Long-term remineralizing effect of casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) on early caries lesions in vivo: A systematic review

Objective

To assess the long-term (>3 months) remineralizing effect of casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) on early caries lesions in vivo.

Data sources

PubMed, Web of Science, Embase, Cochrane-Central, Science Direct, CBM, and CNKI were searched up to April 2013. Only articles in English and Chinese were included. Grey literature was also searched. Randomized or quasi-randomized clinical trials in which CPP-ACP was delivered by any method were considered. All relevant studies underwent two independent reviews.

Study selection

Of the 738 studies screened, 83 studies were reviewed and eight selected for inclusion in the final sample. The follow-up period of the studies included varied from 3 to 24 months. The long-term remineralizing effect of CPP-ACP in vivo was demonstrated in comparison with placebo in randomized controlled trial. However, there is conflicting evidence regarding the clinical efficacy of CPP-ACP when used in conjunction with fluoride toothpastes. No specific side effect related to CPP-ACP usage was found.

Conclusions

CPP-ACP has a long-term remineralizing effect on early caries lesions in comparison with placebo, although this does not appear to be significantly different from that of fluorides. The advantage of using CPP-ACP as a supplement to fluoride-containing products is still unclear. High-quality, well-designed clinical studies in this area are still required before definitive recommendations can be made.

Clinical significance

CPP-ACP is a promising remineralizing agent with a significant remineralizing effect that has been demonstrated in both in vivo and in vitro studies. The evidence to support its synergistic effect with fluoride is insufficient based on the current existing long-term human randomized controlled trials.     

酪蛋白磷酸肽钙磷复合体对变形链球菌粘附影响的实验研究

[目的]研究酪蛋白磷酸肽钙磷复合体(Casein phosphopeptide-Amorphic Calcium Phosphate, CPP-ACP)对变形链球菌粘附的影响,从而进一步探讨CPP-ACP的防龋机制.[方法]采用唾液包被的羟磷灰石(Saliva-coated hydroxyapatite, S-HA)形成实验性膜的体外粘附实验模型,用不同浓度(0.5%～5.0%(W/V)) CPP-ACP处理S-HA,定量观察变形链球菌在S-HA上的粘附情况.[结果]变形链球菌对经各实验浓度的CPP-ACP处理后的S-HA粘附能力明显下降,粘附量(cpm)随CPP-ACP浓度的升高而降低,且粘附抑制率均达100%.[结论]CPP-ACP对变形链球菌在S-HA上的粘附具有抑制作用,随CPP-ACP浓度的升高其抑制作用增强.     

CPP-ACP与含氟制剂抑制牙釉质脱矿效果比较的Meta分析

目的：系统评价局部应用CPP-ACP与含氟制剂比较抑制牙釉质脱矿的临床效果。方法：计算机检索Pubmed、CNKI、CBM、VIP和WanFang Data数据库,查找CPP-ACP与含氟制剂比较抑制牙釉质脱矿的随机对照试验（RCT）,并追溯纳入文献的参考文献,检索时间均为建库至2013年10月18日。由2名评价员按纳入和排除标准独立进行文献筛选、资料提取和评价纳入研究的方法学质量后,采用RevMan5.2软件进行Meta分析。结果：最终纳入7篇文献,11个RCT,共563例受试者。Meta分析结果显示：局部应用CPP-ACP后,其Diagnodent值[MD=2.30,95%CI（0.69,3.91）,P=0.005]及脱矿率[OR=1.40,95%CI（1.09,1.81）,P=0.009]明显低于局部应用含氟制剂,其差异有统计学意义。结论：在早期釉质龋、正畸治疗后出现的釉质白斑病损等牙釉质脱矿的预防和治疗方面,CPP-ACP具有优于含氟制剂的临床疗效,且不存在像含氟制剂的安全问题,因此,CPP-ACP作为一种新型再矿化剂有望替代含氟制剂发挥较优效果。     

Efficacy of CPP-ACP fluoride varnish applied with and without acid etching in preventing enamel demineralization compared to light-curable fluoride varnish

ObjectivesTo compare efficacy of casein phosphopeptide (CPP)–amorphous calcium phosphate (ACP) fluoride varnish and light-curable resin modified glass ionomer fluoride varnish (FV) in preventing white spot lesions and evaluating acid etching prior to CPP-ACPFV application on its efficacy.Materials and MethodsMolars and premolars were transected and halves divided into four groups (n = 18/group): (1) resin-modified glass ionomer FV: etched and Clinpro-XT varnish (3M ESPE, Pymble, New South Wales, Australia) application; (2) CPP-ACPFV: MI varnish (GC America, Alsip, IL) application; (3) Etch+CPP-ACPFV: etched and MI varnish application; (4) Control: etched and no surface treatment. To simulate 12 weeks in an intraoral environment, samples were subjected to thermocycling, brushing, and pH cycling. Enamel surface microhardness was evaluated at baseline and after the simulated 12 weeks. Representative samples were also assessed using scanning electron microscopy (SEM).ResultsAt baseline there was no significant difference in microhardness among groups. After the simulated 12 weeks, all groups showed significant within-group differences (P < .001). Control showed the highest percentage loss of surface microhardness (89%), followed by CPP-ACPFV (58%), RMGIFV (51%), and Etch+CPP-ACPFV (24%). The control group had a significant decrease in microhardness compared to all experimental groups (P < .001). No difference was found between the RMGIFV and CPP-ACPFV varnish groups. The Etch+CPP-ACPFV group had significantly less decrease in microhardness compared to the RMGIFV (P < .001) and CPP-ACPFV groups (P < .001). With SEM, control samples showed signs of enamel surface damage, while experimental groups showed spherical particles on a relatively intact surface.ConclusionsRMGIFV and CPP-ACPFV are effective in reducing enamel demineralization. Acid etching the enamel surface prior to CPP-ACPFV varnish application increased its efficacy.     

A comparative evaluation of ion release characteristics of three different dental varnishes containing fluoride either with CPP-ACP or bioactive glass

ObjectiveTo compare ion release characteristics of three different dental varnishes either containing CPP-ACP and fluoride (CPP-ACPF, MI Varnish GC, Japan), bioactive glass and fluoride (BGAF, Dentsply Sirona USA) or fluoride alone (NUPRO White, Dentsply Sirona USA) using fluoride-Ion Selective Electrode (F-ISE), Inductively Coupled Plasma-Optical Emission Spectroscopy (ICP-OES), X-ray diffraction (XRD), Fourier Transform Infrared Spectroscopy (FTIR), ¹⁹F and ³¹P Magic Angle Spinning-Nuclear Magnetic Resonance (MAS-NMR).MethodsA thin layer (0.0674 ± 0.0005 g) of each varnish (20 × 25 mm in area) was spread on a roughened glass slide (n = 7). They were separately immersed in 10 ml Tris buffer (0.06 M, pH = 7.30), and changed after 1, 2, 4, 6, 24 and 48 h. Fluoride-ion concentration at each time using the F-ISE, whilst calcium and phosphate release were investigated using ICP-OES. XRD, FTIR. MAS-NMR analyses were also performed before and after immersion.ResultsThe cumulative F-ion release was significantly higher in CPP-ACPF (1.113 mmol/g) > BGAF(0.638) > F(0.112) (p < 0.001). The cumulative calcium and phosphorus were higher in the CPP-ACPF (0.137 mmol/g, 0.119) than BGAF (0.067, 0.015) (p < 0.001) respectively. The XRD and ¹⁹F MAS-NMR confirmed the presence of NaF peaks in all cases before immersion. There were less prominent signal and appearance of fluorapatite crystals after immersion. ¹⁹F MAS-NMR revealed CaF₂ formation after immersion in both CPP-ACPF and BGAF. ³¹P MAS-NMR showed phosphate signals in both CPP-ACPF and BGAF before immersion. FTIR failed to show any signs of apatite formation.SignificanceBoth CPP-ACP and bioactive glass enhanced ion release without compromising the bioavailability of fluoride. The CPP-ACPF varnish had the most promising ion release.     

Combined effect of Er,Cr:YSGG laser and casein phosphopeptide amorphous calcium phosphate on the prevention of enamel demineralization:: An in-vitro study

ObjectivesTo compare the effect of use of laser, casein phosphopeptide–amorphous calcium phosphate (CPP–ACP), and their combination on prevention of enamel demineralization using polarized light microscopy to assess lesion depth.Materials and MethodsEighty premolars were randomly allocated to four equal groups (n = 20): Group I: Control group, no preventive measures. Group II: CPP–ACP. Group III: Er,Cr:YSGG laser. Group IV: Er,Cr:YSGG laser followed by CPP–ACP. Specimens were subjected to thermocycling and brushing protocols equivalent to 1 year intraorally. Then, all teeth were subjected to acid challenge. Teeth were then sectioned longitudinally and examined under a polarized light microscope and lesion depth was measured.ResultsGroup IV resulted in the least lesion depth with a significant difference between it and all other groups. CPP–ACP alone and laser alone also showed a significant difference in white spot lesion (WSL) depth compared to the control group; however, no significant difference was found between them.ConclusionsThe combined use of laser and CPP–ACP showed the best prevention against WSL development. The use of CPP–ACP or laser alone also resulted in a significant reduction in lesion depth but was significantly less than their combined use, with no significant difference between them.     

Remineralising effects of fluoride varnishes containing calcium phosphate on artificial root caries lesions with adjunctive application of proanthocyanidin

ObjectivesTo evaluate the remineralising effects of fluoride (F) varnishes containing bioavailable calcium-phosphate compound (Ca-P) based remineralisation systems and 5000 ppm F toothpaste (FTP) on root caries lesions (RCLs) and the potential effects of proanthocyanidin (PA) for the treatments of RCLs when used as an adjunct to F regimens.MethodsDemineralised root dentine and a pH-cycling model were used to mimic RCLs and the oral environment. Remineralising effects of MI Varnish^TM (MIV) containing casein phosphopeptide–amorphous calcium phosphate (CPP-ACP) and Clinpro? White Varnish (CPWV) containing tri-calcium phosphate (TCP) along with FTP and PA were evaluated regarding the birefringence, elemental composition, mechanical properties and mineral density of remineralised dentine with Duraphat^TM as a comparison.ResultsMIV, CPWV and Duraphat^TM promoted the incorporation of F into RCLs and increased mineral density but did not change microhardness of root dentine significantly. Surface microhardness increased significantly when MIV or CPWV was used with 5000 ppm FTP. Application of PA with F regimens significantly increased subsurface mineral density. When PA was applied with MIV or CPWV along with FTP, the highest ion uptake and relative mineral gain (%ΔZ) was achieved, and significant increase of microhardness was up to 30 μm depth. Generally, MIV was associated with a higher mineral content gain than CPWV.SignificanceTreatment of carious root surfaces remains challenging due to the complex pathological processes and difficulty in restoring the highly organised structure of root dentine. Treatment strategies targeting both remineralisation and preservation of the dentinal organic matrix have the potential to improve the fluoride-mediated remineralisation approaches.     

A randomised controlled trial to investigate the remineralising potential of Tooth Mousse™ in orthodontic patients

Objective: To investigate the remineralisation of enamel subsurface lesions treated with fluoride toothpaste (1450 ppm) or a combination of fluoride toothpaste in addition to Tooth Mousse?.

Design: An in situ, cross-over, randomised controlled trial.

Setting: Orthodontic department at Liverpool University Dental Hospital, UK. Participants: Twelve patients receiving fixed orthodontic treatment. Methods: Demineralised subsurface enamel lesions were placed in a carrier and attached onto a fixed orthodontic appliance. Interventions were either standard fluoride toothpaste or CPP-ACP paste (Tooth Mousse?) in addition to the fluoride toothpaste. Participants received both interventions in a randomised order. Transverse microradiography analysis was used to compare lesion mineral content profiles.

Results: Mineral loss was reduced by 15.4 and 24.6% between the fluoride and CPP-ACP groups, respectively (p = 0.023). Lesion depth was reduced by 1.6 and 11.1% between the fluoride and CPP-ACP groups, respectively (p = 0.037). Lesion width was reduced by 4.5 and 15.3% between the fluoride and CPP-ACP groups, respectively (p = 0.015).

Conclusions: Remineralisation occurred regardless of treatment group allocation. However, the addition of Tooth Mousse? resulted in a significantly increased remineralisation effect, compared to fluoride alone. Tooth Mousse? may be beneficial for patients undergoing orthodontic treatment who are at high risk of demineralisation.

Trial Registration: Registered on Current Control Trials http://www.controlled-trials.com/ISRCTN04899524     

酪蛋白磷酸肽钙磷复合体对黏性放线菌黏附影响的实验研究

目的：研究酪蛋白磷酸肽钙磷复合体（casein phosphopeptide-amorphic calcium phosphate,CPP-ACP）对黏性放线菌黏附的影响,进一步探讨CPP-ACP的防龋机制。方法：采用唾液包被的羟磷灰石（saliva-coated hydroxyapatite,S-HA）形成实验性膜的体外黏附实验模型,用不同浓度（0.5%～5.0%（W/V））CPP-ACP处理S-HA,定量观察黏性放线菌在S-HA上的黏附情况。结果：黏性放线菌对经各实验浓度的CPP-ACP处理后的S-HA黏附能力明显下降,黏附量（CPM）随CPP-ACP浓度的升高而降低,且黏附抑制率均达100%。结论：CPP-ACP对黏性放线菌在S-HA上的黏附具有抑制作用,随CPP-ACP浓度的升高其抑制作用增强。