Treatment for cellulite
Neil Sadick, MD ⁎
Department of Dermatology, Weill Cornell Medical College, New York, New York
Sadick Dermatology, New York, New York
Received 14 June 2018
Received in revised form 10 September 2018
Accepted 11 September 2018
Cellulite is a multifactorial condition that is present in 80% to 90% of postpubertal women and is one of the
most intolerable esthetic imperfections. Thereare several theories on thepathophysiologyof cellulite, and a
number of different therapeutic regimens have been developed, from topical treatments to mechanical or
energy-based devices. In this brief review, we summarize the scientiﬁc landscape to determine the clinical
evidence with regard tothe safety and efﬁcacy of cellulite treatment options.Clinical protocols and the au-
thor’s experience using a combination of internal and external procedures are also discussed. Studies using
laser and light modalities along with radiofrequency have shown improvements in cellulite and a good
safety proﬁle, but acoustic wave therapy, subcision, and the 1440-nm Nd:YAG minimally invasive laser
have demonstrated the most beneﬁcial results in cellulite reduction. Although there is paucity of scientiﬁc
evidence for treatments that improve cellulite, future emerging options and their combination may pave
the way to eradicate this primarily cosmetic esthetic concern.
© 2018 Women'sDermatologic Society. Published by ElsevierInc. This is an open access articleunder the CC
BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Cellulite is a skin condition that affects up to 80% of postpubertal
women (Luebberding et al., 2015). Cellulite is different from general-
ized obesity because with obesity, adipocytes undergo hypertrophy
and hyperplasia; cellulite is characterized by large, metabolically sta-
ble adipocytes that are limited to lower body areas (e.g., pelvis,
thighs, and abdomen; Quatresooz et al., 2006). Also known as edem-
atous ﬁbrosclerotic panniculopathy, cellulite was ﬁrst described by
Alquin and Pavot in 1920 and originally thought to be “interstitial
edema associated with an increase in fat content.”
The phenotype of this condition is distinct, with the skin topogra-
phy changing to a surface that resembles an orange peel. This is due
to the herniation of subcutaneous fat lobules through the
dermohypodermal junction, where ﬁbrosis of the collagen septa
leads to their shortening and ultimatelytheir retraction,which causes
the depressions that characterize cellulite. Although several factors
are known to contribute to the development of cellulite (sex, genet-
ics, lifestyle; Querleux, 2004; Querleux et al., 2002), the exact patho-
physiology is not understood. The most prevalent models that have
been proposed span from vascular/inﬂammatory to hormonal and/
or structural causes.
Understanding the etiology of cellulite is key to developing targeted
approaches, and a plethora of options is available to dermatologists
to offer to their patients with cellulite. Topical agents, energy-based
devices, subcision,injectable biologic medications, and more recently
dermal ﬁllers have all been used and studied in peer-reviewed publi-
cations for their safety and efﬁcacy to treat cellulite (Table 1).
Topical agents, combined with vigorous massage, were the earli-
est attempts to treat cellulite. As with all topical treatments, the
main challenge of these therapies is for the active ingredients to
reach their target in sufﬁcient concentration to have a therapeutic ef-
fect. Methylxanthines (aminophylline, theophylline, and caffeine)
and retinoids have been the most extensively evaluated ingredients
used in topical formulations for cellulite.
Methylxanthines are hypothesized to improve cellulite by stimu-
lating lipolysis and inhibiting the enzyme phosphodiesterase, which
increases the concentration of cyclic adenosine monophosphate. Ret-
inoids, on the other hand, are thought to reduce cellulite by increas-
ing dermal thickness, increasing angiogenesis, synthesizing new
connective tissue components, and increasing the number of active
ﬁbroblasts. For both agents, there have been several peer-reviewed
publications with promising data, but the studies have been small
with no long-term follow-up. Overall, certain formulations can
International Journal of Women's Dermatology 5 (2019) 68–72
⁎Department of Dermatology, Weill Cornell Medical College, New York, New York.
E-mail address: email@example.com.
2352-6475/© 2018 Women's Dermatologic Society. Published by Elsevier Inc. Thisis an open access article under theCC BY-NC-ND license (http://creativecommons.org/licenses/
Contents lists available at ScienceDirect
International Journal of Women's Dermatology
improve collagen production and reduce skin laxity, but they are
rarely effective on cellulite, which requires extensive fat, collagen,
and connective tissue remodeling (Bertin et al., 2001; Green et al.,
2015; Lupi et al., 2007; Pierard-Franchimont et al., 2000).
Energy-based devices that harness power from various sources
such as lasers, light, radiofrequency (RF), and acoustic waves have
been extensively tested for the treatment of localized adiposities
and/or skin laxity.
RF devices deliver thermal energy to the dermal/subcutaneous
plane via electrode(s). By elevating the tissue temperature at the tar-
get area, collagen denaturation, remodeling and neocollagenesis is
stimulated, but lipolysis is also triggered. Depending on theelectrode
or generator conﬁguration, RF devices come in various iterations,
starting with the ﬁrst generation (e.g., unipolar, monopolar, and bi-
polar) to the latest generation (e.g., multipolar, multigenerator, and
temperature-controlled) devices. Some RF devices also integrate
other energies in their technological design, such as infrared light,
vacuum suction, and pulsed-electromagnetic ﬁelds (Sadick, 2007;
Sadick and Rothaus, 2016a, 2016b; Sadick and Sorhaindo, 2005;
Sadick et al., 2014).
The latest generation of RF devices have been studied and shown
to be effective in clinical trials to reduce the appearance of cellulite
(Luebberding et al., 2015; Romero et al., 2008; Sadick, 2009; Sadick
and Magro, 2007; Sadick and Mulholland, 2004; Wanitphakdeedecha
et al., 2017). Speciﬁcally, Velasmooth and Velashape systems
(Syneron Medical, Israel) that combine infrared light, bipolar RF,
and mechanical manipulation of the skin with suction and massage
have been shown to reduce cellulite.
In a study by Sadick and Magro (2007) where 16 subjects with
cellulitewere treated twice weekly for 6 weeks with the VelaSmooth
system, there was a 71.87% decrease in thigh circumference and 25%
improvement of cellulite in N50% of subjects at the end of the study.
In another study, where 35 female subjects with cellulite were re-
ceived eight to 16 treatments twice weekly with the VelaSmooth de-
vice, 70% of patients showed a reduction in thigh circumference after
4 weeks of treatment,and 100% of patients showed some level of im-
provement in skin texture and cellulite (Sadick and Mulholland,
2004). Researchers have hypothesized that this is achieved due to in-
creased circulation, stimulation of the adipocyte metabolism, and
mechanical stretching of the ﬁbrous cords.
Other devices that have been approved by the U.S. Food and Drug
Administration (FDA) for the noninvasive treatment of cellulite in-
clude Exilis Elite (BTL Aesthetics, United Kingdom), which is a
monopolar RF device; Venus Legacy (Venus Concept, Ontario, Can-
ada), which is a multipolar RF device with pulsed magnetic ﬁelds;
Endymed Body Shaper (Endymed), a multigenerator RF device, and
ThermiRF (Thermi Aesthetics, Hayward, CA), a novel temperature-
controlled RF device with internal probes (Fig. 1).
Recently, the Venus Legacy devices were used to evaluate their ef-
ﬁcacy to treat abdominal cellulite in 25 healthy adult women who
underwent eight weekly treatments. A reduction in subcutaneous
thickness in the axial and sagittal plane of the abdomen was observed
at 1 week after treatment initiation, and assessments by a blinded in-
vestigator at 1, 4, and 12 weeks after the ﬁnal treatment demon-
strated a signiﬁcant improvement in cellulite appearance. No
adverse effects were reported, and the treatment was well tolerated
(Wanitphakdeedecha et al., 2017).
Laser and light
Laser and light devices, depending on their wavelength, emit en-
ergy to the dermis/subcutaneous plane; by heating the local tissue
they can stimulate collagen remodeling and increase microcircula-
tion, which can improve the appearance of cellulite. The impact of
these devices is not very substantial in terms of adipolysis or even
disruption of the ﬁbrous septa that characterize cellulite, but they
can improve the appearance of the skin and smooth the surface.
The main laser technology that has been proven effective to treat
cellulite is a minimally invasive side-ﬁring ﬁber 1440-nm Nd:YAG
laser (DiBernardo et al., 2013, 2016; Sasaki, 2013). This technology
provides a highly targeted means of delivering laser energy into the
targeted anatomical structures that underlie the cellulite as the ther-
mal-sensing cannula is integrated with the laser delivery system to
provide a safe and even distribution of energy to the treatment site.
Only one treatment is required, and aside from the clinical improve-
ment of cellulite, there is high subject satisfaction and minimal ad-
verse events (Fig. 2).
In a multicenter clinical trial, where 57 patients underwent a
three-step cellulite treatment with a 1440-nm Nd:YAG laser with a
side-ﬁring ﬁber and temperature-sensing cannula, the average im-
provement score was 1.7 for dimples and 1.1 for contour irregulari-
ties at the 6-month follow-up examination. The average satisfaction
score was 5.6 for the physician and 5.3 for the patient on a 6-point
scale. Treatment was well tolerated by patients (DiBernardo et al.,
Acoustic wave therapy
Acoustic wave therapy (AWT) is another energy-based therapy,
whereby pressure waves are transmitted to the subcutaneous tissue
and promote lipolysis, improve local blood ﬂow, enable lymphatic
drainage, and stimulate the production of new collagen. Two types
of acoustic waves have been used to treat cellulite: focused shock
waves (ESWT) and radial shock waves. The main devices that have
been used for cellulite include Cellactor (Storz, Switzerald) and Z-
wave (Zimmer, Irvine, CA; Angehrn et al., 2007; Knobloch and
Kraemer, 2015; Nassar et al., 2015; Russe-Wilﬂingseder et al.,
2013). On average, AWT requires seven treatment sessions, does
not require topical anesthesia, and results in only minor pain (Fig.
3;Schlaudraff et al., 2014).
AstudybyNassar et al. (2015) evaluated the efﬁcacy of ESWT in
15 individuals, and eight sessions during 4 weeks were carried out.
The authors concluded that ESWT was efﬁcient in the improvement
of body contour (i.e., reduction of circumference and fat layer) as
well as in the appearance of cellulite 3 months after treatment. Hexsel
et al. (2017) also recently evaluated the efﬁciency of ESWT in the
treatment of cellulite in 30 women who received 12 sessions over 6
weeks. The treatment reduced cellulite severity from baseline up to
12 weeks after the last treatment session (subjects with severe cellu-
lite: 60%-38%), and the average thickness of the subcutaneous fat tis-
sue decreased (28.3 ± 6.5 mm to 26.7 ± 6.1 mm; pb.001). The
Treatment type Brand
Topical agents Bliss, Clarins, Shisheido, Glytone
Radiofrequency devices Venus Legacy (Venus Concept), Endymed
PRO (Endymed), Velashape (Cynosure)
Laser/light devices Cellulaze (Cynosure)
Acoustic wave therapy Z-wave (Zimmer), Cellactor (Storz)
Subcision Cellﬁna (Merz)
Injectable biologic treatments EN3835 (Endo)
Fillers Calcium hydroxyapatite (Radiesse),
poly-l-lactic acid (Sculptra)
69N. Sadick / International Journal of Women's Dermatology 5 (2019) 68–72
treatment also improved patients’quality of life, and no serious ad-
verse events were reported (Hexsel et al., 2017).
Manual subcision has also been evaluated for the treatment ofcel-
lulite. During this procedure, the areas are numbed with a topical an-
esthetic agent (vasoconstrictor with lidocaine), a needle (18 G) is
inserted under the skin, and a fanning technique is used to release
the ﬁbrous cords of cellulite. Although efﬁcacious, the main draw-
backs of this treatment are the side effects, including edema, discom-
fort, pain, and bruising (Hexcel and Mazzuco, 2000).
Recently, a novel tissue stabilized-guided subsicion (TS-GS) sys-
tem (Cellﬁna System;Merz North America, Inc., Raleigh, NC) was de-
veloped and FDA approved for the improvement of cellulite in the
buttocks and thigh areas of adult women. The beneﬁts of Cellﬁna
over traditional manual subscision with a needle are its precise con-
trol of treatment depth and area of tissue (ﬁbrous septae) and a
unique vacuum-assisted design.Cellﬁna has been shown in multicen-
ter clinical studies to improve cellulite with results lasting N3 years
(Kaminer et al., 2017).
In the latest clinical study, 45 subjects were followed for an ex-
tended period of up to 3 years after receiving a single treatment
using the TS-GS system. The results of this trial supported an FDA
clearance of the device for the long-term reduction in the appearance
of cellulite following TS-GS (Kaminer et al., 2017).
Injectable treatments for cellulite
Among minimally invasive procedures for cellulite, active biologic
agents and dermal ﬁllers have been used to treatcellulite, with prom-
Collagenase Clostridium histolyticum
Collagenase enzymes isolated and puriﬁed from the fermentation
of Clostridium histolyticum are used in clinical trials for the treatment
of cellulite. Collagenase I (AUX-I, Clostridial class I collagenase) and
Collagenase II (AUX-II; Clostridial class II collagenase) are not immu-
nologically cross-reactive and have different speciﬁcities; mixed in a
1:1 ratio, theybecome synergisticand provide a very broad hydrolyz-
ing reactivity toward collagen (Yang and Bennett, 2015). Thus, they
can hydrolyze the triple-helical region of collagen and have the
Fig. 1. Before (left) and after (right) seven treatments in the outer thigh with Venus Legacy (Venus concept, Toronto, Ontario, Canada).
Fig. 2. Before (left) and after (right) one treatment in the buttocks with 1440 nm Cellulaze (photograph courtesy of Cynosure).
70 N. Sadick / International Journal of Women's Dermatology 5 (2019) 68–72
potential to be effective in lysing subdermal collagen, such as those
observed in the dermal septa (underlying cause of cellulite).
In phase 2b trials, a collagenase mixture, EN3835 (Endo pharma-
ceuticals, Malvern, PA), has been shown to be well tolerated by all
dose groups, and most adverse events were mild to moderate and
primarily limited to the local injection area. A phase 3 multicenter,
randomized, double-blind, placebo-controlled study is currently un-
derway to evaluate the safety and efﬁcacy of this agent in reducing
the appearance of cellulite (Callaghan et al., 2017).
Another up-to-date option to treat cellulite is the new generation
dermal ﬁllers injections, such as calcium hydroxyapatite (CaHa) and
poly-l-lactic acid microspheres (Fig. 4). These ﬁllers have been used
extensively to treatscars and can also be applied to smoothen thecel-
lulite-induced skin irregularities. A recent study evaluated the effects
of microfocused ultrasound with visualization (Ultherapy) in combi-
nation with diluted calcium hydroxylapatite (CaHA; Radiesse) on cel-
lulite appearance in 20 women. The results showed statistically
signiﬁcant improvements compared with baseline for each item on
the cellulite severity scale (pb.001) with a 4.5-point improvement
in mean overall score (pb.001) after a single microfocused ultra-
sound with visualization/CaHA treatment. Both procedures were
well tolerated, and subject satisfaction was high (Casabona and
Despite multiple therapeutic approaches that attempt to treatcel-
lulite, no procedures have been proven successful long term. Topical
agents, injectable treatments, and energy-based devices can
ameliorate the appearance of cellulite, sometimes to a satisfactory
degree, but never eradicate cellulite because this involves extensive
In the author’s opinion, a combination approach where internal
and external approaches are used strategically and in a staged man-
ner to yield synergistic results has the best clinical outcome. For ex-
ample, injections with CaHa followed by ﬁve weekly treatments
with an RF device can result in improvements of severe cellulite
around 3 months after the ﬁnal treatment. Other examples of com-
bining strategies can be six sessions ofweekly acoustic wave therapy,
followed by a one-side ﬁring of an 1440 nm laser.
More large-scale studies, particularly with respect to combination
approaches, need to be conducted to evaluate the long-term results
of therapies for cellulite in terms of safety, efﬁcacy, and patient
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