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Osteoporosis: HELP
Articles by Santiago Palacios
Based on 39 articles published since 2010
(Why 39 articles?)

Between 2010 and 2020, S. Palacios wrote the following 39 articles about Osteoporosis.
+ Citations + Abstracts
Pages: 1 · 2
1 Guideline EMAS position statement: The ten point guide to the integral management of menopausal health. 2015

Neves-E-Castro, Manuel / Birkhauser, Martin / Samsioe, Goran / Lambrinoudaki, Irene / Palacios, Santiago / Borrego, Rafael Sanchez / Llaneza, Placido / Ceausu, Iuliana / Depypere, Herman / Erel, C Tamer / Pérez-López, Faustino R / Schenck-Gustafsson, Karin / van der Schouw, Yvonne T / Simoncini, Tommaso / Tremollieres, Florence / Rees, Margaret. ·Clinica da Menopausa, Av. Luis Bivar, 93c-1 Dt, Lisboa 1050-143, Portugal. · Gynaecological Endocrinology and Reproductive Medicine, University of Berne, Gartenstrasse 67, CH-4052 Basel, Switzerland. · Department of Clinical Sciences, SUS University Hospital Lund, Lund University, SE-221 85 Lund, Sweden. · Second Department of Obstetrics and Gynecology, National and Capodestrian University of Athens, Greece. · Instituto Palacios, Salud y Medicina de la Mujer, C/Antonio Acuña, 9, 28009 Madrid, Spain. · DIATROS, Clínica de Atención a la Mujer, Barcelona, Spain. · Department of Obstetrics and Gynecology, University Central Hospital of Asturias, University of Oviedo, 33011 Oviedo, Spain. · Department of Obstetrics and Gynecology, 'Carol Davila' University of Medicine and Pharmacy, Bucharest, Romania; Department of Obstetrics and Gynecology, 'Dr. I. Cantacuzino' Hospital, Bucharest, Romania. · Breast Clinic and Menopause Clinic, University Hospital, De Pintelaan 185, 9000 Gent, Belgium. · Department of Obstetrics and Gynecology, Istanbul University, Cerrahpasa School of Medicine, Valikonagi Cad. No: 93/4, Nisantasi, 34365 Istanbul, Turkey. · Department of Obstetrics and Gynecology, Zaragoza University Facultad de Medicina, Hospital Clínico, Zaragoza 50009, Spain. · Department of Medicine, Cardiology Unit, Centre for Gender Medicine, Karolinska Institutet and Karolinska University Hospital, Thorax N3:05, SE 17176 Stockholm, Sweden. · Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands. · Department of Clinical and Experimental Medicine, University of Pisa, Via Roma, 67, 56100 Pisa, Italy. · Menopause and Metabolic Bone Disease Unit, Hôpital Paule de Viguier, F-31059 Toulouse cedex 09, France. · Women's Centre, John Radcliffe Hospital, Oxford OX3 9DU, UK. Electronic address: margaret.rees@st-hildas.ox.ac.uk. ·Maturitas · Pubmed #25757366.

ABSTRACT: With increased longevity and more women becoming centenarians, management of the menopause and postreproductive health is of growing importance as it has the potential to help promote health over several decades. Women have individual needs and the approach needs to be personalised. The position statement provides a short integral guide for all those involved in menopausal health. It covers diagnosis, screening for diseases in later life, treatment and follow-up.

2 Editorial Association between vitamin D and falls in young postmenopausal women. 2016

Palacios, Santiago. ·Palacios Institute of Women's Health, Madrid, Spain. ·Menopause · Pubmed #26818014.

ABSTRACT: -- No abstract --

3 Editorial Antiresorptives and anabolic therapy in sequence or combination for postmenopausal osteoporosis. 2015

Palacios, S / Mejía, A. ·Palacios Institute of Women's Health , Madrid , Spain. ·Climacteric · Pubmed #25740608.

ABSTRACT: Osteoporosis is a chronic disease which may require treatment for many years and requires not only individual management but often sequential or combination treatments. Monotherapy with antiresorptives is usually the first choice. Sometimes, it is necessary to modify this option for therapeutic failure or for the time of use and risk of side-effects. Due to their different mode of action, therapy with anabolic drugs has increased our options in the treatment of osteoporosis. Postmenopausal women and men with severe and progressive osteoporosis despite antiresorptive treatment ('therapeutic failure') should be evaluated for treatment with an anabolic option. Moreover, anabolic agents are indicated for 18-24 months in patients at high risk. Then, sequential antiresorptive therapy is recommended to maintain drug increases in bone mass and support secondary mineralization of the newly formed bone. Combination therapies of antiresorptives and anabolic agents have shown a significant increase in bone mineral density compared to monotherapies. However, none of the combinations have been studied for the prevention of fractures. Combination therapy may not be recommended because of the possible increase in cost.

4 Review Management of Aromatase Inhibitor-Associated Bone Loss (AIBL) in postmenopausal women with hormone sensitive breast cancer: Joint position statement of the IOF, CABS, ECTS, IEG, ESCEO IMS, and SIOG. 2017

Hadji, Peyman / Aapro, Matti S / Body, Jean-Jacques / Gnant, Michael / Brandi, Maria Luisa / Reginster, Jean Yves / Zillikens, M Carola / Glüer, Claus-C / de Villiers, Tobie / Baber, Rod / Roodman, G David / Cooper, Cyrus / Langdahl, Bente / Palacios, Santiago / Kanis, John / Al-Daghri, Nasser / Nogues, Xavier / Eriksen, Erik Fink / Kurth, Andreas / Rizzoli, Rene / Coleman, Robert E. ·Krankenhaus Nordwest, Frankfurt, Germany. · Genolier Cancer Center, Switzerland. · CHU Brugmann, Université Libre de Bruxelles, Belgium. · Medical University of Vienna, Austria. · University of Florence, Italy. · University of Liège, Belgium. · Erasmus MC, Rotterdam, Netherlands. · Univeristy of Kiel, Germany. · University of Stellenbosch, Cape Town, South Africa. · University of Sydney, Australia. · Indiana University School of Medicine, USA. · University of Southampton, UK. · Aarhus University, Denmark. · Instituto Palacios Madrid, Spain. · Catholic University of Australia, Melbourne, Australia and University of Sheffield, UK. · University of Riyadh, Saudi Arabia. · Autonomous University of Barcelona, Spain. · University of Oslo, Norway. · Klinikum Birkenwerder, Germany. · Geneva University, Switzerland. · University of Sheffield, UK. ·J Bone Oncol · Pubmed #28413771.

ABSTRACT: BACKGROUND: Several guidelines have been reported for bone-directed treatment in women with early breast cancer (EBC) for averting fractures, particularly during aromatase inhibitor (AI) therapy. Recently, a number of studies on additional fracture related risk factors, new treatment options as well as real world studies demonstrating a much higher fracture rate than suggested by randomized clinical controlled trials (RCTs). Therefore, this updated algorithm was developed to better assess fracture risk and direct treatment as a position statement of several interdisciplinary cancer and bone societies involved in the management of AI-associated bone loss (AIBL). PATIENTS AND METHODS: A systematic literature review identified recent advances in the management of AIBL. Results with individual agents were assessed based on trial design, size, follow-up, and safety. RESULTS: Several fracture related risk factors in patients with EBC were identified. Although, the FRAX algorithm includes fracture risk factors (RF) in addition to BMD, it does not seem to adequately address the effects of AIBL. Several antiresorptive agents can prevent and treat AIBL. However, concerns regarding compliance and long-term safety remain. Overall, the evidence for fracture prevention is strongest for denosumab 60 mg s.c. every 6 months. Additionally, recent studies as well as an individual patient data meta-analysis of all available randomized trial data support additional anticancer benefits from adjuvant bisphosphonate treatment in postmenopausal women with a 34% relative risk reduction in bone metastasis and 17% relative risk decrease in breast cancer mortality that needs to be taken into account when advising on management of AIBL. CONCLUSIONS: In all patients initiating AI treatment, fracture risk should be assessed and recommendation with regard to exercise and calcium/vitamin D supplementation given. Bone-directed therapy should be given to all patients with a T-score<-2.0 or with a T-score of <-1.5 SD with one additional RF, or with ≥2 risk factors (without BMD) for the duration of AI treatment. Patients with T-score>-1.5 SD and no risk factors should be managed based on BMD loss during the first year and the local guidelines for postmenopausal osteoporosis. Compliance should be regularly assessed as well as BMD on treatment after 12 - 24 months. Furthermore, because of the decreased incidence of bone recurrence and breast cancer specific mortality, adjuvant bisphosphonates are recommended for all postmenopausal women at significant risk of disease recurrence.

5 Review New options for menopausal symptoms after 15 years of WHI Study. 2017

Palacios, Santiago / Coronado, Pluvio J. ·Director of Instituto Palacios, Madrid, Spain - ipalacios@institutopalacios.com. · Department of Obstetrics and Gynecology, San Carlos Clinic Hospital, Madrid, Spain. ·Minerva Ginecol · Pubmed #27973466.

ABSTRACT: Menopausal symptoms include vasomotor symptoms (VMS), vulvar-vaginal atrophy, and loss of bone mass associated with an increased risk of fracture. Treatment of VMS consists of lifestyle changes, hormone treatment (estrogens with and without progestogens, tissue selective estrogens complex or conjugated estrogens and bazedoxifene [CE/BZA], progestogens, and tibolone), and nonhormonal treatments. Genitourinary symptoms due to vulvar-vaginal atrophy are treated with systemic and local hormones, moisturizer creams and gels, CE/BZA, and a selective estrogen receptor modulator (ospemifene). In addition to lifestyle changes, treatments for the risk of fragility fracture include calcium and vitamin D, hormone treatment, selective estrogen receptor modulators (raloxifene, BZA), bisphosphonates, strontium ranelate, denosumab, and teriparatide. This article reviews treatment options and provides treatment algorithms for women with menopausal symptoms.

6 Review The position of strontium ranelate in today's management of osteoporosis. 2015

Reginster, J-Y / Brandi, M-L / Cannata-Andía, J / Cooper, C / Cortet, B / Feron, J-M / Genant, H / Palacios, S / Ringe, J D / Rizzoli, R. ·Department of Public Health, Epidemiology and Health Economics, University of Liège, 4020, Liège, Belgium. jyreginster@ulg.ac.be. · Metabolic Bone Unit, Department of Internal Medicine, University of Florence, Florence, Italy. · Servicio de Metabolismo Óseo y Mineral, Hospital Universitario Central de Asturias, Universidad de Oviedo, Oviedo, Asturias, Spain. · MRC Lifecourse Epidemiology Unit and NIHR Nutrition Biomedical Research Centre, University of Southampton, Southampton, UK. · Service de Rhumatologie, Hôpital Roger Salengro, Lille, France. · Service de Chirurgie Orthopédique et Traumatologique, Hôpital Saint Antoine, UPMC, Paris, France. · Departments of Radiology, Medicine, Epidemiology and Orthopedic Surgery, University of California, San Francisco, CA, USA. · Instituto Palacios, Salud y Medicina de la Mujer, Madrid, Spain. · Med Klinik 4, Klinikum Leverkusen, Akadem, Lehrkrankenhaus, University of Cologne, Cologne, Germany. · Division of Bone Diseases, Faculty of Medicine, Geneva University Hospital, Geneva, Switzerland. ·Osteoporos Int · Pubmed #25868510.

ABSTRACT: Osteoporosis accounts for about 3 % of total European health-care spending. The low proportion of costs for the pharmacological prevention of osteoporotic fracture means that it is highly cost saving, especially in patient with severe osteoporosis or patients who cannot take certain osteoporosis medications due to issues of contraindications or tolerability. Following recent regulatory changes, strontium ranelate is now indicated in patients with severe osteoporosis for whom treatment with other osteoporosis treatments is not possible, and without contraindications including uncontrolled hypertension, established, current or past history of ischaemic heart disease, peripheral arterial disease, and/or cerebrovascular disease. We review here today's evidence for the safety and efficacy of strontium ranelate. The efficacy of strontium ranelate in patients complying with the new prescribing information (i.e. severe osteoporosis without contraindications) has been explored in a multivariate analysis of clinical trial data, which concluded that the antifracture efficacy of strontium ranelate is maintained in patients with severe osteoporosis without contraindications and also demonstrated how the new target population mitigates risk. Strontium ranelate is therefore an important alternative in today's management of osteoporosis, with a positive benefit-risk balance, provided that the revised indication and contraindications are followed and cardiovascular risk is monitored. The bone community should be reassured that there remain viable alternatives in patients in whom treatment with other agents is not possible and protection against the debilitating effects of fracture is still feasible in patients with severe osteoporosis.

7 Review Bazedoxifene/conjugated estrogens combination for the treatment of the vasomotor symptoms associated with menopause and for prevention of osteoporosis in postmenopausal women. 2015

Palacios, S / Mejía Ríos, A. ·Palacios Institute of Women's Health, Madrid, Spain. ipalacios@institutopalacios.com. · Palacios Institute of Women's Health, Madrid, Spain. ·Drugs Today (Barc) · Pubmed #25756066.

ABSTRACT: The decrease of estrogen in postmenopausal women has been associated with the presence of different symptoms such as vasomotor symptoms, vulvovaginal atrophy, bone loss, sleep disturbances, and mood and sexual activity alterations. Hormone replacement therapy with estrogen and progestins has been used to improve menopausal symptoms; however, there are still concerns regarding its safety and tolerability, as some progestins have been shown to increase breast cancer and cardiovascular risk. Bazedoxifene is a third-generation selective estrogen receptor modulator (SERM) used for osteoporosis management in postmenopausal women at fracture risk that has demonstrated a powerful antiestrogenic effect on the endometrium. Today we have a new alternative called the tissue-selective estrogen complex (TSEC), which combines bazedoxifene and conjugated estrogens and is designed not only to improve menopausal symptoms and vulvovaginal atrophy but also to prevent bone loss. Therefore, it maintains the benefits of estrogen therapy while antagonizing the stimulation effects on the endometrium and mammary gland without the effects associated with progestins.

8 Review Perspective on prescribing conjugated estrogens/bazedoxifene for estrogen-deficiency symptoms of menopause: a practical guide. 2015

Palacios, Santiago / Currie, Heather / Mikkola, Tomi S / Dragon, Erika. ·Instituto Palacios, Madrid, Spain. Electronic address: ipalacios@institutopalacios.com. · NHS Dumfries & Galloway, Dumfries, Scotland, United Kingdom. · Helsinki University Central Hospital, Helsinki, Finland. · Pfizer, Global Innovative Pharma, Europe, Paris, France. ·Maturitas · Pubmed #25684082.

ABSTRACT: Current guidelines recommend that hormone therapy (HT) in postmenopausal women with a uterus include a progestin to protect against endometrial hyperplasia. However, many concerns relating to HT use appear to be related to the progestin component, including cardiovascular risk, breast stimulation, and irregular vaginal bleeding. Conjugated estrogens (CE) combined with the selective estrogen receptor modulator bazedoxifene (BZA) is a new progestin-free HT option for alleviating estrogen deficiency symptoms in postmenopausal women with a uterus for whom treatment with progestin-containing therapy is not appropriate. Five double-blind, randomized, placebo-controlled, phase 3 studies, known as the Selective estrogens, Menopause, And Response to Therapy (SMART) trials have investigated the efficacy of CE/BZA for relieving vasomotor symptoms (VMS), and effect on bone mass, as well as endometrial and breast safety in postmenopausal women. In a 12-week study, CE 0.45 mg/BZA 20 mg significantly reduced the number and severity of hot flushes compared with placebo at weeks 4 and 12. Unlike estrogen-progestin therapy (EPT), CE 0.45 mg/BZA 20 mg did not increase breast density compared with placebo. In clinical trials up to 2 years, CE/BZA had a favorable tolerability profile, demonstrated by amenorrhea rates similar to placebo. Vascular disorders including venous thromboembolic events (pulmonary embolism, retinal vein thrombosis, deep vein thrombosis, and thrombophlebitis) were rare events, occurring in less than 1 per 1000 patients. CE/BZA was associated with significantly higher incidences of amenorrhea and lower incidences of bleeding compared with CE/medroxyprogesterone acetate in 2 comparative trials. Therefore, CE 0.45 mg/BZA 20mg provides an effective, well-tolerated, progestin-free alternative to EPT for postmenopausal women with a uterus.

9 Review [Inhibition of RANK-L in the pathophysiology of osteoporosis. Clinical evidences of its use]. 2013

Luis Neyro, José / Jesús Cancelo, María / Palacios, Santiago. ·Servicio de Ginecología y Obstetricia, Facultad de Medicina y Odontología, Grupo de trabajo de Osteoporosis de la Associación Española para el Estudio de la Menopausia, Universidad del País Vasco, EUH-UPV. jlneyro@sego.es ·Ginecol Obstet Mex · Pubmed #23672116.

ABSTRACT: The increase bone turnover is the most important fact at the physiopathology of postmenopausal osteoporosis. At the molecular level it is the increase of the RANK-L the principal mediator who allows the osteoclasts formation, survival and development of them. Multiple models have been in use in preclinical investigations for evaluating the effects of the inhibition of the RANKL, between which it is included on OPG's over-expression in mice and transgenic mouse and by means of other models that include the treatment with recombinant OPG. The results of these studies show that RANKL's inhibition improves the DMO as well as the geometry and resistance of the bone. Several references clinical trials have investigated the potential of denosumab as antiresorptive drug for the prevention and treatment of bone disease. It is a monoclonal antibody, the first fully human, which were recently published results of randomized clinical trials to eight years for increasing BMD in different locations and five years for the prevention of vertebral and hip fractures. We review the fundamentals of the mechanism of inhibition of RANK-L and the results of several clinical trials of Denosumab.

10 Review EMAS clinical guide: selective estrogen receptor modulators for postmenopausal osteoporosis. 2012

Palacios, Santiago / Brincat, Mark / Erel, C Tamer / Gambacciani, Marco / Lambrinoudaki, Irene / Moen, Mette H / Schenck-Gustafsson, Karin / Tremollieres, Florence / Vujovic, Svetlana / Rees, Margaret / Rozenberg, Serge. ·Palacios Institute of Woman's Health Antonio Acuna, Madrid, Spain. ipalacios@institutopalacios.com ·Maturitas · Pubmed #22176952.

ABSTRACT: Osteoporosis and the resulting fractures are major public health issues as the world population is ageing. Various therapies such as bisphosphonates, strontium ranelate and more recently denosumab are available. This clinical guide provides the evidence for the clinical use of selective estrogen modulators (SERMs) in the management of osteoporosis in postmenopausal women.

11 Review Bazedoxifene acetate for the management of postmenopausal osteoporosis. 2011

Palacios, S. ·Palacios Institute of Women's Health, Madrid, Spain. ipalacios@institutopalacios.com ·Drugs Today (Barc) · Pubmed #21494696.

ABSTRACT: Osteoporosis is a gender-related disease that is especially prevalent in postmenopausal women. New drugs have been developed led by issues of interest and concerns about this disease, each one striving to be more effective and safer than the previous one. Bazedoxifene acetate is a new, third-generation, selective estrogen receptor modulator. This drug is used to treat postmenopausal osteoporosis in women with a high risk of fracture. Bazedoxifene acetate significantly prevents bone mass loss at 20 mg/day in healthy postmenopausal women with normal or low bone mineral density. The risk of vertebral fractures in women with osteoporosis was reduced by 42% (P < 0.05) after 3 years in a pivotal study. Five years later, the reduction was still 35% (P = 0.014). Post hoc analysis in women with a high risk of fractures showed a 50% reduced risk of nonvertebral fractures (P = 0.02) after 3 years and a 37% reduction (P = 0.06) after 5 years. Bazedoxifene acetate shows anti-fracture potential in the first few years after menopause and a greater antiestrogen effect at the level of the uterus. This has made this compound an appropriate option in young postmenopausal women with osteoporosis and a risk of fractures.

12 Review Efficacy and safety of bazedoxifene, a novel selective estrogen receptor modulator for the prevention and treatment of postmenopausal osteoporosis. 2010

Palacios, Santiago. ·Instituto Palacios, Salud y Medicina de la Mujer, Madrid, Spain. ipalacios@institutopalacios.com ·Curr Med Res Opin · Pubmed #20429824.

ABSTRACT: OBJECTIVE: Osteoporosis affects millions of individuals, particularly postmenopausal women, and imposes a severe burden on patients and the healthcare system. Several therapeutic options are commercially available for the prevention and treatment of osteoporosis, including bisphosphonates, hormone therapy, and the selective estrogen receptor modulator (SERM), raloxifene. Because each of these agents has its own individual risk-benefit profile, their use should be tailored to specific patient populations. While many agents are approved for osteoporosis, new therapies are needed that maximize efficacy outcomes and minimize safety concerns. Several new SERMs are being evaluated in an effort to achieve an ideal tissue selectivity profile, with beneficial effects on bone without negative effects on the endometrium and breast. Bazedoxifene is a novel SERM that was recently approved in the European Union and is undergoing regulatory review in the United States for the prevention and treatment of postmenopausal osteoporosis. This article reviews the clinical efficacy and safety data for bazedoxifene in postmenopausal women with or at risk for osteoporosis. METHODS: The PubMed database and relevant congress abstract databases were searched to identify all pertinent literature on bazedoxifene for the prevention and/or treatment of postmenopausal osteoporosis. RESULTS: In phase 3 clinical studies, bazedoxifene has demonstrated significant reduction in the risk of new vertebral fracture versus placebo and positive effects on bone mineral density and bone turnover. Moreover, in a subgroup analysis of women at high risk for fracture, bazedoxifene significantly reduced the risk of nonvertebral fracture versus both placebo and raloxifene. Bazedoxifene was generally safe and well-tolerated in women with and at risk for osteoporosis, with no evidence of endometrial or breast stimulation. Data inclusion for this review article was limited by what was available in the public domain. CONCLUSION: The available clinical data suggest that bazedoxifene may offer a favorable risk-benefit profile for the prevention and treatment of postmenopausal osteoporosis.

13 Clinical Trial Efficacy and tolerability of bazedoxifene in Mexican women with osteoporosis: a subgroup analysis of a randomized phase 3 trial. 2016

Palacios, Santiago / Williams, Robert / Mirkin, Sebastian / Pan, Kaijie / Arias, Lizbeth / Komm, Barry S. ·1Palacios Institute of Women's Health, Madrid, Spain 2Pfizer Inc, Collegeville, PA 3Pfizer Inc, Bosques de las Lomas, Mexico. ·Menopause · Pubmed #27116464.

ABSTRACT: OBJECTIVE: Bazedoxifene (BZA) is a selective estrogen receptor modulator that reduces fracture risk and bone turnover in postmenopausal women with osteoporosis. This analysis evaluated BZA's effects on bone mineral density (BMD) and bone turnover in Mexican women with osteoporosis from the global pivotal trial (Study Evaluating Bazedoxifene Acetate in Osteoporosis in Postmenopausal Women). METHODS: In this 3-year, phase 3, randomized, double-blind trial, healthy postmenopausal women with osteoporosis (N = 7,492) received BZA 20 or 40 mg/d, raloxifene 60 mg/d, or placebo. The subanalyses of Mexican women assessed serum concentrations of osteocalcin and collagen type 1 C-telopeptide, BMD, and tolerability with BZA 20 mg/d versus placebo. RESULTS: In the Mexican subgroup (BZA, n = 39; placebo, n = 37) at month 12, BZA 20 mg/d produced significant (P < 0.001) percentage decreases from baseline in osteocalcin (-40.5 vs -18.5) and C-telopeptide (-45.7 vs -29.4). For BZA versus placebo, percentage change in BMD from baseline to month 36 was 3.3 versus 0.64 for lumbar spine, -0.18 versus -1.8 for total hip, 0.21 versus -2.6 for femoral neck, and -0.55 versus -1.4 for femoral trochanter; differences were not statistically significant. Results were comparable to the overall study population in which differences were statistically significant. Common adverse events (≥20%) included arthralgia, back pain, gastritis, headache, influenza, and pain; none led to study withdrawal. CONCLUSIONS: In Mexican women with osteoporosis, BZA was well tolerated and seems to produce BMD changes comparable to the global phase 3 population, although differences versus placebo were not statistically significant in this smaller subgroup.

14 Clinical Trial The efficacy and safety of bazedoxifene in postmenopausal women by baseline kidney function status. 2014

Adami, S / Palacios, S / Rizzoli, R / Levine, A B / Sutradhar, S / Chines, A A. ·University of Verona , Verona , Italy. ·Climacteric · Pubmed #23937421.

ABSTRACT: INTRODUCTION: Two global, double-blind, placebo- and active-controlled, phase-3 studies (2-year prevention (n = 1583) and 3-year treatment (n = 7492)) have shown that bazedoxifene (BZA) is safe and effective for prevention and treatment of postmenopausal osteoporosis. OBJECTIVE: To evaluate the efficacy/safety of BZA according to baseline kidney function. METHODS: Data for the BZA 20- and 40-mg and placebo groups from both studies were integrated for assessment of bone turnover markers (BTMs), bone mineral density (BMD), and fracture incidence (treatment study only). Safety was assessed using integrated data for the BZA, placebo, and raloxifene 60-mg groups from both studies. Baseline glomerular filtration rate (GFR) was estimated by the Modification of Diet in Renal Disease Study equation; among subjects with baseline GFR, renal function categories were defined by GFR (ml/min per 1.73 m(2)): normal (GFR ≥ 90; n = 1982), mild impairment (60 ≤ GFR < 90; n = 6032), or moderate/severe impairment (GFR < 60; n = 723). RESULTS: Demographics were similar across treatment groups and within GFR subgroups. Across GFR subgroups, BZA 20 and 40 mg reduced BTM levels and improved lumbar spine and total hip BMD versus placebo. At month 24, there were significant treatment-by-GFR (p = 0.003) and treatment-by-serum creatinine (p = 0.034) interactions for the increase in lumbar spine BMD versus placebo. Fracture incidence was lower with BZA than placebo across all GFR categories, with no treatment-by-GFR interaction. There were no significant differences among treatment groups in incidences of overall, serious, or renal-related adverse events across GFR subgroups. CONCLUSIONS: Mild to moderate kidney impairment did not affect the efficacy and safety of BZA in postmenopausal women.

15 Clinical Trial Assessment of the safety of long-term bazedoxifene treatment on the reproductive tract in postmenopausal women with osteoporosis: results of a 7-year, randomized, placebo-controlled, phase 3 study. 2013

Palacios, Santiago / de Villiers, Tobie J / Nardone, Fiorenzo De Cicco / Levine, Amy B / Williams, Robert / Hines, Teresa / Mirkin, Sebastian / Chines, Arkadi A / Anonymous3770764. ·Palacios Institute of Women's Health, Calle Antonio Acuña, 9, 28009 Madrid, Spain. ipalacios@institutopalacios.com ·Maturitas · Pubmed #23871271.

ABSTRACT: OBJECTIVE: To evaluate the clinical safety of bazedoxifene (BZA) on the reproductive tract in postmenopausal women with osteoporosis over 7 years. STUDY DESIGN: This was a second, blinded, 2-year extension of a 3-year, randomized, double-blind, placebo (PBO)- and active-controlled phase 3 trial. In the core study, subjects were randomized to receive BZA 20 or 40mg, raloxifene 60mg, or PBO. During years 4-5, the raloxifene arm was discontinued and subjects receiving BZA 40mg were transitioned to BZA 20mg. Subjects continued to receive BZA 20mg or PBO during years 6-7. MAIN OUTCOME MEASURES: The primary endpoint was the incidence of new vertebral fractures at 7 years (reported separately). Reproductive tract safety findings at 7 years are reported here. Endometrial thickness was assessed by transvaginal ultrasonography for subjects in the endometrial safety substudy. Adverse events (AEs) were recorded throughout the study. RESULTS: At 7 years, the adjusted mean (±standard error) change in endometrial thickness was similar with BZA and PBO (-0.11 ± 0.21 and 0.07 ± 0.32 mm, respectively). The incidence of endometrial hyperplasia was low (0.1% for both groups). BZA showed significantly lower rates than PBO of endometrial carcinoma (0.1% vs. 0.4%; P=0.020) and vaginitis (6.1% vs. 7.6%; P=0.035). There were more cases of ovarian carcinoma with BZA (n=4 [0.1%]) than PBO (n=0); the difference was not statistically significant. Rates of breast-related and other gynecologic AEs were similar among groups. CONCLUSIONS: BZA was associated with a favorable reproductive safety profile in postmenopausal women with osteoporosis over 7 years.

16 Clinical Trial An evaluation of the Fracture Risk Assessment Tool (FRAX®) as an indicator of treatment efficacy: the effects of bazedoxifene and raloxifene on vertebral, nonvertebral, and all clinical fractures as a function of baseline fracture risk assessed by FRAX®. 2013

Kaufman, J-M / Palacios, S / Silverman, S / Sutradhar, S / Chines, A. ·Department of Endocrinology and Unit for Osteoporosis and Metabolic Bone Diseases, Ghent University Hospital, Ghent, Belgium, jean.kaufman@ugent.be. ·Osteoporos Int · Pubmed #23595562.

ABSTRACT: SUMMARY: The relationship between baseline Fracture Risk Assessment Tool (FRAX®) and treatment efficacy was evaluated using data from a pivotal phase 3 study. Relative risk of vertebral, nonvertebral, and all clinical fractures decreased with increasing probability of fracture for bazedoxifene (BZA) versus placebo but remained generally constant for raloxifene (RLX). INTRODUCTION: To determine whether the FRAX® predicts osteoporosis treatment efficacy, we evaluated reductions in fracture incidence associated with BZA and RLX according to baseline fracture risk determined by FRAX® using data from a phase 3 osteoporosis treatment study. METHODS: Hazard ratios (HRs) for effects of BZA and RLX versus placebo on incidence of vertebral, nonvertebral, and all clinical fractures were calculated using a Cox regression model. Cox regression analyses were performed in subgroups at or above 10-year fracture probability thresholds determined by FRAX®. RESULTS: HRs for the risk of vertebral, nonvertebral, and all clinical fractures versus placebo decreased with increasing 10-year fracture probability for BZA, while those for RLX remained stable. In all 10-year fracture probability subgroups, all BZA doses significantly reduced vertebral fracture risk versus placebo (HR = 0.22-0.66). BZA at 20, 40, and 20/40 mg significantly reduced risk of nonvertebral fractures (HR = 0.45, 0.44, and 0.45, respectively) and all clinical fractures (HR = 0.38, 0.41, and 0.40, respectively) for ≥20.0 % fracture probability. Vertebral fracture risk reductions for RLX 60 mg versus placebo were significant in subgroups at lower fracture probabilities (≥2.5- ≥ 10.0 %), but not higher (≥12.5 %), and in no subgroups for nonvertebral or all clinical fractures. CONCLUSION: The antifracture efficacy of BZA increased with increasing baseline FRAX® score, but there was no clear relationship between RLX and baseline FRAX®. These findings provide independent confirmation of current literature, suggesting that the relationship between FRAX® and treatment efficacy varies for different agents.

17 Clinical Trial Arzoxifene versus raloxifene: effect on bone and safety parameters in postmenopausal women with osteoporosis. 2012

Kendler, D L / Palacios, S / Cox, D A / Stock, J / Alam, J / Dowsett, S A / Zanchetta, J. ·University of British Columbia, 600-1285 West Broadway, Vancouver, BC, Canada V6H 3X8. kendler@ca.inter.net ·Osteoporos Int · Pubmed #21374068.

ABSTRACT: INTRODUCTION: To assess the effect of arzoxifene versus raloxifene on change in lumbar spine (LS) bone mineral density (BMD) in postmenopausal women with osteoporosis. METHODS: In this 12-month study (NEXT trial), participants were randomly assigned to arzoxifene 20 mg/day (N = 158) or raloxifene 60 mg/day (N = 162). All received daily calcium and vitamin D. Change in LS BMD was assessed by DXA. Secondary objectives included assessment of femoral neck (FN) and total hip BMD, serum bone turnover markers, and safety. RESULTS: Treatment groups were similar at baseline (mean age 63 years, mean LS BMD T-score -2.9). At 12 months, the increase in LS BMD with arzoxifene was greater than with raloxifene (+2.75% vs. +1.66%), as was FN and total hip BMD (P < 0.05). For LS and FN, this effect was also evident at 6 months. Arzoxifene reduced bone turnover to a greater extent than raloxifene at 3, 6, and 12 months (P < 0.05). The proportion of women reporting ≥ 1 adverse event did not differ between treatment groups, nor did vaginal bleeding. No cases of endometrial polyps, hyperplasia, or cancer were reported. Nasopharyngitis and bronchitis were reported more frequently with arzoxifene versus raloxifene (10.1% vs. 2.5%, and 5.1% vs. 0%, respectively) and new/worsening hot flushes were reported less frequently with arzoxifene (7.0% vs. 16.7%) (P < 0.05). CONCLUSIONS: Arzoxifene increased BMD and suppressed bone turnover to a greater extent than raloxifene and resulted in a lower incidence of new/worsening hot flushes. Based on subsequent findings from a fracture outcome study, this difference did not translate into improved fracture efficacy.

18 Clinical Trial Safety and tolerability of bazedoxifene in postmenopausal women with osteoporosis: results of a 5-year, randomized, placebo-controlled phase 3 trial. 2011

de Villiers, T J / Chines, A A / Palacios, S / Lips, P / Sawicki, A Z / Levine, A B / Codreanu, C / Kelepouris, N / Brown, J P. ·Panorama MediClinic and University of Stellenbosch, Room 118 Parow 7500, Cape Town, South Africa. Tobie@iafrica.com ·Osteoporos Int · Pubmed #20535606.

ABSTRACT: INTRODUCTION: We report safety and tolerability findings from a 5-year randomized, double-blind, phase 3 study of bazedoxifene in postmenopausal women with osteoporosis. METHODS: In the core study, healthy postmenopausal women with osteoporosis (N=7,492; mean age, 66.4 years) were randomized to daily doses of bazedoxifene 20 or 40 mg, raloxifene 60 mg, or placebo for 3 years. During the 2-year study extension, the raloxifene 60-mg treatment arm was discontinued after the 3-year database was finalized, and subjects receiving bazedoxifene 40 mg were transitioned in a blinded manner to bazedoxifene 20 mg (bazedoxifene 40-/20-mg group) after 4 years. Safety and tolerability data are reported for subjects in the bazedoxifene 20- and 40-/20-mg and placebo groups; efficacy findings are reported elsewhere. RESULTS: A total of 3,146 subjects in the bazedoxifene 20- and 40-mg and placebo groups were enrolled in the extension study (years 4 and 5). Overall, the 5-year incidence of adverse events (AEs), serious AEs, and discontinuations due to AEs were similar among groups. The incidence of hot flushes and leg cramps was higher with bazedoxifene compared with placebo. Venous thromboembolic events, primarily deep vein thrombosis, were more frequently reported in the bazedoxifene groups compared with the placebo group. Reports of cardiac disorders and cerebrovascular events were few and evenly distributed among groups. Bazedoxifene showed a neutral effect on the breast and endometrium. CONCLUSION: Bazedoxifene was associated with an overall favorable safety and tolerability profile in postmenopausal women with osteoporosis over 5 years of therapy, consistent with findings at 3 years.

19 Clinical Trial Safety of bazedoxifene in a randomized, double-blind, placebo- and active-controlled Phase 3 study of postmenopausal women with osteoporosis. 2010

Christiansen, Claus / Chesnut, Charles H / Adachi, Jonathan D / Brown, Jacques P / Fernandes, César E / Kung, Annie Wc / Palacios, Santiago / Levine, Amy B / Chines, Arkadi A / Constantine, Ginger D. ·Center for Clinical and Basic Research, Ballerup, Denmark. cc@Nordicbioscience.com ·BMC Musculoskelet Disord · Pubmed #20569451.

ABSTRACT: BACKGROUND: We report the safety findings from a 3-year phase 3 study (NCT00205777) of bazedoxifene, a novel selective estrogen receptor modulator under development for the prevention and treatment of postmenopausal osteoporosis. METHODS: Healthy postmenopausal osteoporotic women (N = 7,492; mean age, 66.4 years) were randomized to daily doses of bazedoxifene 20 or 40 mg, raloxifene 60 mg, or placebo for 3 years. Safety and tolerability were assessed by adverse event (AE) reporting and routine physical, gynecologic, and breast examination. RESULTS: Overall, the incidence of AEs, serious AEs, and discontinuations due to AEs in the bazedoxifene groups was not different from that seen in the placebo group. The incidence of hot flushes and leg cramps was higher with bazedoxifene or raloxifene compared with placebo. The rates of cardiac disorders and cerebrovascular events were low and evenly distributed among groups. Venous thromboembolic events, primarily deep vein thromboses, were more frequently reported in the active treatment groups compared with the placebo group; rates were similar with bazedoxifene and raloxifene. Bazedoxifene showed a neutral effect on the breast and an excellent endometrial safety profile. The incidence of fibrocystic breast disease was lower with bazedoxifene 20 and 40 mg versus raloxifene or placebo. Reductions in total and low-density lipoprotein levels and increases in high-density lipoprotein levels were seen with bazedoxifene versus placebo; similar results were seen with raloxifene. Triglyceride levels were similar among groups. CONCLUSION: Bazedoxifene showed a favorable safety and tolerability profile in women with postmenopausal osteoporosis. TRIAL REGISTRATION NUMBER: NCT00205777; Trial registration date: September 16, 2005.

20 Article Efficacy and safety of ossein-hydroxyapatite complex versus calcium carbonate to prevent bone loss. 2020

Castelo-Branco, C / Cancelo Hidalgo, M J / Palacios, S / Ciria-Recasens, M / Fernández-Pareja, A / Carbonell-Abella, C / Manasanch, J / Haya-Palazuelos, J. ·Clinic Institute of Gynecology, Obstetrics and Neonatology, Hospital Clinic-Institut d'Investigacions Biomédiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain. · Obstetrics and Gynaecology Department, Hospital Universitario de Guadalajara, Guadalajara, Spain. · Universidad de Alcalá, Alcalá de Henares (Madrid), Spain. · Director of Palacios Institute of Woman's Health, Madrid, Spain. · Rheumatology Department, Parc de Salud Mar, Hospital Universitari del Mar, Barcelona, Spain. · CMSc, Departamento I de Prevención y Promoción de la Salud Hortaleza, Madrid, Spain. · Primary Care Health Centre Vía Roma, Universitat de Barcelona, Barcelona, Spain. · Pierre Fabre Ibérica, Dep. Médico-Científico, Barcelona, Spain. · Obstetrics and Gynaecology Department, Hospital General Universitario de Ciudad Real, Ciudad Real, Spain. ·Climacteric · Pubmed #31747785.


21 Article Bone mineral density gains with a second 12-month course of romosozumab therapy following placebo or denosumab. 2019

Kendler, D L / Bone, H G / Massari, F / Gielen, E / Palacios, S / Maddox, J / Yan, C / Yue, S / Dinavahi, R V / Libanati, C / Grauer, A. ·Department of Medicine, University of British Columbia, 150-943 West Broadway, Vancouver, BC, V5Z 4E1, Canada. davidkendler@gmail.com. · Michigan Bone and Mineral Clinic, Detroit, MI, USA. · Instituto de Investigaciones Metabólicas, Buenos Aires, Argentina. · UZ Leuven, Leuven, Belgium. · Instituto Palacios, Madrid, Spain. · Amgen Inc., Thousand Oaks, CA, USA. · Amgen Ltd., Cambridge, UK. · Cambridge Statistics Ltd, Cambridge, UK. · Atara Biotherapeutics, Westlake Village, CA, USA. · UCB Pharma, Brussels, Belgium. · Corcept Therapeutics, Menlo Park, CA, USA. ·Osteoporos Int · Pubmed #31628490.

ABSTRACT: Romosozumab is a therapy that stimulates bone formation and reduces bone resorption. In this study of postmenopausal women with low BMD, a second course of romosozumab following a period off treatment or on denosumab increased or maintained BMD, respectively, and was well tolerated, providing insight into treatment sequence options. INTRODUCTION: In patients with high fracture risk, therapies that stimulate bone formation provide rapid BMD gains; currently available agents, parathyroid hormone receptor agonists, are limited to a 2-year lifetime exposure and generally used for a single treatment course. However, for long-term osteoporosis management, a second treatment course may be appropriate. Romosozumab, a therapy with the dual effect of increasing bone formation and decreasing bone resorption, reduces fracture risk within 12 months. Here, we report efficacy and safety of a second romosozumab course. METHODS: In this phase 2, dose-finding study, postmenopausal women with low bone mass (T-score ≤ - 2.0 and ≥ - 3.5) received romosozumab or placebo (month 0-24) followed by placebo or denosumab (month 24-36); participants then received a year of romosozumab (month 36-48). RESULTS: Of 167 participants who entered the month 36-48 period, 35 had been initially randomized to romosozumab 210 mg monthly. In participants who received romosozumab 210 mg monthly followed by placebo, a second romosozumab course (n = 19) increased BMD by amounts similar to their initial treatment (month 0-12) at the lumbar spine (12.4%; 12.0%, respectively) and total hip (6.0%; 5.5%, respectively). Following denosumab, a second romosozumab course (n = 16) increased BMD at the lumbar spine (2.3%) and maintained BMD at the total hip. Safety profiles were similar between first and second romosozumab courses. CONCLUSIONS: After 12 months off-treatment, a second romosozumab course again led to rapid and large BMD gains. Following denosumab, BMD gains with romosozumab were smaller than with initial treatment. No new safety findings were observed during the second course.

22 Article Effects of Daily Intake of Calcium and Vitamin D-Enriched Milk in Healthy Postmenopausal Women: A Randomized, Controlled, Double-Blind Nutritional Study. 2018

Reyes-Garcia, Rebeca / Mendoza, Nicolas / Palacios, Santiago / Salas, Nancy / Quesada-Charneco, Miguel / Garcia-Martin, Antonia / Fonolla, Juristo / Lara-Villoslada, Federico / Muñoz-Torres, Manuel. ·1 Bone Metabolic Unit (CIBERFES), UGC Endocrinología y Nutrición, Hospital Universitario San Cecilio, Instituto de Investigación Biosanitario de Granada (Ibs. Granada) , Granada, Spain . · 2 Unidad de Endocrinología y Nutrición, Complejo Hospitalario Torrecardenas , Almeria, Spain . · 3 Department of Obstetrics and Gynecology, University of Granada , Granada, Spain . · 4 Palacios Institute of Women's Health , Madrid, Spain . · 5 Nutrition Department, Biosearch S.A., Granada, Spain . · 6 Research and Development Department, Lactalis Puleva, Granada, Spain . ·J Womens Health (Larchmt) · Pubmed #29676968.

ABSTRACT: OBJECTIVE: To determine the effect of the daily intake of calcium and vitamin D-enriched milk (with or without fructooligosaccharides [FOS]) on vitamin D, bone metabolism, and cardiovascular risk factors. MATERIALS AND METHODS: Two-year randomized controlled study, including 500 healthy postmenopausal women, assigned to 500 mL/day of skimmed milk to one of three groups: Low-dose (L): (120 mg/100 mL calcium, vitamin D RESULTS: After 24 months, vitamin D concentrations did not change in the control group, but increased in group A and group B, p < 0.001. We observed an increase in femoral neck BMD and an improvement in fasting plasma glucose, HbA CONCLUSIONS: Daily intake of milk enriched with calcium and vitamin D in postmenopausal healthy women induces a significant improvement in vitamin D status, a significant increase in BMD at femoral neck, and also favorable effects on glucose and lipid profile.

23 Article Effect of conjugated estrogens/bazedoxifene on postmenopausal bone loss: pooled analysis of two randomized trials. 2016

Gallagher, J Christopher / Palacios, Santiago / Ryan, Kelly A / Yu, Ching-Ray / Pan, Kaijie / Kendler, David L / Mirkin, Sebastian / Komm, Barry S. ·1Creighton University School of Medicine, Omaha, NE 2Instituto Palacios, Madrid, Spain 3Pfizer Inc, Collegeville, PA 4Pfizer Inc, New York, NY 5University of British Columbia, Vancouver, BC, Canada. ·Menopause · Pubmed #27404034.

ABSTRACT: OBJECTIVE: Conjugated estrogens/bazedoxifene reduces vasomotor symptoms and prevents postmenopausal bone loss without stimulating the breast and endometrium. We analyzed changes in bone mineral density (BMD) and bone markers using pooled data from two phase-3 trials. METHODS: Selective Estrogens, Menopause, and Response to Therapy (SMART)-1 and SMART-5 were randomized, double-blind, placebo- and active-controlled studies conducted in postmenopausal nonhysterectomized women. BMD and turnover marker data were pooled for women given conjugated estrogens (0.45 or 0.625 mg) plus bazedoxifene 20 mg or placebo over 12 months. Sensitivity analyses were conducted using baseline Fracture Risk Assessment Tool score, age, years since menopause, body mass index, race, and geographic region. RESULTS: There were 1,172 women, mean age 54.9 years, mean 6.21 years since menopause, mean lumbar spine, and total hip T scores -1.05 and -0.58; 58.8% had a Fracture Risk Assessment Tool score less than 5% indicating low fracture risk. At 12 months, adjusted differences (vs placebo) in BMD change in the groups taking conjugated estrogens 0.45 or 0.625 mg plus bazedoxifene 20 mg were 2.3% and 2.4% for lumbar spine, 1.4% and 1.5% for total hip, and 1.1% and 1.5% for femoral neck (all P < 0.001 vs placebo). These increases were unrelated to baseline Fracture Risk Assessment Tool score, age, years since menopause, body mass index, or geographic region. Both doses reduced bone turnover markers (P < 0.001). CONCLUSIONS: Conjugated estrogens/bazedoxifene significantly improved BMD and turnover in a large population of younger postmenopausal women at low fracture risk and is a promising therapy for preventing postmenopausal bone loss.

24 Article Evaluation of efficacy and safety of conjugated estrogens/bazedoxifene in a Latin American population. 2016

Palacios, S / Arias, L / Lavenberg, J / Pan, K / Mirkin, S / Komm, B S. ·a Palacios Institute of Women's Health , Madrid , Spain ; · b Pfizer Inc, Bosques de las Lomas , Mexico ; · c Pfizer Inc, Collegeville , PA , USA. ·Climacteric · Pubmed #26940720.

ABSTRACT: Introduction Conjugated estrogens/bazedoxifene (CE/BZA) relieves menopausal symptoms and increases bone mineral density (BMD). Objective To evaluate CE/BZA in a Latin American subpopulation from randomized, double-blind, phase-3, multinational trials. Methods Safety data were pooled from three trials from non-hysterectomized postmenopausal Latin American women assigned to CE 0.45 mg/BZA 20 mg (n = 227), CE 0.625 mg/BZA 20 mg (n = 222), or placebo (n = 193). Efficacy outcomes from one study included changes in hot flush frequency at week 12 in women with at least seven moderate/severe hot flushes/day or 50/week at baseline (n = 39), and from baseline to month 12 for BMD (n = 381) and genitourinary syndrome of menopause (GSM) (women with baseline GSM; n = 189). Results At week 12, women taking CE/BZA had four to five fewer moderate/severe hot flushes/day vs. placebo. At month 12, percentage changes in BMD with CE 0.45 mg/BZA 20 mg, CE 0.625 mg/BZA 20 mg, and placebo were 1.2%, 1.6%, and -1.1% for lumbar spine and 1.1%, 1.2%, and -0.3% for total hip. GSM improved with treatment (percentage superficial cells: 4.5, 7.4, vs. 2.0; percentage parabasal cells: -9.3, -27.8 vs. 2.8). There were no new/unexpected safety trends. Conclusion CE/BZA improved vasomotor symptoms, GSM, and BMD in Latin American women, with efficacy/safety similar to the global population.

25 Article Treatment with denosumab reduces secondary fracture risk in women with postmenopausal osteoporosis. 2015

Palacios, S / Kalouche-Khalil, L / Rizzoli, R / Zapalowski, C / Resch, H / Adachi, J D / Gallagher, J C / Feldman, R G / Kendler, D L / Wang, A / Wagman, R B / Adami, S. ·a * Institute of Women's Health , Madrid , Spain. · b Amgen (Europe) GmbH , Zug , Switzerland. · c Geneva University Hospitals, Faculty of Medicine , Geneva , Switzerland. · d Amgen Inc. , Thousand Oaks , CA , USA. · e St Vincent Hospital , Vienna , Austria. · f St Joseph's Healthcare, McMaster University , Hamilton , ON , Canada. · g Creighton University Medical School , Omaha , NE , USA. · h Senior Clinical Trials Inc. , Laguna Hills , CA , USA. · i University of British Columbia , Vancouver , BC , Canada. · j University of Verona , Verona , Italy. ·Climacteric · Pubmed #26029985.

ABSTRACT: OBJECTIVES: A history of prior fracture is one of the strongest predictors of a future fragility fracture. In FREEDOM, denosumab significantly reduced the risk of new vertebral, non-vertebral, and hip fractures. We carried out a post-hoc analysis of FREEDOM to characterize the efficacy of denosumab in preventing secondary fragility fractures in subjects with a prior fracture. METHODS: A total of 7808 women aged 60-90 years with a bone mineral density T-score of less than - 2.5 but not less than - 4.0 at either the lumbar spine or total hip were randomized to subcutaneous denosumab 60 mg or placebo every 6 months for 36 months. The anti-fracture efficacy of denosumab was analyzed by prior fracture status, to assess secondary fragility fracture, and by subject age, prior fracture site and history of prior osteoporosis medication use. RESULTS: A prior fragility fracture was reported for 45% of the overall study population. Compared with placebo, denosumab significantly reduced the risk of a secondary fragility fracture by 39% (incidence, 17.3% vs. 10.5%; p < 0.0001). Similar results were observed regardless of age or prior fracture site. In the overall population, denosumab significantly reduced the risk of a fragility fracture by 40% (13.3% vs. 8.0%; p < 0.0001), with similar results observed regardless of history of prior osteoporotic medication use. CONCLUSIONS: Denosumab reduced the risk of fragility fractures to a similar degree in all risk subgroups examined, including those with prior fragility fractures. Identifying and treating high-risk individuals could help to close the current care gap in secondary fracture prevention.