There is little data concerning the morbidity, mortality, and epidemiology of vertebral fracture. The aim of this study was to evaluate the effect of prevalent and incident vertebral fractures as risk factors for further osteoporotic fractures and mortality. The study was performed on a cohort of 316 women and 308 men older than 50 belonging to the EVOS study, randomly selected from our city register. At the beginning of the study and 4 years later, lateral dorsal and lumbar X-rays were performed. In addition, evaluation of the incidence of osteoporotic nonvertebral fractures was performed throughout 8 years. The incidence of all osteoporotic fractures was higher in women than in men (two-fold increase in vertebral fracture incidence and five-fold increase in Colles' and femur incidence). Vertebral fracture was a strong risk factor for a new vertebral fracture [RR=4.7 (1.8-11.9)], hip fracture [RR=6.7 (2.0-22.7)] and Colles' fracture [RR=3.0 (1.1-7.8)]. Prevalent and incident vertebral fractures were associated with a higher risk of having a hip fracture [RR=10.0 (2.0-50.2)] and Colles' fracture [RR=5.5 (1.3-23.4)]. In addition, in women, the vertebral fracture was associated with a higher mortality. By contrast, no association was found in men. These results demonstrate the association between a previous vertebral fracture with increments in the incidence of osteoporotic fractures of any type. In addition, we found a significantly higher mortality rate in women having vertebral fractures. These findings support the necessity of preventing the occurrence of vertebral fractures to limit their strong negative impact on mortality.

The mechanisms by which estrogens modulate PTH are controversial, including whether or not estrogen receptors (ERs) are present in the parathyroid glands. To explore these mechanisms, we combined a rat model of CKD with ovariectomy and exogenous administration of estrogens. We found that estrogen treatment significantly decreased PTH mRNA and serum levels. We did not observe ER␣ or ER␤ mRNA or protein in the parathyroids, suggesting an indirect action of estrogens on PTH regulation. Estrogen treatment significantly decreased serum 1,25(OH) 2 vitamin D 3 and phosphorus levels. In addition, estrogens significantly increased fibroblast growth factor 23 (FGF23) mRNA and serum levels. In vitro, estrogens led to transcriptional and translational upregulation of FGF23 in osteoblast-like cells in a timeand concentration-dependent manner. These results suggest that estrogens regulate PTH indirectly, possibly through FGF23. 20: 200920: -201720: , 200920: . doi: 10.1681 Estrogen deficiency is the main factor implicated in bone loss in postmenopausal osteoporosis. 1 As a consequence of the lack of estrogens, bone turnover increases, leading to an imbalance between bone formation and bone resorption, favoring the latter. 2,3 This imbalance affects calcium-phosphate metabolism and may increase serum parathyroid hormone (PTH) levels. 4 Estrogen replacement therapy prevents bone loss and fractures, 5,6 acting directly on bone cells through their specific estrogen receptors (ERs): ␣ and ␤. 7,8 In addition, in postmenopausal women, estrogens can also reduce PTH serum levels 4,9 through an as of yet poorly understood mechanism. J Am Soc NephrolA possible direct effect of estrogens reducing PTH acting through ER␣ and ER␤ located in the parathyroid cells has been suggested, but the existence of ER␣ and ER␤ in parathyroid tissue is still a controversial issue. 10 -13 Estrogens may also decrease PTH secretion by acting on other factors such as calcium, 14,15 1,25(OH) 2 D 3 (calcitriol), 15 and phosphorus, 16,17 among others. Recently, fibroblast growth factor 23 (FGF23), involved in phosphorus and vitamin D metabolism, 18 has been suggested to influence PTH synthesis and secretion. 19 In women with chronic kidney disease (CKD), little is known about the role that estrogen deficiency plays in the pathogenesis and progression of bone disease. 20,21 Understanding the mechanism through which estrogens act on PTH is also a subject of interest in these patients, because of the high prevalence of secondary parathyroid disorders. 22 Because several aspects of the effects of estrogens on PTH remain unclear, the objective of this study was to investigate the factors and mechanisms involved in the likely effect of estrogens on the parathyroid gland.

It is well known that the adoption of preventive measures for osteoporosis may contribute to minimizing its impact as a result of bone fractures. However, there are well-recognized risk factors involved in the onset of osteoporosis that are not possible to modify. Better knowledge of these non-modifiable factors could aid prevention in subjects at high risk of fractures. The aim of this study was to evaluate the likely association between gynecological, reproductive and family history of hip fracture with the incidence of vertebral and nonvertebral osteoporotic fractures in women older than 50. We studied 255 women aged 50 and over, randomly selected from a Spanish population that had participated in a study of prevalence of vertebral fractures (EVOS study). This cohort was prospectively followed for 8 years by means of four postal questionnaires, in order to find out the incidence of nonvertebral fractures. Concerning the incidence of vertebral fractures, participants were invited to repeat the lumbar spine X-rays 4 years after the initial study. A total of 31 women had incident osteoporotic fractures. The analysis of gynecological variables showed that an increase in the age at menarche was a risk factor for all incident osteoporotic fractures [OR=1.57 (1.04-2.37)]. The presence of amenorrhea at any age during the fertile period was associated with higher incidence of all osteoporotic fractures [OR=6.30 (1.61-24.70)]. Among all the reproductive variables analyzed (pregnancy, number of live births and breast-feeding) only pregnancy was an important protective factor in preventing incident Colles fracture [OR=0.15 (0.03-0.62)]. A family history of hip fracture was associated with a higher incidence of all osteoporotic fractures [OR=3.59 (1.01-12.79)]. In summary, a late age at menarche, the presence of amenorrhea and having close relatives with hip fracture were all risk factors which, independently of bone mineral density (BMD) and age, were associated with higher incidence of all osteoporotic fractures. Pregnancy was an important protective factor for the incidence of Colles fractures.