Calcium Hydroxylapatite Combined with Microneedling and Ascorbic Acid is Effective for Treating Stretch Marks.

BACKGROUND: Stretch marks can have a negative psychological impact on some individuals. Methods are available for treating stretch marks, but high-quality evidence supporting their use is limited. We treat stretch marks using injections of diluted calcium hydroxylapatite (CaHA, Radiesse) filler combined with microneedling and topical ascorbic acid. This retrospective study evaluated the effectiveness of this combined therapy.
METHODS: Subjects presented with red (n = 25) or white (n = 10) striae on their buttocks, thighs, knees, abdomen, and breasts. CaHA filler was diluted 1:1 with lidocaine 2% without epinephrine. A maximum of 3.0 mL of filler was injected per patient at all skin depths using a 23G needle. This was immediately followed by microneedling and topical application of 20% ascorbic acid. Microneedling with ascorbic acid was repeated after 1 and 2 months. Skin biopsies were obtained from a patient who later underwent abdominoplasty.
RESULTS: The mean (±SD) pretreatment Manchester Scar Scale scores were 12.0 (±0.8), decreasing to 7.1 (±1.4) 1 month after the final treatment, indicating improvement in stretch mark appearance (P < 0.001). Subjects were very satisfied (n = 22; 62.9%), satisfied (n = 8; 22.9%), neither satisfied nor dissatisfied (n = 4; 11.4%), or unsatisfied (n = 1; 2.8%) with their treatment results. Analysis revealed a significant correlation between Scar Scale scores and Patient Satisfaction scores (r = 0.483; P = 0.003). Skin biopsies showed increased quantity and quality of collagen and elastin fibers in areas treated with combination therapy. Procedures were well tolerated.
CONCLUSION: Combining 1:1 diluted CaHA with microneedling and topical ascorbic is safe and effective for treating stretch marks.

INTRODUCTION

Striae distensae (stretch marks) are a permanent type of dermal scarring. The unattractive appearance of stretch marks may have a significant negative psychological impact on some individuals. Although their exact etiology is unknown, the incidence of stretch marks is often associated with rapid growth, abrupt changes in weight, and the use of corticosteroids.[1] Consequently, they occur primarily among adolescents, obese individuals, and pregnant women. By the third trimester, approximately 90% of pregnant women develop stretch marks on their abdomen and/or breasts.[2]

Striae generally follow cleavage lines that are transverse to the direction of the greatest tension, where the tissue is the weakest and least able to withstand mechanical stress.[3] They are initially red (striae rubrae), later becoming white and more atrophic (striae albae).[1,4] Histologically, inflammatory changes are initially evident with dermal edema and perivascular lymphocytic cuffing followed by epidermal atrophy and loss of rete ridges.[4] Stretch marks are distinguished from normal skin by densely packed areas of thin, horizontally arranged bundles of collagen lying parallel to the skin surface.[4] Compared with normal skin, the number of vertical fibrillin fibers adjacent to the dermal-epidermal junction and elastin fibers in the papillary dermis are significantly reduced within stretch marks.[4]

A number of different methods are available for treating stretch marks (Table 1); however, high-quality evidence for effective and long-lasting therapies is limited or lacking.[5,6] Thus, there are no consensus guidelines for treating striae. The lack of effective treatment results are either due to the permanence of skin atrophy or poor improvement in skin color.

Table 1.

Available Methods for Treating Stretch Marks

Microneedling is one method of treating stretch marks that works by stimulating intradermal collagen production.[7] Microneedling is also a means for achieving trans-epidermal drug delivery.[8,9] Ascorbic acid, which also enhances the production of normal collagen, can be delivered in this manner.[10] In recent years, hyaluronic acid fillers and poly-L-lactic acid fillers have been used to improve skin depression associated with atrophic acne scars[11-14] and can also be used to improve the appearance of atrophic stretch marks. Calcium hydroxylapatite (CaHA, Radiesse; Merz North America, Raleigh, N.C.) is another type of dermal filler composed of white 25–45 µM microspheres of CaHA suspended in a gel carrier.[15] CaHA is considered both a dermal filler and a biostimulator due to its ability to induce neocollagenesis, neoelastogenesis, and angiogenesis.[16-19] Currently, there are no reports describing the use of CaHA filler for treating atrophic striae.

To address both the skin atrophy and dyspigmentation associated with stretch marks, we have treated patients presenting to our clinic with striae using a combination of intra- and subdermal injections of 1:1 diluted CaHA, microneedling, and topical ascorbic acid. The objective of this retrospective chart review was to evaluate the effectiveness of this combined therapy for improving the appearance of stretch marks.

METHODS

Treatments

All treatments were performed at the Clínica Vida, São Paulo, Brazil, from January 2010 to July 2015. The study subjects (N = 35) were 21 to 34 years old with red (n = 25; 71.4%) or white (n = 10; 28.6%) stretch marks on their buttocks, thighs, knees, abdomen, and breasts. Patients were treated during 3 sessions over an 8-week period (Fig. 1). During the first session, an anesthetic cream containing 7% tetracaine and 7% lidocaine (Pliaglis Cream, Galderma Laboratories, Fort Worth, Tex.; maximum of 10 g/session) was applied to the planned treatment area 30 minutes before treatment. The area was also cleansed with an alcoholic chlorhexidine 0.5% solution.

Fig. 1.

Treatments and assessments. This diagram shows the treatments and assessments performed for each subject.

The first session included the dermal injection of 1.5 mL CaHA diluted 1:1 with 1.5 mL of lidocaine 2% without epinephrine (Cristalia Produtos Quimicos Farmaceuticos Ltda., Santa Cruz, Brazil). Using a microbolus technique, a maximum of 3.0 mL of the diluted filler was injected per patient at all depths from subcutaneous to superficial dermis using a 1 ¼-inch, 23 gauge needle. An aspiration test was performed before each injection. The CaHA injections were followed by vigorous massaging of the area.

CaHA injections were immediately followed by microneedling using needle length of 2.0 mm and a vibration setting of 7 (~85–90 time/sec),[20] which produced more microneedling and less dermabrasion (Dermapen Fractional Micro Needle System; DermapenWorld™, Fort Lauderdale, Fla.). Microneedling was performed in conjunction with the topical application of 20% ascorbic acid (Energy C Professional Treatment, Mesoestetic USA; North Hollywood, Calif.). Ascorbic acid was applied using a sterilized disposable brush before each microneedling pass (N = 20) with an endpoint of mild bleeding (Fig. 2). At the end of the treatment session, the area was cleansed and a plastic bandage was left on for 4 hours. Afterward, patients were advised to avoid sun exposure for at least 6 months. During the 2 subsequent treatment sessions at months 1 and 2, subjects underwent microneedling with ascorbic acid application only.

Fig. 2.

Microneedling. Microneedling was performed in conjunction with 20% ascorbic acid applied using a sterilized disposable brush before each microneedling pass. The endpoint was mild bleeding (after approximately 20 passes).

Assessments

Changes in stretch mark appearance were assessed using the Manchester Scar Scale at baseline and 1 month after the last treatment session (Table 2). Patient satisfaction with the aesthetic results was assessed using a 5-point scale ranging from 1 (very unsatisfied) to 5 (very satisfied). Safety assessments included careful examination of the treated areas and reports of adverse events.

Table 2.

Manchester Scar Scale

One subject with abdominal stretch marks later decided to undergo abdominoplasty to remove excess lax skin following pregnancy. After receiving informed consent, biopsies for histological analysis were obtained from the skin scheduled to be removed. For comparison purposes, the subject received treatment with microneedling and ascorbic acid in an area on one side of the umbilicus and CaHA combined with microneedling and ascorbic acid on the contralateral side. Biospecimens from an untreated area were also collected. Tissue samples were stained with hematoxylin and eosin, Masson’s trichrome and Verhoeff’s stains and assessed by a dermatopathologist for differences in collagen and elastin formation. Posttreatment assessments in the quality and quantity of collagen and elastin fibers included changes in fiber numbers, volume, and thickness.

Changes in Manchester Scar Scale scores were analyzed using Wilcoxon signed-rank test. Spearman’s rank correlation coefficient was used to determine the relationship between Manchester Scar Scale scores and Patient Satisfaction scores.

RESULTS

Efficacy

Manchester Scar Scale scores range from a possible high of 18 to a low of 5, with lower scores indicating better aesthetic appearance (the 10-point visual analog scale was not used).[21] All 35 patients had significantly decreased Manchester Scar Scale scores at the end of the study (Table 3). The mean (±SD) pretreatment scores were 12.0 (±0.8), decreasing to 7.1 (±1.4) at 1 month following the final treatment (P < 0.001). Subjects were very satisfied (n = 22; 62.9%), satisfied (n = 8; 22.9%), neither satisfied nor dissatisfied (n = 4; 11.4%), or unsatisfied (n = 1; 2.8%; Fig. 3). The greatest satisfaction was from subjects treated for striae on the buttocks, abdomen, and breasts (Table 4). There was no apparent difference between striae types.

Table 3.

Manchester Scar Scale Scores, N = 35

Fig. 3.

Patient Satisfaction Scores. Most subjects (85.8%) were satisfied or very satisfied with the appearance of their stretch marks following treatment. Satisfaction scoring: 1 = very unsatisfied; 2 = unsatisfied; 3 = OK (neither satisfied nor unsatisfied); 4 = satisfied; 5 = very satisfied.

Table 4.

Patient Satisfaction by Treatment Area*

The improved aesthetic appearance of striae was related to patient satisfaction. Statistical analysis revealed a significant correlation between Manchester Scar Scale scores and Patient Satisfaction scores (r = 0.483; P = 0.003; Fig. 4).

Fig. 4.

Correlation of Manchester Scar Scale and Patient Satisfaction Scores. Percentage improvement in Manchester Scar Scale scores was significantly correlated with improvement in Patient Satisfaction Scale scores (r = 0.483; P = 0.003).

Examination of stained skin biopsies revealed an increase in the quantity and quality of dermal collagen and elastin fibers in areas treated with the combination therapy versus untreated skin and areas treated with only microneedling and ascorbic acid (Fig. 5). The epidermis showed greater thickening in tissue receiving the combination treatment. There was an increase in the number of collagen and elastin fibers as well as an apparent increase in volume caused by increased fiber thickness. When the subepidermal (papillary dermis) areas were compared, the areas treated with microneedling and combined therapies also showed the presence of increased collagen. Improvements in the appearance of striae observed 1 month after the last treatment session are evident in the subjects in Figures 6 and 7.

Fig. 5.

Histology analysis. Biopsies of treated tissue revealed an increase in the quantity and quality of dermal collagen and elastin fibers in areas treated with the combination therapy vs. untreated skin and areas treated with only microneedling and ascorbic acid. A, D, and G: normal, untreated skin; B, E, and H: tissue treated with microneedling and ascorbic acid only; C, F, and I: tissue treated with 1:1 diluted CaHA injection, microneedling, and ascorbic acid.

Fig. 6.

Pre- and posttreatment images. Pre- and posttreatment images of a 20-year-old subject who developed acute deep striae rubrae in the gluteus region after course of oral prednisone. Baseline appearance of striae (A, B) is much improved after treatment (C) with 1:1 diluted CaHA followed by 3 sessions of topical ascorbic acid and microneedling.

Fig. 7.

Pre- and Post-treatment Images. Pre- and post-treatment images of a 32-year-old subject who developed acute deep striae rubrae in the anterior thigh after pregnancy. Baseline appearance of striae (A) is much improved after treatment with 1:1 diluted CaHA followed by 3 sessions of topical ascorbic acid and microneedling (B).

For the purpose of statistical analysis, all subjects were evaluated 1 month after the final treatment with microneedling and ascorbic acid; however, some patients have maintained their initial results for up to 4 years. This would be expected as the biopsy results demonstrated neocollagenesis and elastogenesis. An 18-year-old subject who was treated on her thighs and buttocks and evaluated after 2 years is shown in Figure 8. At that time, her Manchester Scar Scale score was 9 and her satisfaction score was 4 (satisfied). A small number of patients have required retreatment with microneedling and ascorbic acid after 2 years because of recurring skin atrophy.

Fig. 8.

Two-year posttreatment Images. An 18-year-old subject who was treated on the thighs and buttocks was evaluated after 2 years. At that time, her Manchester Scar Scale score was 9 and her satisfaction score was 4 (satisfied).

Safety

Two subjects with Fitzpatrick skin type III developed postinflammatory hyperpigmentation. Both were treated for 30 days with a whitening cream (Kligman`s formula) with complete resolution. Bruising (n = 32) and erythema (n = 35) resolved within 7 days, and mild pain resolved within 2 days. There were no serious adverse events.

DISCUSSION

The objective of this retrospective study was to assess the effectiveness of combining intra- and subdermal injections of 1:1 diluted CaHA and microneedling with topical ascorbic acid for improving the appearance of red and white stretch marks. As applied in the current study, Manchester Scar Scale scores range from a possible high of 18 to a low of 5, with lower scores indicating better aesthetic appearance. One month after the final treatment, mean subject scores decreased from 12.0 (range, 11.0–13.0) to 7.1 (range, 6.0–10.0), indicating significant aesthetic improvement in striae appearance (P < 0.001). Not surprisingly, these clinical improvements were highly correlated with patients’ satisfaction.

Skin biopsies revealed an increase in the quantity and quality of dermal collagen and elastin fibers in areas treated with the combination therapy versus untreated skin and areas treated with microneedling and ascorbic acid alone. Combined treatments were well tolerated. Reported adverse events from combined treatments seem to reflect those of the individual treatments.

Regardless of the type of therapy used, the goal for treating the atrophic appearance of striae is to stimulate collagen production. Microneedling and dermal filler injections stimulate collagen production via the same signal transduction cascade that occurs following any skin trauma.[22-24] This wound-healing process occurs in several predictable phases.[25,26]

Initially, injury disrupts the vascular endothelium resulting in platelet activation followed by the release of growth factors.[27] Subsequently, there is an influx of inflammatory polymorphonuclear leukocytes. These, together with fibroblasts and endothelial cells, aggregate on the fibrin framework formed by platelet activation.[27] Secretion of additional cytokines and growth factors promote fibroblast proliferation, angiogenesis, and migration of keratinocytes. During the proliferation stage, fibroblasts are also responsible for elastin production and organization of the extracellular matrix.[27] Fibroblasts multiply and increase the production of collagen type III. Eventually, collagen type III is converted into collagen type I, which gradually tightens.[28-30] Treating the skin with microneedling promotes the removal of old damaged collagen and increases new collagen synthesis beneath the epidermis, tightening the skin affected by stretch marks and improving atrophy.[31,32]

Microneedling is also a proven means for delivering medications, such as ascorbic acid, into the skin.[33] Ascorbic acid (vitamin C) is essential for the production of normal collagen. It functions as an essential cofactor for the enzymes lysyl-hydroxylase and prolyl-hydroxylase, which are required for the posttranslational processing of collagen types I and III.[34] Ascorbic acid also stimulates collagen production in the dermis by increasing fibroblast proliferation.[35] It therefore seems likely that ascorbic acid can improve the atrophic appearance of stretch marks. At the level of gene expression, ascorbic acid has also been shown to upregulate collagen synthesis and increase the synthesis of the inhibitor of metalloproteinase I, which decreases ultraviolet-induced collagen degradation.[36]

For more than a decade, CaHA has been used for facial rejuvenation and HIV-associated lipoatrophy by correcting moderate-to-severe wrinkles and folds and soft-tissue volume loss.[37-43] When injected more superficially in its diluted or hyper-diluted form, it has also demonstrated effectiveness in treating volume loss and skin laxity in nonfacial areas, such as neck and décolletage, upper arms, buttocks, thighs, and abdomen.[19,44,45]

In the skin, CaHA results in active, physiologic remodeling of the extracellular matrix by stimulating a 2-step process, whereby collagen type I gradually replaces collagen type III.[18] Increased elastin synthesis stimulated by CaHA also indicates active remodeling. The injection of diluted CaHA (1:1 and 1:0.6 dilutions with 2% lidocaine solution) into the buttocks and thighs has been shown to increase neocollagenesis, with the highest conversion of collagen type III into collagen type I occurring at 90 days with significant improvement in the appearance of cellulite.[46] Although several published reports have described the beneficial effects of CaHA for treating atrophic acne scars,[47-49] a review of the literature failed to identify any reports describing the use of CaHA for treating stretch marks.

CaHA is designed to be injected into deeper planes of the skin, such as the subdermal layer.[15] We have observed that injecting diluted CaHA (1:0.5 to 1:0.25) more superficially can produce a yellowish discoloration of the skin. We therefore hypothesized that, in addition to increasing volume to atrophic striae, the use of CaHA may also add color to provide a more natural appearance of white striae.

This study includes several novel findings. It is the first to demonstrate the effectiveness of 1:1 diluted CaHA combined with topical ascorbic acid and microneedling for improving the aesthetic appearance of both white and red stretch marks. This combination provides 3 potential mechanisms for improving the atrophic appearance of stretch mark tissue: (1) mechanical stimulation of neocollagenesis and neoelastogenesis by CaHA microspheres[18,19]; (2) recruitment of immune cells and subsequent release of growth factors following damage of the skin barrier through microneedling[27]; (3) delivery of ascorbic acid to enhance collagen synthesis.[35] Our encouraging results suggest that this combined treatment technique may produce better results than those obtained when each technique is performed alone. Future studies should include control groups to better demonstrate the beneficial effects of combined treatments and assess long-term results.

CONCLUSIONS

Diluted CaHA, microneedling, and topical ascorbic acid can each increase collagen production in the skin. The results of this retrospective study show that combining these procedures is a safe and effective treatment for both red and white striae.

ACKNOWLEDGMENT

The author acknowledges the editorial assistance of Dr. Carl Hornfeldt during the preparation of this article with funding provided by Merz Pharmaceuticals GmbH, Frankfurt am Main, Germany.