Effect of alendronate on risk of fracture in women with low bone density but without vertebral fractures: results from the Fracture Intervention Trial

CONTEXT: Alendronate sodium reduces fracture risk in postmenopausal women who have vertebral fractures, but its effects on fracture risk have not been studied for women without vertebral fractures. OBJECTIVE: To test the hypothesis that 4 years of alendronate would decrease the risk of clinical and vertebral fractures in women who have low bone mineral density (BMD) but no vertebral fractures. DESIGN: Randomized, blinded, placebo-controlled trial. SETTING: Eleven community-based clinical research centers. SUBJECTS: Women aged 54 to 81 years with a femoral neck BMD of 0.68 g/cm2 or less (Hologic Inc, Waltham, Mass) but no vertebral fracture; 4432 were randomized to alendronate or placebo and 4272 (96%) completed outcome measurements at the final visit (an average of 4.2 years later). INTERVENTION: All participants reporting calcium intakes of 1000 mg/d or less received a supplement containing 500 mg of calcium and 250 IU of cholecalciferol. Subjects were randomly assigned to either placebo or 5 mg/d of alendronate sodium for 2 years followed by 10 mg/d for the remainder of the trial. MAIN OUTCOME MEASURES: Clinical fractures confirmed by x-ray reports, new vertebral deformities detected by morphometric measurements on radiographs, and BMD measured by dual x-ray absorptiometry. RESULTS: Alendronate increased BMD at all sites studied (P<.001) and reduced clinical fractures from 312 in the placebo group to 272 in the intervention group, but not significantly so (14% reduction; relative hazard [RH], 0.86; 95% confidence interval [CI], 0.73-1.01). Alendronate reduced clinical fractures by 36% in women with baseline osteoporosis at the femoral neck (>2.5 SDs below the normal young adult mean; RH, 0.64; 95% CI, 0.50-0.82; treatment-control difference, 6.5%; number needed to treat [NNT], 15), but there was no significant reduction among those with higher BMD (RH, 1.08; 95% CI, 0.87-1.35). Alendronate decreased the risk of radiographic vertebral fractures by 44% overall (relative risk, 0.56; 95% CI, 0.39-0.80; treatment-control difference, 1.7%; NNT, 60). Alendronate did not increase the risk of gastrointestinal or other adverse effects. CONCLUSIONS: In women with low BMD but without vertebral fractures, 4 years of alendronate safely increased BMD and decreased the risk of first vertebral deformity. Alendronate significantly reduced the risk of clinical fractures among women with osteoporosis but not among women with higher BMD.     

Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures. Fracture Intervention Trial Research Group

BACKGROUND: Previous studies have shown that alendronate can increase bone mineral density (BMD) and prevent radiographically defined (morphometric) vertebral fractures. The Fracture Intervention Trial aimed to investigate the effect of alendronate on the risk of morphometric as well as clinically evident fractures in postmenopausal women with low bone mass. METHODS: Women aged 55-81 with low femoral-neck BMD were enrolled in two study groups based on presence or absence of an existing vertebral fracture. Results for women with at least one vertebral fracture at baseline are reported here. 2027 women were randomly assigned placebo (1005) or alendronate (1022) and followed up for 36 months. The dose of alendronate (initially 5 mg daily) was increased (to 10 mg daily) at 24 months, with maintenance of the double blind. Lateral spine radiography was done at baseline and at 24 and 36 months. New vertebral fractures, the primary endpoint, were defined by morphometry as a decrease of 20% (and at least 4 mm) in at least one vertebral height between the baseline and latest follow-up radiograph. Non-spine clinical fractures were confirmed by radiographic reports. New symptomatic vertebral fractures were based on self-report and confirmed by radiography. FINDINGS: Follow-up radiographs were obtained for 1946 women (98% of surviving participants). 78 (8.0%) of women in the alendronate group had one or more new morphometric vertebral fractures compared with 145 (15.0%) in the placebo group (relative risk 0.53 [95% Cl 0.41-0.68]). For clinically apparent vertebral fractures, the corresponding numbers were 23 (2.3%) alendronate and 50 (5.0%) placebo (relative hazard 0.45 [0.27-0.72]). The risk of any clinical fracture, the main secondary endpoint, was lower in the alendronate than in the placebo group (139 [13.6%] vs 183 [18.2%]; relative hazard 0.72 [0.58-0.90]). The relative hazards for hip fracture and wrist fracture for alendronate versus placebo were 0.49 (0.23-0.99) and 0.52 (0.31-0.87). There was no significant difference between the groups in numbers of adverse experiences, including upper-gastrointestinal disorders. INTERPRETATION: We conclude that among women with low bone mass and existing vertebral fractures, alendronate is well tolerated and substantially reduces the frequency of morphometric and clinical vertebral fractures, as well as other clinical fractures.     

Fracture rates and risk factors for fractures in patients with spinal cord injury

AIM: To study fracture rates and risk factors for fractures in patients with spinal cord injuries. MATERIAL AND METHODS: A self-administered questionnaire was mailed to 646 members of the Danish Paraplegic Association and 1000 randomly selected normal controls. 438 patients (309 males, 129 females, 67.8%) and 654 controls (332 males, 322 females, 65.4%) returned the questionnaire. Median age in patients was 42, range 10-80 years, and in controls 43, range 19-93 years (2p = 0.25). RESULTS: The crude fracture rate was 2% per year in patients and 1% per year in controls (RR = 2.0, P < 0.001). Low-energy fractures were much more prominent in patients (19.0% of all fractures) than in controls (1.4%, P < 0.001). The fracture rate did not differ before the injury but increased after the injury to a constant level from the third year and forward. Fractures of the lower extremities were more prominent in patients than controls (femurs: RR = 23.4, P < 0.001, lower legs: RR = 5.2, P < 0.001, feet/toes: RR = 2.4, P = 0.006) while fractures of the forearms (P < 0.001) and clavicles (P = 0.03) were absent among patients. Fractures were more frequent in female patients (RR = 1.6, P = 0.008) and in male patients with a family history of fractures (RR = 2.0, P = 0.004). CONCLUSIONS: Low-energy fractures especially of the lower extremities are frequent in spinal cord injury patients and especially among female patients. The forearms seem protected from fractures.     

Breast cancer risk from low-dose exposures to ionizing radiation: results of parallel analysis of three exposed populations of women

Breast cancer incidence data were analyzed from three populations of women exposed to ionizing radiation: survivors of the Hiroshima and Nagasaki atomic bombs, patients in Massachusetts tuberculosis sanitoria who were exposed to multiple chest fluoroscopies, and patients treated by X-rays for acute postpartum mastitis in Rochester, New York. Parallel analyses by radiation dose, age at exposure, and time after exposure suggested that risk of radiation-induced cancer increased approximately linearly with increasing dose and was heavily dependent on age at exposure; however, the risk was otherwise remarkably similar among the three population, at least for age 10-40 years at exposure, and followed the same temporal pattern of occurrence as did breast cancer incidence in nonexposed women of similar ages.     

Treatment of mandibular fractures with rigid osteosynthesis: using the AO system

PURPOSE: This study evaluated the results achieved in the surgical treatment of all mandibular fractures at two university centers using the 2.7 AO mandibular system. PATIENTS AND METHODS: A total of 227 patients presenting with 180 single fractures and 47 with double fractures (274 osteosyntheses) were included in this prospective study. RESULTS: During a mean follow-up of 27.5 months (minimum, 12 months), an overall complication rate of 7% was observed. No infection justified early removal of the osteosynthesis material. CONCLUSIONS: The systematic use of the technique recommended by AO for treating mandibular fractures, performed by thoroughly experienced operators on a compliant population, results in a low rate of complications and an early return to normal function.     

Blood pressure in women using oral contraceptives: results from the Health Survey for England 1994

Phenylarsonic compounds have been used as poultry and swine feed additives for the purpose of growth promotion and disease prevention. Owing to the lack of suitable analytical methods, however, knowledge of their metabolism, environmental fate and impact remains incomplete. In order to compensate for this, analytical procedures were developed that allow the speciation of arsenic animal feed additives by using microbore high-performance liquid chromatography (microHPLC) coupled on-line with ICP-MS. More specifically, reversed-phase (RP) chromatographic methods were optimised to achieve the separation of various phenylarsonic acids from each other and from the more toxic inorganic arsenic compounds. This mode of chromatography, however, exhibits limitations, especially in the presence of naturally occurring organoarsenic compounds. The application of RP ion-pairing chromatography eliminates such shortcomings by minimising the co-elution of arsenic species. In general, the microHPLC-ICP-MS methods developed in this study provide high selectivity, extremely good sensitivity, low limits of detection (low-ppb or sub-pg amounts of As), require small sample volumes (< 1 microliter), minimise waste and operate most efficiently under low mobile-phase flow rates (15-40 microliters min-1), which are compatible for use with other types of mass spectrometers, e.g., electrospray. Reference materials containing naturally occurring arsenic compounds were spiked with phenylarsonic compounds and then analysed by using the procedures developed in this study.     

Sex bias and sex-role stereotyping in psychotherapy with women: Survey results.

192 female former clients of 49 psychotherapists responded to a 70-item questionnaire developed around 4 themes of sex bias and sex-role stereotyping in psychotherapy. Results suggest that the majority of women were treated in a sex-fair manner. Women with the least amount of formal education and women with children experienced more sex bias in therapy. When bias was noted, it was often in acts of omission in the therapy; this was particularly true for victimized women. The most bias noted was in the areas of fostering traditional roles, lack of acceptance of anger, and lack of a sociocultural context in the therapy. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Mastery is associated with cardiovascular disease mortality in men and women at apparently low risk.

Objective: We examine the prospective relationship between mastery, where limited mastery is defined as the inability to control negative emotions (and perceiving stressful experiences as beyond personal control), and cardiovascular disease (CVD) mortality particularly among individuals at apparently low CVD risk. Design: Prospective population-based study of 19,067 men and women, aged 41–80 years with no previous heart disease or stroke at baseline assessment. Main Outcome Measures: Primary outcome measure CVD mortality. Results: A total of 791 CVD deaths were recorded up to June 2009 during a median 11.3 person-years of follow-up. Limited perceived mastery over life circumstances was associated with an increased risk of CVD mortality, independently of biological, lifestyle, and socioeconomic risk factors (hazard ratio 1.11 per SD decrease in mastery score, 95% confidence interval 1.01–1.21). This association was more pronounced among those participants apparently at low CVD risk (p = .01 for test of interaction according to the number of CVD risk factors at baseline). Conclusions: Limited perceived control over life circumstances is associated with an increased risk of CVD mortality, independently of classical cardiovascular risk factors, and particularly among those at apparently low risk. Future attention should be given to this potentially modifiable personal characteristic, through the design of preliminary intervention studies, to reduce cardiovascular risk. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Duration of the effects of intravenous alendronate in postmenopausal women and in patients with primary hyperparathyroidism and Paget's disease of bone

The effect of a single intravenous (i.v.) infusion of 5 mg alendronate was studied in ten patients with Paget's disease, six patients with primary hyperparathyroidism and ten osteopenic postmenopausal women. Urinary hydroxyproline excretion significantly decreased within few days in all patients (from 113 +/- 67.9 to 58 +/- 35 mmol/mol Cr in Paget's disease, from 21.8 +/- 9 to 12.9 +/- 6 mmol/mol Cr in hyperparathyroidism, from 18.7 +/- 9.5 to 8.5 +/- 4.3 mmol/mol Cr in postmenopausal women). In the patients with Paget's disease urinary hydroxyproline remained suppressed over the 6 months of follow-up, whereas it rose toward pretreatment values within 4 and 6 weeks in the patients with primary hyperparathyroidism and in postmenopausal osteopenic women, respectively. Plasma alkaline phosphatase significantly fell only after 4-6 weeks in patients with primary hyperparathyroidism and in Pagetic patients. In the latter group alkaline phosphatase continued to decline thereafter and a plateau became apparent after 2 months. In postmenopausal women the serum alkaline phosphatase remained unchanged. Thus, the same dose of alendronate induces comparable fractional decreases of bone resorption in the three groups of patients, but the effect is persistent only in Paget's disease. This is consistent with the hypothesis that alendronate inhibits osteoclastic activity only at the level of the existing resorption sites. In osteoporotic and primary hyperparathyroid patients, as soon as the treatment is withdrawn, the appearance of new sites of resorption is not inhibited and bone turnover is resumed to pre-treatment values.(ABSTRACT TRUNCATED AT 250 WORDS)     

Occupation and subclinical carotid artery disease in women: Are clerical workers at greater risk?

The current study examined cardiovascular risk factors and carotid atherosclerosis in 362 women (ages 42-50 years) who were working in clerical, blue-collar, or white-collar jobs or who were not employed. Risk factors were measured premenopausally and ultrasound measures of carotid atherosclerosis were obtained approximately 11 years later. Clerical and blue-collar workers had more atherogenic profiles on physical, behavioral, and psychosocial risk factors when compared with white-collar and nonemployed women. Clerical workers had greater carotid intima-media thickness relative to all other groups and more focal plaque when compared with white-collar workers. Risk factors and workplace characteristics did not account for the greater carotid atherosclerosis observed in clerical workers. Further research is needed to investigate why clerical work may increase cardiovascular risk. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Treatment results in patients with juvenile angiofibroma of the nasopharynx

As shown in this work, antisera obtained after the immunization of animals with vaccines, prepared from Salmonella minnesota strain R595 (Re mutant) or Escherichia coli O14 having enterobacterial common antigen (ECA), as well as human antisera with elevated titers of antibodies to Re glycolipid or to LPS O14 (ECA), inhibited the development of experimental intestinal dysbacteriosis in white mice, induced by the administration of ampyox in large doses. The degree of the inhibiting action of the antisera was proportional to antibody titers, which was indicative of the fact that antibodies possibly played some role in the regulation of the amount of intestinal microflora.     

A cholesterol-lowering diet does not produce adverse psychological effects in children: Three-year results from the Dietary Intervention Study in Children.

The Dietary Intervention Study in Children (DISC), a 2-arm, multicenter intervention study, examined the efficacy and safety of a diet lower in total fat, saturated fatty acids, and cholesterol than the typical American child's diet. A total of 663 8- to 10-year-old children with elevated low-density lipoprotein cholesterol levels were randomly assigned to either an intervention or a usual-care group. Intervention included group and individual counseling sessions to assist participants in adopting a dietary pattern containing 28% or less of calories from total fat (     

Does elective cryopreservation of all embryos from women at risk of ovarian hyperstimulation syndrome reduce the incidence of the condition?

OBJECTIVES: To analyse the incidence and factors associated with the ovarian hyperstimulation syndrome (OHS) in our IVF/GIFT programme before and after the introduction of a strategy to cryopreserve all embryos from women judged to be at risk. DESIGN: Two hundred forty-one consecutive IVF/GIFT cycles from January to December 1989. SETTING: Specialist fertility unit, Manchester, UK. INTERVENTIONS: Pituitary suppression was effected by a daily subcutaneous injection of buserelin (500 micrograms) beginning 7 days before the expected menses. The ovarian stimulation was with variable amounts of human menopausal gonadotrophin. Ovulation was induced with 10,000 i.u. human chorionic gonadotrophin (hCG). From January to May (period A), gametes/embryos were replaced and 2000 i.u. hCG given, irrespective of the serum oestradiol (E2) concentration. From June to December (period B), all the embryos from women with an E2 > 3500 pg/ml on the day of ovulatory trigger were electively cryopreserved. MAIN OUTCOME MEASURES: Serum E2, features of moderate or severe OHS, clinical pregnancies. RESULTS: The OHS occurred in 10/105 (9.5%) and 12/136 (8.8%) cycles in periods A and B, respectively. Fewer women (6% versus 60%, P < 0.05) who had their embryos cryopreserved developed severe OHS compared with women with an E2 > 3500 pg/ml who became pregnant after gamete/embryo transfer in period A. The main factors associated with the development of OHS were serum E2 concentrations > 3500 pg/ml, whether gamete/embryos were replaced and the additional hCG given, the occurrence of a pregnancy and the presence of polycystic ovary disease. CONCLUSION: The elective cryopreservation of all embryos from women with high E2 levels reduced the severity, but not the incidence of symptomatic OHS.     

Comparison of ultrasonographic results of the breast with progesterone levels in women with fibrocystic mastopathy

Measuring the level of progesterone in 80 women who according to the ultrasound images had fibrocystic mastopathy. I've concluded by comparing the ultrasound images with the measurement of hormones that there was conformity of 75%.     

Reduced breast cancer mortality in women under age 50: updated results from the Malm? Mammographic Screening Program

This article provides additional follow-up data of two cohorts from the Malm? Mammographic Screening Trial (MMST). The first cohort, MMST I, contained 7,984 women under age 50 at entry into MMST who were born between 1927 and 1932. Half were assigned to a control group and were not invited for examination until four years after the code was broken in the MMST in 1988. The second cohort, MMST II, contained 17,786 women born between 1933 and 1945. Fifty four percent of these women were randomly invited to screening between 1978 and 1990. The remaining 46%--the control group--was invited to screening between 1991 and 1994. Nine screening rounds were completed in MMST I, and a mean of five rounds were completed in MMST II; the screening interval ranged from 18 to 24 months. The effect of screening on breast cancer mortality was assessed by pooling the two cohorts. At the end of follow-up--December 1993 for MMST I and December 1995 for MMST II--there was a statistically significant 36% reduction in breast cancer mortality in the intervention groups (relative risk = 0.64; 95% CI: 0.45-0.89; P = 0.009). A harm-benefit analysis showed, however, that for every two breast cancer deaths prevented, one clinically insignificant cancer was diagnosed; for each breast cancer death prevented, 63 cancer-free women had been called back for further examinations; and for every 20 lives saved, one radiation-induced breast cancer death may have occurred. Recommendations for screening must therefore weigh mortality benefits against these negative effects.     

HIV testing among Haitian women: lessons in the recognition of risk

Haitian women in Miami, Florida, responded to recruitment for testing of HIV antibody serostatus in ways that demonstrated the value of ethnographic methods for studying reactions to this kind of test, especially pre- and posttest counseling sessions. A total of 155 women between 14 and 61 years old, recruited in Miami in 1992 and 1993, participated. Response to testing identified three primary obstacles to the women's understanding of content presented in pre- and posttest counseling sessions: (1) their confusion about the meaning of positive versus negative, (2) the investigators' difficulty in communicating the concept of antibody, and (3) vagueness of the concept of window period between exposure and presentation of antibody. Retesting of a subset of Haitian participants helped to define sexual risk among these women in terms of having partners who had other partners and perception of supernatural risk.     

Factors influencing the results in the treatment of patients with femoral neck fractures (author's transl)

The results of 213 consecutive operatively treated patients with fractures of the femoral neck were evaluated. Especially the effects of improved operative technique, careful pre- and postoperative care and intensified rehabilitation were observed. The series consisted of 151 women and 62 men, 111 femoral neck fractures and 102 trochanteric fractures. Nailing was performed on 54 femoral neck fracture patients and endoprothesis operation on 57 patients. No statistically significant differences were proved when the two consecutive two years series were compared with one another concerning the nailing results and the frequence of thrombosis and infection. However, by means of early weight-bearing and improved pre- and postoperative care the 6 months mortality decreased statistically significantly (chi2 = 6.58, p less than 0.05).     

Treatment of prolactinoma patients with the new non-ergot dopamine agonist roxindol: first results

We studied the effects of the new non-ergot D2-dopamine agonist roxindol for the treatment of human prolactinomas. Roxindol is a non-ergot drug with additional 5-hydroxytryptamine type 1 A agonist and serotonin reuptake inhibitory activity. Ten patients with prolactin-secreting pituitary adenomas received roxindol three times daily at a dosage of 7.5-30 mg/day for at least 4 weeks according to a prospective protocol. All patients but one had received oral bromocriptine previously without normalization of prolactin levels. Serum prolactin profiles were analyzed once a week during the first month of therapy and at 4-week intervals thereafter. Mean baseline serum prolactin was suppressed from 23,000 +/- 13,600 mU/l (range 1500-141,000 mU/l; 20 mU/l = 1 microgram/l) by 37 +/- 11% after 1 week, by 49 +/- 9% after 4 weeks, and by 65 +/- 11% (n = 8) after 24 weeks of treatment. Serum prolactin was normalized in two patients. A tumor volume reduction of 20-25% was obtained in two subjects. Compared with previous treatment with oral bromocriptine the decrease in serum prolactin was comparable. In contrast, tolerance of roxindol was superior in five of seven patients with major side effects with bromocriptine, including three subjects who had discontinued bromocriptine because of adverse reactions. Four subjects spontaneously reported improvement of psychological and physical performance. One patient had a transient increase of serum transaminases. Thus, for the first time we could show a suppressive effect of roxindol on prolactin secretion in human prolactinomas. Due to its good tolerance roxindol may provide a useful alternative to bromocriptine.     

Syphilis in pregnant women and their children in the United Kingdom: results from national clinician reporting surveys 1994-7

OBJECTIVE: To measure the incidence of syphilis detected in pregnancy and congenital syphilis in the United Kingdom. DESIGN: Surveys through consultants in genitourinary medicine and paediatricians with active surveillance. SETTING: United Kingdom, 1994-7. SUBJECTS: Women treated for syphilis in pregnancy, and children with early congenital syphilis born in the United Kingdom. RESULTS: Over 3 years 139 women were diagnosed with and treated for syphilis in pregnancy; 121 were detected through antenatal screening. Thirty one had confirmed or probable congenitally transmissible syphilis, putting their pregnancies at risk. These were minimum figures but are compatible with the 90 to 100 women newly diagnosed annually as having infectious or early latent syphilis. A universal screening policy would require 18 600 and 55 700 women (maximum numbers) to be screened, respectively, to detect one woman needing treatment and to prevent one case of congenital syphilis. Nine presumptive cases of children with congenital syphilis born in the United Kingdom were reported. Mothers requiring treatment for syphilis were found in almost every health region but were more prevalent in London and the south east. Being born abroad and belonging to an ethnic minority group were strong risk factors, but 14% (19 of 121) of cases treated and six of 31 definite or probably transmissible cases occurred in white women born in the United Kingdom. CONCLUSIONS: Congenitally transmissible syphilis continues to occur among pregnant women in the United Kingdom. Cases would be missed and stillbirths and congenitally infected babies would occur if antenatal screening was abandoned.