Pathologic Fractures

Pathologic fractures represent a growing concern in the field of musculoskeletal oncology. The incidence of pathologic fractures is rising, primarily due to improved diagnosis and treatment of metastatic disease leading to prolonged survival. Therefore, diagnosis of the causative pathology is of paramount importance in the successful treatment of a pathologic fracture and is a prerequisite for proceeding with surgical intervention. Pathologic fractures occur through areas of weakened bone attributed to either primary malignant lesions, benign lesions, metastasis, or underlying metabolic abnormalities, with the common factor being altered skeletal biomechanics secondary to pathologic bone.

Causes

The majority of neoplastic pathologic fractures are caused secondary to metastatic disease rather than primary bone tumors. In a patient 40 years of age or older, the likelihood that a pathologic fracture through an unknown lesion that is metastatic is 500 times more common than the likelihood of it being a primary bone sarcoma. There are five recognized carcinomas that most frequently metastasize to bone, including lung, breast, thyroid, renal, and prostate. The most common sites for skeletal metastasis include the spine, proximal femur, and pelvis. Primary bone sarcomas occur far less frequently, though disregarding the possibility that a pathologic fracture through a solitary bone lesion could be the first evidence of a primary sarcoma could lead to catastrophic consequences, including loss of life or limb.

Osteolytic lesions of bone occur secondary to tumor-induced activation of osteoclasts by upregulation of RANK ligand. Osteoblastic lesions occur secondary to endothelin 1, which is secreted by the tumor. Pathologic fractures occur through these lesions due to altered biomechanics. For example, a lytic lesion or open-section defect might produce a stress concentration that cannot withstand normal or low-demand activity.

The causes are following

  • The repetitive impact – on the lower limb bone with weight-bearing exercises and occupational work cause microfractures, which consolidate to stress and avulsion fractures. [rx] Injury can occur through hyperextension of the wrist in combination with eccentric contraction of the flexor carpi ulnaris (FCU) can result in osteochondral or avulsion fractures or dislocation of the pisiform [], axial force applied to the wrist is hyperextended in a fall from hitting the heel of the hand on a hard surface following a fall onto an outstretched hand, impaction of the hand bone after a fall on an outstretched hand or by avulsion of attached ligaments.  subluxations, higher energy trauma such as a punch delivering a blow, direct trauma to the bone, longitudinal axial loading, clenched fist injuries, axial load via direct trauma to a clenched fist transfers energy to the upper limb bone,
  • Heavy influence – The force of a jump or fall from height can result in a broken knee. It can happen in foot bone fractures even if you jump from a high altitude, lift accident in a big shopping mall, or multilevel apartment. Falling on an extended, displacement of each fracture pattern can be angulated, translated, rotated, or shortened, an impact onto a clenched fist, direct blow, rotational movement, displacement of each fracture pattern can be angulated, translated, rotated, shortened, segmental fractures, 
  • Missteps – Frequently falling from outstretches hand can cause a fracture of the upper extremity if you put your foot, and knee down awkwardly abnormally. Your ankle might twist, suddenly change direction, sprint, kick, leap, or roll your foot joint to the side as you put weight on it. It can also happen in stare up or stare down unconscious.
  • Sports – High-impact sports such as football, cricket, hockey, and volley boll involve intense movements that place stress on the joints, including knee bone fracture examples of high-impact sports include cricket, racing of the bike, soccer, football, horseback riding, hockey, skiing snowboarding, in-line skating, jumping on a trampoline, basketball, and hitting, as in a boxer or a defensive lineman in a football game hitting an offensive lineman to protect the quarterback. Impacts on the upper limb bone with forced hyperextension deviation by a direct blow over the hypothenar eminence in sports where a firm grip is an upper limb such as tennis, baseball, golf, racket, club, bat, volleyball, baseball catchers, golfers, karate, carpenters, polishers, builders, strong dorsopalmar compression
  • In a Race – The injuries are occurring mostly in competitive sports with hitting, running, and sudden direction changes in sprinting, steeplechase, sudden direction-changing sportive activities, sudden accelerating, and decelerating activities, uncontrolled football hitting, repetitive hip movements, and repetitive loads, in high sporting activities in fully grown athletes, dance, soccer, or kicking a soccer ball, football training season, hockey, rugby, cricket, football playing, skating, playing baseball, running or kicking a ball, tennis, fencing, basketball, gymnastics, the excessive passive elongation of the musculotendinous unit during gymnastic movements.
  • Daily collisions accident – The sudden, heavy impact of a car accident, or bike accident can cause knee bone fractures. Often, these types of injuries need surgical repair. boxer playing, catching the ball when playing cricket, or a defensive wicket-keeper, goalkeeper in a football game, hitting, gunshot wound, sudden fall in outstretch hand, crush injury, projectile, sudden acceleration of the bike accelerator or clas, opening cran bottle, door entrapment of hand, ligamentous laxity predisposes to hyper-extension, poor muscle attachment, osteoporosis, abnormal hormonal imbalance, may be associated with concomitant carpal fractures and dislocations, axial carpal instability, etc. The crushing injuries common in car accidents may cause breaks that require surgical repair.
  • Falls from height – Tripping and falling when walking on uneven surfaces can break bones in knee bone fractures, as can landing on your feet after jumping down from just a slight height, sudden landings from the plane in the war field, downhill, violent trauma, etc. Crush injury, ceiling fan accident sudden uprighting hand, heavy impact of a car accident, bike accident, hitting hammer in the workshop.
  • Driving and compressing in the break – It is one of the significant causes of hip microtrauma for the driver of the car, motorbike, truck, bus, bicycle runner, suddenly accelerating (getting faster), and suddenly decelerating (going slower). During driving, such a kind of vehicle frequently has to compress breaks to maintain the car’s speed. Repeated compression causes microtrauma, tendon, cartilage, ligament degeneration in the elbow, wrist, and weakness that may lead to injury in the upper extremity bone fracture.
  • Missteps – Sometimes, just putting your foot down the wrong way can result in a twisting injury that can cause a broken bone. Fracture also occurs when stairs up or stairs down, especially in older people.
  • Unconsciously Toilet Use – A widespread and daily increasing incidence of rupture of the hip, knee joint, foot bone, exceptionally high comodo using time frequently fall by slapping on the floor and causes fracture from abnormal fall.
  • High hell Use – It is the most common cause of fracture in the knee, ankle, foot, or lower limb fracture, especially for women, abnormal arch, foot angle, the lake of the flat foot, abnormal sole of your footwear, muscle, tendon, cartilage, ligament weakness in the knee, ankle joints cause fracture and dislocation.
  • Soldier, armies on the battlefield – With the increasing technology of nuclear weapons on the battlefield, one country is involved in the war from one country to another country. On the battlefield, millions of armies and general people are falling into injury.
  • Have osteoporosis – a disease of your bone that weakens your bones gradually due to inadequate intake of calcium or vitamin D, less exposure to sunlight may lead to fracture of the bone in older age.
  • Weak low muscle mass or poor muscle strength – Lack of agility or older age muscle strength, mass, power, and endurance become weak, and poor balance conditions make you more likely to fall and cause a fracture.
  • Walk or do other activities in the snow or on the ice – Especially north region of the world maximum time is low temperature. That frequent water turns into snow and activities that require a lot of forwarding momenta, such as in-line skating and skiing, snowboarding, in-line skating, Jumping, and playing lead to fracture of the bone in the upper limb.
  • Insufficient vitamin D and sunlight – Insufficient vitamin D and sunlight decrease the intestinal absorption of calcium, leading to abnormal regulation of parathyroid hormone (PTH). Vitamin D also works to upregulate the transcription of genes involved in neovascularization in areas of endochondral ossification, such as a healing fracture site. Vitamin D deficiency is typically characterized as a serum level of 25-hydroxyvitamin D3 of less than 20 ng/mL, and sufficiency is between 20 and 31 ng/mL.[rx]
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Symptoms 

Symptoms of  are include

  • A fracture means intense pain, bleeding, swelling, tenderness, and limited range of motion are the first symptoms
  • May present with pain, swelling, tenderness, and hematoma directly over the hip in athletes. Construction workers may present various pain and swell with paresthesia
  • Pain may be referred to the shoulder, arms, wrist joint, and thumb in the web space between the thumb and index finger
  • Inability to grasp or weakness of grasp between your upper extremity
  • Tenderness to the touch along the phalanges, carpal, and metacarpal bone.
  • Blue or black discoloration of the skin over the thumb
  • Pain with or after regular activity or a noticeable abnormality, such as a bent elbow, arm, or wrist
  • Pain that goes away when resting time and then returns when standing, walking, or during activity respective joint
  • Pinpoint pain at the site of the fracture when touched
  • Swelling but no bruising may be present if it becomes microtrauma
  • Bruising or discoloration that extends to nearby parts of the fractured bones.
  • Pain may decrease with rest but increases again with activity or movement
  • Pain at the fracture site, which in some cases can extend from the upper extremity
  • Blisters, change in color appearance, and bruising may occur over the fracture site after some days.
  • Warmth, bruising, numbness in the forearm or wrist, or radiating pain through
  • This pain may occur or feel in the setting of acute trauma or repetitive microtrauma over weeks to months. One should be suspicious of stress fracture with discomfort or pain of worsening quality or duration over time.
  • Arm pain that gets worse with wrist or elbow movement

Diagnosis

Histology varies based upon the source of the primary malignancy. In general, lesions are graded as low, intermediate, or high grade. The grade of the lesion is determined by the degree of cellular atypia, pleomorphism, active mitosis, matrix production, and necrosis. Lower-grade lesions are biologically less aggressive, while higher-grade lesions are more aggressive and are hence prone to further spread and metastasis.

History and Physical

Pathologic fractures can be preceded by lesions producing prodromal pain or can be indolent until the time of fracture. Patients may or may not report B symptoms, including unintentional weight loss, fevers, etc. Patients may also report symptoms specific to the particular primary carcinoma, such as urinary abnormalities with renal cell carcinoma or shortness of breath and/or cough with lung carcinoma. Patients may additionally report symptoms of hypercalcemia or malignancy, which could masquerade as mild confusion and gastrointestinal abnormalities to cardiac arrhythmia and renal failure.

A physical exam should include a focused assessment of the extremity or a spinal exam when warranted. Careful attention should be paid to neurovascular examination, though the compromise is uncommon in pathologic fractures of the extremities.

When a pathologic fracture is identified through a lesion of unknown origin, a comprehensive workup must be conducted to identify the etiology and stage of the disease.

Laboratory analysis should include a complete blood count, comprehensive metabolic panel (with special attention to serum calcium and alkaline phosphatase), prothrombin/INR, activated partial thromboplastin, erythrocyte sedimentation rate, urinalysis, urinary protein electrophoresis, and serum protein electrophoresis. Disease-specific markers, including prostate-specific antigen (PSA) and carcinoembryonic antigen (CEA), etc., may also be considered. Laboratory abnormalities may exist secondary to malignancy and may elucidate the source of malignancy. For example, a urinalysis may provide some insight into the primary pathology. If hematuria is present, renal cell or uroepithelial carcinoma should be considered. If Bence-Jones proteins are present, multiple myeloma is likely the diagnosis. Pregnancy tests should also be obtained in women of child-bearing age prior to imaging.

Radiological analysis of pathologic fractures begins with orthogonal radiographs of the fracture site and the involved bone in its entirety. A plain radiograph is the single most important imaging modality and provides the most information about a pathologic lesion. There are several aggressive features suggestive of a pathologic lesion that may be identified on X-ray, which include: lesion diameter > 5 cm, cortical interruption, periosteal reaction, and associated pathologies fracture. A chest radiograph should also be obtained. Computed tomography (CT) of the chest, abdomen, and pelvis with oral and intravenous contrast should be obtained for staging purposes. Whole-body bone scintigraphy should also be obtained. Bone scans are particularly useful for identifying osteoblastic activity. If laboratory analysis has confirmed the diagnosis of multiple myeloma, a skeletal survey may be obtained instead of a bone scan, which might fail to identify the degree of osteolysis present in other sites. This comprehensive strategy is the gold standard and is successful in identifying the origin of the lesion in 85% of cases.

Advanced imaging of the extremity may be included for preoperative planning or if there is a concern for primary bone sarcoma. Other reasons to obtain local CT imaging are to evaluate the degree of osteolysis and to better understand the 3-dimensional anatomy of lesions, particularly in locales with complex dimensional anatomy such as the pelvis. Reasons to consider magnetic resonance imaging (MRI) of the extremity include evaluation of the degree of soft-tissue involvement as well as neurovascular involvement. Consider mammography for indicated patients when a primary breast carcinoma cannot be excluded. Positron emission tomography is becoming more popular and is highly sensitive for identifying infection and malignant tumors. The specificity of positron emission tomography alone is only 30%, though it increases to 50% when combined with computed tomography.

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A biopsy is performed following the completion of laboratory and radiological workup. There are six recognized reasons to complete a staging workup before biopsy:

  1. The tumor may be a primary bone sarcoma. Therefore, a staging workup would prevent a poorly placed biopsy location or trajectory.
  2. There may be an additional site of metastasis that is more easily accessible and/or associated with less morbidity than the site of the pathologic fracture.
  3. Pre-operative embolization may be required for intraoperative hemostasis.
  4. An unnecessary biopsy may be avoided altogether if the diagnosis may be made via laboratory analysis alone, such as with multiple myeloma.
  5. Histologic analysis in isolation identifies the source in only 3% of cases.
  6. A combination of pre-operative imaging and laboratory studies with histopathology increases the likelihood that the correct diagnosis will be made.

There are three types of biopsy, including fine-needle aspiration (FNA), core-needle biopsy, and open biopsy, with advantages and disadvantages each. Open biopsies are further subclassified as incisional or excisional. Principles of biopsy of bone lesions have been well-documented and should adhere to strict guidelines. Guidelines include a biopsy through a single compartment via a longitudinal incision without damage to neurovascular structures, in line with the planned surgical incision while maintaining hemostasis throughout. Any deviation from these guidelines will lead to unnecessary surgical field tumor contamination.

Treatment

Treatment algorithms exist for both impending fractures and pathologic fractures and generally involve operative fixation combined with chemotherapy and/or radiotherapy. 

Impending Pathologic Fractures

An impending fracture is a biomechanically weakened area of bone that has a propensity to fracture with far less force than would be required for the normal bone to fracture due to the pathophysiology of the underlying lesion. For instance, normal weight-bearing through a pathologic lesion could tip the scales towards a pathologic fracture due to the biomechanical fragility of the surrounding bony architecture. Impending fractures may require prophylactic fixation, meaning surgical intervention in the form of internal fixation before a fracture event as a means of augmenting inherently weak bone and preventing future failure.

There are two recognized classification systems for impending pathologic fractures:

  1. Harrington criteria were first described by Harrington et al. in 1980 to determine indications for prophylactic internal fixation. Harrington criteria are based on four parameters: lesion involves more than 50% of cortical bone, the lesion is greater than 2.5 cm, presence of pain following radiotherapy, and fracture of the lesser trochanter. There are significant limitations to this grading system as it only applies to the proximal femur and does not account for disease-specific tumor pathology.
  2. Mirel classification was first described by Mirel in 1989 and has been extrapolated as an algorithm for prophylactic fixation. The study was a retrospective analysis of 78 lesions of long bones that had undergone radiation therapy without prophylactic internal fixation. This scoring system is depicted in Table 1. This scoring system has a maximum of 12 points, with more than 8 points indicating the need for prophylactic fixation.

Recently, there has been an interest in alternative scoring systems such as CT-based structural rigidity analysis (CTRA). A study by Damron et al. in 2016 evaluated CTRA compared to Mirel’s criteria in pathologic femoral fractures and found CTRA to have a higher predictive value in identifying impending fractures.

The benefits of prophylactic fixation of an impending fracture are two-fold. Elective fixation removes pain and morbidity associated with a true pathologic fracture and facilitates easier surgical management.

Pathologic Fracture

Pathologic fractures may occur secondary to benign lesions, metastasis, primary bone lesions, or metabolic bone abnormalities. Treatment of pathologic fractures is dictated by the pathophysiology of the causative lesion and the expected survival.

Fracture healing rates, prognosis, and patient activity level must be considered to determine the extent of fixation. It is important to recognize that altered disease biology leads to decreased or destroyed fracture healing potential. For example, the fracture healing rates for metastasis from multiple myeloma, renal, breast, and lung carcinoma are 67%, 44%, 37%, and 0%, respectively. This variation of fracture healing potential across different malignancies highlights the importance of proper diagnosis of the primary lesion for successful preoperative planning. For example, a fracture through a lesion secondary to myeloma has a much greater healing potential than one through a lesion secondary to lung carcinoma. Therefore, a construct involving plates and screws might be sufficient for a myeloma-induced fracture, whereas a more extensive bone-replacing prosthesis would be necessary for a fracture induced by lung cancer.

For renal cell carcinoma, metastases should be widely excised when possible. A review of 887 patients with metastatic renal cell carcinoma revealed a statistically significant improvement in cancer-specific survival (4.8 years versus 1.3 years) when complete metastasectomy was performed. An additional retrospective study by Higuchi et al. on patients with metastatic renal cell carcinoma to bone showed a significant improvement in overall survival and recurrence-free survival for patients undergoing wide resection as compared to local curettage. This same study also revealed that intralesional resection was an independent risk factor for poor prognosis and was associated with significantly more intraoperative blood loss.

In terms of survivability, there are established rates of 6-month survival documented in the literature. For example, 6-month survival for prostate, breast, renal, and lung are 98%, 89%, 51%, and 50%, respectively. Additionally, activity levels must be taken into account. A patient who is wheelchair- or bed-bound requires different fixation than a patient still ambulating and/or weight-bearing through the involved extremity. Recently, there have been leaps of innovation in the fields of artificial intelligence and machine learning, which have helped form models for predicting patient survival. PATHFx 3.0 is one such tool that has been externally validated to estimate the likelihood of survival at 1-month, 3-month, 6-month, 12-months, 18 months, and 24 months after treatment for patients with symptomatic skeletal metastases using a Bayesian belief analysis.

  • Stress fracture: Cortical disruption and/or weakening of bony architecture secondary to repetitive micro-trauma or overuse.
  • Paget’s disease: Metabolic disorder resulting in mixed blastic/lytic lesions of bone.
  • Avascular necrosis: Local ischemia to a region of bone resulting in tissue death.
  • Benign fracture: Cortical disruption secondary to mechanical failure of bone without evidence of malignancy.
  • Infection: The presence of foreign microorganisms invading and multiplying within a bone leading to bone erosion and damage.

Surgical Oncology

Surgical intervention for a pathologic fracture should only be considered following an exhaustive oncological work-up and biopsy of the lesion. General principles of internal fixation are applicable but may differ when a fracture of pathologic nature is involved. For instance, implant selection should generally adhere to the following guidelines:

  • Load-sharing as opposed to load-bearing when possible
  • Durable implants to last the length of patient survival with disease progression
  • Immediate stability allows for immediate weight-bearing
  • The length of the implant should bypass the lesion by two cortical diameters
  • Cement augmentation when necessary

There are particular considerations for implant choice. Titanium implants are typically used in benign fractures because they are MRI-compatible, allowing for future imaging with less artifact than stainless steel. Biomechanically, titanium is more similar to the normal bone than stainless steel in terms of the modulus of elasticity. In pathologic fractures, however, the surrounding bony architecture is inherently weaker than normal bone and may, in certain cases, require stainless steel implants, which are stronger than titanium but preclude future advanced imaging due to increased artifact. More recently, carbon fiber implants have become an area of interest due to their radiolucency, improved fatigue strength, and modulus of elasticity that is more similar to the normal bone than any metal. A study by Zimel et al. compared carbon-fiber-reinforced polyetheretherketone (CFR-PEEK) with titanium intramedullary nails. There was significantly less implant artifact on MRI associated with carbon fiber implants compared with titanium.

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For hip arthroplasty procedures, the choice of utilizing cement versus uncemented press-fit implants is widely debated. Advantages of cement include immediate fixation in pathologic bone without the need for waiting for bony in-growth of the implant. Disadvantages of cement include pulmonary complications such as bone cement implantation syndrome (BCIS), allergic reactions, prolonged surgical time, and increased difficulty with any revision surgery where cement needs to be removed. A retrospective study by Larsen et al. on oncologic patients undergoing either cemented or uncemented hip arthroplasty revealed no difference in terms of complication rate, 30-day mortality, intraoperative blood loss, or functional outcome. Ultimately, it is up to the surgeon’s personal preference to decide whether to cement when performing hip arthroplasty.

Embolization should be considered before operative fixation of pathological fractures to maintain hemostasis for highly vascular tumor subtypes. Embolization is performed by interventional radiology and involves percutaneous embolization of large feeding vessels supplying tumors with polyvinyl alcohol, coils, or gel foam. Well-known malignancies that tend to greater intraoperative blood loss include renal and thyroid cancer, in which case preoperative embolization should be considered. A study by Pazionis et al. evaluated the use of preoperative embolization in renal and thyroid carcinoma. They found that patients who underwent embolization had decreased surgical times, blood loss, and transfusion requirements compared to patients who did not undergo embolization.

Primary sarcomas are aggressive tumors that require wide-excision with a goal of obtaining a cure, as compared to pathologic fractures due to metastatic disease, which are treated as a palliative measure. It is important to properly diagnose the lesion before surgery to avoid iatrogenic dissemination of a sarcoma, which may result in the loss of a limb that otherwise might have undergone a limb-sparing procedure.

Surgery Based on Tumor Location

The following will report general guidelines for surgical procedures based on anatomic location within the skeleton. These are general guidelines only and may not necessarily be ideal, depending on a multitude of factors. Every tumor and patient poses a unique problem that requires an individualized approach.

Upper Extremity

Generally speaking, fractures of the upper extremity are less debilitating than fractures in the lower extremity as they are under lower stress and are not essential for weight-bearing. Pathologic fractures most commonly occur in the proximal humerus and humeral shaft. The following are general recommendations for fixation of pathologic fractures in particular anatomic locations of the upper extremity:

  • The humeral head and anatomic neck of the humerus: shoulder hemiarthroplasty versus total shoulder arthroplasty versus reverse total shoulder arthroplasty versus endoprosthesis versus fixed-angle plate with void filler
  • The surgical neck of the humerus to the proximal-third humeral shaft: fixed-angle locking plate
  • Humeral diaphysis: locked antegrade intramedullary nails versus plate
  • Distal humerus (less common): parallel bridge plating versus distal humeral replacement with total elbow arthroplasty
  • Radius/ulna (uncommon): plating versus excision

Lower Extremity

Pathologic fractures of the lower extremity occur much more commonly than in the upper extremity and are of greater clinical significance due to the necessity for weight-bearing. The following are general recommendations for fixation of pathologic fractures in particular anatomic locations of the lower extremity:

  • Femoral head and neck: hemiarthroplasty versus total hip arthroplasty versus endoprosthesis versus plate or nail fixation with void filler
  • Intertrochanteric, subtrochanteric, diaphyseal fractures: cephalomedullary nails
  • Distal third femoral shaft: locking plate versus retrograde intramedullary nail (a musculoskeletal oncologist must carefully consider any retrograde nailing before proceeding to avoid proximal tumor spread)
  • Supracondylar: distal femur periarticular plate
  • Proximal tibia: locking plate versus endoprosthesis
  • Tibial shaft: intramedullary nail

Pelvis

Smaller lesions or fractures of the ischium and pubis may be treated non-operatively with radiation or radiofrequency ablation. Larger lesions involving weight-bearing portions of the pelvis must be treated more aggressively. Generally, impending or pathologic fractures to the pelvis are treated as follows with the possible addition of cement to fill large defects.

  • Sacral ala: sacroiliac screws
  • Posterior ilium: column screws
  • Extensive posterior pelvic ring disruption: spinopelvic fixation
  • Anterior column: anterior column screws

A Classification was devised by Harrington for the treatment of peri-acetabular defects, as depicted in Table 2. A peri-acetabular lesion with intact subchondral bone can undergo curettage and cement without more extensive management.

Spine

The spine is the most common site of skeletal metastasis. The decision to pursue surgical intervention for spine metastasis is multi-faceted and entails considerations of pain level, stability, and neurological deficits. Similarly, the goals of surgical intervention of the spine include palliation, decompression of neural elements, and stabilization. Multiple algorithms have been developed regarding surgical decision-making about spine metastasis. An algorithm developed by Tokuhashi et al. is used for the prediction of postoperative survival, as depicted in Table 3. A score of greater than 9 points is indicative of greater than 12 months survival and argues for operative intervention, whereas a score of 5 or less indicates less than 3 months’ survival and is an argument against operative intervention.