Starvation, Death and Destruction

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APHON 42nd Annual Conference, 2018 Karyn Brundige MSN CPNP

Starvation, Death, and Destruction: The Battlefield of AVN

Disclosure Statement

STARVATION, DEATH, AND DESTRUCTION: THE BATTLEFIELD OF AVN

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I have no industry relationships to disclose

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I will not discuss off-label use of medications

Karyn Brundige, MSN CPNP

Learning Outcomes

Interesting Trivia

1. Identify three factors that contribute to the development of AVN in children with hematologic or oncologic disorders 2. Contrast evidence-based treatment strategies for childhood AVN based on disease staging

What is the most common cause of AVN of the femoral head during childhood?        

Trauma Legg-Calvé-Perthes disease Slipped capital femoral epiphysis Steroid therapy Radiation therapy Sickle cell disease Gaucher disease Lupus (SLE)

Different Name, Same Game Pathophysiology

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Avascular necrosis Osteonecrosis Aseptic osteonecrosis Atraumatic necrosis Ischemic bone necrosis

Bone is a living tissue that requires blood AVN = death of bone tissue due to lack of blood supply

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APHON 42nd Annual Conference, 2018 Karyn Brundige MSN CPNP

Starvation, Death, and Destruction: The Battlefield of AVN

Normal Bone Growth   

Pathways to Necrosis

Break down: Resorption of old bone by osteoclasts Build: Formation of new bone by osteoblasts AVN = Breakdown faster than repair

Vascular occlusion

• Trauma, stress fracture • SCD, venous stasis

Intravascular coagulation

• Hypercoagulable state • Fat emboli

Primary cell death

Pathways to Necrosis

• Steroids • Radiation therapy

Hips, Shoulders, Knees and Toes

↓ Blood supply to bone (ischemia)

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Infarction and necrosis of bone & marrow cells

Single terminal blood supply that lack collateral circulation, especially the epiphysis of the long bones Can also affect the elbows, wrists, ankles, clavicles, vertebrae and small bones in the hand and feet

Tiny breaks/collapse of bone components Destruction and collapse of joint Mechanical failure

Risk Factors

Sickle Cell Disease and AVN 

Sickle cell disease

Steroids (ALL, HCST)

Orthopedic disorders

Trauma

Lupus

Infection

Coagulation disorders

Gaucher disease

Renal transplant

Radiation therapy

Malignancy

Biphosphonate use

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Homozygous (SS) and heterozygous (SC) disease Acetabulum, head of femur, head of humerus Majority of affected hips are painful Symptomatic hips progress to collapse in 5 years

Joint replacement associated with   

Higher rates of failure Higher rates of early replacement Higher rates of infection

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APHON 42nd Annual Conference, 2018 Karyn Brundige MSN CPNP

Starvation, Death, and Destruction: The Battlefield of AVN

ALL Risk Factors for AVN  

Corticosteroids Age >10 years (girls 10-14 and boys >15)

ALL Risk Factors for AVN ?

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Race (white>black; non-Hispanic>Hispanic) Female sex High BMI, especially at diagnosis Elevated lipid levels

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Genetic mutations

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Other chemotherapy agents

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Steroid Therapy and AVN 

Exact pathogenesis unknown  

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Age and AVN 

Alteration in circulating lipids → microemboli in arteries Stimulate bone marrow fat cells to increase in size/number → blocks venous flow Effect vascular endothelial cells and smooth muscle cells → stasis → increased intraosseous pressure → necrosis

Maturing bones of adolescents, especially long bones that have late epiphyseal closure and contribute to pubertal growth, most susceptible  

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Often multi-joint involvement  Most cases diagnosed within 1 year of starting treatment, but may occur many years later 

HCST and AVN 

AVN after allogeneic transplant (Li, 2014)   

Nested case-control study; AVN (160)/control (478) Median time to develop AVN: 14 months Risk factors 

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Age ≥ 5 years at time of transplant Female gender Myeloablative conditioning regimen Chronic GVHD

Decreased risk  

Epiphyseal closure results in elevated intraosseous pressure? Excessive metabolic activity in growth plates and bones during pubertal growth spurt make them more susceptible to hypoxic effects? Increased susceptibility caused by a markedly increased growth rate and hormonal changes?

HCST and AVN 

AVN after allogeneic transplant (Sharma, 2012)    

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St. Jude Children’s Research Hospital prospective study post-transplant 30% of patients developed AVN of knees and/or hips 45% of lesions had at least 30% epiphyseal involvement Median time to develop AVN: 12.3 months Risk factors  

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>10 years old at time of transplant AVN on MRI prior to transplant

Knees most frequent site, but hips had greater severity

Non-malignant disease Reduced-intensity conditioning regimens

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APHON 42nd Annual Conference, 2018 Karyn Brundige MSN CPNP

Starvation, Death, and Destruction: The Battlefield of AVN

Clinical Symptoms Presentation

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Pain is the most common presenting symptom   

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Physical Examination      

Limp Antalgic gait Restricted ROM Tenderness around bone Joint deformity Muscle wasting

Often described as throbbing, deep, or intermittent May be referred to other areas Symptoms usually start with just weight bearing, then progress to at rest

Affected joints may be asymptomatic Inflammatory symptoms generally absent Sudden, severe onset of pain concerning for joint collapse

Degree of Disability  

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What part of the bone is affected How large an area is involved 

>30% of articular surface of hips or knees

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is associated with worse outcomes <30% of articular surface may heal without collapse

How effectively the bone rebuilds itself

What Modality is Best? Imaging and Staging

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X-ray: Doesn’t identify early changes; may remain normal for months after symptoms first appear MRI: Most sensitive and specific method CT: Used to assess extent of disease and calcification; clearly shows articular deformity and bone collapse Bone scan  

More sensitive than X-ray, less sensitive than MRI Increased uptake mainly due to increased activity of osteoblasts (bone formation)

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APHON 42nd Annual Conference, 2018 Karyn Brundige MSN CPNP

Starvation, Death, and Destruction: The Battlefield of AVN

Stage I

Stage II  

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X-ray: Not detectable MRI: Slight bone marrow edema or effusion; joint effusion most commonly appears in the knees Bone scan: Increased uptake mainly due to increased activity of osteoblasts (bone formation)

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X-ray: Mixed osteopenia (bone mineral density lower than normal) or sclerosis MRI: Evidence of lesion, abnormality in bone tissue Bone scan: Increased uptake

Stage III 

X-ray and MRI: Bone collapse of joint appears imminent

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APHON 42nd Annual Conference, 2018 Karyn Brundige MSN CPNP

Starvation, Death, and Destruction: The Battlefield of AVN

Stage IV 

X-ray and MRI: Collapse of joint

Seek and You Will Find St. Jude’s Total XV Therapy (Kawedia, 2011)  Symptomatic AVN usually diagnosed first year of therapy  17.6% symptomatic AVN at 6-12 months from diagnosis  53.6% asymptomatic AVN diagnosed at end of therapy  25% of patients with asymptomatic MRI changes early in treatment (by week 10) went on to develop symptoms, but  Most symptomatic patients had mild-moderate symptoms, and only a minority required surgical treatment

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APHON 42nd Annual Conference, 2018 Karyn Brundige MSN CPNP

Starvation, Death, and Destruction: The Battlefield of AVN

Can AVN Reverse?

Management

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Study of symptomatic AVN in children with ALL  

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Study of femoral head AVN in 48 children with ALL 

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Treatment 

Goals   

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Stop bone damage Reduce pain Improve function

Considerations    

Age Extent, stage and location of damage Health of patient Risk for recurrence of malignancy

40% had complete resolution of symptoms at 5 years 24 patients with radiology follow-up: 25% partially or completely reversible lesions, 54% stable lesions, 21% progressive lesions

>10 years (40 children): 19 progressed to joint collapse and required total hip replacement; 21 had no improvement at end of monitoring <10 years (8 children): none required hip replacement; 4 had significant improvement at end of monitoring

Non-Surgical Management 

Inconsistent and limited success in preventing disease progression

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Restrict weight-bearing exercise Physical therapy Medications: lipid-lowering drugs, anticoagulants, vasodilators, bisphosphonates, traditional Chinese medications Electromagnetic stimulation Hyperbaric oxygen

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APHON 42nd Annual Conference, 2018 Karyn Brundige MSN CPNP

Starvation, Death, and Destruction: The Battlefield of AVN

Surgical Management 

Joint preserving procedures    

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Core decompression Bone grafts or bone marrow Osteotomy Arthrodesis

Joint replacement (arthroplasty)

Core Decompression  

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Core Decompression and ABMI 

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Autologous bone marrow implantation to induce bone repair in femoral head Procedure      

60-120 mL bone marrow aspirated from anterior iliac crest Concentrated to 15 mL of bone marrow cells Multiple small core drillings in the femoral epiphysis Concentrated marrow slowly injected into the femoral head 24 hour admit for hydration and pain management No cast or brace; 2 month touch down weight-bearing on crutches

Osteotomy 

Remove section of affected bone above or below a weight-bearing joint to change its shape in order to decrease the stress on it

Core Decompression and ABMI 

Pediatric trial (Novais, 2015)  

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11 patients with SCD, 14 hips >90% decreased pain, >80% decreased progression to joint collapse

Adult trial (Daltro, 2015)  

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89 patients with SCD Historically 70% to 90% without intervention progress to collapse/osteoarthritis requiring arthroplasty within 5 years Only 3.4% did not achieve good results No collapse of femoral head in 60-month follow up

Arthroplasty 

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Pre-collapse of joint Single 8-10 mm core into necrotic lesion, or small diameter multiple 3 mm cores Pain relief Reduce intraosseous pressure Create open area for new blood vessels to grow Enhance new bone growth 70-80% success rate at 5 years (Novais, 2015)

Late stage when joint is destroyed (collapsed or severe arthritis) Damaged bone is removed and replaced with an artificial joint

Prolonged post procedure recovery includes extended restricted weight-bearing until healing occurs

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APHON 42nd Annual Conference, 2018 Karyn Brundige MSN CPNP

Starvation, Death, and Destruction: The Battlefield of AVN

Sohail

Steroids and COG Studies

What’s Up With Sohail?

Modifications for AVN

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Do not modify

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Maintenance  

Hold for grade 2 or greater (symptomatic, limiting instrumental ADLs) Consider restarting if joint symptoms resolve and MRI shows normalization or significant improvement

Initial treatment 

Induction or re-induction/delayed intensification

Steroids HELD Nighttime bracing and hip splinting (avoid abduction) Very active, no pain

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3 months: Scans stable

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6 months: Femoral head remodeling 10 months: Restarted steroids

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Off therapy: Normal joint

Maddy

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APHON 42nd Annual Conference, 2018 Karyn Brundige MSN CPNP

Starvation, Death, and Destruction: The Battlefield of AVN

What’s Up With Maddy? 

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Symptoms were not responsive to physical therapy, restricted weightbearing or core decompression Total hip replacement at 14 years old Very active but now has multi-focal AVN in right knee, hip, and shoulders

Joshua

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APHON 42nd Annual Conference, 2018 Karyn Brundige MSN CPNP

Starvation, Death, and Destruction: The Battlefield of AVN

Ben

Take Home Messages   

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AVN results from loss of blood supply to the bone Most commonly affects ends of long bones (hips and knees) Risk factors in our population include sickle cell disease and high dose or prolonged steroids Older patients generally have progressive disease requiring surgical intervention

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