RESUMEN
Epidemiological studies highlight the negative correlation between vitamin D levels and the incidence of many non-skeletal diseases including inflammatory diseases, cancer, and metabolic and neurological disorders. However, most randomized controlled trials (RCTs) with oral vitamin D supplementation give mixed results or are inconclusive. It has been said that "discovery commences with the awareness of anomaly". The "anomaly" between our preclinical and clinical data provides the opportunity to propose an alternative paradigm to the vitamin D endocrine system: the vitamin D autacoid paradigm. In the vitamin D autacoid paradigm, the extra-skeletal effects of vitamin D depend on the tissue reserves of vitamin D metabolites. These vitamin D autacoid systems are inducible oscillatory ecosystems in which 1,25D is produced, acts and is inactivated locally. In the vitamin D autacoid paradigm, attaining adequacy of vitamin D in the systemic circulation is necessary but not sufficient; we must also ensure the repletion of the tissue stores. The co-existence of two different vitamin D systems, endocrine and autacoid, with different functions and regulations leads to "significant shifts in the criteria determining the legitimacy both of problems and of proposed solutions". With respect to our clinical trials of vitamin D supplementation for unconventional effects, the proposed solution is administering and quantifying vitamin D metabolites directly to the target tissue.
Asunto(s)
Autacoides/uso terapéutico , Modelos Biológicos , Ensayos Clínicos Controlados Aleatorios como Asunto/métodos , Vitamina D/uso terapéutico , Tejido Adiposo/metabolismo , Administración Oral , Autacoides/administración & dosificación , Autacoides/farmacocinética , Encéfalo/metabolismo , Calcitriol/sangre , Microambiente Celular , Humanos , Inflamación , Riñón/metabolismo , Hígado/metabolismo , Especificidad de Órganos , Receptores de Calcitriol/fisiología , Proyectos de Investigación , Piel/metabolismo , Piel/efectos de la radiación , Rayos Ultravioleta , Vitamina D/administración & dosificación , Vitamina D/análogos & derivados , Vitamina D/metabolismo , Vitamina D/farmacocinéticaRESUMEN
There is evidence to suggest that tetracyclines have benefit beyond their antimicrobial activity. The ability to inhibit metalloproteinase activity may provide a disease-modifying effect in OA, and available data suggest that further investigation is warranted. Controlled, double-blind, prospective clinical studies have not been completed. The canine cruciate ligament transection model studies are frequently cited as the most convincing in vivo evidence of a benefit of oral tetracycline therapy for the treatment of OA. Until more evidence becomes available, the use of tetracyclines as therapeutic agents for OA should be considered investigational.