Letter to the Editor
Is it necessary to modify the clinical trials about osteoporosis? The serious problem of denosumab
¿Es necesario modificar los ensayos clínicos sobre osteoporosis? El grave problema de denosumab
Manuel Sosa Henríqueza,b,
, M. Jesús Gómez de Tejada Romeroc, Oscar Torregrosa Suaud
Corresponding author
a Universidad de Las Palmas de Gran Canaria, Departamento de Ciencias Médicas y Quirúrgicas, Grupo de investigación en osteoporosis y metabolismo mineral, Las Palmas de Gran Canaria, Las Palmas, Spain
b Unidad Metabólica Ósea, Hospital Universitario Insular, Las Palmas de Gran Canaria, Las Palmas, Spain
c Departamento de Medicina, Universidad de Sevilla, Sevilla, Spain
d Servicio de Medicina Interna, Hospital Universitario de Elche. Elche, Alicante, Spain
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The serious problem of denosumab" "tieneTextoCompleto" => true "saludo" => "Dear Editor," "paginas" => array:1 [ 0 => array:1 [ "paginaInicial" => "184" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Manuel Sosa Henríquez, M. Jesús Gómez de Tejada Romero, Oscar Torregrosa Suau" "autores" => array:3 [ 0 => array:4 [ "nombre" => "Manuel" "apellidos" => "Sosa Henríquez" "email" => array:1 [ 0 => "manuel.sosa@ulpgc.es" ] "referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 2 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "M. Jesús" "apellidos" => "Gómez de Tejada Romero" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] 2 => array:3 [ "nombre" => "Oscar" "apellidos" => "Torregrosa Suau" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "aff0020" ] ] ] ] "afiliaciones" => array:4 [ 0 => array:3 [ "entidad" => "Universidad de Las Palmas de Gran Canaria, Departamento de Ciencias Médicas y Quirúrgicas, Grupo de investigación en osteoporosis y metabolismo mineral, Las Palmas de Gran Canaria, Las Palmas, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Unidad Metabólica Ósea, Hospital Universitario Insular, Las Palmas de Gran Canaria, Las Palmas, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Departamento de Medicina, Universidad de Sevilla, Sevilla, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Servicio de Medicina Interna, Hospital Universitario de Elche. Elche, Alicante, Spain" "etiqueta" => "d" "identificador" => "aff0020" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "¿Es necesario modificar los ensayos clínicos sobre osteoporosis? El grave problema de denosumab" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">The primary objective of randomized clinical trials for drugs used in the treatment of osteoporosis has been to reduce the risk of fracture, over and above changes in bone mineral density. Most of these trials, with few exceptions, have been carried out with a follow-up of 3 years. After confirming the effectiveness in reducing the risk of fracture, the drug follows the approval procedures by the corresponding agencies until its marketing.</p><p id="par0010" class="elsevierStylePara elsevierViewall">However, so far, the design of clinical trials and, above all, the assessment of adverse effects has not taken into account what happens when drugs are discontinued. It is generally accepted that the drug stops working and that the patient goes back to his/her pre-treatment condition: for example, the discontinuation of a lipid-lowering treatment causes the slow and progressive elevation of serum lipid levels to values observed at treatment initiation.</p><p id="par0015" class="elsevierStylePara elsevierViewall">In the field of osteoporosis, the most widely used pharmacological group, bisphosphonates, accumulate in bone tissue and this produces a beneficial residual effect in reducing the risk of fracture in such a way that, in the specific case of zoledronate, its administration for 6 consecutive years has a protective effect on the risk of fracture that lasts for 3 more years.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">1</span></a> This has led to considering the discontinuation of bisphosphonate treatment after a few years of its administration, the so-called therapeutic holidays, which is a highly controversial topic.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">2</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">However, a very detrimental rebound effect has recently been found with a drug widely used in the treatment of osteoporosis, denosumab. And while it is true that while the drug is being administered there is a notable reduction in the risk of vertebral fracture (and much less in non-vertebral fractures), when denosumab is discontinued, a terrible rebound effect is observed, producing a sudden loss of bone mineral density, to the extent that the densitometric values are worse than at the beginning of the treatment<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">3</span></a> and, more seriously, up to 25% of patients have a vertebral fracture, which is often multiple,<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">4</span></a> not knowing the cause of this side effect and not being able to verify the efficacy of a treatment that avoids it, although the empirical use of an antiresorptive treatment is recommended.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">3</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">All this leads us to reflect on whether the design of studies of drugs used in the treatment of osteoporosis should be limited to ascertaining the reduction in fracture risk over a period of time, while the drug is being administered. We know that, in the real world, patients are largely discontinuing osteoporosis drugs. In the specific case of denosumab, the discontinuation rate in Spain reaches 55% at 2 years.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">5</span></a> Therefore, we propose in this paper that the safety study of drugs for the treatment of osteoporosis should include the possible adverse reactions which are observed after discontinuing the drug, extremely harmful to patients who have suffered from them in the case of denosumab.</p><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Conflict of interests</span><p id="par0180" class="elsevierStylePara elsevierViewall">The authors declare no conflict of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0040" "titulo" => "Conflict of interests" ] 1 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Sosa Henríquez M, Gómez de Tejada Romero MJ, Torregrosa Suau O. ¿Es necesario modificar los ensayos clínicos sobre osteoporosis? El grave problema de denosumab. Med Clin (Barc). 2020;155:184.</p>" ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:5 [ 0 => array:3 [ "identificador" => "bib0030" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The effect of 6 versus 9 years of zoledronic acid treatment in osteoporosis: a randomized second extension to the HORIZON-pivotal fracture trial (PFT)" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "D.M. Black" 1 => "I.R. Reid" 2 => "J.A. Cauley" 3 => "F. Cosman" 4 => "P.C. Leung" 5 => "P. Lakatos" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/jbmr.2442" "Revista" => array:6 [ "tituloSerie" => "J Bone Miner Res" "fecha" => "2015" "volumen" => "30" "paginaInicial" => "934" "paginaFinal" => "944" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25545380" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0035" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Caso clínico a debate: vacaciones terapéuticas: ¿sí o no?" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "M. Sosa Henríquez" 1 => "M.J. Gómez de Tejada Romero" 2 => "J. Malouf Sierra" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Rev Osteoporos Metab Miner" "fecha" => "2014" "volumen" => "6" "paginaInicial" => "63" "paginaFinal" => "69" ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0040" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Discontinuation of denosumab therapy for osteoporosis: a systematic review and position statement by ECTS" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "E. Tsourdi" 1 => "B. Langdahl" 2 => "M. Cohen-Solal" 3 => "B. Aubry-Rozier" 4 => "E.F. Eriksen" 5 => "N. Guañabens" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.bone.2017.08.003" "Revista" => array:6 [ "tituloSerie" => "Bone" "fecha" => "2017" "volumen" => "105" "paginaInicial" => "11" "paginaFinal" => "17" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28789921" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0045" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Clinical features of 24 patients with rebound-associated vertebral fractures after denosumab discontinuation: systematic review and additional cases" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "A.D. Anastasilakis" 1 => "S.A. Polyzos" 2 => "P. Makras" 3 => "B. Aubry-Rozier" 4 => "S. Kaouri" 5 => "O. Lamy" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/jbmr.3110" "Revista" => array:6 [ "tituloSerie" => "J Bone Miner Res" "fecha" => "2017" "volumen" => "32" "paginaInicial" => "1291" "paginaFinal" => "1296" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28240371" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0050" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "One and two-year persistence with different anti-osteoporosis medications: a retrospective cohort study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "C. Reyes" 1 => "C. Tebe" 2 => "D. Martinez-Laguna" 3 => "M.S. Ali" 4 => "A. Soria-Castro" 5 => "C. Carbonell" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s00198-017-4144-7" "Revista" => array:6 [ "tituloSerie" => "Osteoporos Int" "fecha" => "2017" "volumen" => "28" "paginaInicial" => "2997" "paginaFinal" => "3004" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28714038" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/23870206/0000015500000004/v2_202008242222/S238702062030317X/v2_202008242222/en/main.assets" "Apartado" => array:4 [ "identificador" => "43309" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Letters to the Editor" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/23870206/0000015500000004/v2_202008242222/S238702062030317X/v2_202008242222/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S238702062030317X?idApp=UINPBA00004N" ]
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