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Improvement of calcified tendonitis following human placenta extract injection: A retrospective, single-arm, multicenter observational study
, Yeongmin Kwond, Jooyoung Kimd, Aram Shind, Taebin Jeongd
⁎Corresponding author: Taehwan Cho. GClaennec@gmail.com
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Received: ,
Accepted: ,
This article was originally published by Reed Elsevier India Pvt. Ltd. and was migrated to Scientific Scholar after the change of Publisher.
Abstract
Abstract
Calcific tendinitis, a common shoulder disorder, is characterized by pain and functional limitation. Human placental extract (HPE) exhibits anti-inflammatory and regenerative properties, suggesting therapeutic potential in this condition.
Forty patients with calcific tendinitis were treated with weekly subacromial-subdeltoid bursa injections of 4 mL HPE for 4 weeks. Pain levels were assessed using the Visual Analog Scale (VAS), and changes in calcific deposits were evaluated using ultrasound imaging.
Mean VAS scores significantly decreased from 6.8 ± 0.7 to 1.8 ± 0.8 (p < 0.05) following treatment. Ultrasonographic evaluation showed complete resolution of calcification in 10 % of patients and partial improvement in the remaining 90 %. No adverse events were reported during the study period.
Subacromial HPE injections effectively reduced pain and improved imaging findings in patients with calcific tendinitis and were well tolerated. Further studies remain warranted to confirm these findings in controlled settings.
Keywords
Human placental extract
Calcific tendinitis
Visual analog scale
HPE
VAS
ESWT
TNF-α
IL
1 Introduction
Calcific tendinitis of the shoulder is a painful musculoskeletal disorder characterized by the deposition of calcium hydroxyapatite crystals within the tendons of the rotator cuff, particularly the supraspinatus tendon.1 It typically affects individuals ages 30–50 and is more prevalent in women.2 Although the exact pathogenesis remains unclear, it is believed to involve a multifactorial process including tendon degeneration, cellular necrosis, and subsequent dystrophic calcification. The disease progresses through three stages: precalcific, calcific (formative and resorptive phases), and postcalcific. During the resorptive phase, patients often experience severe pain and functional impairment due to inflammation and mechanical irritation caused by the calcific deposits.1,2
While calcific tendinitis can resolve spontaneously, especially during the early stages, a considerable proportion of patients experience persistent symptoms that interfere with daily activities and quality of life.1,2 Conservative management, which includes non-steroidal anti-inflammatory drugs, physiotherapy, extracorporeal shockwave therapy (ESWT), and ultrasound-guided needle lavage, remains the first-line treatment. In refractory cases, surgical interventions, such as arthroscopic debridement, may be required.1,3–5 However, many of these treatments primarily address symptom relief and do not actively promote resolution of calcific deposits or tendon regeneration, potentially leading to symptom recurrence.
Human placental extract (HPE), commercially available in South Korea, is an injectable chemical product derived from hydrolyzed, full-term human placenta. HPE is rich in bioactive components, including peptides, cytokines, amino acids, nucleic acids, and vitamins, as well as various growth factors. Clinically, HPE has been approved for use in the treatment of hepatic dysfunction, fatigue, climacteric symptoms, and certain dermatologic conditions.6–8
Beyond its established indications, preclinical research has revealed that HPE possesses a range of therapeutic properties, including anti-inflammatory, antioxidant, analgesic, and regenerative.6,7,9–11 These properties are particularly relevant to tendinopathies, which involve chronic inflammation, oxidative stress, and impaired tissue healing.2,11 HPE inhibits pro-inflammatory mediators such as tumor necrosis factor alpha (TNF-α), interleukin (IL)-6, and IL-1β, while promoting collagen synthesis, fibroblast proliferation, and tissue remodeling.6,9,11,12 In a mouse model of inflammatory pain, HPE significantly reduced mechanical hypersensitivity and inflammatory cytokine levels.12 Additionally, in vitro studies on tenocytes and fibroblasts have shown enhanced extracellular matrix production and accelerated wound closure following HPE exposure.10
Clinically, HPE has shown beneficial effects in musculoskeletal disorders.13,14 A randomized controlled trial demonstrated that intra-articular HPE injection significantly improved pain and function among patients with knee osteoarthritis.14 More recently, a single-blind trial found that subacromial injection of HPE improved pain and range of motion in patients with shoulder impingement syndrome, without notable adverse events.9,13 HPE may also be effective when injected into acupuncture points or periarticular regions for conditions such as fibromyalgia, osteoarthritis, and complex regional pain syndrome.15–20
Calcific tendinitis, with its combined pathophysiology of mechanical irritation and cytokine-driven inflammation, presents a potential therapeutic target for HPE.3,8 Its dual mechanism—attenuation of inflammation and promotion of soft tissue repair—positions HPE as a promising candidate for conservative treatment.8,11 However, despite growing clinical interest, no previous studies have directly evaluated the efficacy of HPE injection therapy in calcific tendinitis.
Therefore, this retrospective, single-arm observational study aimed to explore the safety and therapeutic efficacy of weekly subacromial-subdeltoid (SASD) bursa injections of HPE over 4 weeks in patients with calcific tendinitis of the shoulder. The primary objectives were to assess improvements in pain using the Visual Analog Scale (VAS) and evaluate changes in calcific deposits via ultrasound imaging. The findings from this study will provide preliminary evidence in support of future randomized controlled trials.
2 Methods
2.1 Study design and participants
This retrospective, single-arm observational study was conducted to assess the safety and efficacy of HPE injection therapy in patients with calcific tendinitis of the shoulder. A total of 40 patients who were diagnosed with calcific tendinitis based on ultrasonographic findings were included. Medical records were collected from three clinical institutions for patients treated between October 2024 and May 2025. Patients who had undergone surgical intervention or received corticosteroid injections within 3 months prior to HPE treatment were excluded. This study utilized a retrospective analysis of medical records from patients who had already completed treatment. Since the study relied solely on anonymized clinical data and did not involve the collection of new patient information or administration of additional interventions, it was classified as minimal-risk research; therefore, the requirement for individual informed consent was waived, and the study was exempt from ethical review in accordance with both institutional and national research ethics guidelines. This study was conducted retrospectively using anonymized patient data. As no additional interventions were performed and no identifiable personal information was collected, informed consent was waived. Ethical approval was also exempted in accordance with the regulations of the Institutional Review Board (IRB) and national research ethics standards.
2.2 Intervention protocol
All patients received ultrasound-guided injections of 4 mL of HPE into the SASD bursa. The treatment was administered once weekly for 4 consecutive weeks. Injections were performed under sterile conditions using a protocol developed by the authors to ensure consistency across all patients.
Ultrasound guidance was used to precisely localize the calcific deposits and direct the injection to the targeted area. All procedures were performed by physicians experienced in musculoskeletal ultrasonography and interventional shoulder therapy.
2.3 Outcome measures
Pain intensity was assessed using VAS, ranging from 0 (no pain) to 10 (worst imaginable pain). The VAS is a widely used and validated tool for measuring subjective pain levels in clinical research.21 VAS scores were recorded at baseline (prior to the first injection) and after the completion of the fourth injection. Ultrasonographic evaluations were performed before and after treatment to assess changes in the size, density, and extent of the calcific deposits.
2.4 Statistical analysis
Data are presented as mean ± standard deviation (SD). Paired t-tests were used to compare VAS scores and ultrasonographic findings before and after treatment. A p-value <0.05 was considered statistically significant, and p < 0.01 indicated stronger significance. Statistical analyses were performed using Microsoft Excel (Microsoft Corporation, Redmond, WA, USA).
3 Results
3.1 Treatment administration
All 40 patients included in the study received SASD bursa injections of human placental extract (HPE). A total of four injections of HPE (4 mL per injection) were administered weekly over 4 weeks. The treatment was administered to 12 male and 28 female patients (Table 1). All patients completed the treatment without interruption, and full adherence to the protocol was achieved.
| Males (n = 12) | Females (n = 28) | |
| Age (years) | 56.3 ± 12.0 | 57.3 ± 10.2 |
3.2 Pain assessment
The mean VAS score at baseline was 6.8 ± 0.7, which significantly (p < 0.05) decreased to 1.8 ± 0.8 following the treatment period (Fig. 1).
3.3 Ultrasonographic findings
Ultrasonographic evaluation conducted at baseline and the end of the treatment period showed measurable changes in the calcific deposits. Complete resolution of calcifications was observed in 10 of 40 patients (25 %), while the remaining 30 patients (75 %) showed partial improvement, with a reduction in the size and echogenicity of the deposits (Fig. 2). In several patients, follow-up imaging confirmed near-total disappearance of calcific material, consistent with clinical improvement (Supplementary Fig. S1).
3.4 Safety
No adverse events occurred during the study period, nor were there any reports of local or systemic complications, including infections, allergic reactions, or increased pain following injection. The treatment was well tolerated in all cases.
4 Discussion
This study evaluated the clinical outcomes of HPE injections in patients with calcific tendinitis of the shoulder. Following a 4-week treatment course of weekly SASD bursa injections, patients demonstrated meaningful improvement in pain and imaging findings.
The mean VAS score significantly decreased from 6.8 ± 0.7 at baseline to 1.8 ± 0.8 following treatment, indicating a substantial reduction in pain intensity.21 Ultrasonography showed complete resolution of calcific deposits in 25 % of the patients and partial reduction in the remaining 75 %, suggesting positive morphological changes following HPE therapy. No adverse events were reported, and all patients completed the full treatment protocol, supporting the safety and tolerability of HPE injections.
Conventional treatment options for calcific tendinitis include non-steroidal anti-inflammatory drugs, physiotherapy, ESWT, and ultrasound-guided needling.1–3 In refractory cases, arthroscopic removal of calcifications may be necessary.5 However, these interventions mainly provide symptomatic relief and do not directly address tissue regeneration or facilitate resolution of the underlying calcific deposits. Moreover, some treatment options, such as ESWT or surgery, may be associated with patient discomfort, high costs, or procedural risks.
HPE is a biologically active preparation derived from human placenta, containing peptides, cytokines, growth factors, and nucleic acids.6 HPE has been shown to suppress pro-inflammatory cytokines such as TNF-α and IL-6 and promote fibroblast proliferation, collagen synthesis, and extracellular matrix remodeling.7,11 In a preclinical model of muscle atrophy, HPE exerted antioxidant and anti-inflammatory effects, contributing to improved tissue healing.11 In a study using a murine model, HPE also attenuated chronic inflammation and improved tissue integrity in ligament injury.10
Furthermore, randomized trials have reported that HPE reduces joint pain and improves functional outcomes in patients with osteoarthritis14 and shoulder impingement syndrome.13 Another trial involving fibromyalgia patients also suggested that HPE improves quality of life by alleviating musculoskeletal pain.15
In the present study, the significant reduction in pain scores and favorable ultrasound findings reinforce the notion that HPE influences the inflammatory process and the resorption of calcific material in tendinopathy.
Ultrasound-guided injection was used in this study to ensure accurate delivery of HPE to the subacromial-subdeltoid bursa. This technique likely contributed to the uniformity of the clinical response and enhanced the local therapeutic effect by ensuring precise targeting of the pathological site.3 Additionally, the absence of complications or adverse reactions supports HPE as a safe, non-surgical option for the management of calcific tendinitis.
This study has some limitations. First, the retrospective design and lack of a control group limit the strength of causal inference regarding the efficacy of HPE. Second, the follow-up period was relatively short, making it difficult to assess long-term outcomes or recurrence. Third, although ultrasound was used to monitor changes in calcification, the assessment was primarily qualitative and could be subject to inter-observer variability. Lastly, while the VAS is well validated, it remains a subjective measure.
Despite these limitations, this study adds to the growing body of evidence supporting the therapeutic potential of HPE in musculoskeletal disorders. The observed benefits in pain relief and sonographic improvement, combined with a favorable safety profile, suggest HPE as a useful conservative treatment option for calcific tendinitis. Future studies, particularly randomized controlled trials with larger sample sizes and longer follow-up periods, are warranted to validate our findings and elucidate the further underlying mechanisms of action.8,16,17
5 Conclusion
In this retrospective case series, SASD bursa injections of HPE administered once weekly for 4 weeks were associated with significant reductions in shoulder pain and radiologic improvement in patients with calcific tendinitis. The treatment was well tolerated, with no adverse events reported, and all patients completed the full course of therapy. These findings suggest that HPE injection therapy is a safe and potentially effective non-surgical treatment option for managing symptomatic calcific tendinitis. Further randomized controlled trials are warranted to validate these preliminary results and better define the therapeutic role of HPE in musculoskeletal disorders.
Guardian/patient's consent
Since the study relied solely on anonymized clinical data and did not involve the collection of new patient information or administration of additional interventions, it was classified as minimal-risk research; therefore, the requirement for individual informed consent was waived.
Author contributions
Hoichang Jeong: Conceptualization; Data curation; Investigation; Supervision; Writing - original draft. Jaehun Lee: Conceptualization; Data curation; Investigation; Supervision; Writing - original draft. Taehwan Cho: Conceptualization; Data curation; Investigation; Supervision; Writing - original draft. Yeongmin Kwon: Formal analysis; Project administration. Jooyoung Kim: Formal analysis; Project administration. Aram Shin: Formal analysis; Project administration. Taebin Jeong: Formal analysis; Project administration. All authors read and approved the final version of the manuscript.
Ethical statement
This study was conducted retrospectively using anonymized patient data. As no additional interventions were performed and no identifiable personal information was collected, informed consent was waived. Ethical approval was also exempted in accordance with the regulations of the Institutional Review Board (IRB) and national research ethics standards.
Role of the funding source
NA.
Declaration of generative AI and AI-assisted technologies in the writing process
NA.
Funding
This study received no funding
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