Introduction: This study evaluated the effect of oral alendronate on the BMD of adult patients with osteogenesis imperfecta.Materials and Methods: We carried out a 3-year, randomized, double-blind, placebo-controlled trial of oral alendronate in 64 adult patients with osteogenesis imperfecta. The primary endpoint was the difference between the groups in the mean percent change in lumbar spine BMD at 3 years. Secondary outcomes included changes in BMD of total hip, vertebral and peripheral fracture incidence, pain, hearing loss, and bone turnover biochemical markers. Patients were treated daily with either placebo or 10 mg alendronate. All received 1 g of calcium and 800 IU of vitamin D daily.Results: The mean +/- SD increases in the lumbar spine BMD were 10.1 +/- 9.8% (p < 0.001) and 0.7 +/- 5.7% in the alendronate and placebo groups, respectively. Hip BMD increased in the alendronate group by 3.3 +/- 0.5% (p = 0.001) and decreased in the placebo group by 0.3 +/- 0.6%. The sample size was not sufficient to determine an effect of alendronate on fracture rate. A significant increase of the pain score was noted in the alendronate group (p = 0.04) in the intent-to-treat analysis but not in the per protocol analysis. There was no change in hearing in either group. Bone resorption and formation biochemical markers were significantly decreased in the alendronate group (p < 0.001). There were no differences in severe adverse effects between the groups, but there was an increase in nonsevere upper gastrointestinal effects in the alendronate group (p = 0.003).Conclusions: Oral alendronate increases BMD and increase nonsevere gastrointestinal adverse effects but does not modify the hearing loss in adult patients with osteogenesis imperfecta. More studies are needed to evaluate an effect on the fracture rate.

Dans les pays industrialisés, la prévalence des maladies allergiques s'est considérablement accrue au cours de ces 20 dernières années. L'augmentation de la teneur en allergènes joue un rôle déterminant dans ce phénomène. Pour lutter contre la composante allergique de l'asthme, les moyens thérapeutiques à notre disposition sont l'éviction des allergènes et l'immunothérapie spécifique. L'immunothérapie spécifique en modifiant la réponse Th1/Th2 vis-à-vis des allergènes, pourrait réduire la destruction de l'épithélium respiratoire et le remodelage tissulaire consécutif à l'inflammation bronchique chronique d'origine allergique. Dans cette indication, l'immunothérapie spécifique interviendrait non pas seulement comme une désensibilisation spécifique mais comme un vaccin anti-allergique. L'efficacité d'une immunothérapie spécifique repose sur des indications bien posées mais également sur la qualité des extraits allergéniques utilisés. Cependant une allergénicité forte augmente le risque de réactions anaphylactiques graves, ce qui rend compte de certaines réticences à la pratique de l'immunothérapie spécifique dans l'asthme de l'enfant. Les manipulations génétiques (fragments d'ADN codant pour des allergènes insérés dans des plasmides ou des vecteurs viraux) ou l'utilisation des protéines allergéniques (isoallergènes, peptides recombinants) vont permettre dans l'avenir d'assurer les deux exigences de l'immunothérapie spécifique : pureté et stabilité des allergènes d'une part et diminution du risque anaphylactique d'autre part. La voie sublinguale est une alternative actuelle à la voie injectable. Si son innocuité est démontrée, des études comparatives à trois bras avec la voie injectable et un placebo sont nécessaires pour affirmer son efficacité dans l'asthme de l'enfant. Finalement l'enjeu de l'immunothérapie spécifique est de modifier l'histoire naturelle de la maladie, en se comportant comme une vaccination.

The excitatory amino acid glutamate (Glu) is a potent neurotransmitter in the central nervous system and exerts its action via a variety of glutamate receptors (GluRs). Because we had previously shown that a poly-glutamate (poly-Glu) peptide stimulates bone resorption in vitro, an effect specific to Glu (Raynal, C., Delmas, P. D., and Chenu, C. Bone sialoprotein stimulates in vitro bone resorption. Endocrinology 137:2347–2354; 1996), we investigated the possibility that bone cells express GluRs, and whether they may be important for osteoclast activity. Using immunocytochemistry on rat bone sections, we have shown that all mature bone cells (osteoblasts and osteoclasts) express GluRs, and that the ionotropic N-methyl-D-aspartate (NMDA) receptor 1 subunit (NMDAR1) appears most highly expressed. Osteoclasts isolated from rabbit long bones also possessed NMDAR1 GluRs. Bone resorption in vitro by isolated osteoclasts was inhibited by a monoclonal antibody directed against NMDAR1, as well as by two pharmacological antagonists of this receptor (D-AP5 and MK 801), which also antagonized poly-Glu stimulated bone resorption. These results suggest a possible new mechanism for regulating osteoclast activity and indicate that excitatory amino acids such as glutamate may be important local regulators of bone cell functions.

Bone sialoprotein (BSP) is a protein highly specific for bone, which contains an arginine-glycine-aspartic acid (RGD) cell attachment sequence involved in osteoclast adhesion to bone matrix via the vitronectin receptor. We have investigated its role in in vitro bone resorption using the well described isolated osteoclast resorption pit assay. BSP significantly stimulates bone resorption in a dose-dependent manner, increasing the overall resorbed area on ivory slices and the number of lacunae at concentrations as low as 50 nM. Neither recombinant osteopontin nor intact vitronectin has any effect on bone resorption, suggesting a specific effect of BSP. The stimulation of bone resorption induced by BSP could be partially explained by an increase in osteoclast adhesion to bone via its RGD sequence, and our results suggest another mechanism of action of BSP that might involve another region of the molecule, such as its acidic sequences. Although BSP stimulates bone resorption in a coculture system of bone marrow cells and osteoblastic cells, it dose dependently inhibits the formation of osteoclast-like cells at equivalent concentrations in this culture model. In conclusion, we provide evidence that BSP plays an important role in the bone resorption process and may regulate bone resorption as well as osteoclast formation.

Thirty-one patients undergoing neuro-radiological investigations were anesthetized by methohexital-fentanyl association. Induction of anesthesia was performed by I. V. bolus of these two agents. Anesthesia was maintained by a constant rate perfusion of methohexital and fentanyl, prepared according to body weight. Posology can be reduced hourly by modifying the perfusion rate. First hour: methohexital 2 mg/kg/hour fentanyl 5 microgram/kg/hour; second hour: methohexital 0.4 mg/kg/hour, fentanyl 2 microgram/kg/hour; third hour: methohexital 0,4 mg/kg/hour, fentanyl 1 microgram/kg/hour. If necessary this dosage was modified according to isolate reactions and thus total real consumption was 25 to 30 p. cent higher to estimated theoretical requirements. This protocol of anesthesia with controlled ventilation was well cardiocirculatory tolerated and adapted to these radiological investigations.