Nélida Mondelo

Determination of femur structural properties by geometric and material variables as a function of body weight in rats. Evidence of a sexual dimorphism.

Femur diaphyses of male and female Wistar rats were densitometrically and biomechanically assayed. The BMD-dependent material properties were better in female than in male bones, but cross-section geometric properties were better in male femurs. As a result, mechanical properties of the integrated diaphyses were better in males, but differences disappeared after statistical adjustment of data to a common body weight. Results evidence a feed-back mechanism locally controlling the strain-dependent bone modelling and the corresponding cross-sectional design as related to bone stiffness, with a set-point adjusted to animal biomass. A sexual dimorphism of bone biomechanics is also described for the species.

Effects of large doses of olpadronate (dimethyl-pamidronate) on mineral density, cross-sectional architecture, and mechanical properties of rat femurs

As part of a safety-assessment study, doses of 8, 40, and 200 mg/kg per day, 6 days per week, of sodium olpadronate (dimethyl-APD, Me2-APD) were given by gavage to 10-week-old male and female rats during 27 weeks. Only the 200 mg/kg per day dose provoked toxic effects and a meaningful growth depression, regardless of the animal gender. In male animals, doses of 40 or 200 mg/kg per day improved strength, stiffness, and cross-sectional moment of inertia (CSMI) of femur diaphyses despite the toxic effects observed at the highest dose. Changes in bone mechanical properties were a consequence of those induced in CSMI. Regression analyses showed a treatment-induced improvement in bone modeling (as assessed by CSMI) for the same level of bone material stiffness (as expressed by calculated values of elastic modulus). The high dependency of results on body mass bearing suggested that these effects were exerted through an increase in the efficiency of bone mechanostat. Strikingly, they were not evident in female rats. If not related to a lower bone bioavailability of bisphosphonates in female rats as described by others, this phenomenon may have reflected: (1) their a smaller biomass; and/or (2) a less effective mechanostatic regulation of bone architecture derived from a higher bone material stiffness related to male animals. An increase of BMD with a predominance toward the distal region was observed in all femurs studied. This effect, unrelated to the observed changes in mechanical properties, seems to express a lack of remodeling of primary cartilage or bone tissue.

Intravenous olpadronate restores ovariectomy-affected bone strength. A mechanical, densitometric and tomographic (pQCT) study

Female Wistar rats aged 3 months were ovariectomized (OX, n = 27). Three months later they were given i.v. doses of 150 (6), 300 (7), or 600 (6) ug/kg 2/wk of olpadronate during 12 weeks or left as OX controls (OXc). Bending fracture load of femur diaphyses, reduced in OXc, was recovered by olpadronate. This effect was paralleled by changes in material quality indicators as DEXA-BMD, tomographic (volumetric) BMD, elastic modulus, and maximum elastic stress of cortical bone. No changes were induced by any of the treatments on cross-sectional area or moment of inertia. Diaphyseal stiffness, not reduced by OX, was enhanced to overnormal values by olpadronate at any dose. None of the treatments affected the normal mechanostatic interrelationships between cross-sectional architecture and bone material quality indicators. The positive effects described point out important differences in bisphosphonate action on bone biomechanics according to the experimental conditions assayed.