Improved Neocollagenesis and Skin Mechanical Properties After Injection of Diluted Calcium Hydroxylapatite in the Neck and Décolletage:A Pilot Study

January 2017 | Volume 16 | Issue 1 | Original Article | 68 | Copyright © January 2017

Yana Alexandrovna Yutskovskaya MD PhDa and Evgeniya Alexandrovna Kogan MD PhDb

aPacific State Medical University,Vladivostock, Russia bMoscow Medical University, Moscow, Russia

BACKGROUND: Calcium hydroxylapatite (CaHA; Radiesse (R)) provides safe and effective correction of moderate-to-deep lines, volume replacement, lift and contour, and induction of neocollagenesis and neoelastogenesis for improved skin quality. CaHA hyperdilution takes advantage of its skin-tightening properties without a volumizing effect. OBJECTIVE: To evaluate the collagen- and elastin-stimulating effects of diluted CaHA in subjects with skin laxity in the neck and décolletage. Methods: Twenty subjects with skin laxity in the neck and décolletage received multiple, linear, subdermal injections of CaHA diluted with preserved saline at baseline and 4 months: 1:2 dilution (normal skin), 1:4 dilution (thin skin), and 1:6 dilution (atrophic skin). Subjects also received deep subdermal injection of CaHA (~0.1 ml) of the same dilution in the peri-auricular area for skin biopsy. Biopsy tissue was obtained at baseline, 4 months, and 7 months for immunohistochemical evaluation of neocollagenesis. Changes to skin mechanical properties were measured by ultrasound scanning and cutometry. Subject and investigator satisfaction was evaluated using the Global Aesthetic Improvement Scale. RESULTS: Immunohistochemical analysis of biopsy tissue demonstrated signi cant increases in collagen I expression at 4 months (P less than 0.05) and 7 months (P less than 0.00001) compared with baseline. Increases in collagen III levels were also significant at 4 months (P less than 0.00001); they declined by 7 months but remained above baseline. Staining for elastin and angiogenesis signi cantly increased at 4 months (P less than 0.05 and P less than 0.01, respectively) and 7 months (P less than 0.00001 for both) compared with baseline. Immunohistochemical data correlated with improvements in skin elasticity and pliability evaluated by cutometry, and with ultrasound-assessed increases in dermal thickness. Subject and investigator satisfaction was high, and the procedure was well tolerated. CONCLUSIONS: Injection of diluted CaHA is very effective for skin tightening of the neck and décolletage. J Drugs Dermatol. 2017;16(1):68-74.


Radiesse® (calcium hydroxylapatite [CaHA], Merz North techniques for using higher dilutions of CaHA to take advan- America, Inc., Raleigh, NC, USA) is a very effective tage of its collagen-stimulating effects to reduce skin laxity agent for many areas of facial soft-tissue augmenta- tion and is associated with a high and well-established safety profile.1,2Treatment provides immediate correction that is gradu- ally followed by new tissue formation through neocollagenesis, elastin production, dermal cell proliferation, and angiogenesis. The result is a long-lasting aesthetic effect with tight and elastic skin, and increased skin thickness. In 2009, the FDA approved a protocol for mixing CaHA with lidocaine to improve patient comfort during injection. In 2016, Radiesse® (+) Lidocaine, with integral 0.3% lidocaine, also received a CE mark and is now available to physicians in Europe. Diluted CaHA has become widely used by injectors as it expands the range of indications for which CaHA can be used. The FDA-approved mixing protocol to produce a final lidocaine concentration of 0.3% represents the optimal protocol for preserving the viscoelastic properties of CaHA when used as a volumizing ller. However, many experts have developed techniques for using higher dilutions of CaHA to take advantage of its collagen-stimulating effects to reduce skin laxity without the volumizing effect.Some injectors use lidocaine for the initial dilution to reduce dis- comfort with further dilutions achieved by adding normal saline solution. Others dilute exclusively with hypertonic saline solu- tion, which itself has local anesthetic properties. Dilutions can be titrated depending on the thickness of the patient’s skin and the degree of tissue laxity to ensure smooth placement of product. In a pilot, controlled study, CaHA was diluted with saline solu- tion to achieve nal dilutions of 1:2 and 1:8 [Yana Yutskovskaya, unpublished data]. Six subjects then received peri-auricular in- jection with the 1:2 dilution, seven with the 1:8 dilution and 13 control subjects received saline solution alone. After 3 months, punch biopsies were taken and tissue examined by immuno- histochemistry for collagen types I and III, elastin expression and angiogenesis. Injection of CaHA had remodeled the struc- ture of the dermis promoting statistically signi cant increases