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COSMETIC

Calcium Hydroxylapatite (Radiesse) forCorrection of the Mid- and Lower Face:Consensus Recommendations

Miles H. Graivier, M.D.Lawrence S. Bass, M.D.

Mariano Busso, M.D.Michael E. Jasin, M.D.Rhoda S. Narins, M.D.

Thomas L. Tzikas, M.D.

Roswell, Ga.; New York and WhitePlains, N.Y.; and Coconut Grove,

Tampa, and Delray Beach, Fla.

Summary: Restoring volume in the middle and lower portions of the face isbecoming an indispensable component of modern facial rejuvenation. Radiesse(BioForm Medical, San Mateo, Calif.) is an injectable filler material composedof synthetic calcium hydroxylapatite microspheres (30 percent) suspended in anaqueous carrier gel (70 percent). At present, Radiesse is indicated in the UnitedStates for correction of moderate to deep nasolabial folds and for correction ofthe signs of facial fat loss (lipoatrophy) in people with human immunodeficiencyvirus. Its off-label use in other facial aesthetic indications is widely reported inthe literature. The ability of Radiesse to provide immediate and durable effectshas fueled interest in its use for expanded aesthetic applications, particularly inthe middle and lower face. The authors’ consensus panel, consisting of a cross-section of experts in plastic surgery, facial plastic surgery, and dermatology, wasconvened to review the scientific literature and compare clinical experiencesregarding the use of calcium hydroxylapatite. This report describes the char-acteristic effects of aging in the middle and lower face and reviews the com-position of calcium hydroxylapatite, its safety and durability, and its appropriateuse in a variety of facial applications, including nasolabial folds, correction ofhuman immunodeficiency virus-associated lipoatrophy, augmentation of themalar, submalar, and zygomatic regions, and correction of oral commissuredefects, marionette lines, and prejowl sulcus. Recommendations for Radiesseuse in each area, including anesthesia, and injection techniques are provided.Measures for enhancing patient comfort, anticipating and minimizing potentialcomplications, and optimizing aesthetic results are also discussed. (Plast. Re-constr. Surg. 120 (Suppl.): 55S, 2007.)

Facial aging is a complex process characterizedby thinning of the epidermis, atrophy of sub-cutaneous fat layers, and a degree of bone re-

sorption, as well as progressive loss of organization ofelastic fibers and collagen and weakening of under-lying muscles.1 Fillers are increasingly being used innovel ways to address some of these age-associatedchanges throughout the face. Fillers approved foraesthetic uses include collagen products, such asZyderm, Zyplast, Cosmoderm, and Cosmoplast, and

hyaluronic acid products, such as Restylane, Perlane,Juvederm (Ultra and Ultra Plus), HylaForm, Hyla-Form Plus, and Captique. Longer-lasting syntheticfillers include poly-L-lactic acid (Sculptra), calciumhydroxylapatite (Radiesse), and polymethylmethac-rylate (ArteFill).2,3 Autologous fat can also be usedand requires surgical harvesting. Fillers such as Si-likon are used off label. Other novel approachesinclude the layering of several types of fillers andcombined use of fillers and botulinum toxin type A.4

Private practices; Institute of Reconstructive Plastic Surgery,New York University School of Medicine; and the Universityof Miami.Received for publication July 25, 2007; accepted July 31,2007.Reprinted and reformatted from the original article publishedwith the November 2007 Supplement issue (Plast ReconstrSurg. 2007;120 (Suppl 6S):55S–66S).Copyright ©2012 by the American Society of Plastic Surgeons

DOI: 10.1097/PRS.0b013e318250a9ee

FDA Status and Approved Uses: Radiesse isapproved by the FDA and indicated for sub-dermal implantation for the correction ofmoderate to severe facial wrinkles and folds,such as nasolabial folds. It is also intended forrestoration and/or correction of the signs offacial fat loss (lipoatrophy) in people withhuman immunodeficiency virus.

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Optimal aesthetic results can be achieved byunderstanding the unique profile of each of thesefillers. This article presents consensus recommen-dations on the use of calcium hydroxylapatite inthe middle and lower face. It includes cosmeticuses for aesthetic purposes and reconstructive usesfor persons living with facial lipoatrophy.

CALCIUM HYDROXYLAPATITEComposition

Radiesse (BioForm Medical, San Mateo, Calif.)is an injectable filler material composed of syntheticcalcium hydroxylapatite microspheres (30 percent)suspended in an aqueous carrier gel (70 percent).These uniform microspheres (25 to 45 �m) aresmooth in shape and are identical in composition tothe mineral portion of human bone and teeth.5–7

The components of calcium hydroxylapatite oc-cur naturally in the body and therefore are inher-ently biocompatible. Results from extensive in vitroand in vivo safety studies and in several retrospectivephysician reports, including toxicology assessments,standardized biocompatibility testing, and a 3-yearanimal study, demonstrate that injectable calciumhydroxylapatite is biocompatible, nontoxic, nonir-ritating, and nonantigenic.6 Patient sensitivity testingis not required before use.6

Applications of Calcium HydroxylapatiteCalcium hydroxylapatite has been used for

more than 20 years in various forms in surgery anddentistry.8 In the United States, injectable calciumhydroxylapatite has been used for several years forcorrection of oral/maxillofacial defects, for vocalfold augmentation, and as a radiographic tissuemarker. In 2006, Radiesse was approved in theUnited States for correction of moderate to severefacial wrinkles and folds, including the nasolabialfolds, and restoration and/or correction of thesigns of facial fat loss (lipoatrophy) in people withhuman immunodeficiency virus.

Nasolabial Folds Pivotal TrialThe use of Radiesse in nasolabial folds is based

on a multicenter, evaluator-blinded, randomized,bilateral (split face) comparison, in which 117 pa-tients with moderate to deep nasolabial folds re-ceived injections of calcium hydroxylapatite onone side and human collagen (Cosmoplast; Aller-gan, Irvine, Calif.) on the other.9 No significantdifference in adverse events was observed betweenthe calcium hydroxylapatite folds and the collagenfolds. At 6 months, significantly more patients whoreceived Radiesse (82 percent) showed improve-ment compared with control subjects (27 percent)

(p � 0.001), and the fold treated with Radiesse wasrated more improved in 79 percent of calciumhydroxylapatite patients, compared with 5 percentof control patients (p � .0001).9 The 12-monthresults of this study have been submitted for peer-reviewed publication.

Facial LipoatrophyA pivotal study of Radiesse for facial lipoatro-

phy in patients with human immunodeficiencyvirus receiving highly active antiretroviral therapyshowed that 100 percent of patients who receivedRadiesse to correct lipoatrophy reported signifi-cant improvement at 12 months. Eighty-four per-cent of these patients were very much improved ormuch improved, and the remaining 16 percentwere rated as improved. At 18 months, 91 percentof patients reported significant cosmetic improve-ment. Furthermore, quality-of-life data collectedat 12 months indicated that 100 percent of pa-tients found that Radiesse treatment had beenbeneficial.10

Mechanism of ActionWhen placed into soft tissue, Radiesse provides

immediate correction. Over time, the carrier gel isgradually absorbed and the calcium hydroxylapatiteparticles remain. Local histiocytic and fibroblasticresponse at the site appears to result in the produc-tion of new collagen around the microspheres.11

Preclinical canine studies (Fig. 1, above) have dem-onstrated histologically progressive integration ofcollagen fibers in and around the calcium hydroxy-lapatite microspheres up to 78 weeks after implan-tation (Fig. 1, center and below).

Further studies by Marmur et al.11 verified pre-clinical data by demonstrating dermal matrix in-tegration in biopsy samples harvested from hu-man volunteers. Interestingly, these histologicalfindings were accompanied by evidence of main-tained clinical improvement. There was no evi-dence of granuloma formation, ossification, orforeign body reactions at 1 month or 6 months.

DurabilityOver time, calcium hydroxylapatite particles

are broken down into calcium and phosphate ionsvia normal metabolic processes and eliminatedthrough the body’s normal excretory processes. Inone long-term animal study in the bladder neck,the particles remained intact at the site of injec-tion throughout the entire 3-year study period.12

Our experience with calcium hydroxylapatite usefor facial soft-tissue augmentation has shown re-sults lasting an average period of a year or more in

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most patients. In vivo, durability depends on fac-tors such as injection technique, site of materialplacement, and patient age and metabolism. The

reported longevity of aesthetic correction in theface ranges from 10 to 14 months, with an averagecorrection of 1 year in several studies.13,14 Other

Fig. 1. Scanning electron photomicrographs of (above, left) calcium hydroxylapatite microspheres in sodium carboxy-methylcellulose gel. Note the consistent, smooth, round shape (500�magnification). (Above, right) Calcium hydroxylapatitemicrospheres 30 months after implantation into bladder neck (350� magnification). Note the slowly dissolving particles.(Center and below) Histologic evaluation of calcium hydroxylapatite gel injected intradermally into canine skin over a periodof 4 to78 weeks. Sections stained with picrosirius red denote progressive collagen integration in and around the whitespherule calcium hydroxylapatite particles. Collagen deposition (center, right) 16 weeks, (below, left) 32 weeks, and (below,right) 78 weeks after calcium hydroxylapatite injection. (Photographs and illustrations courtesy of BioForm Medical, Inc.)

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sources report longevity of correction of 12 to 18months.5,15

PREPROCEDURE ANDPOSTPROCEDURE CONSIDERATIONS

Preoperative ProceduresAs with any aesthetic procedure, patient satis-

faction can be optimized by keeping in mind cer-tain treatment considerations and by carefully dis-cussing expectations with each patient whenplanning treatment. The patient’s medical historyshould also be reviewed, with a focus on use ofprescription and nonprescription medications, al-lergies, history of cold sores, presence of autoim-mune disorders, previous facial operations or der-mal filler treatments, and whether the patient ispregnant or nursing. Patients should also be askedabout history of herpesvirus infection, and treat-ment should be delayed if there are active lesions.Prophylactic antiviral therapy (e.g., acyclovir orvalacyclovir) may be prescribed for patients with ahistory of facial herpesvirus.16

Generally, patients should be told to avoid anymedications or supplements that might increasebleeding (e.g., salicylate drugs, nonsteroidal anti-inflammatory drugs, high doses of vitamin E, andcertain herbs).16 Anecdotal evidence of use of Ar-nica montana, bromelain, and 1% vitamin K1 (phy-tonadione) cream as prophylaxis against bruisinghas been reported.

Preinjection ProceduresBefore injection of any filler, the patient should

be counseled about what to expect in terms of anydiscomfort that may occur during or after injec-tion, possible adverse events, the results that he orshe can expect immediately after treatment, andthe likely durability of correction. Informed con-sent should be obtained.

Before beginning the actual procedure, the in-jection site may be identified with a washablemarker, with the patient sitting upright, to takeinto account the normal effect of gravity on thefacial contours. Pretreatment photographs may betaken after the marking.

Anesthesia and Other PatientComfort Measures

Patient comfort can be enhanced by the appro-priate use of anesthetics during injection of anyfiller; this may be especially true in the case of cal-cium hydroxylapatite and other fillers that are de-livered with a larger (e.g., 27-gauge) needle and/orinjected below the superficial layers of the skin. The

choice of infiltration, nerve block anesthesia, topicalanesthesia, infiltration of tiny amounts of local an-esthetic directly into the area, or some combina-tion thereof depends on the preferences of theoperator and the patient.17 The treatment siteshould be marked before administration of anes-thetic, as infiltration may distort the skin surfaceand an infraorbital nerve block may blunt or ef-face somewhat the nasolabial crease.17

Local InfiltrationDepending on the area to be filled, minimal

amounts of lidocaine 1% with epinephrine (1:100,000) may be infiltrated subcutaneously.18

Nerve BlockNerve blocks have the advantage of producing

complete anesthesia while causing minimal alter-ations in superficial contours.18 Blockade of theinfraorbital nerve can produce anesthesia extend-ing from the area of the lower lid, through thecheeks, and the upper lip. This branch of the tri-geminal nerve exits the maxilla through the in-fraorbital foramen. It most often can be foundapproximately 1 cm inferior to the orbital rim atthe midpupillary line.18 Infraorbital nerve blockscan be performed via direct transcutaneous infil-tration of anesthetic agent or via intraoral injec-tion up to 3 to 4 hours before filter injection,depending on type of anesthetic agent used. If theintraoral technique is used, patient comfort can beenhanced by applying topical anesthetic to theoral mucosa before injection.18

Sensation of the lower lip and chin is providedby the mental branch of the trigeminal nerve. Themental nerve may be blocked intraorally, in a fash-ion similar to that used for the infraorbital nerve.18

Nerve blocks in either location create profoundanesthesia within minutes of injection and maylast between 3 and 4 hours.18

In addition, some physicians elect to use facialcooling systems in lieu of blocks [e.g., the ZimmerChiller (Zimmer Medical Systems, Irvine, Calif.)or the Aqueduct Facemask (Aqueduct MedicalInc., San Francisco, Calif.)]. Topical anesthesiaand ice packs may also be used.

Injection TechniqueBecause of the relative viscosity of calcium hy-

droxylapatite, a 27-gauge, 0.5- or 11⁄4-inch needleis recommended. Calcium hydroxylapatite shouldordinarily be injected at the subdermal plane, es-pecially when filling creases, wrinkles, and deeplines. Injection depth can be just in the subcuta-neous space but superior to the periosteum. Theinjection can also be placed on the periosteum if


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the intent is to augment the facial bony skeleton.Placement on the periosteum will not stimulatebone growth in the area.

Depending on the area being treated, calciumhydroxylapatite may be injected in a retrogradefashion using a linear, threading, fanning, and/orcrosshatching technique. Supraperiosteal place-ment usually entails a bolus or depot type of injec-tion, followed by massage or molding of material todesired effect. Injection volumes vary with the loca-tion of the treatment site, the size of the area beingtreated, and individual patient characteristics.

In our experience, a lesser volume of calciumhydroxylapatite may be required to provide thesame degree of correction as hyaluronic acid andcollagen. Two studies support the finding ofsmaller volumes in calcium hydroxylapatite thanin several other soft-tissue fillers. For example, ina split-face study of calcium hydroxylapatite versuscollagen for the nasolabial folds, on average, thecollagen-treated side of the face required twice thevolume of material (2.35 ml) to produce optimalcorrection as compared with the calcium hydroxy-lapatite-treated side (1.22 ml) (p � 0.0001).9 Inanother study, approximately 30 percent less vol-ume of calcium hydroxylapatite was required thanhyaluronic acid for full correction of the nasola-bial folds.19

Massage to ensure no palpable lumps may beappropriate. Some physicians routinely mold theinjected area after treatment; other physicians re-serve molding for correction of undesired shapesin an effort to avoid the amplification of edemaand erythema that molding sometimes creates.

Posttreatment CarePosttreatment photographs may be taken as

soon as the injections have been completed andthe washable markings removed. The typical pro-tocol for posttreatment care involves immediateplacement of ice onto the injected areas to reduceand limit tissue edema and ecchymosis. Some ofthe authors recommend to their patients that theyremain upright for the remainder of the day andsleep with the head elevated to reduce the degreeof edema. In our respective practices, patient fol-low-up visits are typically scheduled 2 to 12 weekslater to document any adverse events and providerefinement treatments as necessary.

Adverse EffectsThe duration and severity of adverse events

associated with calcium hydroxylapatite gel arecomparable to those seen with other filler agents

(e.g., collagen and hyaluronic acids) and chieflyassociated with the delivery of the material ratherthan the material itself. In our experience, red-ness, swelling, and bruising are the most com-monly reported adverse events and are widely seenwith nearly any soft-tissue filler.20 Further, theseevents resolve relatively soon after the injectionprocedure (1 to 2 weeks). Bruising and swellingcan be minimized by treating the tissue with careand taking time to provide necessary cosmetic aug-mentation. There have been no reported granu-lomas in the injected areas nor migration of cal-cium hydroxylapatite gel to other parts of the face.In addition, we have no reason to believe thatcalcium hydroxylapatite, when placed in soft tis-sue, exhibits any osteogenic properties. In the pre-viously cited study of nasolabial folds, there was nosignificant difference in adverse events betweenthe folds treated with calcium hydroxylapatite andthose treated with collagen, and there was no ev-idence of granuloma formation with either mate-rial. In addition, only one nodule was noted in thecalcium hydroxylapatite folds, compared with threein the collagen-treated folds.9

CALCIUM HYDROXYLAPATITE FORCORRECTION IN THE MIDFACE

In the midface area, biometric volume lossplays just as important a role in the appearance ofaging as the development of wrinkles and skinlaxity. As many clinicians and patients have ob-served firsthand, simply redraping or lifting skinhere is often not sufficient to restore a youthfulappearance. Likewise, superficial fill often leavescorrection incomplete. Use of a volumizing fillersuch as calcium hydroxylapatite in this area canimmediately restore volume as well as fill and cor-rect specific creases and defects.

Augmentation of the Malar andSubmalar Regions

With age, volume loss and the descent of malarfat pads may lead to flattening or dropping of thefront of the cheek and distribution of excess skininto adjacent areas. Younger patients who presentwith prominent nasojugal folds or midface soft-tissue or bony deficiency are also good candidatesfor midface augmentation. Augmentation of themalar and submalar regions can reduce the shad-owing effect that aging and deficiency exert onthis area, reduce skin surplus from the nasolabial,suborbital, marionette, and jowl regions, and re-balance midface proportions. Because cheek aug-mentation may affect the face as a whole, malar/


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submalar augmentation should be performed firstwhen treating multiple facial areas.14 Although itis not an approved indication at this time, cheekaugmentation with calcium hydroxylapatite hasbeen reported in the literature.7,14,14,21

Procedures and Techniques for Malar andSubmalar Augmentation

AnesthesiaTo enhance patient comfort during filler in-

jection, administration of an infraorbital nerveblock is recommended. Only a small amount ofanesthetic, 0.2 to 0.3 ml per side, followed by mas-sage, is necessary.14 Some operators use infiltra-tion to provide additional anesthesia during theprocedure.

Injection TechniqueIf the transcutaneous technique is being used,

the area should be approached inferiorly to su-periorly with a plan in mind for sequential injec-tion in the malar area, selecting insertion pointsjust lateral to the nasolabial fold and at the zygomaand then proceeding with injection into the sub-malar soft tissue. The injector may start superfi-cially and then work deep, or vice versa, depend-ing on the injector’s preference. Injections can bestarted in the deep dermis, or above or on theperiosteum, with crisscrossing linear thread injec-tions. Crosshatching and layering of material inthe subdermal and subcutaneous planes providestructural support and projection. The fanning/threading pattern into the malar area roughly ap-proximates the shape of an inverted right triangle.Care should be taken not to inject calcium hy-droxylapatite into the soft tissue above the orbitalrim, as the orbicularis oculi contraction may causeclumping of particulate materials. Although cal-cium hydroxylapatite has been used for fill of thetear trough, hyaluronic acid products may bemore appropriate for this application.

Another technique, the intraoral-supraperios-teal approach, is similar to infraorbital and mentalnerve blocks for placement of Radiesse. Infraor-bital cheek flattening is more common than malarhypoplasia in the aging population. The intraoralinjections lessen the need for transcutaneous fill-ing of the nasolabial fold and marionette lines andmay provide equal or better results. As a conse-quence, less bruising and swelling are likely thanwith transcutaneous injections.

For best aesthetic results, the entire malar areashould be augmented, not merely the areas wheresoft-tissue deficiency is most obvious. Busso andKarlsberg14 recommend extending the correction

laterally and slightly inferiorly along the zygoma toprovide better support for crow’s feet and to en-hance the triangular shape of the face. A secondpass of injection to create a crosshatch is usuallynot required for the zygoma. As is the case with themalar region, injection should not extend beyondthe orbital rim (Fig. 2).

Figure 3 shows a 55-year-old woman beforeand 1 month after injection of 1.8 ml of calciumhydroxylapatite for infraorbital/medial cheek aug-mentation and 0.6 ml for perioral correction.

Facial Augmentation in Human ImmunodeficiencyVirus-Associated Lipoatrophy

Human immunodeficiency virus-associated li-poatrophy can be quite severe and affect substan-tial areas and thus may benefit most from fillerswith volumizing properties. The areas most oftenaffected are the temporal and infraorbital regions,the submalar and malar regions, and the nasola-bial folds. In addition to the previously describedregistrational trial,10 the use of calcium hydroxy-lapatite for human immunodeficiency virus-asso-ciated facial lipoatrophy has also been reportedelsewhere in the literature.7,14,22,23

AnesthesiaAdequate anesthesia should be provided. Typi-

cally, an infraorbital block, a “mini-block,” and/or

Fig. 2. Areas of injection for malar correction (left) and malar/medial correction (right). (Illustration courtesy of BioForm Med-ical, Inc.)


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field infiltration is used, depending on operator andpatient preference.

Injection TechniqueUsing a 25- or 27-gauge, 11⁄4-inch needle, cal-

cium hydroxylapatite is deposited into the deepdermis of the submalar region using a fanningtechnique (Fig. 4). To provide adequate volume,additional threads may be layered into a deeperplane.

While the chief area of concern for humanimmunodeficiency virus lipoatrophy patients istypically the submalar region, we find that extend-ing correction to the malar eminence and peri-orbital region may provide more complete cor-rection. The volume of material injected dependson the extent or severity of disease.

Figure 5 shows a 37-year-old man at baselineand 1 month after injection of 7.2 ml of calcium

hydroxylapatite for correction of human immu-nodeficiency virus-associated facial lipoatrophy.

CALCIUM HYDROXYLAPATITE FORCORRECTION IN THE LOWER FACE

Calcium hydroxylapatite may be particularlyapropos for the lower face because of its ability toreliably fill lines and creases of varying depth andreplace lost volume. Areas of common applicationin the lower face area include the nasolabial folds,oral commissure, marionette lines, prejowl sulcus,labiomental crease, lateral chin (perimental hol-lows), and the mandible.

Augmentation of the Nasolabial FoldsTypically, nasolabial fold creases begin to ap-

pear in individuals in their 20s and deepen asaging continues. Their appearance is exacerbatedby the descent of fat from the malar and medialcheek pads. We find calcium hydroxylapatite to beparticularly appropriate for these folds because itcan be injected deep into the dermal plane tosplint the line as well as deeper in the subdermalplane to provide structural support to the fold. Itprovides relative durability despite the dynamicmotion of this area.

Procedures and Techniques for Correction ofNasolabial Folds

AnesthesiaAnesthesia techniques used when treating the

nasolabial folds vary depending on operator and

Fig. 3. A 55-year-old woman before and 1 month after injectionof 1.8ml of calcium hydroxylapatite for infraorbital/medial cheekaugmentation and 0.6 ml for perioral correction. (Photographcourtesy of Michael Jasin, M.D.)

Fig. 4. Deposition of calcium hydroxylapatite for human immu-nodeficiency virus-associated lipoatrophy. (Figure adapted froman animation, courtesy of BioForm Medical, Inc.)


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patient preference. At a minimum, a topical an-esthetic cream and preinjection cooling may beappropriate. Local infiltration or infraorbital blockmay also be considered.

Injection TechniqueFor correction of the nasolabial folds, calcium

hydroxylapatite gel is injected into the subdermalplane with a 27-gauge, 11⁄4-inch needle using alinear threading and fanning technique. In ourexperience, depositing calcium hydroxylapatitegel in a V or triangular shape can provide greatersupport in this area and enhance correction of theentire fold.24 Crosshatching the area with trans-versely oriented threads of filler helps to flattenthe skin of the upper part of the fold. Because the

gel provides 1:1 correction, overcorrection is notnecessary.

DurabilityIn an open-label study of 22 patients who re-

ceived calcium hydroxylapatite for the nasolabialfolds, 14 patients reported a duration of cosmeticallysignificant correction longer than 12 months, andfour reported correction lasting 10 to 12 months(four patients were lost to follow-up).24 No patientreported correction lasting less than 10 months. Inthis study, the most commonly reported adverseevents were redness, swelling, and bruising. Rednessand swelling resolved without treatment within 1 to5 days and bruising within 4 to 10 days (with oneexception lasting 15 days). There were no visiblenodules or granuloma formation.

In addition, two-thirds of the patients (six outof nine) in the study who had been injected withhyaluronic acid in the past preferred calcium hy-droxylapatite because of its longevity of effect andbecause the patients found the results to be more“aesthetically pleasing.”24

Published Studies of CalciumHydroxylapatite for Correction ofNasolabial Folds

Table 1 lists several published studies in whichpatients received calcium hydroxylapatite for cor-rection of nasolabial folds.7,9,15,21,24–26

Table 1. Studies of Calcium Hydroxylapatite for theNasolabial Folds

StudyNo. of

PatientsReported Duration of

Correction

Tzikas, 20047 60 At 6-month follow-up, 88%of patients reported goodor excellent satisfaction*

Jacovella et al.,200625

24 At 18-month follow-up,100% of patientsreported very good(�83%), good (8.3%), oracceptable (8.3%) results

Cuevas et al.,200621

127 At 1-year follow-up, 75% ofpatients and 100% ofphysicians reportedcomplete satisfaction*

Alam and Yoo,200724

22 14 of 18 patients reportedcosmetically significantcorrection lasting �1 year

Smith et al.,20059

117 N/A

Jansen andGraivier,200615

395 At 12- to 24-month follow-up,patients estimated onaverage that 57%correction wasmaintained*

Sadick et al.,in press26

86 Up to 12 months*

N/A, not applicable.*Reflects all treatment sites, including the nasolabial folds.

Fig. 5. A37-year-old man at baseline and 1 month after injectionof 7.2 ml of calcium hydroxylapatite for correction of human im-munodeficiency virus-associated facial lipoatrophy. (Photo-graph courtesy of Todd Owsley, M.D.)


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Figure 6 shows a 63-year-old man before andimmediately after injection of 2.2 ml of calciumhydroxylapatite for correction of nasolabial foldsand 0.7 ml for the medial cheek.

Chin and Lip SupportEvaluation of the chin and lip position should

include overall assessment of the diffuse volumedeficit as well as the individual lines and depres-sions. Often individual areas, such as the mario-nette lines and the corners of mouth, cannot beadequately addressed without adding additionalsupport by augmenting the prejowl and perimen-tal areas.

Oral CommissureAtrophy of soft tissue at the oral commissure

causes inversion and results in “parenthesis” lines.The corners of the mouth can descend, giving a

negative curve to the lip. The loss of volume at thecommissure includes the labial mucosal side aswell as the cutaneous portion, which dissolves intothe marionette line.27 The appearance of the oralcommissure can often be ameliorated by theskilled physician with the appropriate use of fillers,including calcium hydroxylapatite. Correction ofthis area requires volume to fill the lines and foldsas well as to provide a lifting effect to the cornersof the mouth. Calcium hydroxylapatite for the oralcommissure has been widely reported in theliterature.7,17,25,28,29

Procedure and TechniqueBefore injection, the area should be anesthe-

tized via infiltration or block of the mental nerve.Threads of small amounts of calcium hydroxylapa-tite (approximately 0.05 ml) are then placed in afanning and crisscross pattern into the deep der-mis inferior to the corner of the mouth and ex-tending into the contiguous marionette line.Crisscrossing threads are then placed in deeperlayers to add bulk, splint the depression, and el-evate the corner of the mouth. The mucosa of thecommissure should also be augmented in a Cshape, as this corrects the inversion and elevatesthe corner of mouth.17

A hyaluronic acid or collagen product carriesless risk of palpability or nodularity in this area. Ifthey are deeper, individual “parenthesis lines” canbe filled with calcium hydroxylapatite, but the su-perficial component also needs a hyaluronic acidor collagen.

Figure 7 shows a 56-year-old woman beforeand 1 month after injection of 1.4 ml of calciumhydroxylapatite for correction of the oral commis-sure, marionette lines, and prejowl sulcus, 1.0 mlfor correction of perioral rhytides, and 1.2 ml forcorrection of nasolabial folds.

Marionette LinesSuccessful use of calcium hydroxylapatite for

the marionette lines has been reported in theliterature.7,15,17,21 These lines tend to be difficult toefface completely. Some panel members recom-mend layering of fillers for this area. Typically,calcium hydroxylapatite is injected at the subder-mal level, with Restylane or another hyaluronicacid-based filler layered above it.17,30

Procedure and TechniqueAnesthesia for this area is provided by infiltra-

tion or block of the mental nerve. Calcium hy-droxylapatite is then injected into the dermal andsubdermal planes, again with the use of fanningand crisscrossing threads in each of these layers.

Fig. 6. A63-year-old man before and immediately after injectionof 2.2 ml of calcium hydroxylapatite for correction of nasolabialfolds and 0.7 ml for the medial cheek. (Photograph courtesy ofMichael Jasin, M.D.)


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After injection, the area should be gently mas-saged and contoured to ensure that there are nopalpable lumps. Use of conservative volumes ofcalcium hydroxylapatite is recommended in thisarea, along with a staged, multiple-injection-ses-sions approach.

Figure 8 shows a 73-year-old woman beforeand 3 months after injection of 3.9 ml of calciumhydroxylapatite for correction of the cheeks, na-solabial folds, and marionette lines.

Prejowl Sulcus, Perimental Hollows, LabiomentalCrease, and Chin Projection

The development of the prejowl sulcus, peri-mental hollows, labiomental crease, chin pad pto-sis, and deflation reflects bone loss, tissue atrophy,and descent of soft tissue around fixed folds (i.e.,

nasolabial, marionette). Reinflation of the entirechin complex may include some or all of theseareas and may also be necessary to provide a baseof support for the corners of the mouth. Filling theprejowl area also provides camouflage of the jowlby smoothing the mandibular border, whereas fill-ing the perimental hollows and labiomentalcrease adds additional support for the area.

Procedure and TechniqueTo correct the prejowl sulcus, calcium hy-

droxylapatite is placed in the deep dermis and/orsubdermal plane. The key to correction is re-cre-ation of the inferior border of the mandible ratherthan simple volume fill along the body of themandible. In addition, the facial vein must beavoided to prevent substantial ecchymosis. For thebest aesthetic results and to create a smooth cor-rection that blends well with the adjacent chin andjaw contours, the material should be injected in-crementally and gently massaged. Calcium hy-droxylapatite can be used along the periosteum ofthe inferior mandible to add volume to the atro-phic jawline.

Fig. 7. A 56-year-old woman before and 1 month after injectionof 1.4 ml of calcium hydroxylapatite to correct the oral commis-sure, marionette lines, and prejowl sulcus, 1.0 ml to correct theperioral rhytides, and 1.2 ml to correct the nasolabial folds. (Pho-tograph courtesy of Michael Jasin, M.D.)

Fig. 8. A 73-year-old woman before and 3 months after injectionof 3.9 ml of calcium hydroxylapatite to correct the cheeks, naso-labial folds, and marionette lines. (Photograph courtesy ofThomas Tzikas, M.D.)


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Intraoral, supraperiosteal bolus placement ofRadiesse is another approach. This placementprovides correction with minimal bruising andswelling. This approach also gives correction tothe marionette lines, reducing the need for sub-dermal/dermal injections.

Figure 9 shows a 60-year-old woman beforeand 16 months after injection of 1.6 ml of calciumhydroxylapatite for correction of the prejowl sul-cus and 1.0 for correction of the oral commissure.

DISCUSSIONVolume enhancement is rapidly becoming an

indispensable component of modern facial reju-venation. It is ideal for the patient who is not yetinclined to procedures involving surgical lifting. Itis equally useful for patients who have alreadyundergone surgical lifting. Volume enhancementdoes require judicious use of the appropriateproduct, however. It is our opinion that calciumhydroxylapatite can be the filler of choice for pa-tients in whom subdermal fill and/or volumizingis needed. Depth of injection and injection vol-umes tend to be site-dependent.

Calcium hydroxylapatite provides immediatecorrection of lines and wrinkles and appears torestore lost volume. We have found it to be par-ticularly useful for filling areas such as the naso-labial folds, marionette lines, oral commissure,

and prejowl sulcus and for augmenting the malarand submalar areas. As such, it can play a key rolein nonsurgical rejuvenation of the middle andlower face, an area where botulinum toxin type Ahas limited utility.

Clinicians who are in the early stages of adop-tion should keep several considerations in mindwhen using calcium hydroxylapatite. First, ourown experience, supported by the clinical litera-ture, suggests that smaller volumes are needed toprovide the same degree of correction, comparedwith collagen and hyaluronic acid-based products.It should also be noted that calcium hydroxylapa-tite provides 1:1 correction. Nonetheless, someoperators prefer to bring patients gradually to fullcorrection or to offer follow-up injections 2 weeksto 3 months after initial treatment. Finally, whenlayering calcium hydroxylapatite with other fillers,such as hyaluronic acid, smaller volumes of cal-cium hydroxylapatite than usual may be needed.30

Our experience has also shown calcium hy-droxylapatite to be safe. This observation is borneout by the clinical literature, which demonstratesthat the most common adverse events associatedwith the material are similar to those observed withother fillers, tend to be short-lived, and resolve with-out treatment. Importantly, there is no evidence ofgranuloma formation or osteogenesis when calciumhydroxylapatite is placed in soft tissue. A recent studyby Carruthers et al.31 also confirmed that use of cal-cium hydroxylapatite does not interfere with theinterpretation of radiography.

In conclusion, calcium hydroxylapatite hasemerged as a versatile, durable, and safe durablefiller whose use is anticipated to grow as moreclinicians and patients gain firsthand experiencewith it.

Miles H. Graivier, M.D.North Atlanta Plastic Surgery

1295 Hembree Road, Suite 100Roswell, Ga. 30076

[email protected]

DISCLOSURESDrs. Graivier, Bass, Busso, Jasin, Narins, and Tzikas

are members of the BioForm Medical Clinical AdvisoryBoard. Drs. Graivier, Bass, Busso, Jasin, and Tzikas havereceived compensation for educational presentations aboutRadiesse. Drs. Busso, Narins, and Tzikas have stock op-tions in BioForm Medical.

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Fig. 9. A 60-year-old woman before and 16 months after injec-tion of 1.6 ml of calcium hydroxylapatite to correct the prejowlsulcus and 1.0 to correct the oral commissure and lateral chin.(Photograph courtesy of Michael Jasin, M.D.)


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3. Murray, C. A., Zloty, D., and Warshawski, L. The evolution ofsoft tissue fillers in clinical practice. Dermatol. Clin. 23: 343,2005.

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