Arzoxifene for prevention of fractures and invasive breast cancer in postmenopausal women.
; ; Reginster, Jean-Yves et al
in Journal of Bone and Mineral Research (2011), 26(2), 397-404
BACKGROUND: Arzoxifene is a selective estrogen receptor modulator (SERM) more potent in preclinical testing than currently available agents. Its effects on clinical outcomes are not known. METHODS: In a ... [more ▼]
BACKGROUND: Arzoxifene is a selective estrogen receptor modulator (SERM) more potent in preclinical testing than currently available agents. Its effects on clinical outcomes are not known. METHODS: In a randomized blinded trial, women age 60 to 85 years with osteoporosis, defined as a femoral neck or lumbar spine bone mineral density T-score less than or equal to -2.5 or a vertebral fracture, and women with low bone mass, defined as a bone density T-score less than or equal to -1.0 and above -2.5, were assigned to arzoxifene 20 mg or placebo daily. The primary endpoints were new vertebral fracture in those with osteoporosis, and invasive breast cancer in the overall population. RESULTS: After 3 years, the cumulative incidence of vertebral fractures in patients with osteoporosis was 2.3% lower in the arzoxifene than in the placebo group, a 41% relative risk reduction (95% CI 0.45 to 0.77; P<0.001). In the overall population, the cumulative incidence of invasive breast cancer over 4 years was reduced by 1.3%, with a 56% relative reduction in risk (HR=0.44; 95% CI 0.26 to 0.76; P<0.001); there was no significant decrease in nonvertebral fracture risk. Arzoxifene increased the cumulative incidence of venous thromboembolic events by 0.7%, with a 2.3-fold relative increase (95% CI 1.5 to 3.7). CONCLUSION: Like other SERMs, arzoxifene decreased vertebral fractures and invasive breast cancer while the risk of venous thromboembolic events increased. (c) 2010 American Society for Bone and Mineral Research. [less ▲]Detailed reference viewed: 14 (2 ULg)
Effects of arzoxifene on fracture incidence in postmenopausal women with osteoporosis or with low bone mass
Reginster, Jean-Yves ; ; et al
in Osteoporosis International (2010, May), 21(Suppl.1), 23-24Detailed reference viewed: 21 (0 ULg)
Mutation analysis of the MEN1 gene in multiple endocrine neoplasia type 1, familial acromegaly and familial isolated hyperparathyroidism.
; ; et al
in Journal of Clinical Endocrinology and Metabolism (1998), 83(8), 2621-2626
Multiple endocrine neoplasia type 1 (MEN 1) is an autosomal dominant disease characterized by neoplasia of the parathyroid glands, the endocrine pancreas, and the anterior pituitary gland. In addition ... [more ▼]
Multiple endocrine neoplasia type 1 (MEN 1) is an autosomal dominant disease characterized by neoplasia of the parathyroid glands, the endocrine pancreas, and the anterior pituitary gland. In addition, families with isolated endocrine neoplasia, notably familial isolated hyperparathyroidism (FIHP) and familial acromegaly, have also been reported. However, whether these families constitute MEN 1 variants or separate entities remains speculative as the genetic bases for these diseases are unclear. The gene for MEN 1 has recently been cloned and characterized. Using single strand conformation analysis (SSCA) and sequencing, we performed mutation analysis in: a) a total of 55 MEN 1 families from 7 countries, b) 13 isolated MEN 1 cases without family history of the disease, c) 8 acromegaly families, and d) 4 FIHP families. Mutations were identified in 27 MEN 1 families and 9 isolated cases. The 22 different mutations spread across most of the 9 translated exons and included frameshift (11), nonsense (6), splice (2), missense mutations (2), and in-frame deletions (1). Among the 19 Finnish MEN 1 probands, a 1466del12 mutation was identified in 6 families with identical 11q13 haplotypes and in 2 isolated cases indicating a common founder. One frameshift mutation caused by 359del4 (GTCT) was found in 1 isolated case and 4 kindreds of different origin and haplotypes; this mutation therefore represents a common "warm" spot in the MEN1 gene. By analyzing the DNA of the parents of an isolated case one mutation was confirmed to be de novo. No mutation was found in any of the acromegaly and small FIHP families, suggesting that genetic defects other than the MEN1 gene might be involved and that additional such families need to be analyzed. [less ▲]Detailed reference viewed: 72 (5 ULg)