Fibrodysplasia ossificans progressiva: Still turning into wood after 300 years?

Fibrodysplasia ossificans progressiva (FOP), a rare autosomal dominant disorder, is characterized by symmetrical congenital skeletal abnormalities and progressive heterotopic ossification of the connective tissues. At present, more than 300 years after the first report by Patin in 1648 in which he described the woman who turned to wood, its pathogenesis remains largely unknown and its therapy is limited to symptom-modifying trials. However, significant progress has been recently made and new data on the molecular organization and regulation of normal and disordered bone induction are likely to lead to a more specific therapy. FOP is believed to be a genetic disorder characterized by a disturbed expression of the endochondral osteogenesis programme, and the remarkable clues from the fly reported by Kaplan et al. [8] in 1990 suggest a gain-of-function mutation in the genetic regulation of bone morphogenetic proteins.     

Hard tissue laser ablation mechanisms

The aim of this work is the experimental and theoretical investigation of the influence of variable laser parameters (wavelength, fluence, pulse repetition rate) and of the optical and thermophysical properties of bone tissue (absorption coefficient, tissue inhomogeneity) as well as of the sample thickness on ablation thresholds and ablation rate. Ablation and perforation experiments were conducted using a semiconductively pre-ionized transverse excitation atmospheric pressure (TEA) carbon dioxide (CO₂) laser (10.6m and a sliding discharge TEA [hydrogen fluoride (HF)] laser (2.9m). The experimental data are discussed with respect to the following ablation mechanisms: thermal melting and vaporization process, pressure oscillation of gases released by the thermal decomposition of collagen and/or apatite, stresses due to the expansion of superheated water.     

Impact of different doses of ethinyl oestradiol on reduction of final height in constitutionally tall girls

Fifty-two tall girls were treated for constitutionally tall stature with different ethinyl oestradiol (EE) dosages. They were divided into three different treatment groups: group B (100 g EE/day;n=11); group C (300 g;n=25) and group D (500 g;n=16) and compared with an untreated group A (n=21) matched for age, height, bone age (BA) and height prediction. Using the height prediction method TW II, EE treatment reduced final height compared with the untreated girls in a weak dose-dependent manner, 2.3 cm (100 g/day), 3.0 cm (300 g/day), and 3.8 cm (500 g/day). Such a dose dependency was not found on applying the Bayley-Pineau height prediction method (100 g/day: 4.1 cm; 300 g/day: 4.2 cm; 500 g/day: 4.5 cm). However, there was a striking inverse correlation of the BA at the onset of treatment with the height reduction achieved using the TW II method (r: –0.43;P<0.001). Importantly, girls with a BA below 12 years at the onset of treatment experienced a height reduction of more than 6 cm.The EE dose used in the range of 100–500 g/day is not crucial for the amount of height reduction in tall girls. In general high dose EE treatment should be given restrictively, and especially so in girls with a BA (TW2 RUS-ZH) above 12.0 years.     

Simple, Rapid Enzyme-Linked Immunosorbent Assay (ELISA) for the Determination of Rat Osteocalcin

Determination of the concentration of osteocalcin in rat serum is frequently performed using a commercially available radioimmunoassay (RIA). However, this assay takes 3 days to complete, uses radioactive material, and has a narrow linear range. The limited range of the RIA makes it necessary to test multiple dilutions of the sample which frequently results in values that differ, depending on the dilution. In order to overcome these limitations, we have developed an ELISA that utilizes the same standards and anti-rat osteocalcin antiserum, as is used in the RIA. The principle of the ELISA is that the osteocalcin in the sample competes with osteocalcin previously immobilized on a microtiter plate to bind to the available anti-rat osteocalcin antibodies. The amount of antibody bound to the immobilized osteocalcin is determined colorimetrically using a secondary antibody coupled to alkaline phosphatase. This ELISA has a three-log linear response with a sensitivity of 0.1–0.15 ng/ml and intra- and interassay coefficient of variance (CV) values of less than 10%. Most importantly, the assay is rapid and only requires a 2-hour incubation of the sample with the antiserum. The incubation time is important since we and others have observed a significant decrease in the osteocalcin level from serum samples incubated for long periods of time with the antiserum, presumably due to degradation of the osteocalcin. In general, the commercially available RIA gives osteocalcin values that are one-half to one-fourth that of the ELISA because the RIA requires a 48-hour incubation time. Received: 14 November 1997 / Accepted: 9 July 1998     

High Bilirubin Levels Interfere with Serum Tartrate-Resistant Acid Phosphatase Determination: Relevance as a Marker of Bone Resorption in Jaundiced Patients

Serum tartrate-resistant acid phosphatase (TRAcP) activity is considered to be a biochemical marker of bone resorption. Recently, a lack of specificity of collagen-related markers for assessing bone turnover has been observed in patients with chronic liver disease. Thus, it could be of great interest to determine serum TRAcP activity in such patients. However, nonspecificity of the analytical reaction could occur when hemolyzed, lipemic, or icteric specimens are analyzed. Therefore, we have studied the interference caused by bilirubin in the measurement of serum TRAcP activity using the Hillmann method. The interference was assessed in two pools of serum containing different bilirubin concentrations but with similar total AcP levels. Mixing proportional parts of the two pools, 10 samples were also obtained. Serum activities of total AcP and TRAcP, and the concentration of bilirubin were measured in the 10 samples. Both the actual and the expected values obtained by theoretical calculations were compared. Serum bilirubin values of 2.4 mg/dl showed a negative interference of 15% in the determination of serum TRAcP activity, whereas values of bilirubin higher than 10 mg/dl interfered totally with the measurement of serum TRAcP. Bilirubin did not interfere with the total AcP determination. This study clearly shows the interference of bilirubin in the determination of serum TRAcP. This finding should be considered when bone metabolism disorders are evaluated in jaundiced patients. Received: 6 April 1998 / Accepted: 1 October 1998     

Ipriflavone does not alter bone apatite crystal structure in adult male rats

We have previously found that a short-term treatment with high doses of ipriflavone increased bone density and improved the biomechanical properties of adult male rat bones, without altering their mineral composition. To determine whether this effect can be associated with alterations of bone crystal structure, we have performed X-ray diffraction analysis of bones obtained from rats treated with ipriflavone at doses that were effective in inducing favorable changes on bone density and biomechanics. Eighteen-week-old male Sprague Dawley rats were treated by oral route with either ipriflavone (200 or 400 mg/kg/day), or its vehicle for 12 weeks. The treatment was well tolerated and body weight increased to the same extent in all animals. As a measure of bone crystallinity, we examined the (310) and (002) reflections of the X-ray diffraction patterns, corresponding to the directions perpendicular and parallel to the c-axis of the crystals, respectively. No major differences were observed between ipriflavone-treated and control animals for the broadening parameter 1/2 for (310) and (002) peaks, as well as for lattice parameters. Therefore, a 12-week treatment with ipriflavone at high doses does not induce significant modifications of bone crystallinity. Thus. the positive effect of ipriflavone on bone mineral density appears to be associated with an increased apatite crystal formation rather than an increase of crystal size. These results provide further evidence for the safety and usefulness of ipriflavone in the treatment of osteoporotic syndromes.     

Effects of vitamin D3 metabolites on bone cell calcium transport

Summary The vitamin D₃ metabolite, 25-hydroxycholecalciferol, at concentrations of 0.01 to 10.0 g/ml, decreased calcium uptake by isolated bone cells. The effect occurred within 1 min after the simultaneous addition of metabolite and⁴⁵Ca. Lactic acid and ATP production by the cells was not affected. 24(R), 25-dihydroxycholecalciferol produced a similar decrease in calcium uptake. Vitamin D₃ had no effect at concentrations from 0.01 to 10.0 g/ml. No effect of 1,25-dihydroxycholecalciferol on calcium uptake was observed with concentrations from 0.1 to 100 ng/ml and various preincubation periods extending to 2 h. None of the agents had any effect on calcium efflux. The effects of 25-hydroxycholecalciferol and 24(R), 25-dihydroxycholecalciferol on calcium uptake were not seen in isolated fetal rat skin cell preparations.     

The vascular ‘sunburst’ appearance of osteosarcoma: A new angiographic finding

The angiographic analogue of the sunburst, (right angle) periosteal new bone formation in osteogenic sarcoma is described. The angiographic findings in this tumor and their relationship to the pathologic appearance are discussed.     

Greffe Intertibio-péronière dans le Traitement des Pseudarthroses Fistuleuses Diaphysaires de Jambe

Résumé Les auteurs présentent une série de 30 pseudarthroses fistuleuses de jambe traitées par greffe intertibiopéronière, revues avec un recul allant de 3 à 9 ans.La voie d'abord utilisée pour la greffe est le plus souvent rétropéronière; dans 14 cas l'immobilisation a été réalisée par un plâtre et dans 16 cas par un fixateur externe (chez 9 malades, l'opération a été réalisée après mise en place du fixateur). 28 guérisons sont constatées (25 rapides en 3 à 8 mois, 3 plus lentes) et 2 échecs.Les auteurs insistent sur l'intérêt de la voie rétropéronière qui permet le plus souvent de rester à distance des parties molles «septiques» et du fixateur externe comme moyen de contention.L'indication de cette méthode concerne surtout les pseudarthroses infectées anciennes avec des extrémités osseuses atrophiques ou en cas de perte de substance osseuse. Dans les autres cas, la décortication de Judet est plus simple et permet d'obtenir d'excellents résultats.

---

Intertibio-peroneal graft in the treatment of infected non-united legs

Summary The authors present a series of 30 cases of fistular non united fractures of the leg treated by interosseous bone graft. Survey was performed from 3 to 9 years.In most cases, the surgical approach is made behind the fibula; in 14 cases, immobilization by means of a plaster cast and in 16 cases by means of external fixation (in 9 cases, external fixation bar + screws was realised first).Healing occured in 28 cases (quick in 25 cases, i.e. within 3–8 months, slow in 3 cases) and 2 failures.The authors emphasize the value of the posterior (retrofibular) approach, which avoids the distal septic soft areas, and of the bar-screws device.The procedure is mostly relevant in old infected non united fractures, with atrophic bony extremities or with boneloss.In the other cases, Judet's procedure is more simple and allows excellent results.

     

Comparative assessment of bone mineral density of the forearm using single photon and dual X-ray absorptiometry

Summary Forearm bone mineral density (BMD) was measured at proximal and distal sites by ¹²⁵I single photon absorptiometry (SPA) and by dual energy X-ray absorptiometry (DXA) in 67 consecutive subjects, aged 18–75 years. Correlations and regression equations between these two techniques were determined. All forearm measurements were significantly correlated with each other (r=0.599–0.926; P0.0001). Although SPA and DXA correct for fat in different ways, we found similar correlation and regression equations in women with body mass index measurements above and below the mean. In addition, forearm measurements by both techniques were moderately correlated with vertebral spine and hip BMD. We conclude that overall, SPA forearm measurements in a population can be calibrated to DXA measurements if necessary, and that DXA forearm measurements are as predictive of the remainder of the skeleton as SPA measurements.