Treatment of Osteoporosis and Osteoarthritis in the Oldest Old

Nicholas Fuggle¹, Andrea Laslop², René Rizzoli³, Nasser Al-Daghri⁴, Majed Alokail⁵, Ewa Balkowiec-Iskra^{6

7}, Charlotte Beaudart⁸, Olivier Bruyère⁹, Angie Botto-van Bemden¹⁰, Nansa Burlet¹¹, Etienne Cavalier¹², Francesca Cerreta¹³, Manju Chandran^{14

15}, Antonio Cherubini^{16

17}, Mario Miguel Coelho da Silva Rosa¹⁸, Philip Conaghan^{19

20}, Bernard Cortet²¹, Alfonso Cruz Jentoft²², Elizabeth M Curtis¹, Patrizia D'Amelio²³, Bess Dawson-Hughes²⁴, Elaine M Dennison¹, Mickaël Hiligsmann²⁵, Jean-Marc Kaufman²⁶, Stefania Maggi²⁷, Radmila Matijevic²⁸, Eugene McCloskey²⁹, Daniel Messina³⁰, Daniel Pinto³¹, Maria Concepcion Prieto Yerro³², Régis Pierre Radermecker³³, Yves Rolland³⁴, Carla Torre^{35

36}, Nicola Veronese^{4

37}, John A Kanis^{29

38}, Cyrus Cooper^{1

39

40}, Jean-Yves Reginster^#^{5

9}, Nicholas C Harvey^#^{41

42}

Affiliations

¹ MRC Lifecourse Epidemiology Centre, University of Southampton, Southampton, SO16 6YD, UK.
² Scientific Office, Austrian Medicines and Medical Devices Agency, Vienna, Austria.
³ Division of Bone Diseases, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland.
⁴ Chair for Biomarkers of Chronic Diseases, Biochemistry Department, College of Science, King Saud University, 11451, Riyadh, Saudi Arabia.
⁵ Protein Research Chair, Biochemistry Department, College of Science, King Saud University, 11451, Riyadh, Saudi Arabia.
⁶ Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Warsaw, Poland.
⁷ The Office for Registration of Medicinal Products, Medical Devices and Biocidal Products, Warsaw, Poland.
⁸ Clinical Pharmacology and Toxicology Research Unit, Department of Biomedical Sciences, Faculty of Medicine, NARILIS, University of Namur, Namur, Belgium.
⁹ Research Unit in Public Health, Epidemiology and Health Economics, University of Liège, Liège, Belgium.
¹⁰ Musculoskeletal Research International, Inc., Boston, USA.
¹¹ The European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO), Liege, Belgium.
¹² Department of Clinical Chemistry, CIRM, University of Liège, CHU de Liège, Liège, Belgium.
¹³ European Medicines Agency, Amsterdam, The Netherlands.
¹⁴ Osteoporosis and Bone Metabolism Unit, Department of Endocrinology, Singapore General Hospital, Singapore, Singapore.
¹⁵ DUKE NUS Medical School, Singapore, Singapore.
¹⁶ Geriatria, Accettazione geriatrica e Centro di ricerca per l'invecchiamento, IRCCS INRCA, Ancona, Italy.
¹⁷ Department of Clinical and Molecular Sciences, Università Politecnica delle Marche, Ancona, Italy.
¹⁸ Faculdade de Medicina, Centro de Estudos Egas Moniz, Universidade de Lisboa, Lisbon, Portugal.
¹⁹ Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK.
²⁰ NIHR Leeds Biomedical Research Centre, Leeds, UK.
²¹ Department of Rheumatology, University of Lille, Lille, France.
²² Servicio de Geriatría. Hospital Universitario Ramón y Cajal (IRYIS), Madrid, Spain.
²³ Department of Geriatrics and Geriatric Rehabilitation, Lausanne University Hospital, Lausanne, Switzerland.
²⁴ Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA.
²⁵ Department of Health Services Research, CAPHRI Care and Public Health Research Institute, Maastricht University, Maastricht, the Netherlands.
²⁶ Department of Endocrinology, Ghent University Hospital, Ghent, Belgium.
²⁷ CNR Aging Branch-IN, Padua, Italy.
²⁸ Faculty of Medicine, Clinic for Orthopedic Surgery and Traumatology, Clinical Center of Vojvodina, University of Novi Sad, Novi Sad, Serbia.
²⁹ Division of Clinical Medicine, School of Medicine and Population Health, Centre for Integrated Research in Musculoskeletal Ageing, University of Sheffield, Sheffield, UK.
³⁰ IRO Investigaciones Reumatologicas y Osteologicas SRL Collaborating Centre WHO, University of Buenos Aires, Buenos Aires, Argentina.
³¹ Department of Physical Therapy, Marquette University, Milwaukee, WI, USA.
³² Agencia Española de Medicamentos y Productos Sanitarios, Madrid, Spain.
³³ Department of Diabetes, Nutrition and Metabolic disorders, Clinical pharmacology, University of Liège, CHU de Liège, Liège, Belgium.
³⁴ IHU Health Age, CHU Toulouse, INSERM 1295, Toulouse, France.
³⁵ Faculdade de Farmácia, Universidade de Lisboa, Avenida Professor Gama Pinto, 1649-003, Lisbon, Portugal.
³⁶ Laboratory of Systems Integration Pharmacology, Clinical and Regulatory Science, Research Institute for Medicines of the University of Lisbon (iMED.ULisboa), Avenida Professor Gama Pinto, 1649-003, Lisbon, Portugal.
³⁷ Geriatric Unit, Department of Medicine, University of Palermo, 90127, Palermo, Italy.
³⁸ Mary McKillop Institute for Health Research, Australian Catholic University, Melbourne, Australia.
³⁹ NIHR Southampton Biomedical Research Centre, University of Southampton, Southampton, UK.
⁴⁰ NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UK.
⁴¹ MRC Lifecourse Epidemiology Centre, University of Southampton, Southampton, SO16 6YD, UK. nch@mrc.soton.ac.uk.
⁴² NIHR Southampton Biomedical Research Centre, University of Southampton, Southampton, UK. nch@mrc.soton.ac.uk.

^# Contributed equally.

PMID: 39969778
PMCID: PMC11891106
DOI: 10.1007/s40265-024-02138-w

Review

Treatment of Osteoporosis and Osteoarthritis in the Oldest Old

Nicholas Fuggle et al. Drugs. 2025 Mar.

. 2025 Mar;85(3):343-360.

doi: 10.1007/s40265-024-02138-w. Epub 2025 Feb 19.

Authors

Affiliations

¹ MRC Lifecourse Epidemiology Centre, University of Southampton, Southampton, SO16 6YD, UK.
² Scientific Office, Austrian Medicines and Medical Devices Agency, Vienna, Austria.
³ Division of Bone Diseases, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland.
⁴ Chair for Biomarkers of Chronic Diseases, Biochemistry Department, College of Science, King Saud University, 11451, Riyadh, Saudi Arabia.
⁵ Protein Research Chair, Biochemistry Department, College of Science, King Saud University, 11451, Riyadh, Saudi Arabia.
⁶ Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Warsaw, Poland.
⁷ The Office for Registration of Medicinal Products, Medical Devices and Biocidal Products, Warsaw, Poland.
⁸ Clinical Pharmacology and Toxicology Research Unit, Department of Biomedical Sciences, Faculty of Medicine, NARILIS, University of Namur, Namur, Belgium.
⁹ Research Unit in Public Health, Epidemiology and Health Economics, University of Liège, Liège, Belgium.
¹⁰ Musculoskeletal Research International, Inc., Boston, USA.
¹¹ The European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO), Liege, Belgium.
¹² Department of Clinical Chemistry, CIRM, University of Liège, CHU de Liège, Liège, Belgium.
¹³ European Medicines Agency, Amsterdam, The Netherlands.
¹⁴ Osteoporosis and Bone Metabolism Unit, Department of Endocrinology, Singapore General Hospital, Singapore, Singapore.
¹⁵ DUKE NUS Medical School, Singapore, Singapore.
¹⁶ Geriatria, Accettazione geriatrica e Centro di ricerca per l'invecchiamento, IRCCS INRCA, Ancona, Italy.
¹⁷ Department of Clinical and Molecular Sciences, Università Politecnica delle Marche, Ancona, Italy.
¹⁸ Faculdade de Medicina, Centro de Estudos Egas Moniz, Universidade de Lisboa, Lisbon, Portugal.
¹⁹ Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK.
²⁰ NIHR Leeds Biomedical Research Centre, Leeds, UK.
²¹ Department of Rheumatology, University of Lille, Lille, France.
²² Servicio de Geriatría. Hospital Universitario Ramón y Cajal (IRYIS), Madrid, Spain.
²³ Department of Geriatrics and Geriatric Rehabilitation, Lausanne University Hospital, Lausanne, Switzerland.
²⁴ Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA.
²⁵ Department of Health Services Research, CAPHRI Care and Public Health Research Institute, Maastricht University, Maastricht, the Netherlands.
²⁶ Department of Endocrinology, Ghent University Hospital, Ghent, Belgium.
²⁷ CNR Aging Branch-IN, Padua, Italy.
²⁸ Faculty of Medicine, Clinic for Orthopedic Surgery and Traumatology, Clinical Center of Vojvodina, University of Novi Sad, Novi Sad, Serbia.
²⁹ Division of Clinical Medicine, School of Medicine and Population Health, Centre for Integrated Research in Musculoskeletal Ageing, University of Sheffield, Sheffield, UK.
³⁰ IRO Investigaciones Reumatologicas y Osteologicas SRL Collaborating Centre WHO, University of Buenos Aires, Buenos Aires, Argentina.
³¹ Department of Physical Therapy, Marquette University, Milwaukee, WI, USA.
³² Agencia Española de Medicamentos y Productos Sanitarios, Madrid, Spain.
³³ Department of Diabetes, Nutrition and Metabolic disorders, Clinical pharmacology, University of Liège, CHU de Liège, Liège, Belgium.
³⁴ IHU Health Age, CHU Toulouse, INSERM 1295, Toulouse, France.
³⁵ Faculdade de Farmácia, Universidade de Lisboa, Avenida Professor Gama Pinto, 1649-003, Lisbon, Portugal.
³⁶ Laboratory of Systems Integration Pharmacology, Clinical and Regulatory Science, Research Institute for Medicines of the University of Lisbon (iMED.ULisboa), Avenida Professor Gama Pinto, 1649-003, Lisbon, Portugal.
³⁷ Geriatric Unit, Department of Medicine, University of Palermo, 90127, Palermo, Italy.
³⁸ Mary McKillop Institute for Health Research, Australian Catholic University, Melbourne, Australia.
³⁹ NIHR Southampton Biomedical Research Centre, University of Southampton, Southampton, UK.
⁴⁰ NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UK.
⁴¹ MRC Lifecourse Epidemiology Centre, University of Southampton, Southampton, SO16 6YD, UK. nch@mrc.soton.ac.uk.
⁴² NIHR Southampton Biomedical Research Centre, University of Southampton, Southampton, UK. nch@mrc.soton.ac.uk.

^# Contributed equally.

PMID: 39969778
PMCID: PMC11891106
DOI: 10.1007/s40265-024-02138-w

Abstract

Osteoporosis and osteoarthritis are key diseases of musculoskeletal ageing and are increasing in prevalence and burden with the progressively ageing population worldwide. These conditions are thus particularly common in 'the oldest old', and there are complexities of managing them within the context of extensive multimorbidity, physical and mental disability, and polypharmacy, the rates for all of which are high in this population. In this narrative review, we explore the epidemiology of osteoporosis and osteoarthritis in the oldest old before examining trials and real-world data relating to the pharmacological treatment of these diseases in older adults, including anti-resorptives and bone-forming agents in osteoporosis and symptomatic slow-acting drugs for osteoarthritis, paracetamol, and non-steroidal anti-inflammatory drugs in osteoarthritis, recognising that the oldest old are usually excluded from clinical trials. We then review the potential benefits of nutritional interventions and exercise therapy before highlighting the health economic benefits of interventions for osteoporosis and osteoarthritis. The high prevalence of risk factors for both disease and adverse events associated with treatment in the oldest old mean that careful attention must be paid to the potential benefits of intervention (including fracture risk reduction and improvements in osteoarthritis pain and function) versus the potential harms and adverse effects. Further direct evidence relating to such interventions is urgently needed from future research.

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Conflict of interest statement

Declarations. Funding: The ESCEO working group was funded by the ESCEO. The ESCEO receives unrestricted educational grants to support its educational and scientific activities from non-governmental organisations, not-for-profit organisations, non-commercial, or corporate partners. The choice of topics, participants, content, and agenda of the working groups as well as the writing, editing, submission, and reviewing of the manuscript are the sole responsibility of the ESCEO, without any influence from third parties. Conflict of Interest: NA-D, MA, CB, ABvB, NB, EC, MC, AC, PGC, EC, PD’A, BD-H, J-MK, SM, RM, EM, ODM, DP, MCPY, RPR and JAK, and have no competing interests to declare with respect to this manuscript. NF has received honoraria and speaker fees from Viatris and UCB. RRi has received fees for advisory board participation or lectures from Abiogen, Effryx, and Theramex. NCH has received personal fees, consultancy, lecture fees and/or honoraria from Alliance for Better Bone Health, AMGEN, MSD, Eli Lilly, UCB, Kyowa Kirin, Servier, Shire, Consilient Healthcare, Theramex and Internis Pharma. OB has received consulting or lecture fees from Amgen, Aptissen, Biophytis, IBSA, Mylan, Novartis, Nutricia, Orifarm, Sanofi, UCB, and Viatris. BC has received personal fees, consultancy fees, lecture fees, and honoraria from Alexion, Amgen, Expanscience, Kyowa-Kirin, MSD, Novartis,Theramex, UCB, and Viatris. AC-J has received honoraria for teaching activities from Abbott Nutrition, Fresenius Kabi, Nestlé Health Care, and Nutricia Danone. EMD has received consultancy honoraria and speaker fees from UCB, Pfizer, Viatris, and Lilly. MH has received research grants (paid to institution) from Radius Health and Angelini Pharma and lecture fees from IBSA (paid to institution) and Mylan Pharmaceuticals and was grant advisor for Pfizer (paid to institution). YR has received support from CHU Toulouse, University Paul Sabatier, and INSERM CERPOP1295 (employee); is a shareholder of SARQOL SPRL, a spin-off of the University of Liege; and has received consultancy fees from Longeveron and Biophytis and honoraria for lectures from Pfizer. NV has received personal fees from MYLAN, FIDIA, IBSA, Viatris, and Nestlè. AL is a member of the Scientific Advice Working Party at the European Medicines Agency and has no conflicting interests to declare. EB-I is a member of the CHMP, SAWP, CNSWP, PCWP, and ETF (European Medicines Agency) and has no conflicting interests to declare. FC has no competing interests with respect to this manuscript. CT is a member of the CHMP, PRAC, and MWP (European Medicines Agency) and has no conflicting interests to declare. MMR is a member of the SAWP and CNSWP (European Medicines Agency) and has no conflicting interests to declare. The views expressed in this article are the personal views of the authors and may not be understood or quoted as being made on behalf of or reflecting the position of any employing organisations or the regulatory agencies by which the authors are employed or affiliated, the European Medicines Agency (EMA), or one of its committees or working parties. CC has received personal fees, consultancy, lecture fees and/or honoraria from ABBH, Amgen, Eli Lilly, GSK, Medtronic, Merck, Novartis, Pfizer, Roche, Servier and Takeda. JYR has received consulting fees or paid advisory boards for IBSA-Genevrier, Mylan, Radius Health, Pierre Fabre, Faes Pharma, Rejuvenate Biomed, Samumed, Teva, Theramex, Pfizer, Mithra Pharmaceuticals, lecture fees when speaking at the invitation of the sponsor for IBSA-Genevrier, Mylan, Cniel, Dairy Research Council (DRC), Nutricia, Danone, Agnovos and grant support from IBSA-Genevrier, Mylan, Cniel, Radius Health, TRB. Availability of Data and material: Not applicable. Ethics Approval: This narrative article contains no original data, so issues of ethics, informed consent, and patient confidentiality do not apply. Consent to Participate: Not applicable. Consent for Publication: Not applicable. Code Availability: Not applicable. Author Contributions: All authors contributed to the discussion of the subject matter. NF, AL, RR, JYR, and NCH wrote the draft manuscript. All authors reviewed and commented on the manuscript.

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Treatment of Osteoporosis and Osteoarthritis in the Oldest Old

Affiliations

Treatment of Osteoporosis and Osteoarthritis in the Oldest Old

Authors

Affiliations

Abstract

Conflict of interest statement

References

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