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Pathologic Fractures H.T. Temple, MD

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1 Pathologic Fractures H.T. Temple, MD
Walter W. Virkus, MD Created March 2004; Revised December 2005, October 2008

2 Pathologic Fractures Tumors Metabolic primary
secondary (metastatic) (most common) Metabolic osteoporosis (most common) Paget’s disease hyperparathyroidism

3 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

4 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 fragment”sign (arrow)

5 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

6 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

7 Fibroxanthoma Treatment observation
curetting and bone graft for impending fractures immobilization and reassess after healing for patients with fracture

8 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)

9 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

10 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 (Ewing’s, lymphoma) Osteosarcoma, Ewing’s, malignant fibrous histiocytoma, fibrosarcoma

11 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

12 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

13 Pathologic fracture through MFH arising in antecedent infarct
B Pathologic fracture through MFH arising in antecedent infarct (H&E 100x) Pleomorphic spindled cells with storiform growth pattern A

14 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

15 Intermediate grade chondrosarcoma
Post- Pre-op 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.

16 Pathologic Fractures Primary Malignant Tumors
Treatment Immobilization Traction, ex fix, cast staging biopsy adjuvant treatment (chemotherapy) resection/amputation

17 Metabolic Bone Disease
Fractures through non-neoplastic bone disease 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

18 Paget’s Disease Radiographic appearance Fracture Treatment
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.

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

20 Hyperparathyroidism May be secondary to renal failure Treatment
tertiary Treatment parathyroid adenectomy ORIF for fracture correct calcium Pathologic fracture through brown tumor (arrow)

21 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

22 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

23 Overall Incidence of Metastases to Bone at Autopsy
70% Jaffe, 1958 12% Clain, 1965 32% Johnson, 1970 21% Dominok, 1982

24 Incidence of Metastases at Autopsy by Primary Tumor Site
Primary Site % metastasis to Bone Breast Lung Prostate Hodgkin’s Kidney Thyroid Melanoma Bladder

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

26 Route of Metastases Contiguous Hematogenous most common
Destructive lesions in bone from lung carcinoma (arrows)

27 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

28 Bone Destruction Early Late most important osteoclast mediated
(RANK L) Late malignant cells may be directly responsible

29 Metastases of Unknown Origin
3-4% of all carcinomas have no known primary site 10-15% of these patients have bone metastases

30 Diagnostic Strategy for Patients with Unknown Primary
% Primary Tumor Identified History and Physical 8% Chest X-Ray 43% Chest CT % Abdominal CT 13% Biopsy 8% Rougraff, 1993

31 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

32 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

33 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

34 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

35 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

36 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 Based on a retrospective study of 78 pts with metastatic disease to long bones. 27 patients fractured within 6 months. Their mean Mirels score was 10 while those without fracture had a score of < 7. Score < 7 – no surgery Score > 7 – prophylactic fixation Mirels, H.: Clin. Orthop. 249: 256,

37 Adjuvant Treatment Radiation Radiofrequency ablation Chemotherapy
Radiation alone Complete pain relief in 50% Partial pain relief in 35% Radiofrequency ablation Chemotherapy Hormone treatment Bisphosphonates

38 Adjuvant Treatment Radiation Radiofrequency ablation Chemotherapy
Radiation alone Complete pain relief in 50% Partial pain relief in 35% Radiofrequency ablation Chemotherapy Hormone treatment Bisphosphonates

39 Radiation Therapy Overall 85% response rate
Median duration of pain relief 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

40 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

41 Radiotherapy Pre XRT Prostate CA Post XRT Prostate CA

42 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

43 Treatment Objectives in Metastatic Disease
Decrease pain Restore function Maintain/restore mobility Limit surgical procedures Minimize hospital time Early return to function (immediate weightbearing)

44 Pathologic Fracture Survival
75% of patients with a pathologic fracture will be alive after one year the average survival is ~ 21 months

45 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 40

46 Healing of Path Fractures
Healing rate of pathologic fractures Myeloma- 67% Renal- 44% Breast- 37% Lung- 0%

47 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

48 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

49 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

50 Indications for ORIF/IMN
Diaphyseal lesion Good bone stock Histology sensitive to chemo/radiation Impending fractures Poor prosthetic options

51 Indications For Replacement
Periarticular disease Fracture after radiation Failed fixation Renal cell ca

52 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

53 Cement PMMA no PMMA Pain relief 97% 83% Ambulation 95% 75%
Fixation failure 2 cases 6 cases Haberman, E.T: CORR, 169: 70, 1982

54 Resection for Pathologic and Impending Pathologic Fractures
Radiation and chemotherapy resistant tumors renal thyroid melanoma occasionally lung Solitary metastases (controversial)

55 Renal Cell Carcinoma pre-op pre-op post-op
*pre operative embolization of renal cell mets should be done

56 Post-op renal cell carcinoma
Pre-op renal cell carcinoma

57 Solitary renal cell carcinoma
Soft tissue mass Permeative lysis

58 Post-op intercalary allograft

59 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

60 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

61 Complications Infection Hemorrhage Tumor recurrence
malnutrition hematomyelopoetic suppression Hemorrhage vascular tumors ( renal and thyroid) Tumor recurrence Failure of fixation Thromboembolic disease

62 Embolization Hypervascular tumors Renal cell carcinoma
Thyroid carcinoma Pheochomocytoma

63 Pre embolization Post embolization
Pre-operative embolization can prevent hemorrhage with intra-lesional surgery

64 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

65 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: Eckardt JJ, Endoprosthetic reconstructions for bone metastases. Clin Orthop 2003; 415:S

66 References Ward WG, Metastatic disease of the femur: surgical treatment. Clin Orthop 2003; 415:S Kelly CM, Treatment of metastatic disease of the tibia. Clin Orthop 2003; S van der Linden YM, Simple radiographic parameter predicts fracturing in metastatic femoral bone lesions:results from a randomized trial. Radiotherapy and Oncology 2003; 69: 21-31

67 References Singletary SE, A role for curative surgery in the treatment of selected patients with metastatic breast cancer. Oncologist 2003; Wedin R. Surgical treatment for pathologic fracture. Acta Orthopaedica Scandinavica 2001; 72: 1-29

68 Thank You If you would like to volunteer as an author for the Resident Slide Project or recommend updates to any of the following slides, please send an to OTA about Questions/Comments Return to General/Principles Index

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