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Nelson B. Watts, John P. Bilezikian, Advances in Target-Specific Therapy for Osteoporosis, The Journal of Clinical Endocrinology & Metabolism, Volume 99, Issue 4, 1 April 2014, Pages 1149–1151, https://doi.org/10.1210/jc.2014-1065
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Bone is constantly being remodeled, with resorption preceding formation. In the individual who is not losing bone mass, bone remodeling is balanced, with the osteoblast forming the same amount of bone that has been resorbed by the osteoclast. Remodeling in the aging skeleton, aided and abetted by estrogen deficiency after the menopause, is not balanced, with bone resorption exceeding bone formation; as a result, bone loss ensues. The earliest therapeutic attempts to correct this imbalance were focused on inhibiting bone resorption, thus bringing the bone remodeling unit into better balance.
When alendronate, an amino-containing bisphosphonate, was approved by the US Food and Drug Administration in 1995 (1–3), it was known that it reduced bone resorption, but the molecular mechanism of action (inhibition of a key enzyme in the mevalonate pathway, farnesyl pyrophosphate synthase) was not understood until later (4, 5). Subsequently, other bisphosphonates (risedronate, ibandronate, and zoledronic acid) joined the family of approved bisphosphonates for the treatment of osteoporosis. Along with estrogen, raloxifene (an estrogen analog), and calcitonin, these agents together are called “antiresorptive” drugs. Although it is true that their initial mechanistic effect is to reduce bone resorption, these drugs also reduce bone formation. Their therapeutic effect depends on the inhibition of resorption being greater than inhibition of formation. Although the classification of these drugs as antiresorptives is not correct because they are general antiremodeling agents, it is unlikely that other more accurate terms such as “anticatabolic” or “antiremodeling” will replace the common classification that is universally used. These antiresorptive agents appear to be generally safe and well tolerated and, with specific reference to alendronate, risedronate, and zoledronic acid, are associated with significant increases in bone mineral density (BMD) and reductions in the incidence of vertebral, hip, and nonvertebral fractures. Despite their safety and efficacy, these drugs maintain skeletal microstructure but do not rebuild it.
