From the Guidelines
Long-term use of Prolia (denosumab) is associated with an increased risk of atypical femur fractures and osteonecrosis of the jaw, which can occur after prolonged use, typically beyond 3-5 years, as reported in a study published in 2023 1. The most concerning risks of long-term Prolia use include:
- Atypical femur fractures
- Osteonecrosis of the jaw
- Rebound effect with rapid bone loss if discontinued without transitioning to another osteoporosis medication
- Long-term suppression of bone turnover, potentially impairing the body's natural ability to repair microdamage in bones
- Persistent side effects, including muscle and joint pain, increased risk of infections, and hypocalcemia Some key points to consider when evaluating the risks of long-term Prolia use include:
- The NCCN Guidelines for MM recommend bisphosphonates or denosumab for all patients receiving therapy for symptomatic MM, regardless of documented bone disease, with denosumab preferred in patients with renal disease 1
- Regular monitoring through bone density scans, calcium levels, and dental evaluations is essential for patients on long-term Prolia therapy
- The benefits of continued fracture prevention should be carefully weighed against the potential risks when considering extended treatment beyond 5-10 years
- A baseline dental examination and monitoring for ONJ are recommended for all patients receiving a bone-modifying agent, and monitoring for renal dysfunction is recommended with use of bisphosphonate therapy 1 It is essential to carefully evaluate the risks and benefits of long-term Prolia use and to regularly monitor patients for potential side effects, particularly those with a history of renal disease or other risk factors for atypical femur fractures and osteonecrosis of the jaw.
From the FDA Drug Label
In addition, bone mineral density (BMD) returns to pretreatment values within 18 months after the last injection [see Clinical Pharmacology (12.2), Clinical Studies (14. 1)]. New vertebral fractures occurred as early as 7 months (on average 19 months) after the last dose of Prolia. 5.7 Serious Infections In a clinical trial of over 7800 women with postmenopausal osteoporosis, serious infections leading to hospitalization were reported more frequently in the Prolia group than in the placebo group [see Adverse Reactions (6. 1)]. 5.8 Dermatologic Adverse Reactions In a large clinical trial of over 7800 women with postmenopausal osteoporosis, epidermal and dermal adverse events such as dermatitis, eczema, and rashes occurred at a significantly higher rate in the Prolia group compared to the placebo group. 5.9 Musculoskeletal Pain In postmarketing experience, severe and occasionally incapacitating bone, joint, and/or muscle pain has been reported in patients taking Prolia [see Adverse Reactions (6. 2)]. 5.10 Suppression of Bone Turnover In clinical trials in women with postmenopausal osteoporosis, treatment with Prolia resulted in significant suppression of bone remodeling as evidenced by markers of bone turnover and bone histomorphometry [see Clinical Pharmacology (12.2), Clinical Studies (14. 1)]. The long-term consequences of the degree of suppression of bone remodeling observed with Prolia may contribute to adverse outcomes such as osteonecrosis of the jaw, atypical fractures, and delayed fracture healing.
The cons of long-term use of Prolia (denosumab) include:
- Increased risk of serious infections, such as skin infections, abdominal infections, and endocarditis 2
- Dermatologic adverse reactions, including dermatitis, eczema, and rashes 2
- Musculoskeletal pain, which can be severe and incapacitating 2
- Suppression of bone turnover, which may contribute to adverse outcomes such as osteonecrosis of the jaw, atypical fractures, and delayed fracture healing 2
- Loss of bone mineral density after treatment is discontinued, which may increase the risk of new vertebral fractures 2
From the Research
Cons of Long-Term Use of Prolia (Denosumab)
- Initial safety concerns with denosumab included infections, cancer, skin reactions, cardiovascular disease, hypocalcemia, osteonecrosis of the jaw, and atypical femur fractures 3
- Anecdotal reports have raised concerns about an increased risk of multiple vertebral fractures following discontinuation of denosumab 3, 4
- Long-term use of denosumab may lead to a rebound effect, causing rapid bone density loss and increased risk of fractures if not followed by another anti-osteoporosis therapy 4
- Rare complications associated with long-term denosumab use include osteonecrosis of the jaw (ONJ) and atypical femoral fractures (AFF) 5, 6, 7
- The risk of ONJ may be lower with denosumab compared to bisphosphonates after 2 years of use, with the difference increasing over time 6
- Discontinuation of denosumab without follow-on therapy may lead to a transient rebound of bone turnover, causing rapid bone density loss and increased risk of multiple vertebral fractures 4, 7