Risedronate Reduces the Risk of First Vertebral Fracture in Osteoporotic Women

Risedronate treatment reduces the risk of vertebral fracture in women with existing vertebral fractures, but its efficacy in prevention of the first vertebral fracture in women with osteoporosis but without vertebral fractures has not been determined. We examined the risk of first vertebral fracture in postmenopausal women who were enrolled in four placebo-controlled clinical trials of risedronate and who had low lumbar spine bone mineral density (BMD) (mean T-score =–3.3) and no vertebral fractures at baseline. Subjects received risedronate 5 mg (n= 328) or placebo (n= 312) daily for up to 3 years; all subjects were given calcium (1000 mg daily), as well as vitamin D supplementation (up to 500 IU daily) if baseline serum 25-hydroxyvitamin D levels were low. The incidence of first vertebral fracture was 9.4% in the women treated with placebo and 2.6% in those treated with risedronate 5 mg (risk reduction of 75%, 95% confidence interval 37% to 90%; P= 0.002). The number of patients who would need to be treated to prevent one new vertebral fracture is 15. When subjects were stratified by age, similar significant reductions were observed in patients with a mean age of 64 years (risk reduction of 70%, 95% CI 8% to 90%; P= 0.030) and in those with a mean age of 76 years (risk reduction of 80%, 95% CI 7% to 96%; P= 0.024). Risedronate treatment therefore significantly reduces the risk of first vertebral fracture in postmenopausal women with osteoporosis, with a similar magnitude of effect early and late after the menopause. Received: 12 September 2001 / Accepted: 11 December 2001     

高效液相色谱法测定右旋儿茶素血浆浓度及药代动力学参数

本文建立了体液中右旋儿茶素的RP-HPLC测定方法。采用C_(18)键合相硅胶为填料的固相提取柱进行样品预处理,右旋儿茶素的提取回收率为79.8%.应用二极管阵列检测器对色谱峰纯度进行鉴定。该法精密度好,方法回收率近100%,日内、日间的变异系数为2.4～5.6%,血浓69.6～1160 ng/ml范围内呈线性关系,r=0.9993。家兔静注右旋儿茶素18mg/kg,其药代动力学过程符合二室模型,分布相半衰期为0.129 h,消除相半衰期为1.19h。     

T CELL RECEPTOR DELTA LOCUS POLYMORPHISM IN RHEUMATOID ARTHRITIS

In order to identify new susceptibility markers for Rheumatoid Arthritis (RA), we analysed the dinucleotide repeat polymorphism at the T cell receptor delta locus (TCRD) in 65 RA patients and 99 healthy Belgian controls. A significant under-representation of the A4-A5 TCRD genotype was observed in the RA population.     

Non-linear increase in vertebral density induced by a synthetic steroid (Org OD 14) in women with established osteoporosis

The results of a 2-year placebo-controlled study in 38 female patients with osteoporosis are presented. This study was conducted to evaluate the efficacy of a daily oral dose of 2.5 mg Org OD 14 ((7 alpha, 17 alpha)-17-hydroxy-7-methyl-19-norpregn-5(10)-en-20-yn-3-one) in the treatment of established osteoporosis. Org OD 14 is a steroid which shows combined weak oestrogenic, androgenic and progestational activity. A total of 31 patients completed a 12-month study period (17 placebo, 14 Org OD 14) and 25 of these went on to complete the full 24-months (15 placebo, 10 Org OD 14). A significant increase in bone mineral density as measured by dual photon absorptiometry was recorded in the lumbar spine in the Org OD 14-treated patients at 8, 16 and 24 months. The gain in bone mass after 8 months averaged 4% (P less than 0.01) and after 24 months 8% (P less than 0.001). In the control group, a bone loss rate of 2% per year was recorded in the lumbar spine. No significant changes in bone density in the forearm as assessed by single photon absorptiometry were found in either group. The increase in spinal bone density in the Org OD 14 group was non-linear and followed an S-shaped upward pattern. Org OD 14, while inducing no appreciable endometrial stimulation, was found to be a bone-active compound with anti-resorbing as well as anabolic activity. Org OD 14 warrants consideration not only for the long-term prevention of bone loss but also for curative treatment of post-menopausal osteoporosis.     

The UTX gene escapes X inactivation in mice and humans

We recently have identified a ubiquitously transcribed mouse Y chromosome gene, Uty , which encodes a tetratricopeptide repeat (TPR) protein. A peptide derived from the UTY protein confers H-Y antigenicity on male cells. Here we report the characterization of a widely transcribed X-linked homologue of Uty , called Utx , which maps to the proximal region of the mouse X chromosome and which detects a human X-linked homologue at Xp11.2. Given that Uty is ubiquitously transcribed, we assayed for Utx expression from the inactive X chromosome (Xi) in mice and found that Utx escapes X chromosome inactivation. Only Smcx and the pseudoautosomal Sts gene on the mouse X chromosome have been reported previously to escape inactivation. The human UTX gene was also found to be expressed from Xi. We discuss the significance of these data for our understanding of dosage compensation of X-Y homologous genes in humans and mice.      

L1 knockout mice show dilated ventricles, vermis hypoplasia and impaired exploration patterns

L1 is a neural cell adhesion molecule mainly involved in axon guidance and neuronal migration during brain development. Mutations in the human L1 gene give rise to a complex clinical picture, with mental retardation, neurologic abnormalities and a variable degree of hydrocephalus. Recently, a transgenic mouse model with a targeted null mutation in the L1 gene was generated. These knockout (KO) mice show hypoplasia of the corticospinal tract. Here we have performed further studies of these KO mice including magnetic resonance imaging of the brain, neuropathological analysis and behavioral testing. The ventricular system was shown to be abnormal with dilatation of the lateral ventricles and the 4th ventricle, and an altered shape of the Sylvius aqueduct. Additionally, the cerebellar vermis of the KO mice is hypoplastic. Their exploratory behavior is characterized by stereotype peripheral circling reminiscent of that of rodents with induced cerebellar lesions.