Rheumatic Manifestations of Primary and Metastatic Bone Tumors and Paraneoplastic Bone Disease




Bone tumors can simulate a wide range of rheumatic disorders, delaying tumor diagnosis and therefore the probability of cure. This review describes the clinical presentation of primary and metastatic bone tumors, with particular emphasis on differential diagnosis with other musculoskeletal conditions and atypical symptoms that should alert clinicians of an underlying malignancy. In addition, the authors summarize the most common paraneoplastic syndromes affecting bone and how cancer treatment can affect bone health.


Musculoskeletal symptoms are usually the first manifestation of bone tumors. These symptoms can simulate a wide range of rheumatic disorders, delaying tumor diagnosis and therefore the probability of cure. Tumors can affect the bone through both direct and indirect mechanisms. Primary bone tumors and metastases ( Box 1 ) are responsible for direct effects, whereas paraneoplastic syndromes, metabolic changes, and therapeutic toxicity result in indirect effects on the bone. In this article, the authors first review the clinical presentation of primary and metastatic bone tumors, with particular emphasis on differential diagnosis with other musculoskeletal conditions and atypical symptoms that should alert clinicians of an underlying malignancy. They then summarize the most common paraneoplastic syndromes affecting bone. The metabolic changes of bone caused by cancer and cancer treatment are also described.



Box 1





  • Primary bone malignancies




    • Osteosarcoma



    • Ewing sarcoma



    • Chondrosarcoma



    • Other histologies: Fibrosarcoma; malignant fibrous histiocytoma, hemangiosarcoma, malignant hemangioendothelioma, malignant epithelioid hemangioendothelioma, malignant chondroblastoma, malignant in giant cell tumor of bone, adamantinoma of long bone, malignant odontogenic tumor, malignant ameloblastoma, chordoma, leiomyosarcoma, liposarcoma




  • Hematopoietic tumors




    • Plasma cell myeloma



    • Lymphoma




  • Metastatic malignancy



  • Benign bone tumors




    • Bone-forming tumors: osteoma, osteoid osteoma, osteoblastoma



    • Giant cell tumor



    • Vascular tumors: hemangioma, lymphangioma, glomus tumor



    • Other connective tissue tumors: desmoplastic fibroma, fibrous histiocytoma, lipoma, leiomyoma, neurilemoma, neurofibroma



    • Cartilage-forming tumors: chondroma, enchondroma, osteochondroma, chondroblastoma, chondromyxoid fibroma




  • Miscellaneous lesions




    • Solitary bone cyst



    • Aneurysmal bone cyst



    • Fibrous dysplasia



    • Osteofibrous dysplasia or ossifying fibroma



    • Metaphyseal fibrous defect or nonossifying fibroma



    • Langerhans cell histiocytosis




  • Tumorlike lesions




    • Brown tumor of hyperparathyroidism



    • Reparative granuloma



    • Chronic osteomyelitis (Brodie abscess)



    • Acute osteomyelitis



    • Bone infarct




Bone tumors, miscellaneous and tumorlike bone lesions

Data from Dorfman H, Czerniak B, Kotz R, et al. WHO classification of bone tumours. In: Fletcher C, Krishnan Unni K, Mertens F, editors. Pathology and genetics of tumours of soft tissue and bone. Lyon (France): IARCPress; 2006. p. 227–32.


Bone tumors


Epidemiology


Primary bone and joint cancers represent only 0.2% of all cancers in people older than 20 years but are responsible for more than 5% of all malignancies in the younger population. The peak incidence is between ages 10 and 20 years when these cancers account for 8% of all cancers, as the fourth cause of malignancy, only behind lymphoma, leukemia, and nervous system–related tumors. Osteosarcoma, Ewing sarcoma, and chondrosarcoma are responsible for approximately 80% of all primary bone and joint cancers, the first 2 being the most prevalent cancers in children, whereas chondrosarcoma is the most common in older populations ( Fig. 1 ). After age 40 years, most bone tumors are metastatic, most commonly from breast, prostate, thyroid, lung, and renal carcinomas. Postmortem examination of patients dying from these cancers revealed bone metastases in 73%, 68%, 42%, 36%, and 35% of the cases, respectively.




Fig. 1


Relative frequencies of bone sarcomas by histology type and age group.

( Data from Lewis DR, Ries LAG. Cancers of the Bone and Joint. In: Ries LAG, Young JL, Keel GE, et al, editors. SEER Survival Monograph: Cancer Survival Among Adults: U.S. SEER Program, 1988–2001, Patient and Tumor Characteristics. Bethesda (MD): National Cancer Institute, SEER Program, NIH Pub. No. 07-6215; 2007. p. 81–8; and Gurney JG, Swensen AR, Bulterys M. Malignant Bone Tumors. In: Ries LAG, Smith MA, Gurney JG, et al, editors. Cancer Incidence and Survival among Children and Adolescents: United States SEER Program 1975–1995. Bethesda (MD): National Cancer Institute, SEER Program. NIH Pub. No. 99-4649; 1999. p. 99–110.)


Multiple myeloma is the most frequent hematopoietic neoplasm of the bone and should be included in the differential diagnosis of every patient older than 40 years with multiple osteolytic bone lesions. Primary bone lymphomas are uncommon and represent only 2% of all lymphomas. However, 20% of patients with lymphoma will develop secondary invasion of the bone during the course of their disease.


Unlike bone cancer, the true incidence of benign bone tumors and tumorlike lesions is unknown, with a prevalence of about one-half of that of all bone tumors combined. These conditions usually develop during childhood but can remain asymptomatic or manifest themselves later in life. The most frequent benign bone tumors include osteoid osteoma, osteochondromas, enchondromas, and hemangiomas of the spine ( Table 1 ). Giant cell tumor is another relatively common bone neoplasm, accounting for 8% of primary bone tumors in Western populations but almost 20% in Asians. The peak incidence of this tumor is between 15 and 30 years of age, but this tumor can also occur later in life. Giant cell tumor is considered semimalignant, with a clinical presentation varying from a well-defined intraosseous lesion to an aggressive lesion that breaks the cortex and extends to soft tissues. This tumor has the potential to metastasize, mostly to the lung.



Table 1

Clinical features of most commons benign bone tumors and tumorlike lesions


























































Frequency Typical Clinical Presentation
Benign tumors
Cartilaginous lesions
Osteochondroma 33% of benign bone tumors a Usually located in long bones but may also affect posterior elements of the spine. Only develop symptoms when the tumor compresses nearby structures. Surgical excision is indicated when symptoms are present. Recurrence rate is low
Enchondroma 16% of benign bone tumors a Long bones lesions are usually asymptomatic. Patients with involvement of small bones of hands and feet frequently present fractures and pain. Curettage is indicated only if symptoms are present. Recurrence is extremely rare
Bone-forming lesions
Osteoid osteoma 13% of benign bone tumors a The most frequent sites are femur and tibia but any bone can be affected. Patients classically manifest with intense bone pain that typically worsens at night and presents a fast and excellent response to nonsteroidal antiinflammatory drugs. Treatment includes complete removal of the nidus. Recurrence can be seen only in cases of incomplete removal
Vascular tumors
Hemangioma 10%–12% of general population b Generally located on spine or skull. Asymptomatic. On rare occasions, patients can develop neurologic symptoms due to spinal cord compression
Giant cell tumor 22% of benign bone tumors, a 7.8% of primary bone tumors Usually located in long bones, especially distal femur and proximal tibia. Patients often present pain and swelling. Clinical manifestation depends on tumor aggressiveness and location. Surgery is mandatory. Recurrence rate varies from 25%–50%
Tumorlike lesions
Cyst lesion
Aneurysmal bone cyst 12% of benign bone tumors a Rapidly blood-filled cyst. Located on long bones and posterior elements of the spine. Patients experience pain associated with rapidly enlarging mass. Compression symptoms can be seen, especially when the spine is involved. Curettage is indicated. Recurrence is rare
Simple bone cyst Unknown Fluid-filled cyst. Located in femur and humerus in children and calcaneus and ilium in adults. Asymptomatic. Treatment is indicated only when symptoms are present and includes fluid aspiration and steroids injection
Fibrous lesions
Metaphyseal fibrous defect 35% of children between ages 4–8 y Metaphysis of long bones. Usually asymptomatic and rarely produce pain. A pathologic fracture may be the first and sole manifestation. Treatment is only required in cases with high risk of fracture and includes curettage with bone grafting
Fibrous dysplasia Unknown Bone replacement by fibrous tissue. Mono-ostotic or polyostotic (McCune-Albright syndrome). The most common site is the femoral neck. Generally asymptomatic. Pathologic fracture may be the first and sole manifestation. Treatment included curettage and stabilization if necessary. Recurrence is frequent. Bisphosphonates could be an option

Data from Unni KK, Inwards CY, Bridge JA, et al. Tumor of the bones and joints. AFIP Atlas of tumor pathology. vol. 2. Washington, DC: ARP press; 2005; and Robbins LR, Fountain EM. Hemangioma of cervical vertebras with spinal-cord compression. N Engl J Med 1958;258(14):685–87.

a Surgical series from Mayo clinic files. True incidence is unknown because patients are often asymptomatic and biopsy and surgery are not performed.


b Based on autopsy results.



Tumorlike bone lesions are nonneoplastic conditions that can occur as solitary or multiple bone lesions. The most frequent lesions in this group include metaphyseal fibrous defects and fibrous dysplasia. These fibrous lesions are characterized by fibrous replacement of bone and can result in pain, deformity, and spontaneous fractures. Other common tumorlike lesions are cysts, which include unicameral or simple bone cysts and aneurysmal bone cysts (see Table 1 ).


Clinical Manifestations of Bone Tumors


Benign bone tumors are usually asymptomatic findings on a simple radiograph performed for other reasons. However, depending on the tumor location, extension, aggressiveness, and patient age, these tumors can cause joint effusion, limited mobility, spontaneous fractures, neurovascular compressions, deformities, or growth defects (eg, extremity disparities, scoliosis) (see Table 1 ). Bone pain, an enlarging mass, and constitutional symptoms are considered the 3 cardinal signs and symptoms of malignant bone tumors. In addition, mass effects and system-specific symptoms can occur depending on the location of the tumor.


Pain


Pain is generally the first manifestation of bone tumors. Initially, it is mild and intermittent, with higher intensity at night and during exercise. As the disease progresses, the pain becomes more severe, often requiring higher doses of analgesics. Osteoid osteoma is a benign bone-forming tumor. The tumor is rich in prostaglandins, and patients usually develop intense bone pain with a characteristically fast and excellent response to nonsteroidal antiinflammatory drugs (NSAIDs), usually within 20 to 25 minutes. This rapid response to NSAIDs plus the finding of the classical nidus (small radiolucent mass with well-defined surrounding sclerosis) on conventional radiography is usually sufficient for the diagnosis.


Enlarging mass


An enlarging mass is usually a late manifestation of bone tumors, only evident when the tumor enlarges the bone or extends to extraosseous tissues. Clinical features favoring suspicion of an underlying malignancy are rapid growth, hyperthermia, skin ulceration, and adhesion to surrounding tissues. On the other hand, benign lesions are generally localized and do not adhere to skin or surrounding tissue.


Joint effusion


Tumors adjacent to the joint, including epiphyseal and metaphyseal neoplasms, may cause joint effusion. The presence of an effusion with concomitant joint stiffness can be misleading, suggesting a diagnosis of inflammatory rheumatic disease, especially in pediatric populations.


Limited mobility


Different factors can cause a decrease in joint mobility in patients with bone tumors, including pain, muscle atrophy or spasm, joint effusion, and large tumoral mass.


Pathologic fractures


Pathologic fractures are usually a late manifestation of malignant bone tumors. In contrast, benign lesions are generally asymptomatic, but sometimes a pathologic fracture might be their initial and sole manifestation.


Constitutional symptoms


Ewing sarcoma is the most common primary bone tumor associated with constitutional symptoms. Weight loss, fever, or anemia is present in 20% of the cases. These manifestations often are similar to those seen in subacute osteomyelitis, which needs to be considered as a differential diagnosis. Both conditions can present with fever, anemia, weight loss, an elevated erythrosedimentation rate, bone and soft tissue mass, and increased radionuclide uptake on nuclear scan. However, unlike in osteomyelitis, culture results are negative in Ewing sarcoma.


Neurologic symptoms


Both malignant (eg, Ewing sarcoma, metastases) and benign lesions (eg, osteoid osteoma, osteoblastoma) can involve the spine, including the sacrum. Patients may develop a wide range of neurologic manifestations, including lumbago; sciatica; pain in the hips and buttocks; radiculopathy; and, in more severe cases, spinal cord compression. The skull can also be affected by bone tumors (eg, multiple myeloma, enchondromatosis multiple), resulting in headache and, depending on the location, cranial nerve palsy. Occasionally, tumors of the skull might be misdiagnosed as giant cell arteritis. The eosinophilic granuloma of bone has an especial avidity for the skull. Depending on tumor location, patients with this condition may develop jaw pain, proptosis, otitis refractory to treatment, and central nervous system involvement (especially diabetes insipidus).


Role of Imaging in the Diagnosis and Management of Bone Tumors


In all patients with unexplained bone symptoms, a plain radiograph of the affected area is mandatory. This simple study allows to easily confirm the diagnosis of some benign tumors (eg, metaphysical fibrous defect, fibrous dysplasia, and simple bone cysts) without further studies. However, in a large proportion of patients, more advanced imaging techniques are needed, including computed tomography (CT), magnetic resonance imaging (MRI), radionuclide bone scans, and/or positron emission tomography (PET).


A proper radiologic evaluation of a bone lesion should include a description of the pattern of bone destruction, tumor margins, periosteal reaction, lesion opacity, mineralization, and trabecular pattern. These characteristics in addition to the patient’s age and tumor location narrow the spectrum of possible diagnoses.


Age


Peak age differs among various tumors. In general, before age 5 years, a malignant tumor is often a metastatic neuroblastoma; between 5 and 30 years of age, it is frequently osteosarcoma or Ewing sarcoma; and, after 30 years, a metastasis or multiple myeloma. Benign lesions develop mostly in young patients; however, they can remain asymptomatic for many years and become clinically evident at an older age.


Tumor location


According to Miller, tumor location can be stratified into 3 categories: skeletal (axial or appendicular), longitudinal (diaphyseal, metaphyseal, or epiphyseal), and transversal (medullary, juxtacortical, or cortical) ( Fig. 2 ). In addition, some tumors are typically associated with particular locations, such as hemangiomas with vertebral bodies, aneurysmal bone cysts and osteoblastomas with the posterior elements of the spine, and simple bone cysts and intraosseous lipomas with the calcaneous.




Fig. 2


Classification of tumors according to longitudinal location.

( Data from Miller TT. Bone tumors and tumorlike conditions: analysis with conventional radiography. Radiology 2008;246(3):662–74.)


Patterns of bone destruction and lesion margins


Three classical destruction patterns have been described: geographic, moth eaten, and permeated ( Table 2 ). Evidence suggestive of a nonaggressive lesion includes geographic pattern, narrow transition zone, well-defined borders, and sclerotic margins. On the other hand, a lesion has to be considered aggressive and potentially malignant when the images show a permeated or moth-eaten pattern, wide transition zone, ill-defined borders, and nonsclerotic margins. These rules nevertheless can have exceptions because aggressive patterns can occasionally be seen in benign processes such as osteomyelitis or Langerhans cell histiocytosis.



Table 2

Radiologic patterns of bone destruction

























Pattern Description
Geographic Focal lytic lesion
Type 1a Well defined with sclerotic rim
Type 1b Well defined, no sclerotic rim
Type 1c Ill defined
Moth eaten (Type 2) Patchy lytic holes
Permeated (Type 3) Small lytic patchy lesions

Data from Miller TT. Bone tumors and tumorlike conditions: analysis with conventional radiography. Radiology 2008;246(3):662–74.


Periosteal reaction


The type of periosteal reaction depends on the rate of tumor progression. Nonaggressive lesions usually grow slowly and allow the periosteum to react, developing a thick, solid, and uniform callous. Instead, in aggressive tumors, the periosteum cannot adequately control the tumoral expansion and the radiographic images of the affected bone show perpendicular periosteal reaction (called hair-on-end or sunburst), cortical disruption, and Codman triangle, which is the disruption of an elevated periosteum “broken by the tumor,” an image which can occasionally also be found in some benign lesions.


Lesion opacity


Lesion opacity is another radiologic feature often reported. Tumors can be predominantly sclerotic, predominantly lytic, or mixed. This imaging feature is not always helpful in distinguishing between benign and malignant tumors because both can have lytic or sclerotic appearance. However, it can assist in identifying the origin of the primary tumor when metastatic disease is suspected (see “Multiple Lesions”).


Mineralization pattern


Together with lesion opacity, the calcification pattern can suggest a diagnosis. Osteoid tumors often present a trabecular or cloud-like mineralization pattern. Calcification in a chondroid tumor has been described as ring-and-arcs, popcorn, and stippled or punctate.


Multiple lesions


Multiple bone lesions seen in patients older than 40 years are highly suggestive of metastatic cancer. These lesions are usually classified according to image opacity, with mixed patterns as the most common presentation (eg, breast cancer). Predominantly lytic metastases are seen in renal cell cancer, melanoma, and multiple myeloma, whereas predominantly sclerotic metastases are usually associated with prostate carcinoma, small cell lung cancer, and Hodgkin lymphoma. Multiple lesions are not always malignant and can also be found in patients with multiple hemangiomas, hyperparathyroidism (Brown tumors), fibrous dysplasia, and multiple enchondromatosis. Osteopoikilosis is a rare hereditary disorder that also has to be considered in the presence of multiple sclerotic lesions. Characteristically, these patients develop multiple small radiodensities in bone metaphyses. In general, these patients remain asymptomatic throughout their lifetime.


Advanced imaging techniques


MRI is considered the method of choice for the evaluation of bone and soft tissue masses. Its main advantages include better characterization of nonmineralized chondroid matrix, cysts, and lipomatous and vascular tissues, with high accuracy to define soft tissue involvement and extension and high sensitivity for detection of skip metastases distantly in the bone or transarticular in the opposite side of the adjacent joint.


Although MRI is used more often than CT in the evaluation of bone tumors, the latter technique is sometimes useful to better characterize the involved bone, the mineralization pattern, and the definition of sclerotic margins.


Radionuclide bone scans remain the standard imaging technique to evaluate the extent of metastatic bone disease. However, this technique has some disadvantages, including overestimation of tumor extension (high rate of false positives results) and a poor sensitivity to detect pure lytic lesions (eg, renal cell carcinoma metastases and multiple myeloma).


New imaging techniques have been developed and evaluated during the past decade, such as whole-body MRI and PET. However, the precise role of these techniques in the diagnosis and evaluation of bone tumors and metastases needs to be established.


Experienced radiologists can diagnose some benign bone tumors using 1 or more of these techniques with a degree of certainty, avoiding the need for biopsy. However, when bone sarcoma is suspected because of radiologic features, rapid growth, or prolonged bone pain, prompt consultation with an orthopedic surgeon is mandatory for rapid diagnosis, biopsy, and therapeutic guidance.


Prognosis and Treatment


The prognosis of patients with bone cancer has improved in the last decades. Chondrosarcoma has the longest survival, followed by osteosarcoma and Ewing sarcoma (approximately 10, 7, and 5 years, respectively).


In general, benign bone tumors have a good prognosis. However, depending on tumor aggressiveness and location, patients may develop complications that can occasionally be serious, including neurovascular compressions or growth defects in children. Local recurrence after treatment varies depending on tumor histology and type of treatment.


Malignant transformation of benign lesions is extremely rare except for osteochondromas and enchondromas. Osteochondromas are associated with an increased risk of bone cancer. In a retrospective study, 32 (5%) of 637 patients with bone tumors originating in the cartilage developed malignant transformation. Of the 32 patients, 14 had solitary osteochondroma, 10 had multiple osteochondromas, 6 had enchondromas, 1 had Ollier disease, and 1 had Maffucci syndrome. Ollier disease is a rare condition, characterized by the presence of 2 or more enchondromas; when multiple soft tissue hemangiomas are also present, this syndrome is called Maffucci syndrome. These patients have an increased risk of developing chondrosarcoma. Schwartz and colleagues reported a series of 37 patients with Ollier disease and 7 with Maffucci disease. Ten patients developed chondrosarcoma, 1 osteosarcoma, and 5 cancer in other organs. Giant cell tumors can develop an aggressive course in approximately 20% of patients. They are not considered to be malignant; however, in a retrospective review of 470 patients with giant cell tumors, 24 (5%) developed metastases, most often in the lung. Unlike metastatic sarcoma, giant cell metastases are less aggressive, and, in this series, no patients died during follow-up.




Paraneoplastic bone syndromes


There are 3 main paraneoplastic syndromes affecting the bone: humoral hypercalcemia of malignancy, hypertrophic osteoarthropathy (HOA), and tumor-induced osteomalacia.


Humoral Hypercalcemia of Malignancy


Humoral hypercalcemia of malignancy is a syndrome produced by ectopic secretion of parathyroid hormone–related protein (PTHrP). This hormone shares a similar N-terminal sequence with parathyroid hormone (PTH). Burtis and colleagues reported a series of 38 patients with hypercalcemia of malignancy. Nearly 80% of them showed high levels of PTHrP. In the remaining 8 patients, the hypercalcemia was attributed to osteolytic metastatic disease. Serum levels of PTHrP were low or undetectable in all 60 healthy controls. The most frequent etiology of humoral hypercalcemia was squamous cell cancer, accounting for 40% of the cases.


PTHrP binds to the PTH/PTHrP receptor resulting in similar metabolic effects as those of PTH, including increased bone reabsorption, reduced renal phosphorous reabsorption, and enhanced renal calcium retention. These metabolic changes result in the classical laboratory findings observed in primary hyperparathyroidism, including hypercalcemia, hypocalciuria, hypophosphatemia, and hyperphosphaturia. However, the effects of PTHrP and PTH are not entirely identical. Unlike what is seen in primary hyperparathyroidism, bone formation is totally suppressed in patients with humoral hypercalcemia of malignancy, and their levels of serum 1,25-dihydroxyvitamin D are usually low. The precise mechanisms accounting for these differences have not been clarified yet.


Osteolytic metastases represent the second most common etiology of malignant hypercalcemia and account for 20% of the cases of malignant hypercalcemia, most frequently observed in patients with breast cancer or multiple myeloma. These patients can also have increased bone reabsorption caused by paracrine secretion of cytokines and PTHrP. Other less frequent causes of hypercalcemia have to be considered in patients with cancer, including ectopic secretion of 1,25-dihydroxyvitamin D or intact PTH by the tumoral cells.


Hypercalcemia is usually a late complication of malignancies, carrying a high short-term mortality. Treatment depends on the severity of the hypercalcemia and the underlying tumor.


HOA


HOA is a paraneoplastic syndrome characterized by digital clubbing and periostitis of tubular bones, with or without synovial effusion. Digital clubbing results from the proliferation of the connective tissue between the nail matrix and the distal phalanx in the fingers and/or toes. It can occur in isolation without periostitis in other bones. When advanced, clubbing can cause drumsticklike deformities that are typical and easy to recognize. At early stages, however, additional clinical tests might be needed for diagnosis, including



  • 1.

    Measurement of the nail fold angle as the nail exits the terminal phalanx. An angle greater than 180° is congruent with clubbing.


  • 2.

    Schamroth sign defined as “the absence of diamond shape window when the dorsal surfaces of opposite fingers are opposed.”


  • 3.

    Measurement of the phalangeal depth ratio (distal phalange depth to interphalangeal finger depth). A ratio greater than 1 is considered positive. In addition, a digital index can be calculated summing the phalangeal depth ratios of the 10 fingers, and the diagnosis of clubbing is made when the result is greater than 10.



Periostitis is the hallmark of this syndrome. It generally affects distal long tubular bones, mostly the tibiae, fibulae, radii, ulnae, femora, and hummers. Periostitis can cause intense deep-seated bone pain, usually in the lower extremities, worsening with limb dependency and alleviated by leg elevation. Local tenderness may also be present. On conventional radiography, affected bones show symmetric unilamellated periosteal reaction, separated from the underlying bone by a radiolucent zone. Distal phalanges can exhibit bone proliferation and acro-osteolysis in more severe cases. In early stages, scintigraphy is more sensitive than conventional radiologic testing, with affected bones typically showing a pericortical radionuclide uptake line.


A later manifestation of this syndrome is oligoarthritis or polyarthritis, often symmetric, painful, and affecting knees, ankles, elbows, wrists, and metacarpophalangeal and proximal interphalangeal joints. The synovial fluid is characteristically noninflammatory.


According to its etiology, HOA can be classified as primary or secondary ( Box 2 ). Primary HOA is a hereditary disorder caused by a mutation in the gene that encodes 15-hydroxyprostaglandin dehydrogenase. This enzyme is essential for prostaglandin degradation. Because of the lack of this protein, these patients show high levels of prostaglandin E2 (PGE2) and develop the typical clinical features of HOA. The precise link between PGE2 and HOA has not been elucidated, and the role of prostaglandins in secondary HOA is unclear. Among secondary causes, lung cancer has the highest risk of HOA. Sridhar and colleagues reported a 29% prevalence of clubbing in patients with lung cancer. However, when applying bone scintigraphy changes as diagnostic criteria, the prevalence of HOA in patients with lung cancer is reduced to nearly 1%.


Oct 1, 2017 | Posted by in RHEUMATOLOGY | Comments Off on Rheumatic Manifestations of Primary and Metastatic Bone Tumors and Paraneoplastic Bone Disease
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