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PubMed2005

Optimal timing of preoperative radiation for prophylaxis against heterotopic ossification. A rabbit hip model.

BACKGROUND: In a previous study, we developed a rabbit model of heterotopic ossification and demonstrated that 800 or 1200 cGy of radiation before an operation on the hip significantly decreased postoperative ectopic bone formation compared with that seen after the operation on the non-irradiated, contralateral hip. The purpose of this study was to determine the optimal preoperative timing of radiation prophylaxis against heterotopic ossification following hip surgery in this same experimental model. METHODS: Seventy-two hips in thirty-six New Zealand White rabbits were divided into four treatment groups corresponding to four preoperative points in time (four hours, twenty-four hours, seventy-two hours, and three weeks). The hips were irradiated with 1200 cGy at the different preoperative time points (eighteen hips at each time) to investigate the efficacy of the four preoperative radiation protocols. The rabbits then underwent bilateral hip surgery. They were killed and radiographs were made four months postoperatively. Heterotopic ossification was graded according to a modification of the scale of Brooker et al. The mean grade, the interobserver and intraobserver reliability, and the significance (p < 0.05) of the differences between the groups were evaluated. RESULTS: Radiation delivered at twenty-four hours preoperatively was significantly more effective for prophylaxis against heterotopic ossification than was radiation delivered at four hours or seventy-two hours preoperatively (p < 0.05), and the difference between the twenty-four-hour and three-week groups approached significance (p = 0.088). Furthermore, the twenty-four-hour group had a significantly lower percentage of hips with high-grade heterotopic ossification than did the four-hour (p = 0.02), seventy-two-hour (p = 0.002), and three-week (p = 0.03) groups. CONCLUSIONS: Preoperative irradiation to prevent heterotopic ossification optimally should be administered twenty-four hours before the operation. This latency period probably allows expression of radiation-induced sublethal mutations in the genetic code of pluripotential stem cells and precludes differentiation to osteoblastic cell lines.

Animals↗
PubMed1985

Effect of ibuprofen on heterotopic ossification after hip replacement.

A double-blind, placebo-controlled study was made of the influence of the anti-inflammatory agent ibuprofen on heterotopic ossification after total hip replacement for arthrosis, fracture or rheumatoid arthritis. Seven drop-outs left 21 patients on medication and 22 on placebo in two comparable groups. Heterotopic ossification appeared in one third of the patients in the ibuprofen group and in three fourths in the control group 12 months after surgery. Five patients in the latter group developed true heterotopic bone, compared to one of the patients on medication. Heterotopic ossification was as common among osteoarthritic patients as among others. There was no difference in the range of motion at 12 months postoperatively between patients with and without heterotopic ossification. In the 22 patients with heterotopic ossification this was demonstrated in all but eight within 6 weeks, and in only three did it appear later than 3 months postoperatively. Five of the six patients who showed heterotopic bone with trabecular structure were male. Since inflammation is a dominant feature in the postoperative phase, the effect of ibuprofen on heterotopic ossification is probably its inhibition of the synthesis of prostaglandins. This implies that prevention is most successful if commenced before or at the time of operation.

Aged↗
PubMed1997

Heterotopic ossification after total knee arthroplasty. 54/615 cases after 1-6 years' follow-up.

We found heterotopic ossifications in 54 (9%) of 615 cases after total knee arthroplasty. The largest ossifications were located in the anterior distal femur. In 12 cases smaller ossifications were found in other knee regions. The development of heterotopic ossification showed a positive correlation with hypertrophic arthrosis and a negative correlation with rheumatoid arthritis. We propose a new 3-grade classification which refers only to the anterior distal femoral region. Grade III heterotopic ossifications occurred in 4 patients (4 knees) who had clinical symptoms; 2 were successfully reoperated with removal of the ossifications. Prophylaxis should be considered in patients with marked hypertrophic arthrosis or marked periosteal damage to the anterior distal femur.

Aged↗
PubMed1999

[Prevalence, morphology, and pathologic implications of ossification of lumbar ligamenta flava: a large prospective CT study].

Ossifications of the ligamenta flava are described in all parts of the spine, particularly in the dorsal segment where they can produce thoracic myelopathy. Rarely reported in the cervical spine, they are only occasionally mentioned in the lumbar spine where the main reported pathology of the ligamentum flavum is the arthrosynovial cyst. To study the morphological appearances, the prevalence and the pathological implications of the lumbar ossified ligamenta flava, 1021 lower lumbar CT studies are prospectively reviewed totalizing 6080 ligamenta flava. The prevalence of clearly defined ossifications is 5.44%; it appears relatively independent from the age, sex, vertebral level and presence of spondylolysis. It significant increases with the presence and the stage of articular osteoarthritis. In more than 96% of cases, the ossifications remain confined to the lateral articular portion of the ligament and more central ossifications are very rare; therefore, the essential differential diagnosis is osteophytosis. The ossifications never cause radiculopathy except rarely, in association with more classical processes such as disk protrusions and osteophytosis. Our findings favours an essentially idiopathic and--to a lessen extent--a mechanical cause to explain ossification of the ligamenta flava.

Adolescent↗
PubMed2000

[Heterotopic ossification as a complication of total hip replacement].

Heterotopic ossification is the most common complication after THR. The authors present the distribution of frequency of ectopic ossification after cementless THR using Mittelmeier and Parhofer-Mönch prosthesis and it's influence on THR outcome. 151 hip joints were evaluated with a follow-up period of more than 2 years. All procedures were performed by a lateral approach. The ectopic ossification was verified according to the Brooker classification. Clinical evaluation was performed according to the d'Aubigne-Postel method in Charnley's modification. The 3rd degree ectopic ossification was found in 14 hip joint and 4th degree ectopic ossification in 2 hip joints (together 10.6%). The positive correlation between the degree of ossification (3rd and 4th) and the decrease of range of motion of the hip joint along with an increase in pain after THR was found.

Adolescent↗
PubMed1992

[Prevention of periarticular ossification following endoprosthetic hip replacement using postoperative irradiation].

The development of heterotopic ossification (HO) after total hip replacement or other surgical hip procedures can considerably impair the functional result and quality of life in up to 73% of all patients. Predisposing high risk factors for heterotopic ossification are severe pre-intra- and/or postoperative hip trauma, previous development of ipsi- and/or contralateral heterotopic ossification, hypertrophic osteoarthritis, active rheumatoid spondylarthritis as well as male sex. Over the past two decades a variety of surgical, pharmaceutical and radiotherapeutic prophylactic measurements have been proposed and tested in clinical trials. Since June 1988, we have treated 77 patients or 80 hips respectively with prophylactic irradiation. Individual risk factors included severe coxarthrosis grade IV, ipsi- or contralateral heterotopic ossification and severe hip trauma. As of July 1991 60 patients with a minimum follow-up of six months could be analyzed using clinical and radiological scoring systems. The patients had been prospectively randomized in two different treatment arms: 32 patients were treated with low dose (LD), five times 2 Gy daily fractions to a total dose of 10 Gy, whereas 28 patients were treated with high dose (HD), ten times 2 Gy (eight patients) or five times 3.5 Gy (20 patients). Operative procedures and individual risk factors were equally distributed in both groups. 23 patients (38% received indometacin three times 25 mg for six weeks, 19 patients (32%) diphosphonate EHDP 20 mg/kg body weight and 18 patients (30%) had no additional medication. 56/60 (93%) patients developed no significant heterotopic ossification and/or remained without impairment of their postoperative radiological and clinical hip status according to the applied Brooker and Harris Scores. Only 4/60 (7%) patients demonstrated treatment failures developing postoperative worsening one grade of Brooker score in two patients and two and three grades of Brooker score in the two others. Only 1/49 patients experienced a treatment failure, when radiotherapy had been initiated before and at postoperative day 4 compared to 3/11 patients initiated after postoperative day 4 (p less than 0.001). 3/32 patients (9.4%) in the LD group and 1/28 (3.6%) in the HD group were scored as treatment failures (nonsignificant). Radiotherapy treatment duration and additional medication had no impact on the outcome. In conclusion postoperative radiotherapy has shown high efficacy in prevention of heterotopic ossification as long as the treatment is initiated within the first four days after surgery. With respect to acute toxicity postoperative radiotherapy seems to be without any competition compared to surgical and pharmaceutical approaches including corticoid, diphosphonate and nonsteroid antiphlogistic drugs.

Adult↗
PubMed1992

Deep venous thrombosis associated with heterotopic ossification.

The differential diagnosis of the swollen lower extremity in the patient with spinal cord injury includes deep venous thrombosis, fracture, cellulitis, joint sepsis, heterotopic ossification, hematoma formation, and neoplasm. A patient with an asymmetrically swollen limb who was found to have concurrent ipsilateral acute deep venous thrombosis and active heterotopic ossification is described. The diagnostic workup included various laboratory and radiologic studies. Therapy included anticoagulation with heparin and warfarin. To treat the heterotopic ossification, indomethacin, etidronate, and graded range of motion were used. We learned from this patient and several similar cases that acute deep-venous thrombosis and active heterotopic ossification may occur concurrently, and therapeutic anticoagulation did not lead to bleeding within or around the area of active heterotopic ossification. The possibility of a relationship between heterotopic ossification and deep venous thrombosis is presently being studied at our institution.

Diagnosis, Differential↗
PubMedDate not supplied

Ossification of the peritoneal membrane.

BACKGROUND: Peritoneal dialysis (PD) patients rarely develop sclerosing peritonitis (SP), a severe, life-threatening condition of unknown pathogenesis. Ossification of the peritoneum (PO) is a rare occurrence, which has, however, been reported in PD patients with SP. OBJECTIVE: To investigate etiopathogenetic correlations between PO and SP by histopathological examination. METHOD: We examined biopsy specimens, obtained by laparoscopy or during surgery from 36 patients with SP, from all parts of Italy in the past 8 years for evidence of peritoneal calcification or ossification. Other studies were performed on a sample of dense white material found under the parietal peritoneum of 1 patient during laparoscopy. RESULTS: Ossification of the peritoneum was found in 4/16 patients with calcifications. In addition to PO, we also found bone marrow in two specimens and arterial ossification in one case. In specimens with calcifications, and especially those with ossification, there was evidence of peritoneal inflammation with infiltration of lymphocytes, multinuclear giant cells, macrophages, and mast cells. The chemical composition of the whitish material was 85% calcium chloride and 15% hydroxyapatite. CONCLUSIONS: Calcifications alone were found in 33% (12/36) of cases of SP; 11% of SP cases were complicated by both peritoneal calcification and ossification (4/36), which indicates great availability of calcium under conditions of inflammation. Where does this calcium come from? In 1 patient with PO, the quantity of calcium was enormous and its unusual composition suggested a link with the calcium contained in dialysis solution.

Adult↗
PubMed1986

[Experimental studies on the ossification of the posterior longitudinal ligament of the cervical spine].

Fluor, which is a natural substance contained in rice, vegetables, marine products and some seasonings, is assimilated into the body through ingestion. Approximately 60% of the total amount of this fluor intake would be based on rice. A histological study of cervical spine, knee ligaments, Achilles tendon and viscera of rabbits (approx. 12-16 weeks old) was made after injection with sodium fluoride in this study. The rabbits were divided into three groups: Group A (administered NaF 86.2 mg/kg, 5.7 mg/ml, 7 rabbits); Group B (administered NaF 31.5 mg/kg, 2.85 mg/ml, 6 rabbits) and a Control Group of 3 rabbits. Five rabbits in Group A (71.4%) and all six rabbits in Group B (100%) developed ossification of the posterior longitudinal ligament. Ossification of the yellow ligament was also found in two rabbits in Group A and one in Group B. No ossification was found in the Control Group. Both enchondral and intramembranous ossification were found in ossification of posterior longitudinal ossification in the rabbits.

Animals↗
PubMed1993

[Factors affecting the development of para-articular ossification in total hip replacement].

The authors evaluated the prevalence of paraarticular ossifications in three groups of patients after a minimum interval of one year following the administration of a total prosthesis. For evaluation they used Brooker's classification. The first group comprised 40 patients who during the first six weeks after administration of a cemented prosthesis of the hip joint took 75 mg of Indomethacin per day in three doses. The second control group comprised 50 patients, i.e. 61 operated hip joints (11 bilateral prostheses) to whom Indomethacin was not administered during the postoperative period, nor any other antiphlogistic preparations. The third group comprised 40 patients to whom a non-cemented prosthesis of the hip joint was implanted and who did not use any antiphlogistic preparations after operation. In the first group, i.e. patients after total endoprostheses of the hip joint with preventive administration of Indomethacin, ectopic ossifications were recorded in 32.5% of the operated patients. In the second group, i.e. without preventive Indomethacin administration, ectopic ossifications of various grades were recorded in 51%. In patients with non-cemented prostheses of the hip joint the prevalence of ectopic ossifications was only 18%. The authors selected from the control group a sub-group with bilateral prostheses of the hip joint where an ectopic bone was found. This sub-group comprised 9 operated patients and bilateral ectopic ossifications developed only in 33.3%. From the results ensues that Indomethacin administration is an expedient prevention of development of paraarticular ossifications. Marked reduction of development of ectopic bone formation occurs when bone cement is not used as a fixation medium.(ABSTRACT TRUNCATED AT 250 WORDS)

Cementation↗
PubMed1996

Bilateral duplication of the primary ulnar ossification center in Ellis-van Creveld syndrome.

A patient with Ellis-van Creveld (EvC) syndrome and bilateral duplication of the primary ulnar ossification center is presented. Abnormal ossification involving secondary ossification centers of the femur and tibia as well as duplication of primary ossification centers in the carpal bones are well described in EvC. No abnormality of ulnar ossification has been noted in patients with EvC or any other skeletal dysplasia. The occurrence of bilateral duplication of ulnar ossification centers extends the clinical findings of the EvC syndrome. The gap between the ossified areas could be misinterpreted as a fracture and thus lead to a suspicion of osteogenesis imperfecta prenatally or traumatic fracture postnatally.

Ellis-Van Creveld Syndrome↗
PubMed2004

Development of the microcirculation of the secondary ossification center in rat humeral head.

This work investigated the origin and development of microcirculation in the rat humeral head and the expression of vascular endothelial growth factor (VEGF) as a factor supporting the vascular growth and the development of the secondary ossification centers. Sixty rats aging 1, 3-4, 6-8, 11, and 21 days, 5 weeks, and 4 and 8 months were used. Samples of humeral head were collected for histology and immunohistochemistry for VEGF. Some animals were perfused with Mercox resin in order to obtain vascular corrosion casts (vcc) observed by scanning electron microscopy (SEM). No cartilage canals were present at birth. At 6 days postnatal, blood vessels coming from the perichondrium and the region near the capsule attachment invaded the cartilage; at 11 days postnatal, signs of calcification were present and within the third week some bone trabeculae were formed. Just before the vascular invasion of the epiphysis, a positive reaction for VEGF was localized in chondrocytes of the epiphyseal cartilage close to the capsule insertion. During the development and expansion of the secondary ossification center, VEGF expression was higher in chondrocytes but decreased when epiphysis was diffusely ossified. VEGF was expressed also by mesenchymal cells present in and around the fibrous tissue where the secondary ossification center will develop. SEM vcc confirmed that vessels penetrating into the epiphysis arose merely from the periosteal and the capsular networks, and vascular connections with the diaphyseal circulation were not evident. These observations demonstrated that VEGF production by chondrocytes begun some days after birth, supported the rapid vascular growth from the surrounding soft tissues, and was chronologically related to the development of the secondary ossification center in rat proximal humerus. Finally, the possible role of VEGF as mediator of angiogenesis and, at least indirectly, as a trigger factor also in the ossification and the bone remodeling of the secondary ossification centers has been discussed.

Age Factors↗
PubMed2005

Osteogenic PTHs and vascular ossification-Is there a danger for osteoporotics?

Inflammation in vascular (mostly arterial) walls and heart valves triggered by the trans-endothelial influx of LDL particles and the action of subsequently modified (e.g., by oxidation) LDL particles can trigger true bone formation by valvar fibroblasts, by a subpopulation of re-differentiation-competent VSMCs (vascular smooth muscle cells) or by vascular pericytes. Vascular ossification can lead to heart failure and death. Elderly osteoporotic women who need osteogenic drugs to restore their lost skeletal bone are paradoxically prone to vascular ossification-the "calcification paradox." The recent introduction into the clinic of a potently osteogenic parathyroid hormone peptide, Lilly's rhPTH-(1-34)OH (Forteotrade mark), to reverse skeletal bone loss raises the question of whether this and other potently osteogenic PTHs still in clinical trial might also stimulate vascular ossification in such osteoporotic women. Indeed the VSMCs in human and rat atherosclerotic lesions hyperexpress PTHrP and the PTHR1 (or PTH1R) receptor as do maturing osteoblasts. And the evidence indicates that endogenous PTHrP with its NLS (nuclear/nucleolar localization sequence) does stimulate VSMC proliferation (a prime prerequisite for atheroma formation and ossification) via intranuclear targets that inactivate pRb, the inhibitory G1/S checkpoint regulator, by stimulating its hyperphosphorylation. But neither externally added full-length PTHrP nor the NLS-lacking PTHrP-(1-34)OH gets into the VSMC nucleus and instead they inhibit proliferation and calcification by only activating the cell's PTHR1 receptors. No PTH has an NLS and, as expected from the observations on the externally added PTHrPs, hPTH-(1-34)OH inhibits calcification by VSMCs and cannot stimulate vascular ossification in a diabetic mouse model. Encouraging though this may be for osteoporotics with their "calcification paradox," more work is needed to be sure that the skeletally osteogenic PTHs do not promote vascular ossification with its cardiovascular consequences.

Animals↗
PubMed2005

Sonographic identification and measurement of the epiphyseal ossification centers as markers of fetal gestational age.

PURPOSE: This study was conducted to verify the predictive value of epiphyseal ossification center measurements in estimating gestational age. METHODS: Women with singleton pregnancies of 30-40 weeks gestation (n = 377) were enrolled in this prospective study. The distal femoral, proximal tibial, and proximal humeral ossification centers were identified and measured. A nomogram of fetal bone development was created using the sum of the three diameters. RESULTS: Gestational age correlated well with the diameters of the distal femoral and the proximal tibial epiphyseal ossification centers but even better with the sum of the three ossification centers. Positive predictive values of the fetus having gestational age of at least 37 weeks when the sum of the three centers was 7, 11, and 13 mm were 82%, 94%, and 100%, respectively. A nomogram was created using the sum of the ossification centers for 30-40 weeks' gestational age. CONCLUSIONS: Ultrasonographic visualization of the epiphyses ossification centers may be a useful marker of fetal gestational age.

Adolescent↗
PubMed1989

Role of mechanical loading in the progressive ossification of a fracture callus.

The progressive ossification pattern in a fracture callus was predicted based on a theory that relates the local stimulus for ossification to the tissue mechanical loading history. Two-dimensional finite element analyses of a fracture callus were considered at three different stages of ossification. The sites of callus ossification represented in the initial model were predicted by previous analyses relating mechanical stress and vascularity to the differentiation of mesenchymal tissue in the early callus. The zones of further ossification, bone bridging, and bone consolidation predicted in the present study were found to be similar to the ossification patterns that have been documented by other researchers. The approach used to predict fracture healing is identical to that of previous studies predicting joint morphogenesis, with the exception that fracture healing requires continuous, attached skeletal elements, whereas joint morphogenesis requires discontinuous, articulating skeletal elements.

Bony Callus↗
PubMed2002

A new rapid radiological procedure for routine teratological use in bone ossification assessment: a supplement for staining methods.

BACKGROUND: Presently, bone ossification is assessed by the study of single-stained fetal bones (alizarin red-S) or double-stained bones and cartilaginous structures (alcian blue followed by alizarin red-S). Both methods, especially double-staining, are labor-intensive, time-consuming, and provide qualitative information regarding skeleton ossification. Quantitative evaluation of ossification is more difficult and is usually based on determination of calcium and other minerals in the bone by means of atomic absorption spectrometry. Here we introduce a simple new method that allows quantitative determination of skeleton ossification before routine staining examination. METHODS: Fetuses delivered by laparotomy on the 16th and 21st day of gestation as well as 1-day-old rat pups were examined. The fetuses and pups were prenatally subcutaneously exposed to sodium valproate or to physiological saline. Lateral, prone, and supine digital radiograms of each fetus were taken using the Digora-Soredex digital radiography system and the Planmeca Intra intraoral X-ray machine. According to the best visualization, the data concerning vertebra were analyzed. All the fetuses were then routinely double-stained using alcian blue and alizarin red-S. RESULTS: Malformations of axial skeleton (rib, sternum, and thoracic and sacral vertebra) were found in valproate-treated groups. Unlike cartilage malformations, the bone changes were detected in similar frequency in radiological and staining methods. Differences in densities according to the degree of ossification in the vertebral arches and bodies at different levels of the vertebral column, between drug-treated and negative control groups were noted. CONCLUSIONS: The preliminary results suggest that digital radiography examination is a useful method in determining delaying of skeleton ossification not detectable by other methods. It balances qualitative and quantitative aspects of the presently used methods and is also simple, objective, fast, and relatively inexpensive.

Animals↗
PubMed1982

A study of fetal growth retardation in teratological tests: relationship between body weight and ossification of the skeleton in rat fetuses.

The normal development of preterm rat fetuses (day 19.0 to day 21.0) was investigated with respect to body weight and ossification of the sacrococcygeal vertebrae, supraoccipital bone, sternebrae, and proximal phalanges in the forepaw. Normal standard growth curves were established for these indexes in rat fetuses. A method was devised for the analysis of the relationship between low body weight and retarded ossification induced by teratogenic agents. In normal fetuses, mean body weight and number of ossified sacrococcygeal vertebrae and the ossification stage of the supraoccipital bone increased approximately linearly with advancing fetal age. The number of ossified sternebrae and proximal phalanges in the forepaw increased curvilinearly with advancing fetal age. By use of the standard curves, fetal growth retardation observed in teratological experiments may be expressed as retardation in relation to the standard in hours. The characteristic pattern of growth retardation induced by an agent may be evaluated by comparison of the degree of retardation expressed in a common "hour" scale among various growth indexes. This method was applied to experimental data of fetal growth retardation induced by maternal fasting. The degree of retardation was found to differ among growth indexes; body weight and ossification of the sacrococcygeal vertebrae were the most severely retarded; ossification of the supraoccipital bone and the sternebrae was moderately retarded; ossification of the proximal phalanges in the forepaw was least retarded.

Animals↗
PubMed1988

Caffeine and reduction of fetal ossification in the rat: fact or artifact?

This study was done to determine the gestational period during which the rat fetus is susceptible to reduction of skeletal ossification by caffeine. Caffeine, 100 mg/kg/day by gavage, caused the greatest reduction in ossification, as assessed by staining with alizarin red S, in fetuses exposed between day 16 to 19 of gestation, less in those treated between day 7 to 19, and markedly less in those receiving it between day 7 to 16; a single dose on day 19 had very little effect. This indicates that the fetus is most susceptible late in pregnancy. Bones in early stages of mineralization on day 20 showed a greater reduction in staining than those in later stages. Thus, caffeine appears to lower the rate of ossification rather than reduce its final extent. In the day 7 to 19 caffeine treatment group, but not in the day 16 to 19 group, maternal and fetal body weights were reduced, and 1.6% of the fetuses had aphalangia. The day 7 to 16 caffeine treatment reduced fetal body weight. This argues against an association between reduction in fetal weight and ossification. None of the treatments affected rates of resorption or litter size. A novel and important observation made is that the different caffeine treatments affected the staining by alizarin of both claws and bones in a qualitatively and quantitatively similar manner. Since claws are devoid of osteoid, this observation questions the specificity of alizarin for the assessment of the state of fetal ossification and raises doubt as to the significance of the observed action of caffeine on ossification.

Abnormalities, Drug-Induced↗