Patients with a pathological fracture will present with symptoms similar to any fractured bone: swelling or bruising, deformity, pain in the area of fracture that is worsened with mobility or application of pressure, and loss of function of the injured area [1]. Common anatomical sites for pathological fractures include the femur, vertebrae, humerus, and tibia [2] [3]. Pain related to a fracture that onsets without an injury or trauma raises suspicion of a pathological fracture [4]. Additionally, fractures in patients with pre-existing conditions such as metastatic cancer, advanced stage lung or breast cancer, Paget disease, osteoporosis/osteopenia, history of solid organ transplantation, chronic kidney disease may also indicate a pathological fracture.

A pathological fracture should always be included in the differential when patients with known bone metastases or a history of cancer complain of sudden onset of pain, even without swelling, deformity, or immobility. Pathological fractures of the thoracic or lumbar spine often present with pain upon sitting or standing. On the other hand, pathological spine fractures, particularly at the mid-back (the thoracic/lumbar junction), may present with pain when the patient is in a recumbent position. Cervical spine pathological fractures cause pain upon extension and flexion of the neck [3].

• Easy Bruising

  Symptoms associated with osteogenesis imperfecta include short stature, weak tissues, fragile skin, muscle weakness, loose joints, bleeding, easy bruising, early hearing loss, breathing problems, or curvature of the spine. [fortherecordmag.com]

• Pain

  The following items were assessed for association with pathological fracture or MESCC: tumor size, location, type, and morphology; disease burden; pain; and function. [ncbi.nlm.nih.gov]

  Cervical spine pathological fractures cause pain upon extension and flexion of the neck. [symptoma.com]

• Swelling

  A 50-year-old man with a history of alcohol-induced pancreatitis was admitted to a hospital with swelling and pain of the right ankle, and fever, and was suspected to have osteomyelitis. [ncbi.nlm.nih.gov]

• Weakness

  At 1-year follow-up, no disease recurrence was observed, and the patient had a full range of motion but with slight weakness of the extensor mechanism. [ncbi.nlm.nih.gov]

  A pathologic fracture (also called insufficiency fracture) is a bone fracture caused by disease that led to weakness of the bone structure. [en.wikipedia.org]

• Asymptomatic

  Routine automated biochemical screening has made the diagnosis commonplace in developed countries and the disease is diagnosed early in its course when it is often asymptomatic. [ncbi.nlm.nih.gov]

• Severe Pain

  : A 53-year-old white woman was admitted to the Massachusetts General Hospital complaining of severe pain in the right hip. The patient had twisted the right leg in moving to answer the telephone a few hours before admission. [jamanetwork.com]

  Surgery is normally reserved for those with severe pain, weakness, or inability to feel their arms or legs. [emedicinehealth.com]

  Functional b a Size is determined as a fraction of the cortical thickness. b Functional pain is defined as severe pain or pain aggravated by limb function. [roentgenrayreader.blogspot.com]

  According to the evaluation of Dijkstra et al, 3 an objective pain scale was classified as none (no pain, 0 points), mild (no pain with analgesics, 1 point), moderate (controllable pain with analgesics, 2 points), and severe (no relief of pain even with [healio.com]

• Vomiting

  Tell your doctor if any of these symptoms are severe or do not go away: nausea vomiting pain, swelling, or redness in the area where the medication was injected Some side effects can be serious. [medlineplus.gov]

  Early signs of iron poisoning within 6 hours include vomiting and diarrhea, fever, hyperglycemia, and leukocytosis. Later signs include hypotension, metabolic acidosis, lethargy, seizures, and coma. [webpath.med.utah.edu]

  Hypomagnesemia may be asymptomatic or result in vomiting, diarrhea, and even tetany, confusion and seizures. It is furthermore associated with prolonged QT in the ECG and electrolyte imbalance, including hypocalcemia and hypokalemia. [scielo.isciii.es]

• Nausea

  Patients who have high levels of calcium in their blood may experience nausea, fatigue, confusion, constipation, and frequent urination. Patients with anemia may experience fatigue, weakness, and shortness of breath with exercise. [orthoinfo.aaos.org]

  Tell your doctor if any of these symptoms are severe or do not go away: nausea vomiting pain, swelling, or redness in the area where the medication was injected Some side effects can be serious. [medlineplus.gov]

• Abdominal Pain

  The most common presenting features are abdominal pain and palpable abdominal masses. Pathological fractures of the spine presenting as bilateral lower leg weakness are exceptionally rare. [ncbi.nlm.nih.gov]

• Fracture

  A 12-year-old-girl presented with a fracture of an osteolytic lesion of the distal radius. A 7-year-old girl presented with a fracture of an osteolytic lesion of the femoral shaft. [ncbi.nlm.nih.gov]

• Osteoporosis

  Codes M80 Osteoporosis with current pathological fracture M80.0 Age-related osteoporosis with current pathological fracture M80.00 Age-related osteoporosis with current pathological fracture, unspecified site M80.00XA …… initial encounter for fracture [icd10data.com]

  The correct code for the fracture in ICD-10-CM is M80.08XA (age-related osteoporosis with current pathological fracture, vertebra[e]). Also report Z87.310 (personal history of [healed] osteoporosis fracture). [hcpro.com]

  Primary hyperparathyroidism Simple bone cyst Aneurismal bone cyst Osteoporosis Chronic osteomyelitis Osteogenesis imperfecta Osteomalacia Rickets Renal osteodystrophy Malignant infantile osteopetrosis juvenile osteoporosis juvenile rheumatoid arthritis [en.wikipedia.org]

• Arthritis

  Inflammatory conditions – rheumatoid arthritis 6. Infection N.B. some of these conditions have been discussed elsewhere OSTEOPOROSIS = reduced bone density Important points: Please log in to view the content of this page. [orthoteers.org]

  Primary hyperparathyroidism Simple bone cyst Aneurismal bone cyst Osteoporosis Chronic osteomyelitis Osteogenesis imperfecta Osteomalacia Rickets Renal osteodystrophy Malignant infantile osteopetrosis juvenile osteoporosis juvenile rheumatoid arthritis [en.wikipedia.org]

  Seminars in Arthritis and Rheumatism. avr 1999;28(5):287‑304. Kariv R, Sidi Y, Malnick S, Gur H. Pathologic fractures, anemia, hypercalcemia and hypocalciuria: an association between celiac disease and hyperparathyroidism. [zenodo.org]

  Noncorrectable causes include osteogenesis imperfecta, polyostotic fibrous dysplasia, Paget’s disease of bone, osteopetrosis, postmenopausal bone loss, rheumatoid arthritis, and Gaucher disease. [autoaccident.com]

• Bone Disorder

  This process is most commonly due to osteoporosis, but may also be due to other pathologies such as: cancer, infection (such as osteomyelitis), inherited bone disorders, or a bone cyst. [en.wikipedia.org]

  Causes of bone abnormalities include osteoporosis, malignant or non-malignant tumors, infection, and some inherited bone disorders. [symptoma.com]

  Causes of weakened bone include osteoporosis, tumors, infection, and certain inherited bone disorders. And these are just a few causes; there are dozens of diseases and conditions that can lead to a pathologic fracture. [orthopedics.about.com]

• Seizure

  If the victim has collapsed, had a seizure, has trouble breathing, or can't be awakened, immediately call emergency services at 911. [medlineplus.gov]

  […] ulna Progressive bowing of the femur and tibia Extraskeletal Findings (vary depending on the primary mineral deficiency): Calcipenic rickets – hypoplasia of dental enamel, decreased muscle tone, delayed achievement of motor milestones, hypocalcemic seizures [learn.pediatrics.ubc.ca]

  Following surgery patient developed hypocalcemic tetany and seizures, treated with intravenous calcium gluconate and followed by oral calcium supplements. [bjmp.org]

  Additional mechanisms include violent muscle contractions from seizure activity, electrical shock, and athletic-related trauma. Proximal humeral fractures are most often closed. [emedicine.medscape.com]

  Can also occur during seizures or electric shock when fracture may be associated with a posterior shoulder dislocation. Can also result from a direct blow. [patient.info]

• Hyperactivity

  Neurologic examination revealed mild occipital neuralgia, difficulty with movements of the cranium, hyperactive deep tendon reflexes, but no Babinski sign. [ncbi.nlm.nih.gov]

• Paresthesia

  Subsequently, the patient evolved with lower-limb paresthesia and urine retention, without any pathological diagnosis for the lesion. [scielo.br]

Workup of pathological fracture consists of a medical history (e.g., history of present illness, smoking history and other risk factors for lung, bladder, renal cancers, osteoporosis, previous fractures) [5]. Laboratory and imaging tests can help identify the cause of the pathological fracture (e.g., metastatic disease or benign condition). A bone biopsy will provide a definitive diagnosis.

Imaging tests:

• A plain radiograph is the first test for the evaluation of bone integrity. A pathological fracture due to metastatic disease appears as a lytic lesion of the involved bone on plain radiograph films. About 10% of pathological fractures are not detected by plain radiographs [6].
• Computed tomography (CT) scans are performed in patients with suspected metastatic disease to search for primary tumors, and in patients with known metastatic disease to assess overall disease burden. CT scans are very accurate for assessment of bone cortex integrity, which aids in the diagnosis of a pathological fracture [7].
• Magnetic resonance imaging (MRI) is more sensitive and more specific than CT for the detection of bone metastases. A well-defined low signal T1-weighted abnormality around the fracture is indicative of an underlying tumor. Advanced MRI techniques such as diffusion-weighted MR imaging and dynamic contrast-enhanced imaging allow differentiation between metabolic insufficiency fractures and pathologic fractures [8] [9] [10] [11] [12].
• Integrated 18F-labeled fluorodeoxyglucose-positron emission tomography (PET) with computed tomography (PET/CT) scanning may also help differentiate the type of pathological fractures.

Laboratory tests [13]:

• Serum alkaline phosphatase - Typically elevated with metastatic disease involving bone lesions; it is indicative of osteoblastic response (bone destruction). It may not be elevated in lytic tumors (e.g., plasma cell myelomas) in contrast with the raised levels in Paget disease, benign fractures, and endocrine diseases.
• Serum protein electrophoresis
• Urinalysis, urine protein electrophoresis
• Calcium level

A bone biopsy can be performed to determine the etiology of a pathological fracture (malignancy vs. insufficiency/benign disease process) [14]. Most bone biopsies are performed by fine-needle aspiration. Other methods of obtaining a sample for bone biopsy includes surgical excision.

The mean VAS score decreased from 7.1 (range, 4-9) before treatment to 1.6 (range, 0-6), 1 month after treatment, and to 1.4 (range 0-6) 6 months after treatment. [ncbi.nlm.nih.gov]

Fifty-nine percent underwent surgical treatment in addition to clinical treatment. [scielo.br]

Hypercalcemia and osteolytic bone lesion are important complications in the prognosis of patients with adult T cell leukemia/lymphoma (ATL). [ncbi.nlm.nih.gov]

The prognosis is poor with a mean survival of less than 2 years. [ 12 ]. Conclusion Bone metastases, which may reveal biliary carcinoma, are aggressive, progress rapidly and are the sign of a poor prognosis. Conflict of interest statement None. [em-consulte.com]

Therefore, metastatic tumors with poor prognosis and difficult surgical access were treated conservatively with radiotherapy and chemotherapy, while metastatic tumors with good prognosis, large injury causing instability of the segment, and easy surgical [scielo.br]

Primary hyperparathyroidism revealed by a pathological fracture is very uncommon; in the majority of cases the discovery of lytic bone lesions on imaging examinations evokes in the clinician first a neoplastic etiology and a metabolic origin is often [ncbi.nlm.nih.gov]

The etiology is unknown, and is more common in adults. The clinical manifestations are heterogeneous due to histiocytic infiltration of multiple systems. [scielo.org.co]

[…] manifestations due to the underlying etiology. [icd10data.com]

The epidemiology of peripheral fractures. Bone. 1996. 18:209S-13S. Pedrazzoni M, Abbate B, Verzicco I, Pedrazzini A, Benatti M, Cervellin G. [emedicine.medscape.com]

Proximal humeral fractures Epidemiology 4-5% of all fractures. Mechanism of injury Usually after a fall on to an outstretched hand from standing height. [patient.info]

Benger U: Epidemiological changes over 30 years in an urban population. In Thesis Lund University, Lund Sweden; 1987. 3. Praemer A, Furner S, Rice D: Musculoskeletal condition in the United States. [webmedcentral.com]

Epidemiology of Fractures in Children Incidence 42% of the boys and 27% of the girls sustain at least one fracture from 0 to 16 years of age. Each year 1.6% to 2.1% of all the children sustain a fracture. [boneandspine.com]

In order to establish an efficient IMP, it is important to know the epidemiology of pathogens, as well the mechanisms used by the different control methods to be pooled for managing the disease ( Dik et al ., 2002 ). [onlinelibrary.wiley.com]

Pathophysiology : Although there are many potential etiologies for weakened bone manifesting as pathological fractures, it is simple to divide it into three categories with common etiologies: 1) Metabolic bone disease- eg. [learn.pediatrics.ubc.ca]

Lyons A, Ghazali N (2008) Osteoradionecrosis of the jaws: Current understanding of its pathophysiology and treatment. Br J Oral Maxillofac Surg 46: 653-660. [omicsonline.org]

[…] vessels Injury to muscles and tendons Injury to joints Injury to viscera Local Infection Compartment syndrome Others Avascular necrosis Shortening Joint stiffness Sudeck's dystrophy Osteomyelitis Ischaemic contracture Myositis ossificans Osteoarthritis Pathophysiology [en.wikipedia.org]

Among the various materials that have been used to prevent early reformation of the physeal bar (fat, silastic, cartilage), Peterson recommended the use of Cranioplast, as this material can prevent bar reformation, and it is radiolucent because it does [ncbi.nlm.nih.gov]

Some patients have preventative fixation to prevent bony fracture from occurring. [autoaccident.com]

The brace helps support the back and prevents bending forward, which removes pressure from the fractured vertebrae. If the fracture is caused by osteoporosis, treatment of the osteoporosis can help prevent additional fractures. [columbiaspine.org]

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3. Hu YC, Lun DX, Wang H. Clinical features of neoplastic pathological fracture in long bones. Chin Med J. 2012;125:3127-32.
4. Kontakis G, Koutras C, Tosounidis T, Giannoudis P. Early management of proximal humeral fractures with hemiarthroplasty: a systematic review. J Bone Joint Surg Br. 2008; 90:1407-13.
5. Brickles J, Dadia S, Lidar Z. Surgical management of metastatic bone disease. J Bone Joint Surg Am. 2009; 91:1503-16.
6. Fayad LM, Kamel IR, Kawamoto S, et al. Distinguishing stress fractures from pathologic fractures: a multimodality approach. Skeletal Radiol. 2005;34:245-59.
7. Nazarian A, Entezari V, Zurakowski D, et al. Treatment Planning and Fracture Prediction in Patients with Skeletal Metastasis with CT-Based Rigidity Analysis. Clin Cancer Res. 2015;21:2514-9.
8. Baur A, Stäbler A, Brüning R, et al. Diffusion-weighted MR imaging of bone marrow: differentiation of benign versus pathologic compression fractures. Radiology. 1998;207:349-56.
9. Spuentrup E, Buecker A, Adam G, et al. Diffusion-weighted MR imaging for differentiation of benign fracture edema and tumor infiltration of the vertebral body. Am J Roentgenol. 2001;176:351-8.
10. Herneth AM, Philipp MO, Naude J, et al. Vertebral metastases: assessment with apparent diffusion coefficient. Radiology. 2002;225:889-94.
11. Byun WM, Jang HW, Kim SW, et al. Diffusion-weighted magnetic resonance imaging of sacral insufficiency fractures: comparison with metastases of the sacrum. Spine (Phila Pa 1976). 2007;32:E820-4.
12. Karchevsky M, Babb JS, Schweitzer ME. Can diffusion-weighted imaging be used to differentiate benign from pathologic fractures? A meta-analysis. Skeletal Radiol. 2008;37:791-5.
13. Orita Y, Sugitani I, Matsuura M, et al. Prognostic factors and the therapeutic strategy for patients with bone metastasis from differentiated thyroid carcinoma. Surgery. 2010;147:424-31.
14. Mirels H. Metastatic disease in long bones. A proposed scoring system for diagnosing impending pathologic fractures. Clin Orthop Relat Res. 1989;256-64.