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Scientific Articles   |    
Denosumab Treatment in Postmenopausal Women with Osteoporosis Does Not Interfere with Fracture-HealingResults from the FREEDOM Trial
Silvano Adami, MD, PhD1; Cesar Libanati, MD2; Steven Boonen, MD, PhD3; Steven R. Cummings, MD4; Pei-Ran Ho, MD2; Andrea Wang, MA2; Ethel Siris, MD5; Joseph Lane, MD6; and the FREEDOM Fracture-Healing Writing Group
1 Faculty of Medicine & Surgery, University of Verona, P. le Scuro 10, 37134, Verona, Italy
2 Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320
3 Bone Research Unit, Department of Experimental Medicine, Leuven University, Herestraat 49, B-3000 Leuven, Belgium
4 San Francisco Coordinating Center, California Pacific Medical Center Research Institute and University of California, 158 Berry Street, San Francisco, CA 94107
5 Department of Medicine, Columbia University Medical Center, 630 West 168th Street, New York, NY 10032
6 Department of Orthopedic Surgery, Hospital for Special Surgery, 535 East 70th Street, New York, NY 10021. E-mail address: Lanej@HSS.edu
View Disclosures and Other Information
  • Disclosure statement for author(s): PDF

The data and manuscript were discussed and reviewed throughout by the whole FREEDOM fracture-healing writing group. The listed authors were those who contributed most to the analysis of the data and preparation of the manuscript. FREEDOM fracture-healing writing group: Jonathan D. Adachi, Mohit Bhandari (McMaster University, Hamilton, Ontario, Canada); Silvano Adami (University of Verona, Verona, Italy); Steven Boonen (Bone Research Unit, Department of Experimental Medicine, Leuven University, Leuven, Belgium); Steven R. Cummings (San Francisco Coordinating Center, California Pacific Medical Center Research Institute and University of California, San Francisco, San Francisco, California); Luiz de Gregorio (Center for Clinical and Basic Research, Rio de Janeiro, Brazil); Nigel Gilchrist (Health Care of Elderly, The Princess Margaret Hospital, Christchurch, New Zealand); Pei-Ran Ho, Cesar Libanati, Andrea Wang (Amgen, Thousand Oaks, California); Joseph Lane (Hospital for Special Surgery, New York, NY); George Lyritis (Laboratory for the Study of Musculoskeletal System, Athens, Greece); Gerd Möller (Amgen [Europe] GmbH, Zug, Switzerland); Santiago Palacios (Instituto Palacios, Salud y Medicina de la Mujer, Madrid, Spain); Karel Pavelka (Institute of Rheumatology, Charles University Prague, Prague, Czech Republic); Heinrich Resch (St. Vincent Hospital Vienna, Medical University of Vienna, Vienna, Austria); Christian Roux (Paris Descartes University, Paris, France); Ethel Siris (Department of Medicine, Columbia University Medical Center, New York, NY); and Daniel Uebelhart (Valmont, Private Rehabilitation Clinic, Glion-sur-Montreux, Switzerland).

Investigation performed at 214 centers in Europe, North America, South America, Australia, and New Zealand

This article was chosen to appear electronically on October 24, 2012, in advance of publication in a regularly scheduled issue.

A commentary by Robert J. Pignolo, MD, PhD, is linked to the online version of this article at jbjs.org.



Disclosure: One or more of the authors received payments or services, either directly or indirectly (i.e., via his or her institution), from a third party in support of an aspect of this work. In addition, one or more of the authors, or his or her institution, has had a financial relationship, in the thirty-six months prior to submission of this work, with an entity in the biomedical arena that could be perceived to influence or have the potential to influence what is written in this work. No author has had any other relationships, or has engaged in any other activities, that could be perceived to influence or have the potential to influence what is written in this work. The complete Disclosures of Potential Conflicts of Interest submitted by authors are always provided with the online version of the article.

Copyright © 2012 by The Journal of Bone and Joint Surgery, Inc.
J Bone Joint Surg Am, 2012 Dec 05;94(23):2113-2119. doi: 10.2106/JBJS.K.00774
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Abstract

Background: 

Fracture is the major complication of osteoporosis, and it allows the identification of individuals needing medical intervention for osteoporosis. After nonvertebral fracture, patients often do not receive osteoporosis medical treatment despite evidence that this treatment reduces the risk of subsequent fracture. In this preplanned analysis of the results of the three-year, placebo-controlled FREEDOM trial, we evaluated the effect of denosumab administration on fracture-healing to address theoretical concerns related to initiating or continuing denosumab therapy in patients presenting with a nonvertebral fracture.

Methods: 

Postmenopausal women aged sixty to ninety years with osteoporosis were randomized to receive 60 mg of denosumab (n = 3902) or a placebo (n = 3906) subcutaneously every six months for three years. Investigators reported complications associated with a fracture or its management and with fracture-healing for all nonvertebral fractures that occurred during the study. Delayed healing was defined as incomplete fracture-healing six months after the fracture.

Results: 

Six hundred and sixty-seven subjects (303 treated with denosumab and 364 who received a placebo) had a total of 851 nonvertebral fractures (386 in the denosumab group and 465 in the placebo group), including 199 fractures (seventy-nine in the denosumab group and 120 in the placebo group) that were treated surgically. Delayed healing was reported in seven subjects (two in the denosumab group and five in the placebo group), including one with subsequent nonunion (in the placebo group). Neither delayed healing nor nonunion was observed in any subject who had received denosumab within six weeks preceding or following the fracture. A complication associated with the fracture or intervention occurred in five subjects (2%) and twenty subjects (5%) in the denosumab and placebo groups, respectively (p = 0.009).

Conclusions: 

Denosumab in a dose of 60 mg every six months does not seem to delay fracture-healing or contribute to other complications, even when it is administered at or near the time of the fracture.

Level of Evidence: 

Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

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    Accreditation Statement
    These activities have been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint sponsorship of the American Academy of Orthopaedic Surgeons and The Journal of Bone and Joint Surgery, Inc. The American Academy of Orthopaedic Surgeons is accredited by the ACCME to provide continuing medical education for physicians.
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