Calcium Hydroxylapatite (CaHA)

What is calcium hydroxylapatite (CaHA)?

CaHA is short for calcium hydroxylapatite, a filler that is injected under the skin. It is a synthetic product made of minerals that occur naturally in bone and teeth; it is not of animal origin. It both adds volume and stimulates the tissue's own collagen production.

The product has two components: calcium hydroxylapatite microspheres and a gel called sodium carboxymethylcellulose, which carries them. According to research on collagen stimulators, the microspheres give structural support immediately after treatment; at the same time, they act as a biological scaffold for new collagen formation.

CaHA is not a permanent filler. It is a substance that the body can break down over time, and together with poly-L-lactic acid it is classed as a semi-permanent filler. These substances are broken down by water (hydrolysis) and by enzymes from the cells involved in breaking down bone. They usually stay in the tissue for up to two years; in individual patients, periods of more than five years have also been reported.

You can also find its use for volume and support in the face on the Liquid Facelift with Collagen Stimulators page, and its use for skin quality outside the face on the Collagen Stimulator Treatments page.

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How does it work?

According to research, CaHA works in two stages. First, it adds volume immediately after treatment. It then stimulates the tissue (this is called biostimulation), and the collagen formed in this way gives a longer-lasting correction.

Studies show that CaHA increases cell growth, collagen production and new blood vessel formation in the tissue, as well as the formation of elastic fibres and elastin. However, according to a systematic review of 12 studies on this topic, only seven of these studies had a control group; most had methodological weaknesses, and the evidence remains limited.

Experts also stress one point: replacing a single biological component of the tissue is not enough to count a treatment as one that “regenerates tissue”; what matters is the ratio, type and arrangement of the components. In this consensus statement, prepared by six experts, CaHA is mentioned as an example reported to improve the ratio of type I to type III collagen and to stimulate the production of elastin and proteoglycans (one of the building blocks of connective tissue). This is expert opinion, not a controlled study.

What this means for you: part of the change you see after CaHA appears on the day of treatment, and part depends on a tissue response that develops over time. According to experts, a key part of setting the right expectations is to explain in detail, before treatment, that part of the result will appear later.

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Undiluted CaHA: volume and contour

The first and most studied use of CaHA is undiluted, at its own consistency, for volume and contour support. The areas considered suitable for this use are the mid-face, the lower face and the backs of the hands. CaHA is a highly viscous and elastic filler, meaning it has a firm consistency that holds its shape.

A systematic review that brought together controlled clinical studies examined 13 studies: 8 on the face and 5 on the backs of the hands. CaHA injection was associated with an increase on the global aesthetic improvement scale in both the face and the backs of the hands, and improvement was reported in areas such as the nasolabial folds and jawline. However, because the studies differed greatly from one another, the results could only be assessed qualitatively, and the review stressed that more controlled studies are needed.

In a combined analysis (meta-analysis) of four randomised controlled trials (trials in which participants are randomly assigned to groups) on nasolabial folds, no significant difference was found between CaHA and hyaluronic acid in blood collecting under the skin (haematoma) or nodules (small, firm lumps you can feel under the skin). This suggests that the two substances behave similarly in this area with regard to these two adverse effects; however, the result is based on only four studies.

The upper third of the face is a separate matter. In a study that retrospectively reviewed the records of 70 patients who had CaHA in the forehead, brows and temples, no serious complications were recorded. Even so, the authors state that the gold standard in this area — the first-choice substance — is hyaluronic acid, and that prospective research is needed to establish the value of CaHA here. You can find details of how each area of the face is approached on the Liquid Facelift with Collagen Stimulators page.

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Skin renewal with diluted CaHA

Diluted CaHA means mixing the same substance with a liquid such as saline and injecting it under the skin, spread over a wide area. Here the aim is skin quality and skin laxity rather than volume. The purpose of dilution is to reduce the substance's immediate volumising effect and to increase its spread in the tissue and its interaction with cells, so that collagen and elastin production comes to the fore in the long term.

Consensus guidelines prepared by an international expert panel distinguish between two terms: when one unit of liquid is added to one unit of product, this is called diluted use; when two or more units of liquid are added, it is called highly diluted (hyperdiluted) use. According to the guidelines, this use aims to improve laxity and skin quality in the mid-face and lower face, neck, décolletage, upper arms, abdomen, thighs and buttocks; it can be planned in addition to volumising use or together with other methods.

You should also know the level of evidence for this use. The guidelines describe themselves as preliminary guidelines prepared for a new off-label use of CaHA (outside the manufacturer's intended purpose), and they state that more research is needed. Some of the studies in this area are small: in a pilot study of 20 people on the neck and décolletage, tissue samples (biopsies) showed increases in type I collagen, elastin and blood vessel formation; in 20 patients with neck laxity, improvement was reported at month 3 in ratings based on photographs.

There are few randomised trials. In a multicentre randomised trial of diluted CaHA for décolletage wrinkles, in which the assessors did not know which group participants were in, participants were assigned to two different treatment schedules. When the two groups were assessed together 16 weeks after the last treatment, an improvement of at least one grade on the wrinkle scale was reported in 73.5% of participants.

The consensus guidelines also point out that, in thin skin and darker skin, injecting a less diluted product too superficially can lead to more side effects. In other words, the dilution ratio and the injection depth are not independent decisions. Which preparation is suitable for your skin is assessed at your consultation; you can find area-by-area details on the Collagen Stimulator Treatments page.

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Use with hyaluronic acid

In some treatments, CaHA is used together with hyaluronic acid. There are two ways of doing this: carrying out two separate treatments together in the same plan is called combined use, and mixing the two substances directly from syringe to syringe is called hybrid use.

According to a systematic review of these uses, the two substances stimulate collagen production through different molecular pathways. Combined and hybrid treatments were associated with high aesthetic effectiveness and satisfaction in various areas of the face, and with minor adverse effects that resolved on their own. After the sixth month, however, a slight downward trend was seen in both aesthetic improvement and satisfaction.

However, because the studies differed greatly from one another, only a qualitative assessment was possible; better-designed studies are needed for strong, long-term evidence. In short, although this use looks promising, treatment protocols are not yet clearly established.

There is one more detail you should know when deciding: hyaluronic acid is classed as a filler that can be fully reversed with hyaluronidase, whereas CaHA is classed only as an adjustable filler. The summary of the review on these uses does not address what it means for the CaHA component when the hyaluronic acid in the mixture is dissolved with the enzyme. So if a plan involves a mixture, you need to ask separately whether the whole mixture can be reversed.

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Limits of this substance

CaHA provides volume and collagen support; however, it is not suitable for every area or every goal, and if you do not like the result, it cannot be reversed with an enzyme. Removing excess skin or repositioning sagging tissue is not what this substance does, and none of the studies mentioned here compares CaHA with a surgical method.

The first limit concerns the area. A consensus based on both scientific evidence and expert experience recommends not using CaHA in very mobile areas such as the lips, or in areas where there is no room for error, such as around the eyes. The reason is the substance's high viscosity and elasticity — its firm consistency that holds its shape — and the fact that nodules can be more frequent in these areas. You can find information about lip filler on the Lip Filler page.

The second limit concerns reversibility. Hyaluronic acid is regarded as a filler that can be fully reversed with hyaluronidase, whereas CaHA is regarded only as an adjustable filler. Hyaluronidase breaks down hyaluronic acid fillers; CaHA, by contrast, is broken down by water and by enzymes from the cells involved in breaking down bone. You can find the details in the Can it be reversed? section below.

The third limit is the evidence itself. Although there are controlled studies on undiluted use, more controlled studies are needed because of differences between the studies and their methodological limitations. The consensus guidelines published for diluted use describe themselves as preliminary guidelines prepared for an off-label use. This does not mean that CaHA does not work; it shows that how well it works is so far known from a limited number of studies with differing designs.

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Can it be reversed?

No, CaHA does not dissolve with the enzyme hyaluronidase. Hyaluronidase is an enzyme that breaks down hyaluronic acid fillers. In scientific classification, hyaluronic acid is a filler that can be fully reversed with this enzyme, whereas CaHA is only an adjustable filler. In the body, CaHA is broken down by water (hydrolysis) and by enzymes from the cells involved in breaking down bone.

The search for a dissolving agent for CaHA continues, but the data in this area are experimental. The candidate substance is sodium thiosulfate. In a laboratory and cadaver study, this substance increased breakdown when it came into direct contact with CaHA in the laboratory; however, it did not dissolve CaHA inside the facial arteries of cadavers after 24 hours. A mixture of sodium thiosulfate and hyaluronidase also did not dissolve CaHA inside the blood vessels. The authors concluded that there is no suitable antidote for CaHA that has entered a blood vessel.

In another preclinical study, in pigs, no evidence was found that the microspheres had broken down, and the authors noted that the loss of volume seen may have been due to the substance spreading; in addition, tissue death and bleeding were observed after sodium thiosulfate was given. A review of how fillers break down also states that this substance can stimulate the breakdown of CaHA, but it acts slowly and is not effective in an emergency.

In a case series of three patients with blood vessel problems caused by non-hyaluronic acid fillers, hyaluronidase was added to treatment, and the conditions resolved without tissue death (necrosis) or scarring. The authors put forward the hypothesis that the effect came not from dissolving the filler but from relaxing the narrowed blood vessels. This is a hypothesis based on three cases; it is not an established method of reversal.

At this clinic, for fillers done elsewhere, you are first asked about the type of filler, when it was done and the area; fillers of unknown type, or fillers that cannot be confirmed to be hyaluronic acid, are not dissolved straight away. Where a substance that cannot be dissolved with an enzyme is involved, knowing the type of filler you had before is the starting point for every later decision.

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Does it show up on X-rays and CT scans?

Yes, it can. CaHA is a radiopaque filler, meaning X-rays do not pass through it, and it can leave a trace on imaging. This is not a warning sign but a feature you should know about: a doctor reviewing a future X-ray or scan needs to have this information.

In a study of 58 patients who had CaHA for nasolabial folds or for HIV-related facial fat loss, the substance did not show up consistently on plain X-rays; on computed tomography (CT) done immediately after treatment, however, it was seen in almost all cases. The same study reported that CaHA did not obscure the underlying structures, that there was no sign it had moved, and that it could be told apart from the surrounding bone.

In a study that followed 20 people who had CaHA in the backs of the hands for two years, the substance was seen in 100% of hands on X-rays at month 1 and in 83.3% on X-rays at month 24. At no time point was it found to obscure the bones in a way that would prevent their assessment. This finding shows that the substance can still be seen on X-rays two years later.

A case from a different area of use points the same way: in a patient who had CaHA injected in the vocal cord area, positron emission tomography (PET) showed intense uptake at the injection site, and this appearance lasted for one year. The authors note that this can lead to a misleading, false-positive finding. In practice, this means that if you will have an X-ray, CT or PET scan in the future, it is helpful to tell the doctor reviewing the scan that you have had CaHA.

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Known risks

CaHA injection is a medical procedure and it carries risks. In a systematic review of PLLA (poly-L-lactic acid) and CaHA treatments in the face, the most common adverse effects were mild; the main ones were pain and swelling at the injection site. This review also reported a serious case with CaHA: pressure-related tissue death (compression necrosis). The consensus guidelines for diluted use list the injection-related effects as bruising, swelling, mild pain and firmness.

The main problem specific to CaHA is nodules. In a review covering 5,081 treatments in 2,779 patients, 173 adverse events (3%) were reported, and 166 of these (96%) were nodules. Of these nodules, 49% occurred in mobile areas known to have a high tendency to form nodules. According to the authors, most nodules were not visible from the outside and went away without any intervention.

According to a publication that classifies hyaluronic acid and CaHA nodules, the cause of a nodule often lies less in the product itself than in procedure-related factors such as injection technique and bacterial contamination. The authors recommend ruling out common causes such as infection before treating a nodule, and using ultrasound imaging for persistent nodules to identify the location and nature of the material. In a systematic review of foreign body granulomas (inflammatory lumps that the body forms in reaction to a foreign substance) linked to collagen stimulators, CaHA is among the substances for which this condition has been reported; in the cases in the review, the condition was noticed between one week and fifteen years after treatment.

The most serious risk is the substance being injected into an artery by accident. According to an international expert consensus statement on CaHA, this can cause tissue death, permanent scarring, visual impairment and blindness; although it is rare, it needs immediate treatment. In a systematic review of vision loss linked to collagen stimulators, at least 11 cases of vascular occlusion (a blocked blood vessel) causing visual impairment were reported with CaHA; most of these were associated with injections into the bridge of the nose.

Before the procedure, you will be asked about blood thinners, antiplatelet medicines (which stop platelets from clumping together) and supplements that can affect bleeding. Do not stop any prescribed medicine on your own. If needed, the procedure is planned or postponed after consulting the relevant doctor. How much these risks weigh in your case is discussed at your consultation, together with your medical history.

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How are the product and its intended purpose assessed?

The purpose and areas for which a CaHA product can be used depend on the manufacturer's intended purpose and on what the product has been approved for. According to the consensus guidelines for diluted use, CaHA is approved for correcting moderate to severe wrinkles, folds and soft tissue volume loss in the face and hands; using it diluted for skin laxity, however, is off-label.

The history of the substance is also instructive here: CaHA was first approved, and CE-marked in Europe, for non-aesthetic purposes; for a time it was used for aesthetic purposes outside these approvals, and approval for aesthetic use came later. This history is a reminder that the word “approval” always applies to a specific country, a specific area and a specific purpose.

At this clinic, approval from the US Food and Drug Administration (FDA) is not the only criterion when assessing a product; the product's CE marking, its registration and conformity status in Türkiye and the manufacturer's intended purpose form the basis. The doctor chooses a needle or a cannula (a fine tube with a blunt tip) for each person individually, according to the treatment area and the anatomy. Before treatment, you can ask which area and which purpose the product to be used has been approved for.

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