Hip fractures, primarily observed in elderly and frail people, significantly reduce the quality of life due to chronic pain and limited mobility with a prolonged recovery period. The risk of mortality associated with hip fractures is high immediately post-surgery and remains elevated for up to a year. Pathological fractures arise in bones compromised by underlying conditions. Bone fractures of the hip can severely impact the rates of morbidity, survival, and the overall quality of life 1 ) .
Pathological fractures of the hip may be caused by several factors, such as metastatic disease, primary bone tumors, osteoporosis, osteomalacia, infections, and amyloidosis, among others 2 , 3 ) . Amyloid arthropathy is a disease often observed in patients undergoing dialysis where tissues display an abnormal accumulation of amyloid. In long-term dialysis patients, amyloid arthropathy typically results from an accumulation of the beta-2 microglobulin protein because it cannot be effectively removed by the kidneys.
Amyloid arthropathy can lead to arthritis-like symptoms in joints, particularly in major joints like the hip. In severe cases, it progresses to osteolysis and pathological fractures 4 ) .
This case report highlights a rare instance of bilateral hip amyloidosis that leads to pathological fractures in a long-term dialysis patient. Through our report, we emphasize the importance of early detection and management of amyloid arthropathy. This is the first such case reported in Korea, which underscores the need for heightened clinical awareness regarding hip pain in long-term dialysis patients and offers valuable insights into the benefits of early management.
CASE REPORT
A 48-year-old male patient with no previous history of trauma presented to the hospital with sudden, aggravated pain in the right hip joint on the day of admission. Prior to admission, the patient had been ambulatory without assistive devices and had a history of hemodialysis due to chronic renal failure 30 years earlier. The chronic renal failure was diagnosed as idiopathic in the absence of any known medical conditions. Maintenance hemodialysis was performed three times a week at a local hospital for the past three decades. The patient reported chronic pain that existed over a period of three years in the right hip joint. However, the pain was mild and did not require any treatment. On the day of admission, he sought hospital care because the pain in the right hip rapidly worsened while walking.
We noted tenderness in the right groin and buttocks with unremarkable neurological findings during physical examination. Anterior-posterior and lateral radiographs of the hip joint, taken at the time of admission, showed extensive osteolysis and bone erosion, which primarily involved the femoral necks on both the left and right sides along with a subcapital fracture of the right femoral neck. Computed tomography (CT) of the hip joint revealed similar osteolytic lesions extending to the acetabulum, the medial wall of the pelvis, the region surounding the sacroiliac joint, and the adjacent vertebral bodies. We performed a magnetic resonance imaging (MRI) of the hip joint to further investigate the possibility of pathological fractures and lesions. The MRI of the hip joints revealed extensive, heterogeneous deposits with varied signal intensities. On T1-weighted images, the deposits exhibited low-to-intermediate signal intensity. In contrast, the deposits appeared predominantly hyperintense on T2-weighted images and were consistent with amyloid deposits. We noted widespread involvement of the joint structures on the basis of the findings both within the joint spaces (intra-articular) and in the surrounding soft tissues (extra-articular) with irregular margins and diffuse distribution ( Fig. 1 ). We suspected bilateral amyloid arthropathy accompanied by a pathological fracture of the right femoral neck from the radiological findings.
Blood tests, including tumor marker tests, revealed no specific abnormalities except for elevated levels of 999.8 pg/mL (normal range, 10-65 pg/mL) of parathyroid hormone (PTH). A review of the PTH, calcium, phosphate, and vitamin D levels indicated that the levels were consistent with those for secondary hyperparathyroidism, a condition commonly seen in chronic kidney disease patients undergoing long-term dialysis. There were no clinical findings that suggested infection, and the patient did not complain of other joint pain. We planned to treat the right femoral neck fracture with total hip arthroplasty. Based on Mirels’ criteria, the left hip lesion was scored as follows: 2 points for moderate pain, 3 points for a peritrochanteric location, 3 points for a lytic appearance, and 3 points for lesion size, yielding a total score of 11—well above the threshold of 8 that indicates a high fracture risk requiring prophylactic fixation 2 ) . Similarly, Harrington’s criteria assess fracture risk by evaluating cortical involvement and lesion size. In the case of our patient, the lesion demonstrated more than 50% cortical destruction and measured over 2.5 cm, further supporting the need for prophylactic fixation 3 ) . Hence, we planned a total hip arthroplasty for the left hip to prevent the progression to a complete fracture in the future.
We performed the surgery under spinal anesthesia, and an incision of approximately 10 cm was made through a lateral approach to expose the fracture site. Total hip arthroplasty on the right side was first performed, followed by a contralateral total hip arthroplasty on the left side one week later. During surgery, we observed orange-red deposits around the joint, and the samples were collected for histopathological examination at the time of debridement. Although imaging revealed a significant left acetabular defect, intraoperative assessment indicated that additional interventions, such as bone grafting, were not necessary because the remaining bone stock provided sufficient structural support for the acetabular component and maintained overall joint stability. The femoral head showed sclerotic edges and extensive bone erosion. We also performed a histopathological examination ( Fig. 2 ). To check for amyloid deposits, we performed a histopathological examination of bone and soft tissue. We were able to diagnose amyloid arthropathy by confirming negative birefringence of apple-green with the Congo red-stain ( Fig. 3 ).
The patient began partial weight-bearing ambulation with the assistance of a walker on day two post-surgery. We did not observe any specific complications, such as infection, during the postoperative period. Two weeks post-surgery, there were no signs of implant loosening, dislocation, periprosthetic fracture, or metal failure observed in plain radiographs and computed tomography ( Fig. 4A ). When investigating the underlying cause of amyloidosis with the serum protein electrophoresis test and immunofixation electrophoresis, we did not observe any abnormalities and this suggested the absence of monoclonal gammopathy. There were no unusual findings in a parathyroid scan performed to check for abnormalities in the parathyroid glands due to high PTH levels before surgery. To confirm amyloidosis, the serum-free light chain quantitative test demonstrated elevated levels of kappa (normal range, 3.3-19.4 mg/L) and lambda (normal range, 5.7-26.3 mg/L) light chains at 182 mg/L and 175 mg/L, respectively. These will serve as biomarkers for assessing treatment response and for prognosis during future monitoring and follow-up. To verify the possibility of systemic amyloidosis, we checked for abnormalities in other organs with PET-CT (positron emission tomography-CT), echocardiography, and CT of the chest and abdomen. We did not obtain any specific findings. We further investigated the possibility of secondary amyloidosis because of the osteolytic lesions observed in the sacroiliac joint. We performed the HLA-B27 genetic test to confirm rheumatic diseases such as ankylosing spondylitis. The test results were negative and confirmed the absence of secondary amyloidosis. From our investigation, this case study can be diagnosed as dialysis-related amyloidosis that is a condition that could develop in patients undergoing long-term hemodialysis with clinical manifestations limited to bilateral localized amyloid deposits.
At the one-year outpatient follow-up, the patient was able to walk independently without a limp and reported no pain or joint dysfunction. Furthermore, plain radiographs obtained one year following the surgery demonstrated no signs of implant loosening, dislocation, periprosthetic fracture, or implant failure ( Fig. 4B ).
DISCUSSION
Amyloidosis is a disease in which proteins in the body are transformed abnormally into an insoluble fibrous substance known as amyloid that subsequently accumulates in tissues and organs 5 ) .
Amyloidosis is broadly categorized into five types based on its underlying cause and clinical presentation: (1) primary amyloidosis, (2) secondary amyloidosis, (3) localized amyloidosis, (4) hereditary familial amyloidosis, and (5) degenerative amyloidosis 6 ) . Primary amyloidosis is the most common form and originates from immunoglobulin light chain proteins that are deposited in various organs. Secondary amyloidosis is associated with chronic inflammatory diseases, such as rheumatoid arthritis or Crohn’s disease and mainly affects the kidneys. Localized amyloidosis is characterized by amyloid accumulation confined to specific areas or organs. Hereditary familial amyloidosis is caused by specific gene mutations that result in an accumulation of modified transthyretin protein. Hereditary familial amyloidosis mainly affects the nervous system and heart, causing peripheral neuropathy or heart failure, respectively. Degenerative amyloidosis is an age-related condition that occurs primarily in elderly individuals. In degenerative amyloidosis, beta-2 microglobulin protein accumulates and affects joints and tendons.
The International Society of Amyloidosis classifies amyloidosis on the type of fibril protein—namely AA, AL, AH, ATTR, and Aβ2M—which determines both the deposit site and clinical manifestations. In general, AL deposits are observed in the heart, nervous system, kidneys, and gastrointestinal tract; AA deposits occur in the liver, spleen, and kidneys; AH deposits are found in the kidneys and heart; ATTR deposits are primarily in the heart and peripheral nerves; and Aβ2M deposits are typically seen in long-term dialysis patients and affects joints, tendons, and the digestive system.
Each type is associated with a distinct clinical syndrome, such as AL with plasma cell disorders and AA with secondary inflammatory conditions 7 , 8 ) .
Several studies have reported cases of amyloid arthropathy concurrent with multiple myeloma 9 ) . He et al. 10 ) reported two cases where they emphasized the importance of early diagnosis and treatment of amyloid arthropathy that appeared as the first clinical symptom of multiple myeloma. Cho et al. 11 ) reported a case of hip joint amyloid arthropathy in a domestic patient with multiple myeloma. However, our present case was not associated with either multiple myeloma or other rheumatoid diseases. Instead, it represents a case of dialysis-related amyloid arthropathy involving the hip joint. This is a novel case in that it has not been previously reported in Korea. Even in cases from other countries, it has been rare to observe the pattern of hip joint involvement in dialysis-related amyloid arthropathy and it is typically limited to unilateral manifestations 4 , 12 ) .
Dialysis-related amyloidosis was first recognized in the 1970s as a complication of long-term dialysis. The detection of dialysis-related amyloidosis has increased with improved dialysis technology and extended patient survival. Dialysis-related amyloidosis results primarily from the accumulation of beta-2 microglobulin that is normally cleared by the kidneys.
Impaired renal function leads to the accumulation of beta-2 microglobulin in patients undergoing dialysis 13 ) . Prolonged dialysis is associated with increased beta-2 microglobulin accumulation, and the risk rises significantly in patients who have been on dialysis for over 5 to 10 years 14 ) . According to van Ypersele de Strihou et al. 15 ) , the incidence and severity of dialysis-related amyloidosis, a significant long-term complication of chronic hemodialysis, increases in patients undergoing dialysis for more than 5 to 10 years. Dialysis-related amyloidosis typically presents as arthralgia, spondyloarthropathy, and carpal tunnel syndrome that markedly impair the quality of life. Imaging tests and biopsies confirm amyloid deposits for dialysis-related amyloidosis. Amyloid fibrils are typically identified using Congo red staining and electron microscopy. Early clinical manifestations, such as joint pain, stiffness, and limited mobility often resemble degenerative joint diseases; however, in advanced stages, joint destruction may lead to pathological fractures. In our case study, the patient initially experienced nonspecific, mild hip pain for several years prior to diagnosis, which eventually progressed to severe joint destruction and bilateral pathological fractures. Therefore, it is critical to diagnose dialysis-related amyloid arthropathy early to prevent irreversible joint destruction in patients undergoing long-term hemodialysis and who present with persistent joint pain. On the basis of the findings of our study, we propose a comprehensive diagnostic approach to enable the early detection of dialysis-related amyloid arthropathy, which includes MRI of symptomatic joints, monitoring serum amyloid precursor proteins, such as kappa and lambda light chains as well as β2-microglobulin, and histopathological confirmation through biopsy when indicated.
Given the increasing trend of patients receiving long-term hemodialysis due to the development and generalization of hemodialysis, the incidence of dialysis-related amyloid arthropathy is expected to rise further in the future. When amyloid arthropathy is detected early, dietary management and lifestyle modifications can play a pivotal role in reducing joint stress, maintaining physical function, and slowing disease progression. Efforts are now being made to reduce dialysis-related amyloidosis by improving the clearance of beta-2 microglobulin proteins with the development of high-flux dialysis membranes and hemodialysis filtration methods 16 ) .
Compared to conventional dialysis methods, high-flux dialysis membranes have been shown to lower the risk of amyloidosis by increasing the efficiency of the clearance of beta-2 microglobulin 17 ) . Hemodiafiltration is another modality that effectively increases beta-2 microglobulin clearance by combining both dialysis and filtration. Furthermore, research is actively underway to develop novel therapeutic agents that inhibit the aggregation of beta-2 microglobulin proteins 18 ) .
This case demonstrates that even when amyloid arthropathy progresses to joint destruction and pathological fractures—particularly in the hip—artificial joint replacement surgery can effectively preserve ambulation and maintain joint function. Furthermore, clinicians should remain alert to the possibility of bilateral involvement in amyloid arthropathy and strive for timely diagnosis and intervention to optimize patient outcomes. Due to the relatively short follow-up period in the case of our patient, the impact on long-term outcomes—such as implant loosening, infection, dislocation, and periprosthetic fracture—remain unverified, underscoring the importance of continued monitoring.
Footnotes
Funding
No funding to declare.
Conflict of Interest
No potential conflict of interest relevant to this article was reported.
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