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Keywords:

  • osteonecrosis;
  • septic shock;
  • sepsis;
  • femoral head;
  • ischemia

Abstract

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS AND DISCUSSION
  6. REFERENCES

A case of bilateral femoral head osteonecrosis after septic shock is presented. We suggest that the osteonecrosis was caused by ischemic insults to the proximal femora. The association between septic shock and osteonecrosis has not been previously reported.

Introduction: Osteonecrosis is an uncommon disorder characterized by the in situ death of bone. A diverse range of conditions has been associated with osteonecrosis. We present a case of bilateral femoral head osteonecrosis that occurred after an episode of septic shock.

Materials and Methods: A 66-year-old woman presented with a left-sided renal stone and a urinary tract infection. Her condition rapidly progressed to a life-threatening illness with septic shock complicated by multiorgan failure, which necessitated prolonged intensive care and inotropic support. She made a full recovery but 3 months later developed bilateral osteonecrosis of the femoral heads requiring bilateral total hip joint replacement.

Results and Conclusions: We propose that the osteonecrosis was caused by ischemic insults to the femoral heads as a result of the widespread systemic ischemia that occurred during her initial illness. To our knowledge, septic shock has not been previously described as a cause of osteonecrosis. Clinicians should be aware of this association, particularly in patients presenting with bone pain after episodes of sepsis.


INTRODUCTION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS AND DISCUSSION
  6. REFERENCES

OSTEONECROSIS IS AN uncommon condition that occurs most frequently between 30 and 60 years of age. It is caused by a reduction in blood flow to the affected bone. In most cases (75%), a specific cause can be identified. We describe a patient who developed bilateral femoral head osteonecrosis after septic shock. The association between septic shock and osteonecrosis, in the absence of high-dose glucocorticoid therapy or overt disseminated intravascular coagulation (DIC), has not been previously described.

MATERIALS AND METHODS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS AND DISCUSSION
  6. REFERENCES

A 66-year-old woman presented with left renal colic. Mid-stream urine culture grew Escherichia coli. CT of the renal tract showed an 8 mm calculus in the left ureter at the level of the iliac crest. Proximal to the calculus the ureter was dilated, and there was moderate hydronephrosis. Over the next 36 h, her condition deteriorated. She became oliguric, hypotensive, tachycardic, and dyspneic. A chest X-ray showed pulmonary edema. Arterial blood gas analysis showed marked acidosis and hypoxemia. Cultures of urine and blood grew E. coli. She was treated with inotropic support, ultrasound-guided placement of a nephrostomy tube, cystoscopic placement of a ureteric stent, and intravenous cefuroxime. She was hypotensive for 8 h before the initiation of therapy with inotropes; her lowest blood pressure recorded was 70/45 mm Hg.

Her condition deteriorated further, and she developed anuric renal failure caused by acute tubular necrosis requiring hemofiltration, worsening gas exchange with adult respiratory distress syndrome necessitating mechanical ventilation, and a non-ST elevation myocardial infarction that was treated supportively. Hepatic transaminases rose to greater than 1000 U/liter, and ischemic hepatitis was diagnosed clinically. She developed an abnormal coagulation profile—the activated partial thromboplastin time rose to 54 s (range, 25–37 s), the prothrombin ratio rose to 2.3 (range, 0.8-1.2), and she became thrombocytopenic, with a platelet count of 52,000 (range, 150,000-300,000); however, her fibrinogen levels remained elevated. She was treated with clotting factor replacement, platelet transfusion, and intravenous vitamin K administration. At no time was there clinical or laboratory evidence of overt DIC (maximum score of 3, using the International Society on Thrombosis and Hemostasis algorithm for assessing DIC).(1) She received 48 h of intravenous hydrocortisone (50 mg; 4 times per day) when her condition was at its most precarious.

She received inotropic support for 24 days, which was titrated to keep the mean arterial pressure greater than 70 mm Hg. Specifically, she received epinephrine (up to 2 mg/h) for 12 h, dopamine (up to 40 mg/h) for 5 days, and norepinephrine (up to 5 mg/h) for 24 days. She made a very slow recovery that was complicated by two further episodes of E. coli sepsis. During these episodes, she required higher doses of inotropes to maintain her mean arterial pressure. She required a prolonged course of intravenous antibiotics, placement of a second nephrostomy tube, lithoclast treatment and cystoscopic stone removal, prolonged ureteric stenting, and percutaneous drainage of a perinephric collection. She remained in the critical care unit for 28 days, and the total hospital stay was 52 days. There was no evidence of pancreatitis, hyperlipidemia, or thrombophlebitis during the hospital admission.

She was seen by her general practitioner 3 months later with a 2-week history of left hip pain that was worse on movement. There was no history of recent trauma. Plain X-rays of the hip and pelvis demonstrated a fracture of the left neck of femur. A MRI scan showed extensive geographical areas of variable signal change in the proximal femora, classical for bone infarcts, complicated by a fracture through the left femoral neck (Fig. 1). The T2/STIR-weighted images demonstrated bilateral bone marrow edema in the same regions as the necrosis and a small joint effusion on the left. The findings were consistent with stage 2 bilateral osteonecrosis.

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Figure FIG. 1.. T1-weighted coronal MRI of the hips and pelvis showing geographical areas of signal change in the (A) proximal femora and (B) fracture of the left neck of femur.

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A left total hip joint replacement was performed without complication. Histological analysis of the femoral head showed that the subchondral bone was patchily replaced by fibrous tissue with scattered fragments of devitalized bone and some necrotic fat. There was some focal bone remodeling with new bone formation (Fig. 2). These findings were consistent with osteonecrosis.

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Figure FIG. 2.. Histology of the left femoral head. The section shows a (A) necrotic trabeculum, (B) viable new bone, and (C) marrow fibrosis.

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Two months later she saw her general practitioner for complaints of increasing pain in the right hip while mobilizing for the last 3 weeks. An X-ray of the pelvis showed a fracture of the right neck of femur. A right total hip joint replacement was performed without complication. She again made an uneventful recovery.

She was subsequently referred to the osteoporosis clinic, where it was noted she had had no previous fractures, no prior history of bone or joint disease, and had no risk factors for osteoporosis. She was a nonsmoker and did not drink alcohol. There was no history of gout, diabetes mellitus, or hyperlipidemia. Lumbar spine (L1-L4) BMD T score was −0.5 SD. Human immunodeficiency virus antibody was not detected. Antinuclear antibody (ANA) was positive in a titer of 1 in 320, but double-stranded DNA antibody was not detected. Extracted nuclear antigen was negative. Phospholipid antibodies were not detected. Serum lipid profile was normal. She had no features of connective tissue disease. Since the second hip arthroplasty, she has remained in good health.

RESULTS AND DISCUSSION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS AND DISCUSSION
  6. REFERENCES

Osteonecrosis (avascular necrosis) is defined as the in situ death of a segment of bone. It is believed to occur after disruption of the blood supply to the affected bone by mechanical means (fracture, dislocation, compartment syndrome) or thromboembolic occlusion (vasculitis, hemoglobinopathy).(2) Our patient had evidence of severe systemic ischemia during a prolonged hospital admission with septic shock. We propose that she suffered an ischemic insult to her proximal femora as a result of hypotension, low cardiac output, and blood flow diversion. Other diseases reported to be associated with osteonecrosis(3) were not present. Although the ANA was positive, these antibodies are present in up to 30% of women over the age of 60(4); there were no features of a connective tissue disorder. Osteonecrosis has been described after meningococcemia associated with DIC.(5) To our knowledge, it has not been described after septic shock in the absence of overt DIC or prolonged high-dose corticosteroid therapy. Although our patient received 48 h of corticosteroid therapy, we do not believe that it was a primary factor in the pathogenesis of the osteonecrosis in her case. Osteonecrosis has been described after short courses of corticosteroids, but in much higher doses for longer periods of time than our patient received. Steroid-induced osteonecrosis has been reported after 700 mg of prednisolone administered over 7 days and 480 mg of prednisolone over 30 days.(6)

The relationship between ischemia and osteonecrosis is seen most clearly in trauma. Femoral neck fracture or hip dislocation leads to mechanical disruption of the blood supply to the femoral head, causing necrosis of part or all of the femoral head.(7) In atraumatic cases, the cause and effect relationship is more ambiguous. Patients usually have a risk factor for osteonecrosis, but only a minority of patients with such risk factors will develop the condition. Nonetheless, it is generally believed that compromised blood flow to the bone represents the final common pathway for the development of osteonecrosis.(3) Although not previously reported, systemic hypotension is a rational explanation for local ischemia to the femoral head, especially in the setting of other end-organ ischemia.

MRI is the diagnostic modality of choice in suspected osteonecrosis, and the MRI findings correlate well with the histological findings.(3, 6) Osteonecrosis of the femoral head commonly (up to 98% of cases) occurs bilaterally,(3) and at presentation, up to 42% of patients with symptomatic disease in one hip will have asymptomatic disease in the contralateral hip.(7) Currently, therapy for osteonecrosis is limited to surgical approaches. Older patients with advanced osteonecrosis usually require total hip arthroplasty, whereas in younger patients, therapy is aimed at preserving the native joint for as long as possible through bridging strategies with conversion to total hip arthroplasty when necessary.(2, 7)

There is no efficacious medical therapy for osteonecrosis at present. However, it is plausible that bisphosphonates might attenuate or prevent glucocorticoid-induced osteonecrosis, in which osteoblast and osteocyte apoptosis is likely to have an important pathogenetic role. Mice treated with glucocorticoids for 4 weeks showed a 3-fold increase in osteoblast apoptosis in vertebral cancellous bone and apoptosis in 28% of osteocytes in metaphyseal cortical bone.(8) In humans, abundant apoptosis in osteocytes and cells lining cancellous bone has been identified in histological specimens from patients with glucocorticoid-induced osteonecrosis, but not in osteonecrosis caused by trauma, alcoholism, or sickle cell disease.(9) Because bisphosphonates inhibit osteoblast and osteocyte apoptosis in vitro, they may interrupt an important process in the development of glucocorticoid-induced osteonecrosis.(10) An uncontrolled clinical study suggests that alendronate reduces pain and decreases marrow edema in patients with femoral head osteonecrosis.(11) In addition, bisphosphonates, at doses equivalent to those used to treat osteoporosis, may preserve bone strength in experimental animals by inhibiting the resorption of necrotic bone during revascularization and the early stages of skeletal repair.(12)

In summary, we have described a case of bilateral osteonecrosis of the femoral heads after septic shock in the absence of overt disseminated intravascular coagulation. This association has not, to our knowledge, been reported previously. Low-dose corticosteroid therapy may have been a contributing factor; however, osteonecrosis has not previously been reported at such doses. Osteonecrosis may represent a late complication of severe illness accompanied by evidence of ischemia in other tissues.

REFERENCES

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS AND DISCUSSION
  6. REFERENCES
  • 1
    Taylor FB Jr, Toh CH, Hoots WK, Wada H, Levi M, Scientific Subcommittee on Disseminated Intravascular Coagulation (DIC) of the International Society on Thrombosis and Haemostasis (ISTH) 2001 Towards definition, clinical and laboratory criteria, and a scoring system for disseminated intravascular coagulation. Thromb Haemost 86:13271330.
  • 2
    Mankin HJ 1992 Nontraumatic necrosis of bone. N Engl J Med 326:14731479.
  • 3
    Assouline-Dayan Y, Chang C, Greenspan A, Shoenfeld Y, Gershwin ME 2002 Pathogenesis and natural history of osteonecrosis. Semin Arthritis Rheum 32:94124.
  • 4
    Slater CA, Davis RB, Shmerling RH 1996 Antinuclear antibody testing. A study of clinical utility. Arch Intern Med 156:14211425.
  • 5
    Campbell WN, Joshi M, Sileo D 1997 Osteonecrosis following meningococcemia and disseminated intravascular coagulation in an adult: Case report and review. Clin Infect Dis 24:452455.
  • 6
    Chang CC, Greenspan A, Gershwin ME 1993 Osteonecrosis: Current perspectives on pathogenesis and treatment. Semin Arthritis Rheum 23:4769.
  • 7
    Frankel ES, Urbaniak JR 2001 Osteonecrosis. In: RuddyS, HarrisED, SledgeCB (eds.) Kelley's Textbook of Rheumatology, 6th ed. WB Saunders Co, Philadelphia, PA, USA, pp. 16531665.
  • 8
    Weinstein RS, Jilka RL, Parfitt AM, Manolagas SC 1998 Inhibition of osteoblastogenesis and promotion of apoptosis of osteoblasts and osteocytes by glucocorticoids. Potential mechanisms of their deleterious effects on bone. J Clin Invest 102:274282.
  • 9
    Weinstein RS, Nicholas RW, Manolagas SC 2000 Apoptosis of osteocytes in glucocorticoid-induced osteonecrosis of the hip. J Clin Endocrinol Metab 85:29072912.
  • 10
    Plotkin LI, Weinstein RS, Parfitt AM, Roberson PK, Manolagas SC, Bellido T 1999 Prevention of osteocyte and osteoblast apoptosis by bisphosphonates and calcitonin. J Clin Invest 104:13631374.
  • 11
    Agarwala S, Sule A, Pai BU, Joshi VR 2002 Alendronate in the treatment of avascular necrosis of the hip. Rheumatology (Oxford) 41:346347.
  • 12
    Astrand J, Aspenberg P 2002 Systemic alendronate prevents resorption of necrotic bone during revascularization. A bone chamber study in rats. BMC Musculoskelet Disord 3:19.