Effect of once-yearly zoledronic acid five milligrams on fracture risk and change in femoral neck bone mineral density
Richard Eastell, Dennis M Black, Steven Boonen, Silvano Adami, Dieter Felsenberg, Kurt Lippuner, Steven R Cummings, Pierre D Delmas, Lisa Palermo, Peter Mesenbrink, Jane A Cauley, HORIZON Pivotal Fracture Trial, Dennis Black, Steven Cummings, Pierre Delmas, Richard Eastell, Ian Reid, Steven Boonen, Jane Cauley, Felicia Cosman, Péter Lakatos, Ping C Leung, Zulema Man, Erik Fink Eriksen, Peter Mesenbrink, Edith Lau, Saloman Jasqui, Carlos Mautalen, Theresa Rosario-Jansen, John Caminis, Lawrence Raisz, Peter Bauer, Juliet Compston, David DeMets, Raimund Hirschberg, Olof Johnell, Stuart Ralston, Robert Wallace, Michael Farkough, Mary Flood, Douglas Bauer, Lisa Palermo, Thomas Lang, Eduardo Kerzberg, Zulema Man, Carlos Mautalen, Maria Ridruejo, Guillermo Tate, Jorge Velasco, Michael Hooper, Mark Kotowicz, Peter Nash, Richard Prince, Anthony Roberts, Philip Sambrook, Harald Dobnig, Gerd Finkenstedt, Guenter Hoefle, Klaus Klaushofer, Martin Pecherstorfer, Peter Peichl, Jean Body, Steven Boonen, Jean-Pierre Devogelaer, Piet Geusens, Jean Kaufman, João Brenol, Jussara Kochen, Rubem Lederman, Sebastiao Radominski, Vera Szejnfeld, Cristiano Zerbini, Jonathan Adachi, Jacques Brown, Denis Choquette, David Hanley, Robert Josse, David Kendler, Richard Kremer, Frederic Morin, Wojciech Olszynski, Alexandra Papaioannou, Chiu Kin Yuen, Baoying Chen, Shouqing Lin, Nohemi Casas, Monique Chalem, Juan Jaller, Jose Molina, Hannu Aro, Jorma Heikkinen, Heikki Kröger, Lasse Mäkinen, Juha Saltevo, Jorma Salmi, Matti Välimäki, Claude-Laurent Benhamou, Pierre Delmas, Patrice Fardellone, Georges Werhya, Bruno Allolio, Dieter Felsenberg, Joachim Happ, Manfred Hartard, Johannes Hensen, Peter Kaps, Joern Kekow, Ruediger Moericke, Bernd Ortloff, Peter Schneider, Siegfried Wassenberg, Ping Chung Leung, Adam Balogh, Bela Gomor, Tibor Hidvégi, Laszlo Koranyi, Péter Lakatos, Gyula Poór, Zsolt Tulassay, Rivka Dresner Pollak, Varda Eshed, A Joseph Foldes, Sophia Ish-Shalom, Iris Vered, Mordechai Weiss, Silvano Adami, Antonella Barone, Gerolamo Bianchi, Sandro Giannini, Giovanni Carlo Isaia, Giovanni Luisetto, Salvatore Minisola, Nicola Molea, Ranuccio Nuti, Sergio Ortolani, Mario Passeri, Alessandro Rubinacci, Bruno Seriolo, Luigi Sinigaglia, Woong-Hwan Choi, Moo-Il Kang, Ghi-Su Kim, Hye-Soon Kim, Yong-Ki Kim, Sung-Kil Lim, Ho-Young Son, Hyun-Koo Yoon, Carlos Abud, Pedro Garcia, Salomon Jasqui, Luis Ochoa, Javier Orozco, Javier Santos, Ian Reid, Sigbjørn Elle, Johan Halse, Arne Høiseth, Hans Olav, Høivik Ingun Røed, Arne Skag, Jacob Stakkestad, Unni Syversen, Janusz Badurski, Edward Czerwinski, Roman Lorenc, Ewa Marcinowska-Suchowierska, Andrzej Sawicki, Jerzy Supronik, Eduard Ailamazyan, Lidiya Benevolenskaya, Alexander Dreval, Leonid Dvoretsky, Raisa Dyomina, Vadim Mazurov, Galina Melnichenko, Ashot Mkrtoumyan, Alexander Orlov-Morozov, Olga Ostroumova, Eduard Pikhlak, Tatiana Shemerovskaya, Nadezhda Shostak, Irina Skripnikova, Vera Smetnik, Evgenia Tsyrlina, Galina Usova, Alsu Zalevskaya, Irina Zazerskaya, Eugeny Zotkin, Osten Ljunggren, Johan Lofgren, Mats Palmér, Maria Saaf, Martin Stenström, Paul Hasler, Olivier Lamy, Kurt Lippuner, Claude Merlin, René Rizzoli, Robert Theiler, Alan Tyndall, Daniel Uebelhart, Jung-Fu Chen, Po-Quang Chen, Lin-show Chin, Jawl-Shan Hwang, Tzay-Shing Yang, Mayuree Jirapinyo, Rojanasthien Sattaya, Sutin Sriussadaporn, Soontrapa Supasin, Nimit Taechakraichana, Kittisak Wilawan, Hugh Donnachie, Richard Eastell, William Fraser, Alistair McLellan, David Reid, John Abruzzo, Ronald Ackerman, Robert Adler, John Aloia, Charles Birbara, Barbara Bode, Henry Bone, Donald Brandon, Jane Cauley, Felicia Cosman, Daniel Dionne, Robert Downs Jr, James Dreyfus, Victor Elinoff, Ronald Emkey, Joseph Fanciullo, Darrell Fiske, Palmieri Genaro, M Gollapudi, Richard Gordon, James Hennessey, Paul Howard, Karen Johnson, Conrad Johnston, Risa Kagan, Shelly Kafka, Jeffrey Kaine, Terry Klein, William Koltun, Meryl Leboff, Bruce Levine, E Michael Lewiecki, Cora Elizabeth Lewis, Angelo Licata, Michael Lillestol, Barry Lubin, Raymond Malamet, Antoinette Mangione, Velimir Matkovic, Daksha Mehta, Paul Miller, Sam Miller, Frederik T Murphy, Susan Nattrass, David Podlecki, Christopher Recknor, Clifford Rosen, Daniel Rowe, Robert Rude, Thomas Schnitzer, Yvonne Sherrer, Stuart Silverman, Kenna Stephenson, Barbara Troupin, Joseph Tucci, Reina Villareal, Nelson Watts, Richard Weinstein, Robert Weinstein, Michael Weitz, Richard White, Richard Eastell, Dennis M Black, Steven Boonen, Silvano Adami, Dieter Felsenberg, Kurt Lippuner, Steven R Cummings, Pierre D Delmas, Lisa Palermo, Peter Mesenbrink, Jane A Cauley, HORIZON Pivotal Fracture Trial, Dennis Black, Steven Cummings, Pierre Delmas, Richard Eastell, Ian Reid, Steven Boonen, Jane Cauley, Felicia Cosman, Péter Lakatos, Ping C Leung, Zulema Man, Erik Fink Eriksen, Peter Mesenbrink, Edith Lau, Saloman Jasqui, Carlos Mautalen, Theresa Rosario-Jansen, John Caminis, Lawrence Raisz, Peter Bauer, Juliet Compston, David DeMets, Raimund Hirschberg, Olof Johnell, Stuart Ralston, Robert Wallace, Michael Farkough, Mary Flood, Douglas Bauer, Lisa Palermo, Thomas Lang, Eduardo Kerzberg, Zulema Man, Carlos Mautalen, Maria Ridruejo, Guillermo Tate, Jorge Velasco, Michael Hooper, Mark Kotowicz, Peter Nash, Richard Prince, Anthony Roberts, Philip Sambrook, Harald Dobnig, Gerd Finkenstedt, Guenter Hoefle, Klaus Klaushofer, Martin Pecherstorfer, Peter Peichl, Jean Body, Steven Boonen, Jean-Pierre Devogelaer, Piet Geusens, Jean Kaufman, João Brenol, Jussara Kochen, Rubem Lederman, Sebastiao Radominski, Vera Szejnfeld, Cristiano Zerbini, Jonathan Adachi, Jacques Brown, Denis Choquette, David Hanley, Robert Josse, David Kendler, Richard Kremer, Frederic Morin, Wojciech Olszynski, Alexandra Papaioannou, Chiu Kin Yuen, Baoying Chen, Shouqing Lin, Nohemi Casas, Monique Chalem, Juan Jaller, Jose Molina, Hannu Aro, Jorma Heikkinen, Heikki Kröger, Lasse Mäkinen, Juha Saltevo, Jorma Salmi, Matti Välimäki, Claude-Laurent Benhamou, Pierre Delmas, Patrice Fardellone, Georges Werhya, Bruno Allolio, Dieter Felsenberg, Joachim Happ, Manfred Hartard, Johannes Hensen, Peter Kaps, Joern Kekow, Ruediger Moericke, Bernd Ortloff, Peter Schneider, Siegfried Wassenberg, Ping Chung Leung, Adam Balogh, Bela Gomor, Tibor Hidvégi, Laszlo Koranyi, Péter Lakatos, Gyula Poór, Zsolt Tulassay, Rivka Dresner Pollak, Varda Eshed, A Joseph Foldes, Sophia Ish-Shalom, Iris Vered, Mordechai Weiss, Silvano Adami, Antonella Barone, Gerolamo Bianchi, Sandro Giannini, Giovanni Carlo Isaia, Giovanni Luisetto, Salvatore Minisola, Nicola Molea, Ranuccio Nuti, Sergio Ortolani, Mario Passeri, Alessandro Rubinacci, Bruno Seriolo, Luigi Sinigaglia, Woong-Hwan Choi, Moo-Il Kang, Ghi-Su Kim, Hye-Soon Kim, Yong-Ki Kim, Sung-Kil Lim, Ho-Young Son, Hyun-Koo Yoon, Carlos Abud, Pedro Garcia, Salomon Jasqui, Luis Ochoa, Javier Orozco, Javier Santos, Ian Reid, Sigbjørn Elle, Johan Halse, Arne Høiseth, Hans Olav, Høivik Ingun Røed, Arne Skag, Jacob Stakkestad, Unni Syversen, Janusz Badurski, Edward Czerwinski, Roman Lorenc, Ewa Marcinowska-Suchowierska, Andrzej Sawicki, Jerzy Supronik, Eduard Ailamazyan, Lidiya Benevolenskaya, Alexander Dreval, Leonid Dvoretsky, Raisa Dyomina, Vadim Mazurov, Galina Melnichenko, Ashot Mkrtoumyan, Alexander Orlov-Morozov, Olga Ostroumova, Eduard Pikhlak, Tatiana Shemerovskaya, Nadezhda Shostak, Irina Skripnikova, Vera Smetnik, Evgenia Tsyrlina, Galina Usova, Alsu Zalevskaya, Irina Zazerskaya, Eugeny Zotkin, Osten Ljunggren, Johan Lofgren, Mats Palmér, Maria Saaf, Martin Stenström, Paul Hasler, Olivier Lamy, Kurt Lippuner, Claude Merlin, René Rizzoli, Robert Theiler, Alan Tyndall, Daniel Uebelhart, Jung-Fu Chen, Po-Quang Chen, Lin-show Chin, Jawl-Shan Hwang, Tzay-Shing Yang, Mayuree Jirapinyo, Rojanasthien Sattaya, Sutin Sriussadaporn, Soontrapa Supasin, Nimit Taechakraichana, Kittisak Wilawan, Hugh Donnachie, Richard Eastell, William Fraser, Alistair McLellan, David Reid, John Abruzzo, Ronald Ackerman, Robert Adler, John Aloia, Charles Birbara, Barbara Bode, Henry Bone, Donald Brandon, Jane Cauley, Felicia Cosman, Daniel Dionne, Robert Downs Jr, James Dreyfus, Victor Elinoff, Ronald Emkey, Joseph Fanciullo, Darrell Fiske, Palmieri Genaro, M Gollapudi, Richard Gordon, James Hennessey, Paul Howard, Karen Johnson, Conrad Johnston, Risa Kagan, Shelly Kafka, Jeffrey Kaine, Terry Klein, William Koltun, Meryl Leboff, Bruce Levine, E Michael Lewiecki, Cora Elizabeth Lewis, Angelo Licata, Michael Lillestol, Barry Lubin, Raymond Malamet, Antoinette Mangione, Velimir Matkovic, Daksha Mehta, Paul Miller, Sam Miller, Frederik T Murphy, Susan Nattrass, David Podlecki, Christopher Recknor, Clifford Rosen, Daniel Rowe, Robert Rude, Thomas Schnitzer, Yvonne Sherrer, Stuart Silverman, Kenna Stephenson, Barbara Troupin, Joseph Tucci, Reina Villareal, Nelson Watts, Richard Weinstein, Robert Weinstein, Michael Weitz, Richard White
Abstract
Context: In the Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly - Pivotal Fracture Trial (HORIZON-PFT), zoledronic acid (ZOL) 5 mg significantly reduced fracture risk.
Objective: The aim of the study was to identify factors associated with greater efficacy during ZOL 5 mg treatment.
Design, setting, and patients: We conducted a subgroup analysis (preplanned and post hoc) of a multicenter, double-blind, placebo-controlled, 36-month trial in 7765 women with postmenopausal osteoporosis.
Intervention: A single infusion of ZOL 5 mg or placebo was administered at baseline, 12, and 24 months.
Main outcome measures: Primary endpoints were new vertebral fracture and hip fracture. Secondary endpoints were nonvertebral fracture and change in femoral neck bone mineral density (BMD). Baseline risk factor subgroups were age, BMD T-score and vertebral fracture status, total hip BMD, race, weight, geographical region, smoking, height loss, history of falls, physical activity, prior bisphosphonates, creatinine clearance, body mass index, and concomitant osteoporosis medications.
Results: Greater ZOL induced effects on vertebral fracture risk were seen with younger age (treatment-by-subgroup interaction, P = 0.05), normal creatinine clearance (P = 0.04), and body mass index >or= 25 kg/m(2) (P = 0.02). There were no significant treatment-factor interactions for hip or nonvertebral fracture or for change in BMD.
Conclusions: ZOL appeared more effective in preventing vertebral fracture in younger women, overweight/obese women, and women with normal renal function. ZOL had similar effects irrespective of fracture risk factors or femoral neck BMD.
Trial registration: ClinicalTrials.gov NCT00049829.
Figures
Source: PubMed