Variation of transaminases, HCV-RNA levels and Th1/Th2 cytokine production during the post-partum period in pregnant women with chronic hepatitis C.

This study analyses the evolution of liver disease in women with chronic hepatitis C during the third trimester of pregnancy and the post-partum period, as a natural model of immune modulation and reconstitution. Of the 122 mothers recruited to this study, 89 were HCV-RNA+ve/HIV-ve and 33 were HCV-RNA-ve/HIV-ve/HCVantibody+ve and all were tested during the third trimester of pregnancy, at delivery and post-delivery. The HCV-RNA+ve mothers were categorized as either Type-A (66%), with an increase in ALT levels in the post-partum period (>40 U/L; P<0.001) or as Type-B (34%), with no variation in ALT values. The Type-A mothers also presented a significant decrease in serum HCV-RNA levels in the post-delivery period (P<0.001) and this event was concomitant with an increase in Th1 cytokine levels (INFγ, P = 0.04; IL12, P = 0.01 and IL2, P = 0.01). On the other hand, the Type-B mothers and the HCV-RNA-ve women presented no variations in either of these parameters. However, they did present higher Th1 cytokine levels in the partum period (INFγ and IL2, P<0.05) than both the Type-A and the HCV-RNA-ve women. Cytokine levels at the moment of delivery do not constitute a risk factor associated with HCV vertical transmission. It is concluded that differences in the ALT and HCV-RNA values observed in HCV-RNA+ve women in the postpartum period might be due to different ratios of Th1 cytokine production. In the Type-B women, the high partum levels of Th1 cytokines and the absence of post-partum variation in ALT and HCV-RNA levels may be related to permanent Th1 cytokine stimulation.

Freedom Trial First-Year Extension: Results from 4 Years of Denosumab Exposure in Women with Postmenopausal Osteoporosis

Aims: To investigate the long-term efficacy and safety of denosumab (DMAb) for the treatment of postmenopausal women with osteoporosis in an open-label extension to the 3-year FREEDOM study.1Methods: All women who completed the FREEDOM study were eligible to enter a long-term open-label extension (up to 10 years). After providing informed consent, participants received 6-monthly subcutaneous injections of DMAb (60 mg). Here we report data from the first year of followup. For women randomized to DMAb in the FREEDOM study ('long-term group'), this represents up to 48 months of DMAb exposure (eight 6-monthly injections). For those randomized to placebo ('de novo group') the data are from up to 12 months of exposure (two injections). All participants continued to take calcium (1 g) and vitamin D (≥400 IU) supplements daily. Changes in bone mineral density (BMD) and bone turnover markers (BTM) are reported for subjects enrolled in the extension. No formal statistical testing was planned for this interim report. P-values are descriptive.Results: Overall, 4,550 eligible women (70.2%) who completed the FREEDOM study entered the open-label extension study (long-term, n=2,343; de novo, n=2,207). During the first year of the extension, lumbar spine (LS) BMD in the long-term group further increased by 2.0% (12.1% increase vs. FREEDOM baseline at 48 months), and total hip (TH) BMD further increased by 0.8% (6.5% increase at 48 months) (p<0.0001 for both BMD gains during year 4; Fig. 1). During the first year of the extension, LS and TH BMD increased by 5.4% and 3.0%, respectively in the de novo group (both p<0.0001). After DMAb initiation, serum C-telopeptide (CTX) in the de novo group decreased rapidly and similarly to the long-term group (Fig. 2). Reductions in BTMs continue to attenuate at the end of the dosing interval as previously reported. Adverse event (AE) rates were similar (70.4% of women in the longterm group and 67.9% in the de novo group). Serious Aes were also similar (9.8% and 11.2% of women, respectively). During year 4, osteoporotic nonvertebral fractures were reported in 31 women in the long-term group and 51 in the denovo group.Fig. 1. Percentage change in BMD with denosumab for4 years (long-term) or 1 year (de novo)Fig. 2. Percentage change in sCTX over timeConclusions: These interim results suggest that continuation of DMAb treatment through 48 months is associated with further significant increases in spine and hip BMD with sustained reduction of bone turnover. The de-novo treatment group results confirm the first year active treatment findings previously reported1.Acknowledgements: Amgen Inc. sponsored this study. Figure ©2010, American Society for Bone and Mineral Research, used by permission, all rights reserved. Disclosure of Interest: H. Bone Grant/Research Support from: Amgen, Eli Lilly, Merck, Nordic Bioscience, Novartis, Takeda Pharmaceuticals, Consultant/Speaker's bureau/ Advisory activities with: Amgen, Merck, Takeda Pharmaceuticals, Zelos, S. Papapoulos Consultant/Speaker's bureau/ Advisory activities with: Amgen, Merck, Novartis, Lilly, Procter and Gamble, GSK, M.-L. Brandi Grant/Research Support from: MSD, GSK, Nycomed, NPS, Amgen, J. Brown Grant/Research Support from: Abbott, Amgen, Bristol Myers Squibb, Eli Lilly, Pfizer, Roche, Consultant/ Speaker's bureau/Advisory activities with: Abbott, Amgen, Eli Lilly, Novartis, Merck, Warner Chilcott,, R. Chapurlat Grant/Research Support from: Servier, Sanofi-Aventis, Warner-Chilcott, Novartis, Merck, Consultant/Speaker's bureau/Advisory activities with: Servier, Novartis, Amgen, E. Czerwinski: None Declared, N. Daizadeh Employee of: Amgen Inc., Stock ownership or royalties of: Amgen Inc., A. Grauer Employee of: Amgen Inc., Stock ownership or royalties of: Amgen Inc., C. Haller Employee of: Amgen Inc., Stock ownership or royalties of: Amgen Inc., M.-A. Krieg: None Declared, C. Libanati Employee of: Amgen Inc., Stock ownership or royalties of: Amgen Inc., Z. Man Grant/Research Support from: Amgen, D. Mellström: None Declared, S. Radominski Grant/Research Support from: Amgen, Pfizer, Roche, BMS, J.-Y. Reginster Grant/Research Support from: Bristol Myers Squibb, Merck Sharp & Dohme, Rottapharm, Teva, Lilly, Novartis, Roche, GlaxoSmithKline, Amgen, Servier, Consultant/Speaker's bureau/ Advisory activities with: Servier, Novartis, Negma, Lilly,Wyeth, Amgen, GlaxoSmithKline, Roche, Merckle, Nycomed, NPS, Theramex, UCB, Merck, Sharpe & Dohme, Rottapharm, IBSA, Genvrier, Teijin, Teva, Ebewee Pharma, Zodiac, Analis, Theramex, Novo-Nordisk, H. Resch: None Declared, J. A. Román Grant/Research Support from: Roche, Pharma, C. Roux Grant/Research Support from: Amgen, MSD, Novartis, Servier, Roche, Consultant/ Speaker's bureau/Advisory activities with: Amgen, MSD, Novartis, Servier, Roche, S. Cummings Grant/ Research Support from: Amgen, Lilly, Consultant/Speaker's bureau/Advisory activities with: Amgen, Lilly, Novartis, Merck

Prediction and discrimination of osteoporotic hip fracture in postmenopausal women.

Osteoporotic hip fractures increase dramatically with age and are responsible for considerable morbidity and mortality. Several treatments to prevent the occurrence of hip fracture have been validated in large randomized trials and the current challenge is to improve the identification of individuals at high risk of fracture who would benefit from therapeutic or preventive intervention. We have performed an exhaustive literature review on hip fracture predictors, focusing primarily on clinical risk factors, dual X-ray absorptiometry (DXA), quantitative ultrasound, and bone markers. This review is based on original articles and meta-analyses. We have selected studies that aim both to predict the risk of hip fracture and to discriminate individuals with or without fracture. We have included only postmenopausal women in our review. For studies involving both men and women, only results concerning women have been considered. Regarding clinical factors, only prospective studies have been taken into account. Predictive factors have been used as stand-alone tools to predict hip fracture or sequentially through successive selection processes or by combination into risk scores. There is still much debate as to whether or not the combination of these various parameters, as risk scores or as sequential or concurrent combinations, could help to better predict hip fracture. There are conflicting results on whether or not such combinations provide improvement over each method alone. Sequential combination of bone mineral density and ultrasound parameters might be cost-effective compared with DXA alone, because of fewer bone mineral density measurements. However, use of multiple techniques may increase costs. One problem that precludes comparison of most published studies is that they use either relative risk, or absolute risk, or sensitivity and specificity. The absolute risk of individuals given their risk factors and bone assessment results would be a more appropriate model for decision-making than relative risk. Currently, a group appointed by the World Health Organization and lead by Professor John Kanis is working on such a model. It will therefore be possible to further assess the best choice of threshold to optimize the number of women needed to screen for each country and each treatment.

Le suivi prénatal des femmes accouchant dans le canton de Vaud: etude rétrospective de 854 cas. [Prenatal care of women delivering in the Vaud canton: retrospective study of 854 cases].

The association between prenatal care and infant health has been shown in many studies. Therefore, accurate information on prenatal care is required to assess the organization of preventive measures aiming at a reducing in neonatal mortality any morbidity. We retrospectively collected data on 854 pregnancies. According to a classification scheme developed by Kessner, 61.6% of women had access to adequate prenatal care. Overall, the proportion of adequate prenatal care was lower among multiparas, and in this subgroup we found a lower rate for women with base line insurance. In the primiparas subgroup we found a lower rate of adequate prenatal care for foreigners, women under 20 years or unmarried mothers, and for women without professional activity during pregnancy, besides preterm birth was more frequent amongst women in the group of prenatal care qualified as intermediate or inadequate. The frequency of pregnancy visits and the Kessner index are discussed in a literature review. The association between socio-economic indicators and prenatal care was unexpected considering the overall wealth of Switzerland. With a 6.8% infant mortality registered in 1989, this country can be considered to have one of the lowest rates in the world. These findings nevertheless suggest the way to possible additional gains by interventions targeted to specific socio-economic groups.

Temporal trends in intergenerational social mobility in Switzerland: A cohort study of men and women born between 1912 and 1974

The central question addressed in this paper is to what extent the influence of social origin on life chances has changed over time for both men and women. In order to capture this change, intergenerational social mobility of eight different birth-cohorts, covering most of the entire twentieth century, is analysed using a unique collection of twelve Swiss national population sample surveys. The main results show that social mobility has remained constant across cohorts born in 1912 and those born in 1974. This suggests that unlike some other industrialised countries, inequality based on social origin is persistent in Switzerland.

Lung cancer mortality in European women: trends and predictions.

Female lung cancer mortality increased by 50% between the mid 1960s and the early 2000s in the European Union (EU). To monitor the current lung cancer epidemic in European women, we analyzed mortality trends in 33 European countries between 1970 and 2009 and estimated rates for the year 2015 using data from the World Health Organization. Female lung cancer mortality has been increasing up to recent calendar years in most European countries, with the exceptions of Belarus, Russia, and Ukraine, with relatively low rates, and the UK, Iceland and Ireland, where high rates were reached in mid/late 1990s to leveled off thereafter. In the EU, female lung cancer mortality rates rose over the last decade from 11.3 to 12.7/100,000 (+2.3% per year) at all ages and from 18.6 to 21.5/100,000 (+3.0% per year) in middle-age. A further increase is predicted, to reach 14/100,000 women in 2015. Lung cancer mortality trends have been more favorable over the last decade in young women (20-44 years), particularly in the UK and other former high-risk countries from northern and central/eastern Europe, but also in France, Italy, and Spain where mortality in young women has been increasing up to the early 2000s. In the EU as a whole, mortality at age 20-44 years decreased from 1.6 to 1.4/100,000 (-2.2% per year). Although the female lung cancer epidemic in Europe is still expanding, the epidemic may be controlled through the implementation of effective anti-tobacco measures, and it will probably never reach the top US rates.

Social freezing in Switzerland and worldwide--a blessing for women today?

This is a critical review of the medical, ethical, judicial and financial aspects of the so called "social freezing", the cryopreservation of a woman's oocytes for non-medical purposes. The possibility of storing the eggs of fertile women in order to prevent age-related fertility decline is being widely promoted by fertility centres and the lay press throughout the world. Research data has shown that social freezing should ideally be performed on women around 25 years of age in order to increase their chances of a future pregnancy. In reality, it is mostly performed after the age of 35. Unfortunately, social freezing is in general not a solution for the underlying societal problems to fit in with professionally active women and having children. It only delays the existing problems. Furthermore, it creates a lot of potential new problems. A great deal more should be undertaken to offer real solutions to the underlying societal problems which are in part: pre-school education, care in the event of childhood illness, and the many weeks of school holidays, acceptance of professionally active women having children, and more job offers with a workload <100%.). Furthermore, society should be informed about the decreasing chances of pregnancy with increasing maternal (and paternal) age as well as the increasing risks of miscarriage and obstetric/neonatal complications. Detailed information for woman considering social freezing is crucial. Every doctor, proposing social freezing to his patients, should be up to date with all these details. Follow-up studies on the outcome of these children are needed.

Invisible work, unseen hazards: the health of women immigrant household service workers in Spain

Backgroud: Household service work has been largely absent from occupational health studies. We examine the occupational hazards and health effects identified by immigrant women household service workers. Methods: Exploratory, descriptive study of 46 documented and undocumented immigrant women in household services in Spain, using a phenomenological approach. Data were collected between September 2006 and May 2007 through focus groups and semi-structured individual interviews. Data were separated for analysis by documentation status and sorted using a mixed-generation process. In a second phase of analysis, data on psychosocial hazards were organized using the Copenhagen Psychosocial Questionnaire as a guide. Results: Informants reported a number of environmental, ergonomic and psychosocial hazards and corresponding health effects. Psychosocial hazards were especially strongly present in data. Data on reported hazards were similar by documentation status and varied by several emerging categories: whether participants were primarily cleaners or carers and whether they lived in or outside of the homes of their employers. Documentation status was relevant in terms of empowerment and bargaining, but did not appear to influence work tasks or exposure to hazards directly. Conclusions:Female immigrant household service workers are exposed to a variety of health hazards that could be acted upon by improved legislation, enforcement, and preventive workplace measures, which are discussed.

Use of medicinal plants by black women: ethnography study in a low-income community

Objective To explore beliefs, values and practices related to the use of medicinal plants among low-income black families. Method The research method was ethnography and the participant observation process was done in a low-income community in the peripheral area of the City of São Paulo. Twenty black women were interviewed. Results Two cultural sub-themes, I do use medicines that I learned to make with my mother and with religious practitioners to care for diseases and Home medicines are to treat problems that are not serious, and the cultural theme I do use home medicines to treat simple diseases because I always have them at my disposal, they are free and I don’t need a medical prescription represent beliefs, values, and practices related to the use of medicinal plants among low-income black families. Conclusion The development of such practices, which can hide ethnic and social vulnerability, reveals the resilience of low-income black women in the process of confronting problems during the health-illness process.

Pregnancy and childbirth: What changes in the lifestyle of women who become mothers?

Pregnancy is a period influenced by the interaction of several factors, therefore this study aimed to identify changes in lifestyles due to pregnancy and childbirth in Portuguese and immigrant women in Portugal. This is a qualitative study, using the semi-structured interview, with eighty-two Portuguese and immigrant women. Content analysis was used, with verbatim classification supported by Nvivo 10. It was authorized by an Ethics Commission. Results revealed that the primary changes in lifestyles due to pregnancy were in eating habits (nutrition), daily activity, exposure to danger, sleep and rest patterns, social and family relationships, going out, self-care, work, clothing and footwear, travel, health monitoring and sexual activity and substances consumption. The main change after the birth, manifested by these women, was that their lives began to revolve around their baby.

Predicted effects of small decreases in energy expenditure on weight gain in adult women.

Small daily positive energy imbalances of 200 to 800 kJ (about 50 to 200 kcal) due to reduced resting energy expenditure (REE), reduced diet-induced thermogenesis, or physical inactivity are believed to predispose to obesity. However, estimates of the magnitude of the weight gain often fail to account for concurrent changes in body composition and increases in maintenance energy requirements as weight increases and energy equilibrium is re-established. Using previously reported data on body composition and REE in women and the energy cost of tissue deposition, we used mathematical models to predict the theoretical effect of a persistent reduction in energy expenditure on long-term weight gain, assuming no adaptation in energy intake. The analyses indicate the following effects of a reduced level of energy expenditure in lean and obese women: (i) REE rises more slowly with increasing degrees of obesity due to a declining proportion of the more metabolically active fat-free mass; so, for the same positive energy balance, a significantly greater weight gain is expected for obese than for lean women before energy equilibrium is re-established; (ii) due to the greater energy density of adipose tissue, the time course of weight gain to achieve energy balance is longer for obese subjects: in general, this is approximately five years for lean and ten years for obese women; (iii) the magnitude of weight gain of lean women in response to a reduced energy expenditure of 200 to 800 kJ/day is only about 3 to 15 kg, amounts insufficient to explain severe obesity.

Trabecular bone score is associated with volumetric bone density and microarchitecture as assessed by central QCT and HRpQCT in Chinese American and white women.

Although high-resolution peripheral quantitative computed tomography (HRpQCT) and central quantitative computed tomography (QCT) studies have shown bone structural differences between Chinese American (CH) and white (WH) women, these techniques are not readily available in the clinical setting. The trabecular bone score (TBS) estimates trabecular microarchitecture from dual-energy X-ray absorptiometry spine images. We assessed TBS in CH and WH women and investigated whether TBS is associated with QCT and HRpQCT indices. Areal bone mineral density (aBMD) by dual-energy X-ray absorptiometry, lumbar spine (LS) TBS, QCT of the LS and hip, and HRpQCT of the radius and tibia were performed in 71 pre- (37 WH and 34 CH) and 44 postmenopausal (21 WH and 23 CH) women. TBS did not differ by race in either pre- or postmenopausal women. In the entire cohort, TBS positively correlated with LS trabecular volumetric bone mineral density (vBMD) (r = 0.664), femoral neck integral (r = 0.651), trabecular (r = 0.641) and cortical vBMD (r = 0.346), and cortical thickness (C/I; r = 0.540) by QCT (p < 0.001 for all). TBS also correlated with integral (r = 0.643), trabecular (r = 0.574) and cortical vBMD (r = 0.491), and C/I (r = 0.541) at the total hip (p < 0.001 for all). The combination of TBS and LS aBMD predicted more of the variance in QCT measures than aBMD alone. TBS was associated with all HRpQCT indices (r = 0.20-0.52) except radial cortical thickness and tibial trabecular thickness. Significant associations between TBS and measures of HRpQCT and QCT in WH and CH pre- and postmenopausal women demonstrated here suggest that TBS may be a useful adjunct to aBMD for assessing bone quality.

Breast cancer incidence in younger swiss women

Background Breast cancer in younger women has received increased attention in recent years. Although breast cancer is uncommon in young women, it is the most frequent cancer and the leading cause of cancer death for younger women in developed countries. For Switzerland, the United States and several European countries, declines in breast cancer incidence have been reported since around the year 2000, after decades of increase, among women aged 50 and older. On the other hand an increase in the incidence of breast cancer in younger women has been reported in recent years. Therefore, this study aims to evaluate time trends in breast cancer incidence in younger women in Switzerland. Methods Data on invasive breast cancer cases were obtained from the Swiss Cancer Registries of Basel, Fribourg, Geneva, Graubunden/Glarus, Jura, Neuchatel, St. Gallen-Appenzell, Ticino, Valais, Vaud and Zurich, covering the time period 1996 to 2009. Mid-year population estimates for the respective time period were supplied by the Swiss Federal Statistical Office. For females aged 20-49 years, annual age-standardized incidence rates (ASIRs) (European standard) per 100,000 person-years and corresponding 95%-confidence intervals (95% CI) were calculated. For females aged 20-39 and 40-49 years, ASIRs and incidence rate ratios (IRRs) were calculated by grouped time periods, consisting of 3-5 incidence years. IRRs and corresponding 95% CI were calculated using Poisson regression adjusting for age (reference period 1996-2000). Results ASIRs in females aged 20-49 increased gradually since 1996, being 57.36 per 100,000 person-years in 1996 (95% CI 52.54-62.51) and rising to 68.34 (95% CI 63.40-73.57) per 100,000 person-years in 2009. Comparing the time-period 2007-2009 and the reference period 1996-2000, IRRs show values of 1.17 (95% CI 1.04-1.31) for the age-group 20-39 years and 1.04 (95% CI 0.97-1.10) for the age-group 40-49 years. Conclusions Our findings confirm a slight increase in the incidence of invasive breast cancer in younger women in Switzerland during the period 1996-2009. An increase in breast cancer incidence in younger patients is an important public health problem. It warrants further investigations to identify specific risk factors of this population and to better understand the biology of this particular breast cancer.

Prevention of preterm delivery with vaginal progesterone in women with preterm labour (4P): randomised double-blind placebo-controlled trial.

OBJECTIVE: To evaluate the effectiveness of 200 mg of daily vaginal natural progesterone to prevent preterm birth in women with preterm labour. DESIGN: Multicentre, randomised, double-blind, placebo-controlled trial. SETTING: Twenty-nine centres in Switzerland and Argentina. POPULATION: A total of 385 women with preterm labour (24(0/7) to 33(6/7)  weeks of gestation) treated with acute tocolysis. METHODS: Participants were randomly allocated to either 200 mg daily of self-administered vaginal progesterone or placebo within 48 hours of starting acute tocolysis. MAIN OUTCOME MEASURES: Primary outcome was delivery before 37 weeks of gestation. Secondary outcomes were delivery before 32 and 34 weeks, adverse effects, duration of tocolysis, re-admissions for preterm labour, length of hospital stay, and neonatal morbidity and mortality. The study was ended prematurely based on results of the intermediate analysis. RESULTS: Preterm birth occurred in 42.5% of women in the progesterone group versus 35.5% in the placebo group (relative risk [RR] 1.2; 95% confidence interval [95% CI] 0.93-1.5). Delivery at <32 and <34 weeks did not differ between the two groups (12.9 versus 9.7%; [RR 1.3; 95% CI 0.7-2.5] and 19.7 versus 12.9% [RR 1.5; 95% CI 0.9-2.4], respectively). The duration of tocolysis, hospitalisation, and recurrence of preterm labour were comparable between groups. Neonatal morbidity occurred in 44 (22.8%) cases on progesterone versus 35 (18.8%) cases on placebo (RR: 1.2; 95% CI 0.82-1.8), whereas there were 4 (2%) neonatal deaths in each study group. CONCLUSION: There is no evidence that the daily administration of 200 mg vaginal progesterone decreases preterm birth or improves neonatal outcome in women with preterm labour.

Six Years of Denosumab Treatment in Postmenopausal Women with Osteoporosis: Results From the First Three Years of the FREEDOM Extension

Background/Purpose: Denosumab (DMAb) is an approved therapy for the treatment of postmenopausal women with osteoporosis at increased risk for fracture. A favorable risk/benefit profile was demonstrated in the pivotal, 3-year FREEDOM trial (Cummings et al NEJM 2009). The open-label, active-treatment FREEDOM Extension study is investigating the efficacy and safety of DMAb for up to 10 years. The Extension trial enrolled women who had received DMAb or placebo in FREEDOM and provides an opportunity to evaluate the long-term efficacy and safety of continuous DMAb treatment (long-term group), and to replicate the DMAb findings observed in FREEDOM (cross-over group). Here, we report the results from the first 3 years of the Extension, representing up to 6 continuous years of DMAb exposure. Methods: During the Extension, each woman is scheduled to receive 60 mg DMAb every 6 months and supplemental calcium and vitamin D daily. For the analyses reported here, women from the FREEDOM DMAb group received 3 more years of DMAb for a total of 6 years of exposure (long-term group) and women from the FREEDOM placebo group received 3 years of DMAb exposure (cross-over group). Results: Of the 5928 women eligible for the Extension, 4550 (77%) enrolled (N_2343 long-term; N_2207 cross-over). In the long-term group, further significant mean increases in bone mineral density (BMD) occurred 4044 for cumulative 6-year gains of 15.2% at the lumbar spine and 7.5% at the total hip (Figure). During the first 3 years of DMAb treatment during the Extension, the cross-over group had significant mean gains in BMD at the lumbar spine (9.4%) and total hip (4.8%), similar to those observed in the long-term DMAb group during the first 3 years of FREEDOM (lumbar spine, 10.1%; total hip, 5.7%). Serum CTX was rapidly and similarly reduced after the 1st (cross-over) or 7th (long-term) DMAb dose with the characteristic attenuation observed at the end of the dosing period. In the cross-over group, yearly incidences of new vertebral and nonvertebral fractures were lower than in the FREEDOM placebo group. Fracture incidence remained low in the long-term group. Incidences of adverse events (AEs) and serious AEs did not increase over time with DMAb treatment. There were 2 subjects with AEs adjudicated to ONJ in the cross-over group and 2 in the long-term group. Both cases in the cross-over group healed completely and without further complications; 1 of these subjects continues to receive DMAb. Both women in the long-term group continue to be followed. No atypical femur fractures have been observed to date. Figure. Percent changes in bone mineral density during FREEDOM and the Extension Conclusion: DMAb treatment for 6 continuous years (long-term group) remained well tolerated, maintained reduced bone turnover, and continued to significantly increase BMD. Fracture incidence remained low. DMAb treatment for 3 years in the cross-over group reproduced the original observations in FREEDOM