Concentrados plaquetarios autólogos para el tratamiento de los defectos infraóseos periodónticos
Resumen
Antecedentes
La periodontopatía es un trastorno que afecta los tejidos que sostienen los dientes (encías, hueso alveolar, ligamento periodóntico y cemento), con el potencial de causar efectos adversos graves sobre la salud bucodental. Tiene una patogenia compleja que incluye la combinación de microorganismos específicos y una respuesta predisponente del huésped. Los defectos infraóseos son uno de los tipos morfológicos de defectos óseos alveolares que se pueden observar durante la periodontitis. Los enfoques recientes para el tratamiento de los defectos infraóseos combinan técnicas quirúrgicas avanzadas con factores de crecimiento derivados de plaquetas. Los mismos son polipéptidos sintetizados naturalmente que actúan como mediadores de diversas actividades celulares durante la cicatrización de la herida. Se cree que el uso adyuvante de concentrados plaquetarios autólogos agregados a los procedimientos quirúrgicos periodónticos produce un resultado mejor y más previsible para el tratamiento de los defectos infraóseos.
Objetivos
Evaluar los efectos de los concentrados plaquetarios autólogos (CPA) utilizados como complemento de los tratamientos quirúrgicos periodónticos (desbridamiento de colgajo abierto [DCA], DCA combinado con injerto óseo [IO], regeneración tisular guiada [RTG], DCA combinado con derivados de la matriz del esmalte [DME]) para el tratamiento de los defectos infraóseos.
Métodos de búsqueda
El especialista en información del Grupo Cochrane de Salud Oral (Cochrane Oral Health's Information Specialist) realizó una búsqueda en las siguientes bases de datos: Registro de ensayos del Grupo Cochrane de Salud Oral (Cochrane Oral Health Group) (hasta el 27 de febrero de 2018); Registro Cochrane Central de Ensayos Controlados (Cochrane Central Register of Controlled Trials (CENTRAL; 2018, número 1) en la Cochrane Library (búsqueda 27 de febrero de 2018); MEDLINE Ovid (1946 hasta 27 de febrero de 2018); Embase Ovid (1980 hasta 27 de febrero de 2018); y en LILACS BIREME Virtual Health Library (desde 1982 hasta 27 de febrero de 2018). Se buscaron ensayos en curso en el US National Institutes of Health Ongoing Trials Register (ClinicalTrials.gov) y en la World Health Organization International Clinical Trials Registry Platform el 27 de febrero de 2018. No se impusieron restricciones de idioma ni de fecha de publicación en la búsqueda en las bases de datos electrónicas.
Criterios de selección
Se incluyeron los ensayos controlados aleatorios (ECA) de diseño paralelo y de boca dividida, que incorporaron a pacientes con defectos infraóseos que requerían tratamiento quirúrgico. Los estudios tenían que haber comparado los resultados del tratamiento de una técnica quirúrgica específica combinada con CPA, con la misma técnica utilizada sola.
Obtención y análisis de los datos
Dos autores de la revisión, de forma independiente, realizaron la extracción de los datos y la evaluación del riesgo de sesgo y analizaron los datos siguiendo los métodos Cochrane. Los resultados primarios evaluados fueron: cambio en la profundidad de la bolsa al sondaje (PBS), cambio en el nivel de inserción clínica (NIC) y cambio en el relleno del defecto óseo radiográfico (ROR). Se organizaron todos los datos en cuatro grupos, y cada uno comparó una técnica quirúrgica específica cuando se la aplicó con el complemento de los CPA o sola: 1. CPA + DCA versus DCA, 2. CPA + DCA + IO versus DCA + IO, 3. CPA + RTG versus RTG y 4. CPA + DME versus DME.
Resultados principales
Se incluyeron 38 ECA. Veintidós tenían un diseño de boca dividida y 16 tenían un diseño paralelo. Los datos generales evaluados incluían 1402 defectos. Dos estudios presentaron un riesgo de sesgo general incierto, mientras que en los 36 restantes el riesgo general de sesgo fue alto.
1. CPA + DCA versus DCA solo
Se incluyeron 12 estudios en esta comparación, con un total de 510 defectos infraóseos. Hay evidencia de una ventaja en el uso de CPA a nivel global a partir de los estudios de boca dividida y paralelos en los tres resultados primarios: PBS (diferencia de medias [DM] 1,29; intervalo de confianza [IC] del 95%: 1,00 a 1,58 mm; P < 0,001; 12 estudios; 510 defectos; evidencia de muy baja calidad); NIC (DM 1,47 mm; IC del 95%: 1,11 a 1,82 mm; P < 0,001; 12 estudios; 510 defectos; evidencia de muy baja calidad); y ROR (DM 34,26%; IC del 95%: 30,07% a 38,46%; P < 0,001; nueve estudios; 401 defectos; evidencia de muy baja calidad).
2. CPA + DCA + IO versus DCA + IO
Se incluyeron 17 estudios en esta comparación, con un total de 569 defectos infraóseos. Al considerar todos los seguimientos, así como el de tres a seis meses y de nueve a 12 meses, hay evidencia de una ventaja del uso de CPA a partir de los estudios de boca dividida y paralelos en los tres resultados primarios: PBS (DM 0,54; IC del 95%: 0,33 a 0,75 mm; P < 0,001; 17 estudios; 569 defectos; evidencia de muy baja calidad); NIC (DM 0,72 mm; IC del 95%: 0,43 a 1,00 mm; P < 0,001; 17 estudios; 569 defectos; evidencia de muy baja calidad); y ROR (DM 8,10%; IC del 95%: 5,26% a 10,94%; P < 0,001; 11 estudios; 420 defectos; evidencia de muy baja calidad).
3. CPA + RTG versus RTG sola
Se incluyeron siete estudios en esta comparación, con un total de 248 defectos infraóseos. Al considerar todos los seguimientos, probablemente hay un efecto beneficioso de los CPA para la PBS (DM 0,92 mm; IC del 95%: ‐0,02 a 1,86 mm; P = 0,05; evidencia de muy baja calidad) y el NIC (DM 0,42 mm; IC del 95%: ‐0,02 a 0,86 mm; P = 0,06; evidencia de muy baja calidad). Sin embargo, debido a los intervalos de confianza amplios, podría existir la posibilidad de un efecto beneficioso leve del control. Cuando se consideró el seguimiento de tres a seis meses y de nueve a 12 de meses, no se observaron efectos beneficiosos, excepto por el NIC a los tres a seis meses (DM 0,54 mm; IC del 95%: 0,18 a 0,89 mm; P = 0,003; tres estudios; 134 defectos). No hubo datos disponibles sobre el ROR.
4. CPA + DME versus DME
Hubo dos estudios incluidos en esta comparación, con un total de 75 defectos infraóseos. No hay evidencia suficiente de una ventaja general del uso de CPA en los tres resultados primarios: PBS (DM 0,13 mm; IC del 95%: ‐0,05 a 0,30 mm; p = 0,16; dos estudios; 75 defectos; evidencia de muy baja calidad), NIC (DM 0,10 mm; IC del 95%: ‐0,13 a 0,32 mm; P = 0,40; dos estudios; 75 defectos; evidencia de muy baja calidad), y ROR (DM ‐0,60%; IC del 95%: ‐6,21% a 5,01%; P = 0,83; un estudio; 49 defectos; evidencia de muy baja calidad).
Todos los estudios de todos los grupos informaron de una tasa de supervivencia del 100% para los dientes tratados. No se informó del cierre completo de las bolsas. No fue posible el análisis cuantitativo con respecto a la calidad de vida del paciente.
Conclusiones de los autores
Hay evidencia de muy baja calidad de que el complemento de CPA al DCA o el DCA + IO para tratar los defectos infraóseos puede mejorar la profundidad de la bolsa al sondaje, el nivel de inserción clínica y el relleno del defecto óseo radiográfico. Para la RTG o los DME, no hubo evidencia suficiente de una ventaja del uso de CPA.
PICO
Resumen en términos sencillos
Concentrados plaquetarios autólogos para el tratamiento de los defectos infraóseos periodónticos
Pregunta de la revisión
¿El agregado de concentrados plaquetarios autólogos (CPA) mejora los resultados del tratamiento quirúrgico de los defectos óseos en las enfermedades de las encías?
Antecedentes
Los dientes se mantienen en su posición mediante los tejidos blandos y duros (encías y hueso circundante). La enfermedad de las encías, o periodontitis, es un trastorno inflamatorio de estos tejidos causada por las bacterias presentes en la placa dental. Si no se tratan, las enfermedades de las encías pueden causar que los dientes se aflojen y con el tiempo dar lugar a la pérdida de los dientes. La destrucción del hueso de la mandíbula alrededor de los dientes (llamado hueso alveolar) durante la enfermedad de las encías, puede ser horizontal (donde se reduce el nivel completo del hueso alrededor de la raíz) o vertical, y formar un defecto óseo dentro del hueso (defecto infraóseo). Hay varios tratamientos quirúrgicos disponibles para los defectos infraóseos, que incluyen: 1. el desbridamiento de colgajo abierto en el cual la encía se separa y se levanta hacia atrás quirúrgicamente para limpiar el sarro profundo; 2. el injerto óseo en el cual se coloca una porción de hueso natural o sintético en el área de la pérdida ósea; 3. la regeneración tisular guiada en la que se coloca un trozo pequeño de material similar a la membrana entre el hueso y el tejido de las encías para evitar que éste crezca en el área en que debe haber hueso; y 4. el uso de derivados de la matriz del esmalte, un material similar a un gel que se coloca en el área donde ha ocurrido la pérdida ósea y promueve su regeneración. Para acelerar el proceso curativo, recientemente se han usado concentrados plaquetarios autólogos. Son concentrados de las plaquetas de la propia sangre del paciente con factores de crecimiento que se cree que promueven la regeneración tisular. El objetivo de esta revisión fue evaluar si el agregado de CPA tiene efectos beneficiosos en el tratamiento de los defectos infraóseos cuando se combina con diferentes tratamientos quirúrgicos.
Características de los estudios
Los autores del Grupo Cochrane de Salud Oral (Cochrane Oral Health Group) realizaron esta revisión y la evidencia está actualizada hasta el 27 de febrero de 2018. Se incluyeron 38 estudios y 1042 defectos infraóseos. Se consideraron cuatro tipos diferentes de tratamientos quirúrgicos y cada técnica se comparó con el mismo tratamiento con el agregado de CPA. En general se consideraron estas comparaciones: desbridamiento de colgajo abierto con CPA versus sin CPA; desbridamiento de colgajo abierto e injerto óseo con CPA versus sin CPA; regeneración tisular guiada con CPA versus sin CPA; y derivados de la matriz del esmalte con CPA versus sin CPA.
Resultados clave
Hay evidencia de muy baja calidad de que el agregado de CPA a dos tipos de tratamiento: desbridamiento de colgajo abierto y desbridamiento de colgajo abierto con injerto óseo, puede dar lugar a algunas ventajas en el tratamiento de los defectos infraóseos. Sin embargo, de los otros dos tipos de tratamientos, regeneración tisular guiada y derivados de la matriz del esmalte, no hay evidencia suficiente de un efecto beneficioso.
Calidad de la evidencia
Se consideró que la calidad de la evidencia era muy baja debido a problemas con el diseño de los estudios.
Conclusiones de los autores
Summary of findings
| APC + OFD compared to OFD (9‐12 months follow‐up) for treating periodontal infrabony defects | ||||||
| Patient or population: patients affected by infrabony defects requiring surgical treatment | ||||||
| Outcomes | Illustrative comparative risks* (95% CI) | Relative effect | Number of participants/defects | Quality of the evidence | Comments | |
| Assumed risk | Corresponding risk | |||||
| OFD | APC + OFD | |||||
| Change in probing depth (PD) (mm) (9‐12 months follow‐up) | Mean PD change (gain) across control groups ranged from 2.40 to 3.68 (2.36) mm Mean PD baseline value was 7.92 mm (95% CI 6.25 to 9.54) | The mean PD change (gain) in the intervention groups was 1.29 mm higher (1.00 to 1.58 higher) | Mean difference 1.29 (1.00 to 1.58) mm | 510 | ⊕⊝⊝⊝ | There is evidence of an advantage in using APC |
| Change in clinical attachment level (CAL) (mm) (9‐12 months follow‐up) | Mean CAL change (gain) across control groups ranged from 1.27 to 4.14 (2.03) mm Mean CAL baseline value was 6.78 mm (95% CI 5.56 to 7.54) | The mean CAL change (gain) in the intervention groups was 1.47 mm higher (1.11 to 1.82 higher) | Mean difference 1.47 (1.11 to 1.82) mm | 510 | ⊕⊝⊝⊝ | There is evidence of an advantage in using APC |
| Change in radiographic bone defect filling (RBF) (%) (9‐12 months follow‐up) | Mean RBF change (gain) across control groups ranged from ‐3.60% to 54.20% (16.90%) | The mean RBF change (gain) in the intervention groups was 34.26% higher (30.07 to 38.46 higher) | Mean difference 34.26% (30.07 to 38.46) | 401 | ⊕⊝⊝⊝ | There is evidence of an advantage in using APC |
| *The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence | ||||||
| 1Downgraded by 2 levels for high risk of performance bias. | ||||||
| APC + OFD + BG compared to OFD + BG (all follow‐ups) for treating periodontal infrabony defects | ||||||
| Patient or population: patients affected by infrabony defects requiring surgical treatment | ||||||
| Outcomes | Illustrative comparative risks* (95% CI) | Relative effect | Number of participants/defects | Quality of the evidence | Comments | |
| Assumed risk | Corresponding risk | |||||
| OFD + BG | APC + OFD + BG | |||||
| Change in probing depth (PD) (mm) (All follow‐ups) | Mean PD change (gain) across control groups ranged from 1.90 to 5.30 (3.54) mm Mean PD baseline value was 7.32 mm (95% CI 5.94 to 8.65) | The mean PD change (gain) in the intervention groups was 0.54 mm higher (0.33 to 0.75 higher) | Mean difference 0.54 (0.33 to 0.75) mm | 569 | ⊕⊝⊝⊝ | There is evidence of an advantage in using APC |
| Change in clinical attachment level (CAL) (mm) (All follow‐ups) | Mean CAL change (gain) across control groups ranged from 1.30 to 4.70 (3.20) mm Mean CAL baseline value was 7.34 mm (95% CI 5.21 to 9.82) | The mean CAL change (gain) in the intervention groups was 0.72 mm higher (0.43 to 1.00 higher) | Mean difference 0.72 (0.43 to 1.00) mm | 569 | ⊕⊝⊝⊝ | There is evidence of an advantage in using APC |
| Change in radiographic bone defect filling (RBF) (%) (All follow‐ups) | Mean RBF change (gain) across control groups ranged from 9.20% to 57.20% (40.54%) | The mean RBF change (gain) in the intervention groups was 8.10% higher (5.26 to 10.94 higher) | Mean difference 8.10% (5.26 to 10.94) | 420 | ⊕⊝⊝⊝ | There is evidence of an advantage in using APC |
| *The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence | ||||||
| 1Downgraded by 2 levels for high risk of performance bias. | ||||||
| APC + GTR compared to GTR (all follow‐ups) for treating periodontal infrabony defects | ||||||
| Patient or population: patients affected by infrabony defects requiring surgical treatment | ||||||
| Outcomes | Illustrative comparative risks* (95% CI) | Relative effect | Number of participants/defects | Quality of the evidence | Comments | |
| Assumed risk | Corresponding risk | |||||
| GTR | APC + GTR | |||||
| Change in probing depth (PD) (mm) (All follow‐ups) | Mean PD change (gain) across control groups ranged from 3.19 to 6.00 mm (4.40 mm) Mean PD baseline value was 8.67 mm (95% CI 6.29 to 10.31) | The mean PD change (gain) in the intervention groups was 0.92 mm higher (‐0.02 lower to 1.86 higher) | Mean difference 0.92 mm (‐0.02 to 1.86) | 248 | ⊕⊝⊝⊝ | There is insufficient evidence of an advantage in using APC |
| Change in clinical attachment level (CAL) (mm) (All follow‐ups) | Mean CAL change (gain) across control groups ranged from 3.38 to 5.20 mm (4.38 mm) Mean CAL baseline value was 9.40 mm (95% CI 5.97 to 11.40) | The mean CAL change (gain) in the intervention groups was 0.42 mm higher (‐0.02 lower to 0.86 higher) | Mean difference 0.42 mm (‐0.02 to 0.86) | 248 | ⊕⊝⊝⊝ | There is insufficient evidence of an advantage in using APC |
| *The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence | ||||||
| 1Downgraded by 2 levels for high risk of performance bias. | ||||||
| APC + EMD compared to EMD (all follow‐ups) for treating periodontal infrabony defects | ||||||
| Patient or population: patients affected by infrabony defects requiring surgical treatment | ||||||
| Outcomes | Illustrative comparative risks* (95% CI) | Relative effect | Number of participants/defects | Quality of the evidence | Comments | |
| Assumed risk | Corresponding risk | |||||
| EMD | APC + EMD | |||||
| Change in probing depth (PD) (mm) (All follow‐ups) | Mean PD change (gain) across control groups ranged from 3.87 to 5.90 mm (4.89 mm) | The mean PD change (gain) in the intervention groups was 0.13 mm higher (‐0.05 lower to 0.30 higher) | Mean difference 0.13 mm (‐0.05 to 0.30) | 75 | ⊕⊝⊝⊝ | There is insufficient evidence of an advantage in using APC |
| Change in clinical attachment level (CAL) (mm) (All follow‐ups) | Mean CAL change (gain) across control groups ranged from 3.30 to 5.00 mm (4.15 mm) | The mean CAL change (gain) in the intervention groups was 0.10 mm higher (‐0.13 lower to 0.32 higher) | Mean difference 0.10 mm (‐0.13 to 0.32) | 75 | ⊕⊝⊝⊝ | There is insufficient evidence of an advantage in using APC |
| Change in radiographic bone defect filling (RBF) (%) (All follow‐ups) | Only 1 study reported RBF outcome with a mean change in control groups of 18.30% | The mean RBF change (gain) in the intervention group was 0.60% lower (‐6.21 lower to 5.01 higher) | Mean difference ‐0.60 (‐6.21 to 5.01) | 49 | ⊕⊝⊝⊝ | There is insufficient evidence of an advantage in using APC |
| *The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence | ||||||
| 1Downgraded by 2 levels for high risk of performance bias. | ||||||
Antecedentes
Descripción de la afección
La periodontitis es una enfermedad del periodonto que se caracteriza por la pérdida irreversible de la inserción tisular conectiva y del hueso alveolar de apoyo (Pihlstrom 2005). Para su aparición, es necesaria la presencia de microorganismos específicos junto con una respuesta alterada del huésped. A pesar de que existen muchas variaciones, un curso típico de periodontitis comienza con la formación de bolsas inducida por la placa bacteriana y una destrucción ósea alveolar posterior característica de la periodontitis crónica. La destrucción ósea durante la periodontitis puede tener diferentes modelos morfológicos incluidos los defectos supraóseos (horizontales) y los defectos infraóseos (verticales) (Kinane 2001). Un defecto infraóseo representa las secuelas anatómicas debido al avance apical de la placa dental durante la progresión de la enfermedad (Waerhaug 1979). Dichos defectos, si no se tratan, promueven fácilmente la progresión de la periodontitis y la pérdida adicional de la inserción (Papapanou 1991). Debido a que los defectos infraóseos son frecuentes en la periodontitis (Vrotsos 1999), existe un interés significativo en enfoques que convertirán dichos defectos (con riesgo de progresión de la enfermedad) en sitios de sondaje poco profundos fácilmente mantenibles (Crea 2014).
Descripción de la intervención
El objetivo máximo del tratamiento periodóntico es preservar la dentición natural durante el mayor tiempo posible y mejorar la comodidad y las características estéticas del paciente al mantener y mejorar la salud y la función de todos los tejidos que sostienen los dientes (encías, ligamento periodóntico, cemento, hueso alveolar). El tratamiento convencional de la periodontopatía puede detener la destrucción ósea, pero generalmente no restaura el hueso alveolar ni el tejido conjuntivo periodóntico ya perdidos. Se han desarrollado diversas técnicas quirúrgicas en un intento por proporcionar un tratamiento eficiente de la periodontitis. El desbridamiento de colgajo abierto (DCA) se encuentra entre los procedimientos más tempranos y más prometedores que se pueden administrar (Caffesse 1986; Cortellini 1996). Su objetivo principal es reducir la presencia de los microorganismos que desarrollan y mantienen el proceso inflamatorio. Al hacerlo, como consecuencia, se promueven las propiedades de regeneración del huésped, a pesar de no ser un procedimiento regenerativo. Posteriormente, la combinación del DCA convencional con diversos biomateriales, como los injertos óseos, los derivados de la matriz del esmalte o las membranas (regeneración tisular guiada), dio lugar al desarrollo de protocolos de tratamientos regenerativos con efectos clínicos beneficiosos significativos (Cochran 2003; Cortellini 1996; Esposito 2009; Hoidal 2008; Needleman 2006).
A pesar de los adelantos en los procedimientos quirúrgicos y los materiales, todavía es un reto la regeneración completa y previsible, definida como el desarrollo de hueso nuevo, ligamento periodóntico y cemento en la cara radicular previamente expuesta a la periodontopatía (AAP 1992). En consecuencia, el concepto de ingeniería de tejidos (Rose 2002), que requiere la presencia de células, estructuras y moléculas de señalización, ha generado un interés especial en cuanto a la regeneración periodóntica. Los injertos óseos y las membranas para la regeneración tisular guiada (RTG) pueden servir de estructuras, pero siempre se necesitan moléculas de señalización.
Recientemente, se han investigado los factores de crecimiento de polipéptidos como factores de señalización posibles para mejorar la regeneración periodóntica. Como evidencia preliminar sobre sus aplicaciones potenciales en la cicatrización de las heridas periodónticas, se han identificado varios factores de crecimiento de polipéptidos en los tejidos periodónticos humanos mediante inmunohistoquímica e hibridación in situ (Giannobile 1996). Las plaquetas constituyen una fuente abundante de dichos factores de crecimiento y son fácilmente utilizables en forma de concentrados plaquetarios autólogos (APC). Por lo tanto, el uso adyuvante de CPA en combinación con la intervención quirúrgica periodóntica ha surgido como un instrumento posible para mejorar la previsibilidad del tratamiento de los defectos infraóseos.
Los CPA, basado en el protocolo de preparación, pueden ser de diversos tipos, que incluyen el plasma rico en plaquetas (PRP) (Marx 1998), la fibrina rica en plaquetas (FRP) (Choukroun 2001) y los factores de crecimiento ricos en plasma (FCRP) (Anitua 2001). Hay varias técnicas comerciales disponibles para obtener concentrados plaquetarios. Sin embargo, su indicación de uso ha sido confusa debido a que cada método da lugar a un producto diferente con diferentes propiedades biológicas y aplicaciones posibles. El PRP representa la primera generación de concentrados plaquetarios, y muestra la liberación de diversos factores de crecimiento durante siete días, con una liberación máxima en el primer día de aplicación (Dohan Ehrenfest 2009). La FRP representa el CPA de segunda generación, y la técnica de preparación se simplifica en comparación con el PRP. Además, la FRP mostró una liberación de factores de crecimiento sostenida durante un período de 21 días con una liberación máxima a los siete días (Carroll 2005). Los FCRP también son un concentrado plaquetario de segunda generación, cuya diferencia principal en comparación con PRP es la ausencia de leucocitos y el volumen sanguíneo pequeño requerido para su preparación (Anitua 2001). Después de una actualización en la clasificación (Dohan Ehrenfest 2009), los concentrados plaquetarios se pueden dividir en cuatro categorías, según la presencia de leucocitos y fibrina: PRP‐P (PRP puro, sin leucocitos, que incluye FCRP), PRP‐L (plasma rico en plaquetas y leucocitos), FRP‐P (FRP pura) y FRLP (FRP y leucocitos).
De qué manera podría funcionar la intervención
Se cree que la contribución de plaquetas derivadas de la sangre al proceso de curación ósea se basa en los factores de crecimiento almacenados en sus gránulos y liberados con la activación. Los principales factores de crecimiento liberados de los agregados plaquetarios son los siguientes: factor de crecimiento derivado de plaquetas (FCDP), factor de crecimiento transformante beta (FCT‐β), factor de crecimiento endotelial vascular (FCEV), factor de crecimiento epitelial (FCE), factor 1 de crecimiento similar a la insulina (F1CI) y factor de crecimiento de fibroblastos básico (FCFb), así como tres proteínas sanguíneas que se sabe que actúan como moléculas de adhesión a las células para la osteoconducción (fibrina, fibronectina y vitronectina). El conjunto de estos factores sirven de mediadores biológicos con la capacidad de regular la proliferación de las células, la quimiotaxis y la diferenciación.
Por qué es importante realizar esta revisión
El interés considerablemente mayor en la combinación de CPA con técnicas quirúrgicas para lograr mejores resultados en el tratamiento de los defectos infraóseos, ha dado lugar a que sea necesaria una investigación minuciosa de los efectos beneficiosos reales que se pueden obtener. La primera revisión sistemática que evaluó el efecto del PRP sobre las aplicaciones clínicas en odontología informó de efectos beneficiosos en el tratamiento de los defectos periodónticos (Plachokova 2008). Otra revisión sistemática, que evaluó el efecto de un complemento de PRP en el tratamiento de los defectos intraóseos, destacó los límites y la heterogeneidad de los datos disponibles y estableció la conclusión cautelosa de que la selección específica del tipo de injerto y los procedimientos quirúrgicos combinados con PRP pueden ser importante (Kotsovilis 2010). Una revisión sistemática posterior también evaluó el efecto del plasma rico en plaquetas en diversos procedimientos regenerativos de los defectos periodónticos y estableció la conclusión de que el PRP se puede utilizar de manera ventajosa como un complemento del tratamiento con procedimientos de injerto para los defectos infraóseos (Del Fabbro 2011). Dicha revisión también indicó que el uso de PRP no es efectivo cuando el procedimiento de RTG se utiliza para tratar los defectos infraóseos.
A pesar de los numerosos informes sobre el uso adyuvante del concentrado plaquetario autólogo agregado a los procedimientos quirúrgicos periodónticos, su eficacia todavía es polémica. Lo anterior se debe en parte a una heterogeneidad grande entre los diferentes estudios (Del Fabbro 2011; Del Fabbro 2013), en cuanto a los métodos, el diseño de estudio, los protocolos para la preparación de los concentrados plaquetarios, los criterios de selección de los participantes, las variables de resultado evaluadas, etc. Por lo tanto, una revisión del estado actual de la evidencia es crucial para aclarar si el complemento de los CPA con el tiempo produce mejores resultados en el tratamiento de los defectos infraóseos, y si su efecto mejora en particular cuando se combina con una técnica quirúrgica específica. Al realizarla, se les puede proporcionar a los médicos guías claras y relevantes.
Objetivos
Evaluar los efectos de los concentrados plaquetarios autólogos utilizados como un complemento de los tratamientos quirúrgicos periodónticos (desbridamiento de colgajo abierto [DCA], DCA combinado con injerto óseo, regeneración tisular guiada, DCA combinado con derivados de la matriz del esmalte) para el tratamiento de los defectos infraóseos.
Métodos
Criterios de inclusión de estudios para esta revisión
Tipos de estudios
Ensayos controlados aleatorios de diseño paralelo y de boca dividida.
Tipos de participantes
Pacientes afectados por defectos infraóseos que requerían tratamiento quirúrgico, independientemente de la edad o el sexo.
Tipos de intervenciones
Intervención experimental: concentrados plaquetarios autólogos (CPA) (independientemente del tipo: plasma rico en plaquetas [PRP], factores de crecimiento ricos en plasma [FCRP] o fibrina rica en plaquetas [FRP]) usados junto con una técnica quirúrgica específica (desbridamiento de colgajo abierto [DCA], DCA + injertos óseos [IO], regeneración tisular guiada [RTG], derivados de la matriz del esmalte [DME]).
Intervención de comparación (control): las mismas técnicas quirúrgicas utilizadas solas (sin el complemento de los CPA).
Tipos de medida de resultado
Resultados primarios
Cambio en la profundidad de la bolsa al sondaje (PBS), cambio en el nivel de inserción clínica (NIC) y cambio en el relleno del defecto óseo radiográfico (ROR).
Resultados secundarios
Supervivencia de los dientes, cierre de las bolsas y calidad de vida relacionada con la salud bucodental.
Métodos de búsqueda para la identificación de los estudios
Búsquedas electrónicas
Cochrane Oral Health's Information Specialist conducted systematic searches in the following databases for randomised controlled trials and controlled clinical trials. There were no language, publication year or publication status restrictions:
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Cochrane Oral Health's Trials Register (searched 27 February 2018) (Appendix 1);
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Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 1) in the Cochrane Library (searched 27 February 2018) (Appendix 2);
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MEDLINE Ovid (1946 to 27 February 2018) (Appendix 3);
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Embase Ovid (1980 to 27 February 2018) (Appendix 4);
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LILACS BIREME Virtual Health Library (Latin American and Caribbean Health Science Information database; 1982 to 27 February 2018) (Appendix 5).
Subject strategies were modelled on the search strategy designed for MEDLINE Ovid. Where appropriate, they were combined with subject strategy adaptations of the highly sensitive search strategy designed by Cochrane for identifying randomised controlled trials and controlled clinical trials as described in the Cochrane Handbook for Systematic Reviews of Interventions Chapter 6 (Lefebvre 2011).
Búsqueda de otros recursos
The following trial registries were searched for ongoing studies:
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US National Institutes of Health Ongoing Trials Register ClinicalTrials.gov (clinicaltrials.gov; searched 27 February 2018) (Appendix 6);
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World Health Organization International Clinical Trials Registry Platform (apps.who.int/trialsearch; searched 27 February 2018) (Appendix 7).
An adjunctive search was performed on the reference lists of the included articles and reviews retrieved.
Moreover, a handsearch was performed on the issues since January 2010 (including the 'early view' or equivalent section) of the following journals: International Journal of Periodontics and Restorative Dentistry,Journal of Clinical Periodontology, Journal of Periodontal Research, Journal of Periodontology, Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology and Endodontology (last search was performed on 2 March 2018). Two review authors independently performed the searches (Saurav Panda (SP), Cristina Bucchi (CB)).
We also searched for grey literature, such as conference abstracts, proceedings and theses on the following databases: www.greylit.org; www.opengrey.eu (last search was performed on 2 March 2018, see Appendix 8).
Obtención y análisis de los datos
Selección de los estudios
Following the electronic search, two review authors (Jayakumar Nadathur Doraiswamy (JND), Malaiappan Sankari (MS)) independently screened the titles and abstracts (if available) to exclude all articles clearly not meeting the inclusion criteria. The search was designed to be sensitive and include controlled clinical trials, these were filtered out early in the selection process if they were not randomised. Of all the remaining articles, full texts were obtained and assessed independently by two review authors (JND, MS) and only articles fully meeting the inclusion criteria were considered. In cases of disagreement between the two review authors, a third review author (Massimo Del Fabbro (MDF)) was consulted. Detailed reasons were stated for all excluded studies. This process is summarised in Figure 1.
Extracción y manejo de los datos
Three review authors (SP, Lorena Karanxha (LK), CB) independently extracted and recorded data on ad hoc forms. Any disagreement was solved through discussion, or a third review author was consulted (MDF). In case of missing or unclear information, we contacted the authors of the included reports by email to provide clarification or missing information. In case of missing or incomplete data and absence of further clarification by study authors we excluded the report from the analysis.
We recorded the following data for each included report:
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demographic characteristics of the population;
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defect characteristics (PD, CAL, RBF);
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type of platelet concentrate used (PRP, PRF, PRGF);
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outcome characteristics (outcome variables assessed such as CAL and PD, follow‐up duration);
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when possible, we also recorded the expertise of the clinician (years of experience with using platelet concentrates); and
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source of funding.
Evaluación del riesgo de sesgo de los estudios incluidos
Three review authors (LK, SP, CB) independently assessed the risk of bias in the included studies. In case of disagreement a fourth review author (MDF) was consulted. Since some of the authors of one of the randomised controlled trials included (Panda 2016) are also authors of this review (SP, MDF, Silvio Taschieri (ST)), the risk of bias assessment for that study was carried out by other review authors not involved in the study (LK, CB).
The assessment was conducted following the instructions and the approach described in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). For each study, the following domains were considered: selection bias (random sequence generation and allocation concealment), performance bias (blinding of participants and personnel), detection bias (blinding of outcome assessment), attrition bias (incomplete outcome data addressed), and reporting bias (selective reporting).
For each domain the risk was judged either low, unclear or high. If one study had low risk for all domains, the study was judged at low risk of bias. If it had an unclear risk for at least one domain, the study was judged at unclear risk of bias. If it had a high risk for at least one domain, the study was judged at high risk of bias. It was considered that blinding of patient and clinician might be difficult/impossible, as for many studies involving surgical procedures where interventions are quite different from each other.
We categorised the overall risk of bias of individual studies. Studies were categorised as being at low, high, or unclear risk of bias according to the following criteria:
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low risk of bias (plausible bias unlikely to seriously alter the results) if all domains were at low risk of bias;
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high risk of bias (plausible bias that seriously weakens confidence in the results) if one or more domains were at high risk of bias; or
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unclear risk of bias (plausible bias that raises some doubt about the results) if one or more domains were at unclear risk of bias.
These assessments are reported in the Characteristics of included studies table and also graphically.
Medidas del efecto del tratamiento
For continuous outcomes (e.g. PD, CAL, RBF), mean differences (change score) along with 95% confidence intervals (CIs) were used to summarise data for each treatment group. We expressed the data in mm for PD and CAL and in percentage for RBF, as they were reported in the studies.
Cuestiones relativas a la unidad de análisis
The statistical unit of analysis in parallel studies was the patient, unless the study provided data only for defects. We considered one infrabony defect per patient in studies with parallel design. In the case of split‐mouth studies, the unit of analysis was the defect; a single defect per patient per group was considered.
Manejo de los datos faltantes
In case of missing data, we contacted the corresponding author of the article through e‐mail to obtain complete data. In case of no response, the same e‐mail was sent to co‐authors for a maximum of three times. If no answer was obtained, the study was excluded from the analysis. When feasible, missing standard deviations were estimated using the methods described in Section 7.7.3 of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011).
Evaluación de la heterogeneidad
Heterogeneity among studies was assessed with Cochran's test for heterogeneity, with a significance threshold of P < 0.1. The quantification of the heterogeneity was calculated with I2 statistic. For the interpretation of I2 the ranges suggested in Section 9.5.2 of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011) were considered.
Evaluación de los sesgos de notificación
We assessed publication bias by testing for funnel plot asymmetry, as described in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). If asymmetry was evident, we investigated this and described possible causes.
Síntesis de los datos
The meta‐analysis was performed only with studies with similar comparisons reporting the same outcome measures. We combined mean differences for continuous data, using random‐effects models if at least four studies were included in the meta‐analysis, while if there were less than four studies a fixed‐effect model was chosen. The software RevMan 5 (Review Manager 2014) was used for meta‐analysis computations. Data from split‐mouth and parallel‐group studies were combined (Elbourne 2002). The appropriate standard errors were estimated where they were not present in the trial reports (Follmann 1992). For the split‐mouth studies the standard error was calculated assuming an intraclass correlation coefficient of 0. The generic inverse variance procedure in RevMan 5 was used to combine these two subgroups in the analyses.
Análisis de subgrupos e investigación de la heterogeneidad
In addition to the different surgical protocols for different types of infrabony defects, duration of the follow‐up was investigated as a factor possibly affecting the outcome. The subgroups included data up to 6 months (3 to 6 months) and longer than 6 months (9 to 12 months).
Análisis de sensibilidad
Sensitivity analysis was performed in order to evaluate the effect of risk of bias and source of funding on the overall effects (e.g. omitting studies at unclear or high risk of bias or those sponsored by the manufacturer of the product under investigation). The effect of excluding specific studies that eventually appeared to be outliers was also investigated.
Summary of findings
We produced a 'Summary of findings' table for each comparison in which there was more than one study. We included the change in PD, CAL and RBF of the all follow‐up periods of each comparison group. We used GRADE methods, and GRADEpro software (GRADEpro GDT 2015) for developing 'Summary of findings' tables. We assessed the quality of the body of evidence for each comparison and outcome by considering the overall risk of bias of the included studies, the directness of the evidence, the inconsistency of the results, the precision of the estimates, and the risk of publication bias. We categorised the quality of each body of evidence as high, moderate, low, or very low.
Results
Description of studies
Results of the search
The electronic search retrieved 855 records, four trials were identified by handsearching and none by searching the grey literature. After discarding the duplicates, two review authors (Jayakumar Nadathur Doraiswamy (JND), Malaiappan Sankari (MS)) screened 480 titles and abstracts and rejected 402. The full text was obtained for 78 potentially eligible articles and of these, 40 were excluded with reasons (see Characteristics of excluded studies table). Finally, after agreement among the review authors 38 studies were included in this review (Figure 1).
Included studies
Design
Of the 38 included studies, 22 had a split‐mouth design, reporting for a total of 371 participants and 701 teeth (Agarwal 2014; Agarwal 2015; Agarwal 2016; Arabaci 2017; Aydemir 2016; Camargo 2009; Christgau 2006; Elgendy 2015; Gupta 2014; Hanna 2004; Hassan 2012; Kaushick 2011; Khosropanah 2015; Naqvi 2017; Ozdemir 2012; Panda 2016; Patel 2017; Ravi 2017; Rosamma Joseph 2012; Sezgin 2017; Shukla 2016; Thorat 2017); 16 studies had a parallel design with a total of 645 patients and 721 teeth (Chandradas 2016; Demir 2007; Döri 2007a; Döri 2007b; Döri 2008a; Döri 2008b; Döri 2009; Garg 2017; Kanoriya 2016; Martande 2016; Okuda 2005; Piemontese 2008; Pradeep 2015; Pradeep 2016; Sharma 2011; Thorat 2011). Of the 38 included studies only one was a multicentric study (Elgendy 2015). Finally, two studies declared that they were supported in part by companies whose products were used in the trials (Döri 2008a; Döri 2008b).
Sample size calculation was reported only by 15 studies (Döri 2007a; Döri 2007b; Döri 2008a; Döri 2008b; Döri 2009; Kanoriya 2016; Panda 2016; Patel 2017; Pradeep 2015; Pradeep 2016; Ravi 2017; Rosamma Joseph 2012; Sezgin 2017; Sharma 2011; Thorat 2011), meaning that in almost 60% of cases there was no rationale regarding the choice of the sample size.
Participants
The age range of the participants of included studies was between 17 and 74 years. However, four studies did not report the age of the participants (Agarwal 2016; Gupta 2014; Naqvi 2017; Shukla 2016) and 10 studies (Agarwal 2015; Aydemir 2016; Chandradas 2016; Demir 2007; Elgendy 2015; Hassan 2012; Khosropanah 2015; Okuda 2005; Ozdemir 2012; Sezgin 2017) reported only mean ages, ranging from 36.03 and 55.5 years.
35 studies included both men and women, but with different proportions, and three studies did not report this information (Gupta 2014; Elgendy 2015; Kaushick 2011). Finally, most of the studies did not include smokers (Agarwal 2014; Agarwal 2015; Agarwal 2016; Arabaci 2017; Aydemir 2016; Chandradas 2016; Döri 2007a; Döri 2007b; Döri 2008a; Döri 2008b; Döri 2009; Garg 2017; Gupta 2014; Hassan 2012; Kanoriya 2016; Kaushick 2011; Khosropanah 2015; Martande 2016; Naqvi 2017; Okuda 2005; Ozdemir 2012; Panda 2016; Patel 2017; Piemontese 2008; Pradeep 2015; Pradeep 2016; Ravi 2017; Rosamma Joseph 2012; Sezgin 2017; Sharma 2011; Shukla 2016; Thorat 2011; Thorat 2017).
Interventions
The general comparison was between a group that received autologous platelet concentrates (APC) as an adjunct to surgical treatment (experimental group), and a group that received surgical treatment alone (control group). Four different types of comparisons were assessed, based on the treatment type:
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APC + open flap debridement (OFD) versus OFD alone (12 trials): Agarwal 2016; Arabaci 2017; Chandradas 2016; Kanoriya 2016; Martande 2016; Patel 2017; Pradeep 2015; Pradeep 2016; Rosamma Joseph 2012; Sharma 2011; Thorat 2011; Thorat 2017
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APC + OFD + bone graft (BG) versus OFD + BG (17 trials): Agarwal 2014; Agarwal 2015; Demir 2007; Döri 2009; Elgendy 2015; Garg 2017; Gupta 2014; Hanna 2004; Hassan 2012; Kaushick 2011; Khosropanah 2015; Naqvi 2017; Okuda 2005; Ozdemir 2012; Piemontese 2008; Sezgin 2017; Shukla 2016
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APC + guided tissue regeneration (GTR) versus GTR (7 trials): Camargo 2009; Christgau 2006; Döri 2007a; Döri 2007b; Döri 2008a; Panda 2016; Ravi 2017
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APC + enamel matrix derivative (EMD) versus EMD (2 trials): Aydemir 2016; Döri 2008b.
Outcomes
Primary outcomes
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Change in probing depth (PD), reported by all 38 included studies.
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Change in clinical attachment level (CAL), defined relative attachment level (RAL) in some studies, reported by all 38 included studies.
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Change in radiographic bone defect filling (RBF), reported by 31 studies.
Secondary outcomes
All articles in all groups reported a survival rate of 100% for the treated teeth. No complete pocket closure was reported. No quantitative analysis regarding patients' quality of life was possible.
Excluded studies
We excluded 40 studies from the review, for the following reasons (see Characteristics of excluded studies table):
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no randomisation (Aleksić 2008; Jovicić 2013; Saini 2011)
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no control group (Camargo 2002; Camargo 2005; Lekovic 2012)
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gingival recession, not infrabony defects (Aroca 2009; Dogan 2015; Huang 2005; Jankovic 2010; Padma 2013; Shepherd 2009; Shivakumar 2016; Thamaraiselvan 2015)
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same patients reported in a previous study (Cetinkaya 2014; Döri 2013; Moder 2012; Yajamanya 2017)
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non‐independence of analysing unit (Gupta 2014b; Pradeep 2012a)
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incomplete data (Cieplik 2018; Harnack 2009; Keceli 2008; Keles 2006; Menezes 2012; Shah 2015; Yassibag‐Berkman 2007; Yen 2007)
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no APCs (fibrin glue) (Cortellini 1995; Trombelli 1995; Trombelli 1996)
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APC not the only difference between groups (Cheung 2004; Eren 2014; Jankovic 2012)
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studies with mixed (parallel/split‐mouth) design (Agarwal 2017; Bajaj 2017; Chatterjee 2017; Ouyang 2006; Pradeep 2017; Qiao 2016).
Risk of bias in included studies
The risk of bias in included studies is summarized in Figure 2 and Figure 3. Two studies were at unclear overall risk of bias (Ravi 2017; Rosamma Joseph 2012). The remaining 36 studies had a high overall risk of bias.
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
Allocation
Random sequence generation
The randomisation was performed correctly in most of the studies. The methods used were the tossing of a coin (Agarwal 2014; Agarwal 2015; Camargo 2009; Demir 2007; Gupta 2014; Hanna 2004; Khosropanah 2015; Okuda 2005; Ozdemir 2012; Panda 2016; Patel 2017; Piemontese 2008; Ravi 2017; Rosamma Joseph 2012; Sezgin 2017; Sharma 2011; Thorat 2011), the block approach (Döri 2007a; Döri 2007b; Döri 2008a; Döri 2008b; Döri 2009), the use of a freeware link (Chandradas 2016), computerized generated scheme (Aydemir 2016; Kanoriya 2016; Martande 2016; Pradeep 2016; Shukla 2016; Thorat 2011), biased coin randomisation (Hassan 2012), lottery method (Naqvi 2017), and a table of random numbers (Christgau 2006; Pradeep 2015). The randomisation method was not described in five articles, which were considered to be an unclear risk of bias (Agarwal 2016; Elgendy 2015; Garg 2017; Gupta 2014; Kaushick 2011).
Allocation concealment
The concealment of the allocation was correctly done in 19 studies (Arabaci 2017; Aydemir 2016; Camargo 2009; Chandradas 2016; Christgau 2006; Demir 2007; Döri 2007a; Döri 2007b; Döri 2008a; Döri 2008b; Döri 2009; Khosropanah 2015; Okuda 2005; Ozdemir 2012; Panda 2016; Patel 2017; Piemontese 2008; Ravi 2017; Rosamma Joseph 2012). In the remaining 19 studies, insufficient information was provided regarding the exact method used for allocation concealment (Agarwal 2014; Agarwal 2015; Agarwal 2016; Elgendy 2015; Garg 2017; Gupta 2014; Hanna 2004; Hassan 2012; Kanoriya 2016; Kaushick 2011; Martande 2016; Naqvi 2017; Pradeep 2015; Pradeep 2016; Sezgin 2017; Sharma 2011; Shukla 2016; Thorat 2011; Thorat 2017).
Blinding
Blinding of participants and personnel (performance bias)
Being the intervention surgical in nature, blinding of participants and treating clinicians is almost unfeasible either in a parallel or split‐mouth design: 36 out of 38 studies had a high risk of performance bias. For two studies an unclear risk of performance bias was assigned given that it was stated in the paper that blinding of the operator was performed but without specifying how (Ravi 2017; Rosamma Joseph 2012). The blinding of the personnel was also evaluated, which was reported in most of the studies except for eight studies (Agarwal 2016; Christgau 2006; Elgendy 2015; Garg 2017; Gupta 2014; Kaushick 2011; Okuda 2005; Ozdemir 2012). However, again for the fact that the intervention has a surgical nature, it is unlikely that blinding or not of the personnel could influence the outcome. Therefore such parameter did not influence the assignment of the risk of performance bias.
Blinding of outcome assessment (detection bias)
The blinding of the outcome assessor was done in most of the studies. However, it was not reported in seven studies, which were considered to be at unclear risk of detection bias (Agarwal 2016; Elgendy 2015; Garg 2017; Gupta 2014; Kaushick 2011; Martande 2016; Ozdemir 2012).
Incomplete outcome data
The completeness of outcome data was adequate in all but three studies in which the number of subjects that finished the study was not clear (Elgendy 2015; Garg 2017; Gupta 2014).
Selective reporting
All studies properly reported data for all patients.
Effects of interventions
See: Summary of findings for the main comparison APC + OFD compared to OFD (9‐12 months follow‐up) for treating periodontal infrabony defects; Summary of findings 2 APC + OFD + BG compared to OFD + BG (all follow‐ups) for treating periodontal infrabony defects; Summary of findings 3 APC + GTR compared to GTR (all follow‐ups) for treating periodontal infrabony defects; Summary of findings 4 APC + EMD compared to EMD (all follow‐ups) for treating periodontal infrabony defects
For the meta‐analyses of all follow‐ups, where the study presented multiple follow‐ups, we used the longest one.
1. Autologous platelet concentrates (APC) + open flap debridement (OFD) versus OFD
summary of findings Table for the main comparison.
In this comparison we did not divide the data according to the follow‐up duration, because all studies had a follow‐up duration between 9 and 12 months.
Change in probing depth (PD) (mm)
Follow‐up between 9 and 12 months
There is evidence of an advantage in using APC from both split‐mouth studies (mean difference (MD) 1.86, 95% confidence interval (CI) 1.07 to 2.66; P < 0.001; 5 studies; 158 participants) and parallel studies (MD 0.99, 95% CI 0.90 to 1.07; P < 0.001; 7 studies, 352 participants). Overall, there is evidence of an advantage in using APC (MD 1.29, 95% CI 1.00 to 1.58; P < 0.001) (Figure 4; Analysis 1.1).
Forest plot of comparison: 1 APC + OFD versus OFD (9‐12 months follow‐up); outcome: 1.1 Probing depth (mm).
Change in clinical attachment level (CAL) (mm)
Follow‐up between 9 and 12 months
There is evidence of an advantage in using APC from split‐mouth studies (MD 2.36, 95% CI 1.19 to 3.54; P < 0.001; 5 studies; 158 participants) and parallel studies (MD 0.99, 95% CI 0.84 to 1.14; P < 0.001; 7 studies; 352 participants). Overall, there is evidence of an advantage in using APC (MD 1.47, 95% CI 1.11 to 1.82; P < 0.001) (Analysis 1.2).
Change in radiographic bone defect filling (RBF) (%)
Follow‐up between 9 and 12 months
There is evidence of an advantage in using APC from split‐mouth studies (MD 27.32%, 95% CI 20.92% to 33.72%; P < 0.001; 2 studies; 49 participants) and parallel studies (MD 35.77%, 95% CI 31.20% to 40.35%; P < 0.001; 7 studies; 352 participants). Overall, there is evidence of an advantage in using APC (MD 34.26%, 95% CI 30.07% to 38.46%; P < 0.001) (Analysis 1.3).
2. APC + OFD + bone graft (BG) versus OFD + BG
Change in PD (mm)
All follow‐ups
There is evidence of an advantage in using APC from split‐mouth studies (MD 0.47, 95% CI 0.24 to 0.71; P < 0.001; 12 studies; 360 participants) and from parallel studies (MD 0.81, 95% CI 0.58 to 1.03; P < 0.001; 5 studies; 209 participants). Overall, there is evidence of an advantage in using APC (MD 0.54, 95% CI 0.33 to 0.75; P < 0.001) (Figure 5; Analysis 2.1).
Forest plot of comparison: 2 APC + OFD + BG versus OFD + BG (all follow‐ups); outcome: 2.1 Probing depth (mm).
Follow‐up between 3 and 6 months
There is evidence of an advantage in using APC from split‐mouth studies (MD 0.58, 95% CI 0.25 to 0.92; P = 0.0007; 10 studies; 252 participants). However, there is only one study to consider of parallel design (MD 0.84, 95% CI 0.60 to 1.07; P < 0.001; 20 participants). Overall, there is evidence of an advantage in using APC with a shorter follow‐up duration (MD 0.62, 95% CI 0.30 to 0.94; P = 0.0002) (Analysis 3.1).
Follow‐up between 9 and 12 months
There is evidence of an advantage in using APC from split‐mouth studies (MD 0.49, 95% CI 0.26 to 0.72; P < 0.001; 6 studies; 192 participants), and from parallel studies (MD 0.58, 95% CI 0.09 to 1.06; P = 0.02; 4 studies; 189 participants). Overall, there is evidence of an advantage in using APC (MD 0.50, 95% CI 0.31 to 0.69; P < 0.0001) (Analysis 4.1).
Change in CAL (mm)
All follow‐ups
There is evidence of an advantage in using APC from split‐mouth studies (MD 0.67, 95% CI 0.35 to 0.99; P < 0.001; 12 studies; 360 participants) and from parallel design studies (MD 0.89, 95% CI 0.49 to 1.29; P < 0.001; 5 studies; 209 participants). Overall, there is evidence of an advantage in using APC (MD 0.72, 95% CI 0.43 to 1.00; P < 0.001) (Analysis 2.2).
Follow‐up between 3 and 6 months
There is evidence of an advantage in using APC from split‐mouth studies (MD 0.40, 95% CI 0.02 to 0.77; P = 0.04; 10 studies; 252 participants). However, there is only one study to consider of parallel design (MD 1.00, 95% CI 0.93 to 1.07; P < 0.001; 20 participants). Overall, there is evidence of an advantage in using APC (MD 0.47, 95% CI 0.11 to 0.84; P = 0.01) (Analysis 3.2).
Follow‐up between 9 and 12 months (only split‐mouth studies)
There is evidence of an advantage in using APC (MD 0.84, 95% CI 0.62 to 1.06; P < 0.001; 6 studies; 192 participants) (Analysis 4.2).
Change in RBF (%)
All follow‐ups
There is evidence of an advantage in using APC from both split‐mouth studies (MD 7.73%, 95% CI 4.50% to 10.97%; P < 0.001; 8 studies; 270 participants) and parallel studies (MD 9.66%, 95% CI 5.39% to 13.94%; P < 0.001; 3 studies; 150 participants). Overall, there is evidence of an advantage in using APC (MD 8.10%, 95% CI 5.26% to 10.94%; P < 0.001) (Analysis 2.3).
Follow‐up between 3 and 6 months
There is evidence of an advantage in using APC from split‐mouth studies (MD 3.59%, 95% CI 0.13% to 7.05%; P = 0.04; 5 studies; 142 participants) and from one parallel study (MD 10.00%, 95% CI 4.90% to 15.10%; P = 0.0001; 20 participants). Overall, there is evidence of an advantage in using APC (MD 4.76%, 95% CI 1.27% to 8.25%; P = 0.008) (Analysis 3.3).
Follow‐up between 9 and 12 months
There is evidence of an advantage in using APC from split‐mouth studies (MD 10.16%, 95% CI 6.18% to 14.14%; P < 0.001; 4 studies; 152 participants), and from parallel studies (MD 8.87%, 95% CI 1.03% to 16.71%; P = 0.03; 2 studies; 130 participants). Overall, there is evidence of an advantage in using APC (MD 9.99%, 95% CI 6.44% to 13.55%; P < 0.001) (Analysis 4.3).
3. APC + guided tissue regeneration (GTR) versus GTR
Change in PD (mm)
All follow‐ups
There is evidence of an advantage in using APC from split‐mouth studies (MD 1.52, 95% CI 0.54 to 2.51; P = 0.002; 4 studies; 166 participants) but not from parallel studies (MD 0.25, 95% CI ‐0.15 to 0.64; P = 0.22; 3 studies, 82 participants). Overall, there is evidence of an advantage in using APC (MD 0.92, 95% CI ‐0.02 to 1.86; P = 0.05). However, given the wide confidence intervals, there is a possibility of an advantage for the control group (Figure 6; Analysis 5.1).
Forest plot of comparison: 5 APC + GTR versus GTR (all follow‐ups), outcome: 5.1 Probing depth (mm).
Follow‐up between 3 and 6 months (only split‐mouth studies)
There is insufficient evidence of an advantage in using APC (MD 1.07, 95% CI ‐0.71 to 2.86; P = 0.24; 3 studies; 134 participants) (Analysis 6.1).
Follow‐up between 9 and 12 months
There is insufficient evidence of an advantage in using APC from both split‐mouth studies (MD 1.53, 95% CI ‐0.85 to 3.91; P = 0.21; 2 studies; 82 participants) and parallel studies (MD 0.25, 95% CI ‐0.15 to 0.64; P = 0.22; 3 studies; 82 participants). Overall, there is insufficient evidence of an advantage in using APC (MD 0.68, 95% CI ‐0.66 to 2.02; P = 0.32) (Analysis 7.1).
Change in CAL (mm)
All follow‐ups
There is evidence of an advantage in using APC from split‐mouth studies (MD 0.67, 95% CI 0.20 to 1.14; P = 0.005; 4 studies; 166 participants) but not from parallel studies (MD 0.09, 95% CI ‐0.32 to 0.50; P = 0.66; 3 studies; 82 participants). Overall, there is insufficient evidence of an advantage in using APC (MD 0.42, 95% CI ‐0.02 to 0.86; P = 0.06) (Analysis 5.2).
Follow‐up between 3 and 6 months (only split‐mouth studies)
There is evidence of an advantage in using APC (MD 0.54, 95% CI 0.18 to 0.89; P = 0.003; 3 studies; 134 participants) (Analysis 6.2).
Follow‐up between 9 and 12 months
There is insufficient evidence of an advantage in using APC from both split‐mouth studies (MD 0.51, 95% CI ‐0.72 to 1.73; P = 0.42; 2 studies; 82 participants) and parallel studies (MD 0.09, 95% CI ‐0.32 to 0.50; P = 0.66; 3 studies; 82 participants). Overall, there is no evidence of an advantage in using APC (MD 0.27, 95% CI ‐0.39 to 0.93; P = 0.42) (Analysis 7.2).
4. APC + enamel matrix derivative (EMD) versus EMD
Change in PD (mm)
All follow‐ups
Only one study had a split‐mouth design and showed insufficient evidence of an advantage in using APC (MD 0.13, 95% CI ‐0.05 to 0.31; P = 0.15; 49 participants). Equally only one study had a parallel design which showed insufficient evidence of an advantage in using APC (MD ‐0.10, 95% CI ‐1.32 to 1.12; P = 0.87; 26 participants). Overall, there is insufficient evidence of an advantage in using APC (MD 1.13, 95% CI ‐0.05 to 0.30; P = 0.16) (Analysis 8.1).
Change in CAL (mm)
All follow‐ups
Only one study had a split‐mouth design and showed insufficient evidence of an advantage in using APC (MD 0.12, 95% CI ‐0.12 to 0.36; P = 0.32; 49 participants). The only one study with a parallel design also showed insufficient evidence of an advantage in using APC (MD ‐0.20, 95% CI ‐1.06 to 0.66; P = 0.65; 26 participants). Overall, there is insufficient evidence of an advantage in using APC (MD 0.10, 95% CI ‐0.13 to 0.32; P = 0.40) (Analysis 8.2).
Change in RBF (%)
All follow‐ups
Only one split‐mouth study provided data and showed insufficient evidence of an advantage in using APC (MD ‐0.60%, 95% CI ‐6.21% to 5.01%; P = 0.83; 49 participants) (Analysis 8.3).
Secondary outcomes
All the studies in all groups reported a survival rate of 100% for the treated teeth. No complete pocket closure was reported. No quantitative analysis regarding patients' quality of life was possible.
Discusión
Resumen de los resultados principales
En esta revisión se incluyeron 38 estudios. Dichos estudios evaluaron los efectos de los concentrados plaquetarios autólogos (CPA) utilizados como un complemento de los tratamientos quirúrgicos periodónticos para el tratamiento de los defectos infraóseos. La calidad del grupo de evidencia se evaluó mediante los criterios GRADE, que se presenta en Resumen de los hallazgos, tabla 1 (para CPA + desbridamiento de colgajo abierto [DCA] versus DCA solo); Resumen de los hallazgos, tabla 2 (para CPA + DCA + injerto óseo [IO] versus DCA + IO); Resumen de los hallazgos, tabla 3 (para CPA + regeneración tisular guiada [RTG] versus RTG); y Resumen de los hallazgos, tabla 4 (para CPA + derivados de la matriz del esmalte [DME] versus DME).
Todos los datos se analizaron por separado por subgrupos y según parámetros específicos. En una evaluación general de los resultados, hay evidencia de que la presencia de CPA es ventajosa en el cambio de la profundidad de bolsa al sondaje y el nivel de inserción clínica en dos tipos de intervenciones (CPA + DCA y CPA + DCA + IO), pero no mostró efectos beneficiosos en la profundidad al sondaje en los grupos de CPA + RTG y CPA + DME. Para el resultado del relleno del defecto óseo radiográfico, hay evidencia de que el complemento de CPA tiene efectos beneficiosos en dos tipos de tratamiento (CPA + DCA y CPA + DCA + IO), pero no mostró ser suficientemente ventajosa cuando se asoció con el tratamiento con DME y no hubo datos disponibles para el grupo de RTG. En el segundo grupo de comparación (CPA + DCA + IO versus DCA + IO) hubo evidencia de una ventaja de los CPA en todos los seguimientos y para los tres parámetros: la profundidad al sondaje, el nivel de inserción clínica y el relleno del defecto óseo radiográfico. Por el contrario, al utilizar CPA en combinación con RTG o DME no se observaron efectos beneficiosos suficientes en cualquier período de seguimiento, excepto en el nivel de inserción clínica a los tres a seis meses de seguimiento. Lo anterior indicaría que los efectos beneficiosos potenciales de los CPA son enmascarados por las ventajas bien conocidas de los tratamientos de referencia de los defectos infraóseos como la RTG y los DME.
Con respecto a los resultados secundarios, todos los estudios en todos los grupos informaron de una tasa de supervivencia del 100% de los dientes tratados. No se informó del cierre completo de las bolsas. No fue posible el análisis cuantitativo con respecto a la calidad de vida del paciente.
Compleción y aplicabilidad general de las pruebas
Aunque la mayoría de los estudios fueron realizados por profesionales experimentados en ámbitos universitarios, se cree que con el entrenamiento adecuado las técnicas son aplicables a la práctica diaria general y, por lo tanto, es factible la generalización de los resultados de esta revisión.
Excepto por el relleno óseo radiográfico, todos los otros parámetros clínicos tienen algún nivel de subjetividad en cuanto a las mediciones. Sin embargo, el procedimiento de evaluación generalmente está bien estandarizado y con el entrenamiento básico el resultado puede ser reproducible de un profesional a otro.
Los períodos de seguimiento de los estudios en general fueron adecuados para cada uno de los resultados. Todos los estudios incluidos tuvieron un período de seguimiento de al menos tres meses para los resultados clínicos (profundidad al sondaje y nivel de inserción clínica), que es adecuado para este tipo de resultado. El relleno del defecto óseo radiográfico, que requiere un tiempo más prolongado para ser detectado, se midió en la mayoría de los estudios entre los nueve y los 12 meses.
La gran mayoría de los pacientes completó los períodos de seguimiento en los estudios respectivos y los abandonos nunca excedieron el 20%. Además, los 38 estudios incluidos informaron de los datos numéricos para los principales resultados clínicos (profundidad al sondaje y nivel de inserción clínica), lo que permitió realizar el metanálisis con un número razonable de estudios.
Calidad de la evidencia
Aunque todos los estudios incluidos en esta revisión fueron ensayos controlados aleatorios, 36 presentaron alto riesgo de sesgo, y dos riesgo incierto de sesgo. En consecuencia, se asignó un alto riesgo de sesgo a todos los grupos de estudio debido a que más del 50% de los estudios incluidos en cada grupo tuvo al menos un dominio considerado con alto riesgo de sesgo. Lo anterior dio lugar a una disminución de las evaluaciones GRADE de todos los grupos.
El grupo de la evidencia para los CPA + DCA versus DCA se consideró de muy baja calidad en los tres parámetros (profundidad al sondaje, nivel de inserción clínica y relleno óseo radiográfico). Hubo evidencia de heterogeneidad alta; sin embargo, la población estudiada fue mayor de 400.
El grupo de la evidencia para los CPA + DCA + IO versus DCA + IO se consideró de muy baja calidad para los tres parámetros (profundidad al sondaje, nivel de inserción clínica y relleno óseo radiográfico). Tenían una población de estudio adecuada (mayor de 400), pero una heterogeneidad alta.
El grupo de la evidencia para los CPA + RTG versus RTG se consideró de muy baja calidad para la profundidad al sondaje y el nivel de inserción clínica. Hubo evidencia de imprecisión en ambos parámetros a pesar de una buena consistencia.
El grupo de la evidencia sobre los CPA + DME versus DME se consideró de muy baja calidad para la profundidad al sondaje, el nivel de inserción clínica y el relleno óseo radiográfico. Hubo evidencia de imprecisión alta en todos los parámetros.
Sesgos potenciales en el proceso de revisión
Se realizó una búsqueda electrónica sensible en múltiples bases de datos para identificar estudios adecuados para esta revisión. No se aplicaron restricciones de idioma ni fecha de publicación. En el caso de los estudios en curso que cumplieron con los criterios de inclusión y los estudios ya publicados con datos faltantes, se estableció contacto directo con los autores correspondientes, pero no siempre fue posible tener una respuesta por parte de los mismos. Lo anterior dio lugar a la exclusión de todos los datos faltantes de la revisión. Uno de los autores de la presente revisión (Massimo Del Fabbro) también se encuentra entre los autores de una de las revisiones utilizadas para comparar los resultados de la revisión actual. Se hizo frente a este sesgo al no involucrar a este autor en el proceso de evaluación de la sección de "Acuerdos y desacuerdos con otros estudios o revisiones".
Esta revisión tuvo como finalidad analizar el efecto de cualquier tipo de concentrado plaquetario autólogo para la mejoría de la curación de los defectos infraóseos y no se realizó un análisis separado para cada tipo de CPA. Es posible que el efecto de diferentes CPA sea distinto en diferentes subgrupos, pero se dejó de lado la idea de una comparación entre CPA porque no se encontraron estudios que compararan dos o más CPA entre sí y con un grupo control.
Acuerdos y desacuerdos con otros estudios o revisiones
En general, los resultados concordaron con los de revisiones sistemáticas anteriores.
Una revisión sistemática publicada en Journal of Periodontology (Del Fabbro 2011) incluyó 16 estudios que evaluaron los resultados del tratamiento de los defectos infraóseos y la recesión gingival con o sin el complemento del plasma rico en plaquetas (PRP). Encontraron un efecto positivo significativo del complemento de PRP al DCA para el parámetro del nivel de inserción clínica de los defectos infraóseos. Por otro lado, no se encontraron diferencias significativas entre los grupos con o sin PRP en los defectos infraóseos tratados con RTG. Estos resultados coinciden con los de la presente revisión.
Otra revisión (Roselló‐Camps 2015) evaluó 21 estudios sobre el uso de PRP para la regeneración periodóntica en comparación con otros procedimientos regenerativos como la RTG. Se encontró que los CPA mejoraron significativamente el nivel de inserción clínica y el relleno óseo radiográfico, de modo similar a los resultados de la presente revisión. Sin embargo, no se encontraron efectos beneficiosos adicionales de los CPA para la reducción de la profundidad al sondaje.
Por último, una revisión reciente (Castro 2017) analizó 21 artículos sobre el uso de fibrina rica en leucocitos y plaquetas (FRLP). Como esta revisión sistemática, Castro y cols. encontraron que el CPA fue beneficioso para la reducción de la profundidad al sondaje, la ganancia en el nivel de inserción clínica y el relleno óseo radiográfico, en comparación con el DCA solo. Sin embargo, no encontraron diferencias en estos resultados al comparar la FRLP con los tratamientos que comprendían la utilización del injerto tisular conectivo.
Study flow diagram.
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
Forest plot of comparison: 1 APC + OFD versus OFD (9‐12 months follow‐up); outcome: 1.1 Probing depth (mm).
Forest plot of comparison: 2 APC + OFD + BG versus OFD + BG (all follow‐ups); outcome: 2.1 Probing depth (mm).
Forest plot of comparison: 5 APC + GTR versus GTR (all follow‐ups), outcome: 5.1 Probing depth (mm).
Comparison 1 APC + OFD versus OFD (9‐12 months), Outcome 1 Probing depth (mm).
Comparison 1 APC + OFD versus OFD (9‐12 months), Outcome 2 Clinical attachment level (mm).
Comparison 1 APC + OFD versus OFD (9‐12 months), Outcome 3 Radiographic bone defect filling (%).
Comparison 2 APC + OFD + BG versus OFD + BG (all follow‐ups), Outcome 1 Probing depth (mm).
Comparison 2 APC + OFD + BG versus OFD + BG (all follow‐ups), Outcome 2 Clinical attachment level (mm).
Comparison 2 APC + OFD + BG versus OFD + BG (all follow‐ups), Outcome 3 Radiographic bone defect filling (%).
Comparison 3 APC + OFD + BG versus OFD + BG (3‐6 months), Outcome 1 Probing depth (mm).
Comparison 3 APC + OFD + BG versus OFD + BG (3‐6 months), Outcome 2 Clinical attachment level (mm).
Comparison 3 APC + OFD + BG versus OFD + BG (3‐6 months), Outcome 3 Radiographic bone defect filling (%).
Comparison 4 APC + OFD + BG versus OFD + BG (9‐12 months), Outcome 1 Probing depth (mm).
Comparison 4 APC + OFD + BG versus OFD + BG (9‐12 months), Outcome 2 Clinical attachment level (mm).
Comparison 4 APC + OFD + BG versus OFD + BG (9‐12 months), Outcome 3 Radiographic bone defect filling (%).
Comparison 5 APC + GTR versus GTR (all follow‐ups), Outcome 1 Probing depth (mm).
Comparison 5 APC + GTR versus GTR (all follow‐ups), Outcome 2 Clinical attachment level (mm).
Comparison 6 APC + GTR versus GTR (3‐6 months), Outcome 1 Probing depth (mm).
Comparison 6 APC + GTR versus GTR (3‐6 months), Outcome 2 Clinical attachment level (mm).
Comparison 7 APC + GTR versus GTR (9‐12 months), Outcome 1 Probing depth (mm).
Comparison 7 APC + GTR versus GTR (9‐12 months), Outcome 2 Clinical attachment level (mm).
Comparison 8 APC + EMD versus EMD (all follow‐ups), Outcome 1 Probing depth (mm).
Comparison 8 APC + EMD versus EMD (all follow‐ups), Outcome 2 Clinical attachment level (mm).
Comparison 8 APC + EMD versus EMD (all follow‐ups), Outcome 3 Radiographic bone defect filling (%).
| APC + OFD compared to OFD (9‐12 months follow‐up) for treating periodontal infrabony defects | ||||||
| Patient or population: patients affected by infrabony defects requiring surgical treatment | ||||||
| Outcomes | Illustrative comparative risks* (95% CI) | Relative effect | Number of participants/defects | Quality of the evidence | Comments | |
| Assumed risk | Corresponding risk | |||||
| OFD | APC + OFD | |||||
| Change in probing depth (PD) (mm) (9‐12 months follow‐up) | Mean PD change (gain) across control groups ranged from 2.40 to 3.68 (2.36) mm Mean PD baseline value was 7.92 mm (95% CI 6.25 to 9.54) | The mean PD change (gain) in the intervention groups was 1.29 mm higher (1.00 to 1.58 higher) | Mean difference 1.29 (1.00 to 1.58) mm | 510 | ⊕⊝⊝⊝ | There is evidence of an advantage in using APC |
| Change in clinical attachment level (CAL) (mm) (9‐12 months follow‐up) | Mean CAL change (gain) across control groups ranged from 1.27 to 4.14 (2.03) mm Mean CAL baseline value was 6.78 mm (95% CI 5.56 to 7.54) | The mean CAL change (gain) in the intervention groups was 1.47 mm higher (1.11 to 1.82 higher) | Mean difference 1.47 (1.11 to 1.82) mm | 510 | ⊕⊝⊝⊝ | There is evidence of an advantage in using APC |
| Change in radiographic bone defect filling (RBF) (%) (9‐12 months follow‐up) | Mean RBF change (gain) across control groups ranged from ‐3.60% to 54.20% (16.90%) | The mean RBF change (gain) in the intervention groups was 34.26% higher (30.07 to 38.46 higher) | Mean difference 34.26% (30.07 to 38.46) | 401 | ⊕⊝⊝⊝ | There is evidence of an advantage in using APC |
| *The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence | ||||||
| 1Downgraded by 2 levels for high risk of performance bias. | ||||||
| APC + OFD + BG compared to OFD + BG (all follow‐ups) for treating periodontal infrabony defects | ||||||
| Patient or population: patients affected by infrabony defects requiring surgical treatment | ||||||
| Outcomes | Illustrative comparative risks* (95% CI) | Relative effect | Number of participants/defects | Quality of the evidence | Comments | |
| Assumed risk | Corresponding risk | |||||
| OFD + BG | APC + OFD + BG | |||||
| Change in probing depth (PD) (mm) (All follow‐ups) | Mean PD change (gain) across control groups ranged from 1.90 to 5.30 (3.54) mm Mean PD baseline value was 7.32 mm (95% CI 5.94 to 8.65) | The mean PD change (gain) in the intervention groups was 0.54 mm higher (0.33 to 0.75 higher) | Mean difference 0.54 (0.33 to 0.75) mm | 569 | ⊕⊝⊝⊝ | There is evidence of an advantage in using APC |
| Change in clinical attachment level (CAL) (mm) (All follow‐ups) | Mean CAL change (gain) across control groups ranged from 1.30 to 4.70 (3.20) mm Mean CAL baseline value was 7.34 mm (95% CI 5.21 to 9.82) | The mean CAL change (gain) in the intervention groups was 0.72 mm higher (0.43 to 1.00 higher) | Mean difference 0.72 (0.43 to 1.00) mm | 569 | ⊕⊝⊝⊝ | There is evidence of an advantage in using APC |
| Change in radiographic bone defect filling (RBF) (%) (All follow‐ups) | Mean RBF change (gain) across control groups ranged from 9.20% to 57.20% (40.54%) | The mean RBF change (gain) in the intervention groups was 8.10% higher (5.26 to 10.94 higher) | Mean difference 8.10% (5.26 to 10.94) | 420 | ⊕⊝⊝⊝ | There is evidence of an advantage in using APC |
| *The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence | ||||||
| 1Downgraded by 2 levels for high risk of performance bias. | ||||||
| APC + GTR compared to GTR (all follow‐ups) for treating periodontal infrabony defects | ||||||
| Patient or population: patients affected by infrabony defects requiring surgical treatment | ||||||
| Outcomes | Illustrative comparative risks* (95% CI) | Relative effect | Number of participants/defects | Quality of the evidence | Comments | |
| Assumed risk | Corresponding risk | |||||
| GTR | APC + GTR | |||||
| Change in probing depth (PD) (mm) (All follow‐ups) | Mean PD change (gain) across control groups ranged from 3.19 to 6.00 mm (4.40 mm) Mean PD baseline value was 8.67 mm (95% CI 6.29 to 10.31) | The mean PD change (gain) in the intervention groups was 0.92 mm higher (‐0.02 lower to 1.86 higher) | Mean difference 0.92 mm (‐0.02 to 1.86) | 248 | ⊕⊝⊝⊝ | There is insufficient evidence of an advantage in using APC |
| Change in clinical attachment level (CAL) (mm) (All follow‐ups) | Mean CAL change (gain) across control groups ranged from 3.38 to 5.20 mm (4.38 mm) Mean CAL baseline value was 9.40 mm (95% CI 5.97 to 11.40) | The mean CAL change (gain) in the intervention groups was 0.42 mm higher (‐0.02 lower to 0.86 higher) | Mean difference 0.42 mm (‐0.02 to 0.86) | 248 | ⊕⊝⊝⊝ | There is insufficient evidence of an advantage in using APC |
| *The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence | ||||||
| 1Downgraded by 2 levels for high risk of performance bias. | ||||||
| APC + EMD compared to EMD (all follow‐ups) for treating periodontal infrabony defects | ||||||
| Patient or population: patients affected by infrabony defects requiring surgical treatment | ||||||
| Outcomes | Illustrative comparative risks* (95% CI) | Relative effect | Number of participants/defects | Quality of the evidence | Comments | |
| Assumed risk | Corresponding risk | |||||
| EMD | APC + EMD | |||||
| Change in probing depth (PD) (mm) (All follow‐ups) | Mean PD change (gain) across control groups ranged from 3.87 to 5.90 mm (4.89 mm) | The mean PD change (gain) in the intervention groups was 0.13 mm higher (‐0.05 lower to 0.30 higher) | Mean difference 0.13 mm (‐0.05 to 0.30) | 75 | ⊕⊝⊝⊝ | There is insufficient evidence of an advantage in using APC |
| Change in clinical attachment level (CAL) (mm) (All follow‐ups) | Mean CAL change (gain) across control groups ranged from 3.30 to 5.00 mm (4.15 mm) | The mean CAL change (gain) in the intervention groups was 0.10 mm higher (‐0.13 lower to 0.32 higher) | Mean difference 0.10 mm (‐0.13 to 0.32) | 75 | ⊕⊝⊝⊝ | There is insufficient evidence of an advantage in using APC |
| Change in radiographic bone defect filling (RBF) (%) (All follow‐ups) | Only 1 study reported RBF outcome with a mean change in control groups of 18.30% | The mean RBF change (gain) in the intervention group was 0.60% lower (‐6.21 lower to 5.01 higher) | Mean difference ‐0.60 (‐6.21 to 5.01) | 49 | ⊕⊝⊝⊝ | There is insufficient evidence of an advantage in using APC |
| *The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence | ||||||
| 1Downgraded by 2 levels for high risk of performance bias. | ||||||
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 Probing depth (mm) Show forest plot | 12 | 510 | Mean Difference (Random, 95% CI) | 1.29 [1.00, 1.58] |
| 1.1 Split‐mouth studies | 5 | 158 | Mean Difference (Random, 95% CI) | 1.86 [1.07, 2.66] |
| 1.2 Parallel studies | 7 | 352 | Mean Difference (Random, 95% CI) | 0.99 [0.90, 1.07] |
| 2 Clinical attachment level (mm) Show forest plot | 12 | 510 | Mean Difference (Random, 95% CI) | 1.47 [1.11, 1.82] |
| 2.1 Split‐mouth studies | 5 | 158 | Mean Difference (Random, 95% CI) | 2.36 [1.19, 3.54] |
| 2.2 Parallel studies | 7 | 352 | Mean Difference (Random, 95% CI) | 0.99 [0.84, 1.14] |
| 3 Radiographic bone defect filling (%) Show forest plot | 9 | 401 | Mean Difference (Random, 95% CI) | 34.26 [30.07, 38.46] |
| 3.1 Split‐mouth studies | 2 | 49 | Mean Difference (Random, 95% CI) | 27.32 [20.92, 33.72] |
| 3.2 Parallel studies | 7 | 352 | Mean Difference (Random, 95% CI) | 35.77 [31.20, 40.35] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 Probing depth (mm) Show forest plot | 17 | 569 | Mean Difference (Random, 95% CI) | 0.54 [0.33, 0.75] |
| 1.1 Split‐mouth studies | 12 | 360 | Mean Difference (Random, 95% CI) | 0.47 [0.24, 0.71] |
| 1.2 Parallel studies | 5 | 209 | Mean Difference (Random, 95% CI) | 0.81 [0.58, 1.03] |
| 2 Clinical attachment level (mm) Show forest plot | 17 | 569 | Mean Difference (Random, 95% CI) | 0.72 [0.43, 1.00] |
| 2.1 Split‐mouth studies | 12 | 360 | Mean Difference (Random, 95% CI) | 0.67 [0.35, 0.99] |
| 2.2 Parallel studies | 5 | 209 | Mean Difference (Random, 95% CI) | 0.89 [0.49, 1.29] |
| 3 Radiographic bone defect filling (%) Show forest plot | 11 | 420 | Mean Difference (Random, 95% CI) | 8.10 [5.26, 10.94] |
| 3.1 Split‐mouth studies | 8 | 270 | Mean Difference (Random, 95% CI) | 7.73 [4.50, 10.97] |
| 3.2 Parallel studies | 3 | 150 | Mean Difference (Random, 95% CI) | 9.66 [5.39, 13.94] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 Probing depth (mm) Show forest plot | 11 | 272 | Mean Difference (Random, 95% CI) | 0.62 [0.30, 0.94] |
| 1.1 Split‐mouth studies | 10 | 252 | Mean Difference (Random, 95% CI) | 0.58 [0.25, 0.92] |
| 1.2 Parallel studies | 1 | 20 | Mean Difference (Random, 95% CI) | 0.84 [0.60, 1.07] |
| 2 Clinical attachment level (mm) Show forest plot | 11 | 272 | Mean Difference (Random, 95% CI) | 0.47 [0.11, 0.84] |
| 2.1 Split‐mouth studies | 10 | 252 | Mean Difference (Random, 95% CI) | 0.40 [0.02, 0.77] |
| 2.2 Parallel studies | 1 | 20 | Mean Difference (Random, 95% CI) | 1.0 [0.93, 1.07] |
| 3 Radiographic bone defect filling (%) Show forest plot | 6 | 162 | Mean Difference (Random, 95% CI) | 4.76 [1.27, 8.25] |
| 3.1 Split‐mouth studies | 5 | 142 | Mean Difference (Random, 95% CI) | 3.59 [0.13, 7.05] |
| 3.2 Parallel studies | 1 | 20 | Mean Difference (Random, 95% CI) | 10.0 [4.90, 15.10] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 Probing depth (mm) Show forest plot | 10 | 381 | Mean Difference (Random, 95% CI) | 0.50 [0.31, 0.69] |
| 1.1 Split‐mouth studies | 6 | 192 | Mean Difference (Random, 95% CI) | 0.49 [0.26, 0.72] |
| 1.2 Parallel studies | 4 | 189 | Mean Difference (Random, 95% CI) | 0.58 [0.09, 1.06] |
| 2 Clinical attachment level (mm) Show forest plot | 6 | 192 | Mean Difference (Random, 95% CI) | 0.84 [0.62, 1.06] |
| 2.1 Split‐mouth studies | 6 | 192 | Mean Difference (Random, 95% CI) | 0.84 [0.62, 1.06] |
| 3 Radiographic bone defect filling (%) Show forest plot | 6 | 282 | Mean Difference (Random, 95% CI) | 9.99 [6.44, 13.55] |
| 3.1 Split‐mouth studies | 4 | 152 | Mean Difference (Random, 95% CI) | 10.16 [6.18, 14.14] |
| 3.2 Parallel studies | 2 | 130 | Mean Difference (Random, 95% CI) | 8.87 [1.03, 16.71] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 Probing depth (mm) Show forest plot | 7 | 248 | Mean Difference (Random, 95% CI) | 0.92 [‐0.02, 1.86] |
| 1.1 Split‐mouth studies | 4 | 166 | Mean Difference (Random, 95% CI) | 1.52 [0.54, 2.51] |
| 1.2 Parallel studies | 3 | 82 | Mean Difference (Random, 95% CI) | 0.25 [‐0.15, 0.64] |
| 2 Clinical attachment level (mm) Show forest plot | 7 | 248 | Mean Difference (Random, 95% CI) | 0.42 [‐0.02, 0.86] |
| 2.1 Split‐mouth studies | 4 | 166 | Mean Difference (Random, 95% CI) | 0.67 [0.20, 1.14] |
| 2.2 Parallel studies | 3 | 82 | Mean Difference (Random, 95% CI) | 0.09 [‐0.32, 0.50] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 Probing depth (mm) Show forest plot | 3 | 134 | Mean Difference (Random, 95% CI) | 1.07 [‐0.71, 2.86] |
| 1.1 Split‐mouth studies | 3 | 134 | Mean Difference (Random, 95% CI) | 1.07 [‐0.71, 2.86] |
| 2 Clinical attachment level (mm) Show forest plot | 3 | 134 | Mean Difference (Random, 95% CI) | 0.54 [0.18, 0.89] |
| 2.1 Split‐mouth studies | 3 | 134 | Mean Difference (Random, 95% CI) | 0.54 [0.18, 0.89] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 Probing depth (mm) Show forest plot | 5 | 164 | Mean Difference (Random, 95% CI) | 0.68 [‐0.66, 2.02] |
| 1.1 Split‐mouth studies | 2 | 82 | Mean Difference (Random, 95% CI) | 1.53 [‐0.85, 3.91] |
| 1.2 Parallel studies | 3 | 82 | Mean Difference (Random, 95% CI) | 0.25 [‐0.15, 0.64] |
| 2 Clinical attachment level (mm) Show forest plot | 5 | 164 | Mean Difference (Random, 95% CI) | 0.27 [‐0.39, 0.93] |
| 2.1 Split‐mouth studies | 2 | 82 | Mean Difference (Random, 95% CI) | 0.51 [‐0.72, 1.73] |
| 2.2 Parallel studies | 3 | 82 | Mean Difference (Random, 95% CI) | 0.09 [‐0.32, 0.50] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 Probing depth (mm) Show forest plot | 2 | 75 | Mean Difference (Random, 95% CI) | 0.13 [‐0.05, 0.30] |
| 1.1 Split‐mouth studies | 1 | 49 | Mean Difference (Random, 95% CI) | 0.13 [‐0.05, 0.31] |
| 1.2 Parallel studies | 1 | 26 | Mean Difference (Random, 95% CI) | ‐0.10 [‐1.32, 1.12] |
| 2 Clinical attachment level (mm) Show forest plot | 2 | 75 | Mean Difference (Random, 95% CI) | 0.10 [‐0.13, 0.32] |
| 2.1 Split‐mouth studies | 1 | 49 | Mean Difference (Random, 95% CI) | 0.12 [‐0.12, 0.36] |
| 2.2 Parallel studies | 1 | 26 | Mean Difference (Random, 95% CI) | ‐0.2 [‐1.06, 0.66] |
| 3 Radiographic bone defect filling (%) Show forest plot | 1 | 49 | Mean Difference (Random, 95% CI) | ‐0.6 [‐6.21, 5.01] |
| 3.1 Split‐mouth studies | 1 | 49 | Mean Difference (Random, 95% CI) | ‐0.6 [‐6.21, 5.01] |
