An interesting real world study indicating a survival benefit of bone modifying agents.
Administration and cancer-control outcomes of bone-modifying agents in real-world patients with metastatic castration-resistant prostate cancer, JBMR Plus, Volume 9, Issue 1, January 2025, ziae157, doi.org/10.1093/jbmrpl/ziae157
Mike Wenzel, Benedikt Hoeh, Clara Humke, Maria Welte, Cristina Cano Garcia, Carolin Siech, Fred Saad, Pierre I Karakiewcz, Derya Tilki, Thomas Steuber, Markus Graefen, Miriam Traumann, Felix K H Chun, Philipp Mandel
“In OS analyses, significant median OS differences were observed in favor of patients with bone-modifying agents (58 vs 45 months; hazard ratio [HR]: 0.66), even after multivariable adjustment (HR: 0.37; both p ≤ .01). In bone-modifying agent–stratified analyses, 57% received denosumab vs 43% bisphosphonates, with a significantly higher rate of Eastern Cooperative Oncology Group status of ≥2 in the bisphosphonates group.”
“Taken together, the current study analyzing the administration and use of bone-modifying agents in real-world patients with mCRPC with bone metastasis showed a relatively low rate of bone-modifying agents. Conversely, the use of bone-modifying agents showed better cancer-control outcomes than in patients without any bone-modifying agents. No differences in overall survival were observed between the comparison of bisphosphonates and denosumab, while denosumab showed numerically better results in progression-free survival analysis after adjusting for covariates. Event rates of osteonecrosis to the jaw were low in both groups. Consequently, clinical efforts should be made to increase bone-modifying agent administration rates for better cancer-control outcomes.”
“The cumulative rate of osteonecrosis of the jaw at any treatment time was 12% in both groups and significantly decreased over time. “
Written by
Graham49
To view profiles and participate in discussions please or .
from the paper: “The overall rate of osteonecrosis to the jaw was 11% (n = 26). The rates significantly decreased within more recent years with regular dental assessment (2006–2014 vs 2018–2024: 15.4% vs 5.3%; p = .048).”
You also need to consider the possibility of truly horrible other side effects of denosumab. I just discovered that my severe urinary pain was largely caused by denosumab and the need to take calcium supplements. I need to work out the details with my oncologists but I accidentally missed a day of meds including calcium supplement. Almost immediately there was a major reduction in urinary pain. It is not sure if calcium needs to be supplemented or not if calcium levels are acceptable. But it was explained that without adequate calcium ,denosumab can remove calcium from the bones making matters worse. My oncologist is now saying that i should discontinue denosumab and calcium.
My bladder is full of calcium deposits which are likely a big part of the urinary pain. And the pain does not relent with fentanyl or morphine making life in general very uncomfortable and sleep difficult.
Another "rare" side effect is femur fractures which it seems I might also have. I can barely walk due to the pain when my femur compresses. Xray to be done soon should tell if i have a fracture or not.
So as wonderful as denosumab may or not be there are side effects to consider besides ONJ.
And it may not help with overall survival if we could believe in a clinical trials. I decided not to use denosumab at least until I need xofigo and because xofigo cost 60000 dollars in Australia I will rather wait up to the very end in order to alleviate bone pain when and if comes to that. That is the main reason why I would use xofigo. My first oncologist professor Richard Epstein said that it will be used at the very end. TA suggested to get xofigo early in order to be more effective treatment. We will see. The said thing about xofigo is that despite its use someone experienced that bone Mets were popping up during xofigo treatment. I am really not a doctor just a messenger. My first radiation oncologist said that they are "experimenting" with xofigo. The stress is on experimenting although it should extend life maybe for maximum 4 months?
Q. Could you please find the prescription information from the producer of denosumab?
A. Denosumab is a medication marketed by Amgen under the brand names Prolia® and Xgeva®. Prolia® is primarily used to treat osteoporosis in postmenopausal women and men at high risk for fracture, as well as bone loss associated with certain cancer treatments. Xgeva® is used for the prevention of skeletal-related events in patients with bone metastases from solid tumors and for the treatment of giant cell tumor of bone.
Prolia® (Denosumab) Prescribing Information:
Indications:
Treatment of postmenopausal women with osteoporosis at high risk for fracture.
Treatment to increase bone mass in men with osteoporosis at high risk for fracture.
Treatment of glucocorticoid-induced osteoporosis in men and women at high risk for fracture.
Treatment of bone loss in men receiving androgen deprivation therapy for nonmetastatic prostate cancer.
Treatment of bone loss in women receiving adjuvant aromatase inhibitor therapy for breast cancer.
Dosage and Administration:
The recommended dose is 60 mg administered as a single subcutaneous injection once every six months.
Administer in the upper arm, upper thigh, or abdomen.
Ensure adequate calcium and vitamin D intake during treatment.
Contraindications:
Hypocalcemia.
Pregnancy.
Hypersensitivity to denosumab or any of its components.
Warnings and Precautions:
Monitor for signs of hypocalcemia; correct hypocalcemia prior to initiating therapy.
Consider the risk of osteonecrosis of the jaw; perform a dental examination before starting treatment in patients with risk factors.
Monitor for atypical femoral fractures.
Evaluate for skin infections; patients should seek prompt medical attention if they develop signs or symptoms of cellulitis.
Adverse Reactions:
Common adverse reactions include back pain, pain in extremity, musculoskeletal pain, hypercholesterolemia, and cystitis.
Serious adverse reactions may include hypocalcemia, serious infections, dermatologic reactions, osteonecrosis of the jaw, and atypical femoral fractures.
For comprehensive prescribing information, please refer to the full prescribing document provided by Amgen:
Xgeva® (Denosumab) Prescribing Information:
Indications:
Prevention of skeletal-related events in patients with bone metastases from solid tumors.
Treatment of adults and skeletally mature adolescents with giant cell tumor of bone that is unresectable or where surgical resection is likely to result in severe morbidity.
Dosage and Administration:
The recommended dose is 120 mg administered as a subcutaneous injection every four weeks.
Administer in the upper arm, upper thigh, or abdomen.
Supplement with calcium and vitamin D as necessary to treat or prevent hypocalcemia.
Contraindications:
Hypocalcemia.
Hypersensitivity to denosumab or any of its components.
Warnings and Precautions:
Monitor for hypocalcemia; correct pre-existing hypocalcemia before initiating therapy.
Be vigilant for signs of osteonecrosis of the jaw; consider a dental examination prior to treatment for patients with risk factors.
Assess for atypical femoral fractures.
Monitor for serious infections, particularly in immunocompromised patients.
Adverse Reactions:
Common adverse reactions include fatigue, hypophosphatemia, and nausea.
Serious adverse reactions may include hypocalcemia, osteonecrosis of the jaw, atypical femoral fractures, and serious infections.
For detailed prescribing information, please refer to the full prescribing document provided by Amgen:
Please consult these documents for complete information on indications, dosing, contraindications, warnings, precautions, and potential adverse effects.
Those WITHOUT bone modifying agents had zero percent ONJ. There was also a comparison of ONJ between those who had the two bone agents and that result was 11-12%. In patients with such advanced disease a side effect as serious as ONJ is not what I call minor. It is known that ONJ may occur in such treated patients. It is also known that among such patients who require "deep work" for dental conditions (tooth canal, crown, extraction, etc.) the rate is far higher. This drug forces patients to make difficult decisions.
A retrospective study and unknown why the patients were selected for such agents: Bone density, fracture or fracture risk? I remain reluctant to choose such a drug.
It can also interfere with the immune system the last thing what we want if our disease is under control. I would say. Plus I did extensive research by following the osteoporosis forums and apparently only 8% of people with osteoporosis made a decision to jump into denosumab or other forms of bone strengthening agents like zoledronic acid. The old people are miserable enough without the side effects of denosumab or zoledronic acid. Plus the biggest concern is that if you break a bone while undergoing treatment is that the bone will have difficulties healing. Plus if I good remember the fracture of the spine is only reduced by 5% and if you get the compression fracture of the vertebrae it will not heal.
People usually rearrange their space to make it fall proof in order to avoid falling.
It seems you're sharing a discussion or feedback on the use of bone-modifying agents like denosumab and zoledronic acid, particularly regarding their risks like osteonecrosis of the jaw (ONJ) and potential interference with the immune system. These concerns are valid, especially in patients with advanced disease or osteoporosis.
The decision to use these agents should balance their benefits—such as reducing skeletal-related events in metastatic cancer or preventing fractures in osteoporosis—against their risks. It's also important to consider individual factors like bone density, fracture risk, dental health, and overall patient goals.
If you're weighing whether to start such treatment, it may help to discuss these concerns with your doctor or oncologist, and also consider a second opinion. Ensuring dental health before starting treatment and regular monitoring can mitigate some risks. Additionally, non-pharmacological strategies like fall-proofing your space, as mentioned, are excellent preventative measures.
Would you like more detailed guidance on how to approach this decision or manage potential side effects?
The concern about bone healing difficulties while on denosumab (or other antiresorptive therapies like zoledronic acid) is valid and supported by clinical observations. Denosumab, as a RANKL inhibitor, suppresses bone resorption, which is crucial for normal bone remodeling and healing after a fracture. Here's a breakdown of the issue:
Bone Healing and Denosumab
1. Delayed Healing:
Denosumab may slow the natural bone remodeling process, which is vital for healing fractures. Reports have noted delayed union or nonunion in some patients undergoing treatment, especially in those with high fracture risk or undergoing surgeries involving bone.
2. Fracture Incidence Reduction:
While denosumab reduces the risk of vertebral, hip, and nonvertebral fractures (e.g., spine fracture risk reduction ~68% in osteoporosis), it does not entirely eliminate fractures. If fractures occur, the healing process might be slower due to the suppressed activity of osteoclasts.
3. High-Risk Patients:
The risk of healing difficulties might be higher in patients with pre-existing bone conditions (like osteoporosis, metastases, or prior fractures) or those undergoing invasive dental procedures that affect the jawbone.
Mitigation Strategies
Pause Therapy:
Some experts recommend pausing denosumab in cases of planned surgeries or following a fracture to optimize bone healing, though this should be done cautiously as stopping denosumab abruptly can lead to rebound bone loss.
Adjunctive Care:
Ensuring adequate calcium and vitamin D levels, and potentially using anabolic agents like teriparatide (if appropriate), may support fracture healing during or after denosumab treatment.
Personalized Decisions:
In advanced cancer cases, balancing fracture prevention with healing potential is critical. Discussions with your oncologist, endocrinologist, and potentially a bone health specialist are key to tailoring therapy.
Would you like more information on alternatives or specific ways to minimize risks with these treatments?
I was taking twice that of calcium which was apparently too much. No one monitored my calcium and I do not have osteoporosis or osteoporosis penia. I did have pathological fractures which is apparently why they put me on egeva but no one monitored my calcium etc. I am rather pissed off about this. Also I do not appreciate people saying that chat got is useless. It is just like saying that libraries are useless. Both can provide either valuable information or dangerous misinformation depending on how they are used. Chat can be a very good way to collect information for further analysis just like any other source of information. I just queried the appropriateness of cold packs for upcoming chemo. It took about six back and forth interactions to get the information I wanted and I am running the results through my oncologist before I make a decision. I use chat extensively for computer programming. My memory is not great and chat helps a lot. Some times I get immediate results. Some times I need to refine my question. And some times I realize it is hopeless and time to resort to old fashioned methods. Computer programming is a good test of the capabilities of chat because you immediately know if it works. It is a great way to refine your skills at working with chat gpt. It is like working with a smart partner who can be brilliant and who can also be wrong.
If you use Chat GPT and are happy with it, use it. Why care what others think? If you want to use it to prepare for your next visit, go ahead. Why didn't you ask to have your calcium monitored when you began Xgeva? Or more simply if you're like me, ask the doc to provide the list of side effects and his or her mitigation strategy? I'm not wagging my finger here. I'm asking because what other drugs do you take and their side effects should you be monitoring for?
not taking much and i just listened to my doctor who said i need to take calcium supplements. i do not question everything my doctors say. i should have asked about this but didn't. if i had run it by chat first i probably would have.
I don’t take any calcium, I do take 400 mg magnesium daily. I also take 2000iu D3 daily. My calcium is always above 9. I only get an Xgeva injection every three months because that dosage was found to be non inferior to every month. I have never taken calcium and will not unless my levels drop.
One potential complication is jaw necrosis (death of jawbone tissue). This may cause teeth to become loose and need to be removed. According to the American Dental Association, the risk of jaw necrosis increases if denosumab (prolia), the active drug in Prolia, is used for more than 2 years.
Maybe a more positive experience. I have been on zolendronic acid for quite a while ( about 2 years) after getting osteoporosis of the spine from ADT and have had zero side effects. Only short term impact is feeling like have a cold for a day or two after the 3 monthly injection. I’m due for a bone scan in a couple of months and will see how things are. I’m advanced stage 4 and have full mobility and run/cycle so I’m glad for the assistance with bone strength.
Content on HealthUnlocked does not replace the relationship between you and doctors or other healthcare professionals nor the advice you receive from them.
Never delay seeking advice or dialling emergency services because of something that you have read on HealthUnlocked.
Overall Survival With [177]Lu-PSMA-617 vs Cabazitaxel in Metastatic Castration-Resistant Prostate Cancer
Changes in conditional net survival and dynamic prognostic factors in patients with newly diagnosed metastatic prostate cancer 
"Early initiation of Lu-177 PSMA radioligand therapy prolongs overall survival in metastatic prostate cancer"
Perineural invasion increases soft tissue progression risk in metastatic castration-resistant prostate cancer post-abiraterone resistance
