Calcium Hydroxylapatite Ultradilute, HA Dilution

Introduction

Calcium hydroxylapatite (CaHA; Radiesse, Merz North America, Raleigh, NC) is an opaque, white-colored filler consisting of CaHA microspheres (25–45 μm in diameter) suspended in an aqueous carboxymethylcellulose carrier gel. The synthetic CaHA microspheres are smooth in shape, uniform in size, and composed of minerals (calcium and phosphate) that occur naturally in human bone and teeth, making them physiologically inert and biocompatible. The particles are resorbed and eliminated naturally through the body’s normal metabolic and excretory processes.

The two-staged mechanism of action of CaHA involves volume replacement and subsequent biostimulation. The carrier gel provides an initial volume augmentation and then gradually dissipates, while CaHA microspheres stimulate the endogenous production of collagen and elastin through fibroblast activation. Animal studies have demonstrated neocollagenesis beginning as early as 4 weeks posttreatment and continuing for at least 12 months. A histological study of patients receiving supraperiosteal injections of CaHA demonstrated peak concentrations of newly formed type III collagen at four months, while type I collagen predominated at 9 months, consistent with the process of natural neocollagenesis. Elastin expression and angiogenesis also increased, suggesting that dermal remodeling was accompanied by improved nutrient supply to the skin. It is through these mechanisms that CaHA filler provides sustained aesthetic improvement long after implantation.

In 2006, CaHA received US Food and Drug Administration (FDA) approval for correction of moderate to severe facial lines and folds and correction of soft tissue loss from HIV lipoatrophy. An indication for correcting volume loss in the dorsal hands was approved in 2015. Since then, several other body areas have been treated off-label with good effect. This chapter will briefly discuss the use of CaHA as a volumizing filler and then focus primarily on the increasingly popular off-label use of dilute and hyperdilute CaHA as a biostimulatory agent.

CaHA as a Volumizer

For over a decade, CaHA has been used undiluted or slightly diluted to provide immediate correction of soft-tissue volume loss. This is followed by a biostimulatory effect resulting in tighter and thicker skin. The effects have been shown to last for 15 months on average, and in some cases 30 months or more. Longevity varies depending on treatment location, injection technique, and patient age and metabolism.

CaHA has one of the highest viscosities among the available dermal fillers, which prevents migration in areas without significant muscle movement. It also has a high elasticity (G’), providing it with high lifting capacity. These properties make CaHA well suited for facial volume correction in multiple layers depending on the treatment location. Supraperiosteal implantation of undiluted product provides deep volume restoration, while subcutaneous implantation of slightly diluted product provides contour reconstruction, and superficial dermal implantation of highly diluted product provides skin tightening. When used for volumizing, CaHA can immediately correct creases and hollows ( Video 9.2 ). It can be applied to all areas of the face except the glabella, periorbital area, and lips. Injection techniques and experience have been published for facial areas including the forehead, temples, zygomatic cheeks, jawline, and chin, among others. The ability of CaHA to create angled contours has also made it a popular filler for men. While the amount injected may vary by location, the correction ratio for CaHA is approximately 1:1, so overcorrection should be avoided.

CaHA as a Biostimulatory Agent

More recently, CaHA has been increasingly used off-label in a dilute (1:1, i.e., 1.5 mL of product plus 1.5 mL of diluent) or a hyperdilute (≥ 1:2, i.e., ≥ 3 mL of diluent) form to provide dermal rejuvenation without tissue volumization. Hyperdilution causes the carboxymethylcellulose gel to become dispersed, resulting in little or no volumizing effect, while the CaHA microspheres stimulate long-term tissue remodeling. This allows for a more superficial injection over a larger treatment area. Dilutions up to 1:6 (1.5 mL of CaHA product to 9 mL of diluent) have been shown to stimulate collagen and elastin. However, it is not yet clear yet whether neocollagenesis or neoelastogenesis is optimized by a specific ratio. The ideal CaHA dilution should be titrated based on skin thickness and tissue laxity to ensure smooth product placement. One syringe (1.5 mL) of CaHA is typically used to treat an area of 100 to 300 cm ² , but this may vary based on local anatomical features.

To properly dilute CaHA, a LuerLock syringe containing diluent is connected to the original product syringe through a transfer adaptor in a sterile mixing environment. Up to 1.5 mL of 2% lidocaine with or without epinephrine has been used for its anesthetic effect to dilute CaHA, but bacteriostatic saline solution can be added if higher dilutions are required. The syringes should be large enough to accommodate the total volume of filler plus diluent. At least 20 passes between the two syringes should be performed to adequately mix their contents. The final mixture should be injected immediately after reconstitution since components separate quickly, especially with higher dilutions. The physician injector, rather than an assistant, should perform his/her own dilution procedure.

Two separate expert panels provide consensus guidelines detailing the safe and effective use of dilute and hyperdilute CaHA. Both emphasize that the goal is to deliver a thin, smooth, and uniform coating of product at an appropriate depth. This can be achieved with a fanning injection technique or parallel, serial retrograde linear threads in the deep dermal or subdermal plane. Superficial placement of less diluted CaHA can result in unwanted product visibility, especially in areas of thin or darker skin. Massaging the injected area helps to evenly distribute the final product.

Needles (27–30 gauge) or cannulas (22–25 gauge) may be used for injection. Needles allow for extreme precision of movement and deep injection, but can cause more trauma and placement of material at multiple anatomic levels. Cannulas are less traumatic and allow for the placement of product within the desired tissue plane over large areas. Approximately 0.1 or 0.1 to 0.2 mL aliquots are typically deposited with each pass when using a needle or cannula, respectively.

One panel recommends two to three sessions performed at 1- to 2-month intervals for an optimal skin tightening effect, while another recommends one to three sessions during the first year followed by maintenance injections every 12 to 18 months thereafter. Based on data suggesting that the highest deposition of new collagen and elastin occurs approximately 4 months after injection, the latter group recommends follow-up at 3 to 4 months after the initial treatment with reinjection as needed. The use of higher dilutions in certain body areas may necessitate more frequent evaluation and additional treatment sessions.