts of osteoclastic activity causing bone resorption
◦ Lytic lesions, trabecular and cortical thinning
◦ Osteolytic “fronts”advance longitudinally from bone
end toward middle ( “V”or “flame”shaped, ~1cm/yr)
 2.) Osteoblastic/Sclerotic or Mixed Phase
 Mixed osteoclastic and osteoblastic activity
 Net activity is osteoblastic with deposition of
structurally abnormal bone
 Bone expansion, hyperostosis, osteosclerosis,
heterogeneous ossification

8.  3-Late “Burn Out”Phase↓Activity
 End result: widened, heterogeneously ossified,
but generally sclerotic bones with irregular,
thickened trabeculae
 Phases correlate radiologically and histologically
 􀂆All 3 Phases may be present simultaneously in
the same patient or the same bone

9.  Diseas location
 Monostotic (25%) or polyostotic(75%)
 􀂆Typically affectsPelvis (70%)
 Femur (55%)
 Lumbosacralspine (53%)
 Skull (42%)
 Tibia (32%)
 Rarely in hands, feet
 􀂆No bone-to-bone spread

10.  Clinical Presentation and Complications
 Usually asymptomatic
 Incidental findingAbnormal radiograph or other imaging
 Abnormal labs (↑AlkPhos)
 Bone pain
 Constant
 􀂆Poorly localized
 􀂆Present at rest
Worse on weight-bearing
 pain may be the presenting symptom
due to
 stress fractures
 increased vascularity and warmth
 new onset intense pain and swelling
 be suspicious for Paget's secondary sarcoma in a patient with a known history
of Paget's who complains of new onset intense pain and swelling
◦ cardiac symptoms
 can present with high-output cardiac failure particularly if large/multiple
lesions & pre-existing diminished cardiac function
 Bone/limb deformity

11.  Fracture
 Arthropathy
 ↑incidence of joint disease
 􀂆Specific pattern of joint
 diseases. in hip, ↑freq of
 coxa vera, protrusio,
 concentric joint space
narrowing

12.  ↑Skin temperature
 Hypervascularity due to ↑bone turnover activity
 ↑bone turnover causes ↑cardiac demands and may lead to high-output heart
failure
 High-output cardiac failure is caused by the numerous arteriovenous fistulas
present in the pagetic bones
 Neurologic complaints
 Hearing loss/vertigotemporal bone involvement with auditory nerve
compression
 􀂆Cranial nerve palsies
 􀂆Spine involvementMechanical cord compression
 “vascular steal
 Hypercalcemia
 Rare
 􀂆Usually inactive or bed-ridden patients
 􀂆Signs & SymptomsNausea, vomiting, MSK aches, hyper-reflexia, weakness,
polyuria, headache, lethargy, altered mental status, …coma

13.  Malignant transformation
◦ Paget's sarcoma
 less than 1% will develop malignant Paget's
sarcoma (secondary sarcoma)
 osteosarcoma is the most common, followed by
fibrosarcoma and chondrosarcoma
 most common in pelvis, femur, and humerus
 Paget's sarcoma has a poor prognosis
 5-year survival for non-metastatic Paget's sarcoma is less
than 5%
 appropriate treatment for Paget's sarcoma includes
chemotherapy and wide surgical resection
 Paget's sarcoma typically presents as a destructive lesion
without periosteal reaction.

15.  Diagnosis
 Clinical assessment
 Characteristic radiographic appearance
 Labs (↑AlkPhos)
 Bone Scan
 Usually benign and multiple lesions in old
patients are pagets ,hyperparathyroidism and
bone infarcts
 Rarely:
 CT
 MRI
 Biopsy

16. Long bones bend across the trajectories of mechanical stress; thus the tibia
bows anteriorly and the femur anterolaterally. The limb looks bent and feels
thick, and the skin is unduly warm – hence the term ‘osteitisdeformans’. If
the skull is affected, it enlarges; the patient may complain that old hats no
longer fit. The skull base may become flattened (platybasia), giving the
appearance of a short neck. In generalized Paget’s disease there may also
be considerable kyphosis, so the patient becomes shorter and ape-like,
with bent legs and arms hanging in front of him.
Cranial nerve compression may lead to
impaired vision,
facial palsy, trigeminal neuralgia or
deafness. Another cause of deafness is otosclerosis.
Vertebral thickening may cause spinal cord or nerve
root compression. Steal syndromes, in which blood
is diverted from internal organs to the surrounding
skeletal circulation,
may cause cerebral impairment and spinal cord
ischaemia. I
f there is also spinal stenosis the patient develops
typical symptoms of ‘spinal claudication’ and lower
limb weakness

17.  Radiographs
◦ coarsened trabeculae which give the bone a blastic
appearance
 both increased and decreased osteodensity may exist
depending on phase of disease
 lytic phase
 lucent areas with expansion and thinned, intact cortices
 'blade of grass' or 'flame-shaped' lucent advancing edge
 mixed phase
 combination of lysis and sclerosis with coarsened trabeculae
 sclerotic phase
 bone enlargement with cortical thickening, sclerotic and lucent
area

18. ◦ remodeled cortices
 loss of distinction between cortices and medullary cavity
◦ long bone bowing
 bowing of femur or tibia
◦ fractures
◦ hip and knee osteoarthritis
◦ osteitis circumscripta
 (cotton wool exudates) in skull
◦ Paget's secondary sarcoma
 shows cortical bone destruction
 soft tissue mass
 MRI
◦ may show lumbar spinal stenosis
 Bone scan
◦ accurately marks site of disease
◦ intensely hot in lytic and mixed phase
◦ less hot in sclerotic phase
 CT scan
◦ cortical thickening and coarsened trabeculae

25.  CT/MRI
 Incidental finding
 Evaluation of atypical presentations,
neurological involvement, and possible
malignant transformation
 CT: trabecular/cortical thinning, thickening,
irregularity
 MRI: non-specific marrow changes

27.  Biochemistry
◦ Serum AlkPhosEnzyme found in osteoblastic membrane
◦ Indicator of osteoblastic activity
◦ ↑in Paget’s, but can be normal
◦ Levels correlate with disease extent and activity
◦ elevated urinary hydroxyproline (collagen breakdown marker)
◦ increased urinary N-telopeptide, alpha-C-telopeptide,
and deoxypyridinoline
◦ normal calcium levels
 Other recommended tests ESR -elevation may indicate
malignant transformation
 CRP
 Ca -hypercalcemiamay occur in Paget’s
 PO4
 25-hydroxyvitamin D -rule out osteomalacia
 LFTs-rule out liver disease

28.  Diagnostic Biopsy
 Diagnosis is usually achieved clinically and by
plain radiographic appearance
 Biopsy rarely required
◦ Characteristic HistopathologyDisorganized,
immature trabeculararchitecture with irregular cement
lines (“mosaic”pattern)
◦ Rimming osteoblasts and/or multinucleated osteoclasts

34.  Management Options
 (May require no treatment if asymptomatic)
◦ Supportive Care
◦ Pharmacologic
◦ Surgical (Orthopedic/Neurosurgical
 Supportive Care
◦ Occupational therapy Physical aides
◦ Counseling for fall+fracture prevention
 Physical therapy
 Analgesics
 Weight control

35.  Pharmacologic Management
◦ Goals Relieve symptoms and Prevent potential
complications
 Normalization of serum AlkPhos associated with
better long-term outcomes and disease control
Indications to treat Pain
 Deformity
 Neurologic symptoms
 Asymptomatic, but high-risk for complications
(prophylactic)
 Management of hypercalcemia(rare)
 Pre-op: reduce blood flow and potential
operative blood loss

36.  Calcitonin is the most widely used. It reduces
bone resorption by decreasing both the activity
and the number
of osteoclasts; serum alkaline phosphatase and
urinary
hydroxyproline levels are lowered. Salmon
calcitonin is more effective than the porcine variety;
subcutaneous injections of 50–100 MRC units are
given daily until pain is relieved and the alkaline
phosphatase levels are reduced and stabilized.
Maintenance injections once or twice weekly may
have to be continued indefinitely, but some
authorities advocate stopping the drug and
resuming treatment if symptoms recur. Calcitonin
can also be administered in a nasal spray.
 Bisphosphonates bind to hydroxyapatite crystals,

37. inhibiting their rate of growth and dissolution. It is
claimed that the reduction in bone turnover following
their use is associated with the formation of lamellar
rather than woven bone and that, even after treatment
is stopped, there may be prolonged remission of
disease (Bickerstaff et al., 1990). Etidronate can be
given orally (always on an empty stomach) but dosage
should be kept low (e.g. 5 mg/kg per day for up to 6
months) and vitamin D and calcium should also be
given lest impaired bone mineralization results in
osteomalacia. The newer bisphosphonates (e.g.
alendronate or pamidronate) do not have this
disadvantage, so they should be used as the treatment
of choice; they produce remissions even with short
courses of 1 or 2 weeks.

38.  BisphosphonatesSynthetic analogues of inorganic phosphate, adhere
to mineralized surfaces
 Ingested selectively by osteoclasts
 Disrupts enzyme pathways and reduces osteoclastic bone resorption
 calcitonin
 causes osteoclasts to shrink in size and decreases their bone resorptive activity within
minutes
 administered subcutaneously or intramuscularly
 teriparatide
 is contraindicated in Paget's disease due to risk of secondary osteosarcoma
 Surgical Management
 Few require surgery
◦ Common Procedures Corrective osteotomy of long bone deformity
 indications
 fractures through pathologic bowing of long bones
 impending pathologic fracture of long bone with bowing deformity
◦ Arthroplasty (hip, knee)
 the most common complications include
 malalignment with knee arthroplasty
 bleeding with hip arthroplasty
◦ Combination arthroplasty with osteotomy
◦ Fracture fixation

39. ◦ Preoperative Considerations
◦ Medical assessment for extraskeletalmanifestations eg.
high-output heart failure
 Medical treatment of active disease
 Preoperative autologousblood donation
◦ Thorough planningeg. good quality x-rays for
templatingand device selection
 Intraoperative Considerations
 Blood salvage system
 Expansileapproach + soft tissue release
 Sharp reamers/burrs/drills for IM access
 Extramedullaryguide/navigation systems
 Concomitant osteotomy

40.  PostoperativeConsiderations
 Monitoring for cardiac complications
 Continued medical tx of active disease
◦ ↑Heterotopic ossification Prophylaxis against HO
◦ Possible future excision of HO for pain/ROM

41.  1-Tieg provides a review of Paget's disease of bone and
treatment indications. In his review, he discusses that most
patients with Paget's disease are asymptomatic, but in those that
do present, pain is the most common presenting symptom. He
recommends medical and surgical treatment of asymptomatic
patients who have active disease at sites where complications are
likely to develop
 Altman did a review of 290 patients with Paget's disease of bone.
His findings showed 83% had one or more rheumatic syndromes.
He found the rate of osteoarthritis related to Paget's disease was
elevated in the hip and knee. Rheumatoid arthritis,
hyperuricemia, and gout did not appear increased in this group.
Mangham et al looked the rate of secondary sarcomas as a result
of Paget's disease of bone. They found the rate to be around
0.3%, with male predominance. They also found that widespread
skeletal involvement by Paget's disease was not a significant risk
factor for malignant transformation

42.  Smith et al. reviewed the pathologic complications of
Paget's bone disease. Paget's bone disease
commonly causes osseous weakening (deformity and
fracture) and arthritis in the hip joint. Management
of end stage disease is successful with cemented
and cementless total hip arthroplasty. Bleeding is the
most common intra- and post-operative
complication of surgery.
Gabel et al. retrospectively reviewed thirteen patients
who had had sixteen total knee arthroplasties for
Pagetic gonarthrosis. Unlike total hip arthroplasty
surgery, Paget disease did not increase the amount
of blood lost during the operation or in the
postoperative period. The most common
complication associated with total knee arthroplasty
was malalignment.

43.  Hansen et al. reviewed the incidence of
osteosarcomas complicating Paget's Disease. Of
the typical sites that are usually involved in
Paget's disease (e.g., spine, pelvis, femur, tibia
and humerus), secondary osteosarcoma tends to
spare the spine.
Shaylor et al. reported the mortality rates in 26
patient with osteosarcoma secondary to Paget' s
disease. There was a 47% mortality at 1 year and
75% at 2 years from diagnosis. In their series, no
patient survived for 5 years. All patients died of
metastatic disease.

44.  Langston et al. conducted a randomized trial that
compared the results of symptomatic treatment
versus intensive bisphosphonate therapy in patients
with Paget's disease. Clinical fractures occurred in 46
of 661 patients (7.0%) in the treatment group
compared with 49 of 663 patients (7.4%) in the
symptomatic treatment group. They concluded that
bisphosphonates did not show a significant
beneficial impact on pain, quality of life or fracture
incidence
 Hadjipavlou et al. reviewed Paget's disease of the
bone and its management. Farmers have been
shown to have an increased incidence of Paget's
disease. Average age at presentation is in the 5th
and 6th decade. Symptomatic individuals are
recommended to be treated initially with medical
management. They suggest that bisphosphonates
are more effective than calcitonin at suppressing the
histological and biochemical activity in Paget’s
disease

45.  Summary
 Epid: Very common in elderly
 Path: Abnormal osteoclasts…↑bone
turnover…deposition of abnormal bone
 S&S: Pain, deformity, fracture, arthropathy
 Labs: ↑AlkPhos
 X-ray: Characteristic coarse, thickened
trabeculae
 Bone scan: Very hot
 Rx: Bisphosphonates
 Surgery for arthropathy, fracture, painful
deformity

48. 1. Referral to endocrinology
2. Radiation therapy and chemotherapy
3. Wide resection and reconstruction
4. Radiation therapy, wide resection, and
reconstruction
5. Chemotherapy, wide resection, and
reconstruction

49.  Histiocytosis X or Langerhans cell histiocytosis
is a spectrum of diseases of
the reticuloendothelial system with one of three
general presentations
◦ Eosinophilic granuloma (EG)
 usually a single self-limited lesion found in younger
patients
◦ Hand-Schuller-Christian disease (HSC)
 chronic, disseminated form with bone and visceral lesions
 also known as Langerhans cell histiocytosis with visceral
involvement
◦ Letterer-Siwe disease (LSD)
 fatal form that occurs in young children

50.  Epidemiology
◦ demographics
 most commonly occurs in children (80% of afflicted < 20
years of age)
 HSC disease presents in children > 3 years of age
 LSD occurs in children < 3 years of age
 Male to female ratio of 2:1
◦ location
 eosinophilic granuloma
 commonly presents in the skull, ribs, clavicle, scapula,
mandible
 isolated lesions of the spine (thoracic most common)
 can also occur in diaphyseal regions of long bones and the
pelvis
 HSC
 multiple bony sites
 multiple lytic skull lesions
 visceral involvement of the lungs, spleen, liver, skin, lymph
nodes

51.  Genetics
◦ no clear genetic pattern of inheritance or locus has
been determined
 Prognosis
◦ EG
 isolated involvement generally treatable with local
management
 spine lesions can spontaneously resolve
◦ HSC
 prognosis depends on response to chemotherapy
 worsening prognosis with increasing extraskeletal
involvement
◦ LSD
 generally fatal in children < 3 years of age

52.  Symptoms
◦ skeletal involvement
 pain and swelling at the region of involvement
 limping can be seen with pelvic or lower extremity
involvement
◦ vertebral involvement
 localized or diffuse back pain
 increasingly kyphotic posture
 radiculopathy can occur with more aggressive lesions
◦ HSC
 classic triad of
 multiple lytic skull lesions
 diabetes insipidus
 increased thirst and water intake
 exopthalmos
 visceral involvement
 diffuse or nonspecific abdominal or chest pain

53.  Radiographs
◦ general
 known as "the great mimicker" as it appears similar to many lesions
 radiographic differential includes osteomyelitis, leukemia,
lymphoma, fibrous dysplasia, or Ewing's sarcoma
◦ diaphyseal lesions
 well defined intramedullary lytic or "punched-out" lesion
 cortex may be thinned, expanded, or destroyed
 may have periosteal reaction
◦ metaphyseal lesions
 extend up to but not through the physis
 less central location than diaphyseal lesions
◦ spinal lesions
 vertebra plana (flattened vertebrae) in spine
 increased kyphosis
◦ cranial involvement
 multiple "punched-out" lytic lesions
 MRI
◦ may show a soft tissue mass adjacent to boney lesions
 Bone scan
◦ generally shows increased uptake in the region of boney lesion

55.  Histology
◦ Langerhan's cells
 mononuclear histiocyte-like cells with oval nuclei with well-
defined round or oval cytoplasm.
 a prominent nuclear groove (coffee bean nuclei) can be seen
in most of the nuclei
 eosinophilic cytoplasm (pink generally)
 stain with CD1A
 electronmicroscopy
 birbeck granules seen inside Langerhan's cells
◦ mixture of inflammatory cells also present
◦ giant cells are present
◦ lack of nuclear atypia and atypical mitoses
 differentiates this condition from malignant conditions such
as Ewings sarcoma, lymphoma of bone, and metastatic
neuroblastoma, which may look similar based on the round
cells alone

57. Treatment
•Nonoperative
• observation alone
• indications
• a self-limited process and it is reasonable to treat with observation alone
• bracing
• indications
• to prevent progressive kyphosis of the spine
• outcomes
• will correct deformity in 90% of patients
• vertebral lesions generally regain 50% of their height
• low dose irradiation (600-800 cGy)
• indications
• indicated for lesions in the spine that compromise stability, neurologic status
• lesions not amenable to injection or open treatment
• outcomes
• effective for most lesions
• chemotherapy
• indications
• diffuse HSC
• outcomes
• prognosis is improved with less severe extraskeletal involvement
• corticosteroid injection
• indications
• isolated lesions
• can be performed after curettage as well

58.  Operative
◦ curettage and bone grafting
 indications
 for lesions that endanger the articular surface or are a risk for
impending fractures
◦ spinal deformity correction
 indications
 progressive spine deformity refractory to bracing
 approximately 10% of patients with spine lesion will need
operative intervention for deformity correction
 Destructive multiple lesion in young patients
Are eosinophilic granuloma ,lymphoma and
leukemia
Lymphoma is unlikely to present with
exopthalmos, diabetes insipidus or vertebra plana.
Lymphoma bone lesions are lytic and appear moth
eaten/permeative on radiographs

61.  Formation of bone in atypical, extraskeletal tissues
◦ usually occurs
 spontaneously or following trauma
 within 2 months of neurologic injury (brain or spinal cord)
◦ most common location is between muscle and joint capsule
 Epidemiology
◦ incidence
 (see table below)
◦ demographics
 male:female = 2:1
 especially men with hypertrophic osteoarthritis, and women >65y
◦ location
 traumatic brain injury or stroke
 hip > elbow > shoulder > knee
 elbow HO more common following brain trauma
 occurs on affected (spastic) side
 rarely in the knee (TBI)
 spinal cord injury
 hip > knee > elbow > shoulder
 hip flexors and abductors > extensors or adductors
 medial aspect of the knee

63.  Risk factors

65.  Pathophysiology
◦ exact cause of HO is not known but there appears to be
a genetic pre disposition
◦ experimental HO associated with
 tissue expression of BMP
 IT IS SAID TO BE CAUSED BY activation and proliferation of
mesenchymal stem cells
 Associated conditions
◦ orthopaedic manifestations
 pathologic fractures
 from decreased joint ROM and osteoporotic bone
 nerve impingement
 soft tissue contractures, contributing to the formation of
decubitus ulcers
 joint ankylosis
 HO after THA adversely affects outcome of THA
◦ nonorthopaedic conditions
 skin maceration and hygiene problems

66.  Pathophysiology
 Early in the formation of HO, oedema with exudative
infiltrate is present, followed by fibroblastic
proliferation and immature connective tissue
formation. Posteriorly, osteoid formation is seen with
the subsequent deposition of bone matrix. Primitive
osteoid is deposited as small masses in the periphery
early (within the first two weeks) and osteoblasts are
noted, located irregularly. Osteoblasts produce
tropocollagen, which polymerizes to form collagen
and secrete alkaline phosphatase, which allows
calcium to precipitate and the mineralization of bone
matrix. As mineralization progresses, amorphous
calcium phosphate is progressively replaced by
hydroxyapatite crystals. During the following weeks,
the lesion matures with a centripetal pattern, and
after 6-12 months an appearance of true bone is
noted. The new bone is always extra-articular and
can be contiguous with the skeleton but generally
does not involve the periosteum

67.  IN SUMMARY
 It has been postulated that three conditions
must be met to achieve heterotopic bone
formation ---a stimulating event,
oestrogenic precursor cells and a proper
environment. LIKE hypercalcaemia, tissue
hypoxia, pH changes (alkalosis) or prolonged
immobilization

68. Classification
•Subtypes
• neurogenic HO
• Four clinical stages of HO in people with spinal cord injury were
described by Nicholas in 1973
• traumatic myositis ossificans
• fibrodysplasia ossificans progressiva (Munchmeyer's Disease)

69.  Neurogenic HO
 Symptoms
◦ painless loss of ROM
◦ interferes with ADL
◦ CRPS symptoms
◦ fever
 Physical exam
◦ inspection
 warm, painful, swollen joint
 may have effusion
 skin problems
 decubitus ulcers
 from contractures around skin, muscles, ligaments
 skin maceration and hygiene problems
◦ motion
 decreased joint ROM
 joint ankylosis
 with HO after TKA, might develop quad muscle snapping or patella
instability
◦ neurovascular
 peripheral neuropathy
 HO often impinges on adjacent NV structures

70. Imaging
•Radiographs
• findings
• ossification usually easy to visualize
• maturity of HO
• the appearance of a bony cortex suggests mature HO
• sharp demarcation from surrounding tissue
• trabecular pattern
• sensitivity and specificity
• not useful for early diagnosis
• only useful at 1 week after onset of symptoms
• calcium is deposited 7-10 days later than symptom onset
•Ultrasound
• indications
• for early diagnosis of hip HO
• findings
• echogenic surfaces with posterior acoustic shadowing
•CT
• indications
• useful for preoperative planning
•Triphasic bone scan
• indications
• best for early diagnosis
• most commonly used diagnostic study

71.  Radiographs are extremely useful in the staging of
heterotopic ossification, and will show the
development of sharp cortical margins once the
lesion has reached maturity.
Heterotopic bone is a condition in which lamellar
bone forms in non-ossified soft tissues. In the early
stages, studies such as MRI and bone scan are more
sensitive for diagnosis, as radiographs may appear
normal for the first three weeks. After the appropriate
diagnosis is made, sequential radiographs are useful
for monitoring the progression of the ossification.
Once it has reached the mature stage, sharp cortical
margins will appear, and surgical resection may be
considered.

73.  Labs
◦ elevated serum alkaline phosphatase (>250IU/L)
 ALP removes inhibitors of mineralization
 nonspecific, may be elevated with skeletal trauma
 cannot determine maturity of HO
 elevated 12wks after surgery is predictor
◦ elevated CRP
 correlates with inflammatory activity of HO better than ESR
 normalization of CRP may correlate with maturity of HO
◦ elevated ESR (>35mm/h)
 12wks after THA is predictor
◦ elevated CK
 correlates with involvement of muscle, extent of muscle
involvement
 Histology
◦ mature fatty bone marrow
◦ mature trabecular bone

74.  Heterotopic ossification (HO) most commonly
occurs at the amputation site if the
amputation was performed thru the zone of
injury, especially if the injury was a blast
mechanism.
 Symptomatic heterotopic ossification of the
quadriceps may occur following placement of
a large-diameter Steinmann pin for the
purpose of temporary skeletal traction.

75. Treatment
The prevention of heterotopic ossification is focused on three basic principles:
disrupting the inductive signalling pathways, altering the osteoprogenitor cells
or modifying the environment
•physiotherapy should involve an assisted range of movement exercises with
gentle stretch and terminal resistance training
•Prophylaxis
• bisphosphonates & NSAIDS
• indications
• although no literature supports, are commonly used
• technique
• indomethacin is most commonly used
• dose is 75mg/day for 10days to 6 weeks
• perioperative radiation
• indications
• although no literature supports, commonly used
• is thought to be effective by blocking osteoblast differentiation
• technique
• a single perioperative dose of 700cGy can be given either 4
hours preop or within 72 hours postoperatively
• <550cGy not effective

76.  Nonsteroidal anti-inflammatory drugs (NSAIDs)
 These drugs have demonstrated good results in
preventing heterotopic ossification after total hip
arthroplasty
 A direct effect of NSAIDs on the formation of
heterotopic ossification has been described, due to
the inhibition of the differentiation of
mesenchymal cells into oestrogenic cells. There is
also an indirect effect, which refers to the
inhibition of bone remodelling by suppression of
the prostagland unmediated inflammatory
response (specifically PGE-2)
 Indomethacin has been considered a useful
medication for heterotopic ossification prophylaxis
following total hip replacement
 prescribed for three to six weeks in a dose of
75mg/day, within two months of the injury, may
reduce the incidence of heterotopic ossification by
two to three times

77.  Biphosphonates inhibits precipitation of calcium
phosphate and blocks the aggregation and
mineralisation of hydroxyapatite crystals. In
primary prevention, Banovac et al. [56] have
suggested that the treatment should begin as
soon as elevated alkaline phosphatase is
diagnosed or positive findings in
ultrasonography or bone scans are shown. In
addition, disphosphonates could have long-term
effects on prevention when the treatment is
finished.

78.  Posttraumatic
◦ wide exposure and surgical resection
 indications
 severe loss of motion and decreased function
 technique
 wide exposure required to identify all neurovascular structures
that may be involved
 timing of resection (controversial)
 marked decrease in bone scan activity AND normalization of
ALP
 6 months following general trauma
 1 year following SCI
 1.5 years following TBI
 some data suggests equivalent results when comparing early
versus late resection
 postop
 follow with 5 day course of indomethacin
 early gentle joint mobilization

79.  The surgery is necessary in patients with
symptomatic HO and unsuccessful medical
treatment, such as:
 Loss of range of motion and ankylosis with
associated functional disability, such as sitting
difficulties
 Complications of immobility such as pressure
ulcers
 Facilitate rehabilitation and recovery of muscular
atrophy secondary to prolonged immobilisation
 Difficulties of appropriate hygiene because
access to the perineum or bladder care is needed
 Severe pain refractory to analgesia
 Vascular and/or nerve compression

80.  Advantages to early excision of heterotopic
ossification (vs waiting for maturation) include
decreased soft tissue contracture, better
definition between heterotopic and native bone,
and decreased waiting time for the patient. When
the soft tissue envelope is benign, one may
proceed with operative release. While waiting for
normalization of alkaline phosphatase levels,
inactivity on bone scan, or radiographic maturity,
may decrease risk of recurrent heterotopic
ossification; delaying operative release for these
reasons has not been shown to improve results
of final elbow range of motion after contracture
release.

82.  Gartland recommended surgery after six months
following traumatic heterotopic ossification, one year
following spinal cord injury and 18 months after head
injury
 In the past, waiting until maturity in order to
minimize the rate of recurrence after the surgical
treatment was recommended. Nevertheless, recent
studies do not confirm a higher rate of recurrence
when the HO is excised in an earlier phase In
addition, a long delay before surgery leads to
ankylosis, a high degree of osteoporosis and more
extensive intra-articular injuries. These findings are
associated with bad functional results and potential
complications.

83.  Prevention by
Handle tissue carefully
Avoid excess bleeding
Achieve good hemostasis
Beware of lesions that span internervous tissue
planes
 but if it happens resection of a large enough
amount of bone to allow improvement of the
range of motion and trying to preserve the
joint

84.  A reactive process that is characterized by a well-circumscribed proliferation of
fibroblasts, cartilage, and bone within muscle
 A form of heterotopic ossification that is the result
◦ direct trauma
◦ intramuscular hematoma
 most common location is the diaphysis of long bones
 Must differentiate from tumors
 Fibrodysplasia ossificans progressiva (FOP) is a rare subtype of heterotopic
ossification
◦ involves mutation of the ACVR1 gene (activin A type I receptor gene, a BMP
type-1 receptor)
 Epidemiology
◦ demographics
 most common in young active males (15 to 35 years old)
◦ body locations
 quadriceps, brachialis and gluteal muscles
 Genetics
◦ almost always a posttraumatic condition
 Prognosis
◦ usually self limiting
 mass usually begins to decrease in size after 1 yea

85. Presentation
•Symptoms
• pain, tenderness, swelling and decreased range of motion that usually
presents within days of the injury
• pain and size of the mass decrease with time
• mass increases in size over several months(usually 3 to 6 cm)
• after the mass stops growing it becomes firm
•Physical exam
• palpable soft tissue mass
• restricted range of motion
Imaging
•Radiographs
• peripheral bone formation with central lucent area
• may appear as "dotted veil" pattern
•MRI with gadolinium
• rim enhancement is seen within the first 3 weeks
•CT scan
• lesion has an eggshell appearance

86. •Characteristic histology shows zonal pattern
• periphery of lesion
• mature trabeculae of lamellar and woven bone
• calcification seen on xray
• center of the lesion
• irregular mass of immature fibroblasts
• cartilage component may be present
• (no calcification seen on xray)
• no cellular atypia seen
Treatment
•Nonoperative
• rest, range of motion exercises, and activity modification
• passive stretching is contraindicated (makes it worse)
• physical therapy
• utilized to maintain range of motion
• radiographic monitoring
• obtained to confirm maturation of the lesion
•Operative
• surgical excision
• indicated only if it remains a problem after it matures
• do not operate in acute phase, wait at least six months
• excision of the lesion within 6 to 12 months predisposes to
local recurrence

87.  A 26-year-old man presents with generalized
back and joint stiffness and difficulty opening
his mouth. His elder sister has similar
complaints. Since childhood, he has had 3
surgeries for excision of recurrent bony
prominences around his knees. He walks with
a stooped over posture seen in Figure A.
Radiographs of his feet, knee, hip and spine
are seen in Figures B-E respectively

89.  There are 2 hallmark characteristics:
progressive heterotopic ossification (muscles,
fascia, tendons, ligaments and joint capsules)
and congenital malformation of the great toe
(hallux valgus, malformed first metatarsal
and monophalangism). BMP4, which
contributes to the formation of the skeleton
in the normal embryo, is implicated in this
disease

91. Complications
•Hematoma and intraoperative bleeding
•Infection
• higher rate of infection following joint arthroplasty if HO is
present
•Fractures of osteoporotic bone
• osteopenic from disuse
• during surgery or physiotherapy
•Recurrence
• recurrence rate correlates with neurological injury
• greater recurrence if severe neurological compromise
•AVN
• if extensive dissection or stripping is required

93.  When ISS is below 25, the mortality risk is minimal and above 25, it is
an almost linear increase.
 When ISS is 50, the mortality is 50%
 When above 70, it is close to 100%.
 If an injury is assigned an AIS of 6 (unsurvivable injury), the ISS score
is automatically assigned to 75.
 Highest ISS score obtainable is 75.
 For trauma patients of vehicular accidents, the scoring system is
important for assessing the effectiveness of medical care in reducing
morbidity and mortality.
 Advantages:
 virtually the only anatomical scoring system in use
 correlates linearly with
◦ mortality
◦ morbidity
◦ hospital stay
◦ other measures of severity.
 Weaknesses:
 Any error in AIS scoring increases the ISS error
 Many different injury patterns can yield the same ISS score
 Injuries to different body regions are not weighted
 Not a useful triage tool, as a full description of patient injuries is not
known prior to full investigation & operation

94. ◦ risk factors
 periosteal stripping off anterior femur
 male gender
 obesity
 post traumatic deformity
 Anterior and anterolateral approach
 Cementless
Neurogenic HO around the hip due to SCI occurs more often in
the medial region than in the lateral region, with ossified
tissues extending from the pubic symphysis to the
anteromedial femoral shaft posterior to the femoral
neurovascular structures. Ossification is also seen anteriorly
involving the iliopsoas and femoral neurovascular structures,
laterally within gluteus minimus, and posteriorly extending
from the ilium to the posterior femur encasing the sciatic nerve.

98.  Region I - Heterotopic ossifications are strictly below the
tip of the greater trochanter
 Region II - Heterotopic ossifications are below and above
the tip of the greater trochanter
 Region III - Heterotopic ossifications are strictly above the
tip of the greater trochanter
 Grade A - Single or multiple heterotopic ossifications are
less than 10 mm in maximal extent without contact with
the pelvis or the femur
 Grade B - Heterotopic ossifications are greater than 10
mm without contact with the pelvis but with possible
contact with the femur; there is no bridging from the
femur to the proximal part of the greater trochanter and
no evidence of ankylosis
 Grade C - Ankylosis by means of firm bridging from the
femur to the pelvis is present

99.  excision may be performed. The results of
this procedure are varied. Patients may find
that their range of movement improves, but
pain relief is likely to be limited
 A patient with heterotopic ossification
following total hip arthroplasty is thought to
have a 90-100% chance of developing it on
the contralateral hip if this hip also
undergoes total arthroplasty

100.  it would be prudent to minimize the risk of
heterotopic ossification developing after
arthroplasty by performing surgery whereby the
following are ensured:
 Exposure is meticulous
 Retraction is performed carefully and soft tissue
is handled carefully
 Irrigation is adequate
 Devitalized tissue is excised
 Hemostasis is adequate
 Postoperative drains (when used) are not retained
for longer than necessary
 Perioperative antibiotic prophylaxis is used
 Postoperative anticoagulation (when used for
deep vein thrombosis prophylaxis) is carefully
controlled

101.  sources of knee stiffness.
 1-extrinsic
 severe osteoarthritis of the ipsilateral hip,
 neurologic injury leading to muscle rigidity,
 tight quadriceps or hamstring muscles secondary to muscle injury,
 heterotopic ossification,
 or long-standing juvenile inflammatory conditions limiting knee
range of motion prior to the completion of skeletal growth. When
extrinsic sources are identified, revision total knee arthroplasty is
unlikely to be associated with a favorable outcome without
correction of the extrinsic problem.
 2-intrinsic
 (1) overstuffing of the patellofemoral articulation, (2) an excessively
tight flexion and/or extension gap, (3) a tight posterior cruciate
ligament, (4) femoral and/or tibial malrotation, (5) arthrofibrosis,
and (6) limited bearing excursion in association with a highly
conforming mobile-bearing prosthetic design

102.  Heterotopic Ossification (HO) following primary
Total Knee Replacement (TKR)

 Occurs in 3-90% of TKRs
 3-grade classification system
 No correlation between HO and component
alignment or component position

Clinical findings similar to early infection
 Continuing low-grade fever
 Warm, swollen and erythematous knee
 Normal blood tests
 Possibly an association with HLA-A2 and
B18
 HO patients have worse KSS and function
scores

103.  Patients at HIGH risk for developing HO after
TKR (Knee Arthroplasty) (5)
 Those with limited postoperative knee
flexion
 Increased lumbar bone mineral density
(BMD) on multivariate analysis (3)
 Hypertrophic arthrosis
 Excessive periosteal trauma
 Notching of the anterior femur
 Those who require forced manipulation
after TKA
 47% in revision TKR surgery (6)
 Higher rates in revision TKR cases with
infection (up to 76%

105.  Daugherty/Bell classification of HO of the knee
 0 No evidence of HO
 1 Bone islands in periarticular soft tissue (no
involvement of femur, patella, or tibia) or HO within
quadriceps expansion measuring <1 cm
 2 Spur formation measuring <5 cm that involves
the femur, patella, or tibia; if more than one bone
demonstrates HO, separation of HO spurs
 measure >1 cm or HO within quadriceps expansion
measuring ≥1 cm but <3 cm
 3 Spur formation >5 cm involving femur, patella,
or tibia; if more than one bone demonstrates HO,
separation of HO spurs measure <1 cm or HO
 within quadriceps expansion measuring ≥3 cm
 4 Extensive HO of the knee causing ankylosis

106.  class 2, HO begins to involve the major bones of the
knee joint with spur formation limited to a size of 5
cm
 HO class 2 may be observed in select patients with
 complete ROM and no reported pain. Patients with
class 3
 HO would likely always benefit from surgical excision
followed
 by RT prophylaxis. Certainly patients in either cohort
 with a subclass “B” assignment (symptomatic) would
benefit
 from treatment. All patients with class 4 HO require
treatment
 to alleviate ankylosis

107. ◦ References
◦ Whyte, “Paget’s Disease of Bone”, NEMJ, vol. 355, 2006.
◦ Klein and Parvizi, “Surgical Manifestations of Paget’s
Disease”, JAAOS, vol. 14, 2006.
◦ Orthobullets
◦ Campbell
◦ Apley
◦ Emedicine.com
-Chapter 15 Heterotopic Ossification after
Traumatic Brain Injury
By Jesús Moreta and José Luis Martínez-de los
Mozos
DOI: 10.5772/57343

108.  Questions?
 Thank You