Prophylactic Fixation of Impending Fractures

                                   

                                   Dr. KS Dhillon

Introduction

After the lungs and liver, bone is the third most common site of metastases [1,2]. In patients with advanced breast and prostate cancer, bone metastases occur in 70% of the patients. Bone metastases occur in 15–30% of other common cancers, such as those of the lung, bladder, rectum, colon, kidney, or uterus [3]. The spine is the most common site of skeletal metastases. This is followed in order of frequency by pelvic bones, ribs, and upper and lower extremities [4,5].

In patients with metastatic bone disease pathological fracture is a severe emergency that should be avoided [6]. The median survival of patients without fractures is significantly longer than that of patients with fractures. The presence of a fracture is a negative prognostic factor. Hence, prophylactic osteosynthesis is an important goal before fractures occur [7]. 

A pathological fracture can lead to, a rapid decrease in autonomy, pain, hospitalization, and interruption of adjuvant therapies. 

The orthopedic oncologist has to make a correct diagnosis of impending fracture. Prophylactic osteosynthesis may potentially minimize complications and maximize the patient’s quality of life. There is, however, no consensus on the best criteria for the diagnosis of impending fracture [8].

Complications of metastatic bone disease affect the patient's quality of life and prognosis. They add to the resource utilization and costs of metastatic bone disease. Now that there is improved survival of cancer patients there is likely to be an increase in the prevalence of bone metastases. Prophylactic treatment to prevent fracture will help to maintain patient mobility and function [9]. Moreover, prophylactic fixation can be technically easier and is likely to be associated with less patient morbidity, better recovery, shorter postoperative care, and length of hospital stay [10]. There is still a lack of objective criteria to select patients who would benefit from surgery. 

Impending fracture

The concept of impending fracture was developed to address this difficult skeletal-related problem. In the literature, there is no consensus on the subject and a specific definition of impending fracture has not been established.

The concept of impending fracture is defined as a pathological condition of the bone where there is an imminent fracture risk at a pre-existent bone lesion. An impending fracture refers to the state of a bone where a pathological fracture will occur if no preventative action is taken [11]. Pathological fractures usually occur mainly in the femur (72.5%) and humerus (18.1%). They rarely occur in the spine (2.7%) [12].

The severity of pain and tumor characteristics, including site and size, both affect the risk of a fracture. Accurate prediction of peripheral fractures is necessary to help the orthopaedic surgeon in decision making. For this reason, several scoring systems have been developed. These include Mirels’ scoring system [13] and Harrington’s criteria [14].

There is currently no definitive and useful tool that can be used universally to objectively quantify the risk of sustaining a pathological fracture through a metastatic lesion in a long bone. An ideal classification system would be a clear communication tool that guides treatment planning, enables prediction of prognosis, and has excellent inter and intra-observer reliability. The use of this ideal system would help to circumvent unnecessary surgery and prevent pathological fracture. 

Mirels’ scoring system

The Mirels’ scoring system is the most commonly used scoring system for the risk of metastatic pathological fracture. The British Orthopaedic Association recommends the use of Mirels’ scoring system when determining the need for prophylactic surgery [15].

This scoring system combines several radiological and clinical factors. These include the location such as upper limb, lower limb, peritrochanter, radiographic appearance such as lytic, blastic, or mixed, size of the lesion such as less than 1/3, 1/3–2/3, more than 2/3, and accompanying pain which can be mild, moderate, or functional. Each parameter is scored from 1 to 3. The resulting total score is from a minimum of 4 to a maximum of 12. The initial validation study by Mirels retrospectively analyzed 78 metastatic long-bone lesions [13]. The study found that at 6 months, 51 lesions did not fracture and 27 fractured. When the score increased above 7, the percentage risk of fracture also increased. Lesions with a score of  7 had a low risk (5%) of fracture within a 6-month period. Hence such lesions can be safely irradiated. Lesions with a score of 8 had a 15% risk of fracture. In such situations, clinical judgment is necessary to determine the best course of action as this is a grey area. Lesions with a score of  9 had a very significant risk (33%) of fracture. Such lesions require prophylactic fixation. 

Damron et al [16] investigated the reproducibility, validity, and application of Mirels’ score across various experience levels and training backgrounds. Twelve femoral metastatic lesions before treatment or fracture were analyzed by 53 participants, including musculoskeletal radiologists, fellowship-trained practicing orthopedic oncologists, orthopedic attending physicians, and radiation or medical oncologists. While excluding the radiation and medical oncologists, there was significant agreement across experience categories for overall Kappa and for the concordance for individual and overall scores. The radiation and medical oncologists had the greatest variability in score (SD, 1.54). They also significantly underscored the lesions. The medical professionals in these categories usually see patients with metastasis first. They need a good screening tool to select patients who should be referred to groups with more experience for final decisions regarding prophylactic stabilization. The overall sensitivity of the applied Mirels’ system was 91% for determining the likelihood of pathological fracture. This tool is helpful in ruling out an impending fracture. The overall specificity was 35%. This would mean that the score would overestimate the risk of fracture and a strict application of the Mirels’ guidelines would potentially result in unnecessary procedures in two out of three patients. This limitation was confirmed in 2003 by Van der Linden et al [17]. They studied the prognostic value of conventional risk factors and the scoring system of Mirels in 102 patients with femoral metastases who were treated conservatively. They found that only axial cortical involvement >30 mm (p = 0.01), and circumferential cortical involvement >50% (p = 0.03) were predictive of a fracture. The Mirels’ scoring system was insufficiently specific to predict a fracture (p = 0.36). The use of axial cortical involvement rather than  Mirels’ scoring system or

other conventional risk factors seem to reduce the number of patients referred for unnecessary prophylactic osteosynthesis.

A subsequent study showed that Mirels’ scoring system is not applicable indistinctly to various sites [18]. The differences in load-bearing requirements between the upper and lower extremities mean that the humerus has a different fracture susceptibility profile as compared to the femur. In this study, a total of 17 case histories and plain radiographs of 16 patients with humeral metastases were presented through a web-based survey to 39 physicians with varying training and experience. A Mirels’ threshold of 9 points resulted in a sensitivity level of 14.5% and a specificity level of 82.9%. Lowering the threshold to 7 for the humerus preserved the same level of sensitivity and specificity that the Mirels’ rating had for other long bones. The sensitivity for correctly predicting a humeral fracture increased to 81% but at a cost of reducing specificity to 32%. This would mean that 10% to 20% of impending pathological fractures may be missed using these definitions, and also unnecessary prophylactic stabilization may be performed as has been reported for femoral lesions.

Mirels’ scoring system has been independently validated twice before [16,18]. It was, however, not as consistent as the conventional system in classifying impending pathological fractures [19]. 

Carnesale introduced the conventional system. The conventional system recommends prophylactic surgery for tumors with transverse and

longitudinal diameters of more than 3 cm or cortices involvement of more than 50%.

El-Husseiny and Coleman [19] examined the intra and interobserver reliability of these scoring systems. They found better inter and intra-observer agreement of the conventional system compared with Mirels’ scoring system. This may be because the conventional system was simple and easier to reproduce and had fewer variables. However, neither system assesses the patient's prognosis after the procedure or considers the life expectancy of the patient relative to the possible complications and risks of the intervention. The underlying diagnosis, comorbidities, previous radiotherapy treatment, and other sites of the disease have to be taken into account. Patients with slow-growing primary malignancies appear to recover well from prophylactic procedures [21]. The presence of cerebral, visceral, or multiple skeletal metastases, a poor Eastern Cooperative Oncology Group (ECOG) status, and the use of previous chemotherapy all reduce the survival rate [22]. Weber et al [23] reported that Mirels’ score ‘‘does not take into account the functional demands of patients, their anticipated longevity, or their baseline osteoporosis’’.  

They suggested using Mirels’ score along with assessments of cortical

destruction and the overall functional status of the patient. Numerous

factors should be taken into consideration to develop a new consistent rating system that could predict impending fractures and guide the management of patients with metastatic disease.

Harrington’s criteria

Before Mirels’ publication, Harrington [24] proposed a definition of impending pathological fracture of the long bones.

The definition included the following parameters:

• Cortical bone destruction greater than 50%

• Lesion larger than 2.5 cm

• Pathological avulsion fracture of the lesser trochanter

• Persisting stress pain despite irradiation.

All these were considered to be indications for prophylactic fixation of the femur. At first, these criteria were proposed for lytic lesions and later applied to blastic lesions as well [14]. Even if the blastic lesions appear harder, they reduce the strength of bone so that a small cortical involvement can increase the risk of fracture.

Harrington’s criteria have been quoted as classic guidelines for treating lower extremity bone metastases. They have, however, never been clinically validated and their reliability and reproducibility have been questioned [25].

Treatment Algorithm

For treatment of impending fractures, a tissue diagnosis has to be first obtained unless the patient has a known primary neoplasm with bone biopsy-proven skeletal metastasis. If no tissue diagnosis is available the treating surgeon should biopsy the lesion in question.

The level of the patient's dysfunction and pain is the most important factor to be taken into consideration in deciding the treatment option for the management of impending bone fracture due to bone softening disease. Pain or severe dysfunction demands a treatment that predictably leads to a quick resumption of the painless activities of daily living as well as to prevent fractures. Prophylactic surgical treatment of impending fractures improves outcomes [10]. Early management will help the patient to shorten the treatment period and the need for assistance.

Prophylactic fixation has been recommended for lesions greater than

2.5 cm in dimension or greater than 50% of cross-sectional bone destruction [26]. The consequences of pathological fractures are significant. Prophylactic fixation prevents pathological complications [27,28].

The biological behavior of bony lesions is another factor in determining

the possibility of pathological fracture. The biological aggressiveness can be inferred from whether the lesion is lytic, blastic, or mixed (lytic and blastic).

Zickel and Mouradian [29] reviewed 34 patients and they found that lesions could be listed in ascending order of those that are least likely to fracture. The ascending order of lesions that are least likely to fracture are blastic lesions, mixed blastic and lytic lesions, and purely lytic lesions. The purely lytic lesions are the most prone to pathological fracture.

The treatment of patients with an expected short life span, such as those

suffering from metastatic disease, is considered to be very important to help them. A bone that has lost its structural integrity, even though not fractured, will not support weight bearing for months even if the metastasis has been eliminated. Elimination of the metastatic tumor does not always equate with return to function [30].

Bone softening or bone metastasis should not be allowed to progress to pathological fracture. Function can be returned to these patients with impending fractures. This can be done by surgical stabilization. This will be the best way to return the patient's function while the patient is being treated postoperatively with medical therapy, chemotherapy, or radiotherapy. Comprehensive treatment of patients with soft bone disease requires the participation of an orthopedic surgeon early in the clinical course. Early consultation and mutual follow-up will benefit the patient in maintaining independent function and avoiding irretrievable catastrophes.

Most of the cases with hip affection due to osteomalacia are fixed with dynamic hip screws. During the dynamic hip screw insertion, a biopsy can be taken for diagnostic confirmation. Intramedullary nails can be used for femoral shaft lesions if there is bone destruction without significant focal cortical loss. Insertion of the femoral nail is favourable for most patients with impending fracture from femoral metastasis. This technique provides resistance to torsional stresses as well as angular displacement throughout the full length of the femur, including the femoral neck and intertrochanteric areas [31].

External fixators are used in patients with medical conditions that prevent surgical interference. By surgical stabilization, the length of the hospital stay can be reduced and for those patients who cannot be mobilized because of their primary disease, the nursing care is made easier. 

Conclusion

Complications that result from metastatic bone disease affect the patient's quality of life and prognosis. They also add to resource utilization and costs of metastatic bone disease. Now that there is improved survival of cancer patients there is likely to be an increase in the prevalence of bone metastases. When there is metastatic bone disease there always is the risk of pathological bone fracture. This gives rise to the concept of impending fractures. Prophylactic treatment of impending fractures helps to maintain patient mobility and function [9]. Moreover, prophylactic fixation can be technically easier and is likely to be associated with less patient morbidity, better recovery, shorter postoperative care, and length of hospital stay. There is still a lack of objective criteria to select patients who would benefit from surgery. 

Surgical fixation of fractures in weight-bearing long bones with impending fractures provides pain relief and a functionally stable and durable construct. It helps in early ambulation and prevents fracture

complications. It allows independent function and prevents irretrievable

catastrophes.

References

1. Aaron AD. The management of cancer metastatic to bone. J Am Med Assoc 1994;272:1206–9.

2. Toomey A, Friedman L. Mortality in cancer patients after a fall-related injury: the impact of cancer spread and type. Injury 2014. Mar 27. pii: S0020-1383(14)00132-6.

3. Roodman GD. Mechanisms of disease: mechanisms of bone metastasis. New Engl J Med 2004;350:1655–64.

4. Krammer J, Engel D, Schnitzer A, Kaiser CG, Dinter DJ, Brade J, et al. Is the assessment of the central skeleton sufficient for osseous staging in breast cancer patients? A retrospective approach using bone scans. Skelet Radiol 2013;42:787–91.

5. Nakamoto Y, Osman M, Wahl RL. Prevalence and patterns of bone metastases detected with positron emission tomography using F-18FDG. Clin Nucl Med 2003;28:302–7.

6. Manglani HH, Marco RA, Picciolo A, Healey JH. Orthopedic emergencies in cancer patients. Semin Oncol 2000;27:299–310.

7. Saad F, Lipton A, Cook R, Chen YM, Smith M, Coleman R. Pathologic fractures correlate with reduced survival in patients with malignant bone disease. Cancer 2007;110:1860–7.

8. Arvinius C, Parra JL, Mateo LS, Maroto RG, Borrego AF, Stern LL. Benefits of early intramedullary nailing in femoral metastases. Int Orthop 2014;38:129–32.

9. Eastley N, Newey M, Ashford RU. Skeletal metastases – the role of the orthopaedic and spinal surgeon. Surg Oncol (Oxf) 2012;21: 216–22.

10. Ward WG, Holsenbeck S, Dorey FJ, Spang J, Howe D. Metastatic disease of the femur: surgical treatment. Clin Orthop Relat Res 2003; Oct;(415 Suppl):S230–44.

11. Kronisch C, Balague F, Dudler J. Fear of impending fractures: when to refer? A case-based review. Clin Rheumatol 2014. Jan 3 DOI: 10.1007/s10067-013-2461-6.

12. Heinz T, Stoik W, Vecsei V. Treatment and results of pathologic fractures. A collaborative study from 1965 to 1985 of 16 Austrian hospitals. Der Unfallchirurg 1989;92:477–85.

13. Mirels H. Metastatic disease in long bones: a proposed scoring system for diagnosing impending pathologic fractures. 1989. Clin Orthop Relat Res 2003;Oct;(415 Suppl):S4–13.

14. Harrington KD. Impending pathologic fractures from metastatic malignancy: evaluation and management. Instr Course Lect 1986;35:357–81.

15. Metastatic bone disease: a guide to good practice. British Orthopaedic Association and British Orthopaedic Oncology Society Publication; 2000.

16. Damron TA, Morgan H, Prakash D, Grant W, Aronowitz J, Heiner J. Critical evaluation of Mirels’ rating system for impending pathologic fractures. Clin Orthop Relat Res 2003;Oct;(415 Suppl):S201–7.

17. Van der Linden YM, Dijkstra PD, Kroon HM, Lok JJ, Noordijk EM, Leer JW, et al. Comparative analysis of risk factors for pathological fracture with femoral metastases. J Bone Joint Surg Br Vol 2004;86:566–73.

18. Evans AR, Bottros J, Grant W, Chen BY, Damron TA. Mirels’ rating for humerus lesions is both reproducible and valid. Clin Orthop Relat Res 2008;466:1279–84.

19. El-Husseiny M, Coleman N. Inter- and intra-observer variation in classification systems for impending fractures of bone metastases. Skelet Radiol 2010;39:155–60.

20. Carnesale PG. Malignant Bone Tumors; Campbell’s Operative Orthopaedics. St.Louis: Mosby-Year Book Inc, 1998: 726-727.

21. Wedin R, Bauer HC, Wersall P. Failures after operation for skeletal metastatic lesions of long bones. Clin Orthop Relat Res 1999;Jan; (358):128–39.

22. Katagiri H, Takahashi M, Wakai K, Sugiura H, Kataoka T, Nakanishi K. Prognostic factors and a scoring system for patients with skeletal metastasis. J Bone Joint Surg Br Vol 2005;87:698–703.

23. Weber KL, Randall RL, Grossman S, Parvizi J. Management of lower-extremity bone metastasis. J Bone Joint Surg Am 2006; 88(Suppl. 4):11–9.

24. Harrington KD. New trends in the management of lower extremity metastases. Clin Orthop Relat Res 1982;Sep;(169):53–61.

25. Keene JS, Sellinger DS, McBeath AA, Engber WD. Metastatic breast cancer in the femur. A search for the lesion at risk of fracture. Clin Orthop Relat Res 1986;Feb;(203):282–8.

26. Hipp JA, 6pringٽeld DS, Hayes WC (1995) Predicting pathologic fracture risk in the management of metastatic bone defects. Clin Orthop Relat Res 312: 120-135.

27. O'Donnell P (2013) Impending Fracture & Prophylactic Fixation.

28. Van Geffen E, Wobbes T, Veth RP, Gelderman WA (1997) Operative management of impending pathological fractures: a critical analysis of therapy. J Surg Oncol 64: 190-194.

29. Zickel RE, Mouradian WH (1976) Intramedullary fixation of pathological fractures and lesions of the Subtrochanteric region of the femur. J Bone Joint Surg 58: 1061-1066.

30. Colyer RA (1986) Surgical stabilization of pathological neoplastic fractures. Curr Probl Cancer 10: 117-168.

31. Johnson EW (1957) Intramedullary fixation of pathological fractures. JAMA 163: 417-419.