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PubMed1995

Biochemical analysis of heterotopic ossification in spinal cord injury patients.

Heterotopic ossification (HO) represents a frequent complication in spinal cord injury (SCI) patients. Samples of HO taken from SCI patients were studied and compared to normal bone. We used a procedure of bone particle fractionation (according to their degree of mineralisation) which allowed us to establish a profile reflecting the metabolic remodeling of bone and to analyse the organic matrix of the newly synthesised tissue. In paraplegic patients, we noted that there was a large increase of the proportion of a degree of calcified bone in the HO as we had previously observed in cortical as well as in cancellous bone of the same patients. Based on aminoacid analyses, we observed in the newly synthesised organic matrix of HO a decreased proportion of hydroxyprolyl residues resulting either from an alteration of the prolyl hydroxylation or from the presence of an excess of non-collagen polypeptides. These results are similar to those seen in sublesional bone of the SCI patients. This study demonstrates that HO is a newly formed bone which has a high rate of turnover as is seen in growing bone. This must be taken into account for the treatment of the patients.

Adult↗
PubMed1996

Anterior decompression and fusion for ossification of the posterior longitudinal ligament of the upper thoracic spine causing myelopathy: using the manubrium splitting approach.

The effectiveness and problems associated with the operation of anterior decompression and fusion using the manubrium splitting approach for thoracic myelopathy due to ossification of the posterior longitudinal ligament (OPLL) of the upper thoracic spine carried out in nine patients was investigated. They were followed up for 1 year or more following the operation. The severity of the thoracic myelopathy was evaluated using the Japanese Orthopaedic Association score, and the surgical outcome was evaluated using recovery rates. This study includes investigation of the surgical outcome and of any postoperative complications, and radiographic observation of bony union and the progression of OPLL within the area of the anterior decompression. The caudal limit of the anterior decompression achieved by splitting the manubrium was the T3 vertebral body. A recovery rate of 71% was achieved during an average follow-up period of 35 months. Only one transient recurrent nerve palsy, and in another patient cerebrospinal fluid leakage occurred as postoperative complications. Radiographic examinations confirmed bony union in all of the patients, and there was no instance of spinal canal stenosis caused by progression of the OPLL within the area of the anterior decompression. Anterior decompression and fusion by splitting the manubrium was an effective surgical procedure for OPLL of the upper thoracic spine, to achieve a good outcome, however, the extent of anterior decompression was limited.

Adult↗
PubMed1997

Evaluation and management of heterotopic ossification in patients with spinal cord injury.

Sixty-three patients with paralysis secondary to spinal cord injury (SCI) were screened for heterotopic ossification (HO) by bone scintigraphy 27 +/- 14 (mean +/- SD) days after SCI. There were four female and 59 male patients, 36 had paraplegia and 27 tetraplegia. The age of patients was 28 +/- 9 years. Bone scintigraphy was obtained with a 3-phase test using 99m-technetium labeled diphosphonate, and the positive third phase was used as a criterion for diagnosis of HO. Bone scintigraphy was negative for HO in 27 patients (14 tetraplegic and 13 paraplegic) and positive in 36 patients (13 tetraplegic and 23 paraplegic). The patients with positive HO were treated with etidronate, first with an intravenous dose of 300 mg/day for 3 days, and then with an oral dose of 20 mg/kg/day for 6 months. The follow-up of patients consisted of clinical and radiographic evaluations every 2-4 months. The extent of HO was classified radiographically. In the treated group of patients who completed the entire course of etidronate therapy one patient developed HO, the remaining 28 (97%) patients had no radiographic evidence of HO during the follow-up of 10.6 +/- 4.5 months after initiation of therapy. Our data indicate that: (a) early HO can be detected in the asymptomatic patients using bone scintigraphy on the average of 4 weeks (27 +/- 14 days) after SCI and (b) the therapy with etidronate might be effective in the prevention of HO in majority of patients when the treatment is initiated in an early stage of heterotopic bone formation.

Adolescent↗
PubMed1997

Resection of heterotopic ossification of the hip in spinal cord injured patients.

Twenty nine spinal cord injury patients were treated by resection of heterotopic ossification in 41 hips. The average follow-up period after surgery was 4.2 years. The mean time to surgery after injury was 82.1 months. The indications for surgery were seating problems, loss of function, pressure sores and pain. The average preoperative motion in flexion and extension was 21.95 degrees, the average intraoperative motion was 94.51 degrees. The average motion at follow-up evaluation was 82.68 degrees. Clinical relevant recurrence occurred in three patients. Complications excluding recurrence occurred in 10 hips, including deep and superficial wound infections, fracture, aneurysm and pressure ulcer. The operation was followed by a specific regime of physiotherapy and radiation therapy.

Adult↗
PubMed1998

Influence of heterotopic ossification of the hip on bone densitometry: a study in spinal cord injured patients.

OBJECTIVE: To evaluate (1) the magnitude of falsely elevated bone density results caused by heterotopic ossification (HO) around the hip and (2) effect of age of patients when the measurement was taken, age of patients at injury, and age of injury (time since event) to the prevalence of HO. SUBJECTS AND METHODS: We blindly analyzed plain radiographs of the hip [(obtained within 1 month of dual energy X-ray absorptiometry (DEXA)] in 107 spinal cord injured (SCI) patients for HO and matched the result to the three regions of interest (ROI): the femoral neck, Ward's triangle, and the trochanter. The influence of HO on bone densitometric values was determined by the analysis of variance (ANOVA) and post-hoc analysis. RESULTS: Nineteen (18%) patients had HO; overlying the femoral neck (79%), trochanter (74%) and Ward's triangle (37%), respectively. Significant elevation of densitometric values (P < 0.05 or less) was observed in a various magnitude at each ROI, with the greatest elevation at Ward's triangle. The prevalence of HO was high when the patients were injured at age range of 20-39 years. CONCLUSIONS: HO around the hip can cause significantly elevated bone densitometry results at all ROIs, which can obscure underlying osteoporosis, leading to underestimation of fracture risk. Determination of bone density in this region with corresponding plain radiographs would be of help. In SCI patients, prevalence of HO was high when the age of patients at injury was 20-39 years.

Absorptiometry, Photon↗
PubMed1999

The treatment of immature heterotopic ossification in spinal cord injury with combination surgery, radiation therapy and NSAID.

Heterotopic ossification (HO) is a frequent complication associated with spinal cord injury. Management of HO consists of a combination of range-of-motion, diphosphonates, nonsteroidal antiinflammatory agents, radiation therapy, and in some cases, surgical resection. The appropriate timing of surgical resection has traditionally been based on maturity of the HO. The case presented is that of a 33-year-old male with T8 complete paraplegia who developed HO about the left hip resulting in impaired sitting. The patient underwent successful surgical wedge resection of the HO despite apparent immaturity of the HO. A comprehensive review of the literature is presented which suggests that early resection of immature HO may not be predictive of a higher recurrence rate.

Adult↗
PubMed1999

Radiological pathogenesis of cervical myelopathy in 60 consecutive patients with cervical ossification of the posterior longitudinal ligament.

STUDY DESIGN: The radiological pathogenetic factors for cervical myelopathy in 60 consecutive patients with cervical ossification of the posterior longitudinal ligament (OPLL) were investigated retrospectively. OBJECTIVE: To clarify which patients with OPLL will develop cervical myelopathy. METHODS: Sixty consecutive patients with OPLL were radiologically assessed comparing the myelopathic patient group (M group, n=41) and the mild or non-myelopathic patient group (non-M group, n=19). RESULTS: The narrowing ratio of the spinal canal in the M group (47.1%) was significantly greater (P=0.026) than that in the non-M group (38.3%). The two groups showed a significant difference (P=0.0016) with regard to the Pavlov ratio (M group, 0.73; non-M group, 0.84). The total range of motion of the cervical spine did not differ between the two groups but the per cent range of motion was significantly greater (P=0.037) in the M group than in the non-M group. CONCLUSION: This study suggests that factors important in the onset or aggravation of myelopathy are factors related to pathological compression by OPLL, cervical soft disc herniation, developmentally narrow spinal canal, and local or non-proportional hypermobility.

Adult↗
PubMed2000

Osteonecrosis after treatment for heterotopic ossification in spinal cord injury with the combination of surgery, irradiation, and an NSAID.

STUDY DESIGN: Case report. OBJECTIVE: Heterotopic ossification (HO) is a frequent complication in spinal cord injury (SCI) that is often difficult to treat. Although surgery may become necessary, operative resection has been associated with complications and poor outcome due to a high recurrence rate. Additional methods of treatment to reduce the recurrence rate have been developed, including post operative irradiation and NSAIDs. This article presents three patients, who developed an osteonecrosis of the femoral head after the combined treatment for HO of surgery, irradiation, and an NSAID.

Adult↗
PubMed2000

The efficacy of biochemical markers in patients with ossification of posterior longitudinal ligament of the spine.

STUDY DESIGN: Serum levels of carboxyterminal propeptide of type I collagen (PICP), osteocalcin (OC), carboxyterminal telopeptide of type I collagen (ICTP) and urinary levels of pyridinoline (Pyr) and deoxypyridinoline (Dpyr) were measured in patients with ossification of posterior longitudinal ligament of the spine (OPLL) and age-matched control subjects. OBJECTIVES: To evaluate the efficacy of these biochemical markers of the patients with OPLL. SETTING: Department of Orthopedic Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan. METHODS: Spot urine and blood samples were obtained from 20 healthy males aged 45 - 78 (mean+/-SD; 63. 0+/-11.5) and 22 male patients with OPLL aged 46 - 77 (mean+/-SD; 59. 9+/-8.8), and serum levels of PICP, OC, ICTP and urinary levels of Pyr and Dpyr were measured. RESULTS: There were no significant difference in age, serum PICP, OC, ICTP, urinary Pyr and Dpyr levels between OPLL and control group. CONCLUSION: Neither bone formation nor bone resorption was accelerated in the patients with OPLL.

Aged↗
PubMed2001

Microvascular changes in the lower extremities of paraplegics with heterotopic ossification.

OBJECTIVES: To investigate the morphological aspects of blood microvasculature of the skin and subcutaneous tissues in subjects with paraplegia with heterotopic ossification (HO). METHODS: In two patients with traumatic spinal cord injury and HO, punch biopsies of skin and hypodermic soft tissue in the region of HO near the hip were studied with histological and ultrastructural methods. RESULTS: Alterations of endothelial cell and basement membrane of capillaries and small vessels were observed. Hyperactive endothelium, thickening and reduplication of the basement membrane, changes of the perivascular connective tissues and microcalcifications in the subcutaneous fat tissue were also seen. CONCLUSIONS: This present study indicates microvascular changes in the skin and subcutaneous tissue in the region of HO near the hip of two subjects with paraplegia. In our opinion the described vascular changes may induce hypoxiemic alterations of the soft para-articular tissues leading metabolic changes which may contribute to the development of HO. Therefore, it cannot be concluded whether these changes are directly responsible for HO induction.

Adult↗
PubMed2001

Prevention of heterotopic ossification after spinal cord injury with indomethacin.

STUDY DESIGN: A randomized, prospective, double-blind, placebo-controlled clinical trial. OBJECTIVES: To determine the effect of indomethacin on the prevention of heterotopic ossification (HO) following spinal cord injury (SCI). SETTING: County Hospital, Miami, Florida, USA. METHODS: Sixteen patients were treated with slow-release indomethacin 75 mg daily and 17 patients received placebo for a period of 3 weeks. Prevention was started 21+/-14 days after SCI. In both groups of patients there was similar age of the patients as well as the level of SCI and ASIA impairment scale. Two methods were used to diagnose HO, bone scintigraphy and radiographic examination. Bone scintigraphy with technetium labeled methylene-diphosphonate was used for diagnosis of early stage, while radiography was used for diagnosis of late stage of HO development. RESULTS: A significantly lower incidence of early HO was found in the indomethacin group (25%) than in the placebo group (65%; P<0.001). Similarly there was a significant reduction of late HO in the indomethacin group (12.5%) as compared to the placebo group (41%; P<0.001). CONCLUSION: Our data suggest that indomethacin used during the first 2 months after SCI is effective in prevention of HO in a significant number of patients.

Adult↗
PubMed2002

Neurogenic heterotopic ossification in spinal cord injury.

Neurogenic heterotopic ossification (NHO) is a frequent complication in spinal cord injury (SCI) that is often difficult to treat. This review emphasizes the incidence, risk factors and clinical signs of NHO in SCI patients. Although the exact pathophysiology underlying NHO in neurologic patients is not yet understood, different pathogenic mechanisms have been proposed in the literature. A selection of the most important theories will be given and discussed. Moreover the different diagnostic, therapeutic, and preventive methods currently used in NHO management after SCI will be reviewed.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2003

Deep vein thrombosis and heterotopic ossification in spinal cord injury: a 3 year experience at the Swiss Paraplegic Centre Nottwil.

STUDY DESIGN: Retrospective review of patient data. OBJECTIVES: (i) To determine the incidence and time of deep vein thrombosis (DVT) under low molecular weight heparin (LMWH) prophylaxis in spinal cord injury (SCI), (ii) to determine the incidence and time of heterotopic ossification (HO) and (iii) to assess a possible aetiologic relationship in the pathogenesis of DVT and HO. SETTING: Swiss Paraplegic Centre, Nottwil. METHODS: We analyzed the incidence of DVT and HO in 1209 SCI patients (275 first rehabilitations) at the Swiss Paraplegic Centre Nottwil from 1998 to 2000. Clinical files and laboratory data were scrutinised for particularities preceding DVT and HO. RESULTS: The incidence of DVT was 6.55% for first rehabilitation compared to only 1.59% in all patients hospitalised. DVT was complicated by pulmonary embolism (PE) in 1.45% and 0.47% respectively. Incidence of HO was 8% for first rehabilitation and 1.82% for all patients hospitalised. In first rehabilitation patients the peak for DVT occurred around day 30 contrary to HO with a peak around day 120. In single patients HO was identified by MRI as a rapidly progressing process. Laboratory profiles were inflammatory in both HO and DVT. Increased physical activity preceding HO was observed in four patients. In two patients acute HO was complicated by ipsilateral DVT. CONCLUSION: Prophylaxis with LMWH and elastic stockings significantly reduces the frequency of DVT during first rehabilitation in SCI. DVT and HO are both associated with laboratory parameters of non-infectious inflammation. The later onset of HO coinciding with ongoing mobilisation, argues for a different pathogenetic mechanism. Acute HO of the hip region appears to favour ipsilateral DVT by well known thrombogenic mechanisms.

Adolescent↗
PubMed2004

Prevention of heterotopic ossification after spinal cord injury with COX-2 selective inhibitor (rofecoxib).

STUDY DESIGN: A randomized, prospective, double-blind, placebo-controlled clinical trial. OBJECTIVES: To determine the effect of COX-2-selective inhibitor on the prevention of heterotopic ossification (HO) after spinal cord injury (SCI). SETTING: County and University Teaching Hospital, Miami, FL, USA. METHODS: A total of 76 patients were enrolled in the study. Among them, 39 patients received placebo, and 37 received COX-2-selective inhibitor rofecoxib 25 mg daily for a period of 4 weeks. Prevention was started 3 weeks after spinal cord injury (SCI). In both groups of patients there was similar age as well as the level of SCI and ASIA impairment scale. Two methods were used to diagnose early HO, clinical symptoms and bone scintigraphy. Radiography was used for diagnosis of late stages of HO development. RESULTS: A significantly lower incidence of HO was found in the rofecoxib group (13.4%) than in the placebo group (33.3%: P<0.05). In patients receiving rofecoxib, there was a 2.5 times lower relative risk of developing HO than in the placebo group (95% CI, 2.3-6). There were no patients who discontinued the study due to adverse effects of medication. CONCLUSION: Our data suggest that COX-2-selective inhibitor rofecoxib is an effective medication in prevention of HO after SCI.

Adolescent↗
PubMed2005

Postmortem study of the spinal cord showing snake-eyes appearance due to damage by ossification of the posterior longitudinal ligament and kyphotic deformity.

UNLABELLED: CLINICAL DESIGN: A case report. OBJECTIVES: To elucidate the clinical role of snake-eyes appearance in this case, correlation between radiological, clinical and postmortem study was performed. SETTING: Aichi, Japan. CASE REPORT: A 73-year-old man developed weakness and pain in the upper limbs due to kyphotic deformity secondary to laminectomy for cervical ossification of the posterior longitudinal ligament. Axial magnetic resonance imaging revealed snake-eyes appearance from C4 to C6. He died of acute myocardial infarction 3 months after anterior decompressive surgery. RESULTS: A postmortem examination of the cervical spinal cord showed small cystic six necrotic areas at the junction of the central gray matter and the ventrolateral posterior column, one in the right and one in the left, in association with neuronal loss in the anterior horn. CONCLUSIONS: Bilateral small intramedullary high-signal areas known as 'snake-eyes appearance' located around the central gray matter and the ventrolateral posterior column, are associated with neuronal loss in the compressed anterior horn that played an important role in worsening weakness of the upper limbs.

Aged↗
PubMed2005

Amino-bisphosphonates in heterotopic ossification: first experience in five consecutive cases.

STUDY DESIGN: Retrospective, observational study in five consecutive cases. OBJECTIVES: The management of heterotopic ossification (HO), a frequent complication after spinal cord injury (SCI) and after orthopaedic surgery, is a therapeutic challenge with high recurrence rates of over 50%. Conflicting data were reported for Etidronate. The use of the more potent new generation of amino-bisphosphonates has been put forward in different inflammatory, dysmorphogenic bone disease. In order to try and halt the underlying dysfunctional bone metabolism we have studied the action of pamidronate in five consecutive high-risk patients with established HO of different etiology undergoing surgical removal. SETTING: University Hospital of Basel, Switzerland, Division of Endocrinology, Diabetology and Clinical Nutrition and the Department of Orthopedic Surgery. METHODS: In all five patients, ranging from 47 to 68 years of age, we used continuous pamidronate infusions perioperatively at a dosage of 120 mg in the first 12 h and subsequent reduction to 75-60-30-15 mg/12 h over a period of 10-14 days. RESULTS: None of these patients showed clinical, radiographical and laboratory signs of HO recurrence or new forming HO in the follow-up 5-54 month after surgery. Potential side effects of high-dose bisphosphonate therapy such as osteoporosis and osteomalacia were not reported in any case. CONCLUSION: We postulate that pamidronate might have pronounced beneficial effects in high-risk patients with established HO undergoing excision surgery. Since the therapeutic window of amino-bisphosphonates has not yet been defined and the minimal necessary doses for preventing new HO are unknown, further studies are encouraged to confirm our findings and to identify the necessary dosage and duration of treatment and to pinpoint, which patients will benefit most from this treatment.

Aged↗
PubMed2000

Symptomatic ossification of the posterior longitudinal ligament of the cervical spine: pictorial essay.

Symptomatic ossification of the posterior longitudinal ligament (OPLL) of the cervical spine is a rare but well-documented condition. It is the causative factor in up to 5% of cases presenting with cervical radiculopathy or myelopathy. Computed tomography is the modality of choice in showing the distinctive characteristics and extent of the disease. Magnetic resonance imaging (MRI) is sensitive in detecting cord compression and its attendant complications. Cervical OPLL commonly affects those of middle and advanced age, and the condition is noted to be particularly common in Japanese, although other racial groups are also affected. A 'mushroom' or 'hill' shape on axial CT typifies OPLL. A sharp radiolucent line separating the posterior vertebral margin from the superficial component of the ossified ligament is a characteristic feature.

Cervical Vertebrae↗