2020 Volume 66 Issue 2 Pages 40-51
Antiresorptive drugs, such as the bisphosphonates and the RANKL inhibitor denosumab, are currently the most widely used osteoporosis medications. These drugs increase bone mineral density (BMD) and reduce the risk of vertebral, nonvertebral and hip fractures in postmenopausal women with osteoporosis. Recently, anabolic therapy with teriparatide was demonstrated to be superior to the bisphosphonate risedronate in postmenopausal women with vertebral fracture. Treatment with the sclerostin antibody romosozumab increase BMD more profoundly and rapidly than alendronate and is also superior to alendronate in reducing the risk of vertebral and nonvertebral fracture in postmenopausal women with osteoporosis. For patients with severe osteoporosis and high fracture risk, bisphosphonates alone are unlikely to be able to provide long-term protection against fracture and restore BMD. For those patients, sequential treatment, starting with anabolic drug, followed by an antiresorptive, will likely provide better long-term fracture prevention and should be the golden standard of future osteoporosis treatment. The concept of a “drug holiday” applies only to patients taking bisphosphonates because of a transient residual antiresorptive effect after discontinuation due to skeletal retention of drug. For non-bisphosphonates, a drug holiday is not appropriate because BMD declines rapidly after treatment is stopped.