Available online 2 February 2024

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Osteoporosis is a chronic progressive disease which requires lifelong monitoring and treatment. Sequencing from one treatment to another at different ages and stages of disease is an approach which can maximize benefits and avoid potential risks from long-term treatment with a single agent. When medications are discontinued, in the absence of sequential therapy, bone turnover rates return to baseline or above baseline and bone loss occurs. The rate of bone loss differs for different treatments, with a very slow decline after stopping bisphosphonates and a particularly rapid decline after stopping denosumab. Careful attention to osteoporosis medication transitions can mitigate bone density loss and its consequences. This paper reviews data in postmenopausal women that evaluate the effects of antiresorptive agents followed by other antiresorptives, osteoanabolic agents followed by antiresorptives and antiresorptives followed by osteoanabolic medications. For women who remain at high risk, switching from bisphosphonates to the more potent antiresorptive, denosumab, will result in further improvement in BMD. When indicated, stopping denosumab can be accomplished safely by transition to an adequate bisphosphonate regimen. For high and very high-risk patients, treating with osteoanabolic agents first, followed by antiresorptive agents, produces substantially larger BMD gains than the reverse treatment sequence, with the biggest differences seen for bone density of the hip. Awareness of the importance of treatment sequence can help improve osteoporosis care across the postmenopausal lifespan.

Section snippetsIntroduction:

Strategies to treat osteoporosis have evolved dramatically over the last 25 years. No medical intervention can produce permanent changes to bone mass or structure. With some agents, reductions in fracture risk are seen in the first few years and then maintained (1). Some agents (especially osteoanabolic medications) are designed to be used for only 1-2 years (2). Furthermore, safety concerns may arise upon long-term treatment of any one medication. Therefore, the best approach to manage

Raloxifene Followed by Bisphosphonates or Denosumab

In women with osteoporosis, raloxifene protects against vertebral but not nonvertebral fracture (20). Raloxifene reduces risk of estrogen receptor positive breast cancer substantially but also increases risk of venous thromboembolism (21, 22). Because of the latter safety concern and the lack of protection against nonvertebral or hip fracture, raloxifene is not optimal treatment for older women or those with severe osteoporosis. Beneficial effects of raloxifene on bone wane rapidly after

Sequential Osteoanabolic Followed by Antiresorptive Treatments

In short-term comparative trials, osteoanabolic agents reduce fracture risk more than antiresorptive agents (55, 56, 57) and should be considered as initial therapy in patients at very high risk, such as those with recent fracture or history of multiple fractures (3). Since osteoanabolic agents are usually only used for 1-2 years, longer-term investigations have evaluated the sequence of an osteoanabolic followed by an antiresorptive compared to placebo followed by an antiresorptive (59, 60, 61

Sequential Therapy in Premenopausal Women and Men

There are few studies assessing the effect of sequential data on premenopausal women. In 32 premenopausal women with idiopathic osteoporosis, 2 years of denosumab after 2 years of teriparatide produced additional BMD increases of 6.9% in the LS and 4.6% at TH, with cumulative 4-year increments of 21.9% and 9.8% respectively (79). This transition was also associated with gains in FEA-estimated bone strength at both the LS, distal tibia and radius (80, 81). Sequential treatment has not been

Conclusion:

Women who are diagnosed with low bone mass close to osteoporosis range may benefit from antiresorptive agents used in age-appropriate sequences to prevent the development of osteoporosis. Patients diagnosed with osteoporosis prior to fracture might also benefit from sequential monotherapy beginning with raloxifene in the decades of the 50s and 60s and switching to denosumab or bisphosphonates in older women. Denosumab can be stopped, when appropriate, with careful transition to bisphosphonates.

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© 2024 Published by Elsevier Inc. on behalf of the AACE.