Pathologic Fractures

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

Created March 2004; Revised December 2005, October 2008

Pathologic Fractures
Tumors
primary secondary (metastatic) (most common)

Metabolic
osteoporosis (most common) Pagets 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

Fractures through benign tumors

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 fragmentsign (arrow)

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 caf au lait spots and endocrinopathy (Albrights 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 pharmacologicbisphosphonates

Pathologic Fractures through Primary Malignant Tumors

Relatively rare (often unsuspected) May occur prior to or during treatment May occur later in patients with radiation osteonecrosis (Ewings, lymphoma) Osteosarcoma, Ewings, malignant fibrous histiocytoma, fibrosarcoma

Pathologic Fractures Primary 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 Fractures Primary 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. Pathologic fracture through MFH arising in antecedent infarct

A

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

Pathologic Fractures Primary 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 Fractures Primary Malignant Tumors

Treatment
Immobilization
Traction, ex fix, cast

staging biopsy adjuvant treatment (chemotherapy) resection/amputation

Fractures through non-neoplastic bone disease

Metabolic Bone Disease

Osteoporosis
insufficiency fractures

Pagets disease
early and late stages; most fractures occur in the late stage of disease

Hyperparathyroidism
dissecting osteitis fractures through Brown tumors

Pagets 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 Pagetic bone (arrow). Transverse fracture suggests pathologic bone.

Hyperparathyroidism
Adenoma Polyostotic disease Mental status changes Abdominal pain Nephrolithiasis Polyostotic disease
mixed radiolucent/radiodense
Multiple brown tumors in a patient with primary hyperparathyroidism

Mixed radiodense and radiolucent lesions

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% 12% 32% 21% Jaffe, 1958 Clain, 1965 Johnson, 1970 Dominok, 1982

Incidence of Metastases at Autopsy by Primary Tumor Site

Primary Site Breast Lung Prostate Hodgkins Kidney Thyroid Melanoma Bladder % metastasis to Bone 50-85 30-50 50-70 50-70 30-50 40 30-40 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 site

Metastatic carcinoma In 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

History and Physical Chest X-Ray Chest CT Abdominal CT Biopsy

% Primary Tumor Identified 8% 43% 15% 13% 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 > onethird of the cortex, pain after radiotherapy

Impending Pathologic Fracture

Fidler, 1981
% shaft destroyed 0-25% 25-50% 50-75% >75% Incidence Fx (%) 0% 3.7% 61% 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 doesnt account for tumor biology

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

Mirels Scoring System

1 Score 2
lower limb

3
peritrochanteric

Site Pain Lesion Size

upper limb

mild blastic <1/3

moderate mixed 1/3-2/3

functional lytic >2/3

Score < 7 no surgery Score > 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

Radiotherapy
Pre XRT Prostate CA Post XRT Prostate 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 % Breast Prostate Lung Renal 89 98 50 51 78 83 22 51 3 yrs % 48 57 3 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
Pain relief Ambulation PMMA 97% 95%
2 cases

no PMMA 83% 75%

6 cases

Fixation failure

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)

Renal Cell Carcinoma

post-op pre-op pre-op *pre operative embolization of renal cell mets should be done

Pre-op renal cell carcinoma

Post-op renal cell carcinoma

Solitary renal cell carcinoma

Soft tissue mass

Permeative lysis

 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

Pre embolization

Post embolization

Pre-operative embolization can prevent hemorrhage 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:S254262.

References
Ward WG, et.al. Metastatic disease of the femur: surgical treatment. Clin Orthop 2003; 415:S230244 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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