A. Introduction

1. Means "Death of Bone"
2. Usu occurs in active patients
3. Pain often referred
4. Multitude of associated disease but actual pathophysiology is unclear

B. Causes (Associated Conditions)

1. Glucocorticoid therapy
2. Cushing's Syndrome
3. Alcoholism
4. Sickle Cell (HbSS) and HbSC Disease
5. Trauma
6. Radiation
7. Gaucher's Disease
8. Legg-Calve-Perthe Disease
9. Caisson Disease
10. Osteonecrosis of the Femoral Head [2]
    1. Avascular necrosis of femoral head
    2. Spontaneous and familial forms identified
    3. Familial form is autosomal dominant and linked to gene on chromsome 12q13
    4. Mutations in type II collagen gene on chromosome 12q13 found in familial disease
    5. No mutations in type II collagen gene found in spontaneous form
11. Osteonecrosis of the Jaw [3,4]
    1. Dental procedures and poor dental hygiene increase risk for jaw osteonecrosis
    2. Local radiotherapy and systemic glucocorticoid use also increase risk
    3. Increasing reports of association with certain bisphosphonates [4]
    4. Greatest risk with myeloma and carcinoma metastatic to the skeleton receiving intravenous nitrogen-containing bisphosphonates at greatest risk [4]
    5. Zoledronic acid (Zometa®) has increased risk compared with pamidronate
    6. In myeloma patients on zolendronic acid, up to 10% develop jaw osteonecrosis in 3 years
    7. Oral bisphosphonates appear to have little or no risk of jaw osteonecrosis
    8. Oversuppression of bone turnover is likely major mechanism for bisphosphonate necrosis
    9. Glucocorticoid use did not appear to synergize with bisphosphonates to increase risk
12. Possible Contributors
    1. Antiphospholipid Ab Syndromes (primary and secondary)
    2. Cigarette Smoking
    3. Hyperlipidemia
    4. Vasculitis
    5. Gout
    6. Pancreatitis
    7. Hemodialysis
    8. Pregnancy
    9. Systemic Lupus Erythematosus (separate from antiphospholipid syndrome)

C. Pathophysiology

1. Increased outflow resistance to intraosseous circulation
2. Intravascular Causes
   1. Sickle Syndromes
   2. Platelet Thrombi - including secondary endothelial damage with decompression sickness
3. Extravascular Causes
   1. Usually due to cell proliferation, most commonly adipocytes
   2. Glucocorticoid Use
   3. Alcoholism
   4. Gaucher's Disease - glycogen accumulation in macrophages
4. Predilication for convex joint members
   1. Femoral Head
   2. Knee
   3. Shoulder
5. Possible Mechanisms
   1. Loading of joint leading to displacement of underlying fluid
   2. Venule obstruction prevents fluid egress

D. Diagnosis

1. High suspicion in persons at risk
2. Glucocorticoids appear especially contibutory in patients with:
   1. Systemic Lupus
   2. Organ Transplantation
3. Bilateral involvement is rule, even without symptoms
4. Radiographs may show changes
5. Magnetic Resonance Imaging (MRI) is the gold standard

E. Treatment

1. Prevention is key
2. Four point crutch walking (not swing leg) is highly recommended
3. Attempt to reduce or discontinue precipitating factors
4. Decompression of the femoral head has been advocated and can be considered
5. Osteonecrosis of Jaw [4]
   1. All sites of ptoential jaw infection should be eliminated prior to IV bisphosphonate therapy
   2. Conservative debridement of necrotic bone
   3. Pain control
   4. Infection management including use of oral antimicrobial rinses
   5. Withdrawal of bisphosphonates

References

1. Mankin HJ. 1992. NEJM. 326:1473
2. Liu YF, Chen WM, Lin YF, et al. 2005. NEJM. 352(22):2294
3. Durie BGM, katz M, Crowley J. 2005. NEJM. 353(1):99
4. Woo SB, Hellstein JW, Kalmar JR. 2006. Ann Intern Med. 144(10):753