Secondary Osteonecrosis of the Knee

Etiology

SON has numerous well recognized predisposing factors that can be categorized into direct causes, including sickle cell disease, myeloproliferative disorders, and Gaucher's disease, and indirect causes such as alcohol, obesity, and corticosteroid use. Alcohol abuse and steroid usage are seen in over 90% of cases of SON.[3] Research has shown that alcohol excess and corticosteroid use cause bone marrow adipose cell enlargement, which in turn increases intra-osseous pressure leading to bone ischemia.[4] 

This theory has been extended to several risk factors like Gaucher's disease (glycogen storage disease), dysbaric disorders, and some myeloproliferative disorders.[5] Other risk factors, smoking and sickle cell disease, are thought to cause SON due to their vaso-occlusive effects. In sickle cell disease, the deformable red blood cells are more likely to clump together (sickling) and adhere to the vascular wall causing vascular occlusion. This, in turn, leads to ischemic events in the bone just as it does in other vasculature in the body.[6] There has been no genetic element shown to be of relevance in SON in the literature.

Epidemiology

The knee is the second most common joint to be affected by osteonecrosis after the femoral head and accounts for 10% of all cases.[7] The phenomenon is also seen in the shoulder,[8] ankle,[9] mandible,[10] and spine.[11]

In the knee, SPONK is the most common form of osteonecrosis and typically presents in the 6th decade of life, with a higher incidence seen in females.[3] SPONK presents as a unilateral disorder that only involves a single femoral condyle or the tibial plateau. Patients present with acute onset of localized pain.[12] SPONK is not associated with any known risk factors and does not arise in other joints concurrently. If the lesions are small, typically, the condition responds to conservative management and is usually self-limiting. However, larger lesions can be progressive and lead to subchondral collapse.

Secondary osteonecrosis (SON) is the second most common type in the knee and typically presents in patients before the 4th decade of life and frequently involves multiple lesions in several joints concurrently. In the knee, SON often involves both femoral condyles as well as the epiphysis, diaphysis, and metaphysis of the involved femur and tibial plateau.[13] It is bilateral in 80% of cases, and the femoral head is noted to also be involved in 90% of reported cases.[3]

The true prevalence of secondary osteonecrosis (SON) is difficult to ascertain and may well be underreported due to patients instead presenting with end-stage osteoarthritis, who initially had undiagnosed osteonecrosis.[14]

History and Physical

Patients with SON of the knee classically present with gradual onset, mild symptoms focused over either the medial or lateral femoral condyle, or both.  Typically, these patients are younger than 45 years of age, the symptoms are bilateral, and patients often have co-existing osteonecrosis of other large joints.[13]

On examination, pain both at rest and with load-bearing exercise is common. The most common clinical finding is localized pain on palpation of areas overlying necrotic foci. Range of motion tends to be preserved with mild disease and is only limited by pain.

Evaluation

As a clinician, the ability to recognize high-risk patients presenting with classical symptoms of SON in addition to well-defined associated risk factors is essential. Obtaining urgent bilateral anterior-posterior (AP) and lateral radiographs, with further investigation using magnetic resonance imaging (MRI), is essential to make a timely diagnosis. This will ultimately lead to optimal clinical outcomes for patients.[2]

Traditionally, radionucleotide scanning had been the recommended modality of imaging to investigate and stage ON. However, a report by Mont et al. highlighted that MRI is the gold standard of imaging for the investigation of ON.[15] Their study found that bone scanning detected only 37 (64%) of 53 lesions in symptomatic patients with ON of the knee, whereas MRI detected 100% of the lesions.

To date, there are no high powered studies that report pathognomonic changes on MRI indicative of early stages of SON. However, the distribution pattern of the bone marrow edema on MRI can be suggestive of SON. This is because the epiphysis, metaphysis, and diaphysis can be involved, which is in contrast to SPONK, where the MRI changes are only seen in the subchondral area of the affected femoral condyle.[16]

In addition, there is often a rim or double halo sign, adjacent to the proximal boundary of the osteonecrotic bone displayed on MRI images in SON. Narvaex et al. showed that this finding was present in 70% of his cases with SON but importantly in none of the patient MRI images with SPONK.[5] Further studies are required to investigate MRI changes in SON to assess whether this demarcation rim is indeed indicative of early-stage SON.

Secondary osteonecrosis of the knee can be staged to indicate the severity and thus guide management options. Two classification systems can be used: the Koshino staging system, which was developed for SPONK, and the modified Ficat and Arlet staging system, which has been adapted for the knee after originally being developed for osteonecrosis of the femoral head.[17]

The latter system is in more routine use, and a summary of its classification follows:

• Stage I - Normal radiological appearance.
• Stage II – Cystic or osteosclerotic lesions present, but the absence of subchondral fracture or flattening of the articular surface.
• Stage III – Crescent sign or evidence of subchondral collapse present.
• Stage IV – Narrowing of the joint space with the presence of cysts and osteophytes.

Treatment / Management

Treatment of SON is directed by the extent and severity of the disease and the unique clinical factors of each individual patient. As SON primarily affects the younger population, conservative management, and joint preserving therapies ideally would be at the epicenter of treatment options. Unfortunately, non-operative management is generally not successful. One study found that 80% of patients treated with protected weight-bearing required total knee replacement (TKR) by 6 years from treatment initiation.[18] Thus treatment using conservative management made up of non-steroidal anti-inflammatories (NSAIDs), analgesics, and protected weight-bearing is only recommended for patients with asymptomatic SON stages I – III.

Recent studies have shown promising results of the role of bisphosphonates and prostaglandin I-2 in managing SON. Jaeger et al. found that the most marked clinical and radiological benefits were in patients who were in the early stages of the osteonecrosis disease progress. A very limited benefit was shown from these infusions for patients who had advanced stage osteonecrosis.[19] Large scale prospective studies are required in this area for further evaluation of their efficacy.

Further research has been done into non-operative options in the treatment of osteonecrosis in the femoral head and may, in due course, be applied to the knee, including the use of hyperbaric oxygen,[20] pulsed electromagnetic fields,[21] and extracorporeal shock wave therapy.[22](A1)

There are several joint-preserving methods that have had increasing interest in recent years, primarily as a manner of delaying the necessity of TKR in a patient group who are often young, active, and are more likely to be immunocompromised secondary to a concurrent disease process. If the cartilage surface is not depressed or arthritic, joint-preserving techniques such as core decompression and bone grafting are available.[23]

Mont et al. reported a 92% success rate in both clinical and radiological outcomes by employing a variant of core decompression surgery known as percutaneous drilling. In their study, which had a mean follow up period of 3 years, they concluded that the procedure was quick, had low morbidity, and was an effective alternative to alleviate symptoms and delay the requirement for TKR in a high percentage of patients; thus a worthwhile initial surgical intervention.[24](B2)

TKR is the only viable option for patients with subchondral bone collapse, Ficat stage III and IV disease. TKR aims to restore anatomical joint anatomy to provide a good symptomatic and functional outcome. In cases of SON, unicondylar implants are contraindicated as SON often affects both femoral condyles. A meta-analysis showed that 97% achieved a good outcome with a knee society score of greater than eighty out of one hundred in patients who underwent TKR with cemented components. This included the option of using ancillary stems to ensure good fixation and stability of the prosthesis if required, such as in cases with severe metaphyseal disease or reduced bone strength. This review included data with a mean follow up of 8 years, and it was found that within this follow-up period, the revision rate was 20%.[25]

Differential Diagnosis

The diagnosis of SON can be challenging due to limited knowledge of the disease amongst clinicians. Often knee pain is explained and dismissed as referred pain from known ipsilateral hip disease. If it is investigated, the pathology of an intra-articular nature is scrutinized first. Furthermore, as there is often concurrent hip disease in patients with SON, knee pain should be a red flag triggering further investigation rather than a reason to dismiss the presentation as a symptom of pre-existing hip disease. Secondary osteonecrosis can be easily confused with several other differential diagnoses:[3]

• Postraumatic osteonecrosis
• Osteochondritis dissecans
• SPONK
• Infection
• Fracture
• Meniscal injury

As discussed in this article, the differences between the three types of osteonecrosis can be clearly defined, with few overlapping features, and therefore there is now no excuse to confuse these clinical entities.[2]

Prognosis

A review of the literature has not revealed any studies which examine the natural progression of the disease. Furthermore, most studies focus on the treatment of the disease in its late stages. Ultimately, if undiagnosed, patients with SON will develop end-stage osteoarthritis and require total knee arthroplasty. Several studies have demonstrated outstanding results of TKR in patients with SON, as previously discussed. Modern advances in surgical techniques, improved biomechanical implants, and improved perioperative and postoperative medical management have led to these excellent outcomes in patients undergoing TKR due to SON.[13]

Complications

The pathology of osteonecrosis is the same irrespective of its etiology. Ischemia and necrosis prevent repair, cause bone resorption, and replacement with granulation tissue. The resulting acellular region compromises mechanical stability, which leads to the eventual collapse of the affected condyles.[2]

The degenerative nature of this disease dictates that if left undiagnosed and untreated, the patient's clinical condition will deteriorate. If diagnosed and treated conservatively in the early stages of the disease, the patient may avoid the inherent risks associated with surgery. Unfortunately, in current practice, very few patients with SON are detected in the early stages of the disease, and even if they are, subsequent surgery may well be required.