RESUMEN
Because bisphosphonates (BPs) are potent inhibitors of bone resorption, we hypothesized that they would retard direct remodeling of stress fractures. The aim of this study was to determine the effect of risedronate on direct remodeling and woven bone callus formation following stress fracture formation in the rat ulna. In 135 adult female Wistar rats, cyclic loading of the ulna created stress fractures. Rats were treated daily with oral saline, or risedronate at 0.1 or 1.0 mg/kg. From each bone, histomorphometry was performed on sections stained with toluidine blue at a standard level along the fracture. The high dose of risedronate caused a significant decrease in the percentage of repaired stress fracture and bone resorption along the stress fracture line at 6 and 10 weeks after loading (p < 0.05). At this dose, intracortical resorption was significantly reduced at 10 weeks after loading and intracortical new bone area was significantly reduced at 6 and 10 weeks. Woven bone formation and consolidation phases of stress fracture repair were not affected by low or high doses of risedronate. In conclusion, high dose bisphosphonate treatment impaired healing of a large stress fracture line by reducing the volume of bone resorbed and replaced during remodeling. We also confirmed that periosteal callus formation was not adversely affected by risedronate treatment.
Asunto(s)
Conservadores de la Densidad Ósea/farmacología , Remodelación Ósea/efectos de los fármacos , Ácido Etidrónico/análogos & derivados , Fracturas por Estrés/tratamiento farmacológico , Fracturas del Cúbito/tratamiento farmacológico , Animales , Callo Óseo/efectos de los fármacos , Diáfisis/efectos de los fármacos , Diáfisis/lesiones , Difosfonatos/farmacología , Relación Dosis-Respuesta a Droga , Ácido Etidrónico/farmacología , Femenino , Periostio/efectos de los fármacos , Ratas , Ratas Wistar , Ácido RisedrónicoRESUMEN
Loading of the rat ulna is an ideal model to examine stress fracture healing. The aim of this study was to undertake a detailed examination of the histology, histomorphometry and gene expression of the healing and remodelling process initiated by fatigue loading of the rat ulna. Ulnae were harvested 1, 2, 4, 6, 8, and 10 weeks following creation of a stress fracture. Stress fracture healing involved direct remodelling that progressed along the fracture line as well as woven bone proliferation at the site of the fracture. Histomorphometry demonstrated rapid progression of basic multicellular units from 1 to 4 weeks with significant slowing down of healing by 10 weeks after loading. Quantitative PCR was performed at 4 hours, 24 hours, 4 days, 7 days, and 14 days after loading. Gene expression was compared to an unloaded control group. At 4 hours after fracture, there was a marked 220-fold increase (P<0.0001) in expression of IL-6. There were also prominent peak increases in mRNA expression for OPG, COX-2, and VEGF (all P<0.0001). At 24 hours, there was a peak increase in mRNA expression for IL-11 (73-fold increase, P<0.0001). At 4 days, there was a significant increase in mRNA expression for Bcl-2, COX-1, IGF-1, OPN, and SDF-1. At 7 days, there was significantly increased mRNA expression of RANKL and OPN. Prominent, upregulation of COX-2, VEGF, OPG, SDF-1, BMP-2, and SOST prior to peak expression of RANKL indicates the importance of these factors in mediating directed remodelling of the fracture line. Dramatic, early upregulation of IL-6 and IL-11 demonstrate their central role in initiating signalling events for remodelling and stress fracture healing.
Asunto(s)
Curación de Fractura/genética , Fracturas por Estrés/genética , Fracturas por Estrés/patología , Regulación de la Expresión Génica , Fracturas del Cúbito/genética , Fracturas del Cúbito/patología , Fosfatasa Ácida/metabolismo , Animales , Femenino , Isoenzimas/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas , Ratas Wistar , Fosfatasa Ácida Tartratorresistente , Factores de Tiempo , Fracturas del Cúbito/enzimologíaRESUMEN
This paper describes the clinical and radiological features, surgical techniques used and results obtained in 6 horses with fractures of the tibial tuberosity. The horses were presented between 24 h and 8 weeks following injury. In all 6 cases, the fragments were displaced proximocranially and in 2 of these, there was comminution. Four were treated by open reduction and internal fixation using an AO/ASIF narrow dynamic compression plate and in 2 cases the fragments were removed. All horses returned to full athletic function and remained sound in follow-up times of 17-36 months. Implant removal was necessary in 1 case.