Following the successful expansion of noninvasive rejuvenative procedures for the face, a demand for nonsurgical rejuvenation options for nonfacial areas is also growing. Radiesse (Merz North America, Raleigh, N.C.) is a biocompatible, biodegradable, and resorbable biostimulatory filler containing calcium hydroxyapatite (CaHA) microspheres that can stimulate the endogenous production of collagen. It is a unique product that provides both volume replacement and collagen biostimulation as a primary mechanism of action.1 Initial augmentation is afforded by the presence of the carrier carboxymethylcellulose gel with the implant itself, but after approximately 9–12 months, the CaHA particles are degraded into calcium and phosphate and are eliminated through the renal system.2–6 A highly viscoelastic CaHA filler used undiluted or slightly diluted provides immediate correction that is gradually followed by new tissue formation through neocollagenesis, elastin production, angiogenesis, and dermal cell proliferation and is well suited for supraperiosteal and subdermal placement.6,7 The result is a long-lasting aesthetic improvement for ≥18 months with tight and elastic skin and increased skin thickness.6,7
When used in hyperdiluted form (ie, 1.5 mL of product plus ≥1.5 mL of diluent), Radiesse has a minimal or absent immediate volumizing effect due to carboxymethylcellulose gel dispersion, generating only long-term tissue remodeling by the CaHA microspheres and allowing its injection more superficially for dermal rejuvenation and the treatment of larger areas.3,7,8
This article presents consensus recommendations for hyperdiluted application of CaHA (Radiesse) in both facial and nonfacial areas.
A team of 10 experts in the fields of dermatology and plastic surgery with extensive experience with dermal fillers for facial and body rejuvenation convened in November 2017 for a full-day meeting in São Paulo, Brazil. A questionnaire distributed before the meeting and answered by the experts served as the basis for knowledge regarding medical management with this product and subsequent discussion. The meeting followed a structured consensus approach conducted by an experienced moderator.
“Strong consensus” was defined as agreement of ≥90%, whereas “consensus” was defined as approval ranging from 70% to 89% of all participants.
Suggestions and recommendations focused on providing directions for the use of hyperdiluted CaHA for the face, neck, décolletage, buttocks, thighs, arm, abdomen, knee, and elbow with detailed injection techniques, providing information on insertion points, dosages, and volumes for both needle and cannula injections and the number of required treatment sessions and intervals between them.
CaHA as a Biostimulatory Agent
Since 2004, evidence has indicated that the long-lasting effect of CaHA is secondary to a controlled inflammatory process that generates a predominantly fibroblastic reaction with replacement of the aqueous gel by a dense deposit of collagen.9 Berlin et al.4 observed that the main type of deposit is type 1 collagen, which is associated with improved mechanical properties of the skin, rather than type 3 collagen, which may be associated with fibrotic processes. It was also observed that CaHA produced more type 1 collagen and elastin and resulted in a greater proliferation of fibroblasts compared with hyaluronic acid.10 Couderot et al.11 noticed that in addition to fibroblast proliferation, CaHA also improved contractile function. Another study12 using CaHA in a dilution of 1:1 reported a peak for type 1 collagen production in samples treated with the hyperdiluted product alone or in combination with microfocused ultrasound with visualization (MFU-V). Yutskovskaya and Kogan7 observed through immunohistochemical analysis that even when used in large dilutions (1:2 to 1:6), Radiesse was effective in increasing the production of type 1 collagen and elastin 7 months after injection and found that it improved neck and décolletage laxity after 2 sessions with a 4-month interval. Pavicic13 observed soft tissue enlargement on magnetic resonance imaging examination 2.5 years after injection even after complete absorption of the CaHA particles. Clinically, Silvers et al.6 demonstrated an increase in skin thickness by 50% after 3 months of application, which was maintained in 91% of subjects during the 18-month evaluation period. Wasylkowski14 reported improved laxity and dermal thickness of the abdominal region, arms, and thighs with treatment as soon as 5 weeks after the procedure. Additionally, in 2015, Amselem15 observed improvement of arm laxity after 2 treatment sessions separated by 1 month. To conclude, in 2016 2 consensus meetings on combinations of procedures for the face and body suggested the use of hyperdiluted CaHA for dermal rejuvenation in large areas.3,8
Anesthesia and Dilutions
Pain management is an important issue to consider during aesthetic procedures. In 2009, the Food and Drug Administration approved a protocol for mixing CaHA with lidocaine at a concentration of 0.3% to improve patient comfort during injection.16 Many experts have developed techniques for using higher dilutions of CaHA, exploiting its collagen-stimulating effects to reduce skin laxity but without a volumizing effect.7 Dilutions can be titrated depending on the thickness of a patient’s skin and the degree of tissue laxity to ensure smooth product placement.7 Besides the dilution with lidocaine, some of the experts use topical anesthetics before the procedure.
Needle or Cannula
Needles have the advantage of extreme movement precision. On the other hand, cannulas cause less trauma and allow treatment of larger areas at the selected injection depth. Van Loghem et al.17 compared the precision difference between using needle and cannula for supraperiosteal filler placement in a cadaver study. Using the cannula resulted in product confinement to the deep anatomic layers, whereas the sharp needle technique resulted in material placement at multiple anatomic levels, from the periosteum to more superficial skin layers. In another study,18 10 fresh-frozen cephalic foreheads were injected with radiopaque material using both needles and cannulas, followed by an imaging study with fluoroscopy, computed tomography, and magnetic resonance imaging. In 60% of the injections using a needle, the implanted material changed its plane. Therefore, both studies concluded that using cannulas resulted in more precise placement of the injected material compared with needles. The authors of the consensus considered the possibility of using a blunt cannula or a sharp needle while bearing in mind that with the use of needles, there is a greater risk of superficial placement of the product; therefore, this procedure must be carried out very carefully.
General Consensus Statements on the Aims of Treatment With CaHA
According to consensus members, the following general guidelines for treatment with hyperdiluted CaHA were established. These statements reached strong consensus (agreement of ≥90%) among the expert group members (Table 1).
Soft tissue fillers offer a versatile, nonsurgical option for facial augmentation and contouring with a multitude of potential aesthetic applications.19 Volume loss and displacement of facial fat pads associated with ligament laxity cause skin drooping over a changing bony skeleton.20 Skin aging is related to increased activity of endogenous enzymes, among other factors, that promote the breakdown of collagen and elastin fibers.21,22 The properties of Radiesse provide it with substantial versatility and appropriateness for most aspects of facial rejuvenation, volume restoration, contouring, and skin tightening. In the authors’ experience, Radiesse diluted 1:1 can improve acne scars with minimal volume gain,23 and hyperdiluted use allows the health-care professional to offer patients more global treatment rather than local filling/volumization, as the product can be more easily spread on the skin, providing general skin tightening with progressive, natural, and discrete volume gains (Fig. 1).
Current Practice and Consensus Statements for Face Treatment
According to experts, the following guidelines for face treatment with CaHA were established. The product can be applied via retroinjection using cannulas and fanning or “asterisks” techniques with 2–4 entry points in each hemiface. With needles, the short linear threading technique is preferred (Fig. 2, Table 1). For face treatment, a dilution of 1:1 (1.5 mL of diluent) and usually 1 syringe per session are indicated (Table 1).
Neck and Décolletage
Rejuvenation procedures for the neck and décolletage have increased substantially in recent years. Although CaHA use for neck and décolletage treatment is off-label, its ability to induce extracellular matrix remodeling after subdermal injection may have a significant impact on reducing fine wrinkling, improving skin quality, and promoting local skin tightening.8,24 In one study,24 the authors described a technique for addressing horizontal neck lines by injecting hyperdiluted CaHA. Another trial7 evaluated the stimulating effects of diluted CaHA in subjects with skin laxity in the neck and décolletage. Twenty subjects received subdermal injections of CaHA with different dilutions of preserved saline at baseline and after 4 months according to skin thickness: 1:2 (normal skin), 1:4 (thin skin), and 1:6 (atrophic skin). Changes in skin mechanical properties were measured by ultrasound scanning and cutometry. Immunohistochemical data showed increased collagen and elastin production correlated with improved skin elasticity and pliability, as evaluated by cutometry, and ultrasound revealed increased dermal thickness. Subject and investigator satisfaction were high, and the procedure was well tolerated.
Current Practice and Consensus Statements for Neck Treatment
According to the experts, the following guidelines for neck treatment with CaHA were established. Product application can be performed by cannula via retroinjection with 3–5 entrance points (Fig. 3, Table 1). The short linear threading technique with a needle is an alternative technical option. For neck treatment, a dilution of 1:2 to 1:4 (3–6 mL of diluent) is usually indicated according to the patient’s skin thickness. Usually, 1 syringe per session is indicated (Table 1).
Current Practice and Consensus Statements for Décolletage Treatment
The following guidelines for CaHA décolletage treatment were established. It can be performed by the short linear threading technique with needle or via retroinjections with a cannula (Table 1). Generally, a dilution of 1:2 to 1:4 (3–6 mL of diluent) is indicated according to the patient’s skin thickness. Usually, 0.5–1 syringe per session is indicated (Table 1).
Buttocks and Thighs
Buttocks and thighs play an important role in maintaining or improving body contours. Individuals present with a wide range of complaints: generalized lipohypertrophy or lipohypotrophy, gluteal sagging, and cellulite-induced skin-surface irregularities, among other complaints.8,25–27 Increasing the strength and elasticity of the dermis and superficial fascia is an important aim when treating skin laxity and cellulite dimples. CaHA injections have unequivocally demonstrated collagen-stimulating properties and improvements in skin laxity in different aesthetic applications.12 When used with MFU, the biostimulatory effects of both treatments can be synergistic. One study12 evaluated the effects of MFU-V in combination with diluted Radiesse on cellulite appearance. Twenty women with cellulite and skin laxity on the thighs and buttocks were retrospectively enrolled. MFU-V was applied and immediately followed by subdermal CaHA injection (1.5 mL/buttock or thigh). Two independent evaluators reported statistically significant improvements 90 days after treatment for each item of the cellulite severity scale (P < 0.001). This combination treatment was considered effective for improving the appearance of cellulite and skin laxity. In the authors’ experience, the use of Radiesse alone (1.5 mL diluted with 6 mL of diluent) can also improve skin tightening and the appearance of cellulitis dimples.
Current Practice and Consensus Statements on Buttocks Treatment
The following guidelines for CaHA buttocks treatment were established. For buttocks skin laxity, the product can be applied with a cannula using the fanning or asterisks technique. The product should be applied mainly on the upper and lateral portions of the buttocks and on cellulite dimples (Figs. 4, Table 1). The short linear threading technique can also be used with needles. Usually, 1 syringe per buttock side per session is indicated. For buttocks skin laxity, the dilution may range from 1:1 to 1:4 (1.5–6 mL of diluent), whereas for cellulite dimples, lower dilutions (1:1 or 1:2) can be used (Table 1).
Current Practice and Consensus Statements on Thighs Treatment
The following guidelines for CaHA thigh treatment were established. The product can be applied to the inner and posterior thigh areas. The most frequently used technique for skin laxity is multiple cannula passages with fanning or asterisks injections (Table 1). The short linear threading technique can also be used with needles. Usually, 1 syringe per thigh area (inner or posterior) is indicated. The recommended CaHA dilution may range from 1:1 to 1:4 (1.5–6 mL of diluent) according to the degree of laxity (Table 1).
A body-vectoring technique using CaHA injections demonstrated notable reductions in skin flaccidity and increases in skin density and thickness in the abdomen and thighs 5 weeks after 1 treatment session.28 In 2017, Lapatina and Pavlenko29 evaluated the effectiveness of hyperdiluted CaHA for skin tightening in a case series of 10 women with skin laxity in the abdomen using ultrasound. CaHA diluted 1:4 with saline solution was injected subdermally using the linear threading technique, and the authors concluded that CaHA improved skin elasticity and increased abdominal dermal thickness after only a single treatment.
Current Practice and Consensus Statements of Abdomen Treatment
The following guidelines for CaHA abdomen treatment were established. Product application can be performed by both cannulas (the fanning or asterisk technique) and needles (short linear threading) with distribution across 4 abdominal quadrants (Fig. 5, Table 1). The short needle linear threading technique is particularly indicated for the periumbilical region. Product dilution can range from 1:1 to 1:4 (1.5–6 mL of diluent). Usually, one syringe is indicated for the upper abdominal region and another one is required for the lower half per session (Table 1).
As part of the natural aging process, the skin elasticity and firmness of the upper arms begin to decrease, increasing the visibility of some signs of aging, such as loose-hanging skin and fine wrinkles. In a prospective study,15 30 subjects received CaHA injections to the upper arms (1.5 mL/arm/visit) at 2 separate visits 1 month apart. Four months after the second treatment, flaccidity and volume showed significant improvements, with 77% of the subjects rating the improvements as good or great. In another study,29 improved skin elasticity of the arms was observed by cutometry after hyperdiluted 1:2 CaHA injection using the short linear threading technique (Fig. 6).
Current Practice and Consensus Statements on Arm Treatment
The generally recommended technique is retroinjection with a cannula with 2–4 fanning injections distributed along the inner arm (Fig.7, Table 1). Usually, 0.5–1 syringe per arm is indicated per session. The preferred dilution range is from 1:2 to 1:4 (3–6 mL of diluent) (Table 1).
Knees and Elbows
The knees and elbows show increased laxity with age. Although no clinical studies are available regarding CaHA treatment of these areas, in the authors’ experience, the local aged appearance can be improved by CaHA-generated collagen stimulation.
Current Practice and Consensus Statements on Knee Treatment
Product application can be performed via retroinjection with fanning with a cannula or by the short linear threading technique with needles. Treatment is suggested mainly for the region located above the patella. The recommended dose per session is 1 syringe in total (half per side) (Fig. 8, Table 1). No consensus was reached on the dilution used for the knees, but the authors presented their experiences with different dilutions ranging from 100% (1.5 mL) to 400% (6 mL).
Current Practice and Consensus Statements on Elbow Treatment
According to the experts, the following guidelines for CaHA elbow treatment were established. Product application can be performed by injecting the product with the short linear threading technique with a needle. The treatment is suggested mainly for the superior region of the elbow using 1 syringe in total (half per side) per session (Table 1).
Postprocedure, Adverse Events, and Follow-up Instructions
Exposure of the treated area to excessive sun and heat should be minimized for approximately 24 hours. A cold pack can be used to minimize tenderness, swelling, and bruising. During the treatment session, the treated area may need to be massaged to ensure that the CaHA is distributed evenly.30 If nodules develop, they can be treated with lidocaine or saline followed by vigorous massage. Nodules that do not resolve may respond to a series of ≥3 injections of 5-fluorouracil, triamcinolone, and lidocaine or 5-fluorouracil and lidocaine.31 Based on an extensive literature review of 5,081 treatments with CaHA by Kadouch,1 the product appears to have a good safety profile. In this study,1 45% of the reported nodules occurred in dynamic areas of the face. The current data suggest that if dynamic areas of the face were avoided, the incidence of CaHA nodules would be substantially lower. For facial augmentation, although some concerns about tissue necrosis and serious complications such as embolization have been noted in the literature, no vascular compromise has been observed by the authors on their practice and by Kadouch. However, caution should be the rule when treating the face and the high risky areas like the glabellar region and nose should be avoided. Regarding effect duration, it may depend on many factors, such as the patient’s age and metabolism, and the relative dynamic motion of the area in which the implant is placed. Published data show CaHA treatment results lasting up to 18–24 months.32
Current Practice and Consensus Statements
After an initial treatment cycle, one maintenance session is suggested within a range of 12–18 months. After the procedure, massage should be immediately performed by the physician to evenly distribute the product in the treated area. The patient can also be instructed to massage the injection site area 2 times a day for 3–7 days (Table 1).
Radiesse® (CaHA) is associated with a high and well-established safety profile and is a very effective agent for soft tissue augmentation of different face and body areas. The rising popularity of minimally invasive aesthetic procedures for the face over the last decade has led to greater demands for body rejuvenation interventions to minimize discrepancies between body and face appearance. The characteristic of Radiesse of long-term collagen stimulation reflects its substantial versatility. This consensus provides recommendations for the use of hyperdiluted CaHA as a biostimulatory agent for face and body rejuvenation and to improve skin quality and firmness.
The authors wish to thank Jessica Notario for providing medical writing and editorial assistance on behalf of Springer Healthcare.
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