The Open Orthopaedics Journal




ISSN: 1874-3250 ― Volume 13, 2019

Kümmell’s Disease: Clarifying the Mechanisms and Patients’ Inclusion Criteria



Charalampos Matzaroglou 1, Christos S Georgiou 1, Andreas Panagopoulos*, 1, Kostantinos Assimakopoulos 2, Hans J Wilke 3, Bjoern Habermann 4, George Panos 5, Konstantinos Kafchitsas 5
1 Department of Orthopaedic Surgery, University of Patras, Greece
2 Department of Psychiatry, University of Patras, Greece
3 Institute for Orthopedic Research and Biomechanics, University of Ulm, Germany
4 Department of Orthopaedics and Traumatology, Johannes Gutenberg University, Mainz, Germany
5 Department of Internal Medicine, University of Patras, Greece

Abstract

The three major causes of vertebral body collapse include infection, malignant neoplasia, and trauma and it may be difficult to distinguish between them, particularly in the presence of severe osteoporosis. In 1891, however, Dr Hermann Kümmell, further added another possibility of vertebral body crush; the delayed posttraumatic collapse. As originally described, this rare clinical entity includes patients, who after a trivial trauma and an asymptomatic clinical course they develop a progressive vertebral body collapse and a painful kyphosis. Although more than a century has passed from its initial description, only few cases have been reported in the literature, whereas the main pathologic eliciting event is still under investigation. As a consequence, great controversy exists regarding the discrete features of the clinical course, its radiographic appearance and the histopathological findings. To explain the time lag between the initial trauma and the occurrence of the vertebral collapse, the hypothesis of ischemic necrosis was advanced. Equation of Kümmell’s disease with vertebral osteonecrosis, however, has wrongly led many authors to report cases of Kümmell’s disease, even in the absence of history of spinal trauma. On the other hand, high coincidence of vertebral osteonecrosis and the pathognomonic radiographic finding of intravertebral vacuum cleft, has further added to the confusion. In this review we present an overview of the literature on Kümmell’s disease, focusing on the different proposed eliciting mechanisms. We also highlight controversial subjects on clinical course, diagnosis and treatment of this entity, in an attempt to further clarify patients’ inclusion criteria.

Keywords: Intravertebral vacuum cleft, Kümmell’s disease, research review, vertebral body collapse, vertebral osteonecrosis..


Article Information


Identifiers and Pagination:

Year: 2014
Volume: 8
First Page: 288
Last Page: 297
Publisher Id: TOORTHJ-8-288
DOI: 10.2174/1874325001408010288

Article History:

Received Date: 10/1/2014
Revision Received Date: 31/7/2014
Acceptance Date: 11/8/2014
Electronic publication date: 15 /9/2014
Collection year: 2014

Article Metrics:

CrossRef Citations:
0

Total Statistics:

Full-Text HTML Views: 2147
Abstract HTML Views: 1163
PDF Downloads: 266
Total Views/Downloads: 3576

Unique Statistics:

Full-Text HTML Views: 953
Abstract HTML Views: 618
PDF Downloads: 183
Total Views/Downloads: 1754
Geographical View

© Matzaroglou et al.; Licensee Bentham Open.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.5/) which permits unrestrictive use, distribution, and reproduction in any medium, provided the original work is properly cited.


* Address correspondence to this author at the University of Patras, Department of Orthopaedic Surgery, University Hospital of Patras, Rio, T.K 26504, Greece; Tel: +30 2613603883; E-mail andpan21@gmail.com




INTRODUCTION

Delayed posttraumatic vertebral body collapse, namely Kümmell’s disease (KD), is a rarely reported and poorly documented phenomenon. This eponymous diagnosis represents a posttraumatic vertebral fracture, which is initially asymptomatic, having also unremarkable radiography that gradually become symptomatic and result into vertebral body collapse (VBC) [1Kümmel H. Ueber die traumatischen Erkrankungen der Wirbelsaüle. Dtsch Med Wochenschr 1895; 21: 180-81.]. The lack of adequate imaging and histologic examination, however, between the traumatic event and the eventual vertebral collapse, dissemble the true underlying pathological process. The delayed fashion of the VBC is generally explained by the prevailing hypothesis of ischemic necrosis [2Young WF, Brown D, Kendler A , et al. Delayed post-traumatic osteonecrosis of a vertebral body (Kümmell’s disease). Acta Orthop Belg 2002; 68: 13-19.]. This association of KD with osteonecrosis, however, and further connection with specific radiographic findings (intraverte-bral vacuum cleft) has led many authors in wrongly reporting patients with other pathologies, as having KD [3Swartz K, Fee D. Kümmell's disease a case report and literature review. Spine (Phila Pa 1976) 2008; 33: E152-5., 4Freedman BA, Heller JG. Kummell Disease A Not-So-Rare Complication of Osteoporotic Vertebral Compression Fractures. J Am Board Fam Med 2009; 22: 75-8.]. On the contrary, KD originally involves patients, without any predisposing disorder for ischemic necrosis, other than trauma [5Steel HH. Kümmell’s disease. Am J Surg 1951; 81: 161-7.]. Intravertebral vacuum cleft (IVC), is usually present in KD, but is not exclusive to it [6Mirovsky Y, Anekstein Y, Shalmon E, Peer A. Vacuum clefts of the vertebral bodies. AJNR Am J Neuroradiol 2005; 26: 1634-40., 7Kumpan W, Salomonowitz E, Seidi G, Wittich GR. The intravertebral vacuum phenomenon. Skeletal Radiol 1986; 15: 444-7.].

In this report we review the clinical features, diagnostic tools and treatment options of this interesting disorder. We also discuss current concepts on the pathophysiology of delayed posttraumatic VBC. Finally, in an attempt to discern causative factors, we review the radiologic controversy of compression fractures with an intravertebral vacuum cleft.

HISTORICAL PREVIEW

In 1891 a German surgeon, Dr Hermann Kümmell described a series of 5 patients, presenting with a rare clinical scenario: they sustained a minor spinal trauma, then remained essentially asymptomatic for a period of months or, even, years and, eventually, developed a progressive, painful kyphosis at the lower thoracic or upper lumbar regions [1Kümmel H. Ueber die traumatischen Erkrankungen der Wirbelsaüle. Dtsch Med Wochenschr 1895; 21: 180-81., 5Steel HH. Kümmell’s disease. Am J Surg 1951; 81: 161-7.]. Carl Schulz, a student of Kümmell, first assigned his teacher’s name to this condition in 1911. At about the same time with Kümmell, Verneuil (1823-1895), a French surgeon, described a similar condition. In some instances the syndrome has been referred to as “Kümmell-Verneuil disease” [2Young WF, Brown D, Kendler A , et al. Delayed post-traumatic osteonecrosis of a vertebral body (Kümmell’s disease). Acta Orthop Belg 2002; 68: 13-19.]. For a period of 35 years, after the original dissertation, KD was struggling for acceptance. With the advent of x-ray, it was recognized, that kyphosis was the result of a delayed VBC. Subsequent authors, however, called into question the existence of the delayed collapse; they thought that the fracture was missed initially due to the poor quality of the radiographic studies. With the papers of Rigler (1931) and Steel (1951) was clearly documented that VBC appears only on delayed films and that initial x-rays are usually normal [8Rigler L. Kummell’s disease with report of a roentgenologically proved case. Am J Roentgenol 1931; 35: 749-53., 5Steel HH. Kümmell’s disease. Am J Surg 1951; 81: 161-7.].

The literature on the subject is limited, but recently a renewed interest has been developed. Only 9 cases of KD have been documented, in a total of 14 reports published, since the initial description in 1891 (Table 1).

Table 1

Cases of Kümmell’s disease reported since 1950.




CLINICAL FEATURES

Steel in 1951 divided the clinical course of KD into five stages [5Steel HH. Kümmell’s disease. Am J Surg 1951; 81: 161-7.]. The first stage (initial injury), can be varied in severity and mechanism, while lateral roentgenograms are necessarily negative. The second stage (post-traumatic period) follows with minor symptoms and no limitation in activity. The third stage (latent interval) of relative well-being precedes the onset of progressive disability and usually lasts weeks or months, whereon the patient is not incapacitated. In the different clinical reports of KD, this period varies between 4 weeks and 1 year [2Young WF, Brown D, Kendler A , et al. Delayed post-traumatic osteonecrosis of a vertebral body (Kümmell’s disease). Acta Orthop Belg 2002; 68: 13-19., 3Swartz K, Fee D. Kümmell's disease a case report and literature review. Spine (Phila Pa 1976) 2008; 33: E152-5., 5Steel HH. Kümmell’s disease. Am J Surg 1951; 81: 161-7., 9Brower AC, Downey EF Jr. Kümmell disease report of a case with serial radiographs. Radiology 1981; 141: 363-4.-18Fabbriciani G, Pirro M, Floridi P , et al. Osteoanabolic therapy a non-surgical option of treatment for Kümmell's disease?. Rheumatol Int 2012; 32: 1371-4.]. However, in three cases no asymptomatic interval was observed [10Hermann G, Goldblatt J, Desnick RJ. Kummell disease delayed collapse of the traumatised spine in a patient with Gaucher type 1 disease. Br J Radiol 1984; 57: 833., 14Maheshwari PR, Nagar AM, Prasad SS , et al. Avascular necrosis of spine a rare appearance. Spine 2004; 29: E119-E122., 18Fabbriciani G, Pirro M, Floridi P , et al. Osteoanabolic therapy a non-surgical option of treatment for Kümmell's disease?. Rheumatol Int 2012; 32: 1371-4.]. In the fourth stage (the recrudescent stage), the patient complains for persistent, localized pain, which progressively tends to become more peripheral with root pain. In the last stage (terminal stage), a permanent kyphosis is formed with or without progressive pressure on roots or spinal cord. The complication of greatest detriment is neurologic compromise, although this finding is rare. However, neurologic findings are more commonly a result of vertebral compression after osteonecrosis, rather simple osteoporotic fractures [12Osterhouse MD, Kettner NW. Delayed posttraumatic vertebral collapse with intravertebral vacuum cleft. J Manipulative Physiol Ther 2002; 25: 270-5.]. KD occurs typically in middle-aged and elderly patients with a slight male predominance [5Steel HH. Kümmell’s disease. Am J Surg 1951; 81: 161-7.], although there are few reports in younger individuals [5Steel HH. Kümmell’s disease. Am J Surg 1951; 81: 161-7., 17Matzaroglou C, Georgiou CS, Assimakopoulos K , et al. Kümmell' s disease A rare spine entity in a young adult. Hell J Nucl Med 2010; 13: 52-5.]. Multiple vertebrae may be affected [3Swartz K, Fee D. Kümmell's disease a case report and literature review. Spine (Phila Pa 1976) 2008; 33: E152-5., 14Maheshwari PR, Nagar AM, Prasad SS , et al. Avascular necrosis of spine a rare appearance. Spine 2004; 29: E119-E122.] but a single vertebral involvement is the most common scenario.

Although more than a century has passed since original description of KD, only few cases that fulfill Kümmell’s criteria have been described in the literature (Table 1). They, necessarily, involve patients presented with a delayed VBC and vertebral osteonecrosis after a minor spine injury. Trauma, however, can vary in severity and can be of different nature. In a healthy individual, a minor spinal trauma it may not be noticed or documented at all. The patient may be misdiagnosed with idiopathic avascular necrosis of the vertebral body. This entity has been separately reported [19Chou LH, Knight RQ. Idiopathic avascular necrosis of a vertebral body. Case report and literature review Spine 1997; 22: 1928,-32.]. Originally Kümmell, in his series, has described a hypeflexion pattern of spinal injury, after a fall [1Kümmel H. Ueber die traumatischen Erkrankungen der Wirbelsaüle. Dtsch Med Wochenschr 1895; 21: 180-81.]. Most of the cases reported, correspond to this pattern [3Swartz K, Fee D. Kümmell's disease a case report and literature review. Spine (Phila Pa 1976) 2008; 33: E152-5., 5Steel HH. Kümmell’s disease. Am J Surg 1951; 81: 161-7., 9Brower AC, Downey EF Jr. Kümmell disease report of a case with serial radiographs. Radiology 1981; 141: 363-4., 12Osterhouse MD, Kettner NW. Delayed posttraumatic vertebral collapse with intravertebral vacuum cleft. J Manipulative Physiol Ther 2002; 25: 270-5.-15Ma R, Chow R, Shen FH. Kummell's disease delayed post-traumatic osteonecrosis of the vertebral body. Eur Spine J 2010; 19: 1065-70.] or implicate a direct force [5Steel HH. Kümmell’s disease. Am J Surg 1951; 81: 161-7., 10Hermann G, Goldblatt J, Desnick RJ. Kummell disease delayed collapse of the traumatised spine in a patient with Gaucher type 1 disease. Br J Radiol 1984; 57: 833.] applied to the spinal column. Van Eenenaam and el-Khoury, on the other hand, reported a case with symptomatic onset of KD due to heavy object lifting [11Van Eenenaam DP, el-Khoury GY. Delayed post-traumatic vertebral collapse (Kümmell’s disease): case report with serial radiographs, computed tomographic scans, and bone scans. Spine 1993; 18: 1236-41.]. This patient was under steroidal therapy for temporal arteritis, both known risk factors for avascular necrosis (Table 2). Young et al. described another patient, with diabetes mellitus and with symptoms triggered, after shoveling snow [2Young WF, Brown D, Kendler A , et al. Delayed post-traumatic osteonecrosis of a vertebral body (Kümmell’s disease). Acta Orthop Belg 2002; 68: 13-19.]. These two reports attribute VBC not to direct or indirect trauma, but to hyperfexion loading of the spine. In another report [17Matzaroglou C, Georgiou CS, Assimakopoulos K , et al. Kümmell' s disease A rare spine entity in a young adult. Hell J Nucl Med 2010; 13: 52-5.] repetitive weight-lifting and, thus, hyperflexion spinal strain was the causative pattern for KD. Interestingly, this particular patient had no predisposing factors for avascular necrosis. These factors in general can enhance trauma’s effect in vascular supply. However, with varied mechanisms, they can independently trigger avascular osteonecrosis.

Table 2

Risk factors for avascular vertebral osteonecrosis.




RISK FACTORS FOR AVASCULAR OSTEONECROSIS

Avascular necrosis of the vertebral body is usually associated with a known predisposing factor and these cases, without history of spinal trauma, should not be referred as KD. Systemic steroid therapy is considered a consequential predisposing factor. Chronic administration of corticosteroids stimulates hyperinsulinemia, which increases intramedullary fat deposition, resulting in crushing of the intramedullary vessels and vascular disruption of medullary arterioles. Additionally, chronic microfractures of secondary osteopenia and the effect of fatty microemboli are other potential eliciting mechanisms of avascular osteonecrosis and subsequent VBC [19Chou LH, Knight RQ. Idiopathic avascular necrosis of a vertebral body. Case report and literature review Spine 1997; 22: 1928,-32.]. Idiopathic osteoporosis, on the other hand, can lead to multiple vertebral compression fractures due to bone structural weakness, but can be complicated also with ischemic osteonecrosis [4Freedman BA, Heller JG. Kummell Disease A Not-So-Rare Complication of Osteoporotic Vertebral Compression Fractures. J Am Board Fam Med 2009; 22: 75-8.]. Other predisposing factors include malignancy, infection, radiotherapy, atherosclerosis, diabetes, cirrhosis, vasculitis and pancreatitis [19Chou LH, Knight RQ. Idiopathic avascular necrosis of a vertebral body. Case report and literature review Spine 1997; 22: 1928,-32., 20Allen BL Jr, Jinkins WJ 3rd. Vertebral osteonecrosis associated with pancreatitis in a child.A case report. J Bone Joint Surg Am 1978; 60: 985-7.]. Hemoglobinopathies, such as sickle cell disease, can result in vascular occlusion and vertebral body ischemia [14Maheshwari PR, Nagar AM, Prasad SS , et al. Avascular necrosis of spine a rare appearance. Spine 2004; 29: E119-E122.]. Cushing’s disorder and alcoholism are well-known risk factors for avascular necrosis, probably because of the presence of microscopic fat emboli in the end-arteries [14Maheshwari PR, Nagar AM, Prasad SS , et al. Avascular necrosis of spine a rare appearance. Spine 2004; 29: E119-E122.]. Finally, Ito et al. reported a case of vertebral body osteonecrosis in a patient with sarcoidosis [21Ito M, Motomiya M, Abumi K , et al. Vertebral osteonecrosis associated with sarcoidosis.Case report. J Neurosurg Spine 2005; 2: 222-5.]. The typical noncaseating granuloma in the biopsy specimen of the collapsed vertebra wasn’t observed.

HISTOPATHOLOGY AND PATHOPHYSIOLOGY

Few authors have been reported upon pathologic examination of vertebrae, which had undergone delayed posttraumatic VBC. Schmorl, in 1926, was the first to present autopsy material supporting Kümmell’s hypothesis. The spongiosa of the examined vertebral body was destroyed, resulting in VBC, but no underlying pathological process was found [22Schmorl G, Junghanns H, Eds. The Human Spine in Health and Disease. New York : Grune & Stratton 1971; 167: pp. 268-96.]. Cardis et al. two years later described the histopathologic appearance of KD, after pathologic examination of a collapsed L2 vertebral body. The vertebral body was wedge shaped and showed marked atrophy of the bony framework and multiple hemorrhages in the spongiosa on microscopic examination [23Cardis J, Walker GF, Olver RH. Kummell’s disease. Br J Surg 1928; 15: 616-25.]. Kux described “multiple microscopic fractures”, which resulted in the delayed VBC [24Kux E. Zur Histopathologie der posttraumatischen (Kümmellschen) Wirbelerkrankung. Arch Orthop 1933; 34: 18-23.].

According to Sweet and Madewell [25Sweet DE, Madewell JE, Resnick DK, Niwayama E. Pathogenesis of osteonecrosis. In Diagnosis of bone and joint disorders Philadelphia Saunders 1981; 2780-831.], the area of avascular necrosis has four concentric zones: a central zone of cell death, a zone of ischemic injury, a zone of active hyperemia, and a zone of normal tissue peripherally. There is greater activity in the ischemic and hyperemic zones in the early phases, and these zones are subsequently replaced by new bone or fibrous tissue in the later phases. Thus, in the early stages of avascular necrosis, inflammatory cells and fluid are the major findings, while new bone and fibrous tissue predominate in the later stages [26Naul LG, Peet GJ, Maupin WB. Avascular necrosis of the vertebral body MR imaging. Radiology 1989; 172: 219-22.]. This was confirmed by the only clinical case in the literature reported positive biopsies [3Swartz K, Fee D. Kümmell's disease a case report and literature review. Spine (Phila Pa 1976) 2008; 33: E152-5.]; initial evidence of osteonecrosis was followed by later findings of apparent bony remodeling and medullary fibrosis. Since most patients are middle aged or elderly, degenerative changes and osteoporosis are likely to be universal findings [2Young WF, Brown D, Kendler A , et al. Delayed post-traumatic osteonecrosis of a vertebral body (Kümmell’s disease). Acta Orthop Belg 2002; 68: 13-19.]. Interestingly, inflammatory changes and paravertebral fluid collections [3Swartz K, Fee D. Kümmell's disease a case report and literature review. Spine (Phila Pa 1976) 2008; 33: E152-5.] or soft tissue prominence [11Van Eenenaam DP, el-Khoury GY. Delayed post-traumatic vertebral collapse (Kümmell’s disease): case report with serial radiographs, computed tomographic scans, and bone scans. Spine 1993; 18: 1236-41.] have, also, been described. Histopathologic signs of osteonecrosis were present in 5 cases sampled for biopsy in the contemporary literature [2Young WF, Brown D, Kendler A , et al. Delayed post-traumatic osteonecrosis of a vertebral body (Kümmell’s disease). Acta Orthop Belg 2002; 68: 13-19., 3Swartz K, Fee D. Kümmell's disease a case report and literature review. Spine (Phila Pa 1976) 2008; 33: E152-5., 13Kapoor V, Theruvil B, Foria V , et al. Vertebral collapse in a 71-year-old woman. Clin Orthop Relat Res 2004; 423: 291-8., 14Maheshwari PR, Nagar AM, Prasad SS , et al. Avascular necrosis of spine a rare appearance. Spine 2004; 29: E119-E122., 17Matzaroglou C, Georgiou CS, Assimakopoulos K , et al. Kümmell' s disease A rare spine entity in a young adult. Hell J Nucl Med 2010; 13: 52-5.]. In three of them signs of new bone formation and marrow fibrosis consistent with bone repair coexisted [2Young WF, Brown D, Kendler A , et al. Delayed post-traumatic osteonecrosis of a vertebral body (Kümmell’s disease). Acta Orthop Belg 2002; 68: 13-19., 3Swartz K, Fee D. Kümmell's disease a case report and literature review. Spine (Phila Pa 1976) 2008; 33: E152-5., 14Maheshwari PR, Nagar AM, Prasad SS , et al. Avascular necrosis of spine a rare appearance. Spine 2004; 29: E119-E122.].

As far as the pathogenesis of KD is concerned, there is still no unanimous consensus. Originally Kümmell considered the delayed VBC, a ‘rarefying osteitis’ of inflammatory origin, following a nutritional disorder [1Kümmel H. Ueber die traumatischen Erkrankungen der Wirbelsaüle. Dtsch Med Wochenschr 1895; 21: 180-81.]. He later amended his views; he suggested that the damage to the bone was not the result of inflammation, but always inflicted by the original injury, though not always demonstrable [27Bhalla S, Reinus WR. The linear intravertebral vacuum a sign of benign vertebral collapse. AJR Am J Roentgenol 1998; 170: 1563-9.]. Steel [5Steel HH. Kümmell’s disease. Am J Surg 1951; 81: 161-7.] ascribed KD to multiple, minute trauma of osseus and ligamentous structures, which result in fine cracks and microhemorrhages; these minute ruptures in the spongiosa lead to osteonecrosis. The VBC could be the result of an early strain applied to a deficient material [3Swartz K, Fee D. Kümmell's disease a case report and literature review. Spine (Phila Pa 1976) 2008; 33: E152-5.,5Steel HH. Kümmell’s disease. Am J Surg 1951; 81: 161-7.]. Benedek and Nicholas [28Benedek TG, Nicholas JJ. Delayed traumatic vertebral body compression fracture. II.; Pathologic features. Semin Arthritis Rheum 1981; 10: 271-7.] suggested that the initial trauma cause fine trabecular fractures, unapparent on radiographic imaging; healing will normally occur unless some form of interference is present which can be intrinsic (insufficient vertebral blood supply or herniated Schmorl's nodes) or extrinsic (normal weight-bearing on a weakened bone). Due to this impaired healing process, a vicious circle is developing, leading eventually to the VBC. Another hypothesis, based on spinal angiographies, attributes these structural changes to vascular insufficiency, since the anterior third of the vertebral body is a vascular border zone (“watershed”). The dorsum of the vertebral body receives collateral blood flow while the ventral aspect does not; thus is amenable for ischemic necrosis [3Swartz K, Fee D. Kümmell's disease a case report and literature review. Spine (Phila Pa 1976) 2008; 33: E152-5., 29Stojanovic J, Kovac V. Diagnosis of ischemic vertebral collapse using selective spinal angiography. Rofo 1981; 135: 326-9.]. Schmorl and Junghanns proposed the concept of osteonecrosis after minute ruptures and hemorrhage into the spongiosa [30Schmorl G, Junghanns H. The human spine in health and disease. 1971; 141.].

Currently, avascular osteonecrosis is the prevailing hypothesis for the interpretation of the delayed posttraumatic VBC [2Young WF, Brown D, Kendler A , et al. Delayed post-traumatic osteonecrosis of a vertebral body (Kümmell’s disease). Acta Orthop Belg 2002; 68: 13-19.]. The hypothesis of an ischemic necrosis is generally advanced to explain the time lag between the traumatic event and the eventual VBC. This hypothesis was supported by the following arguments: i) findings of bone necrosis was found in the cases sampled for biopsy [2Young WF, Brown D, Kendler A , et al. Delayed post-traumatic osteonecrosis of a vertebral body (Kümmell’s disease). Acta Orthop Belg 2002; 68: 13-19., 3Swartz K, Fee D. Kümmell's disease a case report and literature review. Spine (Phila Pa 1976) 2008; 33: E152-5., 13Kapoor V, Theruvil B, Foria V , et al. Vertebral collapse in a 71-year-old woman. Clin Orthop Relat Res 2004; 423: 291-8., 14Maheshwari PR, Nagar AM, Prasad SS , et al. Avascular necrosis of spine a rare appearance. Spine 2004; 29: E119-E122., 17Matzaroglou C, Georgiou CS, Assimakopoulos K , et al. Kümmell' s disease A rare spine entity in a young adult. Hell J Nucl Med 2010; 13: 52-5.] ii) a history of steroid treatment or alcohol abuse, which are well known risk factors of avascular necrosis of the femoral head, was found in some patients with KD [9Brower AC, Downey EF Jr. Kümmell disease report of a case with serial radiographs. Radiology 1981; 141: 363-4.-12Osterhouse MD, Kettner NW. Delayed posttraumatic vertebral collapse with intravertebral vacuum cleft. J Manipulative Physiol Ther 2002; 25: 270-5.] iii) coexistence of avascular necrosis of the femoral head and vertebral osteonecrosis was, also, found in some patients [31Lafforgue P, Chagnaud C, Daumen-Legré V , et al. The intravertebral vacuum phenomenon ("vertebral osteonecrosis").Migration of intradiscal gas in a fractured vertebral body Spine (Phila Pa 1976) 1997; 22: 1885-91., 32Queinnec JY, De Bray JM, Audran M, Renier JC. Ostéonécrose vertébrale À propos de 3 cas dont 1 compliqué d'une compression médullaire et 2 associés à une autre localisation nécrotique. Revue du Rhumatisme 1985; 52: 1-5.] and iv) some radiographic analogies between the crescent sign of avascular necrosis of the femoral head and the IVC has been pointed out [33Maldague BE, Noel HM, Malghem JJ. The intravertebral vacuum cleft a sign of ischemic vertebral collapse. Radiology 1978; 129: 23-9.]. Injury seems to trigger vascular supply disruption [5Steel HH. Kümmell’s disease. Am J Surg 1951; 81: 161-7.]. However, all these arguments are a subject for discussion. The association of avascular necrosis of the femoral head and ischemic vertebral collapse is not strongly enough supported, as only three cases have been reported in the literature [31Lafforgue P, Chagnaud C, Daumen-Legré V , et al. The intravertebral vacuum phenomenon ("vertebral osteonecrosis").Migration of intradiscal gas in a fractured vertebral body Spine (Phila Pa 1976) 1997; 22: 1885-91.-33Maldague BE, Noel HM, Malghem JJ. The intravertebral vacuum cleft a sign of ischemic vertebral collapse. Radiology 1978; 129: 23-9.]. Furthermore, contrary to vertebral osteonecrosis, spontaneous intraosseous gas formation is not observed in cases of avascular necrosis of the femoral head [33Maldague BE, Noel HM, Malghem JJ. The intravertebral vacuum cleft a sign of ischemic vertebral collapse. Radiology 1978; 129: 23-9.]. Pathological findings are also questionable; histopathologic findings of vertebral osteonecrosis might simply be the consequence of a severe vertebral crush fracture [33Maldague BE, Noel HM, Malghem JJ. The intravertebral vacuum cleft a sign of ischemic vertebral collapse. Radiology 1978; 129: 23-9.]. It is not clear, if ischemic osteonecrosis or the vertebral collapse is the first step in the sequence [29Stojanovic J, Kovac V. Diagnosis of ischemic vertebral collapse using selective spinal angiography. Rofo 1981; 135: 326-9., 34Libicher M, Appelt A, Berger I , et al. The intravertebral vacuum phenomenon as specific sign of osteonecrosis in vertebral compression fractures results from a radiological and histological study. Eur Radiol 2007; 17: 2248-52.]. We found no imaging or histological investigations focusing on the time between the traumatic event and eventual VBC, that could confirmed the ischemic theory. Avascular necrosis as the main pathologic eliciting event still remains hypothetical [33Maldague BE, Noel HM, Malghem JJ. The intravertebral vacuum cleft a sign of ischemic vertebral collapse. Radiology 1978; 129: 23-9.].

DIAGNOSIS

Kümmell’s disease remains a diagnosis of exclusion. Once VBC has been established, a thorough history and general medical evaluation must be obtained [3Swartz K, Fee D. Kümmell's disease a case report and literature review. Spine (Phila Pa 1976) 2008; 33: E152-5.]. Because VBC can be seen in a variety of other conditions including neoplasm, infection, osteoporosis and predisposing factors to osteonecrosis, laboratory testing should include: complete blood count, complete metabolic panel and especially bone (alkaline phosphatase, serum Ca and P) and liver tests (transaminases, total and direct bilirubin, albumin), erythrocyte sedimentation rate, level of C-reactive protein, tumor markers (CEA, aFP, βhCG, PSA, CA 19-9) and serum electrophoresis. To exclude spinal tuberculosis, a chest X-ray and a skin test are necessary. MRI studies of the spinal column with and without contrast enhancement should always be performed. The MR imaging appearance of avascular necrosis differs from the typical findings associated with malignant neoplasm or infection of the vertebral body [25Sweet DE, Madewell JE, Resnick DK, Niwayama E. Pathogenesis of osteonecrosis. In Diagnosis of bone and joint disorders Philadelphia Saunders 1981; 2780-831.]. Malignant neoplasms have, also, decreased signal intensity on T1-weighted images and increased signal intensity on T2-weighted images. However the high signal intensity on T2-weighted images is more diffuse, as paravertebral soft tissue involvement may occur [26Naul LG, Peet GJ, Maupin WB. Avascular necrosis of the vertebral body MR imaging. Radiology 1989; 172: 219-22.].

There is no pathognomonic radiographic finding for the diagnosis of KD. The best testing is serial imaging, depicting an initially intact vertebral body after trauma, and then the VBC, as the patient becomes symptomatic. Comparison with old films may help establish whether a compression fracture is acute or chronic, but in the absence of relevant films, a bone scan or MRI can help. Kaufmann et al. reported that fracture duration of up to 1 year was associated with a good response to vertebroplasty [35Kaufmann TJ, Jensen ME, Schweickert PA , et al. Age of fracture and clinical outcomes of percutaneous vertebroplasty. AJNR Am J Neuroradiol 2001; 22: 1860-3.] and this appears to be verified by other studies [36McGraw JK, Cardella J, Barr JD , et al. Society of Interventional Radiology quality improvement guidelines for percutaneous vertebroplasty. J Vasc Interv Radiol 2003; 14: 827-31.]. For fractures of uncertain age, an additional indicator of acuteness is marrow edema on MR imaging or increased vertebral-body uptake on bone scanning [37Kallmes DF, Comstock BA, Heagerty PJ , et al. A randomized trial of vertebroplasty for osteoporotic spinal fractures. N Engl J Med 2009; 361: 569-79.]. In the study by Masala et al. [38Masala S, Schillaci O, Massari F , et al. MRI and bone scan imaging in the preoperative evaluation of painful vertebral fractures treated with vertebroplasty and kyphoplasty. In Vivo 2005; 19: 1055-60.], MRI was equivalent to bone scan in selecting patients to be treated with vertebroplasty and kyphoplasty in the first 3 to 4 months, while bone scintigraphy was more accurate in the evaluation of older fractures (> 3/4 months). Thus, bone scan with SPECT or SPECT/CT imaging is helpful for determining activity level in a fracture of unknown age as well as identifying posterior element fractures, additional vertebral body fractures, and even rib fractures [39Matzaroglou C, Georgiou CS, Wilke HJ , et al. Kümmell's disease pathophysiology, diagnosis, treatment and the role of nuclear medicine.Rationale according to our experience. Hell J Nuc Med 2011; 14: 291-9.]. In our experience, even chronic fractures manifesting bone marrow edema or focal radionuclide activity on bone scan may respond to treatment.

On the other hand, although nonspecific, bone scan is considered to be one of the more sensitive imaging tools for the diagnosis of early ischemic necrosis. There are published reports of an observed increased uptake of the radiolabelled osteophilic tracer at the vertebral site being present before the collapse occurred [40Nicholas JJ, Benedek TG, Reece GJ. Delayed traumatic vertebral body compression fracture I. Clinical features Semin Arthritis Rheum 1981; 10: 264-70.] and bone scan has been shown to demonstrate abnormalities during the early phase of KD, when plain x-rays are normal [11Van Eenenaam DP, el-Khoury GY. Delayed post-traumatic vertebral collapse (Kümmell’s disease): case report with serial radiographs, computed tomographic scans, and bone scans. Spine 1993; 18: 1236-41.]. However, bone scan shows absent or minimal uptake if the lesion is chronic, as the normal osteoblastic response within the osseous reconstruction phase would have been indicative of a recent lesion [17Matzaroglou C, Georgiou CS, Assimakopoulos K , et al. Kümmell' s disease A rare spine entity in a young adult. Hell J Nucl Med 2010; 13: 52-5., 26Naul LG, Peet GJ, Maupin WB. Avascular necrosis of the vertebral body MR imaging. Radiology 1989; 172: 219-22., 41Gray L, Vandemark R, Hays M. Thoracic and Lumbar Spine Trauma. Seminars in Ultrasound CT and MRI 2001; 22: 125-134.].

Regarding biopsy specimens in cases of a VBC, they are performed only when a malignancy is suspected or as part of sampling and diagnosis confirmation, when a vertebroplasty or kyphoplasty is scheduled. The diagnosis of KD usually does not require bone biopsies.

TREATMENT

Treatment is based on patient’s symptoms and laboratory workout. Because of the rarity of the condition and the paucity of literature, specific treatment protocols are limited. Early reports focused on conservative treatment, while more recent favor surgical intervention. The advantages of surgery include earlier patient ambulation and correction of the kyphotic deformity [15Ma R, Chow R, Shen FH. Kummell's disease delayed post-traumatic osteonecrosis of the vertebral body. Eur Spine J 2010; 19: 1065-70.]. Factors that should be taken into consideration include the severity of pain, degree of deformity, and neurologic deficits [2Young WF, Brown D, Kendler A , et al. Delayed post-traumatic osteonecrosis of a vertebral body (Kümmell’s disease). Acta Orthop Belg 2002; 68: 13-19., 15Ma R, Chow R, Shen FH. Kummell's disease delayed post-traumatic osteonecrosis of the vertebral body. Eur Spine J 2010; 19: 1065-70.]. In the absence of neurological impairment and with the assumption of an intact posterior vertebral wall, conservative pain management with analgesic drugs, bed rest and bracing can be tried out [2Young WF, Brown D, Kendler A , et al. Delayed post-traumatic osteonecrosis of a vertebral body (Kümmell’s disease). Acta Orthop Belg 2002; 68: 13-19.]. In selected cases teriparatide, a recombinant form of parathyroid hormone may be considered a valid treatment to fill the osseous gap, relieve pain and resolve the related disability [18Fabbriciani G, Pirro M, Floridi P , et al. Osteoanabolic therapy a non-surgical option of treatment for Kümmell's disease?. Rheumatol Int 2012; 32: 1371-4.]. When nonoperative treatment fails or in cases with great kyphotic deformity, minimally invasive procedures (vertebroplasty or kyphoplasty) are indicated to eliminate the motion at the fracture site, to restore spinal alignment and to relieve pain. For vertebroplasty the patients are positioned in prone position with hyperlordosis. Hyperlordosis induces opening of the cleft and restores the height of the vertebral body [16van der Schaaf H. Fransen.Percutaneous vertebroplasty as treatment for Kummell's disease. JBR-BTR 2009; 92: 83-5., 42Krauss M, Hirschfelder H, Tomandl B , et al. Kyphosis reduction and the rate of cement leaks after vertebroplasty of intravertebral clefts. Eur Radiol 2006; 16: 1015-21.]. To prevent cement leakage, cavity-grams with injection of contrast medium may be obtained prior to cement insertion [16van der Schaaf H. Fransen.Percutaneous vertebroplasty as treatment for Kummell's disease. JBR-BTR 2009; 92: 83-5.]. Complete filling of the cleft is advocated to maximize stabilization of the fracture [16van der Schaaf H. Fransen.Percutaneous vertebroplasty as treatment for Kummell's disease. JBR-BTR 2009; 92: 83-5., 43Lane JI, Maus TP, Wald JT , et al. Intravertebral clefts opacified during vertebroplasty pathogenesis, technical implications, and prognostic significance. AJNR Am J Neuroradiol 2002; 23: 1642-6.]. Some propose leaving patients in the prone, hyperextended position for an additional time of 30 minutes after cement injection to prevent any unnecessary motion along the fracture site [43Lane JI, Maus TP, Wald JT , et al. Intravertebral clefts opacified during vertebroplasty pathogenesis, technical implications, and prognostic significance. AJNR Am J Neuroradiol 2002; 23: 1642-6.]. The results after vertebroplasty, for fractures with or without clefts, are quite controversial especially regarding kyphosis correction and cement extrusion [15Ma R, Chow R, Shen FH. Kummell's disease delayed post-traumatic osteonecrosis of the vertebral body. Eur Spine J 2010; 19: 1065-70., 42Krauss M, Hirschfelder H, Tomandl B , et al. Kyphosis reduction and the rate of cement leaks after vertebroplasty of intravertebral clefts. Eur Radiol 2006; 16: 1015-21., 44Ha KY, Lee JS, Kim KW, Chon JS. Percutaneous vertebroplasty for vertebral compression fractures with and without intravertebral clefts. J Bone Joint Surg Br 2006; 88: 629-33.]. In a study by Krauss et al. [42Krauss M, Hirschfelder H, Tomandl B , et al. Kyphosis reduction and the rate of cement leaks after vertebroplasty of intravertebral clefts. Eur Radiol 2006; 16: 1015-21.] who performed vertebroplasty in 44 clefted fractures and 148 vertebrae without cleft, higher reduction of kyphosis angle and lower cement leakage was found in the clefted group. Opening of the IVC with hyperlordosis was considered responsible for better reduction, thus making kyphoplasty unnecessary. The lower rate of cement leakage was attributed to the fact that IVC is an avascular bone area, surrounded by a fibrocartilaginous membrane. However, only 3,1 ml of cement per vertebra was used in this report. Ha et al. [44Ha KY, Lee JS, Kim KW, Chon JS. Percutaneous vertebroplasty for vertebral compression fractures with and without intravertebral clefts. J Bone Joint Surg Br 2006; 88: 629-33.] presented their results of percutaneous vertebroplasty in 39 patients without IVCs and 12 with IVCs. They found also greater initial correction in the clefted group. However, loss of reduction was greater in the same group postoperatively. In contrast to the previous report, they found more leakage in the presence of a cleft, especially type-C leakage through cortical defects. Pain reduction showed no significant difference between both groups, in both reports. However patients with an IVC exhibited higher pain scores in the second report and, thus, more inconvenience in daily life after the operation than those without a cleft.

For chronic VBC or acute VBC with posterior wall disruption surgical stabilization via fusion should be applied. If there is evidence of neurologic compromise, then definitive decompression with stabilization should be performed. The concern with decompression alone, such as laminectomy, is the progression of the kyphotic deformity, which can lead to further complications, thus making stabilization indispensable [45Kempinsky WH, Morgan PP, Boniface WR. Osteoporotic kyphosis with paraplegia. Neurology 1958; 8: 181-6.]. Decompression can be approached either anteriorly [46Kaneda K, Asano S, Hashimoto T , et al. The treatment of osteoporotic-posttraumatic vertebral collapse using the Kaneda device and bioactive ceramic vertebral prosthesis. Spine (Phila Pa 1976) 1992; 17: S295-303.] or posteriorly [47Shikata J, Yamamuro T, Ida H , et al. Surgical treatment for paraplegia resulting from vertebral fractures in senile osteoporosis. Spine (Phila Pa 1976) 1990; 15: 485-9.]. Favorable results have been reported using anterior decompression and fusion with intervertebral tricortical graft [48Hasegawa K, Homma T, Uchiyama S, Takahashi HE. Osteosynthesis without instrumentation for vertebral pseudarthrosis in the osteoporotic spine. J Bone Joint Surg Br 1997; 79: 452-456.] or ceramic glass spacers [46Kaneda K, Asano S, Hashimoto T , et al. The treatment of osteoporotic-posttraumatic vertebral collapse using the Kaneda device and bioactive ceramic vertebral prosthesis. Spine (Phila Pa 1976) 1992; 17: S295-303.]. The advantage of an anterior approach is the technical ease for removing the retropulsed fragment. However, in elderly patients where comorbidities may be significant, violating the thoracic cavity or the retroperitoneal space can have severe consequences; performing a posterior procedure only would, thus, be advantageous [15Ma R, Chow R, Shen FH. Kummell's disease delayed post-traumatic osteonecrosis of the vertebral body. Eur Spine J 2010; 19: 1065-70., 49Kim KT, Suk KS, Kim JM, Lee SH. Delayed vertebral collapse with neurological deficits secondary to osteoporosis. Int Orthop 2003; 27: 65-9.]. Manual reduction of fracture with transpedicular insertion of vertebral body augments (a titanium spacer with bone-ingrowth porous surface) combined with short segment fixation has also been described for KD with cord compromise [50Li KC, Li AF, Hsieh CH , et al. Another option to treat Kümmell's disease with cord compression. Eur Spine J 2007; 16: 1479-87.].

MANAGEMENT OF CHRONIC BACK PAIN

The main symptom of KD is the chronic pain, which continuously increases. Treatment options for patients with chronic back pain are limited. Exercise therapy and non-steroidal antiinflammatories can be beneficial, but it is uncommon for these treatments to lead to a complete resolution of the pain [51van Tulder MW, Koes BW, Bouter LM. Conservative treatment of acute and chronic nonspecific low back pain. Spine 1997; 22: 2128-56.]. The biopsychosocial model is gaining acceptance in low back pain; psychological factors, notably distress, depressive mood, anxiety and somatization, are implicated in the development of chronic low back pain. All these factors contribute towards emotional reactions and pain; as a consequence, treatment of one improves the other [52Pincus T, Burton AK, Vogel S, Field AP. A systematic review of psychological factors as predictors of chronicity/disability in prospective cohorts of low back pain. Spine (Phila Pa 1976) 2002; 27: E109-20.]. In the face of extreme pain, the role of personality factors, affective states and environment become less important, so the psychiatrist should avoid psychological diagnoses and, hence, minimize patients’ complaints in the eyes of others. Patients with psychological problems are more difficult to assess and their complaints are more easily disqualified; hence the consultant must encourage the medical staff to manage their pain as aggressively as that of other patients [52Pincus T, Burton AK, Vogel S, Field AP. A systematic review of psychological factors as predictors of chronicity/disability in prospective cohorts of low back pain. Spine (Phila Pa 1976) 2002; 27: E109-20.]. The psychiatric diagnosis must be explained, to both patients and the medical staff, its impact on sick behavior must be clarified and a treatment strategy must be decided. The psychiatric team should be able to propose ways of optimizing pain treatment, until surgery is performed. This may include cognitive-behavioral methods, supportive psychotherapy and psychiatric medical treatment. Behavioral interventions increase the sense of control and decrease anxiety and pain, whereas psychotherapy aids in differentiating between pain and suffering and encourages appropriate response to both [53Moore JE. Chronic low back pain and psychosocial issues. Phys Med Rehabil Clin N Am 2010; 21: 801-15.]. Pharmacotherapy with new antidepressant agents is also useful until surgical management is decided [54Staiger TO, Gaster B, Sullivan MD, Deyo RA. Systematic review of antidepressants in the treatment of chronic low back pain. Spine (Phila Pa 1976) 2003; 28: 2540-5.].

KÜMMELL’S DISEASE AND INTRAVERTEBRAL VACUUM CLEFT

Despite the considerable amount of literature, a definite correlation between IVC with vertebral osteonecrosis and KD has not been established yet. An Intravertebral Vacuum Cleft is characterized by a radiolucent zone within the vertebral body, filled with gas (Figs. 1, 2). The gas is 95% nitrogen, with small amounts of oxygen and carbon dioxide [55Sarli M, Pérez Manghi FC, Gallo R, Zanchetta Jr. The vacuum cleft sign an uncommon radiological sign. Osteoporos Int 2005; 16: 1210-4.]. However, after prolonged supine positioning, it is replaced by fluid, resulting in a high intensity band on T2-weighted sequences (Fig. 3) [56Malghem J, Maldague B, Labaisse MA , et al. Intravertebral vacuum cleft changes in content after supine positioning. Radiology 1993; 187: 483-7.]. Analysis of this serous fluid showed a consistency similar to synovial fluid [57Hasegawa K, Homma T, Uchiyama S, Takahashi H. Vertebral pseudarthrosis in the osteoporotic spine. Spine (Phila Pa 1976) 1998; 23: 2201-6.] or plasma [14Maheshwari PR, Nagar AM, Prasad SS , et al. Avascular necrosis of spine a rare appearance. Spine 2004; 29: E119-E122., 58Dupuy DE, Palmer WE, Rosenthal DI. Vertebral fluid collection associated with vertebral collapse. AJR Am J Roentgenol 1996; 167: 1535-8.]. Furthermore, biopsies of the cavity lining demonstrated fibrocartilage within a fibrous stroma, findings that represent a pseudosynovium of a nonunion [57Hasegawa K, Homma T, Uchiyama S, Takahashi H. Vertebral pseudarthrosis in the osteoporotic spine. Spine (Phila Pa 1976) 1998; 23: 2201-6., 59Hasegawa K, Homma T, Uchiyama S, Takahashi HE. Osteosynthesis without instrumentation for vertebral pseudarthrosis in the osteoporotic spine. J Bone Joint Surg Br 1997; 79: 452-6.].

Fig. (1)

A 76-year-old female patient, who was under systemic steroid treatment for rheumatoid arthritis, was presented with refractory back pain. Anteroposterior (A) conventional radiograph shows a barely visible horizontal linear IVC in L2 vertebra, which is more apparent on lateral (B) projection (arrows). The L2 vertebra is wedge-shaped, while the IVC appears typically at the anterior third of the vertebral body (B).



Fig. (2)

CT scan of the lumbar spine of the same patient. The intravertebral vacuum cleft phenomenon is identified in the anterior third of the L2 vertebral body on both axial (A) and sagittal (B) CT study of the lumbar spine (large arrows). Minimal retropulsion of bony fragments is observed (small arrow) (B). Note the degenerative disc disease and the coexistent intervertebral disc vacuum phenomena at the levels T11-T12, T12-L1, L1-L2 on the sagittal CT-scan (arrowheads) (B).



Fig. (3)

Sagittal MRI studies of the lumbar spine of the same patient. The intravertebral vacuum cleft shows low signal intensity on T1 (A) and high signal intensity on T2-weighted (B) sequences (arrows). These two different signals represent a fluid collection.



In the past, the presence of such a cleft in an adult patient was considered a pathognomonic radiological sign of vertebral osteonecrosis [33Maldague BE, Noel HM, Malghem JJ. The intravertebral vacuum cleft a sign of ischemic vertebral collapse. Radiology 1978; 129: 23-9.]. Horizontal linear IVCs were suggestive of a benign collapse and had never been associated with acute fracture, infection, or malignacy (either primary or metastatic) [27Bhalla S, Reinus WR. The linear intravertebral vacuum a sign of benign vertebral collapse. AJR Am J Roentgenol 1998; 170: 1563-9., 33Maldague BE, Noel HM, Malghem JJ. The intravertebral vacuum cleft a sign of ischemic vertebral collapse. Radiology 1978; 129: 23-9.]. In the series of Maldague et al. [33Maldague BE, Noel HM, Malghem JJ. The intravertebral vacuum cleft a sign of ischemic vertebral collapse. Radiology 1978; 129: 23-9.] in 14 patients with non-ischemic causes of vertebral collapse (five with metastatic collapse, five with diskitis, and four with simple traumatic fractures), no IVC was present initially and none could be elicited with extension views.

Acute fractures presumed not to show IVCs, as the space between the bone fragments is initially occupied by the fracture hematoma, followed by callus formation. Further confirmation that IVC is related to avascular necrosis came from the study of Libicher et al. [34Libicher M, Appelt A, Berger I , et al. The intravertebral vacuum phenomenon as specific sign of osteonecrosis in vertebral compression fractures results from a radiological and histological study. Eur Radiol 2007; 17: 2248-52.]. They carried out a correlated radiological and histological evaluation of 180 cases of vertebral compression fractures. They found ischemic osteonecrosis on biopsy specimens in 11 of the 12 patients with IVC; only one of the 167 patients without osteonecrosis showed IVC. The resulted cleft sign’s sensitivity was calculated at 85%, while specificity at 99%.

Recent studies, however, have shown that these clefts are not so rare and are frequently associated with osteoporotic fractures [6Mirovsky Y, Anekstein Y, Shalmon E, Peer A. Vacuum clefts of the vertebral bodies. AJNR Am J Neuroradiol 2005; 26: 1634-40., 60Matzaroglou C, Georgiou CS, Wilke HJ , et al. Kümmell's disease is ischemic necrosis or vertebral "microcracking" the first step in the sequence?. Med Hypotheses 2013; 80: 505.]. An incidence of 10-48% has been reported in patients with osteoporotic compression fractures recruited for vertebroplasty [60Matzaroglou C, Georgiou CS, Wilke HJ , et al. Kümmell's disease is ischemic necrosis or vertebral "microcracking" the first step in the sequence?. Med Hypotheses 2013; 80: 505.-62McKiernan F, Faciszewski T. Intravertebral clefts in osteoporotic vertebral compression fractures. Arthritis Rheum 2003; 48: 1414-19.]. The pathogenetic mechanism is still controversial with three possible theories favored in the literature. According to the first, intravertebral vacuum phenomenon is the result of vertebral osteonecrosis [26Naul LG, Peet GJ, Maupin WB. Avascular necrosis of the vertebral body MR imaging. Radiology 1989; 172: 219-22., 33Maldague BE, Noel HM, Malghem JJ. The intravertebral vacuum cleft a sign of ischemic vertebral collapse. Radiology 1978; 129: 23-9.]. Ischemic collapse leads to an overall decrease in the volume of vertebral bone, resulting in intraosseous cleft formation; the generated low pressure in these clefts allows accumulation of gas and produces the IVC phenomenon [63Theodorou DJ. The intravertebral vacuum cleft sign. Radiology 2001; 221: 787-8.]. However, the high incidence of clefts in osteoporotic fractures makes unlikely a causal connection of these clefts with ischemic necrosis [43Lane JI, Maus TP, Wald JT , et al. Intravertebral clefts opacified during vertebroplasty pathogenesis, technical implications, and prognostic significance. AJNR Am J Neuroradiol 2002; 23: 1642-6.]. The second theory supports that intravertebral vacuum phenomenon represents nonunion and pseudarthrosis of a vertebral fracture [6Mirovsky Y, Anekstein Y, Shalmon E, Peer A. Vacuum clefts of the vertebral bodies. AJNR Am J Neuroradiol 2005; 26: 1634-40., 57Hasegawa K, Homma T, Uchiyama S, Takahashi H. Vertebral pseudarthrosis in the osteoporotic spine. Spine (Phila Pa 1976) 1998; 23: 2201-6., 59Hasegawa K, Homma T, Uchiyama S, Takahashi HE. Osteosynthesis without instrumentation for vertebral pseudarthrosis in the osteoporotic spine. J Bone Joint Surg Br 1997; 79: 452-6., 60Matzaroglou C, Georgiou CS, Wilke HJ , et al. Kümmell's disease is ischemic necrosis or vertebral "microcracking" the first step in the sequence?. Med Hypotheses 2013; 80: 505.]. A third theory, which, however, had limited acceptance, suggested that intravertebral gas could be of intradiskal origin, since a high coincidence (83%) of intervertebral disc vacuum was noted in cases of IVC (Fig. 2B) [31Lafforgue P, Chagnaud C, Daumen-Legré V , et al. The intravertebral vacuum phenomenon ("vertebral osteonecrosis").Migration of intradiscal gas in a fractured vertebral body Spine (Phila Pa 1976) 1997; 22: 1885-91.]. Spinal infection, on the other hand, may rarely be accompanied by intradiscal or intraosseous gas so that the latter finding does not entirely exclude the possibility of infection [64Bielecki DK, Sartoris D, Resnick D , et al. Intraosseous and intradiscal gas in association with spinal infection report of three cases. AJR Am J Roentgenol 1986; 147: 83-6.]. Intravertebral vacuum has not been indeed reported in the context of acute spinal trauma, in contrast to intradiskal gas [65Tash RR, Weitzner I Jr. Acute intervertebral gas following vertebral fracture CT demonstration. J Comput Assist Tomogr 1986; 10: 707-8.]. However, if one defines as acute fractures those with symptoms onset less than 3 months [66Laredo JD, Lakhdari K, Bellaïche L , et al. Acute vertebral collapse CT findings in benign and malignant nontraumatic cases. Radiology 1995; 194: 41-8.], IVC is found in such fractures [57Hasegawa K, Homma T, Uchiyama S, Takahashi H. Vertebral pseudarthrosis in the osteoporotic spine. Spine (Phila Pa 1976) 1998; 23: 2201-6., 66Laredo JD, Lakhdari K, Bellaïche L , et al. Acute vertebral collapse CT findings in benign and malignant nontraumatic cases. Radiology 1995; 194: 41-8., 67Jang JS, Kim DY, Lee SH. Efficacy of percutaneous vertebroplasty in the treatment of intravertebral pseudarthrosis associated with noninfected avascular necrosis of the vertebral body. Spine 2003; 28: 1588-92.]. Furthermore, in a review of spinal radiographs of 2000 patients, Kumpan et al. [7Kumpan W, Salomonowitz E, Seidi G, Wittich GR. The intravertebral vacuum phenomenon. Skeletal Radiol 1986; 15: 444-7.] provide the only description within the literature of an IVC in malignant collapse. They found IVCs in 17 of 2000 patients (<1%). Two of these patients were known to have multiple myeloma and neoplastic involvement of the vertebral bodies, which exhibited the vacuum phenomenon confirmed at autopsy. Moreover, one of these patients had visible IVC only after the application of traction. The other patient had a central, rounded radiolucency. It must be noticed, that these round clefts associated with malignancy were reported during traction of the patients, and it is not clear if the IVC was linear in plain films without traction. The authors consider the IVC a nonspecific finding, which does not exclude the presence of malignancy in the affected bone, as previously advocated [27Bhalla S, Reinus WR. The linear intravertebral vacuum a sign of benign vertebral collapse. AJR Am J Roentgenol 1998; 170: 1563-9., 34Libicher M, Appelt A, Berger I , et al. The intravertebral vacuum phenomenon as specific sign of osteonecrosis in vertebral compression fractures results from a radiological and histological study. Eur Radiol 2007; 17: 2248-52.]. Gagnerie et al. [68Gagnerie F, Taillan B, Euller-Ziegler L , et al. Intravertebral vacuum phenomenon in multiple myeloma. Clin Rheumatol 1987; 6: 597-9.] also described a patient with multiple myeloma and a linear IVC in a vertebral body collapse. Histologic evaluation, however, showed evidence of ischemic necrosis only, without signs of myelomatous involvement of the affected vertebra. It must be emphasized that a round intravertebral gas collection is not diagnostic for multiple myeloma; a globular-shaped vacuum cleft have also been found in cases of vertebral osteonecrosis [12Osterhouse MD, Kettner NW. Delayed posttraumatic vertebral collapse with intravertebral vacuum cleft. J Manipulative Physiol Ther 2002; 25: 270-5.], while vertical clefts have been noted in simple osteoporotic fractures [6Mirovsky Y, Anekstein Y, Shalmon E, Peer A. Vacuum clefts of the vertebral bodies. AJNR Am J Neuroradiol 2005; 26: 1634-40.].

IVCs demonstrate dynamic mobility in different body postures thus indicating instability within the fracture [62McKiernan F, Faciszewski T. Intravertebral clefts in osteoporotic vertebral compression fractures. Arthritis Rheum 2003; 48: 1414-19., 69McKiernan F, Jensen R, Faciszewski T. The dynamic mobility of vertebral compression fractures. J Bone Miner Res 2003; 18: 24-9.]. The dynamic mobility of IVCs is expressed by the changes in vertebral body height that can be seen on standing lateral and cross-table supine lateral radiographs [18Fabbriciani G, Pirro M, Floridi P , et al. Osteoanabolic therapy a non-surgical option of treatment for Kümmell's disease?. Rheumatol Int 2012; 32: 1371-4., 69McKiernan F, Jensen R, Faciszewski T. The dynamic mobility of vertebral compression fractures. J Bone Miner Res 2003; 18: 24-9.]. In some cases, the cleft only appears in extension stress views and disappears in flexion [33Maldague BE, Noel HM, Malghem JJ. The intravertebral vacuum cleft a sign of ischemic vertebral collapse. Radiology 1978; 129: 23-9., 56Malghem J, Maldague B, Labaisse MA , et al. Intravertebral vacuum cleft changes in content after supine positioning. Radiology 1993; 187: 483-7.]. This motion within the fracture has been correlated with a high probability of severe, persistent pain [6Mirovsky Y, Anekstein Y, Shalmon E, Peer A. Vacuum clefts of the vertebral bodies. AJNR Am J Neuroradiol 2005; 26: 1634-40.]. Thus, an accurate diagnosis of an IVC requires not only standing lateral, but also extension (cross-table lateral supine) projections, in order to avoid false negative results. Clefts are identifiable with standing lateral radiography, supine cross-table radiography and MRI, at 14%, 64% and 96%, respectively [62McKiernan F, Faciszewski T. Intravertebral clefts in osteoporotic vertebral compression fractures. Arthritis Rheum 2003; 48: 1414-19.]. However, several IVCs remain undetected, until they are filled with opaque cement at the time of vertebroplasty [43Lane JI, Maus TP, Wald JT , et al. Intravertebral clefts opacified during vertebroplasty pathogenesis, technical implications, and prognostic significance. AJNR Am J Neuroradiol 2002; 23: 1642-6.]. On the other hand, the signal intensity of the gas noted on plain radiographs might be different from the expected low signal intensity on T1 and T2 MRI sequences. After prolonged supine positioning, the clefts can be filled with fluid, resulting in a high intensity band on T2-weighted sequences (Fig. 3) [56Malghem J, Maldague B, Labaisse MA , et al. Intravertebral vacuum cleft changes in content after supine positioning. Radiology 1993; 187: 483-7.]. This linear, horizontal, increased on T-2 weighted images signal, follows the same pattern with the signal in cases of avacular necrosis of the femoral head [66Laredo JD, Lakhdari K, Bellaïche L , et al. Acute vertebral collapse CT findings in benign and malignant nontraumatic cases. Radiology 1995; 194: 41-8.]. It is probably a result of prolongation of the T2 relaxation time of the fluid and inflammatory exudate during the early phases of avascular necrosis [25Sweet DE, Madewell JE, Resnick DK, Niwayama E. Pathogenesis of osteonecrosis. In Diagnosis of bone and joint disorders Philadelphia Saunders 1981; 2780-831., 70Mitchell DG, Rao VM, Dalinka MK , et al. Femoral head avascular necrosis correlation of MR imaging, radiographic staging, radionuclide imaging, and clinical findings. Radiology 1987; 162: 709-15.]. This sign has been recognized in all reported cases of KD, when MRI study was available [2Young WF, Brown D, Kendler A , et al. Delayed post-traumatic osteonecrosis of a vertebral body (Kümmell’s disease). Acta Orthop Belg 2002; 68: 13-19., 3Swartz K, Fee D. Kümmell's disease a case report and literature review. Spine (Phila Pa 1976) 2008; 33: E152-5., 13Kapoor V, Theruvil B, Foria V , et al. Vertebral collapse in a 71-year-old woman. Clin Orthop Relat Res 2004; 423: 291-8.-16van der Schaaf H. Fransen.Percutaneous vertebroplasty as treatment for Kummell's disease. JBR-BTR 2009; 92: 83-5.]. However, in patients with later phases of new bone and fibrous tissue formation, a linear area of hyperintensity on T2-weighted images cannot be identified [17Matzaroglou C, Georgiou CS, Assimakopoulos K , et al. Kümmell' s disease A rare spine entity in a young adult. Hell J Nucl Med 2010; 13: 52-5., 26Naul LG, Peet GJ, Maupin WB. Avascular necrosis of the vertebral body MR imaging. Radiology 1989; 172: 219-22.]. Additionally, a peripheral zone of hypointensity can be seen surrounding the hyperintensity on T-2 weighted images (Fig. 4) [2Young WF, Brown D, Kendler A , et al. Delayed post-traumatic osteonecrosis of a vertebral body (Kümmell’s disease). Acta Orthop Belg 2002; 68: 13-19., 3Swartz K, Fee D. Kümmell's disease a case report and literature review. Spine (Phila Pa 1976) 2008; 33: E152-5., 14Maheshwari PR, Nagar AM, Prasad SS , et al. Avascular necrosis of spine a rare appearance. Spine 2004; 29: E119-E122., 16van der Schaaf H. Fransen.Percutaneous vertebroplasty as treatment for Kummell's disease. JBR-BTR 2009; 92: 83-5.]. This finding is termed “double line sign” and corresponds to the IVC [26Naul LG, Peet GJ, Maupin WB. Avascular necrosis of the vertebral body MR imaging. Radiology 1989; 172: 219-22.]. It is thought to represent sclerosis surrounding central granulation tissue and has also been described in cases of avascular necrosis of the femoral head [3Swartz K, Fee D. Kümmell's disease a case report and literature review. Spine (Phila Pa 1976) 2008; 33: E152-5., 70Mitchell DG, Rao VM, Dalinka MK , et al. Femoral head avascular necrosis correlation of MR imaging, radiographic staging, radionuclide imaging, and clinical findings. Radiology 1987; 162: 709-15.].

Fig. (4)

Coronal T2-weighted MRI of the lumbar spine of the same patient. An area of linear hyperintesity (arrows) is surrounded with a hypointensity band (arrowheads). This is termed “double line sign” and corresponds to the intravertebral vacuum cleft.



In conclusion, IVCs represent gross disruption of cortical and cancellous vertebral bone and are time and position dependent, resulting in a variable radiographic appearance. A conflation of pseudarthrotic and osteonecrotic theories could explain their presence [39Matzaroglou C, Georgiou CS, Wilke HJ , et al. Kümmell's disease pathophysiology, diagnosis, treatment and the role of nuclear medicine.Rationale according to our experience. Hell J Nuc Med 2011; 14: 291-9.]. A severe crush fracture of the osteoporotic vertebra could lead to necrosis, if the motion remains. Alternatively, ischemia of the weakened osteoporotic trabeculae could cause a fracture, which would not heal due to the insufficient blood supply and can lead to pseudarthrosis [39Matzaroglou C, Georgiou CS, Wilke HJ , et al. Kümmell's disease pathophysiology, diagnosis, treatment and the role of nuclear medicine.Rationale according to our experience. Hell J Nuc Med 2011; 14: 291-9.]. Clefts can be also observed in a variety of concomitant disorders, benign or malignant. The absence of an IVC, does not exclude avascular necrosis from the differential diagnosis [12Osterhouse MD, Kettner NW. Delayed posttraumatic vertebral collapse with intravertebral vacuum cleft. J Manipulative Physiol Ther 2002; 25: 270-5., 17Matzaroglou C, Georgiou CS, Assimakopoulos K , et al. Kümmell' s disease A rare spine entity in a young adult. Hell J Nucl Med 2010; 13: 52-5.]. Therefore, a vertebral cleft is not specific for KD, thus the IVC shouldn’t be referred as Kümmell’s sign [3Swartz K, Fee D. Kümmell's disease a case report and literature review. Spine (Phila Pa 1976) 2008; 33: E152-5., 4Freedman BA, Heller JG. Kummell Disease A Not-So-Rare Complication of Osteoporotic Vertebral Compression Fractures. J Am Board Fam Med 2009; 22: 75-8., 62McKiernan F, Faciszewski T. Intravertebral clefts in osteoporotic vertebral compression fractures. Arthritis Rheum 2003; 48: 1414-19., 69McKiernan F, Jensen R, Faciszewski T. The dynamic mobility of vertebral compression fractures. J Bone Miner Res 2003; 18: 24-9.].

CONCLUSION

KD is the eponymic designation for the delayed posttraumatic VBC. Although it is weakly validated, hypothesis of ischemic posttraumatic vertebral necrosis is the prevailing theory, which tries to explain the delayed fashion of the VBC. Furthermore, the cause, symptoms, and diagnosis of KD are very individual. There is still no consensus about the nature and how severe the initial trauma has to be, how long the asymptomatic period should be and what types of tests should be used to support the diagnosis. However patients, even young individuals, who have refractory symptoms, after seemingly innocuous thoracolumbar spinal trauma or prolonged spinal hyperflexion loading, should have repeated follow-up radiographic evaluations, even though initial studies were deemed normal. This is particularly true in patients who exhibit potential risk factors for avascular osteonecrosis, notably advanced age, osteoporosis and chronic steroid usage. If a VBC is recognized, patients should undergo an extensive work up to exclude other potential underlying conditions, mainly malignancy or infection. For the nonoperative management of chronic back pain of KD, as well as of simple osteoporotic fractures, interdisciplinary approach with biomedical and psychosocial tools is mandatory. When conservative treatment fails, percutaneous vertebroplasty seems to be the current standard surgical therapy. In this case, it may be important to distinguish cases

of KD from typical compression osteoporotic fractures, since the severe destruction of the vertebrae, associated with ischemic collapse, may increase the risk of retropulsion of bone or methylmethacrylate into the spinal canal during vertebroplasty.

CONFLICT OF INTEREST

The authors declare that they have no conflict of interest.

ACKNOWLEDGEMENTS

Declared none.

REFERENCES

[1] Kümmel H. Ueber die traumatischen Erkrankungen der Wirbelsaüle. Dtsch Med Wochenschr 1895; 21: 180-81.
[2] Young WF, Brown D, Kendler A , et al. Delayed post-traumatic osteonecrosis of a vertebral body (Kümmell’s disease). Acta Orthop Belg 2002; 68: 13-19.
[3] Swartz K, Fee D. Kümmell's disease a case report and literature review. Spine (Phila Pa 1976) 2008; 33: E152-5.
[4] Freedman BA, Heller JG. Kummell Disease A Not-So-Rare Complication of Osteoporotic Vertebral Compression Fractures. J Am Board Fam Med 2009; 22: 75-8.
[5] Steel HH. Kümmell’s disease. Am J Surg 1951; 81: 161-7.
[6] Mirovsky Y, Anekstein Y, Shalmon E, Peer A. Vacuum clefts of the vertebral bodies. AJNR Am J Neuroradiol 2005; 26: 1634-40.
[7] Kumpan W, Salomonowitz E, Seidi G, Wittich GR. The intravertebral vacuum phenomenon. Skeletal Radiol 1986; 15: 444-7.
[8] Rigler L. Kummell’s disease with report of a roentgenologically proved case. Am J Roentgenol 1931; 35: 749-53.
[9] Brower AC, Downey EF Jr. Kümmell disease report of a case with serial radiographs. Radiology 1981; 141: 363-4.
[10] Hermann G, Goldblatt J, Desnick RJ. Kummell disease delayed collapse of the traumatised spine in a patient with Gaucher type 1 disease. Br J Radiol 1984; 57: 833.
[11] Van Eenenaam DP, el-Khoury GY. Delayed post-traumatic vertebral collapse (Kümmell’s disease): case report with serial radiographs, computed tomographic scans, and bone scans. Spine 1993; 18: 1236-41.
[12] Osterhouse MD, Kettner NW. Delayed posttraumatic vertebral collapse with intravertebral vacuum cleft. J Manipulative Physiol Ther 2002; 25: 270-5.
[13] Kapoor V, Theruvil B, Foria V , et al. Vertebral collapse in a 71-year-old woman. Clin Orthop Relat Res 2004; 423: 291-8.
[14] Maheshwari PR, Nagar AM, Prasad SS , et al. Avascular necrosis of spine a rare appearance. Spine 2004; 29: E119-E122.
[15] Ma R, Chow R, Shen FH. Kummell's disease delayed post-traumatic osteonecrosis of the vertebral body. Eur Spine J 2010; 19: 1065-70.
[16] van der Schaaf H. Fransen.Percutaneous vertebroplasty as treatment for Kummell's disease. JBR-BTR 2009; 92: 83-5.
[17] Matzaroglou C, Georgiou CS, Assimakopoulos K , et al. Kümmell' s disease A rare spine entity in a young adult. Hell J Nucl Med 2010; 13: 52-5.
[18] Fabbriciani G, Pirro M, Floridi P , et al. Osteoanabolic therapy a non-surgical option of treatment for Kümmell's disease?. Rheumatol Int 2012; 32: 1371-4.
[19] Chou LH, Knight RQ. Idiopathic avascular necrosis of a vertebral body. Case report and literature review Spine 1997; 22: 1928,-32.
[20] Allen BL Jr, Jinkins WJ 3rd. Vertebral osteonecrosis associated with pancreatitis in a child.A case report. J Bone Joint Surg Am 1978; 60: 985-7.
[21] Ito M, Motomiya M, Abumi K , et al. Vertebral osteonecrosis associated with sarcoidosis.Case report. J Neurosurg Spine 2005; 2: 222-5.
[22] Schmorl G, Junghanns H, Eds. The Human Spine in Health and Disease. New York : Grune & Stratton 1971; 167: pp. 268-96.
[23] Cardis J, Walker GF, Olver RH. Kummell’s disease. Br J Surg 1928; 15: 616-25.
[24] Kux E. Zur Histopathologie der posttraumatischen (Kümmellschen) Wirbelerkrankung. Arch Orthop 1933; 34: 18-23.
[25] Sweet DE, Madewell JE, Resnick DK, Niwayama E. Pathogenesis of osteonecrosis. In Diagnosis of bone and joint disorders Philadelphia Saunders 1981; 2780-831.
[26] Naul LG, Peet GJ, Maupin WB. Avascular necrosis of the vertebral body MR imaging. Radiology 1989; 172: 219-22.
[27] Bhalla S, Reinus WR. The linear intravertebral vacuum a sign of benign vertebral collapse. AJR Am J Roentgenol 1998; 170: 1563-9.
[28] Benedek TG, Nicholas JJ. Delayed traumatic vertebral body compression fracture. II.; Pathologic features. Semin Arthritis Rheum 1981; 10: 271-7.
[29] Stojanovic J, Kovac V. Diagnosis of ischemic vertebral collapse using selective spinal angiography. Rofo 1981; 135: 326-9.
[30] Schmorl G, Junghanns H. The human spine in health and disease. 1971; 141.
[31] Lafforgue P, Chagnaud C, Daumen-Legré V , et al. The intravertebral vacuum phenomenon ("vertebral osteonecrosis").Migration of intradiscal gas in a fractured vertebral body Spine (Phila Pa 1976) 1997; 22: 1885-91.
[32] Queinnec JY, De Bray JM, Audran M, Renier JC. Ostéonécrose vertébrale À propos de 3 cas dont 1 compliqué d'une compression médullaire et 2 associés à une autre localisation nécrotique. Revue du Rhumatisme 1985; 52: 1-5.
[33] Maldague BE, Noel HM, Malghem JJ. The intravertebral vacuum cleft a sign of ischemic vertebral collapse. Radiology 1978; 129: 23-9.
[34] Libicher M, Appelt A, Berger I , et al. The intravertebral vacuum phenomenon as specific sign of osteonecrosis in vertebral compression fractures results from a radiological and histological study. Eur Radiol 2007; 17: 2248-52.
[35] Kaufmann TJ, Jensen ME, Schweickert PA , et al. Age of fracture and clinical outcomes of percutaneous vertebroplasty. AJNR Am J Neuroradiol 2001; 22: 1860-3.
[36] McGraw JK, Cardella J, Barr JD , et al. Society of Interventional Radiology quality improvement guidelines for percutaneous vertebroplasty. J Vasc Interv Radiol 2003; 14: 827-31.
[37] Kallmes DF, Comstock BA, Heagerty PJ , et al. A randomized trial of vertebroplasty for osteoporotic spinal fractures. N Engl J Med 2009; 361: 569-79.
[38] Masala S, Schillaci O, Massari F , et al. MRI and bone scan imaging in the preoperative evaluation of painful vertebral fractures treated with vertebroplasty and kyphoplasty. In Vivo 2005; 19: 1055-60.
[39] Matzaroglou C, Georgiou CS, Wilke HJ , et al. Kümmell's disease pathophysiology, diagnosis, treatment and the role of nuclear medicine.Rationale according to our experience. Hell J Nuc Med 2011; 14: 291-9.
[40] Nicholas JJ, Benedek TG, Reece GJ. Delayed traumatic vertebral body compression fracture I. Clinical features Semin Arthritis Rheum 1981; 10: 264-70.
[41] Gray L, Vandemark R, Hays M. Thoracic and Lumbar Spine Trauma. Seminars in Ultrasound CT and MRI 2001; 22: 125-134.
[42] Krauss M, Hirschfelder H, Tomandl B , et al. Kyphosis reduction and the rate of cement leaks after vertebroplasty of intravertebral clefts. Eur Radiol 2006; 16: 1015-21.
[43] Lane JI, Maus TP, Wald JT , et al. Intravertebral clefts opacified during vertebroplasty pathogenesis, technical implications, and prognostic significance. AJNR Am J Neuroradiol 2002; 23: 1642-6.
[44] Ha KY, Lee JS, Kim KW, Chon JS. Percutaneous vertebroplasty for vertebral compression fractures with and without intravertebral clefts. J Bone Joint Surg Br 2006; 88: 629-33.
[45] Kempinsky WH, Morgan PP, Boniface WR. Osteoporotic kyphosis with paraplegia. Neurology 1958; 8: 181-6.
[46] Kaneda K, Asano S, Hashimoto T , et al. The treatment of osteoporotic-posttraumatic vertebral collapse using the Kaneda device and bioactive ceramic vertebral prosthesis. Spine (Phila Pa 1976) 1992; 17: S295-303.
[47] Shikata J, Yamamuro T, Ida H , et al. Surgical treatment for paraplegia resulting from vertebral fractures in senile osteoporosis. Spine (Phila Pa 1976) 1990; 15: 485-9.
[48] Hasegawa K, Homma T, Uchiyama S, Takahashi HE. Osteosynthesis without instrumentation for vertebral pseudarthrosis in the osteoporotic spine. J Bone Joint Surg Br 1997; 79: 452-456.
[49] Kim KT, Suk KS, Kim JM, Lee SH. Delayed vertebral collapse with neurological deficits secondary to osteoporosis. Int Orthop 2003; 27: 65-9.
[50] Li KC, Li AF, Hsieh CH , et al. Another option to treat Kümmell's disease with cord compression. Eur Spine J 2007; 16: 1479-87.
[51] van Tulder MW, Koes BW, Bouter LM. Conservative treatment of acute and chronic nonspecific low back pain. Spine 1997; 22: 2128-56.
[52] Pincus T, Burton AK, Vogel S, Field AP. A systematic review of psychological factors as predictors of chronicity/disability in prospective cohorts of low back pain. Spine (Phila Pa 1976) 2002; 27: E109-20.
[53] Moore JE. Chronic low back pain and psychosocial issues. Phys Med Rehabil Clin N Am 2010; 21: 801-15.
[54] Staiger TO, Gaster B, Sullivan MD, Deyo RA. Systematic review of antidepressants in the treatment of chronic low back pain. Spine (Phila Pa 1976) 2003; 28: 2540-5.
[55] Sarli M, Pérez Manghi FC, Gallo R, Zanchetta Jr. The vacuum cleft sign an uncommon radiological sign. Osteoporos Int 2005; 16: 1210-4.
[56] Malghem J, Maldague B, Labaisse MA , et al. Intravertebral vacuum cleft changes in content after supine positioning. Radiology 1993; 187: 483-7.
[57] Hasegawa K, Homma T, Uchiyama S, Takahashi H. Vertebral pseudarthrosis in the osteoporotic spine. Spine (Phila Pa 1976) 1998; 23: 2201-6.
[58] Dupuy DE, Palmer WE, Rosenthal DI. Vertebral fluid collection associated with vertebral collapse. AJR Am J Roentgenol 1996; 167: 1535-8.
[59] Hasegawa K, Homma T, Uchiyama S, Takahashi HE. Osteosynthesis without instrumentation for vertebral pseudarthrosis in the osteoporotic spine. J Bone Joint Surg Br 1997; 79: 452-6.
[60] Matzaroglou C, Georgiou CS, Wilke HJ , et al. Kümmell's disease is ischemic necrosis or vertebral "microcracking" the first step in the sequence?. Med Hypotheses 2013; 80: 505.
[61] Kim DY, Lee SH, Jang JS , et al. Intravertebral vacuum phenomenon in osteoporotic compression fracture report of 67 cases with quantitative evaluation of intravertebral instability. J Neurosurg 2004; 100: 24-31.
[62] McKiernan F, Faciszewski T. Intravertebral clefts in osteoporotic vertebral compression fractures. Arthritis Rheum 2003; 48: 1414-19.
[63] Theodorou DJ. The intravertebral vacuum cleft sign. Radiology 2001; 221: 787-8.
[64] Bielecki DK, Sartoris D, Resnick D , et al. Intraosseous and intradiscal gas in association with spinal infection report of three cases. AJR Am J Roentgenol 1986; 147: 83-6.
[65] Tash RR, Weitzner I Jr. Acute intervertebral gas following vertebral fracture CT demonstration. J Comput Assist Tomogr 1986; 10: 707-8.
[66] Laredo JD, Lakhdari K, Bellaïche L , et al. Acute vertebral collapse CT findings in benign and malignant nontraumatic cases. Radiology 1995; 194: 41-8.
[67] Jang JS, Kim DY, Lee SH. Efficacy of percutaneous vertebroplasty in the treatment of intravertebral pseudarthrosis associated with noninfected avascular necrosis of the vertebral body. Spine 2003; 28: 1588-92.
[68] Gagnerie F, Taillan B, Euller-Ziegler L , et al. Intravertebral vacuum phenomenon in multiple myeloma. Clin Rheumatol 1987; 6: 597-9.
[69] McKiernan F, Jensen R, Faciszewski T. The dynamic mobility of vertebral compression fractures. J Bone Miner Res 2003; 18: 24-9.
[70] Mitchell DG, Rao VM, Dalinka MK , et al. Femoral head avascular necrosis correlation of MR imaging, radiographic staging, radionuclide imaging, and clinical findings. Radiology 1987; 162: 709-15.

Endorsements



"Open access will revolutionize 21st century knowledge work and accelerate the diffusion of ideas and evidence that support just in time learning and the evolution of thinking in a number of disciplines."


Daniel Pesut
(Indiana University School of Nursing, USA)

"It is important that students and researchers from all over the world can have easy access to relevant, high-standard and timely scientific information. This is exactly what Open Access Journals provide and this is the reason why I support this endeavor."


Jacques Descotes
(Centre Antipoison-Centre de Pharmacovigilance, France)

"Publishing research articles is the key for future scientific progress. Open Access publishing is therefore of utmost importance for wider dissemination of information, and will help serving the best interest of the scientific community."


Patrice Talaga
(UCB S.A., Belgium)

"Open access journals are a novel concept in the medical literature. They offer accessible information to a wide variety of individuals, including physicians, medical students, clinical investigators, and the general public. They are an outstanding source of medical and scientific information."


Jeffrey M. Weinberg
(St. Luke's-Roosevelt Hospital Center, USA)

"Open access journals are extremely useful for graduate students, investigators and all other interested persons to read important scientific articles and subscribe scientific journals. Indeed, the research articles span a wide range of area and of high quality. This is specially a must for researchers belonging to institutions with limited library facility and funding to subscribe scientific journals."


Debomoy K. Lahiri
(Indiana University School of Medicine, USA)

"Open access journals represent a major break-through in publishing. They provide easy access to the latest research on a wide variety of issues. Relevant and timely articles are made available in a fraction of the time taken by more conventional publishers. Articles are of uniformly high quality and written by the world's leading authorities."


Robert Looney
(Naval Postgraduate School, USA)

"Open access journals have transformed the way scientific data is published and disseminated: particularly, whilst ensuring a high quality standard and transparency in the editorial process, they have increased the access to the scientific literature by those researchers that have limited library support or that are working on small budgets."


Richard Reithinger
(Westat, USA)

"Not only do open access journals greatly improve the access to high quality information for scientists in the developing world, it also provides extra exposure for our papers."


J. Ferwerda
(University of Oxford, UK)

"Open Access 'Chemistry' Journals allow the dissemination of knowledge at your finger tips without paying for the scientific content."


Sean L. Kitson
(Almac Sciences, Northern Ireland)

"In principle, all scientific journals should have open access, as should be science itself. Open access journals are very helpful for students, researchers and the general public including people from institutions which do not have library or cannot afford to subscribe scientific journals. The articles are high standard and cover a wide area."


Hubert Wolterbeek
(Delft University of Technology, The Netherlands)

"The widest possible diffusion of information is critical for the advancement of science. In this perspective, open access journals are instrumental in fostering researches and achievements."


Alessandro Laviano
(Sapienza - University of Rome, Italy)

"Open access journals are very useful for all scientists as they can have quick information in the different fields of science."


Philippe Hernigou
(Paris University, France)

"There are many scientists who can not afford the rather expensive subscriptions to scientific journals. Open access journals offer a good alternative for free access to good quality scientific information."


Fidel Toldrá
(Instituto de Agroquimica y Tecnologia de Alimentos, Spain)

"Open access journals have become a fundamental tool for students, researchers, patients and the general public. Many people from institutions which do not have library or cannot afford to subscribe scientific journals benefit of them on a daily basis. The articles are among the best and cover most scientific areas."


M. Bendandi
(University Clinic of Navarre, Spain)

"These journals provide researchers with a platform for rapid, open access scientific communication. The articles are of high quality and broad scope."


Peter Chiba
(University of Vienna, Austria)

"Open access journals are probably one of the most important contributions to promote and diffuse science worldwide."


Jaime Sampaio
(University of Trás-os-Montes e Alto Douro, Portugal)

"Open access journals make up a new and rather revolutionary way to scientific publication. This option opens several quite interesting possibilities to disseminate openly and freely new knowledge and even to facilitate interpersonal communication among scientists."


Eduardo A. Castro
(INIFTA, Argentina)

"Open access journals are freely available online throughout the world, for you to read, download, copy, distribute, and use. The articles published in the open access journals are high quality and cover a wide range of fields."


Kenji Hashimoto
(Chiba University, Japan)

"Open Access journals offer an innovative and efficient way of publication for academics and professionals in a wide range of disciplines. The papers published are of high quality after rigorous peer review and they are Indexed in: major international databases. I read Open Access journals to keep abreast of the recent development in my field of study."


Daniel Shek
(Chinese University of Hong Kong, Hong Kong)

"It is a modern trend for publishers to establish open access journals. Researchers, faculty members, and students will be greatly benefited by the new journals of Bentham Science Publishers Ltd. in this category."


Jih Ru Hwu
(National Central University, Taiwan)


Browse Contents



Webmaster Contact: info@benthamopen.net
Copyright © 2019 Bentham Open