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Randomized Trial of Alendronate Plus Vitamin D3 Versus Standard Care in Osteoporotic Postmenopausal Women with Vitamin D Insufficiency

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Abstract

Vitamin D insufficiency is common in patients with osteoporosis. We conducted a randomized trial comparing alendronate 70 mg combined with vitamin D3 5,600 IU in a single tablet (ALN/D5600, n = 257) with standard care chosen by the patients’ personal physicians (n = 258) in patients with postmenopausal osteoporosis (BMD T score ≤2.5 or ≤1.5 and a prior fragility fracture) who had vitamin D insufficiency (serum 25[OH]D values 8–20 ng/ml) and who were at risk of falls. Virtually all patients randomized to standard care received bisphosphonate therapy, and in approximately 70% of cases this was combined with vitamin D supplements. However, only 24% took ≥800 IU/day of supplemental vitamin D. At 6 months the proportion of patients with vitamin D insufficiency was 8.6% in the ALN/D5600 group compared with 31.0% in the standard care group (P < 0.001). Those in the ALN/D5600 group also had a greater reduction in urinary NTX/creatinine ratio (−57% vs. −46%, P < 0.001) and bone-specific alkaline phosphatase (−47% vs. −40%, P < 0.001). In the ALN/5600 group, by 12 months the increase in BMD was greater at the lumbar spine (4.9% vs. 3.9%, P = 0.047) and the total hip (2.2% vs. 1.4%, P = 0.035), significantly fewer patients were vitamin D—insufficient (11.3% vs. 36.9%, P < 0.001), and bone turnover marker (BTM) results were similar to those at 6 months. There was no difference between groups in those who experienced falls or fractures, and adverse events were similar. Based on the finding that ALN/D5600 was more effective than standard care at correcting vitamin D insufficiency, increasing BMD, and reducing BTMs in this patient group, greater attention needs to be directed toward optimizing the treatment of osteoporosis and correcting vitamin D deficiency in postmenopausal women.

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Authors and Affiliations

  1. Rheumatic Diseases Unit, Molecular Medicine Centre, Institute of Genetics and Molecular Medicine, Western General Hospital, University of Edinburgh, Edinburgh, EH4 2XU, UK

    Stuart H. Ralston

  2. University of Wisconsin, Madison, WI, USA

    Neil Binkley

  3. Center for Metabolic Bone Disease, University of Leuven, Leuven, Belgium

    Steven Boonen

  4. Institute for Aging Research, Hebrew SeniorLife and Harvard Medical School, Boston, MA, USA

    Douglas P. Kiel

  5. University of Liège, Liège, Belgium

    Jean-Yves Reginster

  6. Paris Descartes University, Paris, France

    Christian Roux

  7. Merck, Whitehouse Station, NJ, USA

    Liang Chen, Elizabeth Rosenberg & Arthur Santora

Authors
  1. Stuart H. Ralston
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  2. Neil Binkley
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  3. Steven Boonen
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  4. Douglas P. Kiel
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  5. Jean-Yves Reginster
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  6. Christian Roux
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  7. Liang Chen
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  8. Elizabeth Rosenberg
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  9. Arthur Santora
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Consortia

Investigators of FOCUS-D (FOSAVANCE vs. Standard Care—Use and Study of Vitamin D) Trial

Corresponding author

Correspondence to Stuart H. Ralston.

Additional information

This study was sponsored by Merck. S. Ralston has received consultancy fees from Merck Sharp & Dohme, a subsidiary of Merck & Co., Inc. N. Binkley has received consultancy fees from Merck Sharp & Dohme, a subsidiary of Merck & Co., Inc. S. Boonen has received research grants and consultancy fees from Merck Sharp & Dohme, a subsidiary of Merck & Co., Inc. D. Kiel has received research grants and consultancy fees from Merck Sharp & Dohme, a subsidiary of Merck & Co., Inc. J. Reginster has received consultancy fees from Merck Sharp & Dohme, a subsidiary of Merck & Co., Inc. C. Roux received honoraria and/or lecture fees and/or research grants from Merck Sharp & Dohme, a subsidiary of Merck & Co., Inc. L. Chen, E. Rosenberg, and A. Santora are employees of Merck & Co., Inc. and may own stock in the company.

Appendix: FOCUS-D Investigators

Appendix: FOCUS-D Investigators

Tara Coughlan, Adelaide & Meath Hospital, Dublin, Ireland; Asma Arabi, American University of Beirut Medical Center, Beirut, Lebanon; Ayse Kucukdeveci, Ankara University, Ankara, Turkey; Naren Savani, Batchworth House Mount Vernon Hospital, Middlesex, UK; Rasa Kausiene, Bendrosios terapijos skyrius, Siauliai, Lithuania; Bruno Pornel, Brussels Menopause Center, Brussels, Belgium; Tom Price, Cannock Chase Hospital, Staffordshire, UK; Claude-Laurent Benhamou, Centre Hop Porte Madeleine, Orleans, France; Maria Aguilar, Centro de Diagnostico Medicont S.A. de C.V., Nezahualcoyotl, Mexico; Mauricio Abello, Centro Integral de Reumatologia del Caribe, Barranquilla, Atlantico, Colombia; Elgardo Tobias, Centro Integral de Reumatologia e Inmunologia, Bogota, Cundinamarca, Colombia; Nadeem Rais, Chowpatty Medical Center, Mumbai, Maharashtra, India; Olga Ershova, Clinical Hospital for Emergency Care n.a. Soloviev, Yaroslavl, Russian Federation; Rene Martz, Clinical Research Hamburg, Hamburg, Germany; Sultan Linjawi, Coffs Endocrine & Diabetes Services, Coffs Harbour, NSW, Australia; Stuart Kramer, Danville Orthopedic Clinic, Danville, VA, USA; Jesus Walliser, Eentro Walliser de Osteoporosis y Metabolismo Mineral, Veracruz, Mexico; Simin Hepguler, Ege University, Bornova, Turkey; Jeffrey Gimble, Family Health Center, Baton Rouge, LA, USA; Olga Lesnyak, Family Medicine Clinic of Ural State Medical Academy, Ekaterinburg, Russian Federation; Philippe Chalem, Fundacion Instituto de Reumatologia Fernando Chalem, Bogota, Colombia; Jose Aramburu, H. de Basurto, Bilbao, Vizaya, Spain; Joseph Foldes, Hadassah Har-Hatzofim Medical Center, Jerusalem, Israel; Yasser Yaghi, Hammoud Hospital, Saida South, Lebanon; Christian Roux, Hopital Cochin, Paris, France; Carlos Abud, Hospital Central Dr. Ignacio Morones Prieto, San Luis Potosi, Mexico; Manuel Muñoz Torres, Hospital Clinico San Cecilio, Granada, Spain; Gilberto González, Hospital Clinico Universidad Catolica de Chile, Santiago, Chile; Georges Weryha, Hospital de Brabois, Vandoeuvre les Nancy, France; Emilio Martín Mola, Hospital Universitario La Paz, Madrid, Spain; Marina Shargordsky, Hypertension Clinic Wolfson Medical Center, Holon, Israel; Neeta Patel Inkosi Albert Luthuli Hospital, Durban, South Africa; Kurt Lippuner, Inselspital–Poliklinik für Osteoporose, Bern, Switzerland; Ruediger Moericke, Institut für Praventive Medizin & Klinische Forschung, Magdeburg, Germany; Basel Masri, Jordan Hospital, Amman, Jordan; Inguta Stura, Juglas Medicinas Centrs, Riga, Latvia; Robert Theiler, Klinik für Rheumatologie und Rehabilitation Stadtsp., Zurich, Switzerland; Nigar Dursun, Kocaeli University, Kocaeli, Turkey; Vincent Thompson, Libra Clinical Research Associates, Brick, NJ, USA; Dac Andersone, Liepajas Metalurga Poliklinika, Liepaja, Latvia; Mark Arya, Maroubra Medical Centre, Maroubra, NSW, Australia; Carl-Peter Anderberg, Me3Plus Clinical Trials AB, Goteborg, Sweden; Michael Pfeifer, MEDWISS Bad Pyrmont, Bad Pyrmont, Germany; Hugo Goldstraj, Multispecialty Medical Center, North Miami Beach, FL, USA; Vidmantas Alekna, Nacionalinis Osteoporozes Centras, Vilnius, Lithuania; Bram Wieskopf, North Georgia Clinical Research, Woodstock, GA, USA; Tobias De Villiers, Panorama Medi Clinic, Parow, Western Cape, South Africa; Salvatore Minisola, Policlinico Umberto I Sapienza University of Rome, Rome, Italy; Jean-Yves Reginster, Polyclinique L. Brull-Exploration de l’Os et du Cartilage, Liège, Belgium; Klaus Heil, Praxis Dr. Klaus Heil, Tuttlingen, Germany; Volkmar Herkt, Praxis Dr. Volkmar Herkt, Dresden, Germany; Jane Rohlf, Premier Research, Trenton, NJ, USA; Albert De Weerd, Pretoria East Private Hospital, Gauteng, South Africa; Sophia Ish-Shalom, Rambam Medical Center, Haifa, Israel; Loreta Bukauskiene, Reumatologijos skyrius, Klaipeda, Lithuania; Lidia Benevolenskaya, Research Institute of Rheumatology, Moscow, Russian Federation; Ruben Mantilla, Riesgo de Feractura S.A., Bogota, Cundinamarca, Colombia; Anthony Woolf, Royal Cornwall Hospitals NHS Trust, Cornwall, UK; William Otero, SERVIMED Bucaramanga, Santander, Colombia; Savithree Nayiager, St. Augustine’s Hospital, Kwazulu Natal, South Africa; Bernard Walsh, St. James’ Hospital–Robert Mayne Day Hospital, Dublin, Ireland; Stephen Newman, Brick, NJ, USA; Nitin Bagul, Synexus Lancashire Clinical Research Centre, Lancashire, UK; Essam Abdulhakim, Synexus Ltd. Merseyside Clinical Research Centre, Liverpool, UK; Shilpa Govindraj, Synexus Manchester Clinical Research Centre, Manchester, UK; Rex Sarmiento Synexus Midlands Clinical Research Centre, Birmingham, UK; Rahul Ellahbadi, Synexus Scotland Clinical Research Centre, Glasgow, UK; Hilary Shaw, Synexus Thames Valley Clinical Research, Berkshire, UK; Hawys Thomas, Synexus Wales Clinical Research Centre, Cardiff, UK; Stanley Lipschitz, The Memory Centre, Johannesburg, South Africa; Sergio Gutierrez, Torre de Especialidades–Ant Hosp. Civil de Gdl, Guadalajara, Mexico; Neil Binkley, University of Wisconsin, Madison, WI, USA; Stuart Ralston, Western General Hospital, Edinburgh, UK; Michael Davey, Westville Hospital, Durban, South Africa; Renato Lauro, Azienda Ospedaliera Universitaria, Rome, Italy; Hector Rodriguez, Central Medical & Therapy Center, Miami, FL, USA; Muataz Al-Ramahi, Jordan University Hospital, Amman, Jordan.

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Ralston, S.H., Binkley, N., Boonen, S. et al. Randomized Trial of Alendronate Plus Vitamin D3 Versus Standard Care in Osteoporotic Postmenopausal Women with Vitamin D Insufficiency. Calcif Tissue Int 88, 485–494 (2011). https://doi.org/10.1007/s00223-011-9482-4

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