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 HA (P=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. 2014;13(9):1047-1052.


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