Cone-Beam Computed Tomography to evaluate changes in trabecular lower jawbone microstructure caused by bone loss and antiresorptive treatment.

For decades, conventional histomorphometry has been the gold standard for analyzing trabecular bone microarchitecture. In recent years, micro-computed tomography (µCT) devices have been validated and are now considered the gold standard for quantifying bone microstructure. Aim: The aim of this preliminary report is to evaluate the usefulness of CBCT to assess trabecular mandible microstructural properties in normal ewes and to compare the quantitative changes associated with ovariectomy and antiresorptive treatment. Material and Method: Twelve adult Corriedale ewes (n=4/group) aged 3-4 years were divided into 3 groups and studied for 28 months. Eight ewes were ovariectomized (OVX) and divided into OVX and OVX+ZOL groups (n=4/group) which were treated as follows, by jugular injection: OVX received saline solution and OVX+ZOL received zoledronate (Zol) (Gador SA, CABA, Argentina) (4 mg/month). Another four ewes were subjected to sham surgery (SHAM group) and received saline solution. Results: Densitometry showed that jaw mineral content (BMC) and density (BMD) were significantly lower in OVX than in SHAM and OVX+ZOL ewes; no difference was observed between OVX+ ZOL and SHAM groups. CBCT analysis showed that bone volume (BV/TV%); trabecular thickness (TbTh); connectivity density (CD) and anisotropy degree (AD) were significantly lower, and trabecular spacing (TbSp), significantly higher in OVX than in SHAM ewes. AD was significantly higher and TbSp significantly lower in OVX+ZOL than in OVX groups. BV/TV%, TbTh and CD showed a clear tendency to being higher in OVX+ZOL than in OVX groups. No statistical difference was observed between OVX+ZOL and SHAM ewes. CBCT in a nondestructive, fast, very precise procedure for measuring bone morphometric indices without biopsies, which are not indicated for morphometric evaluation in osteoporosis. Conclusions: The current study demonstrated the potential of the high-resolution CBCT imaging to assess in vivo quantitative bone morphometry and bone quality of lower jaw cancellous bone under normal conditions and to differentiate changes associated with excessive bone loss induced by estrogen withdrawal and antiresorptive intervention.

Objetivo: El presente informe preliminar evaluó la utilidad de Tomografía Computada de Haz Cónico (CBCT) para analizar las propiedades microestructurales trabeculares del maxilar inferior de ovejas y comparar los cambios cuantitativos asociados con la ovariectomía y tratamiento antirresortivo. Se estudiaron dieciséis ovejas Corriedale adultas de 3-4 años. Materiales y Método: Doce ovejas fueron ovariectomizadas (OVX) y divididas en 2 grupos: OVX y OVX+ZOL (n=4/grupo) cuyo tratamiento por inyección endovenosa en la yugular durante 28 meses fue el siguiente: OVX con solución salina y OVX+ZOL con zoledronato (Gador S.A. CABA. Argentina) (Zol) (4 mg/mes); 4 ovejas fueron sometidas a cirugía simulada (grupo SHAM). Resultados: La densitometría (Lunar DPX) mostró que el contenido mineral del hueso maxilar (CMO) y la densidad (DMO) fueron significativamente más bajos en OVX que en SHAM y OVX+ZOL; no se observaron diferencias entre los grupos OVX+ZOL y SHAM. El análisis de las imágenes por CBCT (Planmeca Promax 3D Classic) mostró que el volumen óseo (BV/TV%); el espesor trabecular (TbTh); la densidad de conectividad (CD) y el grado de anisotropía (AD) fueron significativamente menores (p<0.05), y el espaciado trabecular (TbSp), significativamente mayor en OVX que en SHAM (p<0.05). AD fue significativamente mayor (p<0.05) y TbSp, significativamente menor en OVX+ZOL que en OVX (p<0.05). BV/TV%, TbTh y CD mostró una clara tendencia a ser mayor en OVX+ZOL que en OVX. No se observaron diferencias estadísticas entre OVX+ZOL y SHAM. Conclusiones: En base a nuestros resultados consideramos que CBCT presenta suficiente confiabilidad y validez para evaluar in vivo la morfometría cuantitativa y la calidad del hueso esponjoso del maxilar inferior en condiciones normales, así como para diferenciar los cambios en dichos parámetros asociados a la pérdida ósea excesiva por la caída estrogénica e intervención antirresortiva. Aunque se necesitan estudios futuros, nuestros resultados agregarían una herramienta no invasiva adicional para diferenciar la microestructura del hueso trabecular mandibular en estudios preclínicos , sentando las bases para su futura aplicación en la práctica clínica.

Aminobisphosphonate-treated ewes as a model of osteonecrosis of the jaw and of dental implant failure.

BACKGROUND: Bisphosphonate (BP)-related osteonecrosis of the jaw (BRONJ) and dental implant failure are two negative side effects of chronic aminoBP treatment. METHODS: Eleven ovariectomized (OVX) ewes and four ewes subjected to sham surgery (SHAM) were treated as follows: OVX (n = 5): OVX plus saline solution; zoledronic acid-treated group (ZOL) (n = 6): OVX plus ZOL; SHAM (n = 4): SHAM plus saline solution. Extraction of the first upper molar was performed at 1 year, dental implant placement at 2 years, and sacrifice at 28 months. RESULTS: Implants remained in place in SHAM and OVX ewes but were lost in all ZOL ewes. ZOL sheep (2/6) showed inflammation and necrotic bone at mandibular region. No differences in serum calcium (Ca), inorganic phosphate (Pi) or 25-hydroxyvitamin D were observed, whereas bone alkaline phosphatase levels decreased in the three studied groups (P < 0.05). The significantly lowest levels of carboxy-terminal telopeptide of type I collagen were observed in ZOL (P < 0.05), and showed no differences between SHAM and OVX. OVX showed the lowest and ZOL the highest Ca and Pi contents in femur and maxilla (P < 0.05). Bone volume (BV/TV%) and iliac crest were similar at baseline and at month 4. At the end of the study, BV/TV%, proximal femur and hemi-mandible bone mineral content and bone mineral density, and trabeculae number were similar in SHAM and ZOL, and lower in OVX (P < 0.05). CONCLUSION: All ZOL-treated ewes on a schedule similar to that used in cancer patients showed extensive suppression of bone remodeling and implant failure. Some of the ZOL ewes developed BRONJ.

Cone-Beam Computed Tomography to evaluate changes in trabecular lower jawbone microstructure caused by bone loss and antiresorptive treatment / CBCT para evaluar cambios en la microarquitectura ósea de la mandíbula por pérdida ósea y tratamiento antirresortivo

ABSTRACT For decades, conventional histomorphometry has been the gold standard for analyzing trabecular bone microarchitecture. In recent years, micro-computed tomography (μCT) devices have been validated and are now considered the gold standard for quantifying bone microstructure Aim The aim of this preliminary report is to evaluate the usefulness of CBCT to assess trabecular mandible microstructural properties in normal ewes and to compare the quantitative changes associated with ovariectomy and antiresorptive treatment Material and Method Twelve adult Corriedale ewes (n=4/group) aged 3-4 years were divided into 3 groups and studied for 28 months. Eight ewes were ovariectomized (OVX) and divided into OVX and OVX+ZOL groups (n=4/group) which were treated as follows, by jugular injection: OVX received saline solution and OVX+ZOL received zoledronate (Zol) (Gador SA, CABA, Argentina) (4 mg/month). Another four ewes were subjected to sham surgery (SHAM group) and received saline solution Results Densitometry showed that jaw mineral content (BMC) and density (BMD) were significantly lower in OVX than in SHAM and OVX+ZOL ewes; no difference was observed between OVX+ ZOL and SHAM groups. CBCT analysis showed that bone volume (BV/TV%); trabecular thickness (TbTh); connectivity density (CD) and anisotropy degree (AD) were significantly lower, and trabecular spacing (TbSp), significantly higher in OVX than in SHAM ewes. AD was significantly higher and TbSp significantly lower in OVX+ZOL than in OVX groups. BV/TV%, TbTh and CD showed a clear tendency to being higher in OVX+ZOL than in OVX groups. No statistical difference was observed between OVX+ZOL and SHAM ewes. CBCT in a nondestructive, fast, very precise procedure for measuring bone morphometric indices without biopsies, which are not indicated for morphometric evaluation in osteoporosis Conclusions The current study demonstrated the potential of the high-resolution CBCT imaging to assess in vivo quantitative bone morphometry and bone quality of lower jaw cancellous bone under normal conditions and to differentiate changes associated with excessive bone loss induced by estrogen withdrawal and antiresorptive intervention.

RESUMEN Objetivo El presente informe preliminar evaluó la utilidad de Tomografía Computada de Haz Cónico (CBCT) para analizar las propiedades microestructurales trabeculares del maxilar inferior de ovejas y comparar los cambios cuantitativos asociados con la ovariectomía y tratamiento antirresortivo. Se estudiaron dieciséis ovejas Corriedale adultas de 3-4 años Materiales y Método Doce ovejas fueron ovariectomizadas (OVX) y divididas en 2 grupos: OVX y OVX+ZOL (n=4/grupo) cuyo tratamiento por inyección endovenosa en la yugular durante 28 meses fue el siguiente: OVX con solución salina y OVX+ZOL con zoledronato (Gador S.A. CABA. Argentina) (Zol) (4 mg/mes); 4 ovejas fueron sometidas a cirugía simulada (grupo SHAM) Resultados La densitometría (Lunar DPX) mostró que el contenido mineral del hueso maxilar (CMO) y la densidad (DMO) fueron significativamente más bajos en OVX que en SHAM y OVX+ZOL; no se observaron diferencias entre los grupos OVX+ZOL y SHAM. El análisis de las imágenes por CBCT (Planmeca Promax 3D Classic) mostró que el volumen óseo (BV/TV%); el espesor trabecular (TbTh); la densidad de conectividad (CD) y el grado de anisotropía (AD) fueron significativamente menores (p<0.05), y el espaciado trabecular (TbSp), significativamente mayor en OVX que en SHAM (p<0.05). AD fue significativamente mayor (p<0.05) y TbSp, significativamente menor en OVX+ZOL que en OVX (p<0.05). BV/TV%, TbTh y CD mostró una clara tendencia a ser mayor en OVX+ZOL que en OVX. No se observaron diferencias estadísticas entre OVX+ZOL y SHAM Conclusiones En base a nuestros resultados consideramos que CBCT presenta suficiente confiabilidad y validez para evaluar in vivo la morfometría cuantitativa y la calidad del hueso esponjoso del maxilar inferior en condiciones normales, así como para diferenciar los cambios en dichos parámetros asociados a la pérdida ósea excesiva por la caída estrogénica e intervención antirresortiva. Aunque se necesitan estudios futuros, nuestros resultados agregarían una herramienta no invasiva adicional para diferenciar la microestructura del hueso trabecular mandibular en estudios preclínicos , sentando las bases para su futura aplicación en la práctica clínica.