Condition
Bone Cancer
Bone cancer is abnormal cells growing in bone, either cancers that start there, like osteosarcoma and Ewing sarcoma, or cancers from the breast, prostate or lung that spread to it. The strongest evidence is for denosumab, and studies found it reduced skeletal-related events in people with bone metastases from solid tumors. That finding applies to spread-to-bone disease rather than every type, and evidence for vitamin D and calcium is only moderate.
Sources: PMID 22419768; PMID 36624318
- Supplements studied
- 1
- Medicines and peptides
- 2
- Graded outcomes
- 6
- Trials
- 1
- People studied
- 60
Evidence by supplement
- Strong
- Moderate
- Limited
- Very limited
| Grade | Outcome | Effect | Size | Studies | People | Studies list |
|---|---|---|---|---|---|---|
| Nausea Symptoms Moderate Improvement | Improves (the measure goes down) | Moderate effect | 9 studies | 60 people | ||
Prescription medicines and peptides studied, for context
Denosumab (Prolia/Xgeva)
- Skeletal-Related Events (Cancer): improves
| Grade | Outcome | Effect | Size | Studies | People | Studies list |
|---|---|---|---|---|---|---|
| Skeletal-Related Events (Cancer) Xgeva (120mg monthly) reduces skeletal-related events in patients with bone metastases from solid tumors. | Improves (the measure goes down) | Moderate effect | 22 studies |
Mifamurtide (Mepact)
- Flu-like Symptoms: changes; see studies
- Overall Survival Improvement: improves
- Event-Free Survival: improves
| Grade | Outcome | Effect | Size | Studies | People | Studies list |
|---|---|---|---|---|---|---|
| Flu-like Symptoms Expected immunostimulatory effects: Chills (89%), fever (85%), fatigue (53%), nausea, headache, myalgias. Generally mild-moderate, transient, respond to palliative treatment. Most occur within 2 hours of infusion. Tolerance develops over time. | Changes; see studies | Large effect | 5 studies | |||
| Overall Survival Improvement INT-0133 Phase 3 (n=662 non-metastatic): 6-year OS 78% with mifamurtide vs 70% chemotherapy alone. Relative risk reduction 28% (HR 0.72; 95% CI 0.53-0.97; P=0.031). Represents one-third reduction in death risk. Led to EMA approval. | Improves (the measure goes up) | Moderate effect | 14 studies | |||
| Event-Free Survival INT-0133: Event-free survival improvement not statistically significant as primary endpoint. Significant interaction between mifamurtide and ifosfamide identified. Controversy over endpoint analysis contributed to FDA denial. EFS benefit less clear than OS benefit. | Improves (the measure goes up) | Small effect | 6 studies | |||
| Metastatic/Recurrent Disease EuroSarc-Memos trial: No significant benefit in metastatic or recurrent osteosarcoma. Compassionate use data limited. Currently indicated only for non-metastatic, resectable disease after complete surgical removal. | NoneNo effect | 10 studies |
Key findings
- Nausea SymptomsImproves (the measure goes down)
Safety notes in the studies
- Relative risk reduction 28% (HR 0.72; 95% CI 0.53-0.97; P=0.031).
- Represents one-third reduction in death risk.
- Significant interaction between mifamurtide and ifosfamide identified.
The Bone Cancer Supportive Care protocol
2 primary supplements · 8 supporting supplements
Studies cited
100 studies from PubMed
- Denosumab-bbdz: A Review of the Interchangeable Biosimilar for the Treatment of Osteoporosis.
- Long-Term Efficacy and Safety of Denosumab: Insights beyond 10 Years of Use
- Target tolerance improvement of the immunogenicity assay developed for analysing samples from clinical trials of RGB-14, a proposed biosimilar to Prolia/Xgeva.
- Impact of denosumab on muscle health in older adults in long-term care.
- Tumor Immune Microenvironment-Associated Prognostic and Mifamurtide-Response Gene Signatures for Localized Osteosarcoma: A Correlative Study of the ISG/OS-2 Trial.
- The benefits of combining an immunomodulator with a chemotherapy agent in chondrosarcoma-a proof of concept with mifamurtide.
- Safety and Efficacy of Denosumab in Children With Osteogenesis Imperfecta-the First Prospective Comparative Study.
- Efficacy and safety of candidate biosimilar CT-P41 versus reference denosumab: a double-blind, randomized, active-controlled, Phase 3 trial in postmenopausal women with osteoporosis.
- Efficacy and safety of denosumab and teriparatide versus oral bisphosphonates to treat postmenopausal osteoporosis: a systematic review and meta-analysis.
- Denosumab as treatment of central giant cell granuloma of the jaws. a scoping review.
- Effect of denosumab, an anti-osteoporosis drug, on vascular calcification: A meta-analysis.
- Exploring Denosumab's potential in aneurysmal bone cyst treatment: A scoping review.
- Superiority of denosumab over bisphosphonates in preventing and treating glucocorticoid-induced osteoporosis: a systematic review and meta-analysis with GRADE quality assessment.
- Long-Circulating and Targeted Liposomes Co-loading Cisplatin and Mifamurtide: Formulation and Delivery in Osteosarcoma Cells.
- Denosumab and muscle performance.
- The clinical effectiveness of denosumab (Prolia®) in patients with hormone-sensitive cancer receiving endocrine therapy, compared to bisphosphonates, selective estrogen receptor modulators (SERM), and placebo: a systematic review and network meta-analysis.
- Association between preoperative denosumab and the risk of local recurrence in patients with giant cell tumor of bone: A meta-analysis and systematic review.
- The Clinical Effectiveness of Denosumab (Prolia®) for the Treatment of Osteoporosis in Postmenopausal Women, Compared to Bisphosphonates, Selective Estrogen Receptor Modulators (SERM), and Placebo: A Systematic Review and Network Meta-Analysis.
- Histopathological response to denosumab in giant cell tumours of bone - A review of 11 cases.
- Denosumab in elderly osteoporotic patients. A narrative review.
- Ginger for treating nausea and vomiting: an overview of systematic reviews and meta-analyses
- Microbe-mediated intestinal NOD2 stimulation improves linear growth of undernourished infant mice.
- Denosumab in the Treatment of Osteoporosis: 10 Years Later: A Narrative Review
- Safety of denosumab versus zoledronic acid in the older adults with osteoporosis: a meta-analysis of cohort studies.
- Cost-effectiveness analyses of denosumab for osteoporosis: a systematic review.
- Discontinuing Denosumab: Can It Be Done Safely? A Review of the Literature.
- Denosumab Use in Adults With Fibrous Dysplasia: Case Reports and Review of the Literature.
- The role of neoadjuvant denosumab in the treatment of aneurysmal bone cysts: a case series and review of the literature.
- Effect of ginger in the treatment of nausea and vomiting compared with vitamin B6 and placebo during pregnancy: a meta-analysis
- Effects of Ginger Intake on Chemotherapy-Induced Nausea and Vomiting: A Systematic Review of Randomized Clinical Trials
- Outcomes from a mechanistic biomarker multi-arm and randomised study of liposomal MTP-PE (Mifamurtide) in metastatic and/or recurrent osteosarcoma (EuroSarc-Memos trial)
- The addition of the immunomodulator mifamurtide to adjuvant chemotherapy for early osteosarcoma: a retrospective analysis.
- Mucosal Adjuvants Delivered by a Mucoadhesive Patch for Sublingual Administration of Subunit Vaccines.
- Gut microbial DL-endopeptidase alleviates Crohn's disease via the NOD2 pathway.
- Phase 2 study for nonmetastatic extremity high-grade osteosarcoma in pediatric and adolescent and young adult patients with a risk-adapted strategy based on ABCB1/P-glycoprotein expression: An Italian Sarcoma Group trial (ISG/OS-2).
- Denosumab in chronic kidney disease: a narrative review of treatment efficacy and safety.
- The safety profile of denosumab in oncology beyond the safety of denosumab as an anti-osteoporotic agent: still more to learn.
- Is denosumab associated with an increased risk for infection in patients with low bone mineral density? A systematic review and meta-analysis of randomized controlled trials.
- Denosumab biosimilar in postmenopausal osteoporotic women: A randomized, assessor-blind, active-controlled clinical trial.
- Strategies for Using Muramyl Peptides - Modulators of Innate Immunity of Bacterial Origin - in Medicine.
- The perplexing role of immuno-oncology drugs in osteosarcoma.
- Improved osteosarcoma survival with addition of mifamurtide to conventional chemotherapy - Observational prospective single institution analysis.
- Denosumab in the treatment of giant cell tumor of the spine. Preliminary report, review of the literature and protocol proposal.
- Is Treatment with Denosumab Associated with Local Recurrence in Patients with Giant Cell Tumor of Bone Treated with Curettage? A Systematic Review.
- Hypocalcaemia following denosumab in prostate cancer: A clinical review.
- Pre-operative denosumab is associated with higher risk of local recurrence in giant cell tumor of bone: a systematic review and meta-analysis.
- Hypercalcemia upon denosumab withdrawal in primary hyperparathyroidism: a case report and literature review.
- A Review on the Role of Denosumab in Fracture Prevention.
- Delivery strategies for macromolecular drugs in cancer therapy.
- Relationship Between Bone Mineral Density T-Score and Nonvertebral Fracture Risk Over 10 Years of Denosumab Treatment
- Denosumab versus bisphosphonates for the treatment of bone metastases from solid tumors: a systematic review.
- Denosumab treatment for giant-cell tumor of bone: a systematic review of the literature.
- One Year of Romosozumab Followed by Two Years of Denosumab Maintains Fracture Risk Reductions: Results of the FRAME Extension Study.
- Effects of denosumab on bone metabolism and bone mineral density in kidney transplant patients: a systematic review and meta-analysis.
- Denosumab for Reducing Risk of Fractures in Postmenopausal Women.
- Denosumab-related osteonecrosis of the jaw: a report of 2 cases and review of the literature.
- Denosumab in the treatment of glucocorticoid-induced osteoporosis: a systematic review and meta-analysis.
- Efficacy of Ginger (Zingiber officinale) in Ameliorating Chemotherapy-Induced Nausea and Vomiting and Chemotherapy-Related Outcomes: A Systematic Review Update and Meta-Analysis
- Does the Oral Administration of Ginger Reduce Chemotherapy-Induced Nausea and Vomiting?: A Meta-analysis of 10 Randomized Controlled Trials
- Harnessing the untapped potential of nucleotide-binding oligomerization domain ligands for cancer immunotherapy.
- Incorporating individual historical controls and aggregate treatment effect estimates into a Bayesian survival trial: a simulation study.
- Denosumab: A Review in Postmenopausal Osteoporosis
- Vertebral Fractures After Discontinuation of Denosumab: A Post Hoc Analysis of the Randomized Placebo-Controlled FREEDOM Trial and Its Extension
- Denosumab for the treatment of bone disease in solid tumors and multiple myeloma.
- Denosumab: A Unique Perspective on Adherence and Cost-effectiveness Compared With Oral Bisphosphonates in Osteoporosis Patients.
- Denosumab in the treatment of glucocorticoid-induced osteoporosis.
- Denosumab compared to bisphosphonates to treat postmenopausal osteoporosis: a meta-analysis.
- Immunoallergic interstitial nephritis secondary to denosumab.
- Effects of Denosumab After Treatment Discontinuation : A Review of the Literature.
- Liposomal Formulations to Modulate the Tumour Microenvironment and Antitumour Immune Response.
- The Efficiency and Toxicity of Mifamurtide in Childhood Osteosarcoma.
- 10 years of denosumab treatment in postmenopausal women with osteoporosis: results from the phase 3 randomised FREEDOM trial and open-label extension
- Denosumab: Prevention and management of hypocalcemia, osteonecrosis of the jaw and atypical fractures.
- Discontinuation of Denosumab therapy for osteoporosis: A systematic review and position statement by ECTS.
- The Role of Mifamurtide in Chemotherapy-induced Osteoporosis of Children with Osteosarcoma.
- Osteogenic Sarcoma: Systemic Chemotherapy Options for Localized Disease.
- Immune Therapy for Sarcomas.
- Characteristics and outcomes of patients with advanced sarcoma enrolled in early phase immunotherapy trials.
- Effectiveness of mifamurtide in addition to standard chemotherapy for high-grade osteosarcoma: a systematic review.
- A comprehensive review of denosumab for bone metastasis in patients with solid tumors.
- Osteosarcoma After Hematopoietic Stem Cell Transplantation in Children and Adolescents: Case Report and Review of the Literature.
- Palliative Oncology: Denosumab.
- Denosumab and teriparatide transitions in postmenopausal osteoporosis (the DATA-Switch study): extension of a randomised controlled trial.
- The effectiveness and safety of ginger for pregnancy-induced nausea and vomiting: a systematic review
- Lifetime effectiveness of mifamurtide addition to chemotherapy in nonmetastatic and metastatic osteosarcoma: a Markov process model analysis.
- Review and comparison of clinical evidence submitted to support European Medicines Agency market authorization of orphan-designated oncological treatments.
- An update on chemotherapy for osteosarcoma.
- Denosumab in osteoporosis.
- A systematic review and meta-analysis of the effect and safety of ginger in the treatment of pregnancy-associated nausea and vomiting
- Effects of ginger for nausea and vomiting in early pregnancy: a meta-analysis
- Mifamurtide in metastatic and recurrent osteosarcoma: a patient access study with pharmacokinetic, pharmacodynamic, and safety assessments
- The addition of mifamurtide to chemotherapy improves lifetime effectiveness in children with osteosarcoma: a Markov model analysis.
- Mifamurtide in metastatic and recurrent osteosarcoma: a patient access study with pharmacokinetic, pharmacodynamic, and safety assessments.
- Pharmacokinetics and pharmacodynamics of liposomal mifamurtide in adult volunteers with mild or moderate hepatic impairment.
- Osteosarcoma treatment - where do we stand? A state of the art review.
- Denosumab in breast cancer treatment.
- Ginger (Zingiber officinale) and chemotherapy-induced nausea and vomiting: a systematic literature review
- Denosumab: mechanism of action and clinical outcomes
- Mifamurtide for the treatment of nonmetastatic osteosarcoma
- Randomized comparison of denosumab and zoledronic acid to prevent skeletal-related events in patients with bone metastases from prostate cancer