The concern that all osteoporosis drugs cause osteonecrosis is unfounded, though it is a serious issue for a small subset of patients. Osteonecrosis, which means "bone death," is a rare complication most notably associated with high-dose intravenous (IV) bisphosphonates used for cancer treatment and, to a much lesser extent, with lower-dose oral antiresorptive agents for osteoporosis. Understanding the specific drugs, dosages, and individual risk factors is crucial for both patients and healthcare providers.
Antiresorptive vs. Anabolic Drugs and Osteonecrosis
Osteoporosis medications can be broadly categorized into antiresorptive agents, which slow bone breakdown, and anabolic agents, which promote bone formation. The risk of osteonecrosis is primarily tied to antiresorptive drugs. Anabolic drugs, which build new bone, carry a different side effect profile.
Bisphosphonates and Osteonecrosis
Bisphosphonates are the most widely known class of antiresorptive drugs and include medications such as alendronate (Fosamax), risedronate (Actonel), and zoledronic acid (Reclast).
- Risk levels: The risk of osteonecrosis of the jaw (ONJ) is significantly higher for cancer patients receiving high-dose intravenous bisphosphonates compared to osteoporosis patients on oral versions. A study review found that ONJ occurred more frequently in patients receiving intravenous forms. For osteoporosis patients, the risk with oral bisphosphonates is very low, ranging from 0.001% to 0.01% per person-year of exposure.
- Duration and dosage: The risk of ONJ and atypical femoral fractures (AFFs), another rare complication, increases with a higher cumulative dose and longer duration of bisphosphonate use, typically after several years.
Denosumab and Osteonecrosis
Denosumab (Prolia) is another potent antiresorptive medication, given via injection every six months for osteoporosis. Like bisphosphonates, it has been linked to ONJ, but the risk for osteoporosis patients is still considered low compared to cancer patients on a higher dose.
- Incidence rates: Some studies suggest the incidence of ONJ with denosumab may be slightly higher than with oral bisphosphonates, especially in those previously treated with bisphosphonates. However, the overall risk for osteoporosis treatment remains small, and the benefits of fracture prevention generally outweigh the risks.
- Drug holidays: Unlike with bisphosphonates, the antiresorptive effect of denosumab disappears relatively quickly after discontinuation, so "drug holidays" are not effective for managing ONJ risk.
Anabolic Agents and Osteonecrosis
Anabolic drugs, such as teriparatide (Forteo) and romosozumab (Evenity), promote new bone formation. These drugs are not associated with ONJ. In fact, teriparatide has been used off-label to help heal ONJ lesions in some cases.
Comparison of Osteonecrosis Risk with Common Osteoporosis Drugs
| Drug Class (Example) | Mechanism of Action | Primary Use in Osteoporosis | ONJ Risk for Osteoporosis | Key Risk Factors | Duration of Association with ONJ |
|---|---|---|---|---|---|
| Bisphosphonates (Oral) | Inhibits osteoclasts (bone resorption) | Prevention and treatment | Very low (0.001%–0.01%) | Invasive dental procedures, poor oral hygiene, long-term use (>2 years) | Increases with prolonged use |
| Bisphosphonates (IV) | Potent inhibition of osteoclasts | Often for more severe osteoporosis or cancer | Higher than oral; still low for osteoporosis use | High dose, IV administration, malignancy | Increases with prolonged use |
| Denosumab (Prolia) | Inhibits RANK ligand (bone resorption) | Treatment of postmenopausal osteoporosis | Low, but potentially higher than oral bisphosphonates | Invasive dental procedures, prior bisphosphonate use | Increases with prolonged use; effects subside after discontinuation |
| Anabolic Agents (Teriparatide) | Stimulates bone formation | Severe osteoporosis, treatment failure | Not associated; may aid in healing ONJ | N/A | N/A |
How to Mitigate Osteonecrosis Risk
For patients on antiresorptive medications, taking proactive steps can significantly reduce the already small risk of ONJ:
- Maintain excellent oral hygiene: Regular brushing, flossing, and dental checkups are critical. Poor oral hygiene is a known risk factor.
- Complete dental work beforehand: It is recommended that any invasive dental procedures, such as extractions or implants, are completed and healed before starting antiresorptive therapy.
- Communicate with your dentist: Always inform your dentist that you are taking an osteoporosis medication. This allows them to adjust their procedures and be vigilant for signs of ONJ.
- Consider drug holidays: For patients on oral bisphosphonates for several years, a temporary discontinuation of the medication (a "drug holiday") may be considered before certain major dental surgeries, though evidence for its effectiveness is mixed. This should only be done under the guidance of a physician, as it can temporarily increase fracture risk.
Conclusion: The Risk-Benefit Balance
The short answer to the question "do all osteoporosis drugs cause osteonecrosis?" is no. Osteonecrosis is a rare side effect primarily linked to high-dose antiresorptive therapies, with a very low incidence in patients treated for osteoporosis. The risk associated with bisphosphonates and denosumab for osteoporosis is far outweighed by the proven benefits of reducing major fragility fractures. Anabolic agents, by contrast, are not associated with osteonecrosis risk. Patients can proactively manage their risk by maintaining good oral health and ensuring strong communication between their prescribing doctor and dentist. These preventative measures, combined with the fact that many osteoporosis drugs do not carry this risk, mean patients should not forgo necessary treatment out of fear of this specific complication.
References
[1] Royal Osteoporosis Society. (2024). Osteonecrosis of the jaw (ONJ): Information for patients.
Important Considerations for Osteonecrosis Risk
The Importance of Communication Between Doctors and Dentists
Effective communication between a patient's rheumatologist or endocrinologist and their dentist is a cornerstone of prevention. This ensures that any necessary dental work, especially invasive procedures, is planned with the medication schedule in mind. It also allows for early detection of any issues.
Recognizing Atypical Femoral Fractures (AFFs)
Though different from osteonecrosis, atypical femoral fractures are another rare but serious risk associated with long-term antiresorptive therapy, specifically bisphosphonates and denosumab. Patients on long-term therapy who experience new or unusual thigh or groin pain should be evaluated for this complication.
The Role of Dosage and Duration
The risk of both ONJ and AFFs is clearly correlated with higher dosages and longer treatment durations. This is why the risk is far higher in cancer patients receiving high-dose IV antiresorptives compared to osteoporosis patients receiving standard, lower doses.
The Reality of Side Effects
While it's important to be aware of rare side effects, the media attention on ONJ and AFFs has sometimes caused disproportionate fear. Patients should always balance the potential for a rare side effect against the very real and high risk of fragility fractures if their osteoporosis is left untreated.
How Osteoporosis Drugs Affect Bone
Antiresorptive drugs primarily work by inhibiting osteoclasts, the cells that break down old bone. Over time, this can lead to an accumulation of micro-damage and reduced ability to heal, which is thought to be the mechanism behind both ONJ and AFFs. Anabolic agents work differently by stimulating osteoblasts to build new bone, and thus do not carry these same risks.
Dental Implant Considerations
Dental implant placement is considered an invasive procedure and a risk factor for ONJ in patients on antiresorptive therapy. Patients on long-term treatment should discuss this with their doctors and dentists to determine the best course of action.
The Impact of Other Conditions
Certain other health conditions and medications can increase the risk of ONJ in patients taking osteoporosis drugs, including diabetes, corticosteroid use, and chemotherapy.
Managing ONJ if it Occurs
For the rare cases where ONJ does develop in an osteoporosis patient, conservative, non-surgical treatment is often effective. This includes antibiotic rinses and management of the affected area by a specialist. Surgical intervention is sometimes necessary but is approached with caution due to impaired healing.
