Sequential Therapy for the Long-Term Treatment of Postmenopausal Osteoporosis
Open accessAbstract
Osteoporosis is a chronic condition characterized by decreased bone mass, loss of skeletal integrity, and increased susceptibility to fracture. Drugs used to treat osteoporosis can be classified as those that block bone resorption (antiresorptive), stimulate bone formation (anabolic), or do both. While all currently approved medications reduce the risk of fragility fractures in high-risk populations, they are generally unable to fully restore bone strength in most patients with established disease. Thus, the majority of patients require disease management over many years. Unfortunately, the continuous use of a single drug has limitations, both in terms of efficacy and safety, and so sequential therapy is commonly required. Given the expanding list of pharmacological agents currently available, careful consideration needs to be given as to which drugs to use and in what sequence. This review will evaluate the differential effects of antiresorptive, bone-forming, and dual-acting drugs when used in specific sequences and will explore the current evidence favoring the initial use of bone-forming/dual-acting drugs followed by antiresorptive medications. This review will also examine the notion that long-term treatment with an antiresorptive drug may diminish the efficacy of subsequent treatment with a bone-forming/dual-acting drug. Finally, this review will explore the current evidence pertaining to the specific issue of how to best prevent the clinical ramifications of denosumab cessation.
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Anti-resorptive drugs such as bisphosphonates and denosumab cause severe adverse events, poor compliance, and easy recurrence.
“However, these drugs cause severe adverse events, poor compliance, and easy recurrence61”
From Targeting Msx2 as a brake in the fusion fate of osteoclasts and an anabolic therapy in pre-clinical models of osteoporosis (2025) · cites this paper as [61]
The Abstract (page not provided) identifies rare but serious side effects as a concern with long-term bisphosphonate and denosumab use. The Denosumab Discontinuation section describes rebound bone loss and increased fracture risk after denosumab is stopped, not easy recurrence with both drugs. The passages do not support the claim of poor compliance. (LLM, conf=0.87)
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References 83 · Cited by 86
Research works printed but not linked: 5
- Parfitt AM. Skeletal heterogeneity and the purposes of bone remod- elling: implications for the understanding of osteoporosis. In: Marcus RFD and Kelsey J, eds. Osteoporosis. Academic Press; 1996:315-339.
- Tsai JN, Sassana G, Ramchand SK, Jordan M, Ryan S, Leder BZ. Comparison of alendronate versus raloxifene after denosumab dis- continuation (CARD): A randomized controlled trial. J Bone Miner Res. 2023;38(1):26-34.
- Tsai JN, Nishiyama KK, Lin D, et al. Effects of denosumab and ter- iparatide transitions on bone microarchitecture and estimated 310 The Journal of Clinical Endocrinology & Metabolism, 2024, Vol. 109, No. 2
- strength: the DATA-switch HR-pQCT study. J Bone Miner Res. 2017;32(10):2001-2009.
- McClung MR, Grauer A, Boonen S, et al. Romosozumab in post- menopausal women with low bone mineral density. N Engl J Med. 2014;370(5):412-420.
- Authors
- Ramchand, S. K., & Leder, B. Z.
- Affiliations
- Harvard University (US)
- Corresponding author
- Leder, Benjamin Z
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2023-08-23
- Volume
- 109
- Issue
- 2
- Pages
- 303-311
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W4386116238
- Cited by
- 86
- References
- 83
- Citations by year
- 2026: 36 · 2025: 27 · 2024: 21 · 2023: 2
- FWCI
- 4.75
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
- Health Sciences › Medicine › Oncology › Bone health and treatments
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Menopause: Health Impacts and Treatments
- Keywords
- postmenopausal osteoporosis, sequential therapy, antiresorptive agents, dual-acting drugs, denosumab, treatment switching, denosumab discontinuation
- MeSH terms
- Female, Humans, Osteoporosis, Bone Density, Osteoporosis, Postmenopausal, Bone Density Conservation Agents, Fractures, Bone
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