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      Tratamiento secuencial en osteoporosis. Nuevas tendencias Translated title: Sequential treatment in osteoporosis. New trends

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          Abstract

          Resumen El tratamiento para la osteoporosis suele ser largo en el tiempo, por lo que es necesario en muchas ocasiones recurrir a una estrategia secuencial de tratamiento. El clínico debe saber no solo seleccionar la mejor terapia disponible en cada situación clínica, sino también cómo discontinuar o cambiar de tratamiento en un momento determinado de la evolución de la enfermedad. En este documento presentamos de forma resumida una revisión de los mecanismos de acción y las consecuencias de la discontinuación de cada uno de los fármacos para la osteoporosis, así como qué ocurre en las diferentes secuencias de tratamiento. La discontinuación de denosumab tiene consecuencias claramente negativas para el hueso, y solo los bisfosfonatos, por tener un efecto antirresortivo residual, podrían discontinuarse durante un tiempo limitado (vacaciones terapéuticas). El cambio de un antirresortivo por otro antirresortivo con diferente mecanismo de acción es una opción que puede ser favorable en el manejo de algunos pacientes con osteoporosis. Cambiar un antirresortivo por un osteoformador puede asociarse a una pérdida inicial de densidad mineral ósea que no parece tener consecuencias negativas en la eficacia antifractura. Empezar con un tratamiento osteoformador (teriparatida o romosozumab) y cambiar posteriormente a un antirresortivo constituye la mejor secuencia de tratamiento, por lo que podría ser la opción preferente en pacientes con muy alto riesgo de fractura.

          Translated abstract

          Summary Treatment for osteoporosis is usually long term, so it is often necessary to implement a sequential treatment strategy. The clinician must know not only how to select the best available therapy in each clinical situation, but also how to discontinue or change treatment at a certain point in the evolution of the disease. Here, we briefly review the mechanisms of action and the consequences of discontinuing each of the drugs for osteoporosis, as well as what happens with the different treatment sequences. Discontinuation of denosumab has clearly negative consequences for the skeleton, and only bisphosphonates, due to its particular remaining antiresorptive effect, could be discontinued for a limited time (drug holidays). Switching from antiresorptive to another antiresorptive with a different mechanism of action is an option that may be favorable in the management of some patients with osteoporosis. Switching from antiresorptive to anabolic may be associated with an initial bone mineral density loss that does not appear to have negative consequences on antifracture efficacy. Starting with anabolic (teriparatide or romosozumab) and subsequently switching to antiresorptive is the best treatment sequence, so it could be the preferred option in patients who present a very high risk of fracture.

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          Most cited references57

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          Denosumab for prevention of fractures in postmenopausal women with osteoporosis.

          Denosumab is a fully human monoclonal antibody to the receptor activator of nuclear factor-kappaB ligand (RANKL) that blocks its binding to RANK, inhibiting the development and activity of osteoclasts, decreasing bone resorption, and increasing bone density. Given its unique actions, denosumab may be useful in the treatment of osteoporosis. We enrolled 7868 women between the ages of 60 and 90 years who had a bone mineral density T score of less than -2.5 but not less than -4.0 at the lumbar spine or total hip. Subjects were randomly assigned to receive either 60 mg of denosumab or placebo subcutaneously every 6 months for 36 months. The primary end point was new vertebral fracture. Secondary end points included nonvertebral and hip fractures. As compared with placebo, denosumab reduced the risk of new radiographic vertebral fracture, with a cumulative incidence of 2.3% in the denosumab group, versus 7.2% in the placebo group (risk ratio, 0.32; 95% confidence interval [CI], 0.26 to 0.41; P<0.001)--a relative decrease of 68%. Denosumab reduced the risk of hip fracture, with a cumulative incidence of 0.7% in the denosumab group, versus 1.2% in the placebo group (hazard ratio, 0.60; 95% CI, 0.37 to 0.97; P=0.04)--a relative decrease of 40%. Denosumab also reduced the risk of nonvertebral fracture, with a cumulative incidence of 6.5% in the denosumab group, versus 8.0% in the placebo group (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01)--a relative decrease of 20%. There was no increase in the risk of cancer, infection, cardiovascular disease, delayed fracture healing, or hypocalcemia, and there were no cases of osteonecrosis of the jaw and no adverse reactions to the injection of denosumab. Denosumab given subcutaneously twice yearly for 36 months was associated with a reduction in the risk of vertebral, nonvertebral, and hip fractures in women with osteoporosis. (ClinicalTrials.gov number, NCT00089791.) 2009 Massachusetts Medical Society
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            Romosozumab Treatment in Postmenopausal Women with Osteoporosis.

            Background Romosozumab, a monoclonal antibody that binds sclerostin, increases bone formation and decreases bone resorption. Methods We enrolled 7180 postmenopausal women who had a T score of -2.5 to -3.5 at the total hip or femoral neck. Patients were randomly assigned to receive subcutaneous injections of romosozumab (at a dose of 210 mg) or placebo monthly for 12 months; thereafter, patients in each group received denosumab for 12 months, at a dose of 60 mg, administered subcutaneously every 6 months. The coprimary end points were the cumulative incidences of new vertebral fractures at 12 months and 24 months. Secondary end points included clinical (a composite of nonvertebral and symptomatic vertebral) and nonvertebral fractures. Results At 12 months, new vertebral fractures had occurred in 16 of 3321 patients (0.5%) in the romosozumab group, as compared with 59 of 3322 (1.8%) in the placebo group (representing a 73% lower risk with romosozumab; P<0.001). Clinical fractures had occurred in 58 of 3589 patients (1.6%) in the romosozumab group, as compared with 90 of 3591 (2.5%) in the placebo group (a 36% lower risk with romosozumab; P=0.008). Nonvertebral fractures had occurred in 56 of 3589 patients (1.6%) in the romosozumab group and in 75 of 3591 (2.1%) in the placebo group (P=0.10). At 24 months, the rates of vertebral fractures were significantly lower in the romosozumab group than in the placebo group after each group made the transition to denosumab (0.6% [21 of 3325 patients] in the romosozumab group vs. 2.5% [84 of 3327] in the placebo group, a 75% lower risk with romosozumab; P<0.001). Adverse events, including instances of hyperostosis, cardiovascular events, osteoarthritis, and cancer, appeared to be balanced between the groups. One atypical femoral fracture and two cases of osteonecrosis of the jaw were observed in the romosozumab group. Conclusions In postmenopausal women with osteoporosis, romosozumab was associated with a lower risk of vertebral fracture than placebo at 12 months and, after the transition to denosumab, at 24 months. The lower risk of clinical fracture that was seen with romosozumab was evident at 1 year. (Funded by Amgen and UCB Pharma; FRAME ClinicalTrials.gov number, NCT01575834 .).
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              Romosozumab in postmenopausal women with low bone mineral density.

              Sclerostin is an osteocyte-derived inhibitor of osteoblast activity. The monoclonal antibody romosozumab binds to sclerostin and increases bone formation.
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                Author and article information

                Journal
                romm
                Revista de Osteoporosis y Metabolismo Mineral
                Rev Osteoporos Metab Miner
                Sociedad Española de Investigaciones Óseas y Metabolismo Mineral (Madrid, Madrid, Spain )
                1889-836X
                2173-2345
                December 2021
                : 13
                : 4
                : 107-116
                Affiliations
                [04] Baracaldo País Vasco orgnameUniversidad del País Vasco Spain
                [01] Sabadell orgnameHospital Universitari Parc Taulí orgdiv1Servicio de Reumatología España
                [03] orgnameHospital Universitario Cruces orgdiv1Servicio de Obstetricia y Ginecología España
                [02] orgnameInstitut d'Investigació i Innovació Parc Taulí España
                Article
                S1889-836X2021000400002 S1889-836X(21)01300400002
                10.4321/s1889-836x2021000300002
                cb7599b1-0b74-4b4a-b1d8-cf2b40d41f49

                This work is licensed under a Creative Commons Attribution-NonCommercial 3.0 International License.

                History
                : 21 September 2021
                : 19 January 2021
                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 57, Pages: 10
                Product

                SciELO Spain

                Categories
                Artículo Especial

                sequential therapy,osteoformador,antirresortivo,tratamiento,osteoporosis,terapia secuencial,bone formation,antiresorptive,treatment

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