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Calcium Hydroxylapatite (Radiesse) For Correction of The Mid-And Lower Face: Consensus Recommendations
Calcium Hydroxylapatite (Radiesse) For Correction of The Mid-And Lower Face: Consensus Recommendations
F
acial aging is a complex process characterized hyaluronic acid products, such as Restylane, Perlane,
by thinning of the epidermis, atrophy of sub- Juvederm (Ultra and Ultra Plus), HylaForm, Hyla-
cutaneous fat layers, and a degree of bone re- Form Plus, and Captique. Longer-lasting synthetic
sorption, as well as progressive loss of organization of fillers include poly-L-lactic acid (Sculptra), calcium
elastic fibers and collagen and weakening of under- hydroxylapatite (Radiesse), and polymethylmethac-
lying muscles.1 Fillers are increasingly being used in rylate (ArteFill).2,3 Autologous fat can also be used
novel ways to address some of these age-associated and requires surgical harvesting. Fillers such as Si-
changes throughout the face. Fillers approved for likon are used off label. Other novel approaches
aesthetic uses include collagen products, such as include the layering of several types of fillers and
Zyderm, Zyplast, Cosmoderm, and Cosmoplast, and combined use of fillers and botulinum toxin type A.4
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Volume 129, Number 5S • Calcium Hydroxylapatite (Radiesse)
Optimal aesthetic results can be achieved by (p ⬍ 0.001), and the fold treated with Radiesse was
understanding the unique profile of each of these rated more improved in 79 percent of calcium
fillers. This article presents consensus recommen- hydroxylapatite patients, compared with 5 percent
dations on the use of calcium hydroxylapatite in of control patients (p ⬍ .0001).9 The 12-month
the middle and lower face. It includes cosmetic results of this study have been submitted for peer-
uses for aesthetic purposes and reconstructive uses reviewed publication.
for persons living with facial lipoatrophy. Facial Lipoatrophy
A pivotal study of Radiesse for facial lipoatro-
CALCIUM HYDROXYLAPATITE phy in patients with human immunodeficiency
Composition virus receiving highly active antiretroviral therapy
Radiesse (BioForm Medical, San Mateo, Calif.) showed that 100 percent of patients who received
is an injectable filler material composed of synthetic Radiesse to correct lipoatrophy reported signifi-
calcium hydroxylapatite microspheres (30 percent) cant improvement at 12 months. Eighty-four per-
suspended in an aqueous carrier gel (70 percent). cent of these patients were very much improved or
These uniform microspheres (25 to 45 m) are much improved, and the remaining 16 percent
smooth in shape and are identical in composition to were rated as improved. At 18 months, 91 percent
the mineral portion of human bone and teeth.5–7 of patients reported significant cosmetic improve-
The components of calcium hydroxylapatite oc- ment. Furthermore, quality-of-life data collected
cur naturally in the body and therefore are inher- at 12 months indicated that 100 percent of pa-
ently biocompatible. Results from extensive in vitro tients found that Radiesse treatment had been
and in vivo safety studies and in several retrospective beneficial.10
physician reports, including toxicology assessments,
standardized biocompatibility testing, and a 3-year Mechanism of Action
animal study, demonstrate that injectable calcium When placed into soft tissue, Radiesse provides
hydroxylapatite is biocompatible, nontoxic, nonir- immediate correction. Over time, the carrier gel is
ritating, and nonantigenic.6 Patient sensitivity testing gradually absorbed and the calcium hydroxylapatite
is not required before use.6 particles remain. Local histiocytic and fibroblastic
response at the site appears to result in the produc-
Applications of Calcium Hydroxylapatite tion of new collagen around the microspheres.11
Calcium hydroxylapatite has been used for Preclinical canine studies (Fig. 1, above) have dem-
more than 20 years in various forms in surgery and onstrated histologically progressive integration of
dentistry.8 In the United States, injectable calcium collagen fibers in and around the calcium hydroxy-
hydroxylapatite has been used for several years for lapatite microspheres up to 78 weeks after implan-
correction of oral/maxillofacial defects, for vocal tation (Fig. 1, center and below).
fold augmentation, and as a radiographic tissue Further studies by Marmur et al.11 verified pre-
marker. In 2006, Radiesse was approved in the clinical data by demonstrating dermal matrix in-
United States for correction of moderate to severe tegration in biopsy samples harvested from hu-
facial wrinkles and folds, including the nasolabial man volunteers. Interestingly, these histological
folds, and restoration and/or correction of the findings were accompanied by evidence of main-
signs of facial fat loss (lipoatrophy) in people with tained clinical improvement. There was no evi-
human immunodeficiency virus. dence of granuloma formation, ossification, or
Nasolabial Folds Pivotal Trial foreign body reactions at 1 month or 6 months.
The use of Radiesse in nasolabial folds is based
on a multicenter, evaluator-blinded, randomized, Durability
bilateral (split face) comparison, in which 117 pa- Over time, calcium hydroxylapatite particles
tients with moderate to deep nasolabial folds re- are broken down into calcium and phosphate ions
ceived injections of calcium hydroxylapatite on via normal metabolic processes and eliminated
one side and human collagen (Cosmoplast; Aller- through the body’s normal excretory processes. In
gan, Irvine, Calif.) on the other.9 No significant one long-term animal study in the bladder neck,
difference in adverse events was observed between the particles remained intact at the site of injec-
the calcium hydroxylapatite folds and the collagen tion throughout the entire 3-year study period.12
folds. At 6 months, significantly more patients who Our experience with calcium hydroxylapatite use
received Radiesse (82 percent) showed improve- for facial soft-tissue augmentation has shown re-
ment compared with control subjects (27 percent) sults lasting an average period of a year or more in
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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 hydroxylapatite
microspheres 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 period
of 4 to78 weeks. Sections stained with picrosirius red denote progressive collagen integration in and around the white
spherule 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.)
most patients. In vivo, durability depends on fac- reported longevity of aesthetic correction in the
tors such as injection technique, site of material face ranges from 10 to 14 months, with an average
placement, and patient age and metabolism. The correction of 1 year in several studies.13,14 Other
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Volume 129, Number 5S • Calcium Hydroxylapatite (Radiesse)
sources report longevity of correction of 12 to 18 choice of infiltration, nerve block anesthesia, topical
months.5,15 anesthesia, infiltration of tiny amounts of local an-
esthetic directly into the area, or some combina-
PREPROCEDURE AND tion thereof depends on the preferences of the
POSTPROCEDURE CONSIDERATIONS operator and the patient.17 The treatment site
Preoperative Procedures should be marked before administration of anes-
As with any aesthetic procedure, patient satis- thetic, as infiltration may distort the skin surface
faction can be optimized by keeping in mind cer- and an infraorbital nerve block may blunt or ef-
tain treatment considerations and by carefully dis- face somewhat the nasolabial crease.17
cussing expectations with each patient when Local Infiltration
planning treatment. The patient’s medical history Depending on the area to be filled, minimal
should also be reviewed, with a focus on use of amounts of lidocaine 1% with epinephrine (1:
prescription and nonprescription medications, al- 100,000) may be infiltrated subcutaneously.18
lergies, history of cold sores, presence of autoim- Nerve Block
mune disorders, previous facial operations or der- Nerve blocks have the advantage of producing
mal filler treatments, and whether the patient is complete anesthesia while causing minimal alter-
pregnant or nursing. Patients should also be asked ations in superficial contours.18 Blockade of the
about history of herpesvirus infection, and treat- infraorbital nerve can produce anesthesia extend-
ment should be delayed if there are active lesions. ing from the area of the lower lid, through the
Prophylactic antiviral therapy (e.g., acyclovir or cheeks, and the upper lip. This branch of the tri-
valacyclovir) may be prescribed for patients with a geminal nerve exits the maxilla through the in-
history of facial herpesvirus.16 fraorbital foramen. It most often can be found
Generally, patients should be told to avoid any approximately 1 cm inferior to the orbital rim at
medications or supplements that might increase the midpupillary line.18 Infraorbital nerve blocks
bleeding (e.g., salicylate drugs, nonsteroidal anti- can be performed via direct transcutaneous infil-
inflammatory drugs, high doses of vitamin E, and tration of anesthetic agent or via intraoral injec-
certain herbs).16 Anecdotal evidence of use of Ar- tion up to 3 to 4 hours before filter injection,
nica montana, bromelain, and 1% vitamin K1 (phy- depending on type of anesthetic agent used. If the
tonadione) cream as prophylaxis against bruising intraoral technique is used, patient comfort can be
has been reported. enhanced by applying topical anesthetic to the
oral mucosa before injection.18
Preinjection Procedures Sensation of the lower lip and chin is provided
Before injection of any filler, the patient should by the mental branch of the trigeminal nerve. The
be counseled about what to expect in terms of any mental nerve may be blocked intraorally, in a fash-
discomfort that may occur during or after injec- ion similar to that used for the infraorbital nerve.18
tion, possible adverse events, the results that he or Nerve blocks in either location create profound
she can expect immediately after treatment, and anesthesia within minutes of injection and may
the likely durability of correction. Informed con- last between 3 and 4 hours.18
sent should be obtained. In addition, some physicians elect to use facial
Before beginning the actual procedure, the in- cooling systems in lieu of blocks [e.g., the Zimmer
jection site may be identified with a washable Chiller (Zimmer Medical Systems, Irvine, Calif.)
marker, with the patient sitting upright, to take or the Aqueduct Facemask (Aqueduct Medical
into account the normal effect of gravity on the Inc., San Francisco, Calif.)]. Topical anesthesia
facial contours. Pretreatment photographs may be and ice packs may also be used.
taken after the marking.
Injection Technique
Anesthesia and Other Patient Because of the relative viscosity of calcium hy-
Comfort Measures droxylapatite, a 27-gauge, 0.5- or 11⁄4-inch needle
Patient comfort can be enhanced by the appro- is recommended. Calcium hydroxylapatite should
priate use of anesthetics during injection of any ordinarily be injected at the subdermal plane, es-
filler; this may be especially true in the case of cal- pecially when filling creases, wrinkles, and deep
cium hydroxylapatite and other fillers that are de- lines. Injection depth can be just in the subcuta-
livered with a larger (e.g., 27-gauge) needle and/or neous space but superior to the periosteum. The
injected below the superficial layers of the skin. The injection can also be placed on the periosteum if
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the intent is to augment the facial bony skeleton. (e.g., collagen and hyaluronic acids) and chiefly
Placement on the periosteum will not stimulate associated with the delivery of the material rather
bone growth in the area. than the material itself. In our experience, red-
Depending on the area being treated, calcium ness, swelling, and bruising are the most com-
hydroxylapatite may be injected in a retrograde monly reported adverse events and are widely seen
fashion using a linear, threading, fanning, and/or with nearly any soft-tissue filler.20 Further, these
crosshatching technique. Supraperiosteal place- events resolve relatively soon after the injection
ment usually entails a bolus or depot type of injec- procedure (1 to 2 weeks). Bruising and swelling
tion, followed by massage or molding of material to can be minimized by treating the tissue with care
desired effect. Injection volumes vary with the loca- and taking time to provide necessary cosmetic aug-
tion of the treatment site, the size of the area being mentation. There have been no reported granu-
treated, and individual patient characteristics. lomas in the injected areas nor migration of cal-
In our experience, a lesser volume of calcium cium hydroxylapatite gel to other parts of the face.
hydroxylapatite may be required to provide the In addition, we have no reason to believe that
same degree of correction as hyaluronic acid and calcium hydroxylapatite, when placed in soft tis-
collagen. Two studies support the finding of sue, exhibits any osteogenic properties. In the pre-
smaller volumes in calcium hydroxylapatite than viously cited study of nasolabial folds, there was no
in several other soft-tissue fillers. For example, in significant difference in adverse events between
a split-face study of calcium hydroxylapatite versus the folds treated with calcium hydroxylapatite and
collagen for the nasolabial folds, on average, the those treated with collagen, and there was no ev-
collagen-treated side of the face required twice the idence of granuloma formation with either mate-
volume of material (2.35 ml) to produce optimal rial. In addition, only one nodule was noted in the
correction as compared with the calcium hydroxy- calcium hydroxylapatite folds, compared with three
lapatite-treated side (1.22 ml) (p ⬍ 0.0001).9 In in the collagen-treated folds.9
another study, approximately 30 percent less vol-
ume of calcium hydroxylapatite was required than CALCIUM HYDROXYLAPATITE FOR
hyaluronic acid for full correction of the nasola- CORRECTION IN THE MIDFACE
bial folds.19 In the midface area, biometric volume loss
Massage to ensure no palpable lumps may be plays just as important a role in the appearance of
appropriate. Some physicians routinely mold the aging as the development of wrinkles and skin
injected area after treatment; other physicians re- laxity. As many clinicians and patients have ob-
serve molding for correction of undesired shapes served firsthand, simply redraping or lifting skin
in an effort to avoid the amplification of edema here is often not sufficient to restore a youthful
and erythema that molding sometimes creates. appearance. Likewise, superficial fill often leaves
correction incomplete. Use of a volumizing filler
Posttreatment Care such as calcium hydroxylapatite in this area can
Posttreatment photographs may be taken as immediately restore volume as well as fill and cor-
soon as the injections have been completed and rect specific creases and defects.
the washable markings removed. The typical pro-
tocol for posttreatment care involves immediate Augmentation of the Malar and
placement of ice onto the injected areas to reduce Submalar Regions
and limit tissue edema and ecchymosis. Some of
With age, volume loss and the descent of malar
the authors recommend to their patients that they
fat pads may lead to flattening or dropping of the
remain upright for the remainder of the day and
front of the cheek and distribution of excess skin
sleep with the head elevated to reduce the degree
into adjacent areas. Younger patients who present
of edema. In our respective practices, patient fol-
with prominent nasojugal folds or midface soft-
low-up visits are typically scheduled 2 to 12 weeks
tissue or bony deficiency are also good candidates
later to document any adverse events and provide
for midface augmentation. Augmentation of the
refinement treatments as necessary.
malar and submalar regions can reduce the shad-
owing effect that aging and deficiency exert on
Adverse Effects this area, reduce skin surplus from the nasolabial,
The duration and severity of adverse events suborbital, marionette, and jowl regions, and re-
associated with calcium hydroxylapatite gel are balance midface proportions. Because cheek aug-
comparable to those seen with other filler agents mentation may affect the face as a whole, malar/
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Volume 129, Number 5S • Calcium Hydroxylapatite (Radiesse)
submalar augmentation should be performed first laterally and slightly inferiorly along the zygoma to
when treating multiple facial areas.14 Although it provide better support for crow’s feet and to en-
is not an approved indication at this time, cheek hance the triangular shape of the face. A second
augmentation with calcium hydroxylapatite has pass of injection to create a crosshatch is usually
been reported in the literature.7,14,14,21 not required for the zygoma. As is the case with the
malar region, injection should not extend beyond
Procedures and Techniques for Malar and the orbital rim (Fig. 2).
Submalar Augmentation Figure 3 shows a 55-year-old woman before
and 1 month after injection of 1.8 ml of calcium
Anesthesia hydroxylapatite for infraorbital/medial cheek aug-
To enhance patient comfort during filler in- mentation and 0.6 ml for perioral correction.
jection, administration of an infraorbital nerve
block is recommended. Only a small amount of Facial Augmentation in Human Immunodeficiency
anesthetic, 0.2 to 0.3 ml per side, followed by mas- Virus-Associated Lipoatrophy
sage, is necessary.14 Some operators use infiltra- Human immunodeficiency virus-associated li-
tion to provide additional anesthesia during the poatrophy can be quite severe and affect substan-
procedure. tial areas and thus may benefit most from fillers
Injection Technique with volumizing properties. The areas most often
If the transcutaneous technique is being used, affected are the temporal and infraorbital regions,
the area should be approached inferiorly to su- the submalar and malar regions, and the nasola-
periorly with a plan in mind for sequential injec- bial folds. In addition to the previously described
tion in the malar area, selecting insertion points registrational trial,10 the use of calcium hydroxy-
just lateral to the nasolabial fold and at the zygoma lapatite for human immunodeficiency virus-asso-
and then proceeding with injection into the sub- ciated facial lipoatrophy has also been reported
malar soft tissue. The injector may start superfi- elsewhere in the literature.7,14,22,23
cially and then work deep, or vice versa, depend- Anesthesia
ing on the injector’s preference. Injections can be Adequate anesthesia should be provided. Typi-
started in the deep dermis, or above or on the cally, an infraorbital block, a “mini-block,” and/or
periosteum, with crisscrossing linear thread injec-
tions. Crosshatching and layering of material in
the subdermal and subcutaneous planes provide
structural 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 orbital
rim, as the orbicularis oculi contraction may cause
clumping of particulate materials. Although cal-
cium hydroxylapatite has been used for fill of the
tear trough, hyaluronic acid products may be
more appropriate for this application.
Another technique, the intraoral-supraperios-
teal approach, is similar to infraorbital and mental
nerve blocks for placement of Radiesse. Infraor-
bital cheek flattening is more common than malar
hypoplasia in the aging population. The intraoral
injections lessen the need for transcutaneous fill-
ing of the nasolabial fold and marionette lines and
may provide equal or better results. As a conse-
quence, less bruising and swelling are likely than
with transcutaneous injections.
For best aesthetic results, the entire malar area
should be augmented, not merely the areas where Fig. 2. Areas of injection for malar correction (left) and malar/
soft-tissue deficiency is most obvious. Busso and medial correction (right). (Illustration courtesy of BioForm Med-
Karlsberg14 recommend extending the correction ical, Inc.)
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Volume 129, Number 5S • Calcium Hydroxylapatite (Radiesse)
3. Murray, C. A., Zloty, D., and Warshawski, L. The evolution of 17. Ahn, M. S. Calcium hydroxylapatite: Radiesse. Facial Plast.
soft tissue fillers in clinical practice. Dermatol. Clin. 23: 343, Surg. Clin. North Am. 15: 85, 2007.
2005. 18. Nussbaum, R., Benedetto, A. V., and Lehrer, M. S. Optimiz-
4. Narins, R., Brandt, E., Leyden, J., Lorenc, Z. P., Rubin, M., ing anesthesia in cosmetic fillers. Skinmed 5: 8, 2006.
and Smith, S. A randomized, double-blind, multicenter com- 19. Moers-Carpi, M. M., and Tufet, J. O. Calcium hydroxylapatite
parison of the efficacy and tolerability of Restylane versus versus nonanimal stabilized hyaluronic acid for the correc-
Zyplast for the correction of nasolabial folds. Dermatol. Surg. tion of nasolabial folds: A 12-month, multi-center, prospec-
29: 588, 2003. tive, randomized, controlled split-face trial. Dermatol. Surg.
5. Goldberg, D. J. Calcium hydroxylapatite. Fillers in Cosmetic (in press).
Dermatology. Abingdon, England: Informa UK Ltd., 2006. 20. Lowe, N. J., Maxwell, C. A., and Patnaik, R. Adverse reactions
6. Hubbard, W. BioForm Implants: Biocompatibility. Franksville,
to dermal fillers: Review. Dermatol. Surg. 31: 1616, 2005.
Wis.: Bioform, Inc., 2003.
21. Cuevas, S., Rivas, M. P., Amini, S., and Weiss, E. Radiesse for
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aesthetic soft tissue augmentation. Am. J. Cosmet. Surg. 23:
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8. Hobar, P. C., Pantaloni, M., and Byrd, H. S. Porous hydroxy- 22. Comite, S. L., Liu, J. F., Balasubramanian, S., and Christian,
lapatite granules for alloplastic enhancement of the facial M. A. Treatment of HIV-associated facial lipoatrophy with
region. Clin. Plast. Surg. 27: 557, 2000. Radiance FN (Radiesse). Dermatol. Online J. 10: 2, 2004.
9. Smith, S., Busso, M., McClaren, M., et al. A six-month ran- 23. Roth, J. S. Restorative approaches for HIV-associated lipoa-
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(ASDS) meeting, Atlanta, Ga., October 27–30, 2005. 25. Jacovella, P. F., Peiretti, C. B., Cunille, D., et al.. Long-lasting
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open-label, 18-month trial of calcium hydroxylapatite constr. Surg. 118(Suppl.): 15S, 2006.
(Radiesse) for facial soft-tissue augmentation in patients with 26. Sadick, N. S., Katz, B. B., Roy, D. A multi-center, 47-month
human immunodeficiency virus-associated lipoatrophy: One- study of safety and efficacy of Radiesse for soft tissue aug-
year durability. Plast. Reconstr. Surg. 118(Suppl.): 34S, 2006. mentation of nasolabial folds and other areas of the face.
11. Marmur, E. S., Phelps, R., and Goldberg, D. J. Clinical, his- Dermatol. Surg. (in press).
tologic, and electron microscopic findings after injection of 27. Scalafani, A. P. Soft tissue fillers for management of the aging
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13. Felderman, L. I. Radiesse for facial rejuvenation. Cosmetic
Dermatol. 18: 823, 2005. tissue fillers for facial-volume augmentation. Ann. Plast. Surg.
14. Busso, M., and Karlsberg, P. L. Check augmentation and 33: 30, 2005.
rejuvenation using injectable calcium hydroxylapatite 30. Godin, M. S., Majmundar, M. V., Chrzanowski, D. S., and
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