Two Osteoporosis Medications Shown to Be Equally Effective



Raloxifene is as effective as alendronate at preventing osteoporotic hip fractures in women, shows a new study.


Raloxifene is as effective as alendronate in preventing hip fracture in women with osteoporosis, and that while “prevailing clinical wisdom” favors alendronate as the first-line treatment option, raloxifene should remain an option, a large comparative study published in Science Reports shows.

Separate randomized studies comparing alendronate and raloxifene to placebo have suggested that alendronate has superior fracture prevention benefits,[i],[ii] but there have been few head-to-head randomised studies conducted to confirm this.

Yeesuk Kim, professor of orthopaedic surgery at Hanyang University in Seoul, Republic of Korea, said: “The previous comparative studies have several limitations such as short duration of follow-up, small cohorts or failure of balancing the comparative groups.”

Two observational studies based on data from insurance claims databases found no difference in both vertebral and non-vertebral fracture rates between alendronate and raloxifene patients,[iii],[iv] but did not assess suspected serious adverse events such as atypical femoral fractures (AFF), esophageal cancer, and osteonecrosis of the jaw (ONJ).

To better compare the effectiveness and safety of alendronate and raloxifene in fracture prevention, researchers from the Observational Health Data Sciences and Informatics (OHDSI) collaborative conducted a multicenter retrospective cohort study across nine databases to look at the comparative risks of fractures and adverse events among first-time users of the treatments.

The researchers identified 283,586 alendronate patients and 40,463 raloxifene patients from the databases. Patients in the alendronate group experienced 7.48 hip fractures, 8.18 vertebral fractures, 1.14 atypical femoral fractures, 0.21 esophageal cancers and 0.09 osteonecrosis of the jaw per 1,000 person-years, compared with 6.62, 7.36, 0.69, 0.22 and 0.06 events respectively per 1,000 person-years in the raloxifene group.

The researchers calculated that patients who took alendronate had a similar risk of hip fracture (hazard ratio 1.03, 95% confidence interval [CI] 0.94–1.13), esophageal cancer (HR 0.95, 95% CI 0.53–1.70), and osteonecrosis of the jaw (HR 1.62, 95% CI 0.78–3.34) to patients who took raloxifene, but that they were more likely to have vertebral fractures (HR 1.07, 95% CI 1.01–1.14) and atypical femoral fracture (HR 1.51, 95% CI 1.23–1.84).

Professor Kim said that the researchers did “not suggest changing the guideline in prescription of osteoporotic medication,” emphasising “Bisphosphonates are still the primary choice of osteoporotic medication.” But he pointed out that raloxifene might be a good choice for patients taking a “drug holiday” from bisphosphonates as well as those who experience or are at risk from adverse outcomes from bisphosphonates.

“FDA recommend that doctors should be aware of the possible risk of atypical subtrochanteric and diaphyseal femur fractures in patients taking bisphosphonates,” he said, “so, in cases of long-term users of bisphosphonates, raloxifene might be the secondary choice of osteoporosis medication.”

Thromboembolism was not assessed as an adverse outcome in the study because raloxifene is known to be associated with an increased risk of venous thromboembolic events, which should deter doctors from prescribing it to patients with a high risk of thromboembolism, said Professor Kim. If thromboembolism was included, the results would likely show no or little difference in risk of thromboembolism between the two groups, he explained, which would be misleading and might encourage doctors to prescribe raloxifene to high risk patients.

“We still suggest not to prescribe raloxifene for patients at thromboembolic risk,” he said, and for these patients bisophosphonates or other treatments are the recommended options.


Kim, Y., Tian, Y., Yang, J. et al. Comparative safety and effectiveness of alendronate versus raloxifene in women with osteoporosis. Sci Rep 10, 11115 (2020).

[i] Black, D. M. et al. Bisphosphonates and fractures of the subtrochanteric or diaphyseal femur. N. Engl. J. Med 362, 1761–71. https :// a1001 086 (2010).

[ii] Ettinger, B. et al. Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene: Results from a 3-year randomized clinical trial. multiple outcomes of raloxifene evaluation (more) investigators. JAMA 282, 637–45 (1999).

[iii]Foster, S. A. et al. Fractures in women treated with raloxifene or alendronate: A retrospective database analysis. BMC Womens Health 13, 15. https :// (2013).

[iv]Tanaka, S., Yamamoto, T., Oda, E., Nakamura, M. & Fujiwara, S. Real-world evidence of raloxifene versus alendronate in preventing non-vertebral fractures in Japanese women with osteoporosis: Retrospective analysis of a hospital claims database. J. Bone Miner. Metab. 36, 87–94. https :// 4-016-0809-0 (2018).

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