Efectos positivos de altas dosis de olpadronato sobre el diseño, la tenacidad y la resistencia del fémur de rata, independientes de la mineralización y la rigidez del tejido

RICARDO FRANCISCO CAPOZZA; NÉLIDA MONDELO; PAOLA REINA; LAURA NOCCIOLINO; JOSÉ LUIS FERRETTI; GUSTAVO ROBERTO COINTRY

Buenos Aires

Congreso; XXIX REUNIÓN DE LA AAOMM; 2012

Fracture prevention by bisphosphonates (BPs) cannot be fully explained by their effects on remodeling and crystallinity. A positive interaction with the modulation/orientation of modeling drifts by bone mechanostat by preventing osteocyte/osteoblast apoptosis (already shown in vitro) and a derived improvement of bone toughness can be proposed; but this can only be shown by studying all the diaphyseal design, stiffness, toughness and strength of geometrically regular and only-modeling bones. With that purpose, 28 male rats 3-month old received high oral doses (45 or 90 mg/kg /d) of OPD, and their femur diaphyses were pQCT-scanned and tested in bending. Compared to 8 untreated controls, both OPD doses enhanced significantly 1. cortical bone area (+21%) and bending and torsion moments of inertia (+30, +31%), 2. yield structural stiffness and strength (+15%, +13%), and 3.structural toughness (energy absorption and ultimate strain, +126%, +32%), further than needed for bw-bearing. Ultimate strength increased (+29%) in correlation with the improvements in diaphyseal design and toughness (p<0.001), but not so with tissue mineralization (cortical vBMD) and stiffness (calculated E) which were unaffected. The observed geometric/structural improvements unrelated to mineralization and remodeling in this model can only reflect a positive interaction with the directional modulation of modeling drifts by bone mechanostat, congruent with the anti-apoptotic effects of OPD. In remodeling bones, this could complement the unpredictable mechanical impact of the modest bone mass increase induced by BPs, and even neutralize the structural toughness impairment (inductor of diaphyseal fractures) because of reduced turnover and crystallinity.