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Physiological Reviews Jul 2021Skeletal metastases are frequent complications of many cancers, causing bone complications (fractures, bone pain, disability) that negatively affect the patient's... (Review)
Review
Skeletal metastases are frequent complications of many cancers, causing bone complications (fractures, bone pain, disability) that negatively affect the patient's quality of life. Here, we first discuss the burden of skeletal complications in cancer bone metastasis. We then describe the pathophysiology of bone metastasis. Bone metastasis is a multistage process: long before the development of clinically detectable metastases, circulating tumor cells settle and enter a dormant state in normal vascular and endosteal niches present in the bone marrow, which provide immediate attachment and shelter, and only become active years later as they proliferate and alter the functions of bone-resorbing (osteoclasts) and bone-forming (osteoblasts) cells, promoting skeletal destruction. The molecular mechanisms involved in mediating each of these steps are described, and we also explain how tumor cells interact with a myriad of interconnected cell populations in the bone marrow, including a rich vascular network, immune cells, adipocytes, and nerves. We discuss metabolic programs that tumor cells could engage with to specifically grow in bone. We also describe the progress and future directions of existing bone-targeted agents and report emerging therapies that have arisen from recent advances in our understanding of the pathophysiology of bone metastases. Finally, we discuss the value of bone turnover biomarkers in detection and monitoring of progression and therapeutic effects in patients with bone metastasis.
Topics: Animals; Biomarkers; Bone Density Conservation Agents; Bone Neoplasms; Bone and Bones; Denosumab; Humans
PubMed: 33356915
DOI: 10.1152/physrev.00012.2019 -
Advances in Therapy Jan 2022The fully human monoclonal antibody denosumab was approved for treatment of osteoporosis in 2010 on the basis of its potent antiresorptive activity, which produces... (Review)
Review
The fully human monoclonal antibody denosumab was approved for treatment of osteoporosis in 2010 on the basis of its potent antiresorptive activity, which produces clinically meaningful increases in bone mineral density (BMD) and reduces fracture risk at key skeletal sites. At that time, questions remained regarding the long-term safety and efficacy of this receptor activator of nuclear factor kappa-B ligand (RANKL) inhibitor; and with clinical experience, new questions have arisen regarding its optimal use. Here, we examine these questions through the lens of data from the FREEDOM trial program and other studies to determine where denosumab fits in the osteoporosis treatment landscape. Clinical consensus and evidentiary support have grown for denosumab as a highly effective anti-osteoporosis therapy for patients at high risk of fracture. In the 10-year FREEDOM Extension study, denosumab treatment produced progressive incremental increases in BMD, sustained low rates of vertebral fracture, and further reduction in nonvertebral fracture risk without increased risk of infection, cancer, or immunogenicity. There was no evidence that suppression of bone turnover or mineralization was excessive, and rates of osteonecrosis of the jaw (ONJ) and atypical femoral fracture (AFF) were very low. It is now recognized, however, that transitioning to another anti-osteoporosis therapy after denosumab discontinuation is essential to mitigate a transient rebound of bone turnover causing rapid BMD loss and increased risk of multiple vertebral fractures (MVFs). Taken together, the available data show that denosumab has a favorable benefit/risk profile and is a versatile agent for preventing osteoporotic fractures in the short and long term. Video abstract: Denosumab in the Treatment of Osteoporosis-10 Years Later (MP4 62727 KB).
Topics: Bone Density; Bone Density Conservation Agents; Denosumab; Female; Humans; Osteoporosis; Osteoporosis, Postmenopausal; Osteoporotic Fractures
PubMed: 34762286
DOI: 10.1007/s12325-021-01936-y -
Scientific Reports Jun 2021Denosumab and romosozumab, a recently approved new drug, are effective and widely known molecular-targeted drugs for postmenopausal osteoporosis treatment. However, no... (Comparative Study)
Comparative Study
Denosumab and romosozumab, a recently approved new drug, are effective and widely known molecular-targeted drugs for postmenopausal osteoporosis treatment. However, no studies have directly compared their therapeutic effects or safety in postmenopausal osteoporosis. This retrospective observational registry study compared the efficacy of 12-month denosumab or romosozumab treatment in postmenopausal osteoporosis patients. The primary outcome was the change in bone mineral density (BMD) at the lumbar spine. Secondary outcomes included BMD changes at the total hip and femoral neck, changes in bone turnover markers, and adverse events. Propensity score matching was employed to assemble patient groups with similar baseline characteristics. Sixty-nine patients each received either denosumab or romosozumab for 12 months. The mean 12-month percentage change from baseline in lumbar spine BMD was 7.2% in the denosumab group and 12.5% in the romosozumab group, indicating a significant difference between the groups. The percentage changes in BMD at both the total hip and femoral neck were also significantly higher at 12 months in the romosozumab group than in the denosumab group. In denosumab patients, bone formation and bone resorption markers were significantly decreased at 6 and 12 months from baseline. In the romosozumab group, the bone formation marker was significantly increased at 6 months and then returned to baseline, while the bone resorption marker was significantly decreased at both time points. Adverse events were few and predominantly minor in both groups, with no remarkable difference in the incidence of new vertebral fractures. Romosozumab showed a higher potential for improving BMD than denosumab in this clinical study of postmenopausal osteoporosis patient treatment.
Topics: Aged; Aged, 80 and over; Antibodies, Monoclonal; Biomarkers; Bone Density; Bone Density Conservation Agents; Denosumab; Female; Humans; Middle Aged; Molecular Targeted Therapy; Osteoporosis, Postmenopausal; Propensity Score; Treatment Outcome
PubMed: 34083636
DOI: 10.1038/s41598-021-91248-6 -
Osteoporosis International : a Journal... Jun 2022To evaluate whether treatment sequence affects romosozumab response, this analysis reviewed studies where romosozumab was administered before or following an...
UNLABELLED
To evaluate whether treatment sequence affects romosozumab response, this analysis reviewed studies where romosozumab was administered before or following an antiresorptive (alendronate or denosumab). Initial treatment with romosozumab followed by an antiresorptive resulted in larger increases in bone mineral density of both hip and spine compared with the reverse sequence.
INTRODUCTION
Teriparatide followed by an antiresorptive increases bone mineral density (BMD) more than using an antiresorptive first. To evaluate whether treatment sequence affects romosozumab response, we reviewed randomized clinical trials where romosozumab was administered before (ARCH, FRAME) or following (STRUCTURE, Phase 2 extension) an antiresorptive (alendronate or denosumab, respectively).
METHODS
We evaluated BMD percentage change for total hip (TH) and lumbar spine (LS) and response rates (BMD gains ≥ 3% and ≥ 6%) at years 1 and 2 (except STRUCTURE with only 1-year data available).
RESULTS
With 1-year romosozumab initial therapy in ARCH and FRAME, TH BMD increased 6.2% and 6.0%, and LS BMD increased 13.7% and 13.1%, respectively. When romosozumab was administered for 1 year after alendronate (STRUCTURE) or denosumab (Phase 2 extension), TH BMD increased 2.9% and 0.9%, respectively, and LS BMD increased 9.8% and 5.3%, respectively. Over 2 years, TH and LS BMD increased 7.1% and 15.2% with romosozumab/alendronate, 8.5% and 16.6% with romosozumab/denosumab, and 3.8% and 11.5% with denosumab/romosozumab, respectively. A greater proportion of patients achieved BMD gains ≥ 6% when romosozumab was used first, particularly for TH, versus the reverse sequence (69% after romosozumab/denosumab; 15% after denosumab/romosozumab).
CONCLUSION
In this study, larger mean BMD increases and greater BMD responder rates were achieved when romosozumab was used before, versus after, an antiresorptive agent. Since BMD on treatment is a strong surrogate for bone strength and fracture risk, this analysis supports the thesis that initial treatment with romosozumab followed by an antiresorptive will result in greater efficacy versus the reverse sequence.
Topics: Alendronate; Antibodies, Monoclonal; Bone Density; Bone Density Conservation Agents; Denosumab; Female; Humans; Osteoporosis, Postmenopausal; Teriparatide
PubMed: 35165774
DOI: 10.1007/s00198-021-06174-0 -
Annals of Internal Medicine Feb 2023This guideline updates the 2017 American College of Physicians (ACP) recommendations on pharmacologic treatment of primary osteoporosis or low bone mass to prevent...
DESCRIPTION
This guideline updates the 2017 American College of Physicians (ACP) recommendations on pharmacologic treatment of primary osteoporosis or low bone mass to prevent fractures in adults.
METHODS
The ACP Clinical Guidelines Committee based these recommendations on an updated systematic review of evidence and graded them using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system.
AUDIENCE AND PATIENT POPULATION
The audience for this guideline includes all clinicians. The patient population includes adults with primary osteoporosis or low bone mass.
RECOMMENDATION 1A
RECOMMENDATION 1B
RECOMMENDATION 2A
RECOMMENDATION 2B
RECOMMENDATION 3
RECOMMENDATION 4
Topics: Adult; Female; Humans; Male; Bone Density Conservation Agents; Denosumab; Diphosphonates; Fractures, Bone; Osteoporosis; Physicians; RANK Ligand
PubMed: 36592456
DOI: 10.7326/M22-1034 -
Health Technology Assessment... Jun 2020Fragility fractures are fractures that result from mechanical forces that would not ordinarily result in fracture.
BACKGROUND
Fragility fractures are fractures that result from mechanical forces that would not ordinarily result in fracture.
OBJECTIVES
The objectives were to evaluate the clinical effectiveness, safety and cost-effectiveness of non-bisphosphonates {denosumab [Prolia; Amgen Inc., Thousand Oaks, CA, USA], raloxifene [Evista; Daiichi Sankyo Company, Ltd, Tokyo, Japan], romosozumab [Evenity; Union Chimique Belge (UCB) S.A. (Brussels, Belgium) and Amgen Inc.] and teriparatide [Forsteo; Eli Lilly and Company, Indianapolis, IN, USA]}, compared with each other, bisphosphonates or no treatment, for the prevention of fragility fracture.
DATA SOURCES
For the clinical effectiveness review, nine electronic databases (including MEDLINE, EMBASE and the World Health Organization International Clinical Trials Registry Platform) were searched up to July 2018.
REVIEW METHODS
A systematic review and network meta-analysis of fracture and femoral neck bone mineral density were conducted. A review of published economic analyses was undertaken and a model previously used to evaluate bisphosphonates was adapted. Discrete event simulation was used to estimate lifetime costs and quality-adjusted life-years for a simulated cohort of patients with heterogeneous characteristics. This was done for each non-bisphosphonate treatment, a strategy of no treatment, and the five bisphosphonate treatments previously evaluated. The model was populated with effectiveness evidence from the systematic review and network meta-analysis. All other parameters were estimated from published sources. An NHS and Personal Social Services perspective was taken, and costs and benefits were discounted at 3.5% per annum. Fracture risk was estimated from patient characteristics using the QFracture (QFracture-2012 open source revision 38, Clinrisk Ltd, Leeds, UK) and FRAX (web version 3.9, University of Sheffield, Sheffield, UK) tools. The relationship between fracture risk and incremental net monetary benefit was estimated using non-parametric regression. A probabilistic sensitivity analysis and scenario analyses were used to assess uncertainty.
RESULTS
Fifty-two randomised controlled trials of non-bisphosphonates were included in the clinical effectiveness systematic review and an additional 51 randomised controlled trials of bisphosphonates were included in the network meta-analysis. All treatments had beneficial effects compared with placebo for vertebral, non-vertebral and hip fractures, with hazard ratios varying from 0.23 to 0.94, depending on treatment and fracture type. The effects on vertebral fractures and the percentage change in bone mineral density were statistically significant for all treatments. The rate of serious adverse events varied across trials (0-33%), with most between-group differences not being statistically significant for comparisons with placebo/no active treatment, non-bisphosphonates or bisphosphonates. The incremental cost-effectiveness ratios were > £20,000 per quality-adjusted life-year for all non-bisphosphonate interventions compared with no treatment across the range of QFracture and FRAX scores expected in the population eligible for fracture risk assessment. The incremental cost-effectiveness ratio for denosumab may fall below £30,000 per quality-adjusted life-year at very high levels of risk or for high-risk patients with specific characteristics. Raloxifene was dominated by no treatment (resulted in fewer quality-adjusted life-years) in most risk categories.
LIMITATIONS
The incremental cost-effectiveness ratios are uncertain for very high-risk patients.
CONCLUSIONS
Non-bisphosphonates are effective in preventing fragility fractures, but the incremental cost-effectiveness ratios are generally greater than the commonly applied threshold of £20,000-30,000 per quality-adjusted life-year.
STUDY REGISTRATION
This study is registered as PROSPERO CRD42018107651.
FUNDING
This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in ; Vol. 24, No. 29. See the NIHR Journals Library website for further project information.
Topics: Bone Density Conservation Agents; Clinical Trials as Topic; Cost-Benefit Analysis; Denosumab; Diphosphonates; Humans; Osteoporotic Fractures; Quality-Adjusted Life Years; Raloxifene Hydrochloride; Teriparatide; Treatment Outcome
PubMed: 32588816
DOI: 10.3310/hta24290 -
The Journal of Clinical Endocrinology... Mar 2022We have previously reported that teriparatide is associated with substantial increases in bone mineral density (BMD) at the lumbar spine (LS), total hip (TH), and...
CONTEXT
We have previously reported that teriparatide is associated with substantial increases in bone mineral density (BMD) at the lumbar spine (LS), total hip (TH), and femoral neck (FN) and small declines at the distal radius in 41 premenopausal women with idiopathic osteoporosis (IOP), all severely affected with low trauma fractures and/or very low BMD. Effects of teriparatide dissipate if not followed by antiresorptives.
OBJECTIVE
To assess the effects of 12 and 24 months of denosumab in premenopausal women with IOP completing 24 months of teriparatide.
METHODS
This was a preplanned phase 2B extension study. Premenopausal women with IOP who had completed a course of teriparatide received denosumab 60 mg every 6 months over 24 months. The main outcome measure was within-group change in BMD at the LS at 12 months. Secondary outcomes include change in 12-month BMD at other sites, 24-month BMD at all sites, trabecular bone score (TBS), and bone turnover markers (BTMs).
RESULTS
After completing teriparatide, 32 participants took denosumab for 12 months and 29 for 24 months, with statistically significant increases in BMD at the LS (5.2 ± 2.6% and 6.9 ± 2.6%), TH (2.9 ± 2.4% and 4.6 ± 2.8%), and FN (3.0 ± 3.8% and 4.7 ± 4.9%). Over the entire 24-month teriparatide and 24-month denosumab treatment period, BMD increased by 21.9 ± 7.8% at the LS, 9.8 ± 4.6% at the TH, and 9.5 ± 4.7% at the FN (all P < .0001). TBS increased by 5.8 ± 5.6% (P < .001). Serum BTM decreased by 75% to 85% by 3 months and remained suppressed through 12 months of denosumab. Denosumab was generally well tolerated.
CONCLUSION
These data support the use of sequential teriparatide and denosumab to increase BMD in premenopausal women with severe osteoporosis.
Topics: Bone Density; Bone Density Conservation Agents; Denosumab; Female; Humans; Lumbar Vertebrae; Osteoporosis; Osteoporosis, Postmenopausal; Teriparatide
PubMed: 34849989
DOI: 10.1210/clinem/dgab850 -
The Journal of Clinical Endocrinology... Aug 2016Denosumab and zoledronic acid (ZOL) are parenteral treatments for patients with osteoporosis. (Randomized Controlled Trial)
Randomized Controlled Trial
CONTEXT
Denosumab and zoledronic acid (ZOL) are parenteral treatments for patients with osteoporosis.
OBJECTIVE
The objective of the study was to compare the effect of transitioning from oral bisphosphonates to denosumab or ZOL on bone mineral density (BMD) and bone turnover.
DESIGN AND SETTING
This was an international, multicenter, randomized, double-blind trial.
PARTICIPANTS
A total of 643 postmenopausal women with osteoporosis previously treated with oral bisphosphonates participated in the study.
INTERVENTIONS
Subjects were randomized 1:1 to sc denosumab 60 mg every 6 months plus iv placebo once or ZOL 5 mg iv once plus sc placebo every 6 months for 12 months.
MAIN OUTCOME MEASURES
Changes in BMD and bone turnover markers were measured.
RESULTS
BMD change from baseline at month 12 was significantly greater with denosumab compared with ZOL at the lumbar spine (primary end point; 3.2% vs 1.1%; P < .0001), total hip (1.9% vs 0.6%; P < .0001), femoral neck (1.2% vs -0.1%; P < .0001), and one-third radius (0.6% vs 0.0%; P < .05). The median decrease from baseline was greater with denosumab than ZOL for serum C-telopeptide of type 1 collagen at all time points after day 10 and for serum procollagen type 1 N-terminal propeptide at month 1 and at all time points after month 3 (all P < .05). Median percentage changes from baseline in serum intact PTH were significantly greater at months 3 and 9 with denosumab compared with ZOL (all P < .05). Adverse events were similar between groups. Three events consistent with the definition of atypical femoral fracture were observed (two denosumab and one ZOL).
CONCLUSIONS
In postmenopausal women with osteoporosis previously treated with oral bisphosphonates, denosumab was associated with greater BMD increases at all measured skeletal sites and greater inhibition of bone remodeling compared with ZOL.
Topics: Administration, Oral; Aged; Bone Density; Bone Density Conservation Agents; Denosumab; Diphosphonates; Double-Blind Method; Drug Substitution; Female; Humans; Imidazoles; Middle Aged; Osteoporosis, Postmenopausal; Zoledronic Acid
PubMed: 27270237
DOI: 10.1210/jc.2016-1801 -
European Review For Medical and... May 2021Osteoporosis is a metabolic disease of the skeletal system which currently affects over 200 million patients worldwide. The WHO criteria define osteoporosis as low bone... (Review)
Review
Osteoporosis is a metabolic disease of the skeletal system which currently affects over 200 million patients worldwide. The WHO criteria define osteoporosis as low bone mineral density, with a T-score ≤ -2.5 found in the spine, the neck of the femur, or during a full hip examination. Osteoporosis considerably reduces a patient's quality of life. QoL should be carefully evaluated before fractures occur to enable the development of an appropriate treatment plan. The progression of osteoporosis may be significantly inhibited by following a proper diet, leading a healthy lifestyle, taking dietary supplements, and receiving appropriate treatment. Education and the prevention of the disease play a major role. Potentially modifiable risk factors for osteoporosis are vitamin D deficiency, smoking, alcohol consumption, low calcium intake, low or excessive phosphorus intake, protein deficiency or a high-protein diet, excessive consumption of coffee, a sedentary lifestyle or lack of mobility, and insufficient exposure to the sun. Pharmaceutical treatment for osteoporosis involves bisphosphonates, calcium and vitamin D3, denosumab, teriparatide, raloxifene, and strontium ranelate. Data indicates that 30%-50% of patients do not take their medication correctly. Other methods of treatment include exercise, kinesitherapy, treatment at a health resort, physical therapy, and diet.
Topics: Cholecalciferol; Denosumab; Dietary Supplements; Diphosphonates; Exercise; Humans; Kinesiology, Applied; Osteoporosis; Raloxifene Hydrochloride; Risk Factors; Teriparatide; Thiophenes
PubMed: 34002830
DOI: 10.26355/eurrev_202105_25838 -
The Cochrane Database of Systematic... Jul 2022Medication-related osteonecrosis of the jaw (MRONJ) is a severe adverse reaction experienced by some individuals to certain medicines commonly used in the treatment of... (Review)
Review
BACKGROUND
Medication-related osteonecrosis of the jaw (MRONJ) is a severe adverse reaction experienced by some individuals to certain medicines commonly used in the treatment of cancer and osteoporosis (e.g. bisphosphonates, denosumab, and antiangiogenic agents), and involves the progressive destruction of bone in the mandible or maxilla. Depending on the drug, its dosage, and the duration of exposure, this adverse drug reaction may occur rarely (e.g. following the oral administration of bisphosphonate or denosumab treatments for osteoporosis, or antiangiogenic agent-targeted cancer treatment), or commonly (e.g. following intravenous bisphosphonate for cancer treatment). MRONJ is associated with significant morbidity, adversely affects quality of life (QoL), and is challenging to treat. This is an update of our review first published in 2017.
OBJECTIVES
To assess the effects of interventions versus no treatment, placebo, or an active control for the prophylaxis of MRONJ in people exposed to antiresorptive or antiangiogenic drugs. To assess the effects of non-surgical or surgical interventions (either singly or in combination) versus no treatment, placebo, or an active control for the treatment of people with manifest MRONJ.
SEARCH METHODS
Cochrane Oral Health's Information Specialist searched four bibliographic databases up to 16 June 2021 and used additional search methods to identify published, unpublished, and ongoing studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing one modality of intervention with another for the prevention or treatment of MRONJ. For 'prophylaxis of MRONJ', the primary outcome of interest was the incidence of MRONJ; secondary outcomes were QoL, time-to-event, and rate of complications and side effects of the intervention. For 'treatment of established MRONJ', the primary outcome of interest was healing of MRONJ; secondary outcomes were QoL, recurrence, and rate of complications and side effects of the intervention.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened the search results, extracted the data, and assessed the risk of bias in the included studies. For dichotomous outcomes, we reported the risk ratio (RR) (or rate ratio) and 95% confidence intervals (CIs).
MAIN RESULTS
We included 13 RCTs (1668 participants) in this updated review, of which eight were new additions. The studies were clinically diverse and examined very different interventions, so meta-analyses could not be performed. We have low or very low certainty about available evidence on interventions for the prophylaxis or treatment of MRONJ. Prophylaxis of MRONJ Five RCTs examined different interventions to prevent the occurrence of MRONJ. One RCT compared standard care with regular dental examinations at three-month intervals and preventive treatments (including antibiotics before dental extractions and the use of techniques for wound closure that avoid exposure and contamination of bone) in men with metastatic prostate cancer treated with zoledronic acid. The intervention seemed to lower the risk of MRONJ (RR 0.10, 95% CI 0.02 to 0.39, 253 participants). Secondary outcomes were not evaluated. Dentoalveolar surgery is considered a common predisposing event for developing MRONJ and five RCTs tested various preventive measures to reduce the risk of postoperative MRONJ. The studies evaluated plasma rich in growth factors inserted into the postextraction alveolus in addition to standardised medical and surgical care versus standardised medical and surgical care alone (RR 0.08, 95% CI 0.00 to 1.51, 176 participants); delicate surgery and closure by primary intention versus non-traumatic tooth avulsion and closure by secondary intention (no case of postoperative MRONJ in either group); primary closure of the extraction socket with a mucoperiosteal flap versus application of platelet-rich fibrin without primary wound closure (no case of postoperative MRONJ in either group); and subperiosteal wound closure versus epiperiosteal wound closure (RR 0.09, 95% CI 0.00 to 1.56, 132 participants). Treatment of MRONJ Eight RCTs examined different interventions for the treatment of established MRONJ; that is, the effect on MRONJ cure rates. One RCT analysed hyperbaric oxygen (HBO) treatment used in addition to standard care (antiseptic rinses, antibiotics, and surgery) compared with standard care alone (at last follow-up: RR 1.56, 95% CI 0.77 to 3.18, 46 participants). Healing rates from MRONJ were not significantly different between autofluorescence-guided bone surgery and conventional bone surgery (RR 1.08, 95% CI 0.85 to 1.37, 30 participants). Another RCT that compared autofluorescence- with tetracycline fluorescence-guided sequestrectomy for the surgical treatment of MRONJ found no significant difference (at one-year follow-up: RR 1.05, 95% CI 0.86 to 1.30, 34 participants). Three RCTs investigated the effect of growth factors and autologous platelet concentrates on healing rates of MRONJ: platelet-rich fibrin after bone surgery versus surgery alone (RR 1.05, 95% CI 0.90 to 1.22, 47 participants), bone morphogenetic protein-2 together with platelet-rich fibrin versus platelet-rich fibrin alone (RR 1.10, 95% CI 0.94 to 1.29, 55 participants), and concentrated growth factor and primary wound closure versus primary wound closure only (RR 1.38, 95% CI 0.81 to 2.34, 28 participants). Two RCTs focused on pharmacological treatment with teriparatide: teriparatide 20 μg daily versus placebo in addition to standard care (RR 0.96, 95% CI 0.31 to 2.95, 33 participants) and teriparatide 56.5 μg weekly versus teriparatide 20 μg daily in addition to standard care (RR 1.60, 95% CI 0.25 to 1.44, 12 participants).
AUTHORS CONCLUSIONS
Prophylaxis of medication-related osteonecrosis of the jaw One open-label RCT provided some evidence that dental examinations at three-month intervals and preventive treatments may be more effective than standard care for reducing the incidence of medication-related osteonecrosis of the jaw (MRONJ) in individuals taking intravenous bisphosphonates for advanced cancer. We assessed the certainty of the evidence to be very low. There is insufficient evidence to either claim or refute a benefit of the interventions tested for prophylaxis of MRONJ in patients with antiresorptive therapy undergoing dentoalveolar surgery. Although some interventions suggested a potential large effect, the studies were underpowered to show statistical significance, and replication of the results in larger studies is pending. Treatment of medication-related osteonecrosis of the jaw The available evidence is insufficient to either claim or refute a benefit, in addition to standard care, of any of the interventions studied for the treatment of MRONJ.
Topics: Anti-Bacterial Agents; Denosumab; Diphosphonates; Humans; Male; Osteonecrosis; Osteoporosis; Teriparatide
PubMed: 35866376
DOI: 10.1002/14651858.CD012432.pub3