Regardless of the cause of acquired osteoporosis, it always represents an enhancement of the rate at which osteoclasts degrade the skeleton relative to the bone forming capacity of osteoblasts, thereby eventuating in negative bone balance. Thus, two general approaches to the treatment and prevention of the disease present themselves, namely inhibition of bone resorption or stimulation of bone formation. Despite the real promise of bone anabolism offered by intermittent PTH administration, most patients continue to be treated with antiresorptive agents. There is increasing consensus, in fact, that anabolic drugs offer a relatively short-term strategy to substantially increase bone mass with maintenance to be achieved by antiresorptives (1). Estrogen deprivation is the key event in the pathogenesis of postmenopausal osteoporosis. Thus, hormone replacement, whose principal effect is to dampen bone resorption, had, until relatively recently, been the mainstay of treating the disease. With the realization that supplemental estrogen carries substantial extraskeletal risks, its acceptance as an antiosteoporotic agent has diminished. Fortunately, the bisphosphonates have been effective substitutes. Similar to estrogen, however, concerns about prolonged bisphosphonate therapy are emerging.

Bone is a dynamic tissue, consistently remodeled by the tethered recruitment of osteoclasts and osteoblasts. In this scenario, the prior resorptive activity of osteoclasts, at a specific site, recruits osteoblasts to synthesize bone at the same location. It is important to realize, however, that remodeling represents the coupled appearance of osteoclasts and osteoblasts but not necessarily equal rates of bone degradation and formation. For example, both bone resorption and formation are enhanced in postmenopausal osteoporosis or continuous PTH administration, but the loss of skeletal mass that occurs in both circumstances is reflective of the dominance of the osteoclast. On the other hand, intermittently administered PTH also stimulates recruitment of both osteoclasts and osteoblasts, but the attendant increase in bone density, in this case, establishes osteoblast supremacy. In fact, development of strategies to suppress bone resorption while maintaining formation remains a challenge in the design of antiosteoporotic agents.