Hormonal Therapies and Osteoporosis

Abstract

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.

Aging and physical mobility in group-housed Old World monkeys

“…While this work has been helpful in understanding some of the biological factors that contribute to healthy aging, rodent models are limited by several key characteristics that make them dissimilar to primates and unsuitable for study of the association of physical mobility with risk of many diseases. For example, unlike primates, rodents continue to grow slowly throughout life and their skeletal metabolism differs from that of primates (Jerome 2004). Old World monkeys (e.g.…”

Regulation of Cbfa1 Expression by Total Flavonoids of Herba Epimedii

“…Loss of ovarian function may cause a 30% decrease of skeletal mass in women after menopause, due to their bone resorption increase and imbalance between the amounts of resorbed and formed bone at each remodeling site [10,11]. Bone loss in OVX animals is similar to that in postmenopausal women.…”

Response to an Adequate Dietary Intake of Vitamin D3 Modulates the Effect of Estrogen Therapy on Bone Density

“…Decreased bone mass and bone turnover after menopause in macaques occur to a similar degree as in humans, and 1 year after surgical menopause, macaques experience a level of bone loss comparable to bone loss 3-4 years after natural menopause in women. [22][23][24][25] The findings of comparative research have reported that drug trials using macaque models agree with data available from drug trials in women. 23,26 Macaque models, therefore, are useful in studying bone health because they allow for bone measurements difficult to obtain in women.…”

“…However, cynomolgus monkeys are a well-documented model in which to study these findings. [22][23][24][25][26] Using human models, it is nearly impossible to recreate the tightly controlled environment achieved in this cohort. As we do not know the ideal 25OHD 3 concentrations for optimum health in humans or monkeys, we analyzed the data based on the relationships between higher vs. lower 25OHD 3 concentrations as surrogates for adequate vs. inadequate.…”