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Osteoporosis: HELP
Articles by Steven R. Cummings
Based on 78 articles published since 2008

Between 2008 and 2019, S. Cummings wrote the following 78 articles about Osteoporosis.
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4
26 Article Continuing bisphosphonate treatment for osteoporosis--for whom and for how long? 2012

Black, Dennis M / Bauer, Douglas C / Schwartz, Ann V / Cummings, Steven R / Rosen, Clifford J. ·Department of Epidemiology and Biostatistics, University of California, San Francisco, USA. ·N Engl J Med · Pubmed #22571169.

ABSTRACT: -- No abstract --

27 Article Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture. 2012

Estrada, Karol / Styrkarsdottir, Unnur / Evangelou, Evangelos / Hsu, Yi-Hsiang / Duncan, Emma L / Ntzani, Evangelia E / Oei, Ling / Albagha, Omar M E / Amin, Najaf / Kemp, John P / Koller, Daniel L / Li, Guo / Liu, Ching-Ti / Minster, Ryan L / Moayyeri, Alireza / Vandenput, Liesbeth / Willner, Dana / Xiao, Su-Mei / Yerges-Armstrong, Laura M / Zheng, Hou-Feng / Alonso, Nerea / Eriksson, Joel / Kammerer, Candace M / Kaptoge, Stephen K / Leo, Paul J / Thorleifsson, Gudmar / Wilson, Scott G / Wilson, James F / Aalto, Ville / Alen, Markku / Aragaki, Aaron K / Aspelund, Thor / Center, Jacqueline R / Dailiana, Zoe / Duggan, David J / Garcia, Melissa / Garcia-Giralt, Natàlia / Giroux, Sylvie / Hallmans, Göran / Hocking, Lynne J / Husted, Lise Bjerre / Jameson, Karen A / Khusainova, Rita / Kim, Ghi Su / Kooperberg, Charles / Koromila, Theodora / Kruk, Marcin / Laaksonen, Marika / Lacroix, Andrea Z / Lee, Seung Hun / Leung, Ping C / Lewis, Joshua R / Masi, Laura / Mencej-Bedrac, Simona / Nguyen, Tuan V / Nogues, Xavier / Patel, Millan S / Prezelj, Janez / Rose, Lynda M / Scollen, Serena / Siggeirsdottir, Kristin / Smith, Albert V / Svensson, Olle / Trompet, Stella / Trummer, Olivia / van Schoor, Natasja M / Woo, Jean / Zhu, Kun / Balcells, Susana / Brandi, Maria Luisa / Buckley, Brendan M / Cheng, Sulin / Christiansen, Claus / Cooper, Cyrus / Dedoussis, George / Ford, Ian / Frost, Morten / Goltzman, David / González-Macías, Jesús / Kähönen, Mika / Karlsson, Magnus / Khusnutdinova, Elza / Koh, Jung-Min / Kollia, Panagoula / Langdahl, Bente Lomholt / Leslie, William D / Lips, Paul / Ljunggren, Östen / Lorenc, Roman S / Marc, Janja / Mellström, Dan / Obermayer-Pietsch, Barbara / Olmos, José M / Pettersson-Kymmer, Ulrika / Reid, David M / Riancho, José A / Ridker, Paul M / Rousseau, François / Slagboom, P Eline / Tang, Nelson L S / Urreizti, Roser / Van Hul, Wim / Viikari, Jorma / Zarrabeitia, María T / Aulchenko, Yurii S / Castano-Betancourt, Martha / Grundberg, Elin / Herrera, Lizbeth / Ingvarsson, Thorvaldur / Johannsdottir, Hrefna / Kwan, Tony / Li, Rui / Luben, Robert / Medina-Gómez, Carolina / Palsson, Stefan Th / Reppe, Sjur / Rotter, Jerome I / Sigurdsson, Gunnar / van Meurs, Joyce B J / Verlaan, Dominique / Williams, Frances M K / Wood, Andrew R / Zhou, Yanhua / Gautvik, Kaare M / Pastinen, Tomi / Raychaudhuri, Soumya / Cauley, Jane A / Chasman, Daniel I / Clark, Graeme R / Cummings, Steven R / Danoy, Patrick / Dennison, Elaine M / Eastell, Richard / Eisman, John A / Gudnason, Vilmundur / Hofman, Albert / Jackson, Rebecca D / Jones, Graeme / Jukema, J Wouter / Khaw, Kay-Tee / Lehtimäki, Terho / Liu, Yongmei / Lorentzon, Mattias / McCloskey, Eugene / Mitchell, Braxton D / Nandakumar, Kannabiran / Nicholson, Geoffrey C / Oostra, Ben A / Peacock, Munro / Pols, Huibert A P / Prince, Richard L / Raitakari, Olli / Reid, Ian R / Robbins, John / Sambrook, Philip N / Sham, Pak Chung / Shuldiner, Alan R / Tylavsky, Frances A / van Duijn, Cornelia M / Wareham, Nick J / Cupples, L Adrienne / Econs, Michael J / Evans, David M / Harris, Tamara B / Kung, Annie Wai Chee / Psaty, Bruce M / Reeve, Jonathan / Spector, Timothy D / Streeten, Elizabeth A / Zillikens, M Carola / Thorsteinsdottir, Unnur / Ohlsson, Claes / Karasik, David / Richards, J Brent / Brown, Matthew A / Stefansson, Kari / Uitterlinden, André G / Ralston, Stuart H / Ioannidis, John P A / Kiel, Douglas P / Rivadeneira, Fernando. ·Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands. ·Nat Genet · Pubmed #22504420.

ABSTRACT: Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for replication in 50,933 independent subjects and for association with risk of low-trauma fracture in 31,016 individuals with a history of fracture (cases) and 102,444 controls. We identified 56 loci (32 new) associated with BMD at genome-wide significance (P < 5 × 10(-8)). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal stem cell differentiation, endochondral ossification and Wnt signaling pathways. However, we also discovered loci that were localized to genes not known to have a role in bone biology. Fourteen BMD-associated loci were also associated with fracture risk (P < 5 × 10(-4), Bonferroni corrected), of which six reached P < 5 × 10(-8), including at 18p11.21 (FAM210A), 7q21.3 (SLC25A13), 11q13.2 (LRP5), 4q22.1 (MEPE), 2p16.2 (SPTBN1) and 10q21.1 (DKK1). These findings shed light on the genetic architecture and pathophysiological mechanisms underlying BMD variation and fracture susceptibility.

28 Article Breast cancer incidence in postmenopausal women with osteoporosis or low bone mass using arzoxifene. 2012

Powles, Trevor J / Diem, Susan J / Fabian, Carol J / Neven, Patrick / Wickerham, D Lawrence / Cox, David A / Muram, David / Agnusdei, Donato / Dowsett, Sherie A / Amewou-Atisso, Messan / Cummings, Steven R. ·Breast Unit, The Cancer Centre London at Parkside, Wimbledon, London, UK. trevorpowles@aol.com ·Breast Cancer Res Treat · Pubmed #22484799.

ABSTRACT: The Generations trial, a multicenter, placebo-controlled, double-blind trial, compared arzoxifene 20 mg/day and placebo in 9,354 postmenopausal women with osteoporosis (N=5,252) or low bone mass (N=4,102). Primary outcomes were vertebral fracture in the osteoporotic population and invasive breast cancer in all study participants. Here, we report the detailed breast cancer findings from the trial. Breast cancers were detected by annual mammograms and clinical examination. After 48 months follow-up, breast cancer incidence was compared between treatment groups by estrogen receptor (ER) and progesterone receptor (PR) status and baseline risk factors. Baseline breast cancer risk factors, including age, estimated Gail risk, and bone mineral density, were well balanced between treatment groups. A total of 75 breast cancers occurred 53 in the placebo group and 22 in the arzoxifene group (HR 0.41, 95% CI 0.25-0.68, P<0.001). There were 62 invasive breast cancers, 39 identified as invasive ER-positive (placebo 30, arzoxifene 9; HR 0.30, 95% CI 0.14-0.63, P=0.001) and 30 identified as invasive PR-positive (placebo 23, arzoxifene 7; HR 0.30, 95% CI 0.13-0.71, P=0.003). Breast cancer risk reduction with arzoxifene was similar between Gail risk groups (P interaction=0.31) and between low bone mass and osteoporosis groups (P interaction=0.35). Although generally well tolerated, there was a significant increase in venous thromboembolism, vasomotor symptoms, muscle cramps, and some gynecological events with arzoxifene. These findings demonstrate that in this study arzoxifene reduced the risk of ER-positive breast cancer in this population of postmenopausal women with low bone mass or osteoporosis, an effect similar to that seen with other SERMs.

29 Article Effects of 3 years of lasofoxifene treatment on bone turnover markers in women with postmenopausal osteoporosis. 2012

Eastell, Richard / Reid, David M / Vukicevic, Slobodan / Ensrud, Kristine E / LaCroix, Andrea Z / Thompson, John R / Thompson, David D / Cummings, Steven R. ·Centre for Biomedical Research, Northern General Hospital, Herries Road, Sheffield, South Yorkshire, S5 7AU, UK. r.eastell@sheffield.ac.uk ·Bone · Pubmed #22348983.

ABSTRACT: The aims of this study were to describe the changes in bone turnover markers (BTMs) in response to lasofoxifene therapy; to describe the changes in BTMs in the individual; and to examine the relationships between BTM levels on treatment and treatment outcomes. Women (n=1126) aged 59-80years with femoral neck or spine bone mineral density T-scores ≤-2.5 were randomized to lasofoxifene 0.25mg/d, 0.5mg/d, or placebo for 5years. We measured serum C-telopeptide of type I collagen (CTX) and serum procollagen I N-propeptide (PINP), osteocalcin, and bone alkaline phosphatase (ALP) at baseline and at 1, 3, 6, 12, 24, and 36months. Lasofoxifene therapy resulted in a decrease in the concentrations of bone resorption and bone formation markers compared with placebo; the decrease was maximal between 6 and 24months. The effect of lasofoxifene 0.5mg/d was similar to that of lasofoxifene 0.25mg/d. The decrease in bone ALP was less than the decreases in CTX, osteocalcin, and PINP. Lasofoxifene therapy 0.5mg/d resulted in BTM-defined response rates for CTX (decrease in concentration from baseline >60%), PINP (>50%), and bone ALP (>30%) of 35%, 45%, and 43% of women at month 12, respectively, compared with placebo responses of 4%, 4%, and 7%. In contrast, the increase in BMD took longer (50% responded after 36months of lasofoxifene 0.5mg/d) and was not as specific (15% of placebo group responded). Bone density change was weakly inversely correlated with change in the concentrations of BTMs. BTMs may prove useful in the monitoring of the response to lasofoxifene treatment for women with postmenopausal osteoporosis early in the course of treatment.

30 Article The effect of 3 versus 6 years of zoledronic acid treatment of osteoporosis: a randomized extension to the HORIZON-Pivotal Fracture Trial (PFT). 2012

Black, Dennis M / Reid, Ian R / Boonen, Steven / Bucci-Rechtweg, Christina / Cauley, Jane A / Cosman, Felicia / Cummings, Steven R / Hue, Trisha F / Lippuner, Kurt / Lakatos, Peter / Leung, Ping Chung / Man, Zulema / Martinez, Ruvie Lou Maria / Tan, Monique / Ruzycky, Mary Ellen / Su, Guoqin / Eastell, Richard. ·Department of Epidemiology and Biostastistics, University of California, San Francisco, CA 94107, USA. dblack@psg.ucsf.edu ·J Bone Miner Res · Pubmed #22161728.

ABSTRACT: Zoledronic acid 5 mg (ZOL) annually for 3 years reduces fracture risk in postmenopausal women with osteoporosis. To investigate long-term effects of ZOL on bone mineral density (BMD) and fracture risk, the Health Outcomes and Reduced Incidence with Zoledronic acid Once Yearly-Pivotal Fracture Trial (HORIZON-PFT) was extended to 6 years. In this international, multicenter, double-blind, placebo-controlled extension trial, 1233 postmenopausal women who received ZOL for 3 years in the core study were randomized to 3 additional years of ZOL (Z6, n = 616) or placebo (Z3P3, n = 617). The primary endpoint was femoral neck (FN) BMD percentage change from year 3 to 6 in the intent-to-treat (ITT) population. Secondary endpoints included other BMD sites, fractures, biochemical bone turnover markers, and safety. In years 3 to 6, FN-BMD remained constant in Z6 and dropped slightly in Z3P3 (between-treatment difference = 1.04%; 95% confidence interval 0.4 to 1.7; p = 0.0009) but remained above pretreatment levels. Other BMD sites showed similar differences. Biochemical markers remained constant in Z6 but rose slightly in Z3P3, remaining well below pretreatment levels in both. New morphometric vertebral fractures were lower in the Z6 (n = 14) versus Z3P3 (n = 30) group (odds ratio = 0.51; p = 0.035), whereas other fractures were not different. Significantly more Z6 patients had a transient increase in serum creatinine >0.5 mg/dL (0.65% versus 2.94% in Z3P3). Nonsignificant increases in Z6 of atrial fibrillation serious adverse events (2.0% versus 1.1% in Z3P3; p = 0.26) and stroke (3.1% versus 1.5% in Z3P3; p = 0.06) were seen. Postdose symptoms were similar in both groups. Reports of hypertension were significantly lower in Z6 versus Z3P3 (7.8% versus 15.1%, p < 0.001). Small differences in bone density and markers in those who continued versus those who stopped treatment suggest residual effects, and therefore, after 3 years of annual ZOL, many patients may discontinue therapy up to 3 years. However, vertebral fracture reductions suggest that those at high fracture risk, particularly vertebral fracture, may benefit by continued treatment.

31 Article Effect of denosumab treatment on the risk of fractures in subgroups of women with postmenopausal osteoporosis. 2012

McClung, Michael R / Boonen, Steven / Törring, Ove / Roux, Christian / Rizzoli, René / Bone, Henry G / Benhamou, Claude-Laurent / Lems, Willem F / Minisola, Salvatore / Halse, Johan / Hoeck, Hans C / Eastell, Richard / Wang, Andrea / Siddhanti, Suresh / Cummings, Steven R. ·Oregon Osteoporosis Center, Portland, OR 97213, USA. mmcclung@orost.com ·J Bone Miner Res · Pubmed #21976367.

ABSTRACT: Denosumab reduces the risk of new vertebral and nonvertebral fractures. Previous trials suggest that the efficacy of antiresorptives on fractures might differ by patients' characteristics, such as age, bone mineral density (BMD), and fracture history. In the FREEDOM study, 7808 women aged 60 to 90 years with osteoporosis were randomly assigned to receive subcutaneous injections of denosumab (60 mg) or placebo every 6 months for 3 years. New vertebral and nonvertebral fractures were radiologically confirmed. Subgroup analyses described in this article were prospectively planned before study unblinding to evaluate the effect of denosumab on new vertebral and nonvertebral fractures across various subgroups. Compared with placebo, denosumab decreased the risk of new vertebral fractures in the overall study population over 3 years. This effect did not significantly differ for any of the nine subgroups analyzed (p > 0.09 for all potential interactions). Denosumab also reduced all nonvertebral fractures by 20% in the full study cohort over 3 years. This risk reduction was statistically significant in women with a baseline femoral neck BMD T-score ≤ -2.5 but not in those with a T-score > -2.5; in those with a body mass index (BMI) < 25 kg/m(2) but not ≥ 25 kg/m(2); and in those without but not with a prevalent vertebral fracture. These differential treatment effects were not explained by differences in BMD responses to denosumab. Denosumab 60 mg administered every 6 months for 3 years in women with osteoporosis reduced the risk of new vertebral fractures to a similar degree in all subgroups. The effect of denosumab on nonvertebral fracture risk differed by femoral neck BMD, BMI, and prevalent vertebral fracture at baseline.

32 Article Risk factors for nonvertebral fracture in obese older women. 2011

Premaor, M O / Ensrud, K / Lui, L / Parker, R A / Cauley, J / Hillier, T A / Cummings, S / Compston, J E / Anonymous17990697. ·Department of Clinical Medicine, Federal University of Santa Maria, Santa Maria, Rio Grande do Sul 97105-900, Brazil. mopremaor@bol.com.br ·J Clin Endocrinol Metab · Pubmed #21677038.

ABSTRACT: CONTEXT: A high prevalence of obesity has recently been reported in postmenopausal women with low trauma fracture, suggesting that higher bone mineral density (BMD) in obese individuals may not be protective against fracture. OBJECTIVE: The aim of this study was to compare BMD and other risk factors for nonvertebral fracture in 1377 obese postmenopausal women. DESIGN: Characteristics of obese women with and without incident nonvertebral fracture were investigated among the prospective cohort in the Study of Osteoporotic Fractures. SETTING: The Study of Osteoporotic Fractures is a multicenter study of 9704 women (>99% Caucasian) aged 65 yr and over who were recruited between September 1986 and October 1988 from population-based listings at four U.S. clinical centers. MAIN OUTCOME MEASURE: The main outcome measure was nonvertebral fracture. RESULTS: BMD T-scores in the spine, femoral neck, and total hip were significantly lower in obese women who experienced fractures than in obese women without fracture: mean differences, -0.56 [95% confidence interval (CI) = -0.73 to -0.39], -0.46 (95% CI = -0.57 to -0.36), and -0.51 (95% CI = -0.62 to -0.39), respectively (P < 0.0001 for all). A previous history of fracture [odds ratio = 1.69 (95% CI = 1.33-2.14); P < 0.0001] and femoral neck BMD [1.62 (95% CI = 1.42-1.85) per sd decrease in BMD; P < 0.0001] were independently associated with incident nonvertebral fracture. CONCLUSIONS: Obese postmenopausal women who sustain nonvertebral fractures have significantly lower BMD on average than obese women without fracture and are more likely to have a past history of fracture. Fractures in obese postmenopausal women thus exhibit some characteristics of fragility fractures.

33 Article WHO absolute fracture risk models (FRAX): do clinical risk factors improve fracture prediction in older women without osteoporosis? 2011

Hillier, Teresa A / Cauley, Jane A / Rizzo, Joanne H / Pedula, Kathryn L / Ensrud, Kristine E / Bauer, Douglas C / Lui, Li-Yung / Vesco, Kimberly K / Black, Dennis M / Donaldson, Meghan G / Leblanc, Erin S / Cummings, Steven R. ·Center for Health Research, Kaiser Permanente Northwest/Hawaii, Portland, OR 97227, USA. teresa.hillier@kpchr.org ·J Bone Miner Res · Pubmed #21351144.

ABSTRACT: Bone mineral density (BMD) is a strong predictor of fracture, yet most fractures occur in women without osteoporosis by BMD criteria. To improve fracture risk prediction, the World Health Organization recently developed a country-specific fracture risk index of clinical risk factors (FRAX) that estimates 10-year probabilities of hip and major osteoporotic fracture. Within differing baseline BMD categories, we evaluated 6252 women aged 65 or older in the Study of Osteoporotic Fractures using FRAX 10-year probabilities of hip and major osteoporotic fracture (ie, hip, clinical spine, wrist, and humerus) compared with incidence of fractures over 10 years of follow-up. Overall ability of FRAX to predict fracture risk based on initial BMD T-score categories (normal, low bone mass, and osteoporosis) was evaluated with receiver-operating-characteristic (ROC) analyses using area under the curve (AUC). Over 10 years of follow-up, 368 women incurred a hip fracture, and 1011 a major osteoporotic fracture. Women with low bone mass represented the majority (n = 3791, 61%); they developed many hip (n = 176, 48%) and major osteoporotic fractures (n = 569, 56%). Among women with normal and low bone mass, FRAX (including BMD) was an overall better predictor of hip fracture risk (AUC = 0.78 and 0.70, respectively) than major osteoporotic fractures (AUC = 0.64 and 0.62). Simpler models (eg, age + prior fracture) had similar AUCs to FRAX, including among women for whom primary prevention is sought (no prior fracture or osteoporosis by BMD). The FRAX and simpler models predict 10-year risk of incident hip and major osteoporotic fractures in older US women with normal or low bone mass.

34 Article Raloxifene, a selective estrogen receptor modulator, is renoprotective: a post-hoc analysis. 2011

Melamed, Michal L / Blackwell, Terri / Neugarten, Joel / Arnsten, Julia H / Ensrud, Kristine E / Ishani, Areef / Cummings, Steven R / Silbiger, Sharon R. ·Department of Medicine, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, New York, USA. mmelamed@aecom.yu.edu ·Kidney Int · Pubmed #20927038.

ABSTRACT: Estrogens have a protective effect on kidney fibrosis in several animal models. Here, we tested the effect of raloxifene, an estrogen receptor modulator, on the change in serum creatinine or estimated glomerular filtration rate (eGFR) and incident kidney-related adverse events. We performed a post-hoc analysis of the multiple outcomes of raloxifene evaluation trial, a double-masked, placebo-controlled randomized clinical trial encompassing 7705 post-menopausal women (aged 31-80 years) with osteoporosis. Participants were randomized to either of two doses of raloxifene, 60 or 120 mg/day, or placebo. Serum creatinine was measured at a central laboratory at baseline and annually. Adverse events were assessed every 6 months and uniformly categorized. Compared with those in the placebo group, participants on raloxifene had a slower yearly rate of increase in creatinine (significant at the low dose) and a significantly slower yearly rate of decrease in eGFR for both doses over 3 years of follow-up. Raloxifene was associated with significantly fewer kidney-related adverse events compared with placebo. Thus, treatment with raloxifene was safe and renoprotective. Clinical trials of raloxifene in post-menopausal women with kidney disease designed to look at kidney outcomes are needed to confirm these findings.

35 Article Effects of denosumab on bone turnover markers in postmenopausal osteoporosis. 2011

Eastell, Richard / Christiansen, Claus / Grauer, Andreas / Kutilek, Stepan / Libanati, Cesar / McClung, Michael R / Reid, Ian R / Resch, Heinrich / Siris, Ethel / Uebelhart, Daniel / Wang, Andrea / Weryha, Georges / Cummings, Steve R. ·National Institute for Health Research Bone Biomedical Research Unit, University of Sheffield, Sheffield, United Kingdom. r.eastell@sheffield.ac.uk ·J Bone Miner Res · Pubmed #20839290.

ABSTRACT: Denosumab, a fully human monoclonal antibody to RANKL, decreases bone remodeling, increases bone density, and reduces fracture risk. This study evaluates the time course and determinants of bone turnover marker (BTM) response during denosumab treatment, the percentage of denosumab-treated women with BTMs below the premenopausal reference interval, and the correlations between changes in BTMs and bone mineral density (BMD). The BTM substudy of the Fracture REduction Evaulation of Denosumab in Osteoporosis every 6 Months (FREEDOM) Trial included 160 women randomized to subcutaneous denosumab (60 mg) or placebo injections every 6 months for 3 years. Biochemical markers of bone resorption (serum C-telopeptide of type I collagen [CTX] and tartrate-resistant acid phosphatise [TRACP-5b]) and bone formation (serum procollagen type I N-terminal propeptide [PINP] and bone alkaline phosphatase [BALP]) were measured at baseline and at 1, 6, 12, 24, and 36 months. Decreases in CTX were more rapid and greater than decreases in PINP and BALP. One month after injection, CTX levels in all denosumab-treated subjects decreased to levels below the premenopausal reference interval. CTX values at the end of the dosing period were influenced by baseline CTX values and the dosing interval. The percentage of subjects with CTX below the premenopausal reference interval before each subsequent injection decreased from 79% to 51% during the study. CTX and PINP remained below the premenopausal reference interval at all time points in 46% and 31% denosumab-treated subjects, respectively. With denosumab, but not placebo, there were significant correlations between CTX reduction and BMD increase (r = -0.24 to -0.44). The BTM response pattern with denosumab is unique and should be appreciated by physicians to monitor this treatment effectively.

36 Article Postmenopausal Evaluation and Risk Reduction With Lasofoxifene (PEARL) trial: 5-year gynecological outcomes. 2011

Goldstein, Steven R / Neven, Patrick / Cummings, Steven / Colgan, Terence / Runowicz, Carolyn D / Krpan, Dalibor / Proulx, James / Johnson, Margot / Thompson, David / Thompson, John / Sriram, Usha. ·New York University School of Medicine, New York, NY 10016, USA. steven.goldstein@nyumc.org ·Menopause · Pubmed #20689465.

ABSTRACT: OBJECTIVE: The aim of this study was to establish the gynecological effects of 5 years of treatment with lasofoxifene versus placebo in postmenopausal osteoporotic women. METHODS: A total of 8,556 women aged 59 to 80 years with femoral neck or spine bone mineral density T scores of -2.5 or lower were randomized to receive lasofoxifene 0.25 mg/day, or lasofoxifene 0.5 mg/day, or placebo, for 5 years. RESULTS: Endometrial cancer was confirmed for two women in each lasofoxifene group and for three women in the placebo group. Endometrial hyperplasia occurred in three, two, and zero women in the lasofoxifene 0.25 mg/day, lasofoxifene 0.5 mg/day, and placebo groups, respectively. Vaginal bleeding occurred in 2.2% (P = 0.012 vs placebo), 2.6% (P = 0.001 vs placebo), and 1.3% of women treated with 0.25 mg/day lasofoxifene, 0.5 mg/day lasofoxifene, and placebo, respectively. Lasofoxifene treatment resulted in a small increase in endometrial thickness versus placebo (least-squares mean change from baseline 1.19 mm [P = 0.001], 1.43 mm [P < 0.001], and -0.72 mm for 0.25 mg/day lasofoxifene, 0.5 mg/day lasofoxifene, and placebo). Similar numbers of women required surgery for pelvic organ prolapse or urinary incontinence in the placebo and 0.5 mg/day lasofoxifene groups (1.2% vs 1.6%, P = 0.224; 0.25 mg/day group: 1.9%, P = 0.036). The absolute incidence rates of endometrial polyps were 8.8%, 5.5%, and 3.3% for lasofoxifene 0.25 mg/day (P = 0.003 vs placebo), lasofoxifene 0.5 mg/day (P = 0.163 vs placebo), and placebo groups, respectively. CONCLUSION: These findings indicate that 5 years of lasofoxifene treatment result in benign endometrial changes that do not increase the risk for endometrial cancer or hyperplasia in postmenopausal women.

37 Article Arzoxifene for prevention of fractures and invasive breast cancer in postmenopausal women. 2011

Cummings, Steven R / McClung, Michael / Reginster, Jean-Yves / Cox, David / Mitlak, Bruce / Stock, John / Amewou-Atisso, Messan / Powles, Trevor / Miller, Paul / Zanchetta, José / Christiansen, Claus. ·San Francisco Coordinating Center, California Pacific Medical Center Research Institute and the University of California, San Francisco, CA 94107, USA. scummings@sfcc-cpmc.net ·J Bone Miner Res · Pubmed #20658564.

ABSTRACT: Arzoxifene is a selective estrogen receptor modulator (SERM) that has been shown to be more potent in preclinical testing than currently available agents. Its effects on clinical outcomes are not known. In a randomized, blinded trial, women aged 60 to 85 years with osteoporosis, defined as a femoral neck or lumbar spine bone mineral density T-score of -2.5 or less or a vertebral fracture, and women with low bone mass, defined as a bone density T-score of -1.0 or less and above -2.5, were assigned to arzoxifene 20 mg or placebo daily. The primary endpoints were new vertebral fracture in those with osteoporosis and invasive breast cancer in the overall population. After 3 years, the cumulative incidence of vertebral fractures in patients with osteoporosis was 2.3% lower in the arzoxifene group than in the placebo group, a 41% relative risk reduction [95% confidence interval (CI) 0.45-0.77, p < .001]. In the overall population, the cumulative incidence of invasive breast cancer over 4 years was reduced by 1.3%, with a 56% relative reduction in risk (hazard ratio = 0.44, 95% CI 0.26-0.76, p < .001); there was no significant decrease in nonvertebral fracture risk. Arzoxifene increased the cumulative incidence of venous thromboembolic events by 0.7%, with a 2.3-fold relative increase (95% CI 1.5-3.7). Like other SERMs, arzoxifene decreased vertebral fractures and invasive breast cancer while the risk of venous thromboembolic events increased.

38 Article Serum calcium, phosphorus and cardiovascular events in post-menopausal women. 2011

Slinin, Yelena / Blackwell, Terri / Ishani, Areef / Cummings, Steven R / Ensrud, Kristine E / Anonymous5810651. ·Center for Chronic Disease Outcomes Research, VA Medical Center, Minneapolis, MN 55417, United States. slini001@umn.edu ·Int J Cardiol · Pubmed #20189664.

ABSTRACT: BACKGROUND: There is increasing evidence linking phosphorus and calcium levels to a higher risk of cardiovascular morbidity and mortality in the general population. METHODS: We performed a post hoc data analysis from the Multiple Outcomes of Raloxifene Evaluation (MORE) trial of raloxifene treatment in 7259 postmenopausal women with osteoporosis to test the hypothesis that higher baseline calcium and phosphorus levels are associated with a higher risk of incident cardiovascular events during 4years of follow-up. RESULTS: Baseline mean (SD) values were 2.3 (0.1)mmol/L for serum calcium, 1.2 (0.2)mmol/L for serum phosphorus. Adjusted for multiple covariates including 25(OH)D, parathyroid hormone, and phosphorus, adjusted hazard ratios (AHR) (95% confidence interval (CI)) per SD of calcium were: 1.17(1.01-1.35), p=0.03 for combined cardiovascular outcome, 1.22(0.99-1.49), p=0.06 for cerebrovascular events, 1.12(0.92-1.37), p=0.25 for coronary heart disease, and 1.18(0.94-1.48), p=0.16 for death. While there was some evidence that higher serum phosphorus levels were associated with higher rate of combined cardiovascular outcome (p=0.07) and cerebrovascular events (p=0.03) in pauci-variable analysis, these associations did not persist after adjustment for additional confounders. Adjusted for multiple covariates including 25(OH)D, parathyroid hormone, and calcium, AHR(95% CI) per SD of phosphorus were 0.88(0.77-1.01), p=0.07 for combined cardiovascular outcome, 0.86(0.70-1.06), p=0.15 for ceverbrovascular events, 0.92(0.76-1.10), p=0.35 for coronary heart disease, and 1.00(0.80-1.25) for death. CONCLUSION: We found an independent association between higher baseline serum calcium levels and higher rate of cardiovascular events. Our findings did not support an independent association between serum phosphorus levels and cardiovascular events.

39 Article Breast cancer incidence in the randomized PEARL trial of lasofoxifene in postmenopausal osteoporotic women. 2010

LaCroix, Andrea Z / Powles, Trevor / Osborne, C Kent / Wolter, Kevin / Thompson, John R / Thompson, David D / Allred, D Craig / Armstrong, Róisín / Cummings, Steve R / Eastell, Richard / Ensrud, Kristine E / Goss, Paul / Lee, Andrew / Neven, Patrick / Reid, David M / Curto, Madelyn / Vukicevic, Slobodan / Anonymous3160678. ·Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024, USA. alacroix@whi.org ·J Natl Cancer Inst · Pubmed #21051656.

ABSTRACT: BACKGROUND: Currently available selective estrogen receptor modulators reduce the risk of breast cancer, but they are not widely used. In the Postmenopausal Evaluation and Risk-Reduction with Lasofoxifene (PEARL) trial, lasofoxifene was shown to reduce the risk of estrogen receptor-positive (ER+) breast cancer, nonvertebral and vertebral fractures, coronary artery disease, and stroke, but the effects on total breast cancer (invasive and ductal carcinoma in situ, ER+ and estrogen receptor-negative [ER-]) and ER+ invasive breast cancer are unknown. METHODS: Postmenopausal women (n = 8556) aged 59-80 years with low bone density and normal mammograms were randomly assigned to two doses of lasofoxifene (0.25 and 0.5 mg) or placebo. The primary endpoints of the PEARL trial were incidence of ER+ breast cancer and nonvertebral fractures at 5 years. A nested case-control study of 49 incident breast cancer case patients and 156 unaffected control subjects from the PEARL trial was performed to evaluate treatment effects on risk of total and ER+ invasive breast cancer by baseline serum estradiol and sex hormone-binding globulin levels using logistic regression models. Cox proportional hazards models were used to evaluate risk of total breast cancer and ER+ invasive breast cancer using intention-to-treat analysis. All statistical tests were two-sided. RESULTS: Breast cancer was confirmed in 49 women. Compared with placebo, 0.5 mg of lasofoxifene statistically significantly reduced the risk of total breast cancer by 79% (hazard ratio = 0.21; 95% confidence interval [CI] = 0.08 to 0.55) and ER+ invasive breast cancer by 83% (hazard ratio = 0.17; 95% CI = 0.05 to 0.57). The effects of 0.5 mg of lasofoxifene on total breast cancer were similar regardless of Gail score, whereas the effects were markedly stronger for women with baseline estradiol levels greater than the median (odds ratio = 0.11; 95% CI = 0.02 to 0.51) vs those with levels less than the median (odds ratio = 0.78; 95% CI = 0.16 to 3.79; P(interaction) = .04). CONCLUSION: A 0.5-mg dose of lasofoxifene appears to reduce the risks of both total and ER+ invasive breast cancer in postmenopausal women with osteoporosis.

40 Article Lasofoxifene and cardiovascular events in postmenopausal women with osteoporosis: Five-year results from the Postmenopausal Evaluation and Risk Reduction with Lasofoxifene (PEARL) trial. 2010

Ensrud, Kristine / LaCroix, Andrea / Thompson, John R / Thompson, David D / Eastell, Richard / Reid, David M / Vukicevic, Slobodan / Cauley, Jane / Barrett-Connor, Elizabeth / Armstrong, Roisin / Welty, Francine / Cummings, Steven. ·VA Medical Center, Minneapolis, MN, USA. ensru001@umn.edu ·Circulation · Pubmed #20937977.

ABSTRACT: BACKGROUND: In the Postmenopausal Evaluation and Risk Reduction With Lasofoxifene (PEARL) trial, women assigned to lasofoxifene 0.5 mg/d had a lower risk of major coronary heart disease (CHD) events and stroke, whereas women assigned to lasofoxifene 0.25 mg/d had a lower risk of stroke. Both doses of lasofoxifene increased the risk of venous thromboembolic events. In this report, we provide comprehensive cardiovascular end-point data, including component events comprising the composite end point of major CHD events, and evaluate whether the effect of lasofoxifene 0.5 mg/d is consistent across different categories of CHD risk. METHODS AND RESULTS: In this study, 8556 women 59 to 80 years of age with osteoporosis received lasofoxifene 0.25 mg/d, lasofoxifene 0.5 mg/d, or placebo for 5 years. Cardiovascular events, including major CHD events, were prespecified secondary end points. Compared with placebo, lasofoxifene 0.5 mg/d reduced the risk of major CHD events 32% (hazard ratio, 0.68; 95% confidence interval, 0.50 to 0.93), including the risk of coronary revascularization (hazard ratio, 0.56, 95% confidence interval, 0.32 to 0.98). Reductions in risk of hospitalization for unstable angina (hazard ratio, 0.55; 95% confidence interval, 0.29 to 1.04) and diagnosis of new ischemic heart disease (hazard ratio, 0.52; 95% confidence interval, 0.26 to 1.04) nearly reached significance (P=0.06 for both comparisons). Although both hazard ratios were <1.0, no significant effect of lasofoxifene at 0.5 mg/d was demonstrated for coronary death or nonfatal myocardial infarction. The reduction in CHD events with lasofoxifene 0.25 mg/d was not significant (hazard ratio, 0.76; 95% confidence interval, 0.56 to 1.03; P=0.08). The effectiveness of lasofoxifene 0.5 mg/d in reducing CHD events was similar across strata of major cardiovascular risk factors. CONCLUSIONS: In postmenopausal women with osteoporosis, lasofoxifene 0.5 mg/d for 5 years reduced the risk of CHD events, regardless of the presence or absence of risk factors for cardiovascular disease. The significant reduction in risk of CHD events with lasofoxifene 0.5 mg/d was due primarily to lower risks of coronary revascularization procedures, hospitalization for unstable angina, and diagnosis of new ischemic heart disease. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00141323.

41 Article A common variant in the telomerase RNA component is associated with short telomere length. 2010

Njajou, Omer T / Blackburn, Elizabeth H / Pawlikowska, Ludmila / Mangino, Massimo / Damcott, Coleen M / Kwok, Pui-Yan / Spector, Timothy D / Newman, Anne B / Harris, Tamara B / Cummings, Steven R / Cawthon, Richard M / Shuldiner, Alan R / Valdes, Ana M / Hsueh, Wen-Chi. ·Department of Medicine, University of California San Francisco, San Francisco, California, United States of America. ·PLoS One · Pubmed #20885959.

ABSTRACT: BACKGROUND: Telomeres shorten as cells divide. This shortening is compensated by the enzyme telomerase. We evaluated the effect of common variants in the telomerase RNA component (TERC) gene on telomere length (TL) in the population-based Health Aging and Body Composition (Health ABC) Study and in two replication samples (the TwinsUK Study and the Amish Family Osteoporosis Study, AFOS). METHODOLOGY: Five variants were identified in the TERC region by sequence analysis and only one SNP was common (rs2293607, G/A). The frequency of the G allele was 0.26 and 0.07 in white and black, respectively. Testing for association between TL and rs2293607 was performed using linear regression models or variance component analysis conditioning on relatedness among subjects. RESULTS: The adjusted mean TL was significantly shorter in 665 white carriers of the G allele compared to 887 non-carriers from the Health ABC Study (4.69±0.05 kbp vs. 4.86±0.04 kbp, measured by quantitative PCR, p = 0.005). This association was replicated in another white sample from the TwinsUK Study (6.90±0.03 kbp in 301 carriers compared to 7.06±0.03 kbp in 395 non-carriers, measured by Southern blots, p = 0.009). A similar pattern of association was observed in whites from the family-based AFOS and blacks from the Health ABC cohort, although not statistically significant, possibly due to the lower allele frequency in these populations. Combined analysis using 2,953 white subjects from 3 studies showed a significant association between TL and rs2293607 (β = -0.19±0.04 kbp, p = 0.001). CONCLUSION: Our study shows a significant association between a common variant in TERC and TL in humans, suggesting that TERC may play a role in telomere homeostasis.

42 Article Indicators of "healthy aging" in older women (65-69 years of age). A data-mining approach based on prediction of long-term survival. 2010

Swindell, William R / Ensrud, Kristine E / Cawthon, Peggy M / Cauley, Jane A / Cummings, Steve R / Miller, Richard A / Anonymous1750668. ·Department of Pathology, University of Michigan, School of Medicine, Ann Arbor, MI 48109-2200, USA. wswindel@umich.edu ·BMC Geriatr · Pubmed #20716351.

ABSTRACT: BACKGROUND: Prediction of long-term survival in healthy adults requires recognition of features that serve as early indicators of successful aging. The aims of this study were to identify predictors of long-term survival in older women and to develop a multivariable model based upon longitudinal data from the Study of Osteoporotic Fractures (SOF). METHODS: We considered only the youngest subjects (n = 4,097) enrolled in the SOF cohort (65 to 69 years of age) and excluded older SOF subjects more likely to exhibit a "frail" phenotype. A total of 377 phenotypic measures were screened to determine which were of most value for prediction of long-term (19-year) survival. Prognostic capacity of individual predictors, and combinations of predictors, was evaluated using a cross-validation criterion with prediction accuracy assessed according to time-specific AUC statistics. RESULTS: Visual contrast sensitivity score was among the top 5 individual predictors relative to all 377 variables evaluated (mean AUC = 0.570). A 13-variable model with strong predictive performance was generated using a forward search strategy (mean AUC = 0.673). Variables within this model included a measure of physical function, smoking and diabetes status, self-reported health, contrast sensitivity, and functional status indices reflecting cumulative number of daily living impairments (HR >or= 0.879 or RH The multivariate model we developed characterizes a "healthy aging" phenotype based upon an integration of measures that together reflect multiple dimensions of an aging adult (65-69 years of age). Age-sensitive components of this model may be of value as biomarkers in human studies that evaluate anti-aging interventions. Our methodology could be applied to data from other longitudinal cohorts to generalize these findings, identify additional predictors of long-term survival, and to further develop the "healthy aging" concept.

43 Article Circadian activity rhythms and mortality: the study of osteoporotic fractures. 2010

Tranah, Gregory J / Blackwell, Terri / Ancoli-Israel, Sonia / Paudel, Misti L / Ensrud, Kristine E / Cauley, Jane A / Redline, Susan / Hillier, Teresa A / Cummings, Steven R / Stone, Katie L / Anonymous4820657. ·California Pacific Medical Center Research Institute, San Francisco Coordinating Center, UCSF, 185 Berry Street, Lobby 4, Suite 5700, San Francisco, CA 94107, USA. gtranah@psg.ucsf.edu ·J Am Geriatr Soc · Pubmed #20374404.

ABSTRACT: OBJECTIVES: To determine whether circadian activity rhythms are associated with mortality in community-dwelling older women. DESIGN: Prospective study of mortality. SETTING: A cohort study of health and aging. PARTICIPANTS: Three thousand twenty-seven community-dwelling women from the Study of Osteoporotic Fractures cohort (mean age 84). MEASUREMENTS: Activity data were collected using wrist actigraphy for a minimum of three 24-hour periods, and circadian activity rhythms were computed. Parameters of interest included height of activity peak (amplitude), midline estimating statistic of rhythm (mesor), strength of activity rhythm (robustness), and time of peak activity (acrophase). Vital status, with cause of death adjudicated through death certificates, was prospectively ascertained. RESULTS: Over an average of 4.1 years of follow-up, there were 444 (14.7%) deaths. There was an inverse association between peak activity height and all-cause mortality rates, with higher mortality rates observed in the lowest activity quartile (hazard ratio (HR)=2.18, 95% confidence interval (CI)=1.63-2.92) than in the highest quartile after adjusting for age, clinic site, race, body mass index, cognitive function, exercise, instrumental activity of daily living impairments, depression, medications, alcohol, smoking, self-reported health status, married status, and comorbidities. A greater risk of mortality from all causes was observed for those in the lowest quartiles of mesor (HR=1.71, 95% CI=1.29-2.27) and rhythm robustness (HR=1.97, 95% CI=1.50-2.60) than for those in the highest quartiles. Greater mortality from cancer (HR=2.09, 95% CI=1.04-4.22) and stroke (HR=2.64, 95% CI=1.11-6.30) was observed for later peak activity (after 4:33 p.m.; >1.5 SD from mean) than for the mean peak range (2:50-4:33 p.m.). CONCLUSION: Older women with weak circadian activity rhythms have higher mortality risk. If confirmed in other cohorts, studies will be needed to test whether interventions (e.g., physical activity, bright light exposure) that regulate circadian activity rhythms will improve health outcomes in older adults.

44 Article Serum phosphorus levels and the spectrum of ankle-brachial index in older men: the Osteoporotic Fractures in Men (MrOS) study. 2010

Meng, Jerry / Wassel, Christina L / Kestenbaum, Bryan R / Collins, Tracie C / Criqui, Michael H / Lewis, Cora E / Cummings, Steve R / Ix, Joachim H / Anonymous3210653. ·Division of Nephrology, Department of Medicine, School of Medicine, University of California, San Diego, La Jolla, California, USA. ·Am J Epidemiol · Pubmed #20237150.

ABSTRACT: A higher serum phosphorus level is associated with cardiovascular disease (CVD) events among community-living populations. Mechanisms are unknown. The ankle-brachial index (ABI) provides information on both atherosclerosis and arterial stiffness. In this cross-sectional study (2000-2002), the authors evaluated the association of serum phosphorus levels with low (<0.90) and high (> or =1.40 or incompressible) ABI as compared with intermediate ABI in 5,330 older US men, among whom the mean serum phosphorus level was 3.2 mg/dL (standard deviation, 0.4), 6% had a low ABI, and 5% had a high ABI. Each 1-mg/dL increase in serum phosphorus level was associated with a 1.6-fold greater prevalence of low ABI (95% confidence interval (CI): 1.2, 2.1; P < 0.001) and a 1.4-fold greater prevalence of high ABI (95% CI: 1.0, 1.9; P = 0.03) in models adjusted for demographic factors, traditional CVD risk factors, and kidney function. However, the association of phosphorus with high ABI differed by chronic kidney disease (CKD) status (in persons with CKD, prevalence ratio = 2.96, 95% CI: 1.61, 5.45; in persons without CKD, prevalence ratio = 1.14, 95% CI: 0.81, 1.61; interaction P = 0.04). In conclusion, among community-living older men, higher phosphorus levels are associated with low ABI and are also associated with high ABI in persons with CKD. These associations may explain the link between serum phosphorus levels and CVD events.

45 Article Estimating long-term effects of treatment from placebo-controlled trials with an extension period, using virtual twins. 2010

Vittinghoff, Eric / McCulloch, Charles E / Woo, Claudine / Cummings, Steven R. ·Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA 94107, USA. eric@biostat.ucsf.edu ·Stat Med · Pubmed #20209478.

ABSTRACT: The best information about the benefits of long-term treatment is obtained from a long-term placebo-controlled trial. However, once efficacy has been demonstrated in relatively brief trials, it may not be possible to conduct long-term placebo-controlled trials, for ethical or practical reasons. This paper presents a method for estimating long-term effects of a treatment from a placebo-controlled trial in which some participants originally randomized to active-treatment volunteer to continue on treatment during an extension study, but follow-up of participants originally assigned to placebo ends with the trial, or they are crossed over to active treatment during the extension. We propose using data from the trial to project the outcomes for a 'virtual twin' for each active-treatment volunteer under the counterfactual placebo condition, and using bootstrap methods for inference. The proposed method is validated using simulation, and applied to data from the Fracture Intervention Trial and its extension, FLEX.

46 Article Estimates of the proportion of older white men who would be recommended for pharmacologic treatment by the new US National Osteoporosis Foundation guidelines. 2010

Donaldson, Meghan G / Cawthon, Peggy M / Lui, Lily Y / Schousboe, John T / Ensrud, Kristine E / Taylor, Brent C / Cauley, Jane A / Hillier, Teresa A / Dam, Thuy T / Curtis, Jeff R / Black, Dennis M / Bauer, Douglas C / Orwoll, Eric S / Cummings, Steven R / Anonymous2110652. ·San Francisco Coordinating Center, California Pacific Medical Center, San Francisco, CA 94107, USA. mdonaldson@sfcc-cpmc.net ·J Bone Miner Res · Pubmed #20200971.

ABSTRACT: The new US National Osteoporosis Foundation's (NOF's) Clinician's Guide to Prevention and Treatment of Osteoporosis includes criteria for recommending pharmacologic treatment based on history of hip or vertebral fracture, femoral neck or spine bone mineral density (BMD) T-scores of -2.5 or less, and presence of low bone mass at the femoral neck or spine plus a 10-year risk of hip fracture of 3% or greater or of major osteoporotic fracture of 20% or greater. The proportion of men who would be recommended for treatment by these guidelines is not known. We applied the NOF criteria for treatment to men participating in the Osteoporotic Fractures in Men Study (MrOS). To determine how the MrOS population differs from the general US population of Caucasian men aged 65 years and older, we compared men in MrOS with men who participated in the National Health and Nutrition Examination Survey (NHANES) III on criteria included in the NOF treatment guidelines that were common to both cohorts. Compared with NHANES III, men in MrOS had higher femoral neck BMD values. Application of NOF guidelines to MrOS data estimated that at least 34% of US white men aged 65 years and older and 49% of those aged 75 years and older would be recommended for drug treatment. Application of the new NOF guidelines would result in recommending a very large proportion of white men in the United States for pharmacologic treatment of osteoporosis, for many of whom the efficacy of treatment is unknown.

47 Article Lasofoxifene in postmenopausal women with osteoporosis. 2010

Cummings, Steven R / Ensrud, Kristine / Delmas, Pierre D / LaCroix, Andrea Z / Vukicevic, Slobodan / Reid, David M / Goldstein, Steven / Sriram, Usha / Lee, Andy / Thompson, John / Armstrong, Roisin A / Thompson, David D / Powles, Trevor / Zanchetta, Jose / Kendler, David / Neven, Patrick / Eastell, Richard / Anonymous4350651. ·San Francisco Coordinating Center, California Pacific Medical Center Research Institute, and University of California, San Francisco, San Francisco, USA. scummings@sfcc-cpmc.net ·N Engl J Med · Pubmed #20181970.

ABSTRACT: BACKGROUND: The effects of lasofoxifene on the risk of fractures, breast cancer, and cardiovascular disease are uncertain. METHODS: In this randomized trial, we assigned 8556 women who were between the ages of 59 and 80 years and had a bone mineral density T score of -2.5 or less at the femoral neck or spine to receive once-daily lasofoxifene (at a dose of either 0.25 mg or 0.5 mg) or placebo for 5 years. Primary end points were vertebral fractures, estrogen receptor (ER)-positive breast cancer, and nonvertebral fractures; secondary end points included major coronary heart disease events and stroke. RESULTS: Lasofoxifene at a dose of 0.5 mg per day, as compared with placebo, was associated with reduced risks of vertebral fracture (13.1 cases vs. 22.4 cases per 1000 person-years; hazard ratio, 0.58; 95% confidence interval [CI], 0.47 to 0.70), nonvertebral fracture (18.7 vs. 24.5 cases per 1000 person-years; hazard ratio, 0.76; 95% CI, 0.64 to 0.91), ER-positive breast cancer (0.3 vs. 1.7 cases per 1000 person-years; hazard ratio, 0.19; 95% CI, 0.07 to 0.56), coronary heart disease events (5.1 vs. 7.5 cases per 1000 person-years; hazard ratio, 0.68; 95% CI, 0.50 to 0.93), and stroke (2.5 vs. 3.9 cases per 1000 person-years; hazard ratio, 0.64; 95% CI, 0.41 to 0.99). Lasofoxifene at a dose of 0.25 mg per day, as compared with placebo, was associated with reduced risks of vertebral fracture (16.0 vs. 22.4 cases per 1000 person-years; hazard ratio, 0.69; 95% CI, 0.57 to 0.83) and stroke (2.4 vs. 3.9 cases per 1000 person-years; hazard ratio, 0.61; 95% CI, 0.39 to 0.96) Both the lower and higher doses, as compared with placebo, were associated with an increase in venous thromboembolic events (3.8 and 2.9 cases vs. 1.4 cases per 1000 person-years; hazard ratios, 2.67 [95% CI, 1.55 to 4.58] and 2.06 [95% CI, 1.17 to 3.60], respectively). Endometrial cancer occurred in three women in the placebo group, two women in the lower-dose lasofoxifene group, and two women in the higher-dose lasofoxifene group. Rates of death per 1000 person-years were 5.1 in the placebo group, 7.0 in the lower-dose lasofoxifene group, and 5.7 in the higher-dose lasofoxifene group. CONCLUSIONS: In postmenopausal women with osteoporosis, lasofoxifene at a dose of 0.5 mg per day was associated with reduced risks of nonvertebral and vertebral fractures, ER-positive breast cancer, coronary heart disease, and stroke but an increased risk of venous thromboembolic events. (ClinicalTrials.gov number, NCT00141323.)

48 Article Filtering FRAX. 2010

Watts, Nelson B / Siris, Ethel S / Cummings, Steven R / Bauer, Douglas C. ·University of Cincinnati Bone Health and Osteoporosis Center, Cincinnati, OH, USA. ·Osteoporos Int · Pubmed #20151300.

ABSTRACT: -- No abstract --

49 Article Application of the National Osteoporosis Foundation Guidelines to postmenopausal women and men: the Framingham Osteoporosis Study. 2010

Berry, S D / Kiel, D P / Donaldson, M G / Cummings, S R / Kanis, J A / Johansson, H / Samelson, E J. ·Institute for Aging Research, Hebrew SeniorLife, Boston, MA 02131, USA. sarahberry@hrca.harvard.edu ·Osteoporos Int · Pubmed #19937426.

ABSTRACT: INTRODUCTION: Little is known about the public health impact of the NOF Guidelines. Therefore, we determined the proportion of US Caucasians recommended for treatment of osteoporosis according to NOF Guidelines (2003 and 2008). METHODS: One thousand nine hundred and forty-six postmenopausal women and 1,681 men aged > or =50 years from the Framingham Study with information on bone mineral density (1987-2001) were included. Information on clinical predictors was used to estimate the 10-year probability of hip and major osteoporotic fracture by FRAX (version 3.0). RESULTS: Overall proportion of women meeting treatment criterion was less when the 2008 NOF Guidelines were applied (41.1%) compared with 2003 Guidelines (47.8%). The proportion of women aged <65 years meeting treatment criterion was much less when applying 2008 Guidelines (23.1% in 2003, 8.3% in 2008), whereas the proportion of women aged >75 years increased slightly (78.3% in 2003, 86.0% in 2008). Seventeen percent of men aged > or =50 years met treatment criterion (2.5% aged 50-64 years, 49.8% aged >75 years). CONCLUSIONS: Nearly one half of Caucasian postmenopausal women and one sixth of men aged 50 years and older would be recommended for osteoporosis treatment according to 2008 NOF Guidelines. Given the high proportion of persons recommended for treatment, NOF Guidelines may need to be re-evaluated with respect to budget impact.

50 Article Effect of once-yearly zoledronic acid on the spine and hip as measured by quantitative computed tomography: results of the HORIZON Pivotal Fracture Trial. 2010

Eastell, R / Lang, T / Boonen, S / Cummings, S / Delmas, P D / Cauley, J A / Horowitz, Z / Kerzberg, E / Bianchi, G / Kendler, D / Leung, P / Man, Z / Mesenbrink, P / Eriksen, E F / Black, D M / Anonymous11400639. ·Academic Unit of Bone Metabolism, University of Sheffield, Sheffield, UK. r.eastell@sheffield.ac.uk ·Osteoporos Int · Pubmed #19802508.

ABSTRACT: INTRODUCTION: To investigate bone mineral density (BMD) changes in trabecular and cortical bone, estimated by quantitative computed analysis (QCT) or dual-energy X-ray absorptiometry (DXA), and whether zoledronic acid 5 mg (ZOL) affects bone strength. METHODS: In 233 women from a randomized, controlled trial of once-yearly ZOL, lumbar spine, total hip, femoral neck, and trochanter were assessed by DXA and QCT (baseline, Month 36). Mean percentage changes from baseline and between-treatment differences (ZOL vs placebo, t-test) were evaluated. RESULTS: Mean between-treatment differences for lumbar spine BMD were significant by DXA (7.0%, p < 0.01) and QCT (5.7%, p < 0.0001). Between-treatment differences were significant for trabecular spine (p = 0.0017) [non-parametric test], trabecular trochanter (10.7%, p < 0.0001), total hip (10.8%, p < 0.0001), and compressive strength indices at femoral neck (8.6%, p = 0.0001), and trochanter (14.1%, p < 0.0001). CONCLUSIONS: Once-yearly ZOL increased hip and spine BMD vs placebo, assessed by QCT vs DXA. Changes in trabecular bone resulted in increased indices of compressive strength.

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