|Year : 2020 | Volume
| Issue : 1 | Page : 19-25
Nonarthroplasty management of osteonecrosis of the femoral head
Harrison R Ferlauto1, Evan M Guerrero1, James R Urbaniak1, Grant E Garrigues2
1 Duke University Department of Orthopaedic Surgery, Durham, NC, USA
2 Midwest Orthopaedics at Rush, Rush University Medical Center, Chicago, IL, USA
|Date of Submission||18-Feb-2020|
|Date of Acceptance||18-Sep-2020|
|Date of Web Publication||21-May-2021|
Mr. Harrison R Ferlauto
Duke University School of Medicine, 8 Searle Center Drive, Durham, NC 27710
Source of Support: None, Conflict of Interest: None
It is estimated that 10,000–20,000 new cases of osteonecrosis of the femoral head (ONFH) are diagnosed annually in the United States. Left untreated, this disease results in progressive collapse of the femoral head and destruction of the hip joint, resulting in the need for total hip arthroplasty (THA). However, in younger patients with ONFH, initial treatment with THA is not a practical option because these patients typically outlive the life of their implant, and thus may require multiple revision operations. Therefore, a variety of nonarthroplasty treatments for ONFH have been developed to slow the progression of disease and prolong the time that a person can go before requiring THA. These nonarthroplasty treatments are grouped into three general categories: Pharmacologic, nonpharmacologic/nonoperative, and operative. However, there is no consensus as to the optimal nonarthroplasty management of ONFH. This article provides a review of the literature regarding nonarthroplasty management of ONFH.
Keywords: Femoral head, nonoperative, operative, osteonecrosis, pharmacologic
|How to cite this article:|
Ferlauto HR, Guerrero EM, Urbaniak JR, Garrigues GE. Nonarthroplasty management of osteonecrosis of the femoral head. Duke Orthop J 2020;10:19-25
| Introduction|| |
Osteonecrosis, from the Greek for “bone death,” has a multitude of etiologies, each ultimately resulting in an interruption of blood supply to a particular region of bone. Blood supply can be interrupted by means of intravascular occlusion, extravascular compression, or by mechanical disruption/surgical ligation of a blood vessel. Intravascular occlusion can be caused by thrombi, fat emboli, gas emboli, or abnormally shaped red blood cells. Direct endothelial damage can also result in secondary intravascular occlusion, with some common causes being vasculitis, radiation, chemical toxicity, and trauma. Vessels can be extrinsically compressed by extravasated blood, as well as by elevated intraosseous pressures secondary to increased fat accumulation within the bone marrow. Common medical risk factors for osteonecrosis include corticosteroids use, alcohol abuse, lupus (especially with corticosteroid therapy), human immunodeficiency virus, Gaucher's disease, and sickle cell disease.
Osteonecrosis typically affects patients in the third to fifth decades of life, with the femoral head being the most common site of disease. There are currently an estimated 10,000–20,000 new cases of osteonecrosis of the femoral head (ONFH) diagnosed annually in the United States. When ONFH is left untreated, its natural history is progressive collapse of the femoral head, resulting in deep groin pain and inevitable destruction of the hip joint. Patients presenting with end-stage disease typically require total hip arthroplasty (THA). In fact, ONFH accounts for approximately 5%–12% of THAs performed in the United States. However, most patients presenting with ONFH are relatively young, and given the higher revision risk in younger patients, initial treatment with THA is not ideal. For this reason, it is important to maximize nonarthroplasty treatment to preserve the hip joint and delay or avoid THA in this patient population. This article provides a comprehensive review of the nonarthroplasty treatment modalities for ONFH.
| Classification|| |
Determining the stage of ONFH is critical to any assessment of treatment. Therefore, several systems have been proposed to classify ONFH, with the majority relying on the results of various imaging studies [Table 1]. In general, among all of the classification systems, the stage of disease increases as bony destruction progresses radially outward from the inside of the femoral head toward the acetabulum. Thus, a lesion initially located within the cancellous portion of the femoral head becomes upstaged once it results in destruction and collapse of the articular surface of the femoral head, and again becomes upstaged once there is destruction of the entire joint.
|Table 1: Common classification systems for osteonecrosis of the femoral head|
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In 1964, Ficat and Arlet were the first to classify ONFH based on clinical and radiographic findings. Their original system has since undergone several modifications, most notably by Ficat himself in 1985. The Ficat classification is regarded as the simplest of all the classification systems, and is the one most commonly used today. However, it is limited insofar as it does not utilize advanced imaging modalities, nor does it take into account prognostically relevant details such as size and location of the necrotic lesion. The University of Pennsylvania/Steinberg classification is the second most commonly used classification system, and incorporates magnetic resonance imaging (MRI) findings to identify preradiographic stages of disease. It was also the first system to account for the size of the necrotic lesion. The Association Research Circulation Osseous (ARCO) classification is the third most commonly used system, and is even more granular in nature, incorporating additional details such as location of the lesion within the femoral head. At our institution, the Urbaniak classification is utilized and is similar to the Steinberg classification.
| Pharmaceutical Treatments|| |
To date, a variety of pharmaceutical therapies have been investigated for the prevention and treatment of ONHF. Bisphosphonates act by inhibiting osteoclast activity, decreasing bone resorption relative to production, resulting in increased bone density. Lai et al. performed a randomized controlled trial (RCT) on patients with Steinberg Stage IIC or IIIC ONFH comparing alendronate 70 mg weekly for 25 weeks to placebo with 2 years' follow-up. They found that two of the 29 femoral heads in the alendronate group collapsed versus 19 of 25 in the control group (P < 0.001). One hip went on to THA in the alendronate group versus 16 in Placebo group (P < 0.001). Chen et al., performed a RCT on 52 patients (65 hips) with Steinberg Stage IIC or IIIC osteonecrosis with alendronate versus placebo and found no significant difference in need for THA, progression of disease, or quality of life. Agarwala and Shah studied 40 patients (53 hips), Ficat Stages I, II, or III, treated with 3 years of 10 mg daily alendronate therapy with 10-year follow-up and found that, while 38% of the hips deteriorated and 13% required THA, the natural history was significantly improved over historical trials without treatment. Seven of the 53 hips (13%) required THA in 10 years, compared to 78% of historical controls at a mean of 34 months. Thirty-eight percent of the 53 hips progressed in Ficat stage within 10 years compared to 74% historically at 34 months., Lee et al. randomized 110 patients with Steinberg I or II ONFH to zoledronate versus placebo. At 2 years' follow-up, there was no significant difference in collapse or need for THA. A 2016 meta-analysis of five RCTs looking at bisphosphonate treatment for ONFH determined that bisphosphonates offer no statically significant benefit compared to placebo. Therefore, the evidence for bisphosphonate use in precollapse ONFH is conflicted. Alendronate is a potentially effective treatment option, but with mixed data and a significant risk of adverse side effects, further evidence is needed before bisphosphonate therapy can be routinely recommended for patients with precollapse ONFH.
The hyperlipidemic state from corticosteroids is thought to result in fat accumulation in the bone marrow, leading to intraosseous hypertension and eventual sinusoidal collapse and osteonecrosis. Statins have been proposed to decrease adiposity and pressure in the femoral head, and prevent (or theoretically treat) ONFH, specifically ONFH caused by steroids. Pritchett studied 284 patients taking statins while taking high dose steroids, and found that only 3 patients (1%) developed osteonecrosis compared to the 3%–20% incidence for patients receiving high-dose steroids alone. However, Ajmal et al. found that among 338 transplant patients on statins, 15 (4.4%) developed ON, versus 180 of 2543 (7%) of patients not on statins, a difference that was not statistically significant (P = 0.14). To date, we are aware of no studies evaluating the efficacy of statins in treating patients with established ONFH. There are also no RCTs comparing statins to placebo in patients taking high-dose corticosteroids. However, given the available retrospective data, and the limited side effect profile of statin drugs, it would be reasonable to consider prophylactic statin therapy in patients receiving high-dose corticosteroids for prolonged periods.
Iloprost, a prostacyclin analog, is thought to act by inhibiting platelet aggregation and promoting vasodilation. Multiple studies have shown iloprost treatment to significantly improve pain and MRI findings in the short-term in patients with early osteonecrosis and/or bone marrow edema, which are believed to be a spectrum of the same disease.,, Beckman et al. studied iloprost infusion alone versus core decompression (CD) alone versus CD followed by iloprost infusion and found that each treatment led to significant improvement in Harris hip score (HHS), Western Ontario and McMaster University Osteoarthritis Index score, SF-36 score, and visual analog scale (VAS) after 3 months and 1 year, but that the best results came from combination therapy. However, there are no studies to our knowledge showing decreased femoral head collapse or decreased need for THA following iloprost treatment.
Hypercoagulability and thrombosis play a role in ONFH, making anticoagulation a potential treatment or prevention option. Korompilias et al. studied 216 consecutive patients sent to the Duke University Medical Center for free vascularized fibular grafting (FVFG) for ONFH and found that 83% of patients had an identifiable disorder of hypercoagulability. Glueck et al. studied patients with a thrombophilic-hypofibrinolytic disorder and Ficat Stage I or II ONFH. They found that 19 of 20 patients (95%) with primary idiopathic ONFH treated with enoxaparin did not progress in Ficat stage after 2 years' follow-up, compared to three of 15 patients (20%) with secondary, steroid associated, ONFH treated with enoxaparin, implying that enoxaparin may prevent progression of disease in hypercoagulable patients with primary idiopathic ONFH. Another study by Glueck looked at six patients with familial thrombophilia and found that after four to 16 years of anticoagulation, nine hips in these six patients (eight Ficat II, one Ficat I), did not progress, compared to the 50%–80% 2 years' progression rate among historical controls of Ficat Stage II hips. Furthermore, five of the six patients became pain free and remained asymptomatic through follow-up. Although enoxaparin appears to be a promising treatment option, especially in patients with known hypercoagulable disorders, its long-term subcutaneous injection is inconvenient to patients, and its efficacy has not been studied in large RCTs. Further studies are needed to determine if there is benefit to its use in a more general group of ONFH patients.
Finally, there is currently a multicenter trial by Albers et al. studying aspirin as a treatment option. Preliminary data have been published at a mean follow-up of 3.7 years showing progression of disease in one of 12 hips (8%) in patients taking aspirin compared to 30 of 45 (67%) historical controls (P < 0.002). Aspirin could potentially provide anticoagulation without the inconvenience of subcutaneous injections, and the results of this trial may provide further insight.
| Nonpharmaceutical and Nonoperative Treatments|| |
Extracorporeal shock wave therapy (ESWT) acts by transferring mechanical energy to bone, resulting in local upregulation of bone morphogenetic protein (BMP)-2 and VEGF, which have osteogenic and angiogenic effects. Vulpiani et al. evaluated 36 cases of ONFH treated by ESWT. None of the 26 hips, ARCO stages I and II, progressed on X-ray or MRI at 2 years' follow-up. However, there was clinical deterioration requiring THA in 10 of 15 Stage III patients. Ludwig et al. studied 22 patients with ONFH 1 year after ESWT treatment and found that VAS scores improved from a mean of 8.5 to 1.2, and HHS improved from a mean of 43.3 to 92. MRI results showed complete healing in four patients, a significant decrease in the size of the area with poor perfusion in six patients, unchanged findings in 10 patients, and an increase in the size of area of poor circulation in one patient. Wang et al. compared ESWT to CD and nonvascularized free fibular grafting in a RCT studying 52 hips. The study found that the shock wave group had significantly better HHS and VAS scores, as well as greater mean decrease in lesion size at 6 months, 12 months, and 24 months. The results of ESWT are promising, but larger RCTs would be helpful in determining the efficacy and indications for ESWT in ONFH.
Hyperbaric oxygen therapy (HBO) is believed to treat ONFH by improving oxygenation, reducing edema, and stimulating angiogenesis. Koren et al. reviewed 68 patients with Steinburg stage I or II ONFH treated with HBO. Seventy-four joints had pre and post treatment MRI, and 80% showed improvement after HBO. On follow-up at a mean of 11.1 years, 93% of the joints survived, mean HHS improved from 21 to 81 (P <.0001), and mean physical and mental component of SF-12 improved from 24–46 to 54–59 respectively (P < 0.0001). Camporesi et al., performed a double-blind, randomized, controlled, prospective study on 20 patients with unilateral Ficat Stage II ONFH comparing treatment by HBO versus hyperbaric air (HBA). Each patient received 30 treatments over 6 weeks. There was a significant improvement in pain after 20 and 30 treatments of HBO versus HBA, as well as improved range of motion after 10, 20, and 30 treatments. After 6 weeks, the study was opened and patients were all given the opportunity to use HBO. At 7-year follow-up, all 17 patients reported minimal pain, no decrease in activities of daily living, and none had received THA. The 9 patients with repeat MRI at 7 years follow-up showed continued improvement in radiologic appearance. Reis et al. studied 12 patients with Steinberg Stage I ONFH and found that after 100 days of daily treatment with HBO, 81% showed a return to normal MRI compared to 17% of untreated historical controls. The results of these studies show promise in the treatment of early disease, but larger RCTs would be beneficial to more clearly demonstrate HBO's effect.
Pulsed electromagnetic field therapy (PEMF) stimulates production of local growth factors, stimulates osteoblasts, stimulates angiogenesis, and reduces bone resorption. Bassett et al. studied 118 hips with ONFH treated with PEMF with an average follow-up of 5.3 years. None of the 15 Steinberg stage 0-III hips progressed, and nine of 15 hips actually improved in stage. Eighteen of 79 (23%) Stage IV lesions progressed, one of 21 (5%) Stage V hips worsened, and zero of three Stage VI lesions worsened, with none of the stage IV–VI hips showing improvement. Of 118 hips, with 87% having collapse present when entering the study, only 16% progressed, and patients were shown to have improved symptoms as well as reduced need for THA. Massari et al. studied patients with Ficat Stage I, II, and III ONFH treated with PEMF 8 h daily for an average of 5 months. They found that 94% of Ficat Stage I or II hips were preserved with PEMF therapy. Twenty hips (26%) advanced in Ficat stage, but over half of the hips that advanced were initially at Ficat Stage III. Once again, these studies show promise in precollapse lesions, however, they are insufficiently powered to determine the utility of PEMF in ONFH. Hsu et al. studied the so-called “cocktail therapy,” consisting of ESWT, HBO, and alendronate versus ESWT alone, and although approximately 75% of each group showed clinical improvement, there was no significant statistical difference between the two strategies.
| Operative Treatments|| |
CD of the femoral head was one of the first described and most frequently used operative treatments for ONFH. The procedure was traditionally performed by drilling with an 8–10 mm trephine or cannula, but now it is more common to use smaller diameter drills with or without adjuvant bone grafts, biologics, or implants. CD acts to penetrate the sclerotic rim surrounding the necrotic lesion, reduce intraosseous pressure, and promote neovascularization. Mont et al. demonstrated 32 of 45 hips (71%) had successful clinical outcomes at 2 years after multiple drilling using a 3 mL Steinmann pin. Twenty-four of 30 Ficat Stage I hips (80%) and eight of 15 stage II hips (57%) had successful outcomes with no surgical complications. Song et al. retrospectively reviewed 163 hips (136 patients) who had multiple drilling with 9/64 inch Steinmann pins, with success measured by HHS >75 and no need for additional surgery. They found that all hips with small lesions (<25% femoral head involvement) and 37 of 44 (84%) with medium lesions (25%–50% involvement) had successful outcomes compared to 56 of 104 (54%) with large lesions. Stage inversely correlated with success, with 84% of those with Ficat Stage I disease having successful treatment versus 65% of Stage II and 47% of Stage III. Complications were asymptomatic heterotopic ossification in 23 patients and a subtrochanteric femur fracture 1 week postoperatively in one patient.
Several adjuvants have been described to provide biological and/or structural support after CD. Autologous iliac crest bone mesenchymal stem cell (BMSC) aspirate is a common adjuvant due its osteogenic and angiogenic potential. Hernigou et al. studied 534 hips with Steinberg Stage I and II ONFH with 8–18 years' follow-up and found CD and BMSC grafting to be effective in treating early stage ONFH compared to historical controls treated nonoperatively, with 440 of 534 (82%) avoiding THA. Positive outcomes correlated with the number of cells transplanted. Gangji et al. studied CD with autologous BMSC graft versus CD alone in patients with ARCO Stage I and II ONFH. At 24-month follow-up, five of eight hips with CD alone had progressed to Stage III versus one of 10 hips in the group with CD and BMSC implantation. The time to collapse was also significantly longer in the BMSC group despite the small sample size (P = 0.016). Gangji et al. did a similar study with 5-year follow-up and found that eight of 11 hips in the CD alone group progressed to collapse, whereas three of 13 hips receiving CD and BMSC graft progressed to collapse, with time to collapse being significantly longer in the latter group. A 2017 meta-analysis of 11 RCTs found CD/BMSC combination therapy to be more efficacious that CD alone in the treatment of early ONFH. Recent prospective studies looking at the addition of growth factors such as BMPs and platelet-rich plasma to CD have also shown promising results, but further trials are necessary to better understand the efficacy of these advanced therapies compared to other standards of care.,
Nonvascularized bone grafting can be used to replace necrotic bone, giving structural support and a scaffold for new bone growth. Seyler et al. reviewed 39 hips from 33 patients who received nonvascularized bone graft using the trapdoor technique, inserting cancellous bone chips and bone marrow, with supplemental OP-1 (BMP-7). At a minimum follow-up of 24 months, with mean of 36 months, 25 of 30 (80%) small and medium-sized lesions required no further surgery compared to seven of nine requiring further surgery in large lesions. Eighteen of 22 hips with Ficat stage II disease required no further surgery versus eight of 17 Stage III hips. Keizer et al., reviewed 80 predominantly Ficat Stage II hips in 65 patients with ONFH treated with cortical tibial autograft or fibular allograft. Thirty-four hips (44%) required revision to THA or arthrodesis within 5 years, and there was significantly longer hip survivorship in those treated with tibial autograft compared to fibular allograft.
FVFG is another operative option that serves to decompress and remove necrotic bone and replace it with living bone, which provides both structural support and progenitor cells needed for osteogenesis. Eward et al. reviewed 65 hips in 61 patients who underwent FVFG for precollapse ONFH. The mean graft survival was 15 years, and 49 of 65 hips (75%) had surviving grafts for at least 10 years. Twenty-six hips that did not survive at complete follow-up each underwent conversion to THA at a mean of 8.3 years' postoperatively. Berend and colleagues reviewed 224 hips that were postcollapse without arthrosis treated with FVFG and found that 67.4% of hips survived at a mean of 4.3 years' follow-up, with an average time of conversion to THA of 2.7 years. Eisenschenk et al. reviewed 80 patients with ONFH treated with vascular pedicled iliac crest autograft. HHS was good or excellent in 86.6% of patients, and 56.1% of patients' radiographs remained stable at a mean follow-up of 5 years. In 2017, Cao et al. published a RCT looking at 54 hips in 27 patients with ARCO stage I-III ONFH randomized to treatment with either CD or FVFG. Compared to the group treated with CD, those treated with FVFG were shown to have improved femoral head vascularity and less progression of osteonecrosis based on ARCO staging at 36 months' follow-up. However, there was no difference between the two groups regarding conversion to THA. Overall, FVFG has proven to be a viable option to delay THA in precollapse and prearthrosis postcollapse ONFH, but these procedures are technically challenging and should only be performed by appropriately trained and experienced surgeons.
Femoral osteotomy moves the necrotic area of the femoral head from a position of weight-bearing to a reduced weight-bearing position while moving viable bone to the weight-bearing region, and preserving the native blood supply. Both transtrochanteric and intertrochanteric techniques have been described. Sugioka et al. reviewed 128 hips in 90 patients after receiving transtrochanteric femoral osteotomy. Progressive collapse in the newly created weight-bearing area occurred in 25 of 128 hips, with each of those progressing to collapse having extensive lesions preoperatively. Seventy-six of 80 hips in the group with >1/3 of the total articular surface intact preoperatively showed no collapse of the newly created weight-bearing area. Ito et al., reviewed 34 hips in 28 patients who received intertrochanteric osteotomy. Twenty-five of 34 hips (74%) had a satisfactory result with HHS >80 at a mean follow-up of 18.1 years. Nine of 34 hips showed progression of joint space narrowing or femoral head collapse. Six of 34 hips required THA or hemiarthroplasty, with four hips converted at 10 years and two hips converted at 20 years. Average shortening of the lower extremity was 19 mm. Drawbacks of this procedure include the challenges associated with conversion to THA in the setting of altered anatomy and hardware, and the prerequisite that patients have no osteonecrosis in the superolateral femoral head.
| Conclusion|| |
There are several nonarthroplasty options for the treatment of ONFH, and each has the potential to slow the progression of precollapse disease, helping young patients delay or avoid THA. Many of the studies cited above regarding nonoperative treatments are either retrospective reviews or insufficiently powered RCTs, and there is great need for large RCTs to clarify the roles of these agents in the treatment of ONFH. FVFG has proven to be a viable option to delay or prevent THA in precollapse and prearthrosis postcollapse ONFH, but these procedures are technically challenging and should only be performed by appropriately trained and experienced surgeons. CD, with or without BMSCs, has proven effective in delaying arthroplasty in small-to-medium sized, symptomatic, precollapse lesions and is a viable treatment option in those cases. With many potentially effective treatments and combinations of treatments, but no clear gold-standard of treatment for precollapse disease, it is important to evaluate every case individually and weigh the evidence of efficacy against the potential side effects and risks of each therapy. There is a great opportunity for further clinical trials comparing different treatments, combinations of treatments, and treatments as adjuncts to surgery in ONFH, as well as osteonecrosis of other anatomic locations.
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