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Implications for Fracture Healing of Current and New Osteoporosis Treatments: An ESCEO Consensus Paper

Calcified Tissue International volume 90, pages 343–353 (2012)Cite this article

Abstract

Osteoporotic fracture healing is critical to clinical outcome in terms of functional recovery, morbidity, and quality of life. Osteoporosis treatments may affect bone repair, so insights into their impact on fracture healing are important. We reviewed the current evidence for an impact of osteoporosis treatments on bone repair. Treatment with bisphosphonate in experimental models is associated with increased callus size and mineralization, reduced callus remodeling, and improved mechanical strength. Local and systemic bisphosphonate treatment may improve implant fixation. No negative impact on fracture healing has been observed, even after major surgery or when administered immediately after fracture. Experimental data for denosumab and raloxifene suggest no negative implications for bone repair. The extensive experimental results for teriparatide indicate increased callus formation, improved biomechanical strength, and greater external callus volume and total bone mineral content and density. Case reports and a randomized trial have produced mixed results but are consistent with a positive impact of teriparatide on clinical fracture healing. Studies with strontium ranelate in models of fracture healing indicate that it is associated with improved bone microstructure, callus volume, and biomechanical properties. Finally, there is experimental evidence for a beneficial effect of some of the agents currently being developed for osteoporosis, notably sclerostin antibody and DKK1 antibody. There is currently no evidence that osteoporosis treatments are detrimental for bone repair and some promising experimental evidence for positive effects on healing, notably for agents with a bone-forming mode of action, which may translate into therapeutic applications.

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Acknowledgements

This article was derived from a working group meeting on December 2, 2010, supported by the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO).

Author information

Affiliations

  1. AO Clinical Priority Program “Fracture Fixation in Osteoporotic Bone”, Institute for Biomechanics of ETH, Zurich, Switzerland

    J. Goldhahn

  2. Department of Orthopaedic and Trauma Surgery, Saint Antoine Hospital, AP-HP, UPMC-Sorbonne Universities, Paris, France

    J.-M. Féron

  3. WHO Collaborating Centre for Metabolic Bone Diseases, University of Sheffield Medical School, Sheffield, UK

    J. Kanis

  4. Department of Endocrinology and Metabolic Diseases, Leiden University Medical Center, Leiden, The Netherlands

    S. Papapoulos

  5. Public Health and Health Economics, University of Liège, Liege, Belgium

    J.-Y. Reginster

  6. Division of Bone Disease, Department of Rehabilitation and Geriatrics, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland

    R. Rizzoli

  7. Amgen, Ltd, Uxbridge, UK

    W. Dere

  8. Lilly Corporate Center, Eli Lilly and Company, Indianapolis, IN, USA

    B. Mitlak

  9. Institute de Recherches Internationales Servier, Courbevoie, France

    Y. Tsouderos

  10. Division of Gerontology and Geriatrics, Department of Experimental Medicine, Centre for Metabolic Bone Disease, Leuven University, Leuven, Belgium

    S. Boonen

Authors
  1. J. Goldhahn
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  2. J.-M. Féron
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  3. J. Kanis
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  4. S. Papapoulos
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  5. J.-Y. Reginster
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  6. R. Rizzoli
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  7. W. Dere
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  8. B. Mitlak
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  9. Y. Tsouderos
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  10. S. Boonen
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Corresponding author

Correspondence to J. Goldhahn.

Additional information

S. Boonen has received consulting fees, advisory board fees, lecture fees, and/or grant support from Amgen, Eli Lilly, GlaxoSmithKline, Merck, Novartis, Ono, Roche, Sanofi-Aventis, Servier, and Warner Chilcott. J-M. Feron has received advisory boards or lecture fees from Amgen, Lilly, Novartis, and Servier. W. Dere is an employee of Amgen. J. Goldhahn has received consulting fees or paid advisory board fees from Amgen, Eli Lilly, Novartis, Pfizer, and Servier. J. Kanis has received consulting and lecture fees, on paid advisory boards, and/or grant support from Abiogen, Italy; Amgen, USA, Switzerland and Belgium; Bayer, Germany; Besins-Iscovesco, France; Biosintetica, Brazil; Boehringer Ingelheim, UK; Celtrix, USA; D3A, France; European Federation of Pharmaceutical Industry and Associations, (EFPIA) Brussels; Gador, Argentina; General Electric, USA; GSK, UK, USA; Hologic, Belgium and USA; Kissei, Japan; Leiras, Finland; Leo Pharma, Denmark; Lilly, USA, Canada, Japan, Australia and UK; Merck Research Labs, USA; Merlin Ventures, UK; MRL, China; Novartis, Switzerland and USA; Novo Nordisk, Denmark; Nycomed, Norway; Ono, UK and Japan; Organon, Holland; Parke-Davis, USA; Pfizer USA; Pharmexa, Denmark; Procter and Gamble, UK, USA; ProStrakan, UK; Roche, Germany, Australia, Switzerland, USA; Rotta Research, Italy; Sanofi-Aventis, USA; Schering, Germany and Finland; Servier, France and UK; Shire, UK; Solvay, France and Germany; Strathmann, Germany; Tarsa Therapeutics, US; Tethys, USA; Teijin, Japan; Teva, Israel; UBS, Belgium; Unigene, USA; Warburg-Pincus, UK; Warner-Lambert, USA; Wyeth, USA. B. Mitlak is an employee of Eli Lilly and Company. S. Papapoulos has received consulting, advisory board and/or lecture fees from Amgen, Eli Lilly, GlaxoSmithKleine, Merck & Co, Novartis, Roche, Warner Chilcott and Wyeth. J-Y. Reginster has received consulting fees, advisory board fees, lecture fees, and/or grant support from Servier, Novartis, Negma, Lilly, Wyeth, Amgen, GlaxoSmithKline, Roche, Merckle, Nycomed, NPS, Theramex, UCB, Merck Sharp and Dohme, Rottapharm, IBSA, Genevrier, Teijin, Teva, Ebewee Pharma, Zodiac, Analis, Novo-Nordisk, and Bristol Myers Squibb. R. Rizzoli has received advisory board or lecture fees for Merck Sharp and Dohme, Eli Lilly, Amgen, Novartis, Servier, Nycomed, Nestlé, and Danone. Y. Tsouderos is an employee of Servier.

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Goldhahn, J., Féron, JM., Kanis, J. et al. Implications for Fracture Healing of Current and New Osteoporosis Treatments: An ESCEO Consensus Paper. Calcif Tissue Int 90, 343–353 (2012). https://doi.org/10.1007/s00223-012-9587-4

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  • DOI: https://doi.org/10.1007/s00223-012-9587-4

Keywords

  • Fractures
  • Healing
  • Bone formation
  • Osteoporosis
  • Treatment