190
4, 2006
ORIGINAL ARTICLE
Radiesse for Aesthetic Soft Tissue Augmentation
Silvia Cuevas, MD; Maria Patricia Rivas, MD; Sadegh Amini, MD; Eduardo Weiss, MD
Introduction: Calcium hydroxyapatite (Calla; also
spelled "hydroxylapatite") is the main mineral component
of bone, calcified cartilage, and teeth. It has been used
since the 1970s in many specialties, including orthopedics,
urology, otolaryngology, maxillofacial surgery, and radiol-
ogy, as a bioactive implant that promotes chemical attach-
ment of the soft tissue to its surface. In 2001, Radiance FN
(now Radiesse) was introduced as a CaHa-based product
and approved by the US Food and Drug Administration
(FDA) as a radiographic tissue marker,for soft tissue vocal
fold augmentation, andfor implants in maxillofacial defects.
Currently, it is also used outside the United States and off-
label in the United States for facial soft tissue augmenta-
tion. Microspheres of CaHa are suspended in a mixture of
water, glycerin, and carboxymethylcellulose gel that pro-
vides a scaffold for tissue infiltration. Once injected, the gel
is degraded and the CaHa infiltrates the surrounding cells.
CaHa is nonirritating, and the carrier gel components are
classified as safe by the FDA. Although a great variety of
fillers are currently on the market, CaHa (Radiesse) has
demonstrated the longest duration in tissue without any
reports of antigenicity, migration, or granuloma formation.
In this study, we report our experience with CaHa (Radiesse)
for aesthetic soft tissue augmentation.
Materials and Methods: A total of 139 patients were
treated over an 18-month period at 2 private offices in
Argentina and the United States. Exclusion criteria included
previous use ofpermanent tissue fillers in the treatment area.
Patients with previous use of hyaluronic acid fillers in the
treatment area (up to 1 year prior to the study) were allowed
to participate in the study. Radiesse was injected from I-mL
prefilled syringes with 27 Yz-gauge needles in different areas
such as nasolabial folds, lips, marionettes lines, cheeks, and
cellulite dimples. Patient satisfaction and adverse effects
Received for Publication March 26, 2006.
From Centro Arenales de Estetica Medica Dermatology, Buenos Aires,
Argentina (Dr Cuevas): and University of Miami Dermatology, Holly-
wood. Fla (Dr Rivas, Dr Amini. Dr Weiss).
Corresponding author: Eduardo Weiss, MD. University of Miami
Dermatology. 3850 Hollywood Blvd, Suite 301, Hollywood, FL 33021
(e-mail: eweissI401@ao1.com).
The American Journal of Cosmetic Surgery Vol. 23, No.
were assessed by both physicians and patients during the
procedure and during follow-up visits up to 1 year later.
Results: Minimal pain, erythema, edema, and bruising
were noted during and immediately after the procedure. All
of the patients treated were satisfied with their results after
one visit. There were no long-term adverse effects during
the study period or on follow-up visits. Evaluation of 75%
of the patients 1 year after treatment revealed persistence
offilling effects.
Discussion: CaHa used for aesthetic soft tissue augmen-
tation yields immediate clinical results with high patient
satisfaction.
ince the 1970s, synthetic calcium hydroxyapatite
S (CaHa) has been used in the United States and
Europe in various medical fields. In orthopedics it is
used as a coating often applied to metallic implants to
promote bone ingrowth and as a bone filler for defects
or voids. I ,2 In urology it is used as a treatment for
stress urinary incontinence.' In ophthalmology it is
used for orbital implants," and in otolaryngology it is
used for vocal cord augmentation and middle ear
reconstruction.i''" In dentistry and oral and maxillofa-
cial surgery it is used for dental implants and maxil-
lofacial defects." In neurosurgery it has been used for
reconstruction of cranial defects," and radiologists use
it as a contrast agent." Synthetic CaHa is a bioactive
implant that reacts with tissues to promote attachment
by forming a chemical bond to the surface of the
material, unlike bioinert and biocompatible materials
that work by mechanical attachment to surrounding
tissues.l"
In 2001, Bioform Medical Inc, Franksville, Wis,
initiated the commercialization of a CaHa-based prod-
uct named Radiance FN, which was initially approved
by the FDA as a radiographic tissue marker. In 2004,
Radiance FN received further approval for soft tissue
vocal fold augmentation and for implants in maxillo-
facial defects. Later, it was renamed Radiesse, which is
currently utilized for facial soft tissue augmentation
The American Journal of Cosmetic Surgery Vol. 23, No.4, 2006 191

Areas Treated With Calcium Hydroxyapatite Materials and Methods

Number of mL Injected in
Area Treated Procedures Each Procedure
Nasolabial folds 127
Marionette lines
112
Radial lip lines 76
Lip augmentation 29
Cheek wrinkles 16
Scar revision 4 1
Cheekbones contouring 2 1
Glutei cellulite dimple filling 2 2
Labiomandibular grooves
5 1
outside the United States and used off-label for the
same purposes in the United States. I I Radiesse is a
sterile, latex-free, nonpyrogenic, semisolid, and cohe-
sive subdermal implant arranged in the form of
microspheres. The CaHa is suspended in a mixture of
sterile water, glycerin, and sodium carboxyrnethylcel-
lulose gel that is manufactured so that the micro-
spheres are specifically 25 to 125 microns in diameter
in order to minimize the potential for migration.P"!"
Once injected, the uniform and spherical particles
of CaHa provide a scaffold for tissue infiltration.
Initially, fibrous encapsulation of the particles occurs,
fixing the product at the injection site. This is fol-
lowed by phagocytosis and enzymatic degradation of
the gel carrier with concurrent infiltration by the
surrounding cells. CaHa is a bioceramic nonirritant
to the body, and it is degraded into calcium and
phosphate ions through normal homeostatic mecha-
nisms. I 4--- 16 The carrier gel components have been
extensively used in intramuscular injectable products
and are classified as safe by the FDA. Since the implant
is a totally synthetic product without any animal or
human tissue components, sensitization testing is not
necessary. 14
A great variety of tissue fillers are currently available
on the market. The disadvantages of many fillers
include a short duration of action, skin testing re-
quirement, possible filler migration, and possible gran-
uloma formation. There have been no reports of
migration, granuloma formation, or antigenicity with
the use of CaHa. 14 , 17 , 18 In addition, the CaHA filler
appears to last much longer than traditionally used
fillers. 12,14
In this study we evaluate and report our experi-
ence with CaHa (Radiesse) for aesthetic soft tissue
augmentation.
Patient Selection
A total of 139 patients from 2 private offices, one
in Buenos Aires, Argentina, and the other in Holly-
1
wood, Fla, in the United States were enrolled in
1
1 the study from September 2002 to August 2004.
1 Written consent was obtained from all participant
1 patients.
Patients with a previous history of treatment with
permanent tissue fillers were excluded from the
study. Patients who had undergone treatment with
hyaluronic acid at least 1 year prior to the enrollment
period were not excluded. Patients had to be at least
18 years of age. One hundred twenty women (86.33%)
and 19 men (13.67%) between the ages of 34 and 82
met the study selection criteria and were enrolled in
the study.
Technique
Treated areas included nasolabial folds, lips,
cheeks, and cellulite dimples (Table). Scar revisions
in 4 cases were also performed using CaHa. Topical
anesthetics or a nerve block with 1% lidocaine,
without epinephrine, were used in some patients
before the procedure. Radiesse, supplied in 1-mL
prefilled syringes, was stored at room temperature. A
27 Yz -gauge needle was used for all procedures.
The needle, beveled downward, was placed and
advanced in a 45-degree angle until reaching the deep
reticular dermis near the subcutaneous tissue junction.
The needle was advanced until reaching the distal
portion of the area to be treated. Then the needle was
lowered to an angle of approximately 15 degrees
(Figure lA, B, and C). Prior to initiating injection of
the product, the needle was carefully raised to tent
the tissue. At this time, withdrawal of the needle was
performed using a retrograde or tunneling tech-
nique. An effort was made not to inject too much of
the product within one area to prevent the ap-
pearance of lumps or nodules (Figure 1D, E, and F).
When injecting the lip, visualization of the needle
through the skin was avoided in order to prevent
superficial placement of the product (Figure 2A, B,
and C).
Massaging of the area immediately after treatment
was done until adequate and uniform molding of the
augmented area was achieved. The entire procedure
lasted approximately 30 minutes. Evaluations of the
procedure and adverse effects were performed by
physicians and patients during and immediately after
192 The American Journal of Cosmetic Surgery Vol. 23, No.4, 2006

A B
Injection angle at 45 degrees
Beveled edge downward
, Enlargedetail Epidermis
Paplar Dermis •• :J II

Gi- Inje.ction angle at 45degrees R€liaJIar

Dermis
~"" Beveled edge downward

Needle 27 G ,J ' Suba.Cale<lUS

Cell Tissue

Meetingpont with the- - -'

reticular layer of the dermis

Final position of the needle

o
Finalangle 15 degrees Originalposition 01 theneedle
Elevated position of the needle Bevelededge
downward
" .

E F
Originalposition 01 the needle Product:
Calcium Hldroxiapatite
~ Excess 01 product

y( ~ t ~.; 'j
Trajectory of the needle
and simultaneous deposit of material

Figure 1. Diagram of the injection method creating a "virtual space" with the retrograde technique. (A) Location of
injection site. (B) Injection angle at 45 degrees, beveled edge downward. (C) Trajectory of the needle. The final angle of
the needle is 15 degrees. (D) The entire needle is elevated until a virtual cavity is formed and the retroinjection begins.
(E) Implantation of the product is carried out by means of retroinjection. (F) Example of an incorrect implant . Too much
material should not be injected in one spot because it will cause the formation of a lump that will take a long time to
be reabsorbed, creating the appearan ce of a nodule or granuloma. Graphics prepared by Dr Silvia Cuevas.

injection of the product. Evaluations of results and during each visit in order to qualify the results. The
adverse effects were performed by physicians and results of the evaluation were ranked in 3 categories:
patients at 1 month, 3 months, 6 months, and 1 year no satisfaction, moderate satisfaction, and complete
after treatment. A scale of satisfaction was used satisfaction.
The American Journal of Cosmetic Surgery Vol. 23, No.4, 2006 193

A B c

;.~:: : ::-.-
'"

Figure 2. Technique for Lips. (A) Location of injection. The dotted lines indicate position and introcution angle of the
needle in different instances. (B) Incorrect insertion later. If the needle is positioned in the correct layer, you will not see the
needle through the skin of the lip. (C) When the needle is in the correct layer, you cannot see the needle through the skin.

Results probability of microtraumas and edema formation. All

cases of edema usually disappeared within 72 hours
Evaluation During and Immediately
after local massage and ice application.
After the Procedure
Fifty percent of the patients had bruising of the
Pain or discomfort was minimal in 80% of the pa-
treated areas that resolved 7 to 15 days posttreatment.
tients and nonexistent in 20% of the patients during
This side effect was more evident in patients actively
and immediately after the procedure.
taking blood thinners.
All of the patients had erythema, which was mostly
Twenty-nine patients underwent lip augmentation.
evident after massaging of the area after injection. The
Two of them (6.9%) developed nonvisible lip nodules
erythema was always transient and usually disappeared
that disappeared after 3 months without any further
30 minutes after the procedure.
complications.
Edema occurred in 80% of the patients after treat-
According to our satisfaction scale, both patients and
ment of the oral commissures, in 30% of the patients
physicians reported 100% satisfaction with the imme-
after treatment of the nasolabial folds, in 90% of the
diate results (Figures 3, 4, 5, and 6).
patients after treatment of the lips, and in 2% of the
patients after treatment of the cheeks. These regional
differences in edema development are due to the Evaluation During Follow-Up Visits
presence of more than one wrinkle in the oral com- Eighty percent of the patients treated were evaluated
missures, generating crossing over of the tissues, and 1, 3, and 6 months after treatment, and 75% of the
thus more microtraumas and microhematomas at the patients treated were evaluated after 1 year. During
time of injection. These microhematomas lead to the each follow-up visit, the treated areas showed persis-
formation of edema. On the contrary, the cheeks have tence of results. All of the patients reported that they
plenty of space to work on; thus there is a lower were satisfied with the treatment after one visit. Only

Figure 3. (A) Female patient previous to treatment with calcium hydroxyapatite. (B) Same patient 2 years after lip
augmentation and treatment of nasolabial folds and marionette lines. A total of 1 mL of calcium hydroxyapatite was
used to obtain the observed results.
194 The American Journal of Cosmetic Surgery Vol. 23, No.4, 2006

A B

Figure 4. (A) Female patient before treatment with Radiance. (B) Same patient 2 years after filling of nasolabial folds and
marionette lines. A total of 3 mL was used.

2 patients (1.43%), one with deep nasolabial folds and Discussion

the other with moderate cheek volume loss, required
one additional visit for "touch-up." According to our
scale, complete satisfaction was reported by all patients
at each visit. Furthermore, many patients requested
additional treatment for other areas. According to our
satisfaction scale, all physicians participating in the
study were completely satisfied with the results at each
follow-up visit. Seventy-five percent of the patients
who returned for evaluation 1 year after the treatment
were completely satisfied with the results, according
to our scale of satisfaction. All the physicians who
evaluated these patients 1 year after the treatment
were 100% satisfied with the results, according to the
scale. No adverse reactions, such as granuloma
formation, migration, allergic reactions, or persistent
inflammation, were seen in any of the patients. In
addition, none of the patients who had been pre-
viously treated with hyaluronic acid developed
complications.
Radiesse is currently being used in Europe and South
America for soft tissue augmentation. In the United
States, Radiesse is FDA-approved for radiographic
tissue marking, filling of oral and maxillofacial defects,
and vocal cord insufficiency. The absence of reports
from other medical specialties regarding complications
such as migration, hypersensitivity reactions, and
granuloma formation are some of the reasons why
plastic surgeons and dermatologists have become
increasingly interested in its application as a soft tissue
augmentation alternative.
Since CaHa is a naturally occurring component of
bones and teeth, it is biocompatible.l" Furthermore,
there have not been any reports of ectopic bone for-
mation with its use. Antigenicity when using this
product has not been reported; therefore, skin testing
prior to treatment is currently not required.
We report the successful use of CaHa as an aesthetic
soft tissue filler agent in 139 patients. Treatment sites

Figure 5. (A) Female patient previous to treatment. Notice the pronounced cheek atrophy and deep nasolabial folds.
(B) Same patient 2 years after contouring of the cheeks and filling of the nasolabial folds and marionette lines. This patient
received a total of 2 mL in the first session (1 mL per site) and 1 mL for touch-up during a second session.
The American Journal of Cosmetic Surgery Vol. 23, No.4, 2006
Figure 6. (A) Female pati ent previous to treatment. (B) Same patient 2 years after she underwent treatment of the
nasolabial folds and marionette lines with 1 mL of Radiance.
included nasolabial folds, perioral wrinkles, marionette
lines, cheeks, lips, and cellulite dimples. Radiesse was
injected in the deep reticular dermis with the retrograde
or tunneling technique without overcorrection.
Overcorrection is not recommended, and in cases of
lip augmentation we suggest subtle correction during
the first visit and arrangement of a follow-up visit for
further treatment once swelling has subsided.
Nerve blocks have been recommended previously to
treatment of lips and nasolabial folds. In our case, only
2 patients required local nerve block previous to lip
augmentation. Optimal correction can be achieved
within one visit; however, additional visits may be
required for filling of more pronounced defects (eg,
nasolabial folds).
The most common side effects, all of which were
temporary and have been previously reported,17,19
included ecchymo ses (50%), swelling (80%), and
erythema (l 00%). Similar to other reports in the litera-
ture,17,19 some of the patients (2 of 29) who underwent
lip augmentation developed temporary nonvisible
nodules that resolved within 3 months. According to
Dr Arnold Klein,2o this adverse effect may be due to the
constant movement of the orbicularis oris muscle. In
addition, we believe this adverse effect may be avoided
by injecting small amounts of material into the lip.
Simil
urn ar to other aut hors ' expenence,
. 1719
' we report
high patient satisfaction with the use of Radiesse.
Seventy-five percent of the patients returned for a 1-
year follow-up visit after treatment demonstrating
persistence of filling effect and continued satisfaction,
without any complications. Radiesse is a nonpermanent
tissue filler, with a long-lasting effect. Its longevity
when used for facial filling has not been determined ,
but it is thought to be at least 1 to 2 years.
The use of CaHa for soft tissue filling has not yet
been approved by the FDA in the United States; how-
195
ever, recent studies such as this one attest to its safety
for cosmetic use. Preliminary results reported in the
literature support the need of larger, long-term, multi-
center trials to assess the efficacy, safety, and longevity
of this product as a facial implant.
Of interest, it is important to inform patients that
CaHa is a radiopaque material and that it could become
visible after treatment in any facial or dental X-ray
study.
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