A Prospective, Multicenter, Evaluator-Blinded, Randomized Study of Diluted Calcium Hydroxylapatite to Treat Decollete Wrinkles.

BACKGROUND: Calcium hydroxylapatite (CaHA) dermal filler is used for a variety of aesthetic treatments; however, the safety and effectiveness of diluted CaHA for the treatment of décolleté wrinkles have not been established. OBJECTIVE: To demonstrate the effectiveness and safety of diluted CaHA (Radiesse; 1:2 CaHA:saline) injection for the improvement of décolleté wrinkles in females. METHODS: Eligible females with moderate or severe ratings on the Merz Aesthetic Scale (MAS) Decollete Wrinkles - At Rest received up to 3 injection cycles of diluted CaHA either 8 weeks apart (3 injection cycles) or 16 weeks apart (2 injection cycles). Effectiveness was evaluated by improvement on the MAS. Adverse events were recorded over a 52 week period. RESULTS: Sixteen weeks after the last treatment, the response rate (1-point improvement or greater) on the MAS Decollete Wrinkles - At Rest was 73.5% (P<0.0001; pooled sample) for all patients. The use of diluted CaHA in the decollete also demonstrated a favorable safety profile. CONCLUSIONS: Diluted CaHA is a safe and effective treatment for the improvement of decollete wrinkles in females.J Drugs Dermatol. 2024;23(7):551-556.  doi:10.36849/JDD.8261.

A systematic review of Radiesse® (calcium hydroxylapatite): evidence and recommendations for the body.

A filler composed of calcium hydroxylapatite and carboxymethylcellulose gel (CaHA/CMC) has been shown to possess biostimulatory and skin-tightening properties that have been applied not just to the face but also to the body to boost rejuvenation. Recently, evidence and recommendations for CaHA/CMC treatment of the face have been provided, but they are still lacking in terms of body treatment. This article aims to perform a systematic review of the literature on CaHA/CMC applications on the body and provide evidence from the literature. Currently, the only FDA-approved indication on the body is treating the hands and a recent European Union Medical Device Regulation approval has been released for decolletage treatment. The application of hyperdilutions on the neck, feet, arms, thighs, abdomen, and other body parts has been proven to provide a skin-tightening effect. However, despite their wide use with a good safety profile in clinical practice, recent trends and guidelines of diluted and hyperdiluted CaHA/CMC have yet to be supported by randomized controlled trials.

A systematic review of Radiesse/calcium hydroxylapatite and carboxymethylcellulose: evidence and recommendations for treatment of the face.

Radiesse® is a filler composed of calcium hydroxylapatite microspheres suspended in a carboxymethylcellulose gel (CaHA/CMC). It has robust rheological properties that have been associated with its versatility. CaHA/CMC is employed for both on-label indications of filling wrinkles or lines, volumizing, and contouring of areas as well as off-label indications aiming at biostimulation and skin tightening. However, despite the expanding use of CaHA/CMC, overall evidence and recommendations for treatment are currently lacking. This paper aims to provide an up-to-date overview of CaHA/CMC clinical applications, together with a level of evidence of supporting literature, focusing on the face. Based on the data, CaHA/CMC may be considered a safe and effective treatment option for cheeks, jawline, HIV-related facial lipoatrophy, and nasolabial folds. Treatment of marionette lines, chin, pre-jowl, and corner of the mouth also tends to respond with a high degree of efficacy. Despite the recent trend, guidelines, and safety profile of diluted and hyperdiluted Radiesse® , no randomized controlled trials have been published.

Hydroxyapatite-coated compared with stainless steel external fixation pins did not show impact in the rate of pin track infection: a multicenter prospective study.

PURPOSE: Infection at the pin site remains the most common complication of external fixators (EFs). It is known that hydroxyapatite (HA)-coated pins increase bone adhesion and may lead to reduced rates of reported infections. The present study compares the rates of pin track infection associated with stainless steel and HA-coated pins. METHODS: This is a prospective, multicenter, nonrandomized, comparative intervention study among patients undergoing surgical treatment with EFs of any type between April 2018 and October 2021. Patients were followed up until the removal of the EF, or the end of the study period (ranging from 1 to 27.6 months). The definition of pin track infection was based upon the Maz-Oxford-Nuffield (MON) pin infection grading system. RESULTS: Overall, 132 patients undergoing external fixation surgery were included. Of these, 94 (71.2%) were male, with a mean age of 36.9 years (SD ± 18.9). Infection of any type (score > 1) was observed in 63 (47.7%) patients. Coated and uncoated-pin track-infection occurred in 45.7% and 48.5% of patients, respectively (P= 0.0887). The probability of developing infection (defined as a score ≥ 2) adjusted for comorbidities and follow-up time was not statistically higher among those who received uncoated pins compared to those who received pins coated with HA (odds ratio (OR) = 1.56, 95% confidence interval (95% CI): 0.67-3.67, p <0.05). CONCLUSION: In the present study, the external fixator pin infection rates were similar when using HA coating and standard steel pins.

A Very Rare Complication of Vocal Fold Augmentation With Calcium Hydroxylapatite: Neck Abscess.

INTRODUCTION: Vocal fold injection augmentation is performed routinely for the treatment of glottic insufficiency especially due to unilateral vocal fold paralysis. There are numerous materials that are used for injection laryngoplasty, calcium hydroxylapatite being one of them. CASE REPORT: We present an interesting case of a 64-year-old male patient with metastatic acinic cell carcinoma of the right parotid gland, who underwent right vocal cord injection laryngoplasty with calcium hydroxylapatite for right vocal cord paralysis with glottal insufficiency and developed a neck abscess. DISCUSSION: This is the first report in the literature of neck abscess following vocal fold injection laryngoplasty using calcium hydroxylapatite. It seems that over injection of the vocal fold gave rise to extravasation of the injected material outside the laryngeal framework which later became a nidus for infection. CONCLUSIONS: We present the first case in the literature of neck abscess following vocal fold injection laryngoplasty using calcium hydroxylapatite. Clinicians should be aware of this rare but dangerous complication.

Mid-term efficacy and safety of Escherichia coli-derived rhBMP-2/hydroxyapatite carrier in lumbar posterolateral fusion: a randomized, multicenter study.

PURPOSE: This study aimed to evaluate the mid-term efficacy and safety of Escherichia coli-derived bone morphogenetic protein-2 (E.BMP-2)/hydroxyapatite (HA) in lumbar posterolateral fusion (PLF). METHODS: This multicenter, evaluator-blinded, observational study utilized prospectively collected clinical data. We enrolled 74 patients who underwent lumbar PLF and had previously participated in the BA06-CP01 clinical study, which compared the short-term outcomes of E.BMP-2 with an auto-iliac bone graft (AIBG). Radiographs and CT scans were analyzed to evaluate fusion grade at 12, 24, and 36 months. Visual analog scale (VAS), Oswestry disability index (ODI), and Short Form-36 (SF-36) scores were measured preoperatively and at 36 months after surgery. All adverse events in this study were assessed for its relationship with E.BMP-2. RESULTS: The fusion grade of the E.BMP-2 group (4.91 ± 0.41) was superior to that of the AIBG group (4.25 ± 1.26) in CT scans at 36 months after surgery (p = 0.007). Non-union cases were 4.3% in the E.BMP-2 and 16.7% in the AIBG. Both groups showed improvement in pain VAS, ODI, and SF-36 scores when compared to the baseline values, and there were no statistically significant differences between the two groups. No treatment-related serious adverse reactions were observed in either group. No neoplasm-related adverse events occurred in the E.BMP-2 group. CONCLUSIONS: The fusion quality of E.BMP-2/HA was superior to that of AIBG. E.BMP-2/HA showed comparable mid-term outcomes to that of AIBG in terms of efficacy and safety in one-level lumbar PLF surgery.

Clinical and histological comparative outcomes after injections of poly-L-lactic acid and calcium hydroxyapatite in arms: A split side study.

BACKGROUND: Although much has been published on the use of poly-L-lactic acid (PLLA) and calcium hydroxyapatite (CaHA) for off-face indications, questions remain regarding their exact mechanisms of action in subcutaneous tissue and their comparative efficacy. OBJECTIVE: To present the clinical and histological results of the PLLA and CaHA injections into the opposing arms of the same patients. METHODS: Five women received superficial subcutaneous injections of PLLA into the left arm and CaHA into the right arm. After three sessions, the clinical and histological outcomes were analyzed. RESULTS: After the first session, three patients showed improvement in the right arm (CaHA), but at the end of study, two patients showed better results in the left arm (PLLA). Histologically, moderate to intense lymphocytic and giant cell infiltrate, as well as collagen and elastic fiber neoformation, were observed equally near the particles of both products. Dermis had no inflammatory or fiber alterations. CONCLUSION: In this study, there were no clinical differences between these two fillers. Despite current thinking and previous histological studies, we found both products produced moderate to intense inflammatory reaction, as well as collagenic/elastogenic fiber neoformation, only in the subcutaneous tissue of the immediate vicinity and surrounding the individual filler particles.

Severe Airway Edema Following Calcium Hydroxylapatite (CaHA) Injection Augmentation.

This case study presents an abnormal complication after routine injection augmentation using calcium hydroxylapatite (CaHA) vocal fold filler in-office on a 73-year-old female. The patient presented initially with severe dysphonia, hypophonia, and a past surgical history of total thyroidectomy, bilateral neck dissection, and a right lateral neck dissection for history of metastatic papillary thyroid carcinoma. She also had a past medical history of hypothyroidism. Post-injection of CaHA, the patient developed severe laryngeal edema, limited vocal cord mobility, obliteration of the pyriform, and a significantly reduced airway aperture requiring intensive care monitoring. Although uncommon, injectable fillers can result in complications which can be severe. Careful technique, the volume of injectate, and hypersensitivity should be considered in reducing complications following injection augmentation. There are multiple injection techniques to consider. The most direct approach is with direct laryngoscopy to allow for visualization of glottic incompetence. A smaller slotted laryngoscope can be considered for vocal fold injection as an alternative and without endotracheal intubation. Although these techniques allow for injection, real-time assessment of vocal fold closure is done in an awake patient. Therefore, laryngeal injection can be considered via percutaneous, per-oral, and trans-nasal approaches.

The clinical efficacy of hydroxyapatite and its composites in spinal reconstruction: a meta-analysis.

OBJECTIVE: Synthetic hydroxyapatite (HA) and its related materials have made great progress in basic research and clinical application in spinal repair and reconstruction. However, the effect of HA and its composites used in spinal fusion still remained controversial. This meta-analysis aimed at evaluating the efficacy and safety of HA compared with autologous bone. MATERIALS AND METHODS: A systematic search in PubMed, MEDLINE, China National Knowledge Internet, EMBASE, and the Cochrane Library was conducted for relevant studies from inception until May 2021. Studies investigating the application of HA and its related composites in spinal fusion were selected for analysis. RESULTS: The operation time of patients treated with artificial bone containing HA was less than that of patients with autologous bone (p = 0.02). The amount of operative blood loss in patients in the HA group was less than that in the autograft group (p = 0.007). Patients treated with autologous bone got a more significant advantage in fusion rate at 6 months (p = 0.009). Nevertheless, there was no significant difference in the fusion rate between patients in the two groups at 12 months or no less than 24 months postoperatively (p = 0.24; p = 0.87). Compared to the autograft group, the HA group significantly decreased postoperative adverse events (p = 0.03). Furthermore, there was no significant difference in the Oswestry Disability Index (p = 1.00) nor the Visual Analogue Scale score (p = 0.94) between the two groups. CONCLUSIONS: This meta-analysis suggests that the clinical application of HA and its related composite materials in spinal reconstruction is comparable to that of autologous bone, with satisfactory efficacy and safety.

Calcium Hydroxyapatite Filler With Integral Lidocaine CaHA (+) for Soft Tissue Augmentation: Results from an Open-Label Multicenter Clinical Study.

BACKGROUND: Soft tissue augmentation with calcium hydroxylapatite (CaHA) is a versatile technique for line filling, skin tightening, lifting, contouring, and volumizing. The present study was designed to confirm safety and effectiveness of the product with lidocaine (CaHA (+)) in a holistic treatment of nasolabial folds (NLFs), marionette lines, and/or cheeks. METHODS: A total of 207 subjects with moderate to severe facial volume deficit were treated with CaHA(+) in this open-label study. Effectiveness assessments included Merz Aesthetics Scales® (MAS), investigator- and subject-assessed Global Aesthetic Improvement Scales (iGAIS/sGAIS), and FACE-QTM questionnaires. Responder rates were defined as at least one-point improvement on MAS according to blinded rating. Safety was assessed through adverse event reporting. RESULTS: Primary endpoint was evaluated 12 weeks after last injection. Responder rates were 93.6%, 88.7%, and 81.9% in the NLFs, marionette lines, and cheeks, respectively, and were statistically significant above the pre-defined 60% threshold (P< 0.0001). Investigator- and subject-assessed GAIS were consistent and showed high rates of improvement throughout the study, with peak values of 98.0% at week 4 on iGAIS and 93.5% at 12 weeks after last injection on sGAIS. After 18 months, the majority of subjects (52.5%) still perceived improvement via sGAIS. Moreover, total FACE-Q scores demonstrated high subject satisfaction with treatment. All related treatment emergent adverse events were transient and expected injection-site reactions mostly of mild to moderate intensity. CONCLUSION: CaHA (+) has demonstrated safety and effectiveness in the treatment of NLFs, marionette lines, and cheek volume loss in real-life conditions up to 18 months. J Drugs Dermatol. 2022;21(5):481-487. doi:10.36849/JDD.6737.

Serious Adverse Events With Injectable Fillers: Retrospective Analysis of 7,659 Patient Outcomes.

BACKGROUND: In total, 2.7 million injectable filler treatments were performed in 2019 in the United States. Although generally considered to be a safe treatment modality, adverse events may occur in rare situations. OBJECTIVE: Analyze serious adverse events from injectable filler treatments, including infections, cutaneous necrosis, blindness, or delayed-onset nodule formation, spanning 11 years for 3 board-certified dermatologists and review their incidence, management, and outcomes. MATERIALS AND METHODS: A retrospective analysis was performed of injectable filler treatments spanning 11 years at a multipractitioner outpatient clinic. Serious adverse events were identified, and treatment measures were documented. A literature search was performed to determine recent trends and outcomes for comparison. RESULTS: Between January 2009 and August 2020, 18,013 mL of injectable filler was administered to 7,659 patients. Of the 18,013 mL administered, 74.1% comprised hyaluronic acid derivatives, 19.19% poly-l-lactic acid, and 6.71% calcium hydroxylapatite. Four serious adverse events were identified. Three events were delayed-onset skin nodule formation. One adverse event was related to vascular compromise and subsequent cutaneous necrosis. After appropriate treatment, all adverse events resolved without significant long-term sequelae. CONCLUSION: Serious adverse events associated with injectable fillers, when performed by board-certified dermatologists, are extremely rare and can be successfully managed with appropriate treatment.

A Randomized, Evaluator-Blind, Split-Face Study Evaluating the Safety and Efficacy of Calcium Hydroxylapatite for Jawline Augmentation.

INTRODUCTION: Jawline augmentation with calcium hydroxylapatite has not yet been evaluated in a prospective study with a split-face design. This study aims to perform the first randomized controlled, split-face study on the efficacy and safety of calcium hydroxylapatite for jawline augmentation using the needle and cannula technique. OBJECTIVE: To perform the first randomized controlled, split-face study on the efficacy and safety of calcium hydroxylapatite for jawline augmentation using the needle and cannula technique. MATERIALS AND METHODS: This is a single-site, randomized, evaluator-blind trial enrolling a total of 10 healthy subjects with at least Grade 1 (mild) on a 4-point Jawline Scale. One side of the face was randomized to receive 1 to 2 syringes of calcium hydroxylapatite with lidocaine (total of 3 mL) for correction of wrinkles and folds along the jawline using both the cannula and needle method, and a balancing treatment will be performed 1 month later. Blinded investigator and subject evaluations will be performed immediately after treatment and at the 30-, 60-, and 90-day visits. RESULTS: Ten subjects were enrolled and completed the trial. There was a improvement in the degree of wrinkling and skin sagging in the 4-point Jawline Scale, with an average of a 1.3-point improvement in the scale on the day of treatment and at the Day 30 visit, which remained improved greater than baseline after 3 months as graded by blinded investigators. The Clinician Global Aesthetic Improvement Score for the treated side versus control, as assessed by blinded investigators, demonstrated a improvement with a 2.3-point improvement on the 5-point scale, and by the final visit on Day 90, most patients had a much improved appearance from baseline. CONCLUSION: This study demonstrates that calcium hydroxylapatite is effective and safe for restoration and augmentation of the jawline using the unique needle and cannula technique.

Delayed Complications following Dermal Filler for Tear Trough Augmentation: A Systematic Review.

Tear trough deformity is a popular target for the treatment with filler injections. The side effects are generally mild and transient. However, delayed complications may occur. We aim to perform a thorough systematic review of the published literature related to delayed complications after tear trough filler injections. A search of published literature was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines in June 2021 and included PubMed, ScienceDirect, and Embase databases. The Medical Subject Headings (MeSH) terms used included the following terms: delayed complications, nodules, granulomas, swelling, discoloration, dermal filler, hyaluronic acid (HA), polyacrylamide, calcium hydroxyapatite (CaHA), poly-L-lactic acid (PLLA), eyelid, periorbital, periocular, and tear trough. Twenty-eight articles consisting of 52 individual cases were included in the final analysis. 98% (51/52) of patients were female and had an average age of 48.3 years. HA was the most reported product (71.2%, 37/52), followed by PLLA (4/52, 7.7%), and CaHA (4/52, 7.7%). The most common delayed complication with any dermal filler was swelling (42.3%, 22/52) followed by lumps or nodules (25.0%, 13/52). Xanthelasma-like reaction (17.3%, 9/52), migration (7.7%, 4/52), discoloration (3%, 3/52) also occurred. The average time of onset of any complication was 16.8 months with xanthelasma-like reaction appearing soonest (mean: 10 months) and discoloration appearing latest (mean: 52 months). Most swelling cases were caused by HA. Semi-permanent fillers such as PMMA and synthetic fillers such as PLLA were more likely to be associated with lumps and nodules than other complications. It is important that clinicians who perform tear trough augmentation with dermal fillers have a thorough understanding of the risks of the procedure to diagnose and manage them promptly as well as provide patients with accurate information regarding the potential adverse effects.

Combining Calcium Hydroxylapatite and Hyaluronic Acid Fillers for Aesthetic Indications: Efficacy of an Innovative Hybrid Filler.

BACKGROUND: Limited data are available describing effectiveness of combining the use of calcium hydroxylapatite (CaHA) and hyaluronic acid (HA). METHODS: The authors performed a retrospective chart review of patients injected with a premixed combination of CaHA and a cohesive polydensified matrix (CPM®) HA (CaHA:CPM-HA ) in the authors' aesthetic practices. The midface and lower face were injected. Patients' records were evaluated, and treatment results were scored using the Merz Aesthetics Scale for the jawline® (clinician rated, CR-MASJ). Adverse events were recorded. RESULTS: A total of 41 patients were included, all females with a mean age of 47.5 years (range 21-63 years). The mean CR-MASJ score improved from 2.12 at baseline to 0.68 at t = 3 months (SD = 0.69, 95% CI 1.28-1.60) and 1.27 at t = 12 months (SD = 0.74, 95% CI 0.43-0.74). 100% of the subjects had experienced a ≥1-point improvement in CR-MASJ score at t = 3 months, versus 85% at t = 12 months. No adverse events were reported. CONCLUSION: The results of this study support the volumizing and lifting potential of the hybrid mix CaHA:CPM-HA for treatment of cheeks and jawline. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Safety and Efficacy of Dermal Fillers in Patients With Connective Tissue Disease: A Review.

BACKGROUND: Dermal fillers such as hyaluronic acid, poly-l-lactic acid, and polymethyl-methacrylate are often used to treat cutaneous defects such as lipoatrophy. However, concern exists regarding their use in patients with a connective tissue disease (CTD) because of a theoretical risk of disease reactivation or exacerbation. Evidence regarding their use in patients with CTD also remains limited. OBJECTIVE: This review intends to summarize and evaluate the available literature regarding the use of dermal fillers in patients with CTD. MATERIALS AND METHODS: A literature search until May 2020 was conducted through PubMed, Ovid MEDLINE, and Ovid Embase to identify articles discussing the treatment of cutaneous defects secondary to CTD. Articles discussing the use of autologous fat transfer alone were excluded. RESULTS: Twenty-three articles were reviewed. The amount of available evidence varies between the type of CTD and type of filler with morphea having the most published evidence out of the CTDs discussed and hyaluronic acid having the most published evidence out of the fillers discussed. Most studies demonstrated positive results with no report of disease reactivation or exacerbation. CONCLUSION: Despite limited available evidence, dermal fillers seem to be safe as an adjunctive treatment for cutaneous defects in patients with CTD.