Medicine by the Numbers

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Denosumab for Reducing Risk of Fractures in Postmenopausal Women

 

Am Fam Physician. 2019 May 1;99(9):online.

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DENOSUMAB (PROLIA) FOR REDUCING RISK OF FRACTURES IN POSTMENOPAUSAL WOMEN

BenefitsHarms

1 in 21 did not have a new vertebral fracture

1 in 118 developed an infection

1 in 71 did not have a new non-vertebral fracture

1 in 230 did not have a new hip fracture

DENOSUMAB (PROLIA) FOR REDUCING RISK OF FRACTURES IN POSTMENOPAUSAL WOMEN

BenefitsHarms

1 in 21 did not have a new vertebral fracture

1 in 118 developed an infection

1 in 71 did not have a new non-vertebral fracture

1 in 230 did not have a new hip fracture

Details for This Review

Study Population: Postmenopausal women with diagnosed osteoporosis

Efficacy End Points: Prevention of new vertebral and nonvertebral fractures

Harm End Points: Infection, neoplasm, death

Narrative: As bone density decreases, people are at an increased risk of fractures.1 Denosumab (Prolia) is a fully human monoclonal antibody that binds the receptor activator of nuclear factor kappa B ligand (RANKL), which prevents its interaction with the osteoclast and osteoclast precursor surface receptor, RANK. This inhibits osteoclast-mediated bone resorption by blocking osteoclast function, formation, and survival.2,3 Studies have demonstrated an increase in bone mineral density with the administration of denosumab in postmenopausal women.4,5 This review assesses whether the increase in bone mineral density translates into a reduction in the risk of osteoporosis-related fractures.

The FREEDOM trial is the largest randomized controlled trial to compare denosumab with placebo in the prevention of fractures in postmenopausal women with osteoporosis.2 Women between 60 and 90 years of age with a bone mineral density T-score of less than −2.5 (consistent with the typical definition of osteoporosis) at the lumbar spine or total hip were included in the trial. Patients were randomly assigned to receive subcutaneous injections of 60 mg of denosumab or placebo every six months for 36 months. In this trial, the primary end point was new vertebral fractures based on semi-quantitative grading scales of lateral spine radiographs.2 The treatment with denosumab was associated with significantly lower risk of new vertebral fractures (relative risk [RR] = 0.32;95% CI, 0.26 to 0.41; absolute risk difference [ARD] = 4.8%; number needed to treat [NNT] = 21). Secondary outcomes included nonvertebral fractures (NNT = 71), hip fractures (NNT = 230), new clinical vertebral fractures (NNT = 62), and multiple (at least two) new vertebral fractures (NNT = 103). The study found no significant difference in the incidence of infection, death, or

Author disclosure: No relevant financial affiliations.


Copyright © 2019 MD Aware, LLC (theNNT.com). Used with permission.

This series is coordinated by Dean A. Seehusen, MD, MPH, AFP Assistant Medical Editor, and Daniel Runde, MD, from the NNT Group.

A collection of Medicine by the Numbers published in AFP is available at https://www.aafp.org/afp/mbtn.

References

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1. Curry SJ, Krist AH, Owens DK, et al. Screening for osteoporosis to prevent fractures: U.S. Preventive Services Task Force recommendation statement. JAMA. 2018;319(24):2521–2531....

2. Cummings SR, San Martin J, McClung MR, et al.; FREEDOM Trial. Denosumab for prevention of fractures in postmenopausal women with osteoporosis [published correction appears in N Engl J Med. 2009; 361(19):1914]. N Engl J Med. 2009;361(8):756–765.

3. Zhou Z, Chen C, Zhang J, et al. Safety of denosumab in postmenopausal women with osteoporosis or low bone mineral density: a meta-analysis. Int J Clin Exp Pathol. 2014;7(5):2113–2122.

4. Bone HG, Bolognese MA, Yuen CK, et al. Effects of denosumab on bone mineral density and bone turnover in postmenopausal women. J Clin Endocrinol Metab. 2008;93(6):2149–2157.

5. Brown JP, Prince RL, Deal C, et al. Comparison of the effect of denosumab and alendronate on BMD and biochemical markers of bone turnover in postmenopausal women with low bone mass: a randomized, blinded, phase 3 trial. J Bone Miner Res. 2009;24(1):153–161.

6. Crandall CJ, Newberry SJ, Diamant A, et al. Comparative effectiveness of pharmacologic treatments to prevent fractures: an updated systematic review. Ann Intern Med. 2014;161(10):711–723.

7. Bone HG, Wagman RB, Brandi ML, et al. 10 years of denosumab treatment in postmenopausal women with osteoporosis: results from the phase 3 randomised FREEDOM trial and open-label extension. Lancet Diabetes Endocrinol. 2017;5(7):513–523.

8. Prolia (denosumab) [package insert]. Thousand Oaks, Calif.: Amgen; 2018. https://www.pi.amgen.com/~/media/amgen/repositorysites/pi-amgen-com/prolia/prolia_pi.pdf. Accessed December 27, 2018.

 

 

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