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Article

Early Implant Stability Improved by Nutraceutical Support: Results from a Prospective Randomized Clinical Trial Based on Resonance Frequency Analysis

by
Roberto Lo Giudice
1,*,
Marcella Denaro
2,
Erica Cutè
3 and
Alessia Quattrocchi
2
1
Department of Biomedical and Dental Sciences and Morphofunctional Imaging, Messina University, 98100 Messina, Italy
2
Laboratorio Farmaceutico ERFO S.p.A., Viale Geki Russo, 98049 Messina, Italy
3
Department of Science and Technology for Sustainable Development and One Health, University Campus Bio-Medico of Rome, Via Alvaro del Portillo 21, 00128 Rome, Italy
*
Author to whom correspondence should be addressed.
Appl. Sci. 2026, 16(2), 1087; https://doi.org/10.3390/app16021087
Submission received: 8 December 2025 / Revised: 14 January 2026 / Accepted: 19 January 2026 / Published: 21 January 2026
(This article belongs to the Special Issue Implant Dentistry: Advanced Materials, Methods and Technologies)
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Versions Notes

Abstract

Background: Osseointegration is the cornerstone of long-term implant success, and systemic factors such as nutritional status may influence the biological cascade of peri-implant bone healing. Nutraceuticals have been proposed as adjuvant strategies to enhance bone metabolism, but clinical evidence remains scarce. This study aimed to evaluate the effect of a novel nutraceutical formulation (Osteo-therapy®, Laboratorio Farmaceutico ERFO S.p.A., Messina, Italy; composed of spirulina standardized with 40% phycocyanin, quercetin, vitamin D3, and calcium) on early implant stability. Methods: A prospective, randomized clinical trial (RCT) was conducted in accordance with CONSORT guidelines (PLATFORM Project OR12.1). Sixty healthy patients requiring mandibular implants were enrolled (test n = 30 with Osteo-therapy®; control n = 30). Stability was assessed via RFA (ISQ values) at baseline (T0), 1 month (T1), 2 months (T2), and 3 months (T3). Results: Both groups showed increases in ISQ. No significant differences were found at T0 and T1 (p = 0.149 and p = 0.737). From T2 onward, the test group exhibited significantly higher ISQ values (T2: 73.17 vs. 69.50, p < 0.001; T3: 78.37 vs. 76.63, p = 0.006). Conclusions: Osteo-therapy® significantly enhanced early implant stability, indicating an accelerated transition from primary to secondary stability, potentially supporting earlier loading protocols.

1. Introduction

Dental implants represent the gold standard in the rehabilitation of edentulous patients, providing highly predictable long-term survival rates and improved quality of life compared to conventional prosthetic approaches [1,2]. The foundation of this success lies in osseointegration, a concept introduced by Brånemark to describe the direct and stable structural connection between vital bone and the surface of a load-bearing implant [3]. Despite high overall predictability, osseointegration is influenced by systemic and local factors that may impair bone healing and compromise treatment outcomes [4,5].
Systemic conditions such as diabetes mellitus, osteoporosis, and autoimmune diseases are well recognized for their negative impact on peri-implant bone regeneration [6,7,8]. Hyperglycemia, reduced bone turnover, and immune dysregulation may slow the osseointegration process, decreasing implant stability and success rates [9,10,11]. Moreover, commonly prescribed medications—including bisphosphonates, corticosteroids, and immunosuppressants—interfere with bone metabolism and remodeling, raising the risk of compromised osseointegration [12,13,14].
In recent years, attention has shifted to nutraceuticals as potential adjuvant therapies to support peri-implant bone healing. Nutraceuticals are bioactive compounds derived from food or natural sources with proven health-promoting effects. The nutraceutical investigated in this study, Osteo-therapy® (Laboratorio Farmaceutico ERFO S.p.A., Messina, Italy).
Each component contributes synergistically: spirulina and phycocyanin exert antioxidant and anti-inflammatory effects; quercetin promotes osteoblastic differentiation; vitamin D3 regulates calcium absorption and bone mineralization; and calcium provides the essential mineral substrate for new bone apposition [15,16,17,18]. Specifically, phycocyanin is known to modulate the RANKL/NF-κB signaling pathway, providing crucial biological support by attenuating osteoclastogenesis and excessive bone resorption at the implant-bone interface. This mechanism synergizes with the mineralizing action of Vitamin D3 and calcium to accelerate peri-implant healing. Collectively, these compounds are hypothesized to accelerate and enhance peri-implant osseointegration.
Reliable and standardized monitoring of implant stability is essential for assessing osseointegration. While radiographic methods provide structural insights, they are limited in detecting early biological changes. Resonance Frequency Analysis (RFA), expressed as the Implant Stability Quotient (ISQ), is considered the gold standard for non-invasive, quantitative assessment [17,18]. RFA measures the stiffness of the implant-bone interface, producing reproducible ISQ values from 1 to 100. Higher ISQ values correlate with greater stability, while lower or decreasing values may indicate impaired healing [19]. Importantly, RFA enables repeated monitoring of the transition from primary stability (mechanical anchorage at placement) to secondary stability (biological remodeling and new bone formation), thus providing dynamic insights into the osseointegration process [20,21,22]. Unlike insertion torque, which is measured only at placement, RFA can be repeated over time, ensuring reliable follow-up and evidence-based decision-making regarding loading protocols [23,24].
Despite the growing interest in nutraceuticals as adjunctive therapies, most available evidence remains limited to preclinical investigations or animal models, with only scarce translation into human clinical research [15,16]. Moreover, existing clinical studies often rely on heterogeneous endpoints—such as marginal bone loss or subjective assessments—introducing variability and limiting comparability across studies.
In this context, RFA offers not only clinical validity but also methodological robustness, serving as a reproducible and standardized outcome measure widely applied in clinical trials [18,19]. Its quantitative and operator-independent nature ensures reliability in multicenter and translational research settings [25,26].
To overcome previous limitations, the present investigation was designed as a prospective, randomized cohort study with power analysis–based sample size calculation. Implant stability was objectively monitored through ISQ values at multiple follow-up intervals, enabling the evaluation of both primary and secondary stability with high statistical validity. By combining rigorous design with standardized measurement tools, this research strengthens both the internal validity and the translational impact of the findings.
The study was conducted within the PLATFORM Project (OR12.1—Development and Scale-Up of Nutraceutical Formulations), an initiative that integrates advanced materials, technologies, and personalized approaches to optimize bone healing. Within this translational framework, the present research connects dental implantology with orthopedic models of osteotomy healing, recognizing the shared biomechanical and biological foundations of osseointegration across surgical fields.
Null Hypothesis: The administration of Osteo-therapy® has no effect on implant stability; therefore, no significant differences in ISQ values will be observed between the supplemented and control groups at any time point.

2. Materials and Methods

2.1. Study Design and Ethical Approval

This research was conducted as a prospective, parallel-group, randomized clinical trial (RCT), preregistered within the framework of the PLATFORM Project (OR12.1—Development and Scale-Up of Nutraceutical Formulations). The study protocol and reporting adhered to the CONSORT (Consolidated Standards of Reporting Trials) guidelines. Ethical approval was obtained from the Local Ethics Committee of the University Hospital of Messina (protocol code 95-23, approval date: 20 February 2024). Written informed consent was collected from all participants prior to enrollment. The scientific association that clinically recruited the patient was Cenacolo Odontostomatologico Italiano (COI-AIOG), moreover it calibrated and instructed a researcher for the best practice and the proper management of the protocol. Radiographic assessment via CBCT was performed at baseline primarily for diagnostic purposes and to verify inclusion criteria (sufficient bone volume), rather than as a quantitative outcome measure for this specific report. All ISQ measurements were performed independently by two calibrated examiners blinded to group allocation (Cohen’s kappa > 0.85)

2.2. Population and Eligibility Criteria

Between March and September 2024, 60 healthy patients requiring implant rehabilitation in the mandible were enrolled and allocated into two groups:
Test group (n = 30): received the nutraceutical supplement Osteo-therapy® (Laboratorio Farmaceutico ERFO S.p.A., Messina, Italy).
Control group (n = 30): no supplementation.
Inclusion criteria:
Partial mandibular edentulism for at least 3 months;
Age ≥ 18 years;
Good systemic health;
Adequate bone volume allowing implant placement without regenerative procedures.
Exclusion criteria:
Post-extraction sites;
Smoking;
Ongoing oncological/radiotherapy treatment;
Immunosuppressive therapy;
Diagnosed osteoporosis or osteopenia.

2.3. Nutraceutical Supplementation

Patients in the test group received Osteo-therapy® (Laboratorio Farmaceutico ERFO S.p.A., Messina, Italy), contains spirulina 40% standardized with phycocyanin at 50%, quercetin 10.20%, vitamin D3 1.20%, and calcium carbonate 30%
Supplementation was administered orally once daily, according to the manufacturer’s instructions, for 3 months following implant placement. Compliance was monitored at each follow-up visit through structured patient interviews.

2.4. Surgical Procedure

Implants were placed in the mandible by experienced surgeons (>5 years of clinical practice). All implants had standardized dimensions (4.0 mm diameter × 10 mm length).
The surgical protocol included:
Preoperative low-dose CBCT (FOV 5 × 5 or 8 × 8 cm) for diagnostic evaluation and treatment planning;
Crestal incision with a trapezoidal full-thickness flap and minimal detachment (1–2 mm apical to cortical bone margin);
Sequential osteotomy preparation according to standard surgical procedures;
Placement of the implant fixture (4.0 × 10 mm) in healed mandibular sites;
Healing abutment connection and primary closure by suturing.

2.5. Outcome Measures

The primary outcome was implant stability, assessed by Resonance Frequency Analysis (RFA) and expressed as the Implant Stability Quotient (ISQ). Measurements were recorded at baseline (T0, insertion), 1 month (T1), 2 months (T2), and 3 months (T3) (Figure 1).
All ISQ measurements were performed independently by two calibrated examiners blinded to group allocation. This blinded outcome assessment (PROBE design: Prospective Randomized Open Blinded Endpoint) was implemented to mitigate detection bias, given the open-label nature of the dietary intervention.
Calibration was conducted on a pilot set of 10 implants, yielding a Cohen’s kappa > 0.85.
Secondary exploratory outcomes included:
Radiographic assessment of peri-implant bone levels via CBCT;
Clinical observation of peri-implant mucosa, which showed uneventful healing in all patients;
Absence of intraoperative complications across both groups.

2.6. Randomization

Random allocation into test and control groups was performed using Random Allocation Software (RAS, version 2.0; Isfahan, Iran) with a 1:1 ratio. The allocation sequence was concealed until the time of surgery.

2.7. Follow-Up and Data Collection

Patients were followed monthly for three months postoperatively. Data on ISQ values, radiographic examinations, and clinical parameters were systematically recorded in anonymized electronic case report forms. No patients were lost to follow-up.

2.8. Statistical Analysis

A priori power analysis (G*Power v.3.1.9) with α = 0.05 and power (1 − β) = 0.90 determined that 30 patients per group were sufficient to detect medium effect sizes (Cohen’s d = 0.5) in ISQ differences.
Normal distribution of quantitative data was confirmed using the Kolmogorov–Smirnov test. Descriptive statistics were reported as means ± standard deviations (SD). Between-group comparisons at each time point were performed using independent samples t-tests.
To account for the longitudinal design and the correlation of repeated measurements within subjects, ISQ values were analyzed using a Mixed-Model Repeated Measures ANOVA (Analysis of Variance), with “Time” (T0, T1, T2, T3) as the within-subject factor and “Group” (Test vs. Control) as the between-subject factor. Where a significant Time × Group interaction was found, post hoc pairwise comparisons were performed to identify differences at specific time points (using Bonferroni correction for multiple comparisons). Statistical significance was set at p < 0.05. Analyses were conducted with IBM SPSS Statistics (v.22, Armonk, NY, USA).

3. Results

3.1. Participant Flow and Follow-Up

Sixty patients completed the study (30 per group), with no losses to follow-up. All fixtures were placed in healed mandibular sites and had standardized dimensions 4.0 × 10 mm. Surgery was uneventful, and soft-tissue healing proceeded without complications in all cases. ISQ was recorded at insertion (T0) and at 1, 2, and 3 months (T1–T3).

3.2. Primary Outcome: ISQ over Time

Group means (±SD) are reported in Table 1. At T0 and T1, ISQ values were comparable between groups (p = 0.149 and p = 0.737, respectively). A clear divergence emerged from T2 onward: the Osteo-therapy® group showed higher stability at T2 (Δ = +3.67 ISQ) and T3 (Δ = +1.74 ISQ) compared with controls, with statistically significant differences at both time points. To account for the longitudinal design and the correlation of repeated measurements within subjects, ISQ values were analyzed using a Mixed-Model Repeated Measures ANOVA (Analysis of Variance), with “Time” (T0, T1, T2, T3) as the within-subject factor and “Group” (Test vs. Control) as the between-subject factor. Where a significant Time × Group interaction was found, post hoc pairwise comparisons were performed to identify differences at specific time points (using Bonferroni correction for multiple comparisons). Statistical significance was set at p < 0.05. Analyses were conducted with IBM SPSS Statistics (v.22, Armonk, NY, USA) (Table 2).

3.3. Confidence Intervals and Effect Sizes

To aid clinical interpretation, 95% confidence intervals (CI) were computed for mean differences and for each group mean (Table 3). Between-group standardized effects (Cohen’s d, equal n) were also calculated from the t statistics and corrected to Hedges’ g.

3.4. Interpretation

  • T2 (2 months) shows a large standardized effect (Hedges’ g ≈ 1.18), with a mean difference of +3.67 ISQ (95% CI +2.09 to +5.25).
  • T3 (3 months) remains moderate-to-large (g ≈ 0.74), with +1.74 ISQ (95% CI +0.54 to +2.94).
  • Early time points (T0–T1) are statistically and clinically indistinguishable, consistent with a biologically plausible lag before nutraceutical effects manifest.

3.5. Trajectory and Magnitude of Improvement

Across the 3-month window, mean ISQ increased from 65.87 → 78.37 in the test group (Δ = +12.50, +19.0% from baseline) and from 67.23 → 76.63 in controls (Δ = +9.40, +14.0%). The monthly slope of improvement was +4.17 ISQ/month (test) vs. +3.13 ISQ/month (control), indicating a steeper trajectory with Osteo-therapy®. Although within-group inferential testing of change requires paired data, these descriptive gradients corroborate the between-group findings.

3.6. Measurement Quality and Clinical Observations

Inter- and intra-examiner reproducibility for RFA was high (Cohen’s κ > 0.85). No intraoperative complications were recorded, and peri-implant mucosa exhibited uneventful healing in all participants through T3. Radiographic assessments at routine controls did not show adverse peri-implant changes in either group.

4. Discussion

This randomized clinical trial—conducted within PLATFORM (OR12.1)—found that Osteo-therapy® is associated with higher ISQ from the second month onward, with differences maintained at three months. The absence of between-group differences at T0–T1 and the subsequent divergence at T2–T3 are biologically consistent with a shift from primary mechanical stability to secondary biologic stability driven by bone remodeling (Figure 2).

4.1. How Our ISQ Data Compares with Clinical Literature

Longitudinal RFA data typically show an upward ISQ trend over 2–3 months, with variability dictated by site, bone quality, and protocols. Reviews and clinical analyses confirm that ISQ values are predictive of stability and clinical course, and identify ~70 as a commonly referenced threshold for “high stability,” used to gauge readiness for early loading [“ISQ as indicator and predictor”] [27]. In our cohort, both groups improved over time, but the supplemented arm crossed and consolidated the >70 band earlier, mirroring the literature’s risk-based thresholds for secure loading [20].
Quantitatively, our gross ISQ gains over three months (+12.5 in the test arm; +9.4 in controls) sit within the range reported for early healing trajectories in comparable clinical settings, where increases around 12 ISQ units from placement to 12 weeks are often observed [2,3]. Together with the large effect size at 2 months and moderate–large at 3 months, this suggests a clinically meaningful acceleration of secondary stability.
Measurement quality: Our blinded, calibrated RFA workflow (κ > 0.85) aligns with studies showing high repeatability and reliability of ISQ measurements, supporting their use as primary outcomes in clinical implant research [4,5].

4.2. How Our Findings Align with Nutraceutical Evidence in Implantology

The clearest clinical signal in the implant field concerns vitamin D, for which multiple clinical reports and syntheses associate adequate status or supplementation with more favorable osseointegration indices, including stability and marginal bone behavior—though results are heterogeneous across designs [28,29,30]. A recent randomized clinical trial reported better implant outcomes with vitamin D3 supplementation, reinforcing mechanistic plausibility for a systemic micronutrient effect on early stability [10]. By contrast, large retrospective datasets on serum vitamin D and early failures have sometimes shown non-significant associations, underscoring the need for controlled designs and stratification by deficiency status [31,32].
The test formulation differs from vitamin D-only regimens by adding spirulina/phycocyanin and quercetin, two bioactives with documented anti-inflammatory/antioxidant and pro-osteogenic actions in preclinical models. C-phycocyanin can attenuate RANKL-induced osteoclastogenesis via NF-κB/ROS modulation, a mechanism coherent with reduced early resorption at the interface [33]; spirulina supplementation has also been linked to improved bone modeling and strength in animal systems [34]. Quercetin promotes osteoblast differentiation and reduces osteoclast activity in vitro and in vivo models, supporting its inclusion as a bone-active flavonoid [35,36]. Although these mechanistic signals are strong, human implant trials evaluating combined flavonoid/phytonutrient formulations remain scarce. Our clinical signal (ISQ divergence from month 2) is therefore consistent with component biology but extends it into a clinical endpoint. CBCT was used for safety/exclusion purposes rather than a quantitative outcome in this specific report. Our data show a clinically meaningful acceleration of secondary stability. The absence of significant differences at T0 and T1 is biologically consistent with a phase dominated by mechanical primary stability. The divergence observed at T2 (2 months) coincides with the active phase of bone remodeling, suggesting that the nutraceutical support effectively drives the transition to biological secondary stability. Clinical Relevance of ISQ Differences A critical question is whether the observed statistical difference (ranging from 1.7 to 3.7 ISQ units) translates into clinical benefit. While the absolute magnitude appears limited, in the context of implant loading protocols, small shifts in stability can be clinically decisive. Literature suggests that ISQ values > 70 are often considered the “safety threshold” for immediate or early functional loading. In our control group, mean stability at T2 was borderline (6950), whereas the test group safely surpassed this threshold (73.17). This transition suggests that nutraceutical support may effectively shorten the “window of risk” during the critical phase of stability dip, potentially allowing for more predictable early loading workflows. However, this remains a hypothesis that must be validated by future trials with implant survival as the primary endpoint.

4.3. Comparative View: Compositions and Outcomes in Published Studies

  • Vitamin D-only supplementation (various doses, sometimes with background calcium): associated with improved implant stability and osseointegration indices in controlled settings, though not uniformly across all observational cohorts [6,7,8,9,10,37,38].
  • Omega-3, curcumin, or other nutraceuticals in implant patients: emerging and largely investigational; ongoing trials exist, but robust RCT evidence for ISQ endpoints is limited to date [16].
  • Our combination (D3 + Ca + quercetin + spirulina/40% phycocyanin): introduces anti-resorptive (RANKL/NF-κB) and pro-osteogenic pathways beyond mineral/endocrine support alone, which may explain the earlier and larger ISQ gain observed at T2 versus what is typically reported with standard care. While direct head-to-head trials are lacking, the multi-target profile of our formulation contrasts with single-nutrient strategies, potentially offering additive or synergistic benefits [37,38].

4.4. Clinical Implications

In clinical terms, reaching an ISQ > 70 significantly earlier (at 2 months for the test group) is a critical milestone. This threshold is widely recognized as a predictor for “high stability,” potentially allowing clinicians to safely implement early loading protocols (6–8 weeks) and reduce overall treatment times in straightforward mandibular cases [39]. This aligns with risk-based loading frameworks that leverage ISQ to reduce early micromovement and failure risk [1,3,40,41].

4.5. Strengths and Limitations

Strengths include prospective design, STROBE-compliant reporting, standardized mandibular 4.0 × 10 mm implants, blinded calibrated examiners, no attrition, and a priori power. Limitations include monocentric scope, interview-based adherence (no pill counts/biomarkers), absence of placebo, and 3-month horizon (no survival analysis). The literature comparison is constrained by heterogeneity in endpoints and variable control of deficiency states, especially for vitamin D [42]. Limitations include the absence of baseline serum Vitamin D quantification, which prevents correlating systemic absorption with local stability outcomes. Additionally, adherence was monitored via interview rather than strict pill counts. Furthermore, the absence of serum biochemical markers (e.g., Vitamin D levels, C-terminal telopeptide, Osteocalcin) limits our ability to confirm the exact biological mechanism. While we observed a clear phenotypic effect (improved ISQ), we cannot definitively attribute this to corrected systemic deficiencies versus a direct pharmacological effect of the phytonutrients (Quercetin/Spirulina). Future research should integrate serological monitoring to bridge this gap.

4.6. Future Directions

Head-to-head trials comparing vitamin D ± calcium versus multi-component formulations (adding quercetin and spirulina/phycocyanin) are warranted, with 25(OH)D monitoring, bone-turnover biomarkers (P1NP, CTX), and longer follow-up to test whether early ISQ gains translate into marginal bone stability and survival. As omega-3 and other phytonutrients enter clinical testing, factorial designs may clarify synergy versus redundancy among components [16].

5. Conclusions

Within the limitations of this randomized clinical trial, nutraceutical supplementation with Osteo-therapy® significantly enhanced early implant stability compared with controls. While no differences were observed at baseline and after one month, a statistically and clinically relevant increase in ISQ emerged at two months and persisted at three months, indicating an accelerated transition from primary to secondary stability.
These findings support the hypothesis that systemic nutraceutical support may improve the biological cascade of osseointegration, offering potential advantages in reducing healing times and supporting earlier loading protocols. Larger multicenter trials with longer follow-up are warranted to validate these results and explore the applicability of nutraceutical supplementation in patients with systemic risk factors.

6. Patents

Osteo-therapy® is covered by Italian patent application IT202400029766, currently pending at the Italian Patent and Trademark Office (UIBM).

Author Contributions

Conceptualization, R.L.G. and A.Q.; methodology, software and validation, R.L.G.; formal analysis, E.C.; investigation, R.L.G.; resources, A.Q. and M.D.; data curation, E.C.; writing—original draft preparation, R.L.G.; writing—review and editing, E.C.; visualization, M.D.; supervision, R.L.G.; project administration, M.D.; funding acquisition, A.Q. All authors have read and agreed to the published version of the manuscript.

Funding

This research was funded by the National Research Project PLATFORM (“Materials, Processes, and Advanced Technologies for the Realization, Monitoring, and Functional Validation of Osteotomy Procedures”) under the Italian Ministry of Enterprises and Made in Italy (MIMIT), grant number CUP: B79J23001120005. The APC was funded by Laboratorio Farmaceutico ERFO S.p.A.

Institutional Review Board Statement

The study was conducted in accordance with the Declaration of Helsinki and approved by Local Ethics Committee of the University Hospital of Messina (protocol code 95-23, approval date: 20 February 2024).

Informed Consent Statement

Informed consent was obtained from all subjects involved in the study.

Acknowledgments

The authors would like to thank Laboratorio Farmaceutico Erfo S.p.A. for supporting the publication of this research and for providing technical collaboration within the Osteo-Therapy® development program. The authors would like to thank the Cenacolo Odontostomatologico Italiano (COI-AIOG) for the scientific contribution.

Conflicts of Interest

The authors are inventors of the Italian patent application IT202400029766 concerning the Osteo-therapy® formulation. Some authors (M.D., A.Q.) are affiliated with Laboratorio Farmaceutico Erfo S.p.A., which supported the research within the framework of the PLATFORM project and supported the APC. No other conflicts of interest are declared. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results. To ensure scientific integrity, data collection and formal statistical analysis were conducted solely by the academic authors (R.L.G., E.C.), independently of the commercial sponsor.

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Applsci 16 01087 g001
Figure 1. Resonance Frequency Analysis (RFA) with a dedicated transducer for ISQ measurement.
Figure 1. Resonance Frequency Analysis (RFA) with a dedicated transducer for ISQ measurement.
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Figure 2. Longitudinal trajectory of mean ISQ values (±SD) for Test and Control groups. The graph illustrates the significant Time × Group interaction (p < 0.001): while stability is comparable at baseline and 1 month, the curves diverge significantly from the second month onward, with the Osteo-therapy® group showing a steeper increase in stability.
Figure 2. Longitudinal trajectory of mean ISQ values (±SD) for Test and Control groups. The graph illustrates the significant Time × Group interaction (p < 0.001): while stability is comparable at baseline and 1 month, the curves diverge significantly from the second month onward, with the Osteo-therapy® group showing a steeper increase in stability.
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Table 1. Mean ISQ (±SD) by group and time point (independent-samples t-test).
Table 1. Mean ISQ (±SD) by group and time point (independent-samples t-test).
Time PointTest Group (Osteo-Therapy®)Control GroupDifference (Test–Control)tp-Value
T0 (Baseline)65.87 ± 4.3467.23 ± 2.97−1.36−1.460.149
T1 (1 month)68.07 ± 2.9467.83 ± 2.76+0.240.340.737
T2 (2 months)73.17 ± 3.3869.50 ± 2.72+3.674.64<0.001
T3 (3 months)78.37 ± 1.7176.63 ± 2.82+1.742.900.006
Table 2. Results of the Mixed-Model Repeated Measures ANOVA for Implant Stability (ISQ). *** (high statistical significance); ns (non significant).
Table 2. Results of the Mixed-Model Repeated Measures ANOVA for Implant Stability (ISQ). *** (high statistical significance); ns (non significant).
Source of VariationdfF-Valuep-Value Significance
Time (Within-subject factor)3184.86<0.001***
Group (Between-subject factor)13.510.062ns
Time × Group Interaction36.50<0.001***
Table 3. Precision and magnitude of effects.
Table 3. Precision and magnitude of effects.
TimeTest Mean (95% CI)Control Mean (95% CI)Δ ISQ (Test–Control) (95% CI)Cohen’s d (95% CI)Hedges’ g
T065.87 (64.28–67.46)67.23 (66.14–68.32)−1.36 (−3.22 to +0.50)−0.38 (−0.89 to +0.13)−0.37
T168.07 (67.00–69.14)67.83 (66.82–68.84)+0.24 (−1.17 to +1.65)+0.09 (−0.42 to +0.59)+0.09
T273.17 (71.94–74.40)69.50 (68.51–70.49)+3.67 (+2.09 to +5.25) **+1.20 (+0.65 to +1.75)+1.18
T378.37 (77.75–78.99)76.63 (75.60–77.66)+1.74 (+0.54 to +2.94) **+0.75 (+0.22 to +1.27)+0.74
Notes. CIs for means use t with df = 29; CIs for differences use df = 58; d computed from t·√ (1/30 + 1/30); Hedges’ g applies small-sample correction. ** (statistically significant at p < 0.01).
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Lo Giudice, R.; Denaro, M.; Cutè, E.; Quattrocchi, A. Early Implant Stability Improved by Nutraceutical Support: Results from a Prospective Randomized Clinical Trial Based on Resonance Frequency Analysis. Appl. Sci. 2026, 16, 1087. https://doi.org/10.3390/app16021087

AMA Style

Lo Giudice R, Denaro M, Cutè E, Quattrocchi A. Early Implant Stability Improved by Nutraceutical Support: Results from a Prospective Randomized Clinical Trial Based on Resonance Frequency Analysis. Applied Sciences. 2026; 16(2):1087. https://doi.org/10.3390/app16021087

Chicago/Turabian Style

Lo Giudice, Roberto, Marcella Denaro, Erica Cutè, and Alessia Quattrocchi. 2026. "Early Implant Stability Improved by Nutraceutical Support: Results from a Prospective Randomized Clinical Trial Based on Resonance Frequency Analysis" Applied Sciences 16, no. 2: 1087. https://doi.org/10.3390/app16021087

APA Style

Lo Giudice, R., Denaro, M., Cutè, E., & Quattrocchi, A. (2026). Early Implant Stability Improved by Nutraceutical Support: Results from a Prospective Randomized Clinical Trial Based on Resonance Frequency Analysis. Applied Sciences, 16(2), 1087. https://doi.org/10.3390/app16021087

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