From the Guidelines
Prolia (denosumab) can lead to broken mandibles (jawbones) by causing a rare but serious condition called osteonecrosis of the jaw (ONJ), which occurs in approximately 1% to 9% of patients with advanced cancer, as reported in the 2019 study 1.
Key Points to Consider
- Prolia works by inhibiting a protein called RANK ligand, which reduces bone breakdown but also impairs normal bone remodeling and healing processes.
- The risk of mandibular fractures is higher in patients who have been on Prolia for longer periods and in those with additional risk factors such as poor oral hygiene, periodontal disease, ill-fitting dentures, cancer, chemotherapy, or corticosteroid use.
- To reduce this risk, patients should undergo comprehensive dental examinations before starting Prolia, maintain excellent oral hygiene, inform their dentist about Prolia use, and avoid invasive dental procedures when possible while on the medication.
- If dental surgery is necessary, temporarily discontinuing Prolia might be considered in consultation with the prescribing physician, as suggested by the 2023 study 1.
Recommendations for Patients on Prolia
- Oral hygiene, baseline dental evaluation for high-risk individuals, and avoidance of invasive dental surgery during therapy are recommended to reduce the risk of osteonecrosis of the jaw, as stated in the 2023 study 1.
- Supplemental calcium and vitamin D are recommended to prevent hypocalcemia in patients receiving denosumab.
- Monitoring of creatinine clearance is required to guide dosing of zoledronic acid, but denosumab may be administered to patients with impaired renal function or even patients on hemodialysis, with caution for severe hypocalcemia and hypophosphatemia.
From the FDA Drug Label
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 FDA drug label does not directly answer how Prolia leads to broken mandibles, but it mentions that the long-term consequences of bone remodeling suppression may contribute to osteonecrosis of the jaw, which could be related to broken mandibles.
- Key points:
- Prolia suppresses bone turnover
- Suppression of bone turnover may lead to adverse outcomes such as osteonecrosis of the jaw
- Osteonecrosis of the jaw could be related to broken mandibles 2
From the Research
Prolia and Broken Mandibles
Prolia, also known as denosumab, is a medication used to treat osteoporosis. It works by inhibiting the activity of osteoclasts, cells that break down bone tissue. However, this inhibition of bone breakdown can also lead to an increased risk of osteonecrosis of the jaw (ONJ), a condition in which the jawbone dies due to lack of blood supply.
Risk Factors for ONJ
Several risk factors contribute to the development of ONJ in patients taking Prolia, including:
- Dental extraction or other oral surgery
- Poor oral hygiene
- Chronic inflammation
- Diabetes mellitus
- Ill-fitting dentures
- Use of glucocorticoids or other medications that suppress the immune system
- Previous treatment with bisphosphonates, another type of osteoporosis medication 3
Mechanism of ONJ
The exact mechanism of ONJ is not fully understood, but it is thought to involve a combination of factors, including:
- Inhibition of bone turnover by antiresorptive medications like Prolia
- Local bacterial infection and inflammation
- Trauma to the jawbone, such as dental extraction
- Poor blood supply to the jawbone 4
Treatment of ONJ
Treatment of ONJ typically involves a combination of medical and surgical approaches, including:
- Antibiotic therapy to treat infection
- Surgical debridement to remove dead bone tissue
- Teriparatide therapy to stimulate bone healing 5, 6, 7
- Good oral hygiene and regular dental check-ups to prevent further complications
Incidence of ONJ
The incidence of ONJ in patients taking Prolia is estimated to be around 28.3 per 10,000 patient-years, which is higher than the incidence in patients taking bisphosphonates (4.5 per 10,000 patient-years) 3. The mandible is the most commonly affected site, accounting for around 75.8% of cases 5.