Strontium Ranelate Reduces the Risk of Nonvertebral Fractures in Postmenopausal Women with Osteoporosis: Treatment of Peripheral Osteoporosis (TROPOS) Study

Reginster, J Y.
Seeman, E
De Vernejoul, M C.
Adami, S
Compston, J
Phenekos, C
Devogelaer, J P.
Diaz Curiel, M
Sawicki, A
Goemaere, S
Sorensen, O H.
Felsenberg, D
Meunier, P J.

Department of Epidemiology (J.Y.R.), Public Health and Health Economics, University of Liège, 4020 Liège, Belgium; Endocrine Department (E.S.), Hospital University of Melbourne, 3084 Melbourne, Australia; Institut National de la Santé et de la Recherche Médicale Unité 606 and Fédération of Rheumatologie (M.C.D.V.), Lariboisiere Hospital, 75010 Paris, France; Centro Ospedaliero Clinicizato di Medicina, Riabilitiva e Preventiva di Valeggio (S.A.), 37067 Valeggio Sul Mincio, Italy; Department of Medicine (J.C.), University of Cambridge, Cambridge, CB2 2QQ United Kingdom; Department of Endocrinology (C.P.), Red Cross Hospital, 11526 Athens, Greece; Department of Rheumatology (J.P.D.), Catholic University of Louvain, 1200 Brussels, Belgium; Fundacion Jiménez Diaz (M.D.C.), Servicio de Medicina Interna, Unidad de Metabolismo Oseo, 28040 Madrid, Spain; Warszawskie Centrum Osteoporozy (A.S.), 00-632 Warszawa, Poland; Unit for Osteoporosis and Metabolic Bone Diseases (S.G.), Ghent University Hospital, 9000 Gent, Belgium; The Osteoporosis Research Center (O.H.S.), Department 545, Hvidovre University Hospital, 2650 Hvidovre, Denmark; Universitätklinikum Benjamin Franklin (D.F.), 12200 Berlin, Germany; Department of Rheumatology and Bone Diseases (P.J.M.), Edouard Herriot Hospital, 69372 Lyon, France

Received September 12, 2004. Accepted February 16, 2005.

Address all correspondence and requests for reprints to: Prof. J. Y. Reginster, Department of Epidemiology, Public Health and Health Economics, University of Liège, CHU Centre ville, 45 Quai Godefroid Kurth, 4020 Liège, Belgium. E-mail: [email protected].

This study was supported by Laboratoires Servier.

List of investigators: FRANCE: Prof. P. J. Meunier, Edouard Herriot Hospital, Lyon; Dr. J. P. Aquino, Medical Clinic La Porte Verte, Versailles; Prof. J. Dehais, Pellegrin-Tondu Hospital, Bordeaux; Prof. P. Fardellone, Nord Hospital, Amiens; Prof. G. Werhya, Brabois Hospital, Vandoeuvre; Dr. C. Benhamou, La Madeleine Hospital, Orleans; Prof. M. C. De Vernejoul, Lariboisière Hospital, Paris; Prof. A. Kahan, Cochin Hospital, Paris; Dr. O. Bonidan, E. Muller Hospital, Mulhouse; Prof. C. Marcelli, Regional Hospital and University Centre, Caen; Prof. J. L. Kuntz, Hautepierre Hospital, Strasbourg; Prof. A. Prost, Hôtel Dieu Hospital, Nantes; Prof. P. Bourgeois, Pitié-Salpétrière Hospital, Paris; Prof. F. Blotman, Lapeyronie Hospital, Montpellier; Prof. B. Vellas, La Grave-Casselardit Hospital, Toulouse. BELGIUM: Prof. J. Y. Reginster, Centre Hospitalo Universitaire Centre ville, Liege; Prof. J. P. Devogelaer, Catholic University of Louvain, Brussels; Prof. J. M. Kaufman, Ghent University Hospital, Gent; Dr. M. Walravens, Medical Centre, Tessenderloo and Somedi, Heist-op-den-Berg; Dr. F. Raeman, Jan Palfijin Ziekenhuis, Merksem. DENMARK: Dr. S. Pors Nielsen, Hillerod Hospital, Hillerod; Dr. O. H. Sorensen, The Osteoporosis Research Center, Hvidovre; Prof. H. Beck-Nielsen University Hospital, M. Osteoporosis Centre, Odense; Dr. P. Charles, Aarhus Amtssygehus, Aarhus C. ITALY: Prof. S. Ortolani, Centre Auxologico Italiano, Milano; Prof. S. Adami, Hospital and Clinical Centre of Medecine, Valeggio sul Mincio; Prof. G. Bianchi, Unita Salitaria Locale 3 Hospital “La Colletta”, Arenzano; Dr. M. L. Brandi, General Hospital Careggi, Firenze; Prof. D. Cucinotta, S. Orsola Malpighi Hospital, Bologna; Prof. C. Fiore, Medical Clinic, Vittorio Emanuel Hospital, Catania; Prof. C. Gennari, Institute of Medical Clinic, New General Hospital “Le Scotte”, Siena; Prof. G. Isaia, University of General Medicine, Torino; Prof. G. Luisetto, Univerity Institute of Semeiotica Medica, Padova; Prof. R. Passariello, Institute of Radiology “La Sapienza” University, Rome; Prof. M. Passeri, Parma University, Parma; Prof. G. Rovetta, E. Bruzzone Institute, Genova; Prof. L. Tessari, San Raffaele Hospital, Milano. POLAND: Prof. J. E. Badurski, Center for Osteoporosis and Osteo-Articular Diseases, Bialystok; Dr. K. Hoszowski, Medical Centre, Warsaw; Prof. R. S. Lorenc, Osteoporosis Centre of Krajowe, Warsaw; Dr. A. Sawicki, Warsawian Center of Osteoporosis ad Calcium Metabolism “Osteomed”, Warsaw. HUNGARY: Dr. A. Balogh, Medical and Health Sciences Centre, University of Debrecen, Debrecen; Prof. R. De Chatel, Semmelweis Orvostudomanyi Egyetem, Budapest/Sote, Budapest. UNITED KINGDOM: Dr T. D. Spector, Department of Rheumatology, St. Thomas’ Hospital, London; Dr. D. V. Doyle, Silverthorn Centre, Chingford; Dr. P. Ryan, Medway Hospital Trust, Gillingham; Dr. I. G. Smith, SYNEXUS Ltd. Clinical Research Centre, Manchester; Dr. R. Smith, Banbury Clinical Studies Centre, Banbury; Dr. M. Clements, North London Clinical Studies Centre, Mount Vernon Hospital, Northwood. GREECE: Dr. C. Phenekos, Red Cross Hospital, Athens. AUSTRALIA: Prof. K. W. Ng, St Vincent’s Hospital, Fitzroy Victoria; Prof. J. Wark, Royal Melbourne Hospital, Parkville Victoria; Prof. E. Seeman, Austin and Repatriation Medical Centre, Heidelberg Victoria; Dr. J. Prins, Princess Alexandra Hospital, Wooloongabba, Queensland; Prof. R. Prince, Sir Charles Gairdner Hospital, Nedlands, Western Australia; Dr. J. Graham, Ashford Specialist Centre, Ashford, South Australia. SPAIN: Dr. A. Diez, El Mar Hospital, Barcelona; Dr. A. Roces Varela, Hospital Nuestra Sra de la Candelaria, Santa Cruz de Tenerife, Canarias; Dr. J. M. Padrino, Hospital 12 de Octubre, Madrid; Dr. J. B. Cannata, General Hospital of Asturias, Oviedo; Dr. J. Gijon/Dr. A. Torrijos, La Paz Hospital/Hospital de Rehabilitacion y Traumatologia, Madrid; Dr. M. Díaz Curiel/Dr. A. Rapado, Jiménez Díaz Foundation, Madrid. GERMANY: Prof. E. M. Lemmel, Max Grundig Clinic, Buhl; Dr. D. Felsenberg, Benjamin Franklin Clinical University, Berlin; Prof. J. Hensen, Medical Clinic 1, Erlangen; Dr. G. Stucki, Clinic for Physical Medecine and Rehabilitation, München; Dr. J. Semler, Immanuel Hospital, Berlin; Prof. W. Schmidt, St. Josef-Hospital, Bochum; Prof. H. P. Kruse, Med. Clinical University, Hamburg. SWITZERLAND: Prof. J. P. Bonjour/Prof. R. Rizzoli, Geneva University Hospital, Geneva.

First Published Online February 22, 2005

Abbreviations: AE, Adverse event; BMD, bone mineral density; CHMP, Committee for Medicinal Products for Human Use; 95% CI, 95% confidence interval; ITT, intention-to-treat; 25-OH D, 25-OH vitamin D; RR, relative risk; SOTI, Spinal Osteoporosis Therapeutic Intervention; TROPOS, Treatment of Peripheral Osteoporosis.

Journal of Clinical Endocrinology & Metabolism 90(5):p 2816-2822, May 2005.

Background:

Strontium ranelate, a new oral drug shown to reduce vertebral fracture risk in postmenopausal women with osteoporosis, was studied in the Treatment of Peripheral Osteoporosis (TROPOS) study to assess its efficacy and safety in preventing nonvertebral fractures also.

Methods:

Strontium ranelate (2 g/d) or placebo were randomly allocated to 5091 postmenopausal women with osteoporosis in a double-blind placebo-controlled 5-yr study with a main statistical analysis over 3 yr of treatment.

Findings:

In the entire sample, relative risk (RR) was reduced by 16% for all nonvertebral fractures (P = 0.04), and by 19% for major fragility fractures (hip, wrist, pelvis and sacrum, ribs and sternum, clavicle, humerus) (P = 0.031) in strontium ranelate-treated patients in comparison with the placebo group. Among women at high risk of hip fracture (age ≥74 yr and femoral neck bone mineral density T score ≤−3, corresponding to −2.4 according to NHANES reference) (n = 1977), the RR reduction for hip fracture was 36% (P = 0.046). RR of vertebral fractures was reduced by 39% (P < 0.001) in the 3640 patients with spinal x-rays and by 45% in the subgroup without prevalent vertebral fracture.

Strontium ranelate increased bone mineral density throughout the study, reaching at 3 yr (P < 0.001): +8.2% (femoral neck) and +9.8% (total hip).

Incidence of adverse events (AEs) was similar in both groups.

Conclusion:

This study shows that strontium ranelate significantly reduces the risk of all nonvertebral and in a high-risk subgroup, hip fractures over a 3-yr period, and is well tolerated. It confirms that strontium ranelate reduces vertebral fractures. Strontium ranelate offers a safe and effective means of reducing the risk of fracture associated with osteoporosis.