Cell-Free DNA-Based Non-invasive Prenatal Screening for Common Aneuploidies in a Canadian Province: A Cost-Effectiveness Analysis.

OBJECTIVE: Yearly, 450 000 pregnant Canadians are eligible for voluntary prenatal screening for trisomy 21. Different screening strategies select approximately 4% of women for invasive fetal chromosome testing. Non-invasive prenatal testing (NIPT) using maternal blood cell-free DNA could reduce those invasive procedures but is expensive. This study evaluated the cost-effectiveness of NIPT strategies compared with conventional strategies. METHODS: This study used a decision analytic model to estimate the cost-effectiveness of 13 prenatal screening strategies for fetal aneuploidies: six frequently used strategies, universal NIPT, and six strategies incorporating NIPT as a second-tier test. The study considered a virtual cohort of pregnant women of similar size and age as women in Quebec. Model data were obtained from published sources and government databases. The study predicted the number of chromosomal anomalies detected (trisomies 21, 13, and 18), invasive procedures and euploid fetal losses, direct costs, and incremental cost-effectiveness ratios. RESULTS: Of the 13 strategies compared, eight identified fewer cases at a higher cost than at least one of the remaining five strategies. Integrated serum screening with conditional NIPT had the lowest cost, and the cost per case detected was $63 139, with a 90% reduction of invasive procedures. The number of cases identified was improved with four other screening strategies, but with increasing of incremental costs per case (from $61 623 to $1 553 615). Results remained robust, except when NIPT costs and risk cut-offs varied. CONCLUSION: NIPT as a second-tier test for high-risk women is likely to be cost-effective as compared with screening algorithms not involving NIPT.

Genomics-based non-invasive prenatal testing for detection of fetal chromosomal aneuploidy in pregnant women.

BACKGROUND: Common fetal aneuploidies include Down syndrome (trisomy 21 or T21), Edward syndrome (trisomy 18 or T18), Patau syndrome (trisomy 13 or T13), Turner syndrome (45,X), Klinefelter syndrome (47,XXY), Triple X syndrome (47,XXX) and 47,XYY syndrome (47,XYY). Prenatal screening for fetal aneuploidies is standard care in many countries, but current biochemical and ultrasound tests have high false negative and false positive rates. The discovery of fetal circulating cell-free DNA (ccfDNA) in maternal blood offers the potential for genomics-based non-invasive prenatal testing (gNIPT) as a more accurate screening method. Two approaches used for gNIPT are massively parallel shotgun sequencing (MPSS) and targeted massively parallel sequencing (TMPS). OBJECTIVES: To evaluate and compare the diagnostic accuracy of MPSS and TMPS for gNIPT as a first-tier test in unselected populations of pregnant women undergoing aneuploidy screening or as a second-tier test in pregnant women considered to be high risk after first-tier screening for common fetal aneuploidies. The gNIPT results were confirmed by a reference standard such as fetal karyotype or neonatal clinical examination. SEARCH METHODS: We searched 13 databases (including MEDLINE, Embase and Web of Science) from 1 January 2007 to 12 July 2016 without any language, search filter or publication type restrictions. We also screened reference lists of relevant full-text articles, websites of private prenatal diagnosis companies and conference abstracts. SELECTION CRITERIA: Studies could include pregnant women of any age, ethnicity and gestational age with singleton or multifetal pregnancy. The women must have had a screening test for fetal aneuploidy by MPSS or TMPS and a reference standard such as fetal karyotype or medical records from birth. DATA COLLECTION AND ANALYSIS: Two review authors independently carried out study selection, data extraction and quality assessment (using the QUADAS-2 tool). Where possible, hierarchical models or simpler alternatives were used for meta-analysis. MAIN RESULTS: Sixty-five studies of 86,139 pregnant women (3141 aneuploids and 82,998 euploids) were included. No study was judged to be at low risk of bias across the four domains of the QUADAS-2 tool but applicability concerns were generally low. Of the 65 studies, 42 enrolled pregnant women at high risk, five recruited an unselected population and 18 recruited cohorts with a mix of prior risk of fetal aneuploidy. Among the 65 studies, 44 evaluated MPSS and 21 evaluated TMPS; of these, five studies also compared gNIPT with a traditional screening test (biochemical, ultrasound or both). Forty-six out of 65 studies (71%) reported gNIPT assay failure rate, which ranged between 0% and 25% for MPSS, and between 0.8% and 7.5% for TMPS.In the population of unselected pregnant women, MPSS was evaluated by only one study; the study assessed T21, T18 and T13. TMPS was assessed for T21 in four studies involving unselected cohorts; three of the studies also assessed T18 and 13. In pooled analyses (88 T21 cases, 22 T18 cases, eight T13 cases and 20,649 unaffected pregnancies (non T21, T18 and T13)), the clinical sensitivity (95% confidence interval (CI)) of TMPS was 99.2% (78.2% to 100%), 90.9% (70.0% to 97.7%) and 65.1% (9.16% to 97.2%) for T21, T18 and T13, respectively. The corresponding clinical specificity was above 99.9% for T21, T18 and T13.In high-risk populations, MPSS was assessed for T21, T18, T13 and 45,X in 30, 28, 20 and 12 studies, respectively. In pooled analyses (1048 T21 cases, 332 T18 cases, 128 T13 cases and 15,797 unaffected pregnancies), the clinical sensitivity (95% confidence interval (CI)) of MPSS was 99.7% (98.0% to 100%), 97.8% (92.5% to 99.4%), 95.8% (86.1% to 98.9%) and 91.7% (78.3% to 97.1%) for T21, T18, T13 and 45,X, respectively. The corresponding clinical specificities (95% CI) were 99.9% (99.8% to 100%), 99.9% (99.8% to 100%), 99.8% (99.8% to 99.9%) and 99.6% (98.9% to 99.8%). In this risk group, TMPS was assessed for T21, T18, T13 and 45,X in six, five, two and four studies. In pooled analyses (246 T21 cases, 112 T18 cases, 20 T13 cases and 4282 unaffected pregnancies), the clinical sensitivity (95% CI) of TMPS was 99.2% (96.8% to 99.8%), 98.2% (93.1% to 99.6%), 100% (83.9% to 100%) and 92.4% (84.1% to 96.5%) for T21, T18, T13 and 45,X respectively. The clinical specificities were above 100% for T21, T18 and T13 and 99.8% (98.3% to 100%) for 45,X. Indirect comparisons of MPSS and TMPS for T21, T18 and 45,X showed no statistical difference in clinical sensitivity, clinical specificity or both. Due to limited data, comparative meta-analysis of MPSS and TMPS was not possible for T13.We were unable to perform meta-analyses of gNIPT for 47,XXX, 47,XXY and 47,XYY because there were very few or no studies in one or more risk groups. AUTHORS' CONCLUSIONS: These results show that MPSS and TMPS perform similarly in terms of clinical sensitivity and specificity for the detection of fetal T31, T18, T13 and sex chromosome aneuploidy (SCA). However, no study compared the two approaches head-to-head in the same cohort of patients. The accuracy of gNIPT as a prenatal screening test has been mainly evaluated as a second-tier screening test to identify pregnancies at very low risk of fetal aneuploidies (T21, T18 and T13), thus avoiding invasive procedures. Genomics-based non-invasive prenatal testing methods appear to be sensitive and highly specific for detection of fetal trisomies 21, 18 and 13 in high-risk populations. There is paucity of data on the accuracy of gNIPT as a first-tier aneuploidy screening test in a population of unselected pregnant women. With respect to the replacement of invasive tests, the performance of gNIPT observed in this review is not sufficient to replace current invasive diagnostic tests.We conclude that given the current data on the performance of gNIPT, invasive fetal karyotyping is still the required diagnostic approach to confirm the presence of a chromosomal abnormality prior to making irreversible decisions relative to the pregnancy outcome. However, most of the gNIPT studies were prone to bias, especially in terms of the selection of participants.

Convergence of a diabetes mellitus, protein energy malnutrition, and TB epidemic: the neglected elderly population.

BACKGROUND: On a global scale, nearly two billion persons are infected with Mycobacterium tuberculosis. From this vast reservoir of latent tuberculosis (TB) infection, a substantial number will develop active TB during their lifetime, with some being able to transmit TB or Multi-drug- resistant (MDR) TB to others. There is clinical evidence pointing to a higher prevalence of infectious diseases including TB among individuals with Diabetes Mellitus (DM). Furthermore, ageing and diabetes mellitus may further aggravate protein-energy malnutrition (PEM), which in turn impairs T-lymphocyte mediated immunologic defenses, thereby increasing the risk of developing active TB and compromising TB treatment. This article aims to a) highlight synergistic mechanisms associated with immunosenescence, DM and PEM in relation to the development of active TB and b) identify nutritional, clinical and epidemiological research gaps. METHODS: To explore the synergistic relationship between ageing, DM, tuberculosis and PEM, a comprehensive review was undertaken. The MEDLINE and the Google Scholar databases were searched for articles published from 1990 to March 2015, using different MESH keywords in various combinations. RESULTS: Ageing and DM act synergistically to reduce levels of interferon gamma (IFN- γ), thereby increasing susceptibility to TB, for which cell mediated immunity (CMI) plays an instrumental role. These processes can set in motion a vicious nutritional cycle which can predispose to PEM, further impairing the CMI and consequently limiting host defenses. This ultimately transforms the latent TB infection into active disease. A clinical diagnostic algorithm and clinical guidelines need to be established for this population. CONCLUSION: Given the increase in ageing population with DM and PEM, especially in resource-poor settings, these synergistic tripartite interactions must be examined if a burgeoning TB epidemic is to be averted. Implementation of a comprehensive, all-encompassing approach to curb transmission is clearly indicated. To this end, clinical, nutritional and epidemiological research gaps must be addressed without a delay.

Dabigatran versus warfarin under standard or pharmacogenetic-guided management for the prevention of stroke and systemic thromboembolism in patients with atrial fibrillation: a cost/utility analysis using an analytic decision model.

BACKGROUND: Atrial fibrillation (AF) is the most common form of heart arrhythmia and a leading cause of stroke and systemic embolism. Chronic anticoagulation is recommended for preventing those complications. Our study aimed to compare the cost/utility (CU) of three main anticoagulation options: 1) standard warfarin dosing (SD-W) 2) warfarin dosage under the guidance of CYP2C9 and VKORC1 genotyping (GT-W) and 3) dabigatran 150 mg twice a day. METHODS: A Markov state transition model was built to simulate the expected C/U of dabigatran, SD-W and GT-W anticoagulation therapy for the prevention of stroke and systemic thromboembolism in patients with atrial fibrillation over a period of 5 years under the perspective of the public health care system. Model inputs were derived from extensive literature search and government's data bases. Outcomes considered were the number of total major events (thromboembolic and hemorrhagic events), total costs in Canadian dollars (1CAD$ = 1$US), total quality-adjusted life years (QALYs), costs/QALYs and incremental costs/QALYs gained (ICUR). RESULTS: Raw base case results show that SD-W has the lowest C/U ratio. However, the dabigatran option might be considered as an alternative, as its cost per additional QALY gained compared to SD-W is CAD $ 4 765, i.e. less than 50 000, the ICUR threshold generally accepted to adopt an intervention. At the same threshold, GT-W doesn't appear to be an alternative to SD-W. Our results were robust to one-way and multi-way sensitivity analyses. CONCLUSION: SD-W has the lowest C/U ratio among the 3 options. However, dabigatran might be considered as an alternative. GT-W is not C/U and should not currently be recommended for the routine anticoagulotherapy management of AF patients.

Cost-effectiveness of the management of rh-negative pregnant women.

OBJECTIVE: The purpose of this study was to determine the most cost-effective option to prevent alloimmunization against the Rh factor. METHODS: A virtual population of Rh-negative pregnant women in Quebec was built to simulate the cost-effectiveness of preventing alloimmunization. The model considered four options: (1) systematic use of anti-D immunoglobulin; (2) fetal Rh(D) genotyping; (3) immunological determination of the father's Rh type; (4) mixed screening: immunological determination of the father's Rh type, followed if positive by fetal Rh(D) genotyping. Two outcomes were considered, in addition to the estimated costs: (1) the number of babies without hemolytic disease, and (2) the number of surviving infants. RESULTS: In a first pregnancy, two options emerged as the most cost-effective options: systematic prophylaxis and immunological Rh typing of the father, with overlapping confidence intervals between them. In a second pregnancy, the results were similar. In all cases (first or second pregnancy or a combination of the two) fetal genotyping was not found to be a cost-effective option. CONCLUSION: Routine prophylaxis and immunological Rh typing of the father are the most cost-effective options for the prevention of Rh alloimmunization. Considering that immunological typing of the father would probably not be carried out by the majority of clinicians, routine prophylaxis remains the preferred option. However, this could change if the cost of Rh(D) fetal genotyping fell below $140 per sample.

Objectif : Cette étude avait pour objectif d'identifier l'option la plus rentable pour la prévention de l'allo-immunisation contre le facteur Rh. Méthodes : Une population virtuelle québécoise de femmes enceintes séronégatives pour le facteur Rh a été créée pour simuler la rentabilité de la prévention de l'allo-immunisation. Ce modèle a pris en considération quatre options : (1) l'utilisation systématique d'immunoglobuline anti-D; (2) le génotypage Rh(D) fœtal; (3) la détermination immunologique du type Rh du père; (4) le dépistage mixte : détermination immunologique du type Rh du père, suivie (en présence de résultats positifs) du génotypage Rh(D) fœtal. Deux critères d'évaluation ont été pris en considération, en plus des coûts estimés : (1) le nombre d'enfants nés sans maladie hémolytique et (2) le nombre de nouveau-nés survivants. Résultats : Dans le cas d'une première grossesse, deux options se sont avérées les plus rentables : la prophylaxie systématique et la détermination immunologique du type Rh du père; leurs intervalles de confiance se chevauchaient. Dans le cas d'une deuxième grossesse, les résultats ont été semblables. Dans tous les cas (première ou deuxième grossesse, ou une combinaison des deux), nous avons constaté que le génotypage fœtal ne constituait pas une option rentable. Conclusion : La mise en œuvre systématique d'une prophylaxie et la détermination immunologique du type Rh du père constituent les options les plus rentables pour la prévention de l'allo-immunisation contre le facteur Rh. Puisqu'il est peu probable que la détermination immunologique du type Rh du père soit mise en œuvre par la majorité des cliniciens, la prophylaxie systématique demeure l'option à privilégier. Cependant, cela pourrait changer si le coût du génotypage Rh(D) fœtal chutait en deçà de 140 $ par prélèvement.

Pregnant women's and policymakers' preferences for the expansion of noninvasive prenatal screening: A discrete choice experiment approach study.

Background and Aims: Quantitative approaches for eliciting preferences for new interventions are mostly conducted by patients and rarely by policymakers. This study aimed to quantify the preferences of pregnant women and policymakers regarding the addition of a new test to prenatal screening programs for detecting chromosomal abnormalities. Methods: A discrete choice experiment was conducted to measure the respondents' preferences for a new prenatal test. A seven-attribute instrument was built based on interviews with pregnant women and policymakers. The data were analyzed using robust conditional logistic regression and nested logit models. Results: In total, 272 pregnant women and 24 policymakers completed the questionnaire (response rates of 48% and 55%, respectively). Overall, all attributes were statistically significant in the pregnant women group, whereas only three attributes (test performance, degree of test result certainty, and cost) were statistically significant in the policymakers group. Statistically significant differences in test performance and information were observed between the two groups. Conclusion: Policymakers differed from pregnant women in their appraisal of attributes related to their preference for a new prenatal screening intervention. The low response rates observed in both groups suggest that further investigation of the relevance of this approach must be conducted.

Development of a discrete choice experiment questionnaire to elicit preferences by pregnant women and policymakers for the expansion of non-invasive prenatal screening.

OBJECTIVE: An instrument for measuring intervention preferences applicable to both patients and policymakers would make it possible to better confront the needs of the supply and demand sides of the health care system. This study aimed to develop a discrete choice experiments (DCE) questionnaire to elicit the preferences of patients and policymakers. The instrument was specifically developed to estimate preferences for new conditions to be added to a screening program for fetal chromosomal anomalies. METHODS: A DCE development study was conducted. The methods employed included a literature review, a qualitative study (based on individual semi-structured interviews, consultations, and a focus group discussion) with pregnant women and policymakers, and a pilot project with 33 pregnant women to validate the first version of the instrument and test the feasibility of its administration. RESULTS: An initial list of 10 attributes was built based on a literature review and the qualitative research components of the study. Five attributes were built based on the responses provided by the participants from both groups. Eight attributes were consensually retained. A pilot project performed on 33 pregnant women led to a final instrument containing seven attributes: 'conditions to be screened', 'test performance', 'moment at gestational age to obtain the test result', 'degree of test result certainty to the severity of the disability', 'test sufficiency', 'information provided from test result', and 'cost related to the test'. CONCLUSION: It is possible to reach a consensus on the construction of a DCE instrument intended to be administered to pregnant women and policymakers. However, complete validation of the consensual instrument is limited because there are too few voting members of health technology assessment agencies committees to statistically ascertain the relevance of the attributes and their levels.

Expansion of non-invasive prenatal screening to the screening of 10 types of chromosomal anomalies: a cost-effectiveness analysis.

OBJECTIVES: To determine the cost-effectiveness of the addition of chromosomal anomalies detectable by non-invasive prenatal screening (NIPS), in a prenatal screening programme targeting common aneuploidies. DESIGN, SETTING AND PARTICIPANTS: A simulation study was conducted to study the addition of chromosomal anomalies detectable by NIPS (sex chromosome aneuploidies, 22q11.2 deletion syndrome, large deletion/duplication >7 Mb and rare autosomal trisomies) to five basic strategies currently aiming the common trisomies: three strategies currently offered by the public healthcare systems in Canada, whose first-tier test is performed with biochemical markers, and two programmes whose first-tier test consists of NIPS-based methods. OUTCOME MEASURES: The total number of cases of chromosomal anomalies detected and the costs related to the consumption of medical services. RESULTS: The most effective and the most cost-effective option in almost all prenatal screening strategies is the option that includes all targeted additional conditions. In the strategies where NIPS is used as first-tier testing, the cost per additional case detected by adding all possible additional anomalies to a programme that currently targets only common trisomies is $C25 710 (95% CI $C25 489 to $C25 934) for massively parallel shotgun sequencing and $C57 711 (95% CI $C57 141 to $C58 292) for targeted massively parallel sequencing, respectively. The acceptability curves show that at a willingness-to-pay of $C50 000 per one additional case detected, the expansion of NIPS-based methods for the detection of all possible additional conditions has a 90% probability of being cost-effective. CONCLUSION: From an economic perspective, in strategies that use NIPS as a first-tier screening test, expanding the programmes to detect any considered chromosomal anomalies other than the three common trisomies would be cost-effective. However, the potential expansion of prenatal screening programmes also requires consideration of societal issues, including ethical ones.

Temporal changes in diet quality and the associated economic burden in Canada.

A high-quality diet is associated with a reduced of risk of chronic disease and all-cause mortality. In this study, we assessed changes in diet quality and the associated economic burden in the Canadian population between 2004 and 2015. We used a prevalence-based cost-of-illness approach. We first calculated the diet quality using the Healthy Eating Index-Canada-2010 (HEI-C-2010) and 24-hour recall data from the Canadian Community Health Surveys (CCHS) on nutrition (CCHS 2004 cycle 2.2 and the CCHS-NU 2015). We then retrieved relative risks of HEI-2010 quintiles for chronic diseases from meta-analyses. Based on the proportions of the population following diets of varying qualities and these relative risks, we computed the population-attributable fractions and attributable costs (direct health care and indirect costs) by survey year (2004 and 2015) as well as by age and sex group. Costs were estimated in 2017 Canadian dollars for comparison purposes. We observed that on average the diet quality of Canadians improved between 2004 and 2015: the proportion of the Canadian population that did not eat a diet of high quality decreased from 83% to 76%. This improvement in diet quality translated in a decrease in economic burden of $133 million, down from $13.21 billion in 2004 to $13.08 billion in 2015. The economic burden decreased by $219 million among males but increased by $86 million among females. It also decreased among people under the age of 65 years ($333 million) but increased among those over 65 years ($ 200 million). Our findings suggest that, despite some temporal improvements, the diet of the majority of Canadians is of poor quality resulting in a high attributable economic burden. Policy and decision makers are encouraged to expand nutrition programs and policies and to specifically target the elderly in order to prevent chronic diseases and reduce health care costs.

Decentralized control of human visceral leishmaniasis in endemic urban areas of Brazil: a literature review.

OBJECTIVES: Human migration and concomitant HIV infections are likely to bring about major changes in the epidemiology of some parasitic infections in Brazil. Human visceral leishmaniasis (HVL) control is particularly fraught with intricacies. It is against a backdrop of decentralized health care that the complex HVL control initiatives are brought to bear. This comprehensive review aims to explore the obstacles facing decentralized HVL control in urban endemic areas in Brazil. METHOD: A literature search was carried out in December 2015 by means of three databases: MEDLINE, Google Scholar, and Web of Science. RESULTS: Although there have been many strides that have been made in elucidating the eco-epidemiology of Leishmania infantum, which forms the underpinnings of the national control program, transmission risk factors for HVL are still insufficiently elucidated in urban settings. Decentralized HVL epidemiological surveillance and control for animal reservoirs and vectors may compromise sustainability. In addition, it may hamper timely human HVL case management. With the burgeoning of the HIV-HVL co-infection, the potential human transmission may be underestimated. CONCLUSION: HVL is a disease with focal transmission at a critical juncture, which warrants that the bottlenecks facing the control program within contexts of decentralized healthcare systems be taken into account. In addition, HIV-driven HVL epidemics may substantially increase the transmission potential of the human reservoir. Calculating the basic reproductive number to fine-tune interventions will have to take into consideration the specific socio-economic development context.

Revisiting zoonotic human African trypanosomiasis control in Uganda.

OBJECTIVES: Human migration and concomitant HIV infections are likely to bring about major changes in the epidemiology of zoonotic parasitic infections. Human African trypanosomiasis (HAT) control is particularly fraught with intricacies. The primarily zoonotic form, T.b. rhodesiense, and the non-zoonotic T.b. gambiense co-exist in Northern Uganda, leading to a potential geographic and genetic overlap of the two foci. This region also has the highest HIV prevalence in Uganda plus poor food security. We examine the bottlenecks facing the control program in a changed political and economic context. METHOD: We searched the literature in July 2015 using three databases: MEDLINE, Google Scholar, and Web of Science. FINDINGS: Decentralized zoonotic HAT control for animal reservoirs and vectors compromise sustainability of the control programs. Human transmission potential may be underestimated in a region with other endemic diseases and where an HIV-HAT epidemic, could merge two strains. CONCLUSION: Our comprehensive literature review concludes that enhanced collaboration is imperative not only between human and animal health specialists, but also with political science. Multi-sectorial collaborations may need to be nurtured within existing operational national HIV prevention frameworks, with an integrated surveillance framework.

Cost-effectiveness analysis of antiviral treatment in the management of seasonal influenza A: point-of-care rapid test versus clinical judgment.

BACKGROUND: A point-of-care rapid test (POCRT) may help early and targeted use of antiviral drugs for the management of influenza A infection. OBJECTIVE: (i) To determine whether antiviral treatment based on a POCRT for influenza A is cost-effective and, (ii) to determine the thresholds of key test parameters (sensitivity, specificity and cost) at which a POCRT based-strategy appears to be cost effective. METHODS: An hybrid « susceptible, infected, recovered (SIR) ¼ compartmental transmission and Markov decision analytic model was used to simulate the cost-effectiveness of antiviral treatment based on a POCRT for influenza A in the social perspective. Data input parameters used were retrieved from peer-review published studies and government databases. The outcome considered was the incremental cost per life-year saved for one seasonal influenza season. RESULTS: In the base-case analysis, the antiviral treatment based on POCRT saves 2 lives/100,000 person-years and costs $7600 less than the empirical antiviral treatment based on clinical judgment alone, which demonstrates that the POCRT-based strategy is dominant. In one and two way-sensitivity analyses, results were sensitive to the POCRT accuracy and cost, to the vaccination coverage as well as to the prevalence of influenza A. In probabilistic sensitivity analyses, the POCRT strategy is cost-effective in 66% of cases, for a commonly accepted threshold of $50,000 per life-year saved. CONCLUSION: The influenza antiviral treatment based on POCRT could be cost-effective in specific conditions of performance, price and disease prevalence.

An economic evaluation: Simulation of the cost-effectiveness and cost-utility of universal prevention strategies against osteoporosis-related fractures.

A patient-level Markov decision model was used to simulate a virtual cohort of 500,000 women 40 years old and over, in relation to osteoporosis-related hip, clinical vertebral, and wrist bone fractures events. Sixteen different screening options of three main scenario groups were compared: (1) the status quo (no specific national prevention program); (2) a universal primary prevention program; and (3) a universal screening and treatment program based on the 10-year absolute risk of fracture. The outcomes measured were total directs costs from the perspective of the public health care system, number of fractures, and quality-adjusted life-years (QALYs). Results show that an option consisting of a program promoting physical activity and treatment if a fracture occurs is the most cost-effective (CE) (cost/fracture averted) alternative and also the only cost saving one, especially for women 40 to 64 years old. In women who are 65 years and over, bone mineral density (BMD)-based screening and treatment based on the 10-year absolute fracture risk calculated using a Canadian Association of Radiologists and Osteoporosis Canada (CAROC) tool is the best next alternative. In terms of cost-utility (CU), results were similar. For women less than 65 years old, a program promoting physical activity emerged as cost-saving but BMD-based screening with pharmacological treatment also emerged as an interesting alternative. In conclusion, a program promoting physical activity is the most CE and CU option for women 40 to 64 years old. BMD screening and pharmacological treatment might be considered a reasonable alternative for women 65 years old and over because at a healthcare capacity of $50,000 Canadian dollars ($CAD) for each additional fracture averted or for one QALY gained its probabilities of cost-effectiveness compared to the program promoting physical activity are 63% and 75%, respectively, which could be considered socially acceptable. Consideration of the indirect costs could change these findings.