Effects of anticatabolic and anabolic therapies at the tissue level

The recent decade has seen the emergence of a wide variety of new effective therapies for osteoporosis. Although hormone replacement therapy and calcium supplementation were the only available therapies 20 yr ago, we now have a wide variety of anticatabolic (antiresorptive) therapies (bisphosphonates, calcitonin, selective estrogen receptor modulators SERMs]) and anabolic therapies in the form of recombinant parathyroid hormone PTH(1–34) and PTH(1–84)] approved and commercially available. Our initial perceptions around these therapies were quite primitive, being mainly based on bone mineral density measurements. However, recent progress in imaging technology and structural and histological evaluation of bone has yielded important new insights into the mechanism of action of the various treatments. This article summarizes current knowledge about both anticatabolic and the more recent anabolic therapies, with special emphasis on the results obtained from histological and structural analyses of bone biopsies. The evidence currently available indicates that anticatabolic therapies exert their significant antifracture efficacy through a pronounced reduction of bone turnover. This reduction in remodeling activity causes preservation of trabecular structure and a decrease in cortical porosity, both effects that will preserve bone biomechanical strength. Although anticatabolic drugs preserve bone architecture, bone-forming (anabolic) therapies, in this context exemplified by PTH, are able to reverse the deterioration of cancellous and cortical bone architecture seen during age-dependent bone loss and osteoporosis. Recent analyses using techniques enabling analysis of bone matrix constituents suggest that both anticatabolic and anabolic therapies also alter the properties of bone tissue components like mineralization and collagen crosslinking.