Osteonecrosis of the humeral head under corticosteroid therapy for non-medical reason in a 14-year-old female patient: A case report

Abstract

Osteonecrosis of the humeral head is a debilitating condition caused by disruption of blood supply to the bone, leading to bone death and potential collapse. Corticosteroid therapy, widely used for its anti-inflammatory effects, is a major risk factor for non-traumatic osteonecrosis, particularly in the shoulder. We present the case of a 14-year-old overweight girl (83 kg, 171 cm, BMI 28.38 kg/m²) admitted for evaluation of a suspected tumor in the upper end of the left humerus, with a history of prolonged corticosteroid use not for medical reasons but aimed at weight gain. Histopathological analysis ruled out malignancy and confirmed osteolysis with inflammatory phenomena. The pathogenesis of corticosteroid-induced osteonecrosis remains debated, with two main theories: fat embolism causing blood flow obstruction and local bone changes including adipocyte accumulation and reduced bone cell differentiation. Early diagnosis, especially with MRI, is crucial for effective management. Conservative treatments are successful in early stages, while surgery is reserved for advanced disease. Corticosteroid therapy remains a significant risk factor for humeral head osteonecrosis, and early diagnosis with appropriate stage-based management is essential to improve patient outcomes.

Introduction

Osteonecrosis is a common condition in which a segment of bone loses its blood supply, leading to significant changes that can be severely disabling and deforming at times [1]. Common causes include trauma, long-term corticosteroid therapy, and systemic diseases such as sickle cell disease, systemic lupus erythematosus, or alcoholism [2].

The diagnosis is based on a combination of clinical examination and radiographic evaluation, with magnetic resonance imaging (MRI) being the most sensitive method for early detection, and Early diagnosis is crucial to prevent joint collapse and enhance outcomes. While conservative treatments are employed in the early stages, they carry a risk of disease progression since they do not modify its course, unlike surgical options like spinal decompression. Arthroplasty is reserved for more advanced stages, when signs of collapse are present [3].

This case report presents the clinical course of a 14-year-old female patient who developed osteonecrosis of the humeral head following corticosteroid use for non-medical purposes. This article aims to highlight the potential risks associated with such therapy in pediatric patients and to raise awareness of the importance of early diagnosis and appropriate management to prevent long-term joint dysfunction.

Case report

This is a 14-year-old patient, weighing 83 kg and standing 171 cm tall (BMI: 28.38 kg/m²), admitted for left shoulder pain with limited movement, which has been evolving for three months. Clinically, the patient presented with restricted abduction and external rotation, with the arc of motion initially estimated at 0°. Physical examination revealed localized edema, inflammatory signs, and hyperchromic cutaneous striae. No neurovascular complications were identified.

Laboratory tests

• •Sodium (Na): 139 mmol/L (Reference range: 135 - 145 mmol/L).
• •Potassium (K): 3.8 mmol/L (Reference range: 3.5 - 5.0 mmol/L).
• •Chlorides (Cl): 107 mmol/L (Reference range: 98 - 107 mmol/L).
• •Bicarbonate (Alkaline Reserve): 22 mmol/L (Reference range: 22 - 28 mmol/L).
• •Total Proteins: 71 g/L (Reference range: 60 - 80 g/L).
• •Glucose (Glycemia): 0.81 g/L (Reference range: 0.70 - 1.10 g/L or 3.9 - 6.1 mmol/L).
• •Urea (BUN): 0.14 g/L (Reference range: 0.10 - 0.40 g/L).
• •Phosphorus (P): 39.0 mg/L (Reference range: 2.5 - 4.5 mg/dL or 0.8 - 1.5 mmol/L).
• •Uric Acid (UA): 47 mg/L (Reference range: 2.4 - 7.0 mg/dL or 0.14 - 0.42 mmol/L).
• •AST (ASAT): 16 UI/L (Reference range: 10 - 40 UI/L).
• •ALT (ALAT): 11 UI/L (Reference range: 10 - 40 UI/L).
• •Alkaline Phosphatase (ALP): 118 U/L (Reference range: 30 - 120 U/L).
• •LDH (Lactate Dehydrogenase): 246 U/L (Reference range: 140 - 280 U/L).
• •Ferritin: 41.79 ng/mL (Reference range for adolescents: 20 - 200 ng/mL).

Complete Blood Count (CBC)

• •Red Blood Cells (RBC): 4.50 × 10^6/µL (Reference range: 4.00 - 5.50 × 10^6/µL)
• •Hemoglobin (Hb): 12.30 g/dL (Reference range for adolescent females: 11.5 - 15.5 g/dL)
• •Mean Corpuscular Volume (MCV): 81.1 µ3 (Reference range: 80 - 100 µ3)
• •Mean Corpuscular Hemoglobin (MCH): 27.33 pg (Reference range: 27 - 33 pg)
• •Mean Corpuscular Hemoglobin Concentration (MCHC): 33.7 g/dL (Reference range: 32 - 36 g/dL)
• •Platelets (PLT): 267 × 10^3/µL (Reference range: 150 - 450 × 10^3/µL)
• •White Blood Cells (WBC): 10,080/µL (Reference range: 4,000 - 10,000/µL)

• ○ Neutrophils (PNN): 5574/mm³ (Reference range: 2,000 - 7,500/mm³)

• ○ Lymphocytes: 2591/mm³ (Reference range: 1,000 - 3,000/mm³)

• ○ Monocytes: 1381/mm³ (Reference range: 0 - 800/mm³)

Procalcitonin (PCT)

• •Procalcitonin (PCT): < 0.05 ng/mL (Reference range: < 0.05 ng/mL, indicating no bacterial infection)

C-Reactive Protein (CRP)

• •CRP: 16.4 mg/L (Reference range: < 5 mg/L, a value higher than this suggests inflammation or infection)

Imaging

Standard X-ray (AP View):

The initial anteroposterior (AP) X-ray of the left shoulder showed a heterogeneous, remodeled appearance of the upper humeral head. This could indicate bone remodeling as part of the inflammatory process, but the X-ray alone was insufficient for a definitive diagnosis (Fig. 1).

• 1.CT Scan: A CT scan was performed on a 16-slice scanner, with 2 mm slice thickness, revealing highly heterogeneous lacunar images within the epiphyseal nucleus of the left humeral head. The presence of irregularities and cortical disruption in some areas indicated structural changes within the bone, raising suspicion for conditions like osteonecrosis or a bone tumor (Fig. 2).
• 2.MRI: An MRI was then performed using a 1.5 Tesla MRI machine with a dedicated shoulder coil. The MRI protocol involved T1-weighted, T2-weighted, STIR, and fat-suppressed images to assess both bone marrow abnormalities and soft tissue changes. The MRI revealed an epiphyseal lesion in the left humeral head, initially raising the possibility of a tumoral origin, such as a chondroblastoma or a giant cell tumor. In addition, there was a joint effusion, indicating synovitis (Fig. 3). These findings were suggestive of a serious pathology, but further diagnostic steps were required to confirm the diagnosis.

Fig. 1.

Standard X-ray of the Left Shoulder (frontal view): Heterogeneous remodeled appearance of the upper end of the humerus (Red arrow).

Fig. 2.

An axial CT scan image of the shoulder, non-contrast, showing highly heterogeneous lacunar images of the epiphyseal nucleus of the left humeral head (yellow arrow), with intra-articular effusion (blue star).

Fig. 3.

MRI images of the left shoulder, weighted in DP, T1, and after Gadolinium injection, showing a lobulated lesion in the humeral head, appearing hypointense on T1 and with a heterogeneous signal on T2. The lesion contains calcifications and small fluid-filled cavities, showing heterogeneous enhancement. Its size is 30 × 33 × 21mm (AP x width x height). Additionally, there is a significant glenohumeral groove effusion (blue star), with synovial enhancement following Gadolinium injection (red arrow). Orange arrow: double-line sign

Differential diagnosis

Given the radiological findings, the initial differential diagnoses included:

• •Chondroblastoma
• •Giant cell tumor
• •Osteomyelitis
• •Avascular necrosis (ON)

  The lesion's features were concerning for a tumor, but the absence of infection-related findings (e.g., fever, elevated CRP) and the bone's overall appearance prompted further investigation.

Biopsy and histopathological results

To clarify the diagnosis, both bone and synovial biopsies were performed, and the histological study (Fig. 4) came back in favor of:

Fig. 4.

Histopathological images of the synovial (A) and bone (B) biopsy of the humeral head from our patient: (A) Acellular bone tissue with acidophilic necrosis, characterized by the loss of cells and a pink coloration due to cellular degradation (H&E stain, × 40 magnification). (B) Acellular bone sequestra with surrounding fibrous areas, indicating a fibrovascular repair process around the necrotic bone (H&E stain, × 10 magnification).

Bone biopsy

• •Cell types: The bone biopsy demonstrated necrotic bone tissue with osteocytes absent from the central areas of the necrosis, which is characteristic of avascular necrosis. Fibroblasts and some vascular tissue were observed at the periphery of the necrotic areas, suggesting ongoing fibrovascular repair.
• •Necrotic Bone: There was clear evidence of diffuse osteolysis, with large areas of bone destruction and no evidence of malignancy or granulomatous inflammation.
• •Marrow Fat Changes: In adjacent areas, the bone marrow exhibited fatty infiltration, a common feature in stages of avascular necrosis, where there is increased marrow adiposity due to bone resorption and altered blood supply.
• •Osteocyte Loss: Loss of osteocytes was evident in the necrotic regions, further supporting the diagnosis of avascular necrosis.
• •Fibrovascular Repair: In some areas, fibrovascular tissue was observed attempting to fill the necrotic gaps, indicating an ongoing healing process, although no new bone formation was present.

Synovial biopsy

• •Cell types: The synovial biopsy showed features of acute fibrinoid and lymphoid synovitis, with an infiltration of lymphocytes and some plasma cells, which likely reflects an inflammatory response.
• •Synovitis: This could be part of an underlying arthritis process, but there were no granulomatous features or other indicators of infection.
• •Lymphoid Infiltrates: The presence of lymphoid aggregates in the synovium suggests an immune-mediated component of the disease, potentially related to secondary synovitis due to joint ischemia or degeneration.

After a follow-up interview, it was revealed that the patient had been using long-term corticosteroids, not for a medical reason, but with the goal of gaining weight, The corticosteroid used was identified as Prednisone; however, the exact commercial name could not be confirmed. The medication was taken orally over an estimated period of approximately 9 months. Precise information regarding the dosage and frequency of administration was not available. The corticosteroids were obtained over the counter without a medical prescription. No reliable information could be obtained regarding similar use among family members or close contacts.

Therefore, the diagnosis of osteonecrosis of the humeral head secondary to corticosteroid therapy was established. Our patient was managed with analgesic therapy combined with functional rehabilitation. Follow-up at one year demonstrated clinical improvement, evidenced by an increased range of motion, with abduction exceeding 110°.

Discussion

Osteonecrosis occurs when there is a temporary or permanent loss of blood supply to a portion of bone [4], leading to the collapse of the affected bone tissue.

The disruption of blood supply can be caused by either traumatic or atraumatic factors [5]. The humeral head is the second most common site for atraumatic osteonecrosis after the femoral head [6].

Steroid therapy is a significant cause of avascular necrosis. Due to their anti-inflammatory and immunomodulatory properties, corticosteroids are frequently used in preoperative and postoperative settings, as well as for managing inflammatory conditions such as rheumatoid arthritis, severe asthma, vasculitis, and tenosynovitis. In our case, after a thorough interview with the patient, it was discovered that she had used corticosteroids for a non-medical reason (to gain weight), which consequently led to the development of obesity.

Research shows that prolonged use of oral or intravenous corticosteroids is linked to non-traumatic osteonecrosis [7,8]. It is well-established that patients receiving systemic corticosteroids or repeated intra-articular steroid injections face an increased risk of developing osteonecrosis [9,10]. However, the exact dosage of steroids required to cause avascular necrosis is not clearly defined, and there is limited understanding of the specific risk level associated with corticosteroid therapy in the development of this condition [8].

Two main theories explain the pathogenesis of corticosteroid-induced osteonecrosis. The first theory, proposed by Jones et al.,[11] suggests that corticosteroids cause fatty liver and hypertriglyceridemia, leading to systemic fat embolism. This embolism can obstruct the blood vessels that supply the subchondral bone, disrupting circulation and causing osteonecrosis. The second theory posits that corticosteroids induce local changes within the bone. Specifically, they lead to increased differentiation of mesenchymal stem cells (MSCs) into adipocytes, resulting in fat cell hypertrophy, decreased differentiation of osteoclasts and osteoblasts, and apoptosis of osteocytes. Both mechanisms whether through fat embolism or local bone changes lead to increased intramedullary pressure and reduced blood flow, which ultimately contribute to osteonecrosis.

According to Assouline-Dayan et al. (2001), the pathogenesis of non-traumatic osteonecrosis appears to involve vascular compromise, cell and bone death, or defective bone repair as the primary event [4]. Adolescents are particularly vulnerable due to the plasticity of their bones and their active bone growth.

X-rays are the first-line imaging examination for patients suspected of having osteonecrosis, but MRI remains the gold standard for diagnosing osteonecrosis, as it shows the location and extent of the lesions, particularly in asymptomatic patients and those with normal X-rays in the early stages of the disease. Osteonecrosis becomes symptomatic when there is intra-articular effusion and bone marrow edema.

Osteonecrosis is characterized by its distinct boundary and relative preservation of the peripheral bone structure in the early stages:

Double Line Sign (Pathognomonic): Visible on T2 sequences, it shows an external dark band (condensed bone/sclerosis) and an inner bright band (hypervascular granulation tissue).

Serpentine Line (T1): A low-signal line demarcates the necrotic area, which often retains a normal fat signal (high signal on T1) at its center in the early stages.

Topography: Typically located at the superior pole (weight-bearing zone) of the femoral head.

Absence of invasion: Unlike tumors, ONF does not extend beyond the bone boundaries or invade the adjacent soft tissues [[12], [13], [14]].

Imaging-guided diagnostic approach

Osteonecrosis, particularly when related to steroid use, requires careful and early diagnostic evaluation, where imaging plays a crucial role. MRI, in particular, allows for a clear differentiation between osteonecrosis and other pathologies like tumors or infections, thanks to characteristic signs such as the “double line sign” in T2 sequences.

Recent studies, such as one on Sturge-Weber syndrome in an infant [15] illustrate how appropriately tailored MRI protocols can be critical in distinguishing a non-tumoral cause from neoplasia, highlighting the role of MRI in clinical management, especially when deciding if a biopsy is needed. Additionally, a case on isolated renal hydatid cyst demonstrates how imaging, when combined with other investigations, can resolve complex clinical presentations and avoid diagnostic errors [16].

These examples emphasize the importance of systematic imaging follow-up, preferably with MRI, for early diagnosis of osteonecrosis, especially in young patients. This approach helps guide clinical decisions and avoid unnecessary interventions such as biopsies.

Osteonecrosis caused by corticosteroid use can be multifocal. According to Nawala et al., the hips and knees are the most commonly affected sites. They recommended that any osteonecrosis detected in the hip and/or knee joints should lead to a follow-up MRI screening of the shoulders [17].

Key points

• •Osteonecrosis in adolescents can be caused by non-medical corticosteroid use, which reduces bone blood flow and promotes marrow fat accumulation.
• •The classic MRI “double-line sign” and absence of extra-osseous mass help distinguish osteonecrosis from tumors and infections.
• •Early diagnosis and multidisciplinary management are crucial in managing osteonecrosis in young patients, with orthopedic consultation required at early stages to prevent joint destruction.

The classification used for osteonecrosis of the humeral head is the Cruess classification. It is divided into five stages, which are detailed in the figure below (Fig. 3).

It is important to note that the use of corticosteroids has recently increased globally due to their role in treating patients with severe forms of coronavirus disease 2019 (COVID-19). Li et al. conducted a meta-analysis which showed that 32% of patients with severe acute respiratory syndrome (SARS) developed osteonecrosis after receiving high-dose corticosteroid treatment [18].

The objectives of treatment are to enhance shoulder function, alleviate pain, and prevent the progression of osteonecrosis. Conservative treatment options are proposed and effective in stages I and II. Invasive options, such as resurfacing, hemiarthroplasty (HA), and total shoulder arthroplasty (TSA), are reserved for advanced stages (III, IV, or V). Conservative treatment remains a feasible option for elderly patients with end-stage osteonecrosis [19].

In cases of suspected osteonecrosis in a young patient, the strategy involves systematic multicentric screening using MRI, including the hips, knees, and shoulders, even in the absence of clinical symptoms, as the condition is bilateral or multifocal in more than 50% of steroid-related cases [20]. The radiologist must integrate the patient into a multidisciplinary care pathway involving rheumatologists or internists (for steroid weaning and hemostasis workup) and orthopedic surgeons. An orthopedic consultation is imperative and should be sought early (at stages I or II of ARCO), before any subchondral collapse occurs. The radiology report must clearly specify the location in the weight-bearing zone and the necrotic volume (Kerboul index), as involvement exceeding 30% of the articular surface is a formal indication for conservative surgery, such as core decompression, to attempt to prevent irreversible joint destruction [21].

Our patient received analgesic treatment along with functional rehabilitation, and the course was marked by clinical improvement with an increase in the arc of motion (abduction > 110°) at one year (Fig. 5).

Fig. 5.

Illustration and MRI findings of the stages of progression of osteonecrosis of the humeral head according to Cruess. (A) Stage I, preradiological stage characterized by a total absence of radiological changes. MRI findings include small focal lesion with a hyperintense signal abnormality in T2 weighted sequences. (B) Stage II, the curvature of the humeral head is maintained with radiologic signs of repair, including diffuse osteoporosis and mottled sclerosis. MRI findings include bone marrow signal abnormality and the double-line sign: a bright line (granulation tissue) and dark line (necrosis and sclerosis). (C) Stage III is defined by the presence of classical radiographic sign of osteonecrosis “the crescent sign.” This stage represents collapse of the subchondral bone. MRI findings include the crescent sign and associated bone marrow signal abnormality. (D) Stage IV is characterized for extensive collapse of the subchondral bone and severe deformity of the humeral head because of superior flattening. MRI findings include flattening of the humeral head and narrowing of the articular space. (E) Stage V shows pathologic changes in the glenoid in addition to the changes seen in Stage IV. MRI findings include severe humeral head collapse, glenoid cartilage wear, and osteoarthritic changes [19].

Conclusion

Osteonecrosis of the humeral head, associated with corticosteroid therapy, presents a significant issue due to the widespread use of these drugs in treating inflammatory conditions. Addressing this concern involves understanding the associated risks, ensuring early detection, and applying effective management strategies to enhance patient outcomes and avert long-term joint damage. Ongoing research and vigilant clinical oversight are crucial for elucidating the mechanisms involved and optimizing treatment approaches for affected individuals.

Patient consent

Written informed consent was obtained from the patient’s legal guardians for the publication of this case report.