➢ Most patients with osseous sarcoidosis present in their early forties, with a higher proportion being African-American. Typical clinical presentation is characterized by localized pain and swelling, most commonly in the vertebrae and the small bones of the hands and feet; the most common associated extraosseous symptoms are lymphadenopathy and pulmonary involvement.
➢ Biopsies are mandatory for confirming a diagnosis of osseous sarcoidosis, but imaging modalities may be useful adjuncts. Radiographs may show lytic, sclerotic, or mixed patterns, and magnetic resonance imaging (MRI) studies may reveal typical T1 and T2 findings useful for monitoring lesion regression. Laboratory studies used in diagnosing or following extraosseous manifestations of sarcoidosis are not reliable for osseous sarcoidosis.
➢ Corticosteroids are the first line of treatment for symptomatic, nonstructural osseous sarcoidosis. For refractory cases, adjuvant therapies may need to be added, including immunomodulators (methotrexate or tumor necrosis factor [TNF] alpha inhibitors) and nonsteroidal anti-inflammatory drugs (NSAIDs). Indications for operative intervention include irreversible bone pain, hypercalcemia, and radiographic evidence of severe cortical destruction.
➢ For patients with isolated osseous lesions without a prior diagnosis of sarcoidosis, the orthopaedic surgeon should perform a thorough evaluation for extraosseous manifestations of sarcoidosis through a multimodal approach and should recommend vigilant follow-up.
Sarcoidosis, or sarcoid, is a multisystem disease affecting Americans at an incidence of ten to thirty-five per 100,000 and may involve any organ through the formation of characteristic noncaseating granulomas1,2. Although bilateral hilar lymphadenopathy, erythema nodosum, uveitis, and pulmonary infiltrates are most indicative of this disease, multiple studies have also shown the neurological, cardiac, and renal manifestations of sarcoidosis1,2. However, few studies have described the skeletal involvement of sarcoid.
Osseous sarcoidosis may be categorized into osseous or arthritic sarcoid3. Polyarthritis and arthralgia secondary to sarcoidosis are relatively common sequelae of the disease, with upwards of 25% of patients having articular involvement. In comparison, 3% to 13% of patients with sarcoid are reported to have osseous involvement, and the rarity of osseous disease is reflected by the overall state of the literature3. Besnier in 1889 described the first incident of osseous sarcoidosis in his description of a patient presenting with lupus pernio, an erythematous to violaceous cutaneous manifestation of sarcoidosis consisting of symmetrically distributed plaques and nodules4. Kreibich in 1904 reported cystic lesions in the phalanges of a patient presenting with lupus pernio5, and Jungling in 1928 reported similar cystic lesions in the phalanges of four patients with presumed sarcoidosis6. Although the first case report was published more than a century ago, the literature on osseous sarcoidosis has since remained fragmented and consists largely of case reports.
The purpose of this article was to review the presentation, diagnosis, and treatment of patients with osseous sarcoidosis. Through a multistep, systematic approach, we searched for all primary articles and case reports on the subject. Trends from randomized control trials, cohort studies, case series, and case reports are presented. Because the majority of the literature on osseous sarcoidosis is reported through individual case reports, we conducted subsequent analysis in which we pooled information from case reports to provide quantitative summaries of patient presentation, diagnosis, and treatment. We conclude by providing recommendations to the practicing orthopaedist on the workup and treatment of osseous sarcoidosis.
Methods: Search Strategy and Inclusion Criteria
Articles describing osseous sarcoidosis were identified with use of PubMed’s MeSH (Medical Subject Headings) term database. The research question was to determine the proper course for the practicing orthopaedic surgeon for the diagnosis, treatment, and management of patients with osseous manifestations of sarcoidosis without a prior diagnosis of sarcoidosis; to do this, we reviewed and compared all studies of patients with osseous sarcoid lesions, with and without a prior diagnosis of sarcoidosis. MeSH searches were done to identify osseous sarcoidosis, localized by anatomic site. The terms “sarcoid” and “sarcoidosis” in addition to a series of terms identifying anatomic sites were searched in PubMed’s MeSH term database. Please refer to the Appendix for a complete list of all MeSH headings, search terms, and operators, along with the corresponding number of articles found. Through these methods, 982 aggregate articles were found and were reviewed to determine if they met the inclusion criteria.
Any articles solely describing sarcoid involvement of the cranium or musculoskeletal manifestations of sarcoid without direct osseous involvement (i.e., tendon involvement or arthropathy) were excluded. In addition, only articles written in English were chosen, and any abstracts found without complete available articles were excluded. A total of 880 articles did not meet these inclusion criteria, leaving 102 unique articles from MeSH searches. The references of these 102 articles were reviewed for additional articles meeting initial inclusion criteria. An additional ninety-two articles were identified, resulting in 194 articles.
All 194 potential articles underwent a secondary screening by one reviewer (V.S.) on the basis of principles from Hayden et al. to determine whether high-quality data would be extractable for purposes of this review7. Case reports were included if they contained high-quality data in at least one of three categories: patient presentation, diagnostic workup, or treatment. Patient presentation consisted of information on age, sex, race, presenting symptoms, anatomic location, and any history of sarcoidosis. Diagnostic workup consisted of findings from radiographs, computed tomographic (CT) scans, magnetic resonance imaging (MRI) studies, whole-body bone scans, biopsies, laboratory studies, cultures or stains, and the diagnostic impact of these modalities in identifying osseous sarcoidosis. Finally, treatment consisted of various treatment modalities, any failed treatments, clinical and radiographic resolution of symptoms, and any relapses while on continued treatment. Please refer to Figure 1 for a visual, step-by-step delineation of this process with the specific enumeration of articles at each step.
A total of 113 case reports representing 118 cases and fifty-three additional primary articles were chosen for analysis after this secondary screen. After analyzing trends from these articles, summary tables based on the 118 cases were created on the basis of information extracted from these case reports (Table I, Table II, and Table III).
Most patients with osseous sarcoidosis are African-American adults, with diagnoses established during the fifth decade of life8-13. However, there is a substantial age distribution in the population that presents with this disease; for example, the incidence of osseous lesions in children with sarcoidosis is estimated to be as high as 29%8,14-16. Although 1% to 13% of patients with sarcoidosis may have cortical and bone marrow involvement, nearly 36% of patients with sarcoidosis reporting musculoskeletal pain will have osseous disease17-19. Thus, musculoskeletal symptoms suggest but are not a prerequisite for osseous disease in patients with sarcoidosis; up to 50% of patients with osseous sarcoid may be asymptomatic, particularly those patients with appendicular skeletal involvement11,12,17,20-48. Furthermore, autopsy studies suggest an even higher prevalence, as they have demonstrated osseous lesions in numerous deceased patients with sarcoidosis who had no clinical or radiographic symptoms24,34,49,50. Table I summarizes the patient presentation characteristics and findings in 118 cases of osseous sarcoid.
Patients with this disease tend to develop osseous involvement as a secondary manifestation of sarcoidosis, with 50% of patients demonstrating prior cutaneous involvement and more than 90% of patients having prior pulmonary involvement9,13,20-24,49,51-61. Lupus pernio and bilateral hilar and mediastinal lymphadenopathy in the setting of restrictive lung disease are the most commonly associated dermatologic and pulmonary manifestations of osseous sarcoidosis20,25-29,62-64. Furthermore, osseous manifestations are associated with long-standing sarcoidosis; some patients have prolonged asymptomatic periods as long as twenty years prior to presenting with symptoms related to osseous disease10,45,49. Some consider osseous involvement to be a negative prognostic sign, as there are mortality rates upwards of 20% in patients with osseous disease compared with approximately 5% in patients with non-osseous sarcoidosis; however, it is unclear whether osseous involvement is a proxy for disease duration11,12,45.
When considering osseous manifestations, the most common location of osseous sarcoidosis involves the small bones of the hands and feet, although this is debated in some studies11,12,17,20,25,26,29,31-33,35-38,42,50,65-67. Of these small bones, phalangeal involvement of the fingers is the most common, followed by carpal involvement, and, finally, phalangeal involvement of the feet53,68. Although the proximal phalanx is the most likely location for osseous sarcoid of the hand, the middle and distal phalanges can also be involved13,29,54,63,69-75. Sarcoid involvement of the feet may rarely also involve bones other than the phalanges, such as sarcoid infiltration of the calcaneus43,53. Patients with lesions in the small bones tend to present with a triad of pain, erythema, and localized swelling over the affected region10,31,58,63,69-71,74,76-80. However, this is by no means the only presentation of osseous sarcoid; some patients have alternate presentations, for example, pathological fractures manifested by stiffness and gross deformity29,81. Establishing the diagnosis of osseous sarcoid in these locations is difficult given the overall similarity in symptoms with arthritic sarcoidosis and other common phalangeal osseous lesions1,2,53,68.
Vertebral sarcoidosis is the second most common anatomic location of osseous sarcoid and is most often a secondary manifestation of the disease23,27,28. The majority of these patients have an underlying diagnosis of sarcoidosis and often have involvement of other bones as well23,34,38,55,82-84. Patients tend to be symptomatic and report diffuse nonradicular back pain exacerbated by physical activity and alleviated with rest. However, infiltration of vertebral facets can cause local inflammation around exiting nerve roots, resulting in reproducible radicular pain as a presenting symptom. In addition, patients with symptomatic presentations have tenderness to palpation over the affected vertebrae25,27,31,33,44,45,49,50,52,55,73,77,82,85-93. The vertebrae involved are most commonly in the thoracolumbar region; any part of the vertebrae proper may be affected, with vertebral body involvement more common in comparison with pedicle or facet infiltration26-28,30,31,34,49,94-100. Associated spinal cord lesions are rare, although patients may present with paraspinal masses due to a confluence of granulomas26-28,49,65,84,94,95,101. Despite these trends, cases in the literature illustrate the wide variety in presentation, including completely asymptomatic patients, patients presenting with vertebral crush fractures, and patients developing tetraplegia secondary to osseous involvement of the cervical spine, among others34,102,103. Because of the variety of presentations and overlapping symptoms with other conditions, only one of every three patients with vertebral sarcoidosis is appropriately diagnosed49,104.
In comparison with sarcoidosis of the hands, feet, and vertebral column, sarcoid lesions of the pelvis, ribs, and long bones are much rarer18,23,26,38,45-47,49,59,65,90,105,106. Presentation for these patients is variable, ranging from clinically asymptomatic to pain with palpation and/or movement of the affected bone14,18,20,28,42,51,59,70,72,81,87,95,106-113. Long bone involvement may have associated soft-tissue swelling and local effusions contributing to focal pain16. In addition, pathologic fractures may be a part of the initial presentation in long bones, with reported cases involving the ulna, femur, and ribs9,10,51,72,78,79,83,97,114,115. Some patients initially present with bilateral and symmetric long bone involvement, although overall this is a rare pattern for presentation10,18,22,51,114. Unlike phalangeal involvement, in which the entirety of the cortex may be diffusely affected, sarcoidosis has a propensity to affect only the distal regions of long bones18,72. Rib fractures due to sarcoid usually present with pain over the chest wall and may occur in isolation or in the presence of sarcoid infiltration in other bones15,20,44,82,97,102,106,116. Sarcoid infiltration of the sternum is even rarer still15,32,86,117,118.
Many modalities have been used to diagnose osseous sarcoidosis because of overlapping radiographic and/or clinical presentations with other diagnoses, including multiple myeloma, brucellosis, histoplasmosis, osteopetrosis, tuberculosis, lymphoma, pyogenic or fungal infections, Hodgkin lymphoma, leukemia, metastatic disease, osteomyelitis, histiocytosis, Paget disease, fibrous dysplasia, hyperparathyroidism, and enchondromas9,10,18,24,26,27,31,37-39,44,49,50,62,69,72,73,78,84,89,97,99,103,104,110,111,119-125. Furthermore, noncaseating granulomas indicative of sarcoid are found in carcinomatous lymph nodes associated with Hodgkin lymphoma and primary seminomas126. These overlapping similarities often result in extensive workups that delay definitive diagnosis and treatment41,73,82,96. Table II summarizes 118 cases providing information on diagnostic workup; this pooled information is further elaborated in the subsequent discussion and represents the current diagnostic trends in the literature.
On radiographs, osseous sarcoid appears as a lytic lesion, a sclerotic lesion, or a mixed lytic-sclerotic lesion with central osteolysis surrounded by a rim of sclerosis15,18,20,24,25,28,30,44,50,55,58,66,69,79,81,84,94,108,114,120,127. Lytic lesions are found in 83% of cases and are indicative of cysts in the cortex and medulla of the affected bone. These lesions are often described as “punched out” on radiographic reads and measure smaller than 5 mm in diameter71,97,105,116. Osteolytic lesions may also present with permeative or reticular patterns on radiographs as cortical bone is displaced by granulomas spreading through Haversian canals. Periosteal reactions in these settings are uncommon9,11,128. Sclerotic lesions are even rarer and may mimic metastases from a primary carcinoma25,28. These lesions tend to have an axial predominance with some cases describing patients presenting with entirely sclerotic lesions involving vertebrae38,46,59,129-131.
Anatomically, phalangeal lesions can present with either an osteolytic pattern due to the confluence of multiple cysts or a reticular pattern due to the destruction of osseous trabeculations by sarcoid20,25,26,29,31-33,35,37,38,42,50,65,67. However, long bone lesions are better defined and tend to display permeative destructive patterns10,17,28,42,46,48,105. Vertebral body involvement is often a mixed lytic-sclerotic pattern on radiographs with a rim of sclerosis around the central osteolysis15,25,26,48,104. Despite these general trends, overall, radiographs are insensitive and may miss many potential lesions. Moreover, the patterns seen are nonspecific and, on more sensitive imaging modalities, the same lesions may present with entirely different patterns67,111. Some authors have argued that certain radiographic signs (e.g., cortical thinning secondary to sarcoid infiltration) can lead to lesion detection earlier in the disease course, but we did not find this to be substantiated in the literature as a whole9,27,39,42,49,51,55,73,107,108.
MRI studies have been used extensively in the workup of sarcoidosis as diagnostic modalities and prognostic tools to monitor the disease course. Osseous lesions are hypointense on T1 signals and are either isointense or hyperintense on T2-weighted images, with enhancement of these lesions across all modalities with contrast10,23,25-27,31,35,37,55-57,62,65,68,73,86,87,94-96,102,104,106,109,111,120,132-136. Enhancement patterns fall into one of three types: peripheral inhomogeneous enhancement, dense homogenous enhancement, or mild homogenous enhancement that is isointense with surrounding bone marrow26,37,87,94,96,137. Although MRI can be quite sensitive, the T1 and T2 signal patterns are not very specific for identifying osseous sarcoid independently; rather, its utility lies in its ability to monitor radiographic treatment effect by following T1 and T2 signal changes during treatment17,27,36,37,40,42,52,55,62,73,77,87,90,94,136. However, some authors have argued otherwise. A 2012 study by Moore et al. investigated thirty-four patients who had either osseous sarcoidosis (n = 12) or osseous metastatic carcinoma (n = 22). They found that experienced musculoskeletal radiologists could differentiate osseous sarcoidosis from osseous metastasis with a specificity of 97.4%; however, the sensitivity for detecting osseous sarcoidosis lesions was only 46.3% in that study138.
Bone scans are a sensitive imaging modality used to identify missed or nondiagnostic lesions on radiographs. Upwards of 30% of lesions missed on radiographs may be detected with scintigraphy, and this sensitivity is increased in cases with long-standing disease or sclerotic lesions18,19,24,25,28,30,42,45,49,58,67,112,128,139. However, these gains are anatomically dependent, as the sensitivity for lesions in the hands and feet in bone scans is poor compared with that in radiographs120. Furthermore, this modality is limited in its ability to accurately localize lesions, which is particularly important with vertebral involvement, in which identifying specific levels are required prior to surgical treatment23,25-27,31,41,55,62,67,71,81,112,140,141. Scintigraphy is especially useful in finding potential biopsy sites, although some studies have supported the use of MRI and CT imaging for this purpose as well19,21,23,25,41,42,45,62,73,85,97,108,109,120.
Specific radioisotopes have specific utilities, and their use in diagnostic scintigraphy depends on the clinical context. Technetium-99m scans have demonstrated greater efficacy when compared with gallium-67 scans in detecting osseous lesions26,55,108,112,142. In contrast, gallium-67 scans demonstrate superior performance in identifying extraosseous lesions once osseous involvement has been confirmed25,43,55,58,86,111,140,143. Despite the sensitivity of scintigraphy for detecting osseous lesions, the low prevalence of osseous sarcoidosis limits the utility of scintigraphy as a screening tool144. Milman et al. investigated the use of routine scintigraphy in sixty-three patients with pulmonary sarcoidosis; of these sixty-three patients, only twenty-four (38.1%) showed minor bone abnormalities and only one had imaging indicative of true osseous sarcoid144.
Positive emission tomography-computed tomography (PET-CT) with fludeoxyglucose is a more sensitive modality than CT alone in detecting osseous lesions and is used to monitor disease progress in a similar way as MRI42,58,145. Additionally, PET-CT can be utilized after the diagnosis of osseous sarcoidosis is made to stage the extent of osseous involvement42,49,58. The radiographic finding of a lambda sign, a visualization of characteristic uptake of paratracheal and bilateral hilar lymph nodes, in a patient with osseous sarcoidosis suggests diffuse involvement with pulmonary lesions58. Macrophages that are responsible for granuloma formations are especially prone to fludeoxyglucose uptake because of increased metabolic activity under an inflammatory state17,42,146. However, this can also mimic radiographic patterns of cancer, leading to higher false diagnosis rates with PET-CT compared with CT42,58. In comparison with other sensitive modalities, studies have suggested that PET-CT with fludeoxyglucose is more sensitive than gallium-67 and technetium-99m scintigraphy; however, gallium-67 may be more sensitive for clinically occult lesions, particularly in soft tissues20,43,58.
Although osseous manifestations of sarcoidosis may be diagnosed clinically, the consensus in the literature is that biopsies of osseous lesions are required for definitive diagnosis of osseous sarcoid13,17-20,27,29,31,33,35,39-41,46,56,67,77,85,90,105,108,109,136,138,140,144,147. This is particularly true when the vertebrae are involved46,86. Although biopsies are the preferred method of disease diagnosis, alternative methods are described in the literature. For example, if clinical suspicion for osseous sarcoidosis is high in the setting of extraosseous lesions, biopsy of an extraosseous lesion may be used to make the diagnosis without a direct bone biopsy101,148. In addition, diagnosis may also be made through bone marrow aspiration with histological identification101,103,107,126,129,149.
Serology is often a useful primary or secondary diagnostic modality in detecting extraosseous sarcoidosis; however, those laboratory studies are unreliable for diagnosing osseous sarcoidosis. In particular, the literature reveals the difficulty in reproducing marker levels and finding reliable cutoffs for patients with osseous sarcoidosis presenting with very similar lesions57,147. In fact, some authors have suggested that routine metabolic, inflammatory, and blood panel values do not change in the setting of osseous sarcoidosis, but, in general, the literature has shown trends of increased serum angiotensin-converting enzyme values, anemia, leukopenia, elevated levels of inflammatory markers (erythrocyte serum rate and C-reactive protein), reduced serum albumin levels, hypercalcemia, elevated alkaline phosphatase levels, and hypergammaglobinemia19,25,33,53,55,78,105,147.
The current mainstay for treatment of symptomatic, nonstructural osseous sarcoidosis consists of a corticosteroid bolus followed by a tapered course9,10,15,18,21,25,27-29,31,32,35,36,39-41,43-45,49,59,60,62,65,70,76,80,82,97,101,106,107,112,132,133,137,140,147. Although corticosteroids are very effective in providing symptomatic relief, they are not disease-modifying drugs in the treatment of osseous sarcoidosis13. Some patients may progress into remission with continued therapy10,45,49, but several studies have shown persistent radiographic findings despite clinical resolution of symptoms with steroid treatment9,15,35,41,44,45,55,63,70,76,101,106,112,140,150. Some studies have shown spontaneous resolution of both clinical symptoms and radiographic findings in the absence of any intervention, although this is very much a minority finding24,58,105. To combat steroid-induced side effects such as osteoporosis, calcitonin and bisphosphonates may be added as adjuvant therapies13,49.
Table III summarizes ninety-five case reports providing information on treatment. Taken together, these cases reflect the current trends in the literature. The majority (74%) of cases were treated with corticosteroids, with almost 100% of cases reporting clinical improvement and 48% reporting radiographic improvement. Methotrexate, tumor necrosis factor (TNF)-alpha inhibitors, nonsteroidal anti-inflammatory drugs (NSAIDs), and bisphosphonates each were involved in <10% of cases, but all had 100% clinical resolution, especially in refractory cases in which corticosteroid treatments failed. Surgery was associated with a high recurrence rate (37%), reflecting the often-reported failure of surgery in cases with phalangeal involvement. Thirteen case reports did not employ any treatment but found 100% clinical resolution in symptoms.
A minority of osseous sarcoid cases may be refractory to steroid treatment9,15,53,76,135. Symptoms may persist, exacerbate, or become complicated by corticosteroid treatment, such as nonunion of pathological fractures51,83,114. In cases in which corticosteroids have been ineffective, multiple alternative therapies have been described, such as methotrexate and hydroxychloroquine10,32,40,53,77,132,135. In fact, in limited cases, methotrexate has shown equal efficacy when compared with corticosteroids as a primary treatment for osseous sarcoidosis77,151. In addition, TNF-alpha inhibitors have been used to treat refractory cases, targeting the macrophages responsible for granuloma formation30,152-154. Other treatments that have been utilized for symptom relief include colchicine, NSAIDs, or a combination of gabapentin and physical therapy56,77. Interestingly, according to one case report, itraconazole treatment of pulmonary aspergillosis was associated with the remission of osseous sarcoid lesions155. Although the literature has shown a diverse and progressing range of medical treatments, most of these treatments are in their infancy, and the initial means for symptom relief should be approached through corticosteroid treatment.
Operative intervention is saved for cases with irreversible bone pain, hypercalcemia, or radiographic evidence of severe cortical destruction9,25,41,49. Operative correction of phalangeal sarcoidosis consists of curettage and reduction, whereas pathological fractures in the long bones are treated with excision followed by osteosynthetic reconstruction with grafts10,51,72,79,83. Hand fractures secondary to sarcoid generally require operative correction given poor healing and response to corticosteroids, although there are reports of hand fractures secondary to sarcoid involvement healing without surgical intervention9,54,70,78. However, even with surgical intervention, failure is common in cases of phalangeal sarcoidosis9,54,70,78. Most cases of vertebral involvement require spinal fusion, especially in cases with spinal instability and neurological involvement20,50,102.
Conclusion: Recommendations for Isolated Osseous Sarcoidosis
The state of the literature advises a broad, open-ended approach to the patient with a prior history of sarcoidosis presenting with symptomatic bone pain. Because of its sensitivity and its utility in monitoring osseous lesions, MRI is a practical initial study. Scintigraphy may be used in addition to confirm uptake in osseous lesions and stage the extent of lesions. However, orthopaedists must have low thresholds to depend on biopsies to make a definitive diagnosis as early biopsies decrease workup time and avoid unnecessary tests that are lower yield. For the treatment of osseous sarcoid, the literature has shown that a course of tapered corticosteroids is an efficacious treatment for symptomatic cases; operative treatment is indicated for patients with refractory pain, hypercalcemia, or severe cortical destruction and particularly for patients presenting with phalangeal lesions, spinal instability, or long bone fractures.
A challenge to the orthopaedic surgeon nevertheless remains in the management of patients who present with isolated osseous lesions without prior diagnoses of sarcoidosis. On the basis of our review, we suggest that these patients should undergo a thorough evaluation including chest radiographs for bilateral hilar lymphadenopathy or interstitial lung disease suggestive of pulmonary sarcoid. Other manifestations of sarcoidosis (such as uveitis, anemia, lymphopenia, anemia, subcutaneous nodules, and/or peripheral nerve involvement) should be assessed through routine laboratory and physical examinations. Biopsies of extraosseous lesions should be taken for confirmation of systemic sarcoid. Treatment should be directed directly at osseous lesions as clinically indicated (i.e., surgery for spinal instability or clinically symptomatic disease or fracture) in conjunction with systemic treatment through tapered corticosteroids.
As evidenced by the frequency of extraosseous manifestations in patients with osseous sarcoidosis and the associated diagnostic challenges, a multispecialty approach for acute treatment and long-term management is essential, involving the orthopaedist, the primary care physician, and necessary specialists. Appropriate corticosteroid dosing should cover extraosseous lesions as well as clinically silent osseous lesions. Follow-up for surgical patients should be more vigilant and should involve periodic radiographs of the affected bone and chest to monitor the disease course. Repeat scintigraphy and MRI should be regularly conducted to detect silent lesions. Patients should undergo follow-up for at least one year after clinical and radiographic resolution of symptoms per the standard advised by the current literature.
In spite of these recommendations, the state of the literature remains incomplete for osseous sarcoidosis, and additional high-quality studies are needed. Nevertheless, through our review and case report analysis, trends among case reports reflect patterns of the literature and may serve as a useful guide to diagnostic and treatment approaches in the interim.
The MeSH terms and identified articles are shown in Table A1.
Source of Funding: There was no external source of funding for this study.
Investigation performed at Vanderbilt Orthopaedic Oncology, Nashville, Tennessee
Disclosure: None of the authors received payments or services, either directly or indirectly (i.e., via his or her institution), from a third party in support of any aspect of this work. None of the authors, or their institution(s), have had any financial relationship, in the thirty-six months prior to submission of this work, with any entity in the biomedical arena that could be perceived to influence or have the potential to influence what is written in this work. Also, no author has had any other relationships, or has engaged in any other activities, that could be perceived to influence or have the potential to influence what is written in this work. The complete Disclosures of Potential Conflicts of Interest submitted by authors are always provided with the online version of the article.
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