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Six-Month Safety Results of Calcium Hydroxylapatite forTreatment of Nasolabial Folds in Fitzpatrick Skin Types IV to VI
ELLEN S. MARMUR, MD,� SUSAN C. TAYLOR, MD,y PEARL E. GRIMES, MD,z CHARLES M. BOYD, MD,y
JENNIFER P. PORTER, MD,z AND JANE Y. YOO, MPP�
BACKGROUND Recently, the cosmetic market has seen an increase in the options for treatment forpeople with dark skin.
OBJECTIVES This study evaluates the use of calcium hydroxylapatite (CaHA), a dermal filler indicatedfor the correction of moderate to severe facial wrinkles and folds, including the nasolabial folds (NLFs) inindividuals with dark skin.
METHODS This open-label, nonrandomized, prospective, five-center trial enrolled 100 patients aged 18and older with Fitzpatrick skin types IV to VI. CaHA was injected subdermally with a 25- to 27-gaugeneedle. Participants received a range of 0.6 to 2.8 mL of CaHA and returned at 3 and 6 months to beassessed for keloid formation, hypertrophic scarring, and hyper- or hypopigmentation. If necessary,each subject was offered a touch-up at the conclusion of the 6-month visit.
RESULTS No reports of keloid formation, hypertrophic scarring, hypo- or hyperpigmentation, or otherclinically significant adverse events were recorded.
CONCLUSIONS People with dark skin injected subdermally with CaHA do not show signs of keloidformation, hypertrophic scarring, or hyper- or hypopigmentation. Because of this safety feature, as wellas other characteristics of the product already shown in clinical literature, CaHA is an attractive dermalfiller in this population.
BioForm Medical, Inc. provided the products and equipment for this study. Drs. Marmur and Boyd aremembers of the Medical Education Faculty of Bioform.
There has been an increase in discussions of
cosmetic treatment for people with dark skin in
recent years,1 and differences in skin types2 have
become key features in determining the best cosmetic
outcomes for this population. Perhaps because of the
differences in skin types, people with dark skin are
perceived as being more prone to keloid formation,
hypertrophic scarring, and hypo- and hyperpigmen-
tation than other skin types. Indeed, the manufac-
turers of several notable dermal fillersFthis one
includedFhave been required to provide follow-up
studies specifically in persons of color.3 Although
published dermal filler studies have included patients
of a variety of races and skin tones, the authors
found scant mention of studies published on the
outcomes in patient populations with only darker
skin types.4,5
This study evaluated the use of calcium hydroxy-
lapatite (CaHA; Radiesse, BioForm Medical,
San Mateo, CA), a dermal filler indicated for the
correction of moderate to severe facial wrinkles
and folds, including the nasolabial folds (NLFs), in
people with dark skin. As a condition of approval,
the Food and Drug Administration requested a
postapproval study to assess the likelihood of
hypertrophic scarring, keloid formation, and
hyper- or hypopigmentation in patients with dark
& 2009 by the American Society for Dermatologic Surgery, Inc. � Published by Wiley Periodicals, Inc. �ISSN: 1076-0512 � Dermatol Surg 2009;35:1641–1645 � DOI: 10.1111/j.1524-4725.2009.01311.x
1 6 4 1
�Division of Dermatologic and Cosmetic Surgery, Department of Dermatology, Mount Sinai Medical Center, New York,New York; ySociety Hill Dermatology, Philadelphia, Pennsylvania; zVitiligo and Pigmentation Institute of SouthernCalifornia, Los Angeles, California; yBoyd Gillard Institute of Aesthetic and Dermatologic Surgery, Ypsilanti, Michigan;zChevy Chase Facial Plastic Surgery, Chevy Chase, Maryland
skin color, the results of which are presented in
this article.
Mechanism of Action of CaHA
Composed of CaHA microspheres (25–45 mm) in an
aqueous carboxymethylcellulose gel carrier, CaHA
provides immediate correction after injection that is
predictable and controllable. Within several weeks,
the body absorbs the gel carrier, leaving the micro-
spheres to serve as a scaffold for the development of
new collagen. The duration of effect in the face may
depend on the motility of the area injected, but
rough estimates suggest facial duration of approxi-
mately 1 year.6–10 The product has been commer-
cially available in the United States as a cosmetic
dermal filler since late 2006.
Study Objective
This study was designed to assess the incidence of
hypertrophic scarring, keloid formation, and hyper-
or hypopigmentation after CaHA injection for NLF
treatment in patients with Fitzpatrick skin types IV,
V, and VI.
Materials and Methods
Patient Selection
This open-label, nonrandomized, prospective, five-
center trial enrolled 100 patients aged 18 and older
(94 women, 6 men) with Fitzpatrick skin types IV to
VI (Table 1). Patients ranged in age from 25 to 78;
mean patient age was 52711. In the study popu-
lation, 85% of patients were African American, 12%
were Hispanic, 2% were Asian, and 1% self-defined
as other.
Inclusion criteria were aged 18 and older; Fitzpatrick
skin type IV, V, or VI; and understanding and ac-
ceptance of the obligation not to receive any other
procedures or treatments in the NLF for 6 months.
Exclusion criteria were history of hyper- or hypo-
pigmentation in the NLFs, keloid formation, or
hypertrophic scarring; known bleeding disorder or
current drug therapy that could increase the risk of
bleeding; NLFs that were too severe to be corrected
in one treatment session; received any dermal filler
or other injections, grafting, or surgery in either
NLF; and pregnant, lactating, or not using accept-
able contraception.
Treatment
At the initial visit, CaHA was injected subdermally
with a 25- to 27-gauge needle using a linear
threading and fanning technique. Injection volumes
to bring the patient to full correction were at the
discretion of the investigator. Overcorrection was
not permitted. Anesthetization of the area was per-
formed at the discretion of the treating physician. Ice
or cool compresses could be applied pre- and post-
injection. Medications to reduce swelling and bruis-
ing could also be prescribed at the discretion of the
treating physician. Participants received a range of
0.6 to 2.8 mL of CaHA (mean 1.24 mL). Patients
were scheduled to return at 3 and 6 months to be
assessed for keloid formation, hypertrophic scarring,
and hyper- or hypopigmentation. Incidence, type,
severity, duration, and causality of adverse reactions
were also recorded at both visits.
TABLE 1. Fitzpatrick Skin Type
Fitzpatrick
Skin Type Description
Patients
%
I Burns easily, never tans 0
II Burns easily, tans mini-
mally with difficulty
0
III Burns moderately, tans
moderately and uni-
formly
0
IV Burns minimally, tans
moderately and easily
24
V Rarely burns, tans profusely 35
VI Never burns, tans profusely 41
Astner and Anderson,2 p. 2.
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At the conclusion of the 6-month visit, if necessary,
each subject was offered a touch-up. Photographs
were taken at the discretion of the investigator.
3-Month and 6-Month Follow-Up Visits
At 90730 days from the injection visit (3-month
visit), patients returned for a safety assessment of
their NLFs. Assessment included the presence of
keloid formation (firm, smooth, hard growth),
hypertrophic scarring (red, raised bump), and hypo-
or hyperpigmentation (lightened or darkened area
of the skin) in their NLFs.
At 180730 days from the initial injection (6-month
visit), patients returned for an additional safety
assessment of their NLFs. Patients were assessed in
the same manner as described for the 3-month visit.
Subject participation was considered complete at the
end of the 6-month visit.
Statistical Considerations
The incidence, type, severity, and duration of all
adverse events were reported. Incidence rates of local
implant site adverse events were also provided, in
addition to any other systemic adverse events re-
ported. The number of patients with events and the
total number of adverse events were recorded for
each adverse event type and overall at study com-
pletion. Overall adverse event rates were presented
using exact 95% confidence intervals. Baseline de-
mographic and procedural information was sum-
marized for all patients. This study was not designed
for efficacy analyses or statistical power.
Results
Three-month and 6-month study results are shown
in Table 2. No reports of keloid formation, hyper-
trophic scarring, hypo- or hyperpigmentation, or
other clinically significant adverse events were re-
corded. All 100 subjects received a 3-month follow-
up assessment (4 of 100 were by phone because
of scheduling conflicts). At 6 months, 98 subjects
received a follow-up assessment (3 of 98 were by
phone, also because of scheduling conflicts). Two
subjects were lost to follow-up at 6 months.
Figures 1 to 3 are representative before-and-after
results of patients participating in the study. Note the
absence of any keloids, hyper- or hypopigmentation,
TABLE 2. Adverse Events at 3 and 6 Months
Adverse Event
Patients, %
3 Months
(n = 100)
6 Months
(n = 98)
Keloid formation 0 0
Hypertrophic
scarring
0 0
Hypopigmentation 0 0
Hyperpigmentation 0 0
Figure 1. (A) This 44-year-old man received a total of 1.4 mLof calcium hydroxylapatite (0.5 mL in his left nasolabial fold,0.9 mL in his right nasolabial fold). (B) Post-treatment photo-graph at 6 months.
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or hypertrophic scarring in the postinjection
photographs.
Discussion
People with dark skin and their providers must
understand the differences between skin types
that could make a cosmetic procedure unattractive
or attractive. It is therefore important to have
data on the effect of cosmetic procedures on
persons with dark skin before initiation of any
procedures that might cause an adverse event, and
this study has shed light on some of the questions.
CaHA was found to be safe and well tolerated,
with no reports of keloid formation, hypertrophic
scarring, hypo- or hyperpigmentation, or other
clinically significant adverse events for the correction
of NLFs in patients with Fitzpatrick skin types
IV to VI. The lack of hypo- or hyperpigmentation
may be because the filler is placed at a deeper
level than hyaluronic acids, allowing for
shorter-lived erythema. In addition, patients were
instructed to stay out of the sun after the injection,
lessening the incidence of postinflammatory
hyperpigmentation.
The scarcity of clinical data in aesthetic dermatology
on persons with dark skin color is self-apparent;
we believe that any new data, especially in soft tissue
augmentation, in this population will be of great
benefit to providers and patient. Our data show that
people with dark skin, if injected subdermally with
CaHA, do not show signs of keloid formation,
hypertrophic scarring, or hyper- or hypopigmenta-
tion. Because of this safety feature, as well as other
characteristics of the product already shown in
clinical literature, CaHA is an attractive dermal filler
in this population.
Figure 2. (A) This 43-year-old man received a total of 1.2 mLof calcium hydroxylapatite (0.6 mL in his left nasolabial fold,0.6 mL in his right nasolabial fold). (B) Post-treatment pho-tograph at 3 months.
Figure 3. (A) This 64-year-old woman received a total of0.8 mL of calcium hydroxylapatite (0.4 mL in her left naso-labial fold, 0.4 mL in her right nasolabial fold). (B) Post-treatment photograph at 3 months.
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References
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Address correspondence and reprint requests to:Ellen S. Marmur, MD, Chief, Division of Dermatologic& Cosmetic Surgery, Department of Dermatology,The Mount Sinai Medical Center, 5 East 98th Street,Fifth Floor, Box 1048, New York, NY 10029-6574, ore-mail: [email protected]
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