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

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�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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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: Ellen.Marmur@MountSinai.org

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