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Estimates of heritability for ossification of the cartilages of the front feet in the Finnhorse.

REASONS FOR PERFORMING STUDY: Ossification of the cartilages in the foot is common in coldblooded horses, but prevalence as well as ossification pattern varies between breeds; research on estimation of heritability for the condition has been limited. OBJECTIVES: Our purpose was to calculate estimates of 1) heritability for ossification parameters of the cartilages in the front feet of the Finnhorse and 2) genetic correlations between the different ossification parameters. METHODS: Estimates of heritability for different ossification parameters of the cartilages in the front feet and of genetic correlations between different parameters were evaluated in data consisting of dorsopalmar radiographs of the front feet and pedigree up to the fourth generation of 964 Finnhorses (age > or = 2 years; 345 females and 619 males). Ossification at the base of the cartilages and total ossification, including separate centres of ossification, were graded 0-5 according to the most proximal point of ossification and the presence of separate centres of ossification was recorded separately. The data were analysed using a model including a fixed sex-age subclass effect and a random animal effect. Variance and covariance components were estimated with the restricted maximum likelihood (REML) method assuming an animal model. RESULTS: Females had more ossification than males and this difference increased with age. The ossification in the medial cartilages progressed significantly with age in females but not in males. In the lateral cartilages, the increase in ossification with age was evident in both sexes. Separate centres of ossification were an incidental finding. Estimates of heritability for the ossification parameters varied slightly between the cartilages as well as between the front feet. For total ossification, the estimates of heritability varied between 0.31 (right lateral) and 0.50 (left medial) and were slightly higher for ossification at the base of the cartilages. High genetic correlations were found for total ossification between the medial and lateral cartilages in the foot and for parallel ossification parameters between the right and left foot. CONCLUSIONS: The estimates of heritability were relatively high, and both cartilages and front feet have a similar genetic tendency to ossify. POTENTIAL RELEVANCE: This information is useful in further studies assessing other factors contributing to the ossification process and also in the planning and modifying breeding programmes.

Aging↗

Insulin secretory response is positively associated with the extent of ossification of the posterior longitudinal ligament of the spine.

BACKGROUND: Glucose intolerance is frequently found in patients with ossification of the posterior longitudinal ligament of the spine. This study was undertaken to examine the relationship between glucose intolerance and the extent of ossification in patients with ossification of the posterior longitudinal ligament. METHODS: A total of 100 patients with ossification of the posterior longitudinal ligament (the overall study group), including fifty-two inpatients who were scheduled to have an operation (the inpatient group) and forty-eight outpatients who had undergone an operation, were analyzed. Indices of glucose metabolism-fasting plasma glucose and serum insulin levels, hemoglobin A1c level, and insulinogenic index (a ratio of the increment of the serum level of insulin to that of glucose)-as well as age and body-mass index were correlated with the extent of ossification, as determined by the number of vertebral levels affected with ossification of the posterior longitudinal ligament (extent of ossification), in the inpatient group. In addition, a similar analysis was performed in twenty-eight inpatients (the selected inpatient group) whose ages and body-mass indices were within one standard deviation of the mean values of those of the inpatient group. Association of a polymorphism in the gene of insulin receptor substrate-1, an essential substrate in insulin signaling, with the extent of ossification was evaluated with genomic DNA extracted from the overall study group. RESULTS: Multiple-regression analysis revealed direct correlations of age (p = 0.038), body-mass index (p = 0.006), and insulinogenic index (p = 0.0003) with the extent of ossification of the posterior longitudinal ligament in the inpatient group. The fasting plasma glucose level, the hemoglobin A1c level, and the stage of glucose tolerance were not associated with the extent of ossification. In the analysis of the selected inpatient group, only the insulinogenic index was correlated with the extent of ossification (p = 0.002). However, no significant association was seen between the insulin receptor substrate-1 polymorphism and the extent of ossification. CONCLUSIONS: The insulin secretory response was associated with the extent of ossification of the posterior longitudinal ligament. Since insulin receptor substrate-1 is expressed both in the spinal ligament and in the tissues regulating glucose metabolism, we speculate that some other molecules related to insulin signaling that are impaired only in the tissues regulating glucose metabolism may be responsible for the progression of ossification. We also speculate that the upregulation of insulin production due to the impairment of insulin action may stimulate osteoprogenitor cells in the ligament to induce ossification. CLINICAL RELEVANCE: The insulinogenic index may be useful as a serum marker for the prediction of progression of ossification of the posterior longitudinal ligament. This study may serve as a stimulus for evaluation of the use of various drugs that may improve the response to insulin in the tissues regulating glucose metabolism to prevent the progression of ossification.

Adult↗

Preoperative irradiation for prevention of heterotopic ossification following total hip arthroplasty.

Eighty-six hips in eighty-five patients who were considered to be at risk for heterotopic ossification following a total hip arthroplasty were prospectively randomized or assigned to one of two treatment groups that received a single 800-centigray dose of limited-field radiation either preoperatively (Group I) or postoperatively (Group II). The risk factors for postoperative heterotopic ossification included previous heterotopic ossification following an operation about the hip, hypertrophic osteoarthrosis or post-traumatic osteoarthrosis characterized by the presence of extensive osteophytes, radiographic evidence of diffuse idiopathic skeletal hyperostosis, and ankylosing spondylitis. The hips in Group I were irradiated within 6.1 hours before the operation and those in Group II, within 51.3 hours after the operation. Either extra-field ossification or heterotopic ossification was observed in forty-one (48 per cent) of the eighty-six hips, thereby confirming the high risk for the population in this study. After a minimum duration of follow-up of six months, thirty-seven (76 per cent) of the forty-nine hips that had been treated with preoperative irradiation exhibited no new heterotopic ossification and eleven, progression to grade-I or II ossification. The remaining hip in that group was in a woman who had Paget disease as well as previous grade-IV (ankylosing) heterotopic ossification about the ipsilateral hip; heterotopic ossification progressed from grade II on the radiographs made immediately after the index revision procedure to grade III at the most recent follow-up assessment. Of the thirty-seven hips that had been treated with postoperative irradiation, twenty-seven (73 per cent) exhibited no new heterotopic ossification and nine had progression from grade-0 to grade-I ossification. The remaining hip in that group was in a man who had Parkinson disease and previous grade-III ossification about the ipsilateral hip; heterotopic ossification progressed from grade III immediately post-operatively to grade IV at the time of the most recent evaluation. Extra-field ossification was identified in twelve (24 per cent) of the forty-nine hips that had been irradiated preoperatively compared with three (8 per cent) of the thirty-seven hips that had been irradiated postoperatively (p = 0.05). Extra-field ossification was not associated with clinical symptoms of bursitis of the greater trochanter in any hip. Three of the ten hips that had a revision operation subsequently had a non-union of the greater trochanter; all three had been treated with preoperative irradiation. The findings of the present study suggest that pre-operative irradiation is effective for the prevention of heterotopic ossification following total hip arthroplasty and that it eliminates the discomfort and morbidity that are associated with conventional postoperative treatment. Furthermore, the efficacy of preoperative irradiation suggests that osteogenic precursor cells that are active in this process are derived from the local tissues within the operative field rather than from distant blood-borne cell lines.

Adult↗

Relationship between the ossification center and cartilaginous anlage in the normal hindfoot in children: study with MR imaging.

OBJECTIVE: Although many reports have documented when ossification centers can first be visualized on radiographs, few studies have evaluated the position of the ossification center within its cartilaginous anlage. In the skeletally immature child, the ossification centers of the tarsals are used to evaluate the positions of the tarsals and their interrelationships. It is convenient to assume that tarsal ossification begins in the center of its cartilaginous anlage and proceeds in a radial fashion; however, this may not be the case. Accordingly, we used MR imaging to evaluate the location of the ossification centers of the tarsals within their cartilaginous anlage in the mid and hindfoot in children. MATERIALS AND METHODS: MR studies of 69 feet in 40 children, 3 months to 7 years old (mean, 2.5 years), were reviewed retrospectively. The location of the ossification center within its cartilaginous anlage and the percentage of ossification of the cartilaginous anlagen of the talus, calcaneus, cuboid bone, and navicular bone were determined from coronal and sagittal images. In the talus, the difference between the orientation of the long axis of its ossification center and the long axis of its cartilaginous anlage was measured on coronal and sagittal images. RESULTS: Early talar ossification was centered on the neck of the talus; the proximal aspect of the bone ossified last. The long axis of the talar ossification center and the long axis of its cartilaginous anlage differed in orientation. Early calcaneal ossification was centered on the distal two thirds of the cartilaginous anlage of the calcaneus; the proximal aspect and the area of the subtalar joint ossified last. Early navicular ossification was centered on the central or lateral third of the navicular cartilaginous anlage; the medial aspect ossified last. The ossification center of the cuboid bone was in the middle of the cuboidal cartilaginous anlage. CONCLUSION: Our results show that early ossification in the talus, calcaneus, and navicular bones does not begin in the center of the bones' cartilaginous anlagen. The orientations of the long axis of the talar ossification center and the long mid axis of its cartilaginous anlage are different. Therefore, part of the changes in the alignment of the tarsals seen on radiographs with growth is due to ossification beginning and proceeding eccentrically within the cartilaginous anlage and not to a true change in the alignment of the tarsals. These data provide new information about the normal development of the child's hindfoot and midfoot.

Cartilage↗

Progression of ossification of the posterior longitudinal ligament following en bloc cervical laminoplasty.

BACKGROUND: Ossification of the posterior longitudinal ligament often causes compressive myelopathy. Ossification is a progressive disease, and it has been reported that the area of ossification increases after decompressive surgery. However, it is uncertain how the progression of ossification affects the long-term outcome after cervical laminoplasty. This study was performed to clarify the relationship between the progression of ossification of the posterior longitudinal ligament and the clinical results following en bloc cervical laminoplasty. METHODS: Forty-five patients who were followed for more than ten years after laminoplasty participated in this study. Radiographs and tomograms of the cervical spine of each patient were made before and after the operation and at the time of the latest follow-up. The extent of ossification in the longitudinal and sagittal axes was evaluated. Neurological function was graded with use of the Japanese Orthopaedic Association scoring system. The relationship between the progression of ossification and the score-based rate of recovery was analyzed. RESULTS: Thirty-three (73%) of the patients had progression of ossification of the posterior longitudinal ligament after laminoplasty. Progression was frequent in patients with the mixed type of ossification and in those with the continuous type, whereas it was rare in patients with the segmental type. The patients with progression of the ossification were significantly younger than those without progression (p = 0.018). The Japanese Orthopaedic Association score improved rapidly within one year and continued to improve up to five years after surgery. The score tended to decrease thereafter. For thirteen patients, the score had worsened at the time of the latest follow-up. Three patients had neurological deterioration following an increase in the thickness of the ossification. CONCLUSIONS: Progression of ossification of the posterior longitudinal ligament was often observed during the long-term follow-up period after laminoplasty. Young patients with mixed and continuous types of ossification had the greatest risk for progression. Preventive measures, such as the use of a wider laminar opening during the laminoplasty, should be considered for patients who are at risk for progression of ossification.

Adult↗

Anterior decompression for myelopathy resulting from thoracic ossification of the posterior longitudinal ligament.

STUDY DESIGN: A retrospective study was conducted to investigate the anterior decompression and fusion of 12 patients with thoracic ossification of the posterior longitudinal ligament. OBJECTIVE: To evaluate the effect of myelopathy management in which the thoracic ossification of the posterior longitudinal ligament is removed. SUMMARY AND BACKGROUND DATA: Very few reports have described operative treatments for thoracic ossification of the posterior longitudinal ligament. The condition is extremely rare, even in Japan. Consequently, operative procedures for myelopathy resulting this disorder have not been established. METHODS: This study involved 12 patients with thoracic ossification of the posterior longitudinal ligament. All the patients underwent direct removal of the ossification and spinal fusion using an anterior approach. A scapula-releasing technique was used in five patients who had major ossification of the posterior longitudinal ligament at Th4. The follow-up period ranged from 2.5 to 10 years (mean, 6.5 years). The clinical effect of the decompression was evaluated with a Japanese Orthopedic Association score for cervical myelopathy. The efficacy of the decompression was determined by postoperative computed tomography scan. RESULTS: Complete removal of the ossification was achieved in eight patients. In four patients, however, residual ossification was noted. The Japanese Orthopedic Association score before the operation ranged from 4 to 7 points (mean, 5.3 +/- 0.4 points). It showed a change 3 months after the operation, ranging from 1 to 8 points (mean, 6.9 +/- 0.5 points). At 1 year after the operation, it had changed to a range of 1 to 10 points (mean, 7.2 +/- 0.6 points). At the final consultation, it had changed further to a range of 1 to 10 points (mean, 6.9 +/- 0.5 points). Patients whose ossification was not completely removed showed severe or minor postoperative deterioration. CONCLUSIONS: Total removal of the ossification might be required to manage severe myelopathy in patients with thoracic ossification of the posterior longitudinal ligament. Complete removal of the ossification gave good results in eight patients. Patients whose ossification of the posterior longitudinal ligament had not been completely removed, however, had a poor outcome.

Adult↗

Clinical significance of ossification of the cartilages of the front feet based on nuclear bone scintigraphy, radiography and lameness examinations in 21 Finnhorses.

REASONS FOR PERFORMING STUDY: Research on the clinical significance of ossification of the cartilages of the foot has been limited, despite the common nature of the condition and conflicting reports in previous literature. HYPOTHESIS: Some radiographic features in the ossification of the cartilages, such as incomplete fusion lines between separate centres of ossification and the ossified base, are of clinical significance. METHODS: The relationships between radiopharmaceutical uptake in bone phase nuclear scintigraphy at the heels (palmar processes of the distal phalanx, including ossification of the cartilages of the foot), radiographic extent and type of ossification of the cartilages and clinical lameness were evaluated retrospectively in 21 Finnhorses (age > or = 4 years) in a total of 36 front feet. RESULTS: No significant relationship between height of the ossifications and radiopharmaceutical uptake at the ipsilateral heels existed. Clearly separate centres of ossification were not associated with increased uptake. Moderately increased uptake was suspected to be associated with ossification of the adjacent cartilage in only one foot. Intense uptake was present unilaterally in 4 horses, at one medial and 3 lateral heels. In 2 of these horses, a unilateral palmar digital nerve block relieved the mild lameness; 2 horses had no obvious lameness but had a history of being stiff or having locomotion problems during high speed trot. At 2 of the lateral heels, an incomplete fusion line was present between a large separate centre of ossification and the base, and the third horse had a high sidebone with bony protrusions, suggestive of chronic entheseopathy in a narrow foot. At the medial heel, an oblique radiograph revealed a faint radiolucent line at the base of the ossification. In all cartilages with intense radiopharmaceutical uptake at the heel and/or lameness, the ossified part of the cartilage was wider and more irregular compared to other ossifications of the front feet of the individual. CONCLUSIONS: Increased radiopharmaceutical uptake, associated with a different radiographic appearance from that of other ossifications of the front feet, was a conclusive sign of clinical significance. Obscure locomotion problems were more commonly associated with ossification of the cartilages than true lameness. POTENTIAL RELEVANCE: This information is useful in lameness and prepurchase examinations and is likely also to be applicable to other coldblooded breeds used for athletic purposes.

Animals↗

"Missing" sternal ossification center: potential mimicker of disease in young children.

PURPOSE: To evaluate the frequency of "missing" sternal ossification center (asynchronous non-ossification) in young children. MATERIALS AND METHODS: Lateral chest radiographs obtained in 229 children (mean age, 3.7 years) were retrospectively evaluated for sternal ossification. Four superior sternal segments were considered normal if they were ossified to a similar degree. A segment was considered asynchronous if decreased ossification, as compared with the remaining sternal segments, was demonstrated or if ossification was absent. Asynchronous ossification of inferior sternal segment 5 was recorded separately. Logistic regression analysis was applied to determine if there was a statistically significant relationship (P <.05) between age or sex and pattern of sternal ossification (normal vs asynchronous). RESULTS: Of the 916 superior four sternal segments (four segments in each of 229 patients) evaluated, 32 (3.5%) showed asynchronously decreased or absent ossification. Locations of these 32 segments follow: segment 1, two (0.2%) instances; segment 2, 14 (1.5%) instances; segment 3, two (0.2%) instances; and segment 4, 14 (1.5%) instances. Inferior segment 5 was not ossified in 73 (31.9%) patients. There was a statistically significant relationship between decreased age and increased likelihood of occurrence of asynchronous ossification of one of the sternal ossification centers 1-4 (P >.003) and of occurrence of asynchronous ossification at sternal segment 2 (P <.018). CONCLUSION: Missing sternal ossification centers occur most commonly at segments 2 and 4. Such asynchronous non-ossifications become less common in older children.

Child↗

Cochlear ossification after meningitis.

OBJECTIVE: This study aimed to assess the pathologic processes that result in ossification of the cochlear lumen after bacterial meningitis. STUDY DESIGN: The study design was a retrospective case review. SETTING: The study was conducted at a tertiary referral center. PATIENTS: Profoundly deaf postmeningitic patients who underwent cochlear implantation were studied. INTERVENTIONS: Diagnostic and therapeutic observations were performed. MAIN OUTCOME MEASURES: The extent of cochlear ossification is classified and related to age at which infection occurred, cerebrospinal fluid leukocyte count, Gram's stain, organism, and delay between meningitis and implantation. The extent of ossification noted on high-definition computed tomographic (CT) scan is compared with surgical findings and related to the time delays between meningitis, imaging, and surgery. RESULTS: Ossification fell into three groups: gross ossification of the scala tympani and variable amounts of the scala vestibuli; partial ossification localized to the basal turn of the scala tympani; and no ossification. There was no correlation between the extent of ossification and the age when infected, type of pathogen, cerebrospinal fluid leukocyte count, and time delay between meningitis and implantation. Visualization of bacteria on Gram's stain was a highly sensitive measure of ossification (0.93) but was not specific (0.6) with positive and negative predictive values of 0.76 and 0.86, respectively. High-definition CT underestimated the extent of ossification in 50% of cases when performed within 6 months of meningitis. CONCLUSIONS: Ossification is either gross or localized to the basal turn of the scala tympani. If ossification does occur, it is rapid and complete within a few months of infection. The visualization of bacteria on Gram's stain is a sensitive indicator for the presence of ossification but has low specificity. High-definition CT, if performed within the first 6 months of meningitis, can be an inaccurate diagnostic tool and therefore should be performed as close to the date of surgery as possible.

Adolescent↗

[Anterior intertrochanteric ossification after total hip arthroplasty].

AIM: Heterotopic paraarticular ossifications are usually identified by an anterior-posterior radiograph of the corresponding hip and are consecutively classified by the well accepted methods of Brooker, Arcq or deLee. In these methods ossifications are solely evaluated by the means of a single a-p radiograph, hence a major part of ossifications located in the anterior intertrochanteric region cannot be evaluated. Our study deals with the incidence of ossifications exclusively verifiable by an axial radiograph. METHOD: In the present study 209 patients' axial radiographs were retrospectively analysed by using our simple method of classification. In the axial projection these ossifications are situated anterior of the intertrochanteric region, therefore we created the term "anterior intertrochanteric ossification (AIO)". After developing a simple topographic scheme we classified these appearances by localisation and size. RESULTS: After total hip arthroplasty by using the transgluteal approach ossifications situated in the anterior intertrochanteric region can develop. These ossifications appear as bone islands, shield or clip like (without fixed connection to the femoral cortical bone) or as solid exostoses. Due to their strict anterior localisation these formations are often solely verifiable by the means of an axial (Lauenstein) radiograph. We were able to identify anterior intertrochanteric ossifications (AIO) in 97 out of 209 patients (48.4 %), 27 patients (13 %) developing an anterior intertrochanteric ossification were classified grade 0 according to the methods of Brooker, Arcq and deLee. CONCLUSION: According to the widely accepted methods of classification of paraarticular ossifications depending on a single a-p radiograph of the corresponding hip, 13 % of paraarticular ossifications would remain undocumented because of their strict anterior intertrochanteric position.

Anti-Inflammatory Agents, Non-Steroidal↗

Ossification of the posterior longitudinal ligament in vitamin D-resistant rickets: case report and review of the literature.

STUDY DESIGN: A case report of cervical myelopathy caused by ossification of the posterior longitudinal ligament in a patient with vitamin D-resistant rickets is presented together with a review of literature. OBJECTIVE: To report the diagnosis of ossification of the posterior longitudinal ligament in a white woman with vitamin D-resistant rickets. SUMMARY OF BACKGROUND DATA: The association between ossification of the posterior longitudinal ligament and untreated vitamin D-resistant rickets has been reported in Japan, but infrequently in white populations. In whites, ossification of the posterior longitudinal ligament is closely associated with diffuse idiopathic skeletal hyperostosis. A clear association between ossification of the posterior longitudinal ligament and vitamin D-resistant rickets in white populations has not yet been established. METHODS: The medical record and imaging studies of a patient treated at the authors' institution for cervical myelopathy caused by ossification of the posterior longitudinal ligament in the setting of treated vitamin D-resistant rickets were reviewed. A Medline search of the medical literature between 1966-1999 was performed to identify pertinent studies and similar case reports. RESULTS: The occurrence of spinal stenosis in untreated adults with vitamin D-resistant rickets has been reported in all regions of the spine in Japanese patients. The association between ossification of the posterior longitudinal ligament and untreated vitamin D-resistant rickets was first reported in Japan, where ossification of the posterior longitudinal ligament is endemic. This association may be incidental, because reports on ossification of the posterior longitudinal ligament in whites are not as frequent as in Japanese, reflecting the higher prevalence of this condition in Japan. CONCLUSION: Ossification of the posterior longitudinal ligament and ossification of the posterior longitudinal ligament associated with deranged calcium or phosphate metabolism may be different pathologic entities sharing a common outcome. Adequate treatment of vitamin D-resistant rickets may not always prevent or reverse ossification of the posterior longitudinal ligament.

Bone Density↗

Retroviral delivery of Noggin inhibits the formation of heterotopic ossification induced by BMP-4, demineralized bone matrix, and trauma in an animal model.

BACKGROUND: The heterotopic ossification of muscles, tendons, and ligaments is a common problem faced by orthopaedic surgeons. We investigated the ability of Noggin (a BMP [bone morphogenetic protein] antagonist) to inhibit heterotopic ossification. METHODS: Part 1: A retroviral vector carrying the gene encoding human Noggin was developed and used to transduce muscle-derived stem cells. Part 2: Cells transduced with BMP-4 were implanted into both hind limbs of mice along with either an equal number, twice the number, or three times the number of Noggin-expressing muscle-derived stem cells (treated limb) or with nontransduced muscle-derived stem cells (control limb). At four weeks, the mice were killed and radiographs were made to look for evidence of heterotopic ossification. Part 3: Eighty milligrams of human demineralized bone matrix was implanted into the hind limbs of SCID (severe combined immunodeficiency strain) mice along with 100,000, 500,000, or 1,000,000 Noggin-expressing muscle-derived stem cells (treated limbs) or nontransduced muscle-derived stem cells (control limbs). At eight weeks, the mice were killed and radiographs were made. Part 4: Immunocompetent mice underwent bilateral Achilles tenotomy along with the implantation of 1,000,000 Noggin-expressing muscle-derived stem cells (treated limbs) or nontransduced muscle-derived stem cells (control limbs). At ten weeks, the mice were killed and radiographs were made. RESULTS: Part 1: An in vitro BMP inhibition assay demonstrated that Noggin was expressed by muscle-derived stem cells at a level of 280 ng per million cells per twenty-four hours. Part 2: Three varying doses of Noggin-expressing muscle-derived stem cells inhibited the heterotopic ossification elicited by BMP-4-expressing muscle-derived stem cells. Heterotopic ossification was reduced in a dose-dependent manner by 53%, 74%, and 99%, respectively (p < 0.05). Part 3: Each of three varying doses of Noggin-expressing muscle-derived stem cells significantly inhibited the heterotopic ossification elicited by demineralized bone matrix. Heterotopic ossification was reduced by 91%, 99%, and 99%, respectively (p < 0.05). Part 4: All eleven animals that underwent Achilles tenotomy developed heterotopic ossification at the site of the injury in the control limbs. In contrast, the limbs treated with the Noggin-expressing muscle-derived stem cells had a reduction in the formation of heterotopic ossification of 83% and eight of the eleven animals had no radiographic evidence of heterotopic ossification (p < 0.05). CONCLUSIONS: The delivery of Noggin mediated by muscle-derived stem cells can inhibit heterotopic ossification caused by BMP-4, demineralized bone matrix, and trauma in an animal model. CLINICAL RELEVANCE: Gene therapy to deliver Noggin may become a powerful method to inhibit heterotopic ossification in targeted areas of the body.

Achilles Tendon↗

Ossification of the cartilages in the front feet of young Norwegian coldblooded horses.

The purpose of the present study was to evaluate the nature of ossification of the cartilages in the front feet of young, about 2-year-old Norwegian coldblooded horses, and to compare offspring of different sires in this respect. Dorsopalmar radiographs of the front feet of 392 horses (187 female and 205 male) were evaluated for ossification at the base of the cartilage and for separate centres of ossification. The horses were offspring of 45 different sires. Ossification extending above the navicular bone and separate centres of ossification were considered as significant. Minimal to mild ossification at the base of the cartilages was commonly seen, and significant ossification was present in one or more of the cartilages in 11.5% of the horses. The lateral compared to medial cartilages had more ossification and females had more ossification and more separate centres of ossification than males. The prevalence of horses with significant ossifications was significantly higher (46.3%) among offspring of one frequently used stallion than in the group consisting of offspring of 4 other popular stallions (3.5%) and in another group consisting of offspring of other, less frequently used stallions (9.6%). Ossification of the cartilages is considered to have a hereditary background in Norwegian coldblooded horses.

Animals↗

[Clinical aspects, differential diagnosis and histogenesis of heterotopic ossification].

Investigations regarding proliferation behaviour, histogenesis and bone transformation were carried out on soft tissue samples with 133 heterotopic ossifications (HO), collected from the surgical material of the Institute of Pathology, Berufsgenossenschaftliche Kliniken Bergmannsheil, using methods of conventional histology, histochemistry, immunohistochemistry, electron microscopy and molecular biology, yielding the following results: 1. There is only a limited pathognomonic growth pattern for the variant of non-traumatic heterotopic ossification. Basically, the ossification foci may be divided into central, intermediate and peripheral zones. Expression intensities of the proliferation markers PCNA and MIB-1 show the proliferation behaviour in peripheral areas of osteogenesis to be similar to that found in autonomous osseous neoplasias. The phenotypical picture of zonal architecture found in HO can be seen by the simultaneous demonstration of variable image sequences of multifocally arising ectopic formations of new bone with varying degrees of maturation. 2. Vascular endothelium and pericytes are integrated into the formal histogenesis of heterotopic ossification and belong to osteoprogenitor cells as "stem cells" of heterotopic ossification. 3. The histochemically established expression pattern of alkaline phosphatasis is in good correlation with the degree of activity of the step-by-step development of heterotopic ossification. The intracellular demonstration of alkaline phosphatasis is an indicator for the transformation towards an osteogenic direction. In HO, the enzyme is a major characteristic of osteoprogenitor cells. 4. According to our immunohistochemical results, the proteoglycanes Decorin and PG 100-osteogenic matrix proteins-show a phase-like expression and are involved in osteoneogenesis. They are predominantly found in the area of mineralization. The proteoglycane 100 experiences a "modulation" and can be demonstrated almost selectively in osteoclasts in advanced stages of osteodevelopment. 5. Using in situ hybridization-with digoxigenin labeled cDNA probes- and a propidium iodide counterstaining a co-expression of collagene types I, II and III-mRNA could be demonstrated in samples of ossification. The expression pattern is similar to the collagen expression I. in early phases of embryonal bone development II. with callus proliferation and shows III. also similarities to chondral neoplasias. The results underline the reactive-neoplastic character of heterotopic ossification. 6. TGF-beta 1 mRNA shows a polytopic expression pattern with accumulation in areas of osteogenesis. TGF-beta 1 was found mostly in cartilage cells of heterotopic ossifications, as were collagene types I (alpha 1) and III (alpha 1) mRNAs. In sum, our in situ hybridization results underline the central part of cartilage cells in the ossification process in ectopic osteoneogenesis. This is also indicated by a phenotypical alteration of collagen expression as well as by an accumulation of TGF-beta 1 in chondral ossification areas. In situ hybridization propidium iodide counterstaining offers a reproducable image of morphological structures in the histological slide sample by means of fluorescence microscopy. 7. Phenotyping of osteroclasts in HO revealed their derivation from mature local macrophages. The immunohistochemical characterization with the demonstration of the vitronectin receptor classified the multinucleate giant cells of HO as original osteoclasts. Their origin is in accordance with the histogenetical concept of original bone. 8. Summarizing, the results characterize heterotopic ossification as a reactive proliferative and reversible neoplasia in chronically damaged soft tissue. From the formal pathogenetical point of view, relations could be established to orthotopic osteoneogenesis as well as to impaired proliferation kinetics, similar to osseous autonomous neoplastic lesions. (ABSTRACT TRUNCATED)

Biomarkers↗

[Prevention of heterotopic ossifications in hip arthroplasty: effectiveness of selective Cox-2 inhibitors (celecoxib) versus ketoprofen].

PURPOSE OF THE STUDY: Peri-prosthetic ossifications are a frequent complication of total hip arthroplasty, which, if effective preventive measures are not taken, occur in 60% of patients. Numerous classic antiinflammatory agents have shown their preventive efficacy. New selective Cox-2 inhibitors offer the possibility of reducing the adverse effects of antiinflammatory drugs but remain to be proven effective in this indication. The purpose of this pilot study was to compare the efficacy of celecoxib versus ketoprofen. MATERIAL AND METHODS: In order to obtain sufficient statistical power to have a 70% chance of detecting a 25% difference between the two treatments with a 5% risk of error, we evaluated the incidence of peri-prosthetic ossifications of the hip in a prospective monocentric series of 52 patients receiving 400 mg celecoxib a day during a week. It was compared with the incidence in a control series of 52 matched patients (same age, gender, diagnosis, operator experience) given 200 mg ketoprofen iv for 48 hr then 300 mg po for 5 days as preventive treatment. Ossifications were studied on the plain AP view of the pelvis at a mean follow-up of more than 11 months (11.4 vs 11.9). The Brooker classification was determined. RESULTS: The percent of patients presenting peri-prosthetic ossifications was equivalent. For the celecoxib group, 60% of the patients were free of ossifications; 28.9% presented stage 1 ossification and 11.1% stage 2 ossification; none of the hip exhibited a higher stage. In the ketoprofen control group, 53.2% of patients were free of ossification, 38.2% had stage 1 ossification, 6.4% stage 2, and 2.1% stage 3; there was no patient with stage 4. Fisher's exact test did not demonstrate a significant difference between the groups (p<0.51). Compared with an older series of patients who were not given preventive treatment, there was a significant reduction in incidence of peri-prosthetic ossification (p=0.014). DISCUSSION: The two study groups were not significantly different for age, gender, or underlying disease. There were an equivalent number of cases of intolerance to treatment in the two groups. CONCLUSION: These findings appear to indicate an equivalent efficacy for celecoxib and ketoprofen for the reduction of peri-prosthetic ossifications. Based on these results, a randomized prospective comparative study can be undertaken without risk of losing effective prevention in one group. This prospective study should enable a more precise evaluation of treatment equivalence and quantify any potential gain in morbidity obtained with celecoxib.

Aged↗

Bone mineral density in patients with ossification of the posterior longitudinal ligament. Minimal decrease of bone mineral density with aging.

STUDY DESIGN: Bone mineral density of individuals with ossification of the posterior longitudinal ligament and that of normal people was determined by dual-energy x-ray absorptiometry. OBJECTIVES: To determine whether bone mineral density in the people with ossification of the posterior longitudinal ligament is higher than that in normal individuals even in body parts other than the spine, and to evaluate the relation between bone mineral density and age in patients with ossification of the posterior longitudinal ligament. SUMMARY OF BACKGROUND DATA: It is unknown whether the bone mineral density of patients with ossification of the posterior longitudinal ligament is greater in body parts other than the spine. If so, it provides a basis for the theory that certain systemic factors are involved in the pathogenesis of ossification of the posterior longitudinal ligament. Because bone mineral density decreases physiologically after middle age, the influence of age must be considered in evaluating bone mineral density. METHODS: In the rib area and upper and lower limb areas, which are not affected by ossification of the spinal ligament, bone mineral density of 45 men with ossification of the posterior longitudinal ligament of the cervical spine was compared with that of 25 men without ossification of the posterior longitudinal ligament (normal group). RESULTS: Bone mineral density was higher in the group with ossification of the posterior longitudinal ligament in each part and significantly higher in the rib and lower limb areas (rib: P < 0.01, lower limb: P < 0.05). The age-related decrease was significantly less in the group with ossification of the posterior longitudinal ligament (rib: P < 0.01, upper limb: P < 0.05, lower limb: P < 0.01). CONCLUSIONS: Systemic factors that increase bone mineral density appear to be involved in the pathogenesis of ossification of the posterior longitudinal ligament, and these factors may be activated after middle age.

Absorptiometry, Photon↗

Variation in the ossification process of the anconeal and medial coronoid processes of the canine ulna.

This morphological and radiographic study investigates the ossification process of the anconeal and medial coronoid processes of the ulna in a sample of 142 dogs ranging in age from neonatal to 44 weeks. The anconeal process was noted to develop by appositional ossification, formation of a separate ossification center, or a combination of both. Several developmental stages of the ossification center of the anconeal process as well as its anatomic position and radiographic appearance are described. Differences have been noted in the shape of this ossification center as well as the ossification process itself. The medial coronoid process develops exclusively by appositional ossification. Unlike ossification of the anconeal process, ossification of the medial coronoid process was completed earlier (p < 0.05) in smaller than in the larger dogs. In smaller dogs, both the medial coronoid and anconeal processes were found to be mature by the age of 16 weeks. In the larger dogs, ossification of the anconeal process was completed not before 14 weeks of age and ossification of the medial coronoid process was completed about 6 weeks later.

Animals↗

The development of centres of ossification of bones forming elbow joints in young swine.

Epiphyseal centres of ossification in the bones forming the elbow joints of pigs between one day and 15 weeks of age were examined radiographically, macroscopically, mesoscopically and microscopically. Thoracic limbs from 39 pigs were perfused with India ink or silicone rubber injection compound and the bones were dissected free of soft tissues. The humerus, ulna and radius were fixed in formalin or ethyl alcohol and then cleared by the modified Spalteholz technique. Bones were radiographed, examined grossly, and then cut into slabs for mesoscopical evaluation. Foci considered to be calcifying within cartilaginous anlage were selected for microscopical examination. It was concluded that the epiphyseal centre of ossification develops at different times in different sites in the bones forming the elbow joint. Centres of ossification are initiated when foci of chondrocytes adjacent to one side of a cartilage canal undergo hypertrophy and the inter-territorial matrix becomes calcified. Osteogenesis then proceeds in the calcified focus, presumably with osteoprogenitor cells that originate within the cartilage canals. Subsequently, each epiphyseal centre of ossification enlarges by one of two methods. Firstly, the layer of cartilage adjacent to the centre undergoes endochondral ossification, thus allowing for the circumferential growth of the epiphyseal centre of ossification. Secondly, foci of calcification develop adjacent to the ends of cartilage canals near the epiphyseal centre of ossification and eventually the focus of calcification coalesces with the developing epiphyseal centre of ossification, thus establishing a new ossification front. Endochondral ossification continues at the periphery of the mass of bone. Mesoscopical examination is more useful than radiographical evaluation for identifying small foci of calcification which precede epiphyseal centres of ossification.

Animals↗