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Zol3.0
Zoledronate – Forschung
Überwiegend Mechanismus / Beobachtung
30 begutachtete Studien
Was die Evidenz sagt
Überwiegend Mechanismus / Beobachtung
Die meisten Studien zu Zoledronate sind mechanistisch oder beobachtend statt RCTs, die einen klinischen Effekt messen — betrachte die Ergebnisse als vorläufig.
Die meiste Evidenz stammt aus hochwertigen Meta-Analysen und randomisierten Studien, veröffentlicht 2007–2026 mit einer typischen Studiengröße von 211 Teilnehmenden.
Basierend auf 30 Studien · 3 Meta-Analysen · 5 RCTs · 70,330 Teilnehmende insgesamt
Konfidenz
Hohe Konfidenz
Nach Outcome
Fracture & boneNachgewiesene Reduktion klinischer sowie vertebraler/Hüftfrakturen bei Osteoporose · Jahre
Überwiegend Mechanismus / Beobachtung22 Studien
Safety profile
Überwiegend Mechanismus / Beobachtung7 Studien
Mortality & aging
Überwiegend Mechanismus / Beobachtung5 Studien
Aktives Forschungsgebiet
26 Studien in den letzten 5 Jahren · Neueste Meta-Analyse: 2026
Ferraro MC, O'Connell NE, Goebel A, Hill R, Curtis F, Wilkinson J, Center JR, Gustin SM, Cashin AG, McAuley JH. · Annals of internal medicine (2026)
Data synthesis Eleven trials (754 participants; CRPS type I, 97%), evaluating alendronate ( n = 2), clodronate ( n = 1), neridronate ( n = 5), pamidronate ( n = 1), and zoledronate ( n = 2), were included.
Bisphosphonates may result in little to no difference in pain intensity in the immediate term (≤4 weeks; 0-to-100 scale; mean difference [MD], -9.1 [95% CI, -19.2 to 1.1]; low certainty).
Evidence mostly applies to CRPS type I and includes non-U.S.-approved formulations (neridronate, clodronate).
Conclusions Ten years after trial initiation, zoledronate administered at baseline and 5 years was effective in preventing morphometric vertebral fracture in early postmenopausal women. (Funded by the Health Research Council of New Zealand; Australian New Zealand Clinical Trials Registry number, ACTRN12612000270819.).
Bolland MJ, Nisa Z, Mellar A, Gasteiger C, Pinel V, Mihov B, Bastin S, Grey A, Reid IR, Gamble G, Horne A. · The New England journal of medicine (2025)
The primary end point was morphometric vertebral fracture, which was assessed semiquantitatively and defined as at least a 20% change in vertebral height from that seen on the baseline radiograph.
Results Of 1054 women with a mean age of 56.0 years at baseline, 1003 (95.2%) completed 10 years of follow-up.
Lan Z, Lin X, Xue D, Yang Y, Saad M, Jin Q. · Clinical orthopaedics and related research (2025)
Due to the low heterogeneity among the studies, as evidenced by the low statistical heterogeneity (that is, a low I 2 statistic), we opted for a fixed-effects model, indicating that the effect size is consistent across the studies.
Results The use of bisphosphonates did not reduce the overall risk of mortality in patients with osteoporosis (risk ratio 0.95 [95% CI 0.88 to 1.03]).
Conclusion Based on our comprehensive meta-analysis, there is high-quality evidence suggesting that bisphosphonate therapy for patients with osteoporosis does not reduce the overall risk of mortality despite its effectiveness in reducing the risk of fractures.
The evidence supports the protective effect of these biomaterials as a scientifically grounded preventive approach for BRONJ.
Paulo S, Abrantes AM, Laranjo M, Marto CM, Paula A, Trancoso P, Botelho F, Serra A, Ferreira MM. · Journal of functional biomaterials (2026)
Biomaterials based on synthetic hydroxyapatite and beta-tricalcium phosphate have been investigated as potential preventive agents.
Their therapeutic rationale is supported by two key principles: the well-documented chemical interaction of calcium phosphates with bisphosphonates when used as drug carriers, and the established clinical use of synthetic calcium phosphate biomaterials in dentistry for bone regeneration.
This review examines the underlying mechanisms of this preventive therapeutic strategy and evaluates studies investigating synthetic calcium phosphate biomaterials for BRONJ prevention through zoledronate adsorption at jaw wound sites, thereby reducing soft tissue toxicity and promoting healing.
In particular, it discusses the limited utilization of zoledronate in early postmenopausal women and its inpatient use in older adults after hip fractures.
Sung N, Novik R, Cohn M, Batur P. · Journal of women's health (2002) (2026)
The clinical update offers a concise overview of recently published, high-impact journal articles that may influence clinical practice, summarized for our readers.
This edition highlights recent studies related to the diagnosis and management of osteoporosis.
It reviews essential international guidelines on the clinical use of trabecular bone score (TBS) and a goal-oriented approach to treatment, alongside emerging data on the cardiovascular safety of romosozumab and evidence underscoring the underuse of zoledronate.
Participating sites also received accrual support from the Canadian Cancer Clinical Trials Network [3CTN].).
Clemons M, Stober C, Pond GR, Conter H, Simos D, Dhesy-Thind S, Mates M, Trinkaus M, Hilton J, Savard MF, Fergusson D, Vandermeer L, Awan AA. · NEJM evidence (2026)
After 5 years of follow-up, there were no significant differences in the incidence of osteonecrosis of the jaw (0% vs. 0%) or fragility fractures (5% vs. 2%) in the single-infusion group versus the 6-monthly infusion group, respectively.
Conclusions At 3 years of follow-up, a single infusion of zoledronate had previously been shown to be associated with increased patient convenience, less toxicity, and lower rates of treatment discontinuation compared with treatment every 6 months.
Participating sites also received accrual support from the Canadian Cancer Clinical Trials Network [3CTN].).
Additional evidence is necessary to evaluate the real-world clinical impact of these findings, clarify the effects on risk for SCC, and investigate denosumab.
Gal ZT, Wetzel EA, Nahed BV, Saylor PJ, Hirsch JA, Marciscano AE, Raje NS, Tobert DG, Yee AJ, Shankar GM. · The spine journal : official journal of the North American Spine Society (2026)
Compared to no treatment or placebo, lower-potency bisphosphonates were associated with a reduction in the risk for vertebral fractures, with a pooled RR of 0.72 (95% CI: 0.61-0.85, p=.0001), suggesting a 28% reduction in risk.
Zoledronate was the most efficacious bisphosphonate in the network meta-analysis, with a 64% reduction in vertebral fracture risk compared to no treatment or placebo (RR=0.36, 95% CI: 0.16-0.77, p=.009).
Conclusions The body of literature indicates that bisphosphonates, particularly zoledronate, significantly reduce the risk for vertebral fractures in patients with MM, at least in trial conditions.
Our findings suggest that patients with chronic kidney disease treated with denosumab should receive careful monitoring of mineral and hormone levels, especially at treatment initiation.
Xiao R, Faucon AL, He N, Javaid MK, Ji D, Xu Y, Carrero JJ. · American journal of kidney diseases : the official journal of the National Kidney Foundation (2026)
Results Twenty-five percent of the study population had eGFR < 60 mL/min/1.73 m 2 (chronic kidney disease [CKD] stage 3a [15%] and 3b [8%]).
The denosumab-associated absolute risk differences for hypocalcemia (RD, 2.12% versus 0.19%; P for interaction = 0.04) and SHPT (RD, 4.84% versus 0.03%; P for interaction < 0.001) were greater in patients with eGFR < 60 versus ≥60 mL/min/1.73 m 2 .
We studied adults aged 50 years or older in Stockholm, Sweden, to examine whether these risks differ by kidney function.
This review highlights the need for standardised protocols and provides quantitative guidance for modelling MRONJ and testing regenerative interventions.
Florez-Martin M, Radu AM, Shakib K, Jell G. · Bone (2026)
At 48-71 h, osteoblasts tolerated higher ZOL concentrations compared to later timepoints (p≤0.05).
Media composition influenced responses, with higher calcium (≥1.8 mM) media protective of negative effects, likely due to ZOL-Ca complex formation.
Conclusion ZOL exerts direct, dose-dependent inhibitory effects on osteoblasts in-vitro, with outcomes influenced by exposure time and media composition.
Emerging data suggest that concurrent teriparatide and zoledronate may attenuate rebound risk in long-term Dmab users requiring urgent discontinuation, although prospective validation is needed before routine adoption.
Lu KH, Lin RC, Chang IL, Fu SH, Tsai MY, Yang SF. · Clinical pharmacology and therapeutics (2026)
Discontinuation of denosumab (Dmab) may be necessary due to adverse events or an unfavorable long-term risk-benefit profile.
However, accumulating evidence demonstrates pronounced rebound phenomena after withdrawal, most notably a marked increase in multiple vertebral fractures, and, in some reports, elevated mortality.
Emerging data suggest that concurrent teriparatide and zoledronate may attenuate rebound risk in long-term Dmab users requiring urgent discontinuation, although prospective validation is needed before routine adoption.
However, multicentre studies and prospective cohort quality studies should be performed for confirmation.
Linde KN, Rytter S, Langdahl BL, Madsen F, Stilling M. · The bone & joint journal (2025)
Results At one year, the mean difference in MTPM between zoledronate and placebo was 0.43 mm (95% CI 0.01 to 0.85; p = 0.043), and 0.42 mm (95% CI 0.00 to 0.83; p = 0.048) between denosumab and placebo.
At five years, the intervention groups showed less y-translation (subsidence) than placebo: mean difference of 0.50 mm for zoledronate (95% CI 0.23 to 0.78; p < 0.001) and 0.30 mm for denosumab (95% CI 0.03 to 0.58; p = 0.031).
Conclusion Both interventions decreased cementless tibial implant migration by suppressing bone resorption.
CONCLUSIONS: This study highlights the potential risks of root canal therapy failure in BMA-treated patients, emphasizing the need to evaluate treatment appropriateness and risk-benefit ratio carefully.
Mauceri R, Coppini M, Caponio VCA, Zamparini F, Prati C, Campisi G. · BMC oral health (2025)
In the last one only 4.8% of patients under BMAs developed MRONJ.
The most common BMA used was zoledronate.
A total of 223 teeth underwent root canal therapy.
Rat BRONJ models were more consistently reproducible when the zoledronate administration route was tailored to achieve specific research objectives.
Surboyo MDC, El Fadhlallah PM, Sato-Yamada Y, Sirisereephap K, Fang M, Maeda T, Tomihara K, Tabeta K, Yoshiba N, Rosenkranz AL, Maekawa T. · Bone (2025)
IP and IV zoledronate injection in mice produced a clinical BRONJ model.
Neither mice nor rats exhibited differences in BRONJ characteristics according to sex.
Conclusions Rodent models of BRONJ mimic the staging and characteristics of BRONJ observed in humans.
Lee CC, Wang CY, Yen HK, Hung CC, Lai CY, Hu MH, Wang TM, Li CY, Fu SH. · JAMA network open (2024)
Main outcomes and measures The coprimary outcomes were BMD percentage changes in the lumbar spine (LS-BMD), total hip (TH-BMD), and femoral neck (FN-BMD), respectively.
Results This study included 101 patients (95 women [94.1%]; median age, 72.0 [IQR, 67.0-76.0] years).
There were 25 patients in group A (23 women [92.0%]; median age, 74.0 [IQR, 70.0 to 78.0] years) and 76 in group ZOL (72 women [94.7%]; median age, 71.0 [IQR, 65.7 to 76.0] years).
Reid IR, Horne AM, Mihov B, Bava U, Stewart A, Gamble GD. · The lancet. Diabetes & endocrinology (2024)
Findings Of the 1000 women randomly assigned to receive zoledronate in the core trial, 796 participants were eligible for the extension, of whom 762 (96%) entered the extension between Sept 24, 2015, and Dec 13, 2017.
Non-vertebral fracture rates increased from a nadir of 15 fractures per 1000 woman-years (95% CI 10-21) in the last 2 years of the core trial to 24 fractures (17-33) in years 6-8 and 42 fractures (32-53) in years 8-10, similar to that in the placebo group in the last 2 years of the core trial.
Total hip BMD (relative risk per 0·1 g/cm 2 0·73, 95% CI 0·57-0·93; p=0·011) and a previous history of non-vertebral fracture (1·74, 1·12-2·69; p=0·013) at year 6 predicted incident fractures but change in total hip BMD did not.
However, it remains crucial to conduct further research to confirm these findings and determine the most effective treatment strategy.
Tang Y, Jin Z, Lu Y, Chen L, Lv S, Xu T, Tong P, Chen G. · Orthopaedic surgery (2024)
A Bayesian network meta-analysis (NMA) was carried out for calculating the standardized mean difference (SMD) and the surface under cumulative ranking curve (SUCRA) of the BMD in calcar (Gruen zone 7) at 6 months, 12 months, and 24 months and over.
At 12 months, clodronate ranked highest (SUCRA = 0.96), followed by denosumab (SUCRA = 0.84) and teriparatide (SUCRA = 0.82).
For interventions with a duration of 24 months and over, denosumab had the highest SUCRA value (SUCRA = 0.96), followed by raloxifene (SUCRA = 0.90) and zoledronate (SUCRA = 0.75).
Trial Protocol, statistical analysis plan, participant data and other materials (including data dictionary) can be accessed on request to the corresponding author.
Pickering ME, Morel V, Nicolas M, Dualé C, Sortais E, Graven-Nielsen T, Pereira B, Pickering G. · Aging clinical and experimental research (2026)
It shows a dysfunction of pain inhibitory pain pathways and its non-reversibility with treatments.
It points towards the lack of any analgesic effect of zoledronate, and above all to a latent vulnerability of osteoporotic women who are at a potential risk of fracture with a poor pain modulation that needs to be researched further to limit future chronification.
Trial registration number (NCT05328154), 15/03/2022.
Two consecutive zoledronate infusions and the double-switching regimen with resumed denosumab showed promising BMD preservation, making them advisable clinical alternatives after denosumab discontinuation.
Yen HK, Lee CC, Wang CY, Lin TC, Fu SH, Huang CC, Hung CC, Groot OQ, Li CY. · Clinical pharmacology and therapeutics (2026)
The primary outcome was the percent change in the lumbar spine (LS) bone mineral density (BMD), total hip BMD (TH-BMD), and femoral neck BMD (FN-BMD).
LS-BMD increased by 1.77% in the denosumab group, by 2.25% in the double-switching group, while decreasing by 0.71% in the annual-zoledronate group and by 2.76% in the biennial-zoledronate group.
One-third of patients in the biennial-zoledronate group showed LS-BMD loss exceeding the least significant change (LSC), and 22% required rescue zoledronate infusions.
This suggests that routine BMD monitoring may not be necessary for low-risk women considering the option of less frequent zol for long-term fracture risk reduction.
Bolland MJ, Nisa Z, Mellar A, Gasteiger C, Pinel V, Mihov B, Bastin S, Grey A, Reid IR, Gamble G, Horne A. · The Journal of clinical endocrinology and metabolism (2026)
Results Morphometric vertebral fractures were not reduced in the years 0 to 5 following zol but were reduced in years 5 to 10 by 58% (95% CI, 21%-77%) (zol-zol) and 57% (21%-77%) (zol-placebo).
There were no interactions between treatment effect and baseline variables (including age, body mass index, BMD, falls or fracture history, and estimated fracture risk) or between treatment effect and changes in BMD with zol.
Conclusion Fracture reductions with single-dose or 5-yearly zol appear greater during years 5 to 10 than years 0 to 5.
CONCLUSIONS: The study suggests that romosozumab might be safe and well tolerated in cancer survivors, with no impact on disease progression or recurrence at least in the short term, even in patients undergoing radiation therapy and those with hematological malignancies.
RESULTS: Of the 131 patients treated at our center, 15% (19/131) had a history of cancer.
Among the women with cancer, 32% had breast cancer, 32% had reproductive tract tumors, 21% had hematological malignancies, 11% had cutaneous melanoma and one patient had anal cancer.
At the follow-up, 79% of patients completed the 12-month cycle of romosozumab, while the remaining 21% were still undergoing the anti-osteoporotic treatment.