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The case of a man suffering from undifferentiated seronegative spondyloarthropathy (uSpA) without spine involvement and with iliolumbar ligament ossification is reported. Unlike a similar previously published case showing ossification only of the middle part of the left ligament, our patient had ossification of the whole course of both ligaments.
The osteosclerotic (oc/oc) mouse, a genetically distinct murine mutation that has a functional defect in its osteoclasts, also has rickets and shows an altered endochondral ossification in the epiphyseal growth plate. The disorder is morphologically characterized by an abnormal extension of hypertrophic cartilage at 10 days after birth, which is later (21 days after birth) incorporated into the metaphyseal woven bone without breakdown of the cartilage matrix following vascular invasion of chondrocyte lacunae. In situ hybridization revealed that the extending hypertrophic chondrocytes expressed type I and type II collagen mRNA, as well as that of type X collagen and that the osteoblasts in the metaphysis expressed type II and type X collagen mRNA, in addition to type I collagen mRNA. The topographic distribution of the signals suggests a possible co-expression of each collagen gene in the individual cells. Immunohistochemically, an overlapping deposition of type I, type II, and type X collagen was observed in both the extending cartilage and metaphyseal bony trabeculae. Such aberrant gene expression and synthesis of collagen indicate that pathologic ossification takes place in the epiphyseal/metaphyseal junction of oc/oc mouse femur in different way than in normal endochondral ossification. This abnormality is probably not due to a developmental disorder in the epiphyseal plate but to the failure in conversion of cartilage into bone, since the epiphyseal plate otherwise appeared normal, showing orderly stratified zones with a proper expression of cartilage-specific genes.
The occurrence of heterotopic ossification (HO) is a well-recognized problem after total hip replacement. In a retrospective study, we investigated 32 patients who had undergone surgical excision of symptomatic HO followed by radiation with 7 Gy and nonsteroidal anti-inflammatory drug therapy between 1994 and 1999. The mean follow-up was 20 months (range: 12-60). Clinical and radiographic follow-up examinations included Harris hip score and classification according to Brooker. The preoperative Brooker class was III in 16 cases and IV in 16 patients. Comparison of the Brooker classification at follow-up revealed a statistically significant improvement (p < 0.0001; class 0:3, class I: 14, class II: 8, class III: 7 patients). In one case with symptomatic Brooker class III ossification, surgical reexcision of HO was necessary. A statistically significant increase (p < 0.05) in mean range of motion (ROM) was observed in flexion [preoperative: 57 degrees (+/- 26), follow-up: 83 degrees (+/- 21)], in abduction [preoperative: 17 degrees (+/- 12), follow-up: 24 degrees (+/- 9)], and in rotation (preoperative: 16 degrees (+/- 17), follow-up: 31 degrees (+/- 18)]. Comparison of preoperative Harris hip score (60 +/- 11) and Harris hip score at the time of follow-up examination (73 +/- 17) revealed a statistically significant increase (p < 0.0001) after treatment. At the time of follow-up examination, 18 patients (56%) assessed their pain symptoms as low but 6 patients (19%) reported strong pain symptoms. Nevertheless, the score at the time of examination (35 +/- 10) was statistically improved (p < 0.02) when compared to the preoperative score (30 +/- 8). Surgical excision of Brooker class III or IV heterotopic ossification with limited ROM followed by irradiation and anti-inflammatory prophylaxis results in significant improvement in flexion, abduction, and rotation arc and significant reduction of HO in radiographic examination at follow-up, but pain relief was only satisfactory.
AIM: The sonographic early diagnosis of heterotopic ossifications after total hip replacement. MATERIAL AND METHOD: 53 patients were sonographically and radiologically examined after a total hip-replacement. RESULTS. In the sonographic exam,positive findings were shown in 49.1% (n=26) one week, 66% (n=35) three weeks,73.6% (n=39) six weeks and 77.3% (n=41) twelve weeks after surgery. 88.5% of patients showing positive results in the sonographic exam carried out one week after surgery, later on showed positive x-ray findings (p<0.001). Of the three-week positive x-ray findings (n=19), 78.9% had condensations in the sonographic exam (p<0.001). CONCLUSIONS: Sonographic imaging after hip-replacement seems to be a sensitive and specific method which allows an early diagnosis of ossifications one week after surgery in 2/3 of patients. In this context a therapy concept which helps avoiding the development ossifications would be welcome.
Heterotopic ossification is a frequent and potentially disastrous complication of acute spinal cord injury. Pathogenesis and etiology are not well described, initial clinical symptoms are uncharacteristic, specific laboratory findings do not exist. Between March 1997 and May 2000 all 290 patients admitted to our facility with acute spinal cord injury underwent standardized sonographic examinations of the soft tissue around the hip joint every three weeks, starting as early as two weeks after injury. In 12% of the patient population characteristic sonographic findings for heterotopic ossification were present while the regular x-ray examination was still unremarkable. Laboratory findings (alkaline phosphatase, C-reactive protein, anorganic phosphate) were unspecific. Clinical findings were present only in a few patients. All patients underwent radiotherapy consisting of the administration of 5 times 3 Gy to the area as soon as possible. Follow up demonstrated no progression of the heterotopic bone formation in these cases. In conclusion, regular ultrasound examination proved to be a secure, fast and reproducible method for the very early diagnosis of heterotopic ossification after acute spinal cord injury.
Osteoprotegerin (OPG) is a novel secreted member of the tumor necrosis factor receptor family which plays a crucial role in negative regulation of osteoclastic bone resorption. We investigated both the quantity and quality of heterotopic new bone induced by crude bone morphogenetic protein (BMP) as a means of examining bone metabolism by bisphosphonate administration in OPG-/- mice. Four weeks after implantation of crude BMP, the volume of heterotopic new bone in OPG-/- mice without alendronate was significantly less than in wild-type (WT) mice. Alendronate treatment of OPG-/- mice resulted in enhancement of the volume of heterotopic new bone. Histological findings revealed that WT mice showed normal bone formation with persistent cartilage that was interspersed with islands of bone. In contrast, the cartilage was replaced by trabecular bone and bone marrow adipocytes in OPG-/- mice without alendronate. However, some cartilage was still present in OPG-/- mice with alendronate compared to those without alendronate. All bone formation-related parameters and bone resorption-related parameters were significantly lower in OPG-/- mice with alendronate than in those without alendronate. These findings suggest that in stimulated osteoclastogenesis without OPG, osteoinductive activity induced by crude BMP is inhibited and endochondral ossification induced by crude BMP is accelerated. On the other hand, alendronate treatment of OPG-/- mice caused osteoinductive activity induced by crude BMP to increase and endochondral ossification induced by crude BMP to be decelerated. In conclusion, inhibition of stimulated osteoclastogenesis results in the enhancement of new bone formation and normalization of endochondral ossification.
Heterotopic ossification is the formation of bone in the soft tissues. Soft tissue bone deposition may range from the minimal and inconsequential to massive and clinically significant. In some clinical settings it is a predictable finding with an unpredictable course and in other settings it may be diagnostically confounding. Heterotopic ossification may be encountered in clinically disparate disease processes and circumstances. We review the genetic, neurogenic, post-traumatic, post-surgical and "reactive" causes of heterotopic ossification and discuss some current concepts of its pathogenesis.
We report three cases of spinal osteoblastoma with ossification of the ligamentum flavum (OLF) adjacent to the tumor. The patients in this report, all young adults, had no symptoms except for back pain. Computed tomography (CT) demonstrated a typical radiolucent nidus in the spinal pedicle/lamina with a dense sclerotic rim. In addition, ectopic bone formation at the insertion point of the ligamentum flavum adjacent to the tumor was clearly illustrated. Magnetic resonance imaging (MRI) revealed the tumor and surrounding inflammatory responses, but OLF was not detected clearly. Histological examination revealed endochondral ossification of the ligamentum flavum that is quite unusual for normal young adults. Immunohistochemical assays in one case demonstrated that bone morphogenetic protein (BMP)-2/4 was expressed in the osteoblastic tumor cells. This case raises the possibility that BMPs secreted from the tumor cells triggered ectopic ossification in the spinal ligament.
We studied 178 patients undergoing total hip arthroplasty (66 men and 112 women) retrospectively, with regard to the incidence and severity of heterotopic ossification and the significance of postoperative prophylaxis with non-steroid anti-inflammatory drugs. The overall incidence of heterotopic ossification was 32% 1 year after surgery. The factors increasing the incidence were male gender, previous arthroplasty of the contralateral hip joint, previous surgery on the hip, absence of preoperative treatment with non-steroidal anti-inflammatory drugs and an operating time of more than 100 min. The incidence of heterotopic ossification was lower in the patients of O blood group.
Heterotopic ossification of gastric adenocarcinomas is very rarely observed in humans. In rats such lesions could be induced by ingestion of nitroso compounds. We describe the case of a 70-year-old patient with an extended, initially spleen-infiltrating tubular adenocarcinoma of the stomach with a mucinous component, heterotopic ossifications and pronounced regressive alterations after neoadjuvant chemotherapy. Various speculations regarding the pathogenesis of heterotopic ossifications in gastrointestinal adenocarcinomas are discussed.
The aim of this work was to assess the incidence of disseminated pulmonary dendriform ossification in usual interstitial pneumonia and nonspecific interstitial pneumonia, and to correlate thin-section computed tomography (CT) and histopathologic findings. We retrospectively reviewed thin-section CT and pathologic specimens of biopsy-proven usual interstitial pneumonia (75 patients, 57 men and 18 women, mean age 60 years, range 29-83 years) and nonspecific interstitial pneumonia (44 patients, 9 men and 35 women, mean age 55 years, range 20-73 years). On review of CT and histopathologic specimens, diffuse dendriform ossification was identified in five (four men and one woman, age range 41-68 years, mean 58 years) of 75 patients (6.7%) with usual interstitial pneumonia. It was not seen in any of 44 patients with nonspecific interstitial pneumonia. With thin-section CT (osteoporosis window; window width 818, level 273), disseminated dendriform pulmonary ossification was detected as multiple tiny calcifications in bibasilar subpleural lungs (100% sensitive and 100% specific when compared with histopathologic findings as the gold standard). The thin-section CT finding of multiple tiny calcifications in bibasilar subpleural lungs might be of some help in the differential diagnosis between usual interstitial pneumonia and nonspecific interstitial pneumonia, considering they were not seen in any patients with nonspecific interstitial pneumonia (0%, 0/44) in our series.
In a series of six cochlear-implant candidates, including three small children, labyrinthine ossification in various stages of development was observed at CT. In four of the candidates the ossifying process was more advanced in the semicircular canals than in the cochleae, and in two equally distributed. The ossifying process developed during a period of 4-5 months in two of the children. Asymmetry of its extension was found in four patients. The causative organisms were Hemophilus influenzae and Streptococcus pneumoniae. The radiologic assessment of cochlear-implant candidates should include the semicircular canals where the ossification may start, and herald the development of cochlear ossification.
We conducted a multiple regression analysis on the surgical results (minimum follow-up of 5 years) of 55 patients who underwent expansive open-door laminoplasty (open-door ELAP) for cervical myelopathy due to ossification of the posterior longitudinal ligament (OPLL) in order to determine statistically the impact of factors influencing the results. Duration of myelopathy was found to be a significant factor indicating poor results, while progression of ossification and age at the time of surgery were significant factors indicating deterioration. Three other factors (preoperative severity of myelopathy, degree of spinal canal expansion and changes of the curve indices before and after surgery) did not have a significant influence on the results. To improve the surgical results, it is thus essential to operate on patients as soon as they develop symptoms of myelopathy. There exists a certain limitation in posterior decompression for OPLL including open-door ELAP until prevention of the progression of ossification becomes possible.
Ossification of the posterior longitudinal ligament (OPLL) of the cervical spine is a frequent pathological entity in people of Japanese and Asian extraction and is reported with increasing frequency also in the USA; on the contrary, reports in the European and particularly in the Italian literature remain rare. This paper describes 8 Italian patients with cervical spine stenosis due to OPLL extending three to five vertebral segments (and above C3 in four cases). Magnetic resonance imaging shows the extent of the ossification well in terms of height and cord compression, while computed tomography is useful to measure the thickness of the bone mass and the residual spinal canal. Anterior cervical decompression by discectomy, corpectomy, and removal of the ossified ligament is the treatment of choice and results in clinical improvement in most cases. Decompressive laminectomy may be reserved for patients with ossification extending to four or five levels and above C3. The surgical technique and intraoperative findings are discussed.
OPLL (ossification of the posterior longitudinal ligament of the spine) is a common form of human myelopathy with a prevalence of as much as 4% in a variety of ethnic groups. To clarify the genetic factors that predispose to OPLL, we have studied ttw (tiptoe walking), a mouse model that presents ectopic ossification of the spinal ligaments similar to OPLL and have found that the ttw phenotype is caused by the nonsense mutation of the gene encoding nucleotide pyrophosphatase (NPPS), a membrane-bound glycoprotein thought to produce inorganic pyrophosphate, a major inhibitor of calcification and mineralization. To investigate a possible role of NPPS in the etiology of OPLL, we have examined its genetic variations in OPLL patients. A total of 323 OPLL patients was screened by means of polymerase chain reaction/single-strand conformation polymorphism analysis covering all the exons and their surrounding introns, plus about 1.5-kb of the promoter region. We identified ten nucleotide variations in the NPPS gene; five of the alterations caused amino-acid substitutions, and two of them were found specifically in OPLL patients. Subsequently, we performed an association study using these variations and found a significant association of an allele, viz., a deletion of T at a position 11 nucleotides upstream from the splice acceptor site of intron 20 (IVS20-11delT), with OPLL; the proportion of the individuals having this deletion was significantly higher (P = 0.0029) in OPLL patients than in controls, indicating that those who have this variation may be more susceptible to the abnormal ossification of the spinal ligaments. Thus, our study suggests that NPPS plays an important role in the etiology of human OPLL.
Thoracic ossification of ligamentum flavum (OLF) caused by skeletal fluorosis is rare. Only six patients had been reported in the English literature. This study reports findings from the first clinical series of this disease. This was a retrospective study of patients with thoracic OLF due to skeletal fluorosis who underwent surgical management at the authors' hospital between 1993 and 2003. Diagnosis of skeletal fluorosis was made based on the epidemic history, clinical symptoms, radiographic findings, and urinalysis. En bloc laminectomy decompression of the involved thoracic levels was performed in all cases. Cervical open door decompression or lumbar laminectomy decompression was performed if relevant stenosis was present. Neurological status was evaluated preoperatively, at the third day postoperatively, and at the end point of follow-up using the Japanese Orthopaedic Association (JOA) scoring system of motor function of the lower extremities. A total of 23 cases were enrolled, 16 (69.6%) males and 7 (30.4%) females, age ranging from 42 to 72 years (mean 54.8 years). All patients came from a high-fluoride area, and 22 (95.7%) had dental fluorosis. Medical imaging showed OLF together with ossification of many ligaments and interosseous membranes, including interosseous membranes of the forearm (18/23 patients 78.3%), leg (14/23 patients 60.9%), and ribs (11/23 patients 47.8%). OLF was classified into five types based on MRI findings: localized (4/23 patients 17.4%), continued (12/23 patients 52.2%), skip (3/23 patients 13.0%), combining with anterior pressure (2/23 patients 8.7%), and combining with cervical and/or lumbar stenosis (2/23 patients, 8.7%). Urinalysis showed a markedly high urinary fluoride level in 14 of 23 patients (60.9%). Patients were followed up for an average duration of 4 years, 5 months. Paired t-test showed that the JOA score was slightly but nonsignificantly increased relative to preoperative measurement 3 days after surgery (P = 0.0829) and significantly increased at the end of follow-up (P = 0.0001). In conclusion, Fluorosis can cause ossification of thoracic ligamentum flavum, as well as other ligaments. Comparing with other OLF series, a larger number of spinal segments were involved. The diagnosis of skeletal fluorosis was made by the epidemic history, clinical symptom, imaging study findings, and urinalysis. En bloc laminectomy decompression was an effective method.
Some histological analyses of the ossification of the posterior longitudinal ligament (OPLL) have been reported, but no ultrastructural studies of the ligamentum flavum (LF) in patients with OPLL have been published to date. To understand the pathology of the ossification of the spinal ligament, we examined, by electron microscopy, ultrastructural changes in the LF in cases of OPLL and made a comparison with the LF in cervical spondylotic myelopathy (CSM). Subjects were three men and two women with cervical OPLL who underwent longitudinal spinous process-splitting laminoplasty. During surgery, a small piece of the LF was collected from C2-C3 to C7-T1 and was then analyzed by light and electron microscopy. We observed atrophic elastic bundles with a two-layer structure and disarrangement, a partially torn area, the disappearance of microfibrils, and an enlarged interstitium with an irregular alignment of collagen fibrils. We observed some properties of a cell preceding its death: the initial phase may be the disappearance of the plasma-membrane, followed by the scattering of many organellae around its degenerated nucleus. Finally, many extracellular plasma membrane-invested particles that resemble matrix vesicles remain there without phagocytosis. These results suggest that ultrastructural abnormalities exist in the spinal ligament in cases of ossification of the spinal ligament.
Heterotopic ossifications of the shoulder are uncommon. Rarely, these ossifications are seen after open or even arthroscopic shoulder surgical procedures. Here, we report a patient who underwent a rotator cuff repair, complicated with an axillary nerve paralysis. Postoperatively he developed substantial ossification of the supraspinatus tendon. A review of the literature was done. To our knowledge no other cases similar to this have been reported.