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PubMed2001

Prevention of heterotopic ossification after total hip replacement: a prospective comparison of indomethacin and salmon calcitonin in 60 patients.

We did a prospective consecutive study of prophylaxis for heterotopic ossification (HO) comparing indomethacin (100 mg/day) and salmon calcitonin (3 MRC-U/kg/day) for 14 days. Each group consisted of 30 patients. 19 patients in the indomethacin group and 2 in the calcitonin group developed HO. We conclude that use of calcitonin in the prophylaxis of HO after total hip replacement is more effective than indomethacin.

Aged↗
PubMed2002

Prophylaxis of heterotopic ossification after total hip arthroplasty: a prospective randomized study comparing indomethacin and meloxicam.

We performed a randomized, prospective study on the prophylaxis of heterotopic ossification (HO) after total hip arthroplasty (THR), comparing indomethacin and the selective COX-2 inhibitor meloxicam. From the day after surgery, 272 patients were treated with 7.5 mg meloxicam, 15 mg meloxicam, or 2 x 50 mg indomethacin a day, for 14 days. After 6 months, radiographs of patients treated with 7.5 mg meloxicam showed that HO had occurred in one third. This treatment was therefore stopped after 26 patients have been assigned to this group. According to the intention-to-treat principle, patients given 15 mg meloxicam developed HO in 25% (20% Brooker grade I, 4% grade II and 1% grade III) and those given indomethacin in 10% (7% Brooker grade I, 1% grade II and 2% grade III), a statistically significant difference.

Aged↗
PubMedDate not supplied

Fine structure of ossification in craniopharyngiomas.

Three cases of adamantinomatous craniopharyngiomas were examined by light and electron microscopy and special attention was paid to the formation of ossified tissue. The tumors were composed of neoplastic epithelial cells with keratinized cell nests and fibrous connective tissue. Keratinized cell masses sometimes directly contacted fibrous connective tissue. In these border areas, multipotential mesenchymal cells in the latter may have differentiated into osteoblasts. Ultrastructurally, these osteoblastic mesenchymal cells were surrounded by amorphous ground matrix and collagen fibrils. Membrane-bound vesicles were occasionally seen among the spaces between the collagen fibrils. These vesicles were presumably derived from osteoblastic mesenchymal cells and were morphologically similar to matrix vesicles. Precipitation of hydroxyapatite crystals in these vesicles was considered to be the initial stage of ossification. Further mineralization of adjacent collagen fibrils resulted in the formation of small bone trabeculae. Then apositional growth of ossified tissue occurred in the surrounding keratinized cell masses.

Bone and Bones↗
PubMedDate not supplied

Resection of heterotopic ossification and Didronel therapy--regaining wheelchair independence in the spinal cord injured patient.

Ankylosis of the joints secondary to heterotopic ossification in the spinal cord injured is not uncommon. Five patients had ankylosis of the hip and knee joints which limited their ability to function in their wheelchairs. They underwent eight resections to improve their functional capabilities. All patients were treated pre- and postoperatively with disodium etidronate (EHDP, DIDRONEL). The average interval from injury to surgery was nine years nine months and the average interval from surgery to follow-up was two years three months. With clearly defined goals, proper patient selection, good pre- and postoperative management and intense rehabilitation combined with Didronel, optimum functional results were achieved.

Etidronic Acid↗
PubMed1992

Heterotopic ossification of the extensor tendons in the hand associated with traumatic spinal cord injury.

Heterotopic ossification (HO) occurs in spinal cord injury (SCI), most frequently in the large joints such as hips, shoulders, knees, and elbows. It always occurs below the level of neurologic lesion. In the upper extremities, HO associated with SCI usually involves the flexor side of the involved joint. HO has only been reported once to involve the hands and rarely develops parallel to the long bones. We present a 44-year-old male with C5 traumatic SCI who developed HO involving the extensor tendons of one hand. The HO was discovered four months after the SCI and involved the extensor sheaths of the second, third, and fourth digits, from the metacarpal-phalangeal joint to the proximal inter-phalangeal joint. The patient had been improving neurologically with poor to fair extension of the right wrist allowing for tenodesis finger flexion, but with the onset of HO he lost some functional grasp. Diagnosis, possible etiology, and treatment (including options of radiation therapy and surgery) are discussed.

Adult↗
PubMed2006

Intracranial plasma cell-granuloma with extensive ossification.

Intracranial plasma-cell granuloma is non-neoplastic proliferation of plasma cells which occurs rarely. We present an unusual case of an 18-year-old female patient with extensively ossified intracranial plasma-cell granuloma. Computed Tomography (CT) and Magnetic Resonance Image (MRI) demonstrated a left frontoparietal mass with extensive calcification. The lesion was removed subtotally. Histopathological findings revealed diffuse inflammatory cells consisting mostly of reactive plasma cells, histiocytes and neutrophils, several lymphocytes, lymphoplasmacytic cells, a few eosinophils throughout the dura and adjacent brain. Widespread psammomatous and dystrophic calcifications, and very extensive ossification with trabecular bone formation were present within the lesion. In the case of an intracranial mass lesion with calcification, plasma-cell granuloma, although rare, should be included in the differential diagnosis.

Adolescent↗
PubMed2003

Acquired heterotopic ossification in the settings of cerebral anoxia and alternative therapy: two cases.

Acquired Heterotopic Ossification (HO) has been well described in the literature as a recognized complication following spinal cord injury, traumatic brain injury and joint arthroplasty. Commonly, large proximal limb joints are affected. The underlying mechanisms for ectopic bone formation remain poorly elucidated. Post-stroke hemiplegia as a cause of neurogenic HO is rare, and no published reports of HO occurring after anoxic brain injury in adults have been documented. This study reports two unusual cases of acquired HO: (1) Polyarticular HO involving the ankle joint in a 24-year-old Chinese female who suffered severe anoxic encephalopathy following near drowning which resulted in persistent vegetative state; and (2) Elbow HO in chronic post-stroke hemiplegia occurring as a complication of alternative therapy following repeated forceful manipulation by a traditional practitioner in a 46 year-old male.

Adult↗
PubMed2002

In situ gene expression analysis during BMP2-induced ectopic bone formation in mice shows simultaneous endochondral and intramembranous ossification.

We examined the molecular progression of ectopic bone development upon application of recombinant human bone morphogenetic protein-2 (rhBMP2), using a commercial collagen type I carrier, in the hind quarter muscles of mice. We performed a gene expression study using mRNA in situ hybridisation to compare embryonic cartilage and bone formation with BMP2-induced ectopic bone formation. As bone growth can be induced postnatally or in adult animals, we examined the expression of molecules regulating embryonic bone development. We found that the mRNAs of the same molecules, such as Indian hedgehog (IHH), parathyroid hormone (PTH)/PTH-related peptide receptor (PPR) and BMPs, that regulate embryonic cartilage and bone development, are expressed during BMP-induced ectopic bone formation, suggesting parallels in the mechanisms controlling these processes. Our studies support by molecular means the previous findings in rats that BMP2-induced ectopic bone formation in mice undergoes bone development involving both modes, endochondral and intramembranous ossification, simultaneously at different sites of the implant.

Animals↗
PubMed1995

Ossification of the posterior longitudinal ligament of the spine: a case report.

Ossification of the posterior longitudinal ligament of the spine (OPLL) is a common cause of severe myelopathy and radiculopathy in Oriental populations. It typically involves the cervical spine. We present a 60-year-old Asian male with OPLL who developed progressively worsening cervical myopathy. The diagnosis and management are discussed.

Bone Transplantation↗
PubMed1995

An unusual location for heterotopic ossification: lumbar anterior longitudinal ligament.

Heterotopic ossification (HO) is a well known complication of spinal cord injury. It usually affects the hips and knees, with less common involvement of the shoulders and elbows. We present a patient with incomplete tetraplegia who developed HO in the left hip and in the plane of the lumbar anterior longitudinal ligament from L3 to L5. During evaluation for the patient's complaints of low back pain, a fracture was noted in the HO which was confirmed by three-dimensional CT scan. We postulate that this fracture contributed to his symptoms. Review of the literature on HO in spinal cord injured patients indicates this to be an unusual location for HO. Although HO of the lumbar anterior longitudinal ligament is a rare occurrence, this possibility should be considered in the evaluation of back pain in spinal cord injured patients.

Cervical Vertebrae↗
PubMed1999

Heterotopic ossification: diagnosis and management, current concepts and controversies.

HO is a pathologic process in which soft tissues undergo ossification. The etiology is unknown. Patients with neurologic deficits develop HO in the proximal joints. An incidence of 20% to 30% is commonly reported; 8% to 10% of these patients develop severe functional limitations. Routine prophylaxis in patients with SCI cannot be justified. Early diagnosis and treatment with EHDP or other anti-inflammatory medications have been shown to result in good functional outcomes. Elevated SAP levels and positive radionuclide scan, in addition to restriction of joint ROM, are indicative of HO formation. Role of other anti-inflammatories, radiation, and early surgical excision without bone maturity in these patients need to be studied further. A small percentage of patients require surgery to improve function. Joint manipulation to produce pseudoarthrosis is not indicated in patients with SCI.

Humans↗
PubMed2001

Refractory heterotopic ossification with complications.

BACKGROUND: Heterotopic ossification (HO) following spinal cord injury can lead to various complications, including venous thrombosis, autonomic dysreflexia, and pressure ulcers. We report refractory, complicated HO in a 19-year-old man with C8 incomplete tetraplegia. He first presented at 9 weeks postinjury with fever and swelling of his right leg. Ultrasound indicated a deep venous thrombosis (DVT). Persistent symptoms prompted triple-phase bone scan and magnetic resonance imaging (MRI), which revealed HO compressing the right external iliac vein and no evidence of DVT. The HO was complicated by hypercoagulability. CLINICAL COURSE: The HO was refractory to oral indomethacin and etidronate; therefore, intravenous etidronate was instituted, resulting in only a transient decrease in alkaline phosphatase. Local irradiation of the right hip did not decrease the activity of HO. The patient was discharged on oral etidronate, indomethacin, and warfarin. This complicated case raises issues regarding early diagnosis and aggressive treatment of HO, as well as treatment of associated hypercoagulability.

Constriction, Pathologic↗
PubMed2002

Heterotopic ossification complicating prolonged intubation: case report and review of the literature.

BACKGROUND: Within the past decade several reports have been published concerning heterotopic ossification (HO) in adult respiratory distress syndrome patients subjected to prolonged mechanical ventilation. The knee has been the most common site of involvement, which tends to differentiate this entity of HO from those previously described. METHOD: Case report and literature review. FINDINGS: HO associated with prolonged intubation differs in clinical presentation from HO seen in spinal cord injury (SCI) and other trauma. Use of neuromuscular blockade does not appear to explain this risk. An unidentified humoral response mechanism may underlie the development of HO in these cases. Certain individuals may be genetically predisposed to develop HO. CONCLUSION: Increased awareness of this relatively new entity may assist early diagnosis, medical treatment, and eventually direct rehabilitation. Investigation of the pathogenesis of different types of HO may provide clues to the prevention and treatment of HO in individuals with SCI and other central nervous system trauma.

Adult↗
PubMed2003

The value of serum creatine kinase in early diagnosis of heterotopic ossification.

BACKGROUND: Heterotopic ossification (HO) is a complication of spinal cord injury (SCI) characterized by formation of ectopic bone. Early diagnosis is critical, but available diagnostic methods have drawbacks. Serum creatine kinase may be a marker for the development and severity of HO. PARTICIPANTS: 18 SCI patients with diagnosed HO based on clinical findings and bone scintigraphy. METHODS: Serum creatine kinase levels were taken at the time of diagnosis of HO and during subsequent etidronate therapy. RESULTS: Of the 14 patients with normal creatine kinase values, 13 had no evidence of HO on follow-up radiographic examination. Of the 4 patients with elevated creatine kinase, all developed radiographic signs of HO. CONCLUSION: Elevated serum creatine kinase may be associated with a more aggressive course of HO as well as resistance to etidronate therapy. Further studies are needed to determine whether creatine kinase may serve as a marker for early, active HO.

Adult↗
PubMed2004

C-reactive protein and erythrocyte sedimentation rate in patients with heterotopic ossification after spinal cord injury.

BACKGROUND/OBJECTIVE: Formation of heterotopic ossification (HO) in soft tissue after spinal cord injury (SCI) is associated with various degrees of inflammation. Recent studies have shown that inhibition of inflammatory reaction with nonsteroidal anti-inflammatory drugs is an effective prevention of HO after SCI. The goal of this study was to monitor the activity of the most widely used indicators of acute inflammation--namely, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)--in patients with HO. METHODS: In a retrospective study, the results of 37 patients with HO were evaluated. There were 25 patients with tetraplegia and 12 with paraplegia. The age (mean +/- SD) of the patients was 28 +/- 8 years (range = 19-46 years). The patients were admitted to the rehabilitation center 2 to 5 weeks after SCI. HO was confirmed by bone scintigraphy. Blood samples were obtained from the patients at the time of diagnosis of HO and during the therapy. ESR was measured with the Westergren method, and serum CRP was determined by enzyme-linked immunosorbent assay. RESULTS: In the acute stage of HO, both tests were elevated in all patients. In the later stages when clinical signs and symptoms of inflammation were resolving, both tests showed a gradual decline. When clinical signs and symptoms of inflammation (fever, acute soft tissue swelling, and erythema) were not present, the concentration of CRP was normal in 91.2% of patients, whereas only 17.6% of patients had normal ESR. Mean serum concentrations of CRP were 8.9 +/- 5.6 mg/L in the inflammatory phase and 0.9 +/- 0.6 mg/L in the noninflammatory phase. CONCLUSION: The data indicate that serum CRP is a useful and more specific test than is ESR for monitoring the inflammatory activity of HO after SCI. The normalization of CRP was seen during the first 3 to 4 weeks of etidronate therapy, indicating a resolution of acute-phase inflammatory reaction.

Adult↗
PubMed2004

Prevention and treatment of heterotopic ossification after spinal cord injury.

BACKGROUND/OBJECTIVES: Heterotopic ossification (HO) is a frequent, irreversible complication after spinal cord injury (SCI). The objective of this article is to explain the etiology of HO; present new advances in prevention, diagnosis, and management of this complication; and provide a suggested algorithm for clinical management. ETIOLOGY: Although still hypothetical, trauma and overexpression of bone morphogenic protein(s) in traumatized soft tissue appear to play important roles as initiating factors of HO. PREVENTION: Preventive use of nonsteroidal antiinflammatory agents (NSAIDs) reduces the incidence of HO by a magnitude of 2 to 3. MANAGEMENT: Early determination of serum creatine phosphokinase may have a diagnostic value in predicting the onset and severity of HO, and an NSAID may be added to etidronate therapy in the initial inflammatory phase of HO formation until C-reactive protein levels return to normal range. Surgery is indicated in a subset of patients, and a regimen that includes radiation therapy may prevent postoperative recurrence. CONCLUSION: Significant progress has been made in the early prevention and management of HO. Further studies are needed to elucidate the etiology.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2005

Do non-steroidal anti-inflammatory drugs cause endoprosthetic loosening? A 10-year follow-up of a randomized trial on ibuprofen for prevention of heterotopic ossification after hip arthroplasty.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are known to be potent inhibitors of new bone formation. We investigated whether NSAIDs given at surgery influence the long-term results after total hip arthroplasty (THA). PATIENTS AND METHODS: We performed a 10-year follow-up on 142 of 144 patients who had taken part in a randomized trial on the preventive effects of the NSAID ibuprofen on heterotopic ossification after THA. 96 patients were treated with ibuprofen: 48 for 1 week postoperatively, 48 for 2 weeks postoperatively, and 48 patients were not treated. RESULTS: 13 patients had been revised. All revisions except 1 belonged to groups treated with ibuprofen. The 10-year risk for revision was significantly higher in the ibuprofen-treated patients (p = 0.05). Eleven of the revisions occurred due to fractures of the femur (2) or aseptic loosening (9), reasons that may be attributed to negative effects of ibuprofen. For these patients, the 10-year risk for revision was not statistically significantly different between treated and untreated patients (p = 0.08). In addition to the revised patients, 94 other patients were alive at the 10-year follow-up and 84 underwent radiographic examination. 9 loose prostheses were found radiographically, but these were equally distributed between ibuprofen-treated and untreated hips. INTERPRETATION: The high proportion of revisions in the ibuprofen groups, in combination with clinical and experimental evidence of inhibitory effects on new bone formation of NSAIDs, warrants further investigation of the effects of these drugs on prosthetic fixation.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1998

Genetic mapping of ossification of the posterior longitudinal ligament of the spine.

Ossification of the posterior longitudinal ligament of the spine (OPLL) is recognized as a common disorder among Japanese and throughout Asia. Estimates of its prevalence are in the range of 1. 9%-4.3%. Although its etiology is thought to involve a multiplicity of factors, epidemiological and family studies strongly implicate genetic susceptibility in the pathogenesis of OPLL. In this study we report an identification of a predisposing locus for OPLL, on chromosome 6p, close to the HLA complex. The evidence for this localization is provided by a genetic-linkage study of 91 affected sib pairs from 53 Japanese families. In this sib-pair study, D6S276, a marker lying close to the HLA complex, gives evidence for strongly significant linkage (P = .000006) to the OPLL locus. A candidate gene in the region, that for collagen 11A2, was analyzed for the presence of molecular variants in affected probands. Of 19 distinct variants identified, 4 showed strong statistical associations with OPLL (highest P = .0004). These observations of linkage and association, taken together, show that a genetic locus for OPLL lies close to the HLA region, on chromosome 6p.

Chromosome Mapping↗