Pathologic Fractures

H.T. Temple, MDWalter W. Virkus, MD

Created March 2004; Revised December 2005, October 2008

Pathologic Fractures

• Tumors– primary– secondary (metastatic) (most common)

• Metabolic– osteoporosis (most common)– Paget’s disease– hyperparathyroidism

Pathologic Fractures Benign Tumors

• Fractures more common in benign tumors (vs malignant tumors)– most asymptomatic prior to fracture– antecedent nocturnal/rest symptoms rare– most common in children

• humerus

• femur

– unicameral bone cyst, NOF, fibrous dysplasia, eosinophilic granuloma

Unicameral Bone Cyst

• Fractures observed more often in males than females

• May be active or latent

• Almost always solitary

• First two decades

• Humerus and femur most common sites

Fracture through UBC “fallen fragment”sign (arrow)

Fractures through benign tumors

Unicameral Bone Cyst

• Treatment - impending fractures– observation – aspiration and injection methylprednisolone,

bone marrow or bone graft – curetting and bone graft (+/-) internal fixation

• Treatment - fractures– allow fracture to heal and reassess– ORIF for femoral neck fractures

Fibroxanthoma

• Most common benign tumor• Femur, distal tibia, humerus• Multiple in 8% of patients

(associated with neurofibromatosis)

• Increased risk of pathologic fracture in lesions >50% diameter of bone and >22mm length

Fibroxanthoma

• Treatment– observation– curetting and bone graft for impending

fractures– immobilization and reassess after healing for

patients with fracture

Fibrous Dysplasia

• Solitary vs. multifocal (solitary most common)

• Femur and humerus • First and second decades • May be associated with

café au lait spots and endocrinopathy (Albright’s syndrome)

Fibrous Dysplasia

• Treatment– observation– curetting and bone graft (cortical structural

allograft) to prevent deformity and fracture (+/-) internal fixation

– expect resorption of graft and recurrence– pharmacologic—bisphosphonates

Pathologic Fracturesthrough Primary Malignant

Tumors• Relatively rare (often unsuspected)

• May occur prior to or during treatment

• May occur later in patients with radiation osteonecrosis (Ewing’s, lymphoma)

• Osteosarcoma, Ewing’s, malignant fibrous histiocytoma, fibrosarcoma

Pathologic FracturesPrimary Malignant Tumors

• Suspect primary tumor in younger patients with aggressive appearing lesions– poorly defined margins (wide zone of

transition, lack of sclerotic rim)– matrix production– periosteal reaction

• Patients usually have antecedent pain before fracture, especially night pain

Pathologic FracturesPrimary Malignant Tumors

• Pathologic fracture complicates but does not mitigate against limb salvage

• Local recurrence is higher• Survival is not compromised• Patients with fractures and underlying suspicious

lesions or history should be referred for biopsy

A

B

A. Pathologic fracture through MFHarising in antecedent infarct

B. (H&E 100x) Pleomorphic spindledcells with storiform growth pattern

Pathologic FracturesPrimary Malignant Tumors

• Always biopsy solitary destructive bone lesions even with a history of primary carcinoma

• Case:A 62 year-old woman with a history of breast carcinoma presented with a pathologic fracture through a solitary proximal femoral lesion

Pre-op Post-

Intermediate grade chondrosarcoma*fixation of primary bone tumors must not be performed until proper evaluation has been performed and the diagnosis has been established in order to prevent potential for spread of tumor.

Pathologic FracturesPrimary Malignant Tumors

• Treatment– Immobilization

• Traction, ex fix, cast

– staging– biopsy– adjuvant treatment (chemotherapy)– resection/amputation

Metabolic Bone Disease

• Osteoporosis– insufficiency fractures

• Paget’s disease– early and late stages; most fractures occur in

the late stage of disease

• Hyperparathyroidism– dissecting osteitis– fractures through Brown tumors

Fractures through non-neoplastic bone disease

Paget’s Disease• Radiographic appearance

– Thickened cortices– Purposeful trabeculae– Mixed sclerosis/lysis– Bowing deformities– Joint arthrosis

• Fracture – delayed healing– malignant transformation

• Treatment– Osteotomy to correct alignment– Excessive bleeding– Joint arthroplasty vs. ORIF

Fracture through Pageticbone (arrow). Transverse fracture suggests pathologic bone.

Hyperparathyroidism

• Adenoma

• Polyostotic disease

• Mental status changes

• Abdominal pain

• Nephrolithiasis

• Polyostotic disease– mixed radiolucent/radiodense

Mixedradiodense

andradiolucent

lesions

Multiple brown tumors in a patient with primary hyperparathyroidism

Hyperparathyroidism

• May be secondary to renal

failure– secondary

– tertiary

• Treatment – parathyroid adenectomy

– ORIF for fracture

– correct calcium

Pathologic fracture through brown tumor (arrow)

Fractures in Patients with Metastatic Disease and Myeloma

• Aside from osteoporosis, most common causes of pathologic fracture

• Fifth decade and beyond

• Appendicular sites: femur and humerus most common

• All metastatic tumors are not treated the same

Not All Mets Created Equal

• Breast – radiosensitive, chemosensitive

• Lung – moderately radiosensitive, chemo sensitivity variable

• Prostate – radiosentive, chemosensitive

• Thyroid – radiosensitive, chemosensitive

• Renal – minimally radiosensitive, variable chemosensitivity

Overall Incidence of Metastases to Bone at Autopsy

• 70% Jaffe, 1958

• 12% Clain, 1965

• 32% Johnson, 1970

• 21% Dominok, 1982

Incidence of Metastases at Autopsy by Primary Tumor Site

Primary Site % metastasis to Bone

Breast 50-85

Lung 30-50

Prostate 50-70

Hodgkin’s 50-70

Kidney 30-50

Thyroid 40

Melanoma 30-40

Bladder 12-25

Incidence of Metastases

• 60% of patients with early identified cancer may already have metastases

• 10-15% of all patients with primary carcinoma will have radiologic evidence of bone metastases during course of disease

Route of Metastases

• Contiguous

• Hematogenous– most common

Destructive lesions in bone from lung carcinoma (arrows)

Mechanism of Metastases• Release of cells from the

primary tumor• Invasion of efferent lymphatic

or vascular channels• Dissemination of cells• Endothelial attachment and

invasion at distant site• Angiogenesis and tumor growth

at distant siteMetastatic carcinomaIn body pedicle junction

Bone Destruction

• Early– most important– osteoclast mediated – (RANK L)

• Late– malignant cells may be

directly responsible

Metastases of Unknown Origin

• 3-4% of all carcinomas have no known primary site

• 10-15% of these patients have bone metastases

Diagnostic Strategy for Patients with Unknown Primary

% Primary Tumor Identified

History and Physical 8%

Chest X-Ray 43%

Chest CT 15%

Abdominal CT 13%

Biopsy 8%Rougraff, 1993

Defects

• Cortical defects weaken bone especially in torsion

• Two types– stress riser - smaller than the diameter of bone– open section defect - larger than the diameter of

bone…. causes a 90% reduction in load to failure and demand augmentation and fixation

Impending Pathologic Fracture

• 61% of all pathologic fractures occur in the femur

• 80% are peritrochanteric

• fracture in this area results in significant morbidity

• historic data on impending pathologic fracture involves the proximal femur

Impending Pathologic Fracture• Parrish and Murray, 1970

– increasing pain with advancing cortical destruction of lesions involving >50% of the shaft diameter

• Beals, 1971– lesions >2.5 cm are at increased risk to fracture

• Murray, 1974– increased fracture with destruction of > one-

third of the cortex, pain after radiotherapy

Impending Pathologic Fracture• Fidler, 1981% shaft destroyed Incidence Fx (%)0-25% 0%25-50% 3.7%50-75% 61%>75% 79%

• Conclusion: Patients with tumors destroying >50% of the diameter of bone require prophylactic internal fixation

Indication for Prophylactic Internal Fixation

• “Harrington criteria”– >50% of diameter of bone– >2.5 cm– pain after radiation– fracture of the lesser trochanter

• Limitations– only for proximal femur– doesn’t account for tumor biology

Harrington, K.D.: Clin. Orthop. 192: 222, 1985

Mirels Scoring System

Score

1 2 3

Site upper limb lower limb peritrochanteric

Pain mild moderate functional

Lesion blastic mixed lytic

Size <1/3 1/3-2/3 >2/3

Score < 7 – no surgeryScore > 7 – prophylactic fixation

Mirels, H.: Clin. Orthop. 249: 256, 1989.

Adjuvant Treatment

• Radiation– Radiation alone

• Complete pain relief in 50%• Partial pain relief in 35%

• Radiofrequency ablation

• Chemotherapy

• Hormone treatment

• Bisphosphonates

Adjuvant Treatment

• Radiation– Radiation alone

• Complete pain relief in 50%• Partial pain relief in 35%

• Radiofrequency ablation

• Chemotherapy

• Hormone treatment

• Bisphosphonates

Radiation Therapy

• Overall 85% response rate

• Median duration of pain relief 12-15 weeks

• Tumor necrosis followed by collagen proliferation, woven bone formation, and replacement by lamellar bone

• Recalcification by 2-3 months

• More than half respond within 1-2 weeks

• Various dose and fractionization schedules

Radiation Therapy

• Townsend, et al., Journal of Clinical Oncology, 1994– 64 surgical stabilization procedures, 35 with post-op

radiation, 29 with no radiation

– Functional use of extremity, avoidance of revision surgery, and survival time increased in radiation group

RadiotherapyPre XRTProstate

CA

Post XRTProstate

CA

Bisphosphonates• “Long-term prevention of skeletal

complications of metastatic breast cancer with pamidronate: Protocol 19 Aredia Breast Cancer Study Group”

• Hortobagyi, et al. Journal of Clinical Oncology, 1998

• “Zoledronic acid reduces skeletal-related events in patients with osteolytic metastases”

• Berenson, et al. Cancer 2001

Treatment Objectives in Metastatic Disease

• Decrease pain

• Restore function

• Maintain/restore mobility

• Limit surgical procedures

• Minimize hospital time

• Early return to function (immediate weightbearing)

Pathologic Fracture Survival

• 75% of patients with a pathologic fracture will be alive after one year

• the average survival is ~ 21 months

Survival Time

• Poor prognostic factors– Presentation with

metastatic disease– Short time from initial

diagnosis to first met– Visceral mets– Non-small cell lung

cancer

6 mos % 1 yr % 3 yrs %

Breast 89 78 48

Prostate 98 83 57

Lung 50 22 3

Renal 51 51 40

Healing of Path Fractures

• Healing rate of pathologic fractures– Myeloma- 67%– Renal- 44%– Breast- 37%– Lung- 0%

Fracture Healing

• 129 patients

• overall rate = 35%

• 74% for patients surviving > 6 months

• radiotherapy <30 GY did not adversely affect fracture healing

Gainor, B.J.: CORR 178: 297, 1983

Pathologic Fracture Treatment

• Biopsy especially for solitary lesions• Nails versus plates versus arthroplasty

– plates, screws and cement superior for torsional loads

– interlocked nails stabilize entire bone

• Cement augmentation• Radiation/chemotherapy/bisphosphonates• Aggressive rehabilitation

Indications for Surgical Treatment

• Ratio of survival time to surgical recovery time

• Ability to ambulate

• Ability to use extremity

• Capacity to return to full function

• Pain not controlled by analgesics

• Location of disease – high risk area

Indications for ORIF/IMN

• Diaphyseal lesion• Good bone stock• Histology sensitive to

chemo/radiation• Impending fractures• Poor prosthetic options

Indications For Replacement

• Periarticular disease• Fracture after radiation• Failed fixation• Renal cell ca

Pathologic Fracture Treatment

• Periarticular fractures, especially around the hip are more appropriately treated with arthroplasty

• Periacetabular fractures– protrusio shell,

cement, arthroplasty

– saddle prosthesis

– Structural

allograft-prosthesis

composite

Cement

PMMA no PMMA

Pain relief 97% 83%

Ambulation 95% 75%

Fixation failure 2 cases 6 cases

Haberman, E.T: CORR, 169: 70, 1982

Resection for Pathologic and Impending Pathologic Fractures

• Radiation and chemotherapy resistant tumors– renal– thyroid– melanoma– occasionally lung

• Solitary metastases (controversial)

pre-op pre-op post-op

Renal Cell Carcinoma

*pre operative embolization of renal cell mets should be done

Pre-opPre-oprenal cellrenal cellcarcinomacarcinoma

Post-oprenal cellcarcinoma

Solitary renal cell carcinoma

Permeative lysis

Soft tissue mass

• Post-op intercalary allograft

Renal Cell• Kollender, et al., Journal of Urology, 2000

– 45 lesions treated with wide or marginal resection

– 91% with pain relief, 89% with good/excellent functional outcome

• Les, et al., CORR, 2001– 41 renal cell patients treated with intralesional excision,

37 treated with marginal or wide resection

– Re-operation recommended for 41% in group I, 3% in Group II

– Median survival 20 months in group I, 35 months in group II

Renal Cell

• Wedin, et al., CORR 1999– 228 metastatic lesions treated with endoprosthetic or

osteosynthesis

– 24% failure rate in renal cell lesions

– 20% failure rate in diaphyseal and distal femur lesions

– 14% failure rate for osteosynthesis, 2% for endoprosthesis

Complications

• Infection– malnutrition

– hematomyelopoetic suppression

• Hemorrhage– vascular tumors ( renal and thyroid)

• Tumor recurrence• Failure of fixation• Thromboembolic disease

Embolization

• Hypervascular tumors– Renal cell carcinoma– Thyroid carcinoma– Pheochomocytoma

Post embolizationPre embolization

Pre-operative embolization can preventhemorrhage with intra-lesional surgery

Summary

• Diagnosis and treatment requires a multidisciplinary approach

• Aggressive surgical treatment relieves pain, restores function, and facilitates nursing care

• Biopsy all solitary lesions or refer appropriately

• Understand tumor biology and tailor treatment

References• Mirels H. Metastatic disease in long bones. A

proposed scoring system for diagnosing impending pathologic fractures. Clin Orthop 1989; 249:256

• Gainor BJ, Buchert P. Fracture healing in metastatic bone disease Clin Orthop 1983; 176:297-302.

• Eckardt JJ, et.al. Endoprosthetic reconstructions for bone metastases. Clin Orthop 2003; 415:S254-262.

References

• Ward WG, et.al. Metastatic disease of the femur: surgical treatment. Clin Orthop 2003; 415:S230-244

• Kelly CM, et.al. Treatment of metastatic disease of the tibia. Clin Orthop 2003; S219-219

• van der Linden YM, et.al. Simple radiographic parameter predicts fracturing in metastatic femoral bone lesions:results from a randomized trial. Radiotherapy and Oncology 2003; 69: 21-31

References

• Singletary SE, et.al. A role for curative surgery in the treatment of selected patients with metastatic breast cancer. Oncologist 2003; 214-251

• Wedin R. Surgical treatment for pathologic fracture. Acta Orthopaedica Scandinavica 2001; 72: 1-29

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