treatment options for avascular necrosis AVN of the hip cover

Avascular Necrosis of Hip: Treatment Options

Treatment options for AVN of the hip are typically separated into operative and nonoperative management. Many factors will affect options for management. There is no definitive or clear pattern on speed of progression, which complicates decision making. It is important to rule out secondary causes of avascular necrosis of the femoral head (AVNFH) and ask historical questions about chronic steroid use, alcohol use, clotting disorders, sickle cell disease, autoimmune disease, or trauma. 

Historically, age and staging are the most important factors in regards to definitive treatment options. The goal of all forms of treatment is to maintain the patient’s anatomy as long as possible, delaying the need for arthroplasty in young patients. It is ideal to delay arthroplasty due to the possibility of one or more revision surgeries during their lifetime. Older age, severely collapsed femoral head, and arthritic patients are accepted as candidates for arthroplasty.

In general, nonoperative management studies have conflicting results. It is important to identify risk factors and treat them accordingly e.g. anticoagulation if clotting disorder is present, halt alcohol use, etc. Bisphosphonates act to slow bone resorption and treatment with this class has conflicting evidence. One uncontrolled study with 294 patients showed improvement in pain and clinical function when taking alendronate 10 mg daily. The benefit was shown at three years, but not eight years [1]. Another study with 40 patients showed less collapse [7 vs. 76 percent] while taking alendronate 70 mg weekly [2]. One two year randomized controlled trial did not find a significant difference in outcome with oral alendronate versus placebo and a 2016 meta-analysis concluded bisphosphonate therapy did not significantly reduce the progression to collapse [3-4]. 

Statins are sometimes used to treat steroid-induced AVN. One retrospective analysis reported a lower incidence of AVN in 284 patients over a seven year period that were starting chronic glucocorticoid therapy (1% compared to 3-20%) [5]. More trials are currently ongoing, but none have been significant thus far. Iloprost, which is a prostacyclin analog, was shown to have lower VAS (Visual analog scores) in patients in ARCO stages 1 and 2 over a 3 year period and is an option for treatment [6].
staging of avascular necrosis AVN of the hip

Image 1. Staging of AVN of the hip (courtesy of AAOS)

Nonpharmacologic options with overall limited evidence include electrical stimulation, hyperbaric oxygen and extracorporeal shock wave therapy (ESWT). Most studies have been prospective or retrospective, but results have been encouraging for patients in early stages (0-2 in Ficat or ARCO). There have been mild improvements in clinical and radiographic procedures with these studies [7-11]. Similar results have been found with ESWT with improvements in pain and function, but results varied in regards to radiology. Studies were similar with a smaller sample size and were uncontrolled and not blinded [11-15]. The evidence with hyperbaric oxygen is very limited and one study in 68 patients showed improvement on MRI in 88% of patients with Steinberg stages I-II AVN, along with improvement in clinical scores [16].

Platelet rich plasma (PRP) and mesenchymal stem cells (MSCs) have also been used for nonoperative treatment of AVNFH. PRP is a centrifuged fraction of plasma that is a thrombocyte concentrate; it is an autologous source of cellular growth factors that aids in and augments tissue repair along with the other cells of wound healing. MSCs are capable of enhancing tissue regeneration by differentiating into various mesenchymal phenotypes, such as osteoblasts, chondrocytes, and adipocytes [44]. They are often used in conjunction and there are very limited studies on usage without surgery. 

Pak published two case reports for 4 patients with stage IV ONFH who received treatment by the injection of a PRP and adipose derived stem cell mixture into the femoral head under ultrasound guidance, which showed the long-term improvement in pain and motion range and the regeneration of bone by MRI for at least 7 to 12 months [40-42]. In another case report from Pak et al. [43], one patient received a PRP and adipose derived stem cell mixture treatment once and PRP treatment every week for 4 weeks for subsequent treatment. Eventually, this patient displayed the complete resolution of hip pain and motion function abnormalities at a 21-month follow-up, and MRI showed significant signal changes in both the T1 and T2 views of the femoral head before and after treatment. More randomized and long term studies are needed.
In young patients, many will elect for joint preservation surgery for many reasons. Core decompression (CD) reduces the pressure in the bone, opens up the hardening zone that hinders the repair of osteonecrosis, stimulates the formation of blood vessels around the decompression tunnel, enhances the replacement of the new bone, and delays the progression of osteonecrosis . This is the most common joint preservation surgery [18]. A recent meta-analysis showed an overall success rate of 65% with higher success rates occurring with earlier stages (Fig. 1). Although there is a paucity of studies within the last 10 years assessing long-term (>10 years) outcomes, one study with 128 hips had a 10 year follow up. The hip survival rates those in Ficat stages I, II, and III of disease were 96, 74, and 35 %, respectively [23].
staging and success rate avascular necrosis AVN hip

Table 1. Staging and success rate of AVN of the hip (Adopted from [23])

More recent methods include combining CD with autologous bone marrow concentrate from the iliac crest or ex-vivo marrow. The success rate of CD with ex-vivo marrow was 74% and the success rate of CD with autologous bone was 81%. Both were higher than the overall success rate for CD alone (65%) [19]. Li et al. compared the use of bone marrow cell therapy (BMC) to core decompression alone in a meta-analysis of 4 studies of 219 total hips and demonstrated that significantly less patients in the BMC cohort required additional surgeries and/or procedures than those in the core decompression cohort [22].

Both vascularized (VBG) and non-vascularized bone grafts (NVBG) have also been used for supplementation. NVBGs can be categorized as autograft versus allograft, cancellous, and cortical. Vascularized bone grafts are categorized as free or pedicled grafts. Free vascularized bone grafts involve removal of bone from its original (donor) blood supply, transplanting it to the affected area, and anastomosing the graft to the local blood supply. Historically, free vascularized bone graft (VBG) applications for the upper extremity have included reconstructions after tumor resection, significant infections, or trauma [20]. 

A diagram of a hip with a bone and a wire.

Image 2. Illustration of microsurgical vascularized bone graft for hip AVN (courtesy of pennmedicine.org)

The best results have been reported with free vascularized bone grafts with 70% and 91% in two small case series and a separate review found the best results with the absence of collapse and less than age 40 [20]. Kim et al. in 2005 compared 19 patients (23 hips) who underwent free vascularized fibular graft with 19 patients (23 hips) who underwent non-vascularized fibular graft. After a mean follow-up of 4 years, the vascularized patients enjoyed significantly better increase in outcome scores (70 % increase versus 35 % in the non-vascularized group), as well as significantly decreased postoperative dome depression and rate of collapse when compared to the non-vascularized group [21].
Advanced core decompression (ACD) is a relatively new technique that allows more efficient removal of necrotic tissue from the femoral head followed by refilling of the drill hole and the defect with an injectable bone graft substitute. It was introduced within the past five years and usually used concentrated autologous bone marrow aspirate, which is osteoinductive and osteogenetic, as opposed to osteoconductive. Early results have shown similar hip survival overall, but ACD was shown to be slightly better for Steinberg stage 2 hips [24].
Transtrochanteric rotational osteotomy (TRO) has become one of the hip-preserving alternatives for AVNFH. The principle of TRO is to replace necrotic bone with healthy bone in weight-bearing area through anterior or posterior rotation after intertrochanteric osteotomy [25]. It is typically used only for small lesions with less than 15 percent involvement in which the lesion can be rotated away from a weight bearing surface. The clinical outcomes of TRO remain controversial because the promising results of several Japanese studies could not be confirmed by American and European studies [26-28]. One recent meta-analysis concluded hip survival was better in Asain populations [29].
In more advanced cases in younger patients, more limited options exist. Vascularized iliac bone grafting was combined with tantalum rods to achieve better results in large lesions and advanced stages of disease. One retrospective study with 56 hips with AVNFH (ARCO stages 2-4) were followed for 5 years. The 5-year joint-preserving success rate of entire group was 87.5%, with 95% for Association Research Circulation Osseous stage II hips, 92% for Association Research Circulation Osseous stage III hips, and 63.6% for Association Research Circulation Osseous stage IV hips. Mean Harris Hip score (clinical hip score) of the 49 hips improved significantly from 50 to 91 points. Forty-three (76.8%) of 56 hips remained stable on radiographs [30].

Total hip arthroplasty (THA) remains a mainstay in treatment with advanced disease and in developed countries it is estimated to be responsible for 5 to 12% of total hip arthroplasties. It is preferred to be done in patients older than 40 years old. Younger patients have been shown to have a greater amount of aseptic loosening, a higher rate of linear wear of the polyethylene liner and a higher rate of osteolysis. More recent techniques including a cemented stem and cementless cup have yielded excellent long-term outcomes [32]. 

Two x - rays of a person's hip and knee.

Image 3. Before and after a hip replacement for AVN (courtesy of researchgate.net)

Some papers suggest that steroid-induced and alcohol-related AVN are associated with a less satisfactory outcome after THA compared with other causes of AVN [32-34] . Dorr et al identified AVN, especially alcohol-induced AVn as a negative prognostic indicator in patients younger than 40 years of age who were treated with THA [34]. Kim et al compared the results of 50 third-generation cemented femoral components and 98 second-generation cementless femoral components in 98 patients with AVn with a mean age of 47.3 years [36]. The survival rate with revision as an endpoint was 98% for both groups at 10 years. The same authors, in a study with the use of a ceramicon-ceramic bearing in 93 cementless THAs in 64 patients with AVN younger than 45 years old, reported no revision or loosening after a mean follow-up of 11.1 years [37]. More recently, studies have focused on long term effects and quality of life with ceramic-on-ceramic, ceramic-on-highly cross-linked polyethylene and traditional metal on polyethylene. Functional outcomes, complication rate, radiographic results and quality of life have shown similar outcomes with a slightly higher complication rate due to wear with metal on polyethylene [38-39].
In summary, many factors have to be taken into account when determining treatment options. Some providers will order laboratory studies to help guide treatment. Most patients below 40 years old without femoral head collapse will elect for nonoperative or joint preserving surgery. Nonoperative management including pharmacologic options have had mixed success, but have been shown to be safe. Core decompression is typically paired with either bone grafting or cell therapy and has generally yielded better results when compared to core decompression alone. In patients with advanced stages or osteoarthritis, total hip arthroplasty remains a mainstay in treatment. There are newer techniques such as advanced core decompression and hip arthroplasty using different components that have shown promise.
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