Hormonal therapies and osteoporosis.
Osteoporosis, now defined as a disease characterized by low bone mass and a microarchitectural deterioration of bone tissue leading to enhanced bone fragility and fracture risk, is a major public health problem. Classic hormonal therapies to prevent and treat osteoporosis associated with menopause have recently been questioned due to the risk/benefit ratio of prolonged treatment. There is a critical need for safe and effective alternative therapeutics for this disease. Nonhuman primates have been used as models to assess bone changes associated with estrogen deficiency because their trabecular and cortical bone remodeling processes, monthly menstrual cycles, and reproductive-hormone patterns are similar to those of humans. The ovariectomized nonhuman primate has become the preferred model in which to study effects on bone remodeling, particularly with regard to bone mass, architecture, and strength, in fulfillment of studies required by international guidelines for the development of antiosteoporotic drugs. The nonhuman primate is amenable to several methodologies that assess bone quantity and quality, including dual energy x-ray absorptiometry (DXA), quantitative computed tomography (QCT), histology, static and dynamic histomorphometry, and biomechanical testing, as well as assays developed for clinical use, which serve as biomarkers of bone metabolic processes. The use of the nonhuman primate model in the assessment of osteoporosis therapeutics, both hormonal (sex steroids and their analogues, parathyroid hormone) and nonhormonal (bisphosphonates), has provided valuable information on the safety and efficacy as well as the mechanisms of bone loss associated with estrogen deficiency that is directly applicable to the human situation.
Jerome
Christopher P
CP
SkeleTech, Inc., Bothell, WA, USA.
D000818:Animals; D016723:Bone Remodeling / Q000502:physiology; D001842:Bone and Bones / Q000502:physiology; D004164:Diphosphonates / Q000627:therapeutic use; D004195:Disease Models, Animal; D004967:Estrogens / Q000172:deficiency*; D005260:Female; D012739:Gonadal Steroid Hormones / Q000627:therapeutic use; D006801:Humans; D010024:Osteoporosis / Q000188:drug therapy / Q000503:physiopathology*; D011323:Primates / Q000502:physiology*
D004164:Diphosphonates; D004967:Estrogens; D012739:Gonadal Steroid Hormones