[Preclinical toxicology of bisphosphonates].

Bisphosphonates regulate bone turnover by inhibiting osteoclastic bone resorption. Due to their pharmacodynamic and pharmacokinetic characteristics, bisphosphonates have a special pharmacotoxicological profile related to their high degree of specificity: low or non-existent distribution in soft tissues and strong affinity for calcified tissues. Some general conclusions may be drawn from the pre-clinical toxicological studies, whose main aim is to identify the toxicity target organ/s and estimate the safety margins of a "prospective therapeutic agent" in laboratory animals.

[Effects of bisphosphonates on the mechanical efficiency of normal and osteopenic bones].

Bone mechanical competence (stiffness, strength) at organ level is determined by mechanical quality (intrinsic stiffness) and spatial distribution (macro-architecture) of bone material in cortical tissue (in every bone) and trabecular network (in vertebral bodies). These properties are inter-related and controlled according to mechanical usage by a feed-back mechanism known as mechanostat. Therefore, the effects on bone fragility of any treatment should be evaluated concerning the way they may have affected bone material or geometric properties as well as the mechanostatical interactions between them.

[Experimental effects of olpadronate and pamidronate on bone mass].

Ovariectomy and immobilization in rats have demonstrated to be useful models for osteopenia and they are considered to mimic some aspects of human osteoporosis associated with a deficit of ovarian hormones and the absence of mechanical function (disuse of the bone). Pamidronate (APD) and Olpadronate (OLPA), a new dimethylated aminobisphosphonate, on a continuous oral scheme (APD: 8 and OLPA: 0.8 mg/kg/day) or on an intermittent parenteral scheme (APD: 1.

The kallikrein-kinin system in early state of diabetes.

The kallikrein-kinin system was studied in 9 normals, healthy subjects (6 men, 3 women, age range 1 to 14 years) and 15 diabetic patients (9 men, 6 women age range 2 to 14 years) with an evolution of the disease between 1 to 14 years. Diabetic patients with low microalbuminuria (6.62 +/- 0.