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Pathologic fracture

A pathologic fracture is a break in a bone that occurs due to underlying bone weakness from disease or abnormality, rather than from significant trauma, distinguishing it from typical traumatic fractures.^[1]^[2] These fractures commonly arise from conditions that compromise bone integrity, such as metastatic cancer spreading to the bone (most frequently from primary sites like the breast, lung, prostate, kidney, or thyroid), primary bone tumors (benign or malignant), osteoporosis, osteomalacia, Paget's disease, or infections like osteomyelitis.^[1]^[2] Bone metastases are a leading cause, affecting approximately 5% of the 2,041,910 projected annual cancer patients in the United States as of 2025, with about 8% of those with bone involvement experiencing a pathologic fracture.^[2]^[3] The most affected sites include the spine, proximal femur, pelvis, humerus, and ribs, where osteolytic lesions from tumor-induced osteoclast activation erode bone structure, leading to biomechanical failure even under normal loads.^[2] Symptoms typically include sudden or gradual pain at the fracture site, often worsening with movement or weight-bearing, along with swelling, tenderness, bruising, deformity, and limited mobility; in some cases, the fracture may occur spontaneously without noticeable trauma.^[1] Diagnosis involves a combination of clinical evaluation, imaging such as X-rays (which reveal lytic or blastic lesions), MRI or CT scans for detailed assessment, bone scintigraphy for detecting metastases, and laboratory tests like complete blood count or metabolic panels to identify underlying causes, with biopsy confirming malignancy in suspicious cases.^[1]^[2] Management focuses on stabilizing the fracture, treating the underlying condition, and preventing complications; non-surgical options include immobilization with casts or splints and pain control, while surgical interventions such as internal fixation (plates, intramedullary nails), prosthetic replacement, or prophylactic stabilization for impending fractures (guided by criteria like Mirels' score) are often necessary, particularly in metastatic cases where radiotherapy or chemotherapy addresses the primary disease.^[1]^[2] Prognosis varies widely based on the etiology—for instance, patients with prostate cancer metastases have a 98% six-month survival rate, compared to 50% for lung cancer—but healing generally takes several months, with risks of nonunion, malunion, or further fractures if the underlying weakness persists.^[2] Prevention emphasizes early detection and management of predisposing conditions, such as bisphosphonates or denosumab for osteoporosis and bone metastases, alongside lifestyle measures like calcium/vitamin D intake and fall prevention.^[1]

Overview

Definition and Classification

A pathologic fracture is defined as a bone break that occurs through abnormal or weakened bone due to an underlying disease process, such as a neoplasm or metabolic disorder, leading to failure under minimal trauma or even spontaneously—conditions that would not fracture healthy bone.^[2] This contrasts with traumatic fractures, which result from high-energy forces applied to structurally normal bone, emphasizing biomechanical compromise rather than the magnitude of applied stress.^[1] Pathologic fractures are classified primarily by the underlying pathology into neoplastic and non-neoplastic categories. Neoplastic causes involve primary bone tumors, which may be benign (e.g., osteoid osteoma) or malignant (e.g., osteosarcoma), or secondary metastatic lesions from distant primaries such as breast, lung, or prostate cancers, which erode bone integrity through tumor invasion and osteolysis.^[2] Non-neoplastic causes stem from systemic or local conditions that impair bone quality without tumor involvement, including metabolic disorders like osteoporosis (characterized by reduced bone density) and osteomalacia (due to defective mineralization).^[2] Other examples include Paget disease of bone, which causes abnormal remodeling and cortical thinning.^[4] Further subclassification considers fracture characteristics and location. By pattern, fractures are complete (extending fully across the bone), incomplete (partial disruption, often seen in trabecular bone), or impending (a high-risk state without actual breakage, defined by significant structural compromise such as greater than 50% cortical destruction in weight-bearing bones).^[4] Impending fractures are assessed using tools like the Mirels score, which evaluates four components—lesion site (upper limb: 1 point, lower limb: 2, peritrochanteric: 3), pain (mild: 1, moderate: 2, functional: 3), lesion size (<1/3 diaphyseal width: 1, 1/3–2/3: 2, >2/3: 3), and radiographic appearance (blastic: 1, mixed: 2, lytic: 3)—with a total score exceeding 8 indicating prophylactic intervention to prevent actual fracture.^[5] Common locations include long bones (e.g., femur, humerus), spine (vertebral compression), and pelvis, where weakened areas are prone to collapse under normal loads.^[1]

Epidemiology

Pathologic fractures represent a significant clinical burden, particularly in the context of underlying malignancies. In the United States, an estimated 2,041,910 new cancer cases are diagnosed annually, with approximately 5% of these patients developing bone metastases that predispose them to fractures, of whom approximately 8% experience a pathologic fracture.^[6]^[7]^[2] The overall incidence of pathologic fractures is increasing, driven by advances in cancer diagnosis and treatment that extend survival times, allowing more patients to reach stages where skeletal complications manifest.^[2] Globally, the prevalence of pathologic fractures is estimated at about 28% among patients with metastatic bone disease, though this varies by population and underlying condition. These fractures are most frequent in specific cancers: up to 43% of patients with multiple myeloma experience them at diagnosis, followed by 35% in breast cancer, 17-25% in lung cancer, and around 19% in prostate cancer.^[8]^[9] Primary bone and soft tissue sarcomas, though rarer, contribute to cases, with approximately 13,000 new soft tissue sarcomas and 3,600 bone sarcomas diagnosed annually in the US.^[10]^[11] Demographically, pathologic fractures are far more common in adults over 40 years of age, where the likelihood of a lesion causing fracture being metastatic is 500 times greater than it being a primary bone tumor.^[2] Gender patterns show a skew toward females in cases related to osteoporosis—a non-neoplastic cause weakening bone—while males predominate in prostate cancer-associated fractures.^[2] Geographically and temporally, rates are rising in developed countries due to aging populations and enhanced oncology care prolonging life expectancy in cancer patients.^[2] This trend underscores the growing need for preventive strategies in high-risk groups.

Etiology

Neoplastic Causes

Neoplastic causes of pathologic fractures primarily arise from tumors that compromise bone integrity through direct invasion, osteolysis, or excessive bone formation. Metastatic disease is the most common cause, accounting for the majority of such fractures, originating from various primary malignancies that spread hematogenously to bone, leading to involvement in 30-75% of advanced cases depending on the cancer type.^[2]^[12]^[13] Common primaries include breast cancer, which produces predominantly osteolytic lesions but can also cause mixed or osteoblastic changes; lung cancer, typically resulting in purely lytic destruction; prostate cancer, characterized by osteoblastic reactions; and renal cell carcinoma or thyroid cancer, both often lytic in nature.^[14]^[15]^[16] These metastases weaken cortical bone, increasing fracture risk, with breast cancer being a leading cause.^[9] Primary bone tumors, in contrast, are rare, comprising only 1-2% of neoplastic pathologic fractures, as they represent less than 1% of all malignancies overall.^[2]^[17] These tumors elevate fracture risk through rapid proliferation and cortical erosion. Osteosarcoma, the most common primary malignant bone tumor, predominantly affects adolescents and arises in the metaphysis of long bones, such as the distal femur or proximal tibia.^[18] Ewing sarcoma occurs mainly in children and involves the diaphysis of long bones, like the femur or humerus.^[19] Chondrosarcoma, more typical in adults over 40, frequently develops in the pelvis or proximal humerus/shoulder girdle, leading to insidious bone weakening and fracture.^[20]^[21] Tumors in both metastatic and primary contexts induce bone resorption via activation of osteoclasts, primarily through the RANKL (receptor activator of nuclear factor kappa-B ligand) pathway, where tumor cells or stromal interactions upregulate RANKL expression, promoting focal osteolysis and structural compromise.^[22] This mechanism underlies the diffuse lytic lesions seen in multiple myeloma, a hematologic neoplasm that causes pathologic fractures in up to 43% of patients.^[9]^[23] Impending fracture risk in these cases is evaluated using the Mirels scoring system, which sums points across four criteria: site (upper limb = 1, lower limb = 2, peritrochanteric = 3), pain (mild = 1, moderate = 2, functional = 3), lesion type (blastic = 1, mixed = 2, lytic = 3), and size (less than 1/3 of bone diameter = 1, 1/3 to 2/3 = 2, greater than 2/3 = 3); a total score exceeding 7 indicates high risk and consideration for prophylactic intervention.^[24]^[25]

Non-Neoplastic Causes

Non-neoplastic causes of pathologic fractures encompass a range of systemic and local conditions that weaken bone integrity without involving malignancy, including metabolic bone diseases, infections, and other disorders such as radiation exposure or endocrine abnormalities.^[2] Metabolic bone diseases represent a primary category, with osteoporosis being the most prevalent etiology, particularly in postmenopausal women and the elderly due to reduced bone mineral density from imbalanced remodeling. This condition predisposes individuals to fractures in weight-bearing sites like the vertebrae, hip, and wrist, often occurring with minimal trauma. Osteoporosis is a leading cause of pathologic fractures in older adults.^[1]^[2] Osteomalacia, resulting from vitamin D deficiency or impaired mineralization, leads to softened bones and increased fragility, manifesting as looser zone fractures or complete breaks in long bones and ribs. This disorder is less common than osteoporosis but significantly elevates fracture risk through defective bone matrix formation.^[26]^[27] Paget's disease of bone involves disordered remodeling with excessive osteoclast activity followed by chaotic osteoblast response, resulting in enlarged, deformed, and brittle bones, commonly affecting the skull, pelvis, and long bones. This leads to a heightened fracture risk, estimated at up to several-fold higher than in unaffected individuals, due to structural weakening.^[28]^[29] Infectious causes primarily include osteomyelitis, a bacterial infection often due to Staphylococcus aureus, which erodes cortical bone through inflammation and abscess formation, culminating in pathologic fractures of long bones as a rare but serious complication. Chronic osteomyelitis increases this risk by persistent bone destruction, with fractures reported in 1-2% of cases involving long bone shafts.^[2]^[30]^[31] Tuberculous spondylitis, known as Pott's disease, causes chronic vertebral destruction via granulomatous infection, leading to compression fractures and kyphotic deformities from bone necrosis and collapse. This form often presents insidiously with back pain mimicking degenerative changes.^[32]^[33] Other non-neoplastic etiologies include radiation-induced bone changes, where prior radiotherapy for adjacent malignancies causes osteonecrosis and vascular compromise, fracturing irradiated fields with an incidence ranging from 1% to 25%, particularly in the ribs, pelvis, and extremities. Hyperparathyroidism promotes excessive bone resorption, forming brown tumors—benign osteolytic lesions that weaken bone and precipitate fractures, often in the jaw, long bones, or spine. Fibrous dysplasia, a benign fibro-osseous disorder typically in children and young adults, replaces normal bone with fibrous tissue, rendering sites like the femur or tibia prone to pathologic fractures due to cortical thinning.^[2]

Pathophysiology

Mechanisms of Bone Weakening

Pathologic fractures arise from underlying diseases that compromise bone integrity through various cellular and mechanical pathways, primarily involving dysregulated bone remodeling. In osteolytic processes, prevalent in conditions such as skeletal metastases and multiple myeloma, tumor cells stimulate osteoclast hyperactivity by secreting factors like parathyroid hormone-related protein (PTHrP) and receptor activator of nuclear factor kappa-B ligand (RANKL). PTHrP, commonly produced by breast and lung cancer metastases, mimics parathyroid hormone to enhance osteoclast differentiation and activity via cyclic AMP-mediated pathways, leading to excessive bone resorption.^[34] Similarly, in multiple myeloma, malignant plasma cells upregulate RANKL expression on osteoblasts and stromal cells, binding to RANK on osteoclast precursors to promote their maturation and survival, resulting in focal cortical thinning and the formation of lytic lesions that act as stress risers.^[34] This resorption can reduce bone volume by up to 30%, causing up to 30% loss in mechanical strength, as the remaining trabecular architecture becomes insufficient to withstand normal physiological loads.^[35] Angiogenesis further exacerbates osteolytic weakening by facilitating lesion expansion; tumor-derived vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8) promote neovascularization, which supplies nutrients to proliferating tumor cells and osteoclasts, accelerating bone destruction at the lesion periphery.^[34] These localized defects disrupt the bone's uniform load distribution, creating stress concentrations where normal forces exceed the material's yield strength, predisposing to fracture under minimal trauma. In contrast, osteoblastic responses, observed in metastases from prostate or breast cancers, involve excessive woven bone formation driven by tumor-secreted endothelin-1 (ET-1) and bone morphogenetic proteins (BMPs). ET-1 activates osteoblast proliferation and mineralization through endothelin receptors, while BMPs, particularly BMP-2 and BMP-4, induce differentiation of mesenchymal stem cells into osteoblasts, leading to disorganized, immature bone deposition.^[34] This hyperostotic bone lacks the organized lamellar structure of normal cortical bone, rendering it brittle and susceptible to fatigue failure from repetitive loading, despite apparent increased density on imaging.^[2] Biomechanically, both lytic and blastic alterations compromise bone's ability to resist deformation. Lytic lesions function as notches, amplifying local stresses according to fracture mechanics principles, where progressive microdamage accumulates without adequate repair, culminating in impending or complete fracture. Specific predictors include greater than 50% cortical destruction in long bones, which significantly elevate fracture risk by reducing the bone's moment of inertia and load-bearing capacity.^[2] These thresholds highlight how localized weakening transforms routine activities into high-risk events for structural failure.

Clinical Features

Symptoms

Patients with pathologic fractures often experience prodromal symptoms weeks to months prior to the event, primarily manifesting as localized, persistent bone pain that worsens at night or with weight-bearing activities due to periosteal stretching from underlying bone lesions.^[2] This pain commonly serves as a key warning sign of impending fracture risk.^[2] Upon acute fracture, patients typically report sudden, severe pain at the fracture site, accompanied by localized swelling, deformity, and inability to bear weight, particularly in long bones like the femur or humerus.^[2] For spinal pathologic fractures, which account for a substantial portion of cases, acute symptoms include intense back pain as the most common presentation, often with associated radiculopathy such as numbness, tingling, or weakness in the extremities due to nerve root involvement; in severe instances, spinal cord compression may lead to bowel or bladder dysfunction.^[36]^[2] In non-neoplastic causes such as osteoporosis or osteomalacia, symptoms may be more insidious, with gradual onset of pain during routine activities rather than a distinct prodrome, though acute fracture pain remains similar to neoplastic cases.^[2] Associated systemic symptoms arise from the underlying disease process and may include weight loss, fatigue, and anorexia in patients with malignancies such as multiple myeloma or metastatic cancer.^[2] In cases involving lytic bone metastases, hypercalcemia can contribute additional symptoms like nausea, vomiting, confusion, and polyuria.^[2] For hematologic malignancies like lymphoma or myeloma, B symptoms such as fever, night sweats, and further weight loss may accompany the localized complaints.^[2]

Physical Examination Findings

During physical examination of a suspected pathologic fracture, local signs at the affected site commonly include tenderness upon palpation, localized swelling, ecchymosis, and crepitus in displaced cases.^[37] Limited range of motion due to pain and guarding is frequently observed, along with instability elicited by stress testing, such as in femoral neck fractures.^[2] Deformity may manifest as apparent shortening or abnormal rotation of the affected limb in long bone fractures, often leading to gait disturbances or antalgic limp. Functional assessment reveals potential neurovascular deficits, including weakness or foot drop from peroneal nerve involvement in lower extremity fractures.^[38] Systemic signs in malignancy-associated pathologic fractures can include cachexia evidenced by unintentional weight loss and muscle wasting, as well as palpable lymphadenopathy. Signs of hypercalcemia, such as dehydration or altered mental status with confusion, may also be present.^[2] In spinal pathologic fractures, localized tenderness over the vertebrae is noted, accompanied by neurological deficits like hyperreflexia or sensory changes suggestive of cord compression.^[38] Specific to femoral pathologic fractures from metastatic disease, patients often present with inability to walk or bear weight, highlighting the functional impact. Neurovascular compromise, though uncommon overall, occurs in some cases—particularly with spinal or vascular proximity—and necessitates urgent evaluation to prevent irreversible damage.^[2]^[38]

Diagnosis

Imaging Techniques

Plain radiography serves as the initial imaging modality for suspected pathologic fractures, providing essential visualization of bone integrity and underlying lesions. It typically reveals fracture lines traversing areas of weakened bone, such as lytic or blastic lesions, cortical destruction, and aggressive features including periosteal reaction or lesions exceeding 5 cm in size. In metastatic disease, plain radiographs often demonstrate osteolytic patterns, which are common in metastases from primaries like breast or lung cancer (approximately 70-80% lytic in breast cancer), but vary by primary site (e.g., more blastic in prostate cancer); they may appear as punched-out or moth-eaten erosions particularly in multiple myeloma. Orthogonal views of the fracture site and the entire affected bone are recommended, along with a chest radiograph to screen for primary malignancies.^[2]^[39]^[40] Advanced imaging techniques offer enhanced characterization of pathologic fractures, assessing extent, soft tissue involvement, and multifocal disease. Magnetic resonance imaging (MRI) excels in evaluating marrow infiltration and soft tissue extension, showing T1-hypointense lesions with corresponding T2 hyperintensity or STIR enhancement; it achieves sensitivities of 91-100% for detecting bone metastases and is urgently indicated for suspected spinal cord compression via targeted spinal protocols. Computed tomography (CT) provides detailed fracture patterns and cortical involvement, identifying impending fractures when more than 50% of the cortex is destroyed; it is particularly useful for preoperative planning and biopsy guidance, with sensitivities ranging from 71-100%. Bone scintigraphy using technetium-99m detects multifocal osteoblastic activity as hot spots in up to 90% of metastatic cases, serving as a standard whole-body protocol for staging.^[39]^[41]^[2] Positron emission tomography-computed tomography (PET-CT) integrates metabolic activity assessment, highlighting hypermetabolic tumors with high sensitivity for malignancy, though specificity is typically greater than 95% when combined with CT anatomy; it is valuable for detecting occult lesions and monitoring response in neoplastic causes. Emerging modalities like 18F-sodium fluoride (18F-NaF) PET/CT offer improved sensitivity (>90%) for bone metastases detection. For multiple myeloma, skeletal surveys via plain radiography or low-dose whole-body CT are preferred over scintigraphy due to the purely lytic nature of lesions, which may not uptake tracer. These modalities collectively guide differentiation from non-pathologic fractures by revealing endosteal scalloping, soft tissue masses, or permeative destruction absent in stress injuries.^[39]^[2]^[42]^[39]

Laboratory Evaluation and Biopsy

Laboratory evaluation for pathologic fractures begins with a complete blood count (CBC), which may reveal anemia in cases associated with multiple myeloma due to bone marrow infiltration by plasma cells.^[43] Leukocytosis can indicate an underlying infection contributing to bone weakening and fracture.^[44] A comprehensive metabolic panel is essential, focusing on serum calcium levels, as hypercalcemia often occurs in lytic bone diseases such as multiple myeloma or metastases, resulting from osteoclast activation and calcium release from resorbed bone.^[2] Elevated alkaline phosphatase (ALP) levels are commonly seen in conditions like Paget's disease or osteosarcoma, reflecting increased bone turnover.^[28] Tumor markers are selected based on suspected primary malignancies; for instance, prostate-specific antigen (PSA) is useful in evaluating prostate cancer metastases, while cancer antigen 15-3 (CA 15-3) aids in monitoring breast cancer with bone involvement, where elevated levels correlate with metastatic spread.^[12]^[45] In suspected multiple myeloma, serum protein electrophoresis (SPEP) is performed to detect a monoclonal protein (M-spike), present in approximately 80% of cases, confirming the diagnosis when combined with other findings.^[46]^[47] Biopsy is indicated following imaging to confirm the underlying pathology, particularly in cases of unknown primary tumors, which account for about 10-25% of metastatic bone disease presentations.^[48]^[49] Techniques include imaging-guided core needle biopsy or open biopsy, with the former preferred for its minimally invasive nature and high diagnostic yield.^[50] Histopathological analysis distinguishes tumor types, such as adenocarcinoma from sarcoma in neoplastic cases, or identifies metabolic changes like thin trabeculae in osteoporosis for non-neoplastic causes.^[51] Biopsy confirms the diagnosis in up to 97% of cases when adequately performed, often integrated after initial TNM staging to guide management of metastases.^[52] Risks include tumor seeding along the biopsy tract, which is rare (less than 2% with modern techniques), though this rate is minimized with proper technique.^[53]

Management

Conservative Approaches

Conservative management of pathologic fractures is primarily indicated for stable, non-displaced fractures in patients with low risk of progression or limited life expectancy, focusing on pain relief, fracture stabilization, and addressing the underlying etiology without surgical intervention.^[2] Immobilization techniques, such as bracing or casting, are employed for stable pathologic fractures to promote healing and prevent further displacement, particularly in weight-bearing bones or the spine. For instance, vertebral body braces are commonly used for spinal pathologic fractures to maintain alignment and reduce pain. These approaches are recommended for lesions with a low Mirels score (less than 7), where the risk of fracture progression is minimal, or in patients with a short life expectancy of less than 3 months, for whom invasive procedures may not be beneficial.^[54]^[55] Pharmacotherapy plays a central role in symptom control and reducing skeletal complications. Analgesics, including opioids for severe pain, are essential for managing acute discomfort associated with the fracture. Bisphosphonates and denosumab inhibit osteoclast activity, thereby reducing skeletal-related events such as pathologic fractures by 31-41% in patients with bone metastases from cancers like lung, prostate, or breast. Radiation therapy serves as a palliative option for painful lesions, typically delivered as 30 Gy in 10 fractions, providing complete pain relief in 31% of cases for radiosensitive tumors such as myeloma, lymphoma, prostate, or breast cancers, and partial relief in 54%. This modality can also help prevent progression to fracture in impending cases by promoting remineralization.^[2]^[56]^[57]^[2] Treatment of the underlying disease is integral to conservative strategies. For neoplastic causes, chemotherapy or hormonal therapies, such as tamoxifen for breast cancer metastases, target the primary malignancy to halt bone destruction. In infectious etiologies, antibiotics are administered to control the underlying osteomyelitis, often in combination with immobilization to support fracture healing. Such conservative measures are suitable for patients with expected survival under 3 months, prioritizing quality of life over aggressive intervention.^[58]^[59]^[55]

Surgical Interventions

Surgical interventions for pathologic fractures are indicated in cases of unstable fractures, such as those with displacement or greater than 50% bone destruction, impending fractures assessed by a high Mirels score greater than 8, or when neurovascular compromise is present; the primary goals are to restore function, enable early mobilization, and alleviate pain.^[2]^[5] Prophylactic surgery is particularly recommended for lesions in weight-bearing bones to prevent complete fracture and associated morbidity, especially in patients with expected survival exceeding 3-6 months.^[60] Common techniques include intramedullary nailing for diaphyseal fractures of long bones like the femur and humerus, which provides internal stabilization with minimal soft-tissue disruption and facilitates early weight-bearing.^[60] For periarticular fractures, plate and screw fixation offers precise alignment and allows for tumor curettage, while endoprosthetic replacement is preferred for extensive proximal lesions in the femur or humerus to achieve immediate stability.^[2] In spinal pathologic fractures, vertebroplasty involves percutaneous injection of bone cement into the vertebral body, and kyphoplasty uses balloon tamping prior to cement augmentation to restore height and reduce kyphosis; these minimally invasive procedures are suitable for osteolytic compression fractures without instability.^[61] Adjuvant measures often incorporate polymethylmethacrylate (PMMA) cement to fill lytic defects and augment fixation, enhancing mechanical stability particularly in osteoporotic or metastatic bone.^[2] For solitary metastases in patients with prolonged expected survival, wide resection followed by reconstruction may be performed to address the underlying tumor burden.^[60] These interventions generally allow early ambulation and improve mobility in the majority of patients, with vertebroplasty and kyphoplasty providing marked pain relief in approximately 84% of cases involving metastatic spinal disease.^[62]^[63] Complication rates range from 10% to 30%, with common issues including infection (8-12%) and hardware failure (up to 17%), particularly in lower limb lesions where surgical stabilization is prioritized to support weight-bearing.^[64]^[65]

Prognosis and Complications

Survival Outcomes

Pathologic fractures signify advanced underlying malignancy, often indicating widespread metastatic disease and thereby substantially reducing overall patient survival. The 6-month survival rates following such fractures vary significantly by primary tumor type, with prostate cancer patients exhibiting the highest rate at 98%, followed by breast cancer at 89%, renal cell carcinoma at 51%, and lung cancer at 50%.^[2] Several factors influence survival outcomes in patients with pathologic fractures. The primary tumor type is a key determinant, with hormone-sensitive cancers such as breast and prostate generally conferring better prognosis due to responsiveness to systemic therapies, whereas aggressive primaries like lung and renal cell carcinoma are associated with poorer outcomes. Fracture location plays a role as well, with spinal fractures linked to worse survival owing to heightened risks of neurological complications, spinal instability, and cord compression. Additionally, patient performance status profoundly affects prognosis; an Eastern Cooperative Oncology Group (ECOG) score greater than 2 is associated with roughly halved survival compared to lower scores, reflecting diminished functional reserve and treatment tolerance.^[2]^[66]^[9] Specific data underscore these trends in certain malignancies. In multiple myeloma, the occurrence of pathologic fractures correlates with increased mortality risk compared to patients without fractures, attributable to exacerbated skeletal morbidity and disease progression. Overall, pathologic fractures from bone metastases elevate mortality risk relative to metastatic disease without fracture, highlighting their role as a marker of frailty and accelerated decline.^[67]^[9] Complications arising from pathologic fractures further compromise survival. Hypercalcemia, driven by osteolytic activity in metastatic lesions, can be fatal if untreated due to cardiac arrhythmias, renal failure, and altered mental status. Postoperative infections following surgical stabilization contribute to sepsis and prolonged hospitalization that worsen outcomes. Deep vein thrombosis, exacerbated by immobility and hypercoagulability in cancer, is a frequent sequela that heightens the risk of pulmonary embolism and multiorgan failure.^[68]^[69]^[70]

Preventive Measures

Preventive measures for pathologic fractures focus on identifying at-risk individuals early and implementing interventions to strengthen bone integrity or stabilize lesions before breakage occurs. In patients with high-risk malignancies such as multiple myeloma, routine screening with dual-energy X-ray absorptiometry (DXA) scans is recommended at baseline and periodically to assess bone mineral density (BMD), as myeloma-induced bone loss increases fracture susceptibility. Emerging AI-based predictive models are also being developed to refine fracture risk assessment beyond traditional tools like the Mirels score.^[71]^[72] For metastatic bone disease, the Mirels scoring system evaluates impending fracture risk based on site, pain, lesion size, and radiographic appearance; scores of 8 or higher typically warrant consideration for prophylactic surgical intervention to avert fracture.^[24] Pharmacologic strategies play a central role in reducing skeletal-related events (SREs), including pathologic fractures, particularly in patients with bone metastases from cancers like breast or prostate. Intravenous bisphosphonates, such as zoledronic acid, inhibit osteoclast activity and have been shown to decrease the incidence of SREs by approximately 25-30% when initiated early in the course of metastatic disease.^[73] Denosumab, a monoclonal antibody targeting RANKL, demonstrates superior efficacy to zoledronic acid in preventing pathologic fractures in some randomized trials, with a relative risk reduction of up to 18% for SREs in breast cancer patients with bone metastases.^[74] Supplementation with calcium and vitamin D is advised for patients with underlying osteoporosis to support BMD and modestly lower fracture risk, especially in those receiving cancer therapies that exacerbate bone loss.^[75] Lifestyle modifications and supportive therapies further mitigate risk by enhancing bone health and minimizing mechanical stress on weakened sites. Weight-bearing exercises, such as walking or resistance training, promote bone remodeling and improve balance, thereby reducing fall-related fracture incidence in at-risk elderly patients.^[76] Fall prevention programs, including home safety assessments and balance training, are particularly beneficial for older adults with metastatic disease.^[77] Adjuvant treatments like radiation therapy or systemic chemotherapy can stabilize bone lesions by reducing tumor burden, preventing progression to fracture when applied to impending lesions.^[78] Prophylactic surgical fixation, such as intramedullary nailing of the femur in high-risk metastatic lesions (Mirels score ≥8), prevents actual fracture in the majority of cases and helps maintain ambulation while avoiding complications.^[79] Early integration of these measures in multidisciplinary care for underlying diseases can substantially lower the overall burden of pathologic fractures.^[80]

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Jun 17, 2021 · Osteomalacia · generalized bone and muscle pain · fractures of long bones, ribs and vertebrae · proximal muscle weakness weakness · fatigue.
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Paget Bone Disease - StatPearls - NCBI Bookshelf - NIH
Aggressive physical activity is not recommended, as fracture risk is high. However, muscle-strengthening exercise at a low level is recommended.
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Fracture risk among patients with Paget's disease - PubMed - NIH
Localized disruption of bone architecture leads to an increased risk of pathological fractures in patients with Paget's disease.
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Pathological fracture in acute osteomyelitis of long bones ... - PubMed
Pathologic fracture is a rare complication of acute bacterial osteomyelitis in adults. Community-acquired methicillin-resistant Staphylococcus aureus ...
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pathological fractures in osteomyelitis - JBJS
Pathological fracture in cases of osteomyelitis of the shafts of long bones has occurred in one and two-thirds per cent. of a total of 1086 cases.
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Pott Disease - StatPearls - NCBI Bookshelf - NIH
The initial compression in TB is secondary to vertebral body collapse, leading to anterior spinal tract involvement (exaggerated deep tendon reflexes and ...Introduction · History and Physical · Treatment / Management · Prognosis
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Tuberculosis of the spine (Pott's disease) presenting as ... - PubMed
Objective: Case reports of two women with tuberculosis (TB) of the spine (Pott's disease) presenting with severe back pain and diagnosed as compression fracture ...
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Pathological fracture after radiotherapy: systematic review of literature
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Treatment of pathological fractures due to brown tumours in a ...
Brown tumours, known also as osteitis fibrosa cystica, are benign osteolytic lesions found in 5–15% of patients with hyperparathyroidism.
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Oct 28, 2015 · ... pathologic fractures, spinal cord compression syndromes, disorders ... Basic mechanisms responsible for osteolytic and osteoblastic bone ...
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The decrease in structural properties (K and FU) caused by simulated single lytic lesions ranged from 3% to 30%. Single lesions occupying 4% and 12% of the ...
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Prodrome distribution of pathological fractures | Download Table
The most common symptoms include pain and neurologic deficits. The most serious complications of bone metastases are skeletal-related events (SRE), defined as ...
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https://pubmed.ncbi.nlm.nih.gov/19207068/
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Radiologic and clinical characteristics of vertebral fractures in ...
... pathologic fracture in the setting of multiple myeloma. Given the fact that ... Back pain was the most common presenting symptom (84%), followed by ...
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Pathologic fractures occur when mild or minimal force causes a fracture of an area of bone weakened by a disorder (eg, osteoporosis, cancer, infection, bone ...
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Oct 29, 2024 · Pathologic fractures can be secondary to a benign lesion (eg, Paget disease, giant cell tumor of bone, hemangioma) or a malignant tumor, which ...
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X-rays necessitate a 1-cm diameter mass and 50% bone mineral loss at minimum for detection. Up to 40% of lesions will be unidentified by x-rays, presenting ...
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Distinction of Long Bone Stress Fractures from Pathologic Fractures ...
Compared with stress fractures, pathologic fractures are more commonly associated with muscle signal abnormalities. These abnormalities, however, were not ...
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Multimodality imaging of osseous involvement In haematological ...
Thinning of the inner cortical bone (scalloping) and multiple small lesions producing a “moth-eaten” appearance can also be seen. In the skull, diffuse lytic ...
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Multiple Myeloma - StatPearls - NCBI Bookshelf
History and Physical Bone pain resulting from the osteolytic lesions often results in pathologic fractures and vertebral collapse, reducing height, spinal cord ...
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The Relationship Between Colles' Fractures and Leukocytosis ... - NIH
Sep 26, 2022 · Leukocytosis is a common sign of infection, particularly bacterial infection, and should prompt physicians to search for other signs and ...
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CA15-3 may be helpful in determining the extent of the spread of breast cancer. A high CA15-3 would be a symptom of metastasis, especially bone metastases. It ...
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May 22, 2019 · ... 80% there was no M-spike. In majority of the cases (70%), the plasma cell was >10%. In 12% of cases, it was more than 50% (Figure 3). Non ...
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Imaging-guided core biopsy is a reliable method for obtaining a tissue diagnosis in pathologic fracture of the appendicular skeleton with a high rate of ...Missing: techniques risks
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Although open biopsy is considered the reference standard in achieving a tissue diagnosis, with a reported accuracy of 98%, it is not without the risk of ...
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The pathology femoral peritrochanteric fracture with multiple brown ...
Brown tumor with Mirels' score less than 7 scores should be applied a conservative treatment. ... Mirels' score ≥ 9 indicates high risk of fracture and ...
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Denosumab moderately reduces the likelihood of pathological fractures in comparison to ZA in patients with bone metastases with statistical significance.
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Jul 15, 2017 · Unfortunately, some patients sustain pathologic fracture even after radiation therapy; various rates of pathologic fracture have been reported.
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Jul 2, 2025 · This study aims to assess a stepwise treatment plan for the acute incidence of PF in long bones following pediatric acute Hematogenous osteomyelitis (AHO).
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May 31, 2016 · Bone metastases of the long bones often lead to pain and pathological fractures. Local treatment consists of radiotherapy or surgery.
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Apr 6, 2025 · Vertebroplasty and kyphoplasty are percutaneous interventional procedures used to treat symptomatic, nonhealing fragility fractures of the spine.
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Surgical Treatment of Pathological Fractures Occurring at the ... - NIH
Surgical treatment of pathological fractures at the proximal femur provided early ambulation, and excellent pain relief. The surgery was well tolerated ...Missing: interventions | Show results with:interventions
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Vertebroplasty and kyphoplasty are effective treatment options for the reduction of pain associated with vertebral body compression fractures.
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Safety aspects in surgical treatment of pathological fractures of the ...
Dec 7, 2013 · ... fracture, hardware failure or ... complication rate for intramedullary nails in actual pathologic fractures than in impending fractures.
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Local surgical complication rates in patients receiving surgery ... - NIH
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Mar 21, 2023 · Patients with malignant hypercalcemia develop hypercalcemia at a very high level and in a short time, and therefore they are more symptomatic ...
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Sep 12, 2024 · The 30-day postoperative complication and mortality rates were 32.30% (n = 73) and 17.26% (n = 39), respectively. The most common complications ...
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Advanced Imaging of Multiple Myeloma Bone Disease - Frontiers
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Reducing the risk of skeletal complications from bone metastasis
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Denosumab for the prevention of skeletal complications in ...
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Jul 27, 2022 · Other randomized, controlled trials and meta-analyses have shown that vitamin D and calcium coadministration reduce fracture risk modestly.
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Strong, steady and straight: UK consensus statement on physical ...
This consensus statement aimed to determine the physical activity and exercise needed to optimise bone strength, reduce fall and fracture risk, improve posture
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The Effects of Physical Exercise on Balance and Prevention of Falls ...
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Palliative Radiation Therapy For Bone Metastases - StatPearls - NCBI
Mar 10, 2024 · The primary reason for treating bone metastases is to prevent further skeletal injury and improve symptoms. ... fracture risk with metastatic ...
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Mirels Scores in Patients Undergoing Prophylactic Stabilization for ...
This retrospective study of prophylactically stabilized metastatic lesions revealed that more than 90% of patients had Mirels scores greater than 8.Missing: formula | Show results with:formula
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Clinical trial results show that bisphosphonates reduce the occurrence of skeletal complications in patients with breast cancer and bone metastases (Table 1).