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 infarctB
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, et.al. Endoprosthetic reconstructions for bone metastases. Clin Orthop 2003; 415:S

66. References
Ward WG, et.al. Metastatic disease of the femur: surgical treatment. Clin Orthop 2003; 415:S
Kelly CM, et.al. Treatment of metastatic disease of the tibia. Clin Orthop 2003; S
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

67. References
Singletary SE, et.al. 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

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