Is denosumab (Prolia) effective in the treatment of osteoporosis?

Updated: Jan 20, 2021
  • Author: Rachel Elizabeth Whitaker Elam, MD, MSc; Chief Editor: Herbert S Diamond, MD  more...
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Approval for use in GIOP was based on an international phase 3 study in which denosumab proved more effective than the bisphosphonate risedronate for increasing BMD at the lumbar spine. In patients who had been on steroids for at least 3 months (n=505), the change from baseline in BMD at 12 months was 4.4% with denosumab versus 2.3% with risedronate (P < 0.0001); in those who had started steroids less than 3 months previously (n=290), the change was 3.8% vs 0.8% (P < 0.0001). [203]

In postmenopausal women with osteoporosis, denosumab reduces the incidence of vertebral, nonvertebral, and hip fractures. [204]  Denosumab also increases bone mass in men at high risk for fracture who are receiving androgen deprivation therapy for nonmetastatic prostate cancer, [205]  and in women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer. 

A meta-analysis of 10 randomized, controlled trials concluded that denosumab improved BMD significantly more than bisphosphonate treatment at the lumbar spine, total hip, and femoral neck at 12 and 24 months. However, only 1 of the 10 studies demonstrated greater osteoporotic fracture reduction with denosumab treatment. [206]

In patients with multiple myeloma or bone metastases from breast cancer, a single subcutaneous dose of denosumab decreases bone turnover markers within 1 day, and this effect is sustained through 84 days at higher doses. [199] Denosumab has been shown to increase BMD and decrease bone resorption in postmenopausal women with osteoporosis over a 12-month period. Because the overactivity of RANKL is a major factor in bone loss in patients with autoimmune and inflammatory disorders, such as ulcerative colitis, denosumab may become first-line therapy for these patients. [207]  Denosumab in combination with teriparatide has been shown to increase BMD more than either drug alone, [208]  although combination therapy with osteoporosis medications is not currently recommended in clinical practice.

Denosumab has uniquely been associated with rebound lumbar vertebral fractures after denosumab discontinuation. These vertebral fractures are often multiple and occur within months of the time that the next dose of denosumab would be due for administration. [209]  For this reason, denosumab should be continued indefinitely or followed by bisphosphonate therapy, if not contraindicated.

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