A Randomized, Split-Face, Histomorphologic Study Comparing a Volumetric Calcium Hydroxylapatite and a Hyaluronic Acid-Based Dermal Filler
September 2014 | Volume 13 | Issue 9 | Original Article | 1047 | Copyright © September 2014
Yana Yutskovskaya MD,a Evgenjia Kogan MD,b and Eugene Leshunov MDa
aDepartment of Cosmetology, Pacific State Medical University, Moscow, Russia
bDepartment of Pathology and Department of National Scientific Center of Obstetrics, Gynecology and
Perinatology of Russian Federation, First Moscow State Medical University, Moscow, Russia
BACKGROUND: Soft-tissue augmentation with fillers is an aesthetic procedure for restoring age-related volume loss.
OBJECTIVE: To compare neocollagenesis and elastin production stimulated by Radiesse® (calcium hydroxylapatite; CaHA, Merz Pharmaceuticals
GmbH) and a hyaluronic acid-based filler (HA; Juvéderm® VOLUMA®).
METHODS: Twenty-four women, aged 35–45, participated in this split-face, comparative study. Punch biopsies were taken 4 and 9
months after supraperiostal injection of each filler into the ipsilateral or contralateral postauricular area. Samples were analyzed for
collagens type I and III, elastin, Ki-67, and inflammatory and angiogenic markers.
RESULTS: At month 4, collagen type III was greater with CaHA vs HA (P
=0.0052). By month 9, type I staining was higher with CaHA vs
=0.0135), whereas type III was lower with CaHA than HA (P
=0.0019). Staining for elastin, Ki-67 and angiogenesis was greatest
with CaHA at both timepoints. Inflammatory markers increased most with HA treatment.
CONCLUSIONS: CaHA resulted in more active, physiologic remodeling of the extracellular matrix than HA by stimulating a two-step
process whereby collagen type I gradually replaced type III. Increased elastin stimulated by CaHA also indicates active remodeling.
The results of this study suggest that, in the first 9 months after treatment, by reconstituting tissue homeostasis without inducing
inflammation suggests CaHA has more desirable characteristics for a dermal filler than HA.
J Drugs Dermatol.
Soft-tissue augmentation with dermal fillers is a popular,
minimally invasive aesthetic procedure.1 In 2012, in
the USA, most non-surgical augmentation treatments
performed with a dermal filler used a product based on
hyaluronic acid (HA), with the second most popular type being
the calcium hydroxylapatite (CaHA)-based filler, Radiesse®
(Merz Pharmaceuticals GmbH, Frankfurt, Germany), hereafter
referred to as CaHA gel matrix.2
Several HA-based fillers are available, including the product
Juvéderm® VOLUMA® (Allergan Inc., Irvine, CA), hereafter
referred to as ‘HA gel’, an injectable cross-linked gel implant
intended to restore the volume of the face. It is a member of
a family of HA-based fillers that differ with respect to their
degree of cross-linking and HA concentration.3,4 The CaHA gel
matrix is formulated to immediately augment volume and,
subsequently, to stimulate collagen production.5 As a subdermal
implant, CaHA gel matrix is indicated for plastic and
reconstructive surgery of the facial area, including the correction
of moderate-to-severe facial wrinkles and folds, such as
nasolabial folds (NLF) and restoration and/or correction of the
signs of facial fat loss (lipoatrophy) in people with human immunodeficiency
virus (HIV) infection.6
Studies have shown that the HA gel, which is a combination
of a low (<1 mDa) and high (>1 mDa) molecular weight HA
(20 mg/mL), is effective and well-tolerated in restoration of
facial volume loss.4,7 Similarly, the porous CaHA gel matrix
has well-established tolerability,8 having been used in reconstructive
and orthopedic surgery and dentistry for over 20
years.9 The CaHA gel matrix has been studied in many clinical
trials for volume augmentation in facial aesthetics and has
demonstrated efficacy, safety, and good tolerability in the correction
of NLF,10-12 as well as the volume loss associated with
HIV infection.13 In one direct comparison study of CaHA gel
matrix and another HA gel product (Juvéderm® 24; HA 24; 24
mg/mL HA; Allergan Inc.) for the improvement of NLF, CaHA gel
matrix was more efficacious and longer-lasting than HA 24.14
The CaHA gel matrix has also been shown to stimulate an
increase in the production of collagen within the injected region.
15 Collagen and elastin are components of the extracellular
matrix (ECM) that confer important biomechanic properties to
the skin.16 Dermal collagen in adult skin accounts for 77% of the
fat-free dry weight of the skin, and is primarily composed of collagen
types I and III. These collagen subtypes provide the skin
with its tensile strength and structural support, and are known