As osteonecrosis of the femoral head (ONFH) progresses, it can impair a patient’s ability to walk, and hip arthroplasty is often the only effective long-term option. Other interventions to relieve the pain of ONFH include surgical decompression of the femoral head, which is generally effective but often does not change the natural history of the process. Once the femoral head collapses and loses sphericity, degenerative arthritis of the hip follows quickly. Well-documented risk factors for ONFH include excessive alcohol consumption and corticosteroid use. But why do some patients with these risk factors develop osteonecrosis, while others do not.
In the September 16, 2020 issue of The Journal, Zhang et al. address that clinical quandary with a genomewide association study on a chart-reviewed cohort of 118 patients with ONFH and >56,000 controls. The findings shed light on what is obviously a condition with multifactorial etiology and complex gene-environment interactions. The case-control study identified 1 gene (PPARGC1B) and 4 single nucleotide variants associated with ONFH overall, and with 2 subgroups—those exposed to corticosteroids and those with femoral head collapse. Steroid intake was highly prevalent in both cohorts—90.7% of the ONFH patients had at least one 3-week course of corticosteroids, compared with 68.3% of controls.
For readers interested in the detailed genetic bases for osteonecrosis, this study offers a treasure trove of data. But for all of us, these findings, after they are verified in other populations, may very well form the basis for pharmacologic and gene-modifying strategies in patients at risk for ONFH. Moreover, osteonecrosis of the femoral head is just one of many musculoskeletal conditions that can probably be addressed with this type of genome-based research strategy.
Marc Swiontkowski, MD
A recent report in Radiology citing possible complications from injecting steroids into painful joints with osteoarthritis (OA) has received lots of attention in the mainstream media. Radiologists from Boston, Germany, and France reviewed the existing literature and found an association between intra-articular steroid injections and a small increased risk of four adverse joint findings: accelerated OA progression, subchondral insufficiency fracture, complications from osteonecrosis, and bone loss. However, the study did not include a control group that did not receive injections, and therefore it cannot be used to assess whether injections are associated causally with the adverse joint findings.
In an interview with Boston radio station WBUR, lead author Ali Guermazi, MD stressed the point that readers should not conclude from this report that steroid injections cause these complications, adding that additional research in this area is “urgently needed.” In the same radio coverage, Jeffrey Katz, MD, a professor of orthopaedic surgery at Boston’s Brigham & Women’s Hospital and a Deputy Editor at JBJS, said patients who have received such injections or plan to should not be overly worried. However, he added that “for clinicians and patients who’ve been doing injections for several years, it’s worth it to pause and say, ‘Do we want to discuss [again] what we think are the benefits and risks of this.’”
The exact cause of osteonecrosis in the setting of developmental dysplasia of the hip (DDH) is unknown. However, some pediatric orthopaedists are concerned that DDH treatment in the absence of the ossific nucleus of the femoral head increases the risk of subsequent osteonecrosis. That concern has to be weighed against evidence that delayed DDH treatment may lead to more difficult reduction and potentially necessitate additional procedures.
In the May 3, 2017 issue of JBJS, Chen et al. performed a meta-analysis of cohort and case-control studies to clarify this potential “conflict of interests” in DDH treatment. Twenty-one observational studies were included. Of the 969 hips with an ossific nucleus present before reduction, 198 hips (20.4%) had eventual osteonecrosis events; among the 608 hips without an ossific nucleus, 129 (21.2%) had osteonecrosis events. The authors state that this difference “is neither clinically important nor [statistically] significant.”
A sub-analysis determined that the presence of the ossific nucleus was not associated with significantly decreased odds of osteonecrosis even among patients who later developed more severe (grades II to IV) osteonecrosis. Chen et al. also performed a “meta-regression” of studies with short- and long-term follow-ups, finding “no evidence for a protective effect of the ossific nucleus with either short or long-term follow-up.”
Although 11 of the 21 studies in the meta-analysis were deemed high quality and 10 were of moderate quality, the inherent limitations of a meta-analysis derived predominantly from retrospective data prompted the authors to call for “further prospective studies with long-term follow-up and blinded outcome assessors.” Nevertheless, these findings lend additional support to the belief that treatment for DDH should not be delayed based on the absence of the femoral head ossific nucleus.
In the November 16, 2016 edition of The Journal of Bone & Joint Surgery, Kim et al. improve our understanding of how blood flow is restored to the necrotic femoral head in Legg-Calve-Perthes disease. Using a series of perfusion MRI scans, the authors evaluated 30 hips with Stage-1 or -2 disease; 15 of the hips were treated conservatively, and 15 underwent one of three operative interventions.
Revascularization rates varied widely (averaging 4.9% ± 2.3% per month), but the revascularization pattern was similar, converging in a horseshoe-shaped pattern toward the anterocentral region of the femoral epiphysis from the posterior, lateral, and medial aspects of the epiphysis. The MRIs yielded no evidence of regression or fluctuation of perfusion of femoral heads, which casts some doubt on the proposed repeated-infarction theory of pathogenesis for this disease.
In a related commentary, Pablo Castaneda emphasizes that the study was not designed to evaluate the effects of different treatments, but he says knowing about an MRI pattern that is predictive of final outcomes in Legg-Calve-Perthes disease “has potential for improving our prognostic abilities.” Still, neither the commentator nor the authors suggest routinely obtaining serial MRIs in this patient population.
Every month, JBJS publishes a Specialty Update—a review of the most pertinent and impactful studies published in the orthopaedic literature during the previous year in 13 subspecialties. Click here for a collection of all OrthoBuzz Specialty Update summaries.
This month, James Ninomiya, MD, MS, lead author of the September 21, 2016 Specialty Update on Hip Replacement, selected the five most clinically compelling findings from among the nearly 70 studies summarized in the Specialty Update.
–A meta-analysis found no differences in short- and medium-term implant survivorship among the following three bearing combinations used in THA patients younger than 65 years of age: ceramic on ceramic, ceramic on highly cross-linked polyethylene, and metal on highly cross-linked polyethylene.1
Insight into Aseptic Loosening
–Pathogen-associated molecular patterns (“endotoxins”) on particulate wear debris may be partially responsible for aseptic loosening. An in vitro/in vivo study found that macrophages that did not express the pathogen-associated molecular pattern receptor called TIRAP/Mal had significantly diminished secretion of inflammatory proteins. Patients with a genetic polymorphism suppressing that receptor exhibited decreased osteolysis during in vivo experiments. This suggests that some patients may be genetically more prone to aseptic loosening.
THA in Patients with RA
–A systematic review/meta-analysis of patients who were and were not taking a TNF-α inhibitor for rheumatoid arthritis prior to hip replacement found that those taking the drug had an increased risk of perioperative infection, with an odds ratio of 2.47.2 These results suggest that in order to decrease the risk of perioperative infections, it may be prudent to discontinue these drugs in advance of proposed joint replacement surgery.
Delaying THA for Femoral Head Osteonecrosis
–A systematic review/meta-analysis of patients with femoral head osteonecrosis concluded that injection of autologous bone marrow aspirate containing mesenchymal stem cells during core decompression was superior by a factor of 5 to core decompression alone in preventing collapse of the femoral head and delaying conversion to THA.3 This information may lead to new treatment paradigms for osteonecrosis.
Preventing Post-THA Dislocations
–A systematic review/meta-analysis that included more than 1,000 patients who underwent THA with a posterior or anterolateral approach found similar dislocation rates among those who were and were not given post-procedure restrictions in motion or activity.4 This suggests that the use of traditional hip precautions may not be necessary, and in fact may impede the rate of recovery following joint replacement surgery.
- Wyles CC, Jimenez-Almonte JH, Murad MH, Norambuena-Morales GA, Cabanela ME, Sierra RJ, TrousdaleRT. There are no differences in short- to mid-term survivorship among total hip-bearing surface options: a network meta-analysis. Clin Orthop Relat Res. 2015 Jun;473(6):2031-41. Epub 2014 Dec 17.
- Goodman SM, Menon I, Christos PJ, Smethurst R, Bykerk VP. Management of perioperative tumour necrosis factor α inhibitors in rheumatoid arthritis patients undergoing arthroplasty: a systematic review and meta-analysis. Rheumatology (Oxford). 2016 Mar;55(3):573-82. Epub 2015 Oct 7.
- Papakostidis C, Tosounidis TH, Jones E, Giannoudis PV. The role of “cell therapy” in osteonecrosis of the femoral head. A systematic review of the literature and meta-analysis of 7 studies. Acta Orthop. 2016 Feb;87(1):72-8. Epub 2015 Jul 29.
- Van der Weegen W, Kornuijt A, Das D. Do lifestyle restrictions and precautions prevent dislocation after total hip arthroplasty? A systematic review and meta-analysis of the literature. Clin Rehabil. 2016 Apr;30(4):329-39. Epub 2015 Mar 31.
This month’s Image Quiz from the JBJS Journal of Orthopaedics for Physician Assistants (JOPA) presents the case of a 74-year-old woman with a 2-month history of left knee pain. She was given an intra-articular knee injection for presumed osteoarthritis, which failed to provide any relief. At a follow-up visit, clinicians obtained the MRI shown here.
Pick among five possible diagnoses: secondary osteonecrosis, transient osteoporosis, spontaneous osteonecrosis, osteochondritis dissecans, or bone marrow edema lesion.
Osteonecrosis of the femoral head is a dreaded complication for patients with a slipped capital femoral epiphysis (SCFE). This complication is far more common with acutely displaced and unstable slips. Safely reducing the femoral head back on the neck while preserving blood supply can often be accomplished with closed reduction maintained by in situ cannulated screw fixation, although some recent efforts to treat SCFE have focused on open approaches.
In the June 15, 2016 edition of The Journal, Schrader et al. demonstrate the benefits of using a simple intracranial pressure (ICP) monitoring probe (see photo) inserted through the cannulated screw to measure femoral head perfusion. While using this technique intraoperatively on 26 hips with SCFE, the authors encountered six hips in which there was no blood flow to the femoral head after closed reduction and screw stabilization. In these situations, they performed percutaneous capsular decompression.
The fact that all patients—even those with no initial femoral head perfusion—left the operating room with measurable blood flow confirms the long-held principle that lack of perfusion can be treated with capsulotomy. The ICP device uses waveforms to measure blood flow and is an accurate gauge of perfusion. Moreover, the technology is available in most hospitals with trauma centers or neurosurgery services.
Having researched femoral head perfusion myself as a young orthopaedist and having kept abreast of more recent findings in this area, I think the monitoring protocol described by Schrader et al. is the best yet published to limit the devastating complication of hip osteonecrosis. I feel that if ICP monitors are available, this protocol should be adopted by all centers treating patients with acute SCFE.
Marc Swiontkowski, MD
Fractures of the femoral head are uncommon. Typically associated with hip dislocations, they are found in association with high-energy trauma. They occur more commonly in men than women. Because of their relatively rare occurrence, large series with validated outcomes have not been reported. As noted by Marecek et al. in the November 2015 issue of JBJS Reviews, the goals of treatment are to achieve early and safe reduction and fixation and, in doing so, avoid complications, including osteonecrosis and heterotopic ossification.
To accomplish these goals, it is important to identify any associated life-threatening injuries and to achieve prompt reduction. A distinction is made between infrafoveal and suprafoveal fractures and the presence of associated femoral neck or acetabular fractures. Operative treatment is usually accomplished through the direct anterior or surgical hip dislocation approach, depending on the associated injury patterns. The use of mini-fragment lag screw fixation is generally preferred.
The initial treatment of femoral head fractures follows advanced trauma life support (ATLS) protocols. If hip dislocation is present, urgent reduction is performed in conjunction with skeletal relaxation to decrease the risk of osteonecrosis of the hip. Nonoperative treatment is reserved for patients with infrafoveal fractures with a concentric hip joint and no intra-articular debris and patients in whom operative intervention carries a morbid risk of complications. The timing of intervention for femoral head fractures remains controversial, and at least one randomized controlled trial demonstrated significantly worse outcomes for patients who had closed manipulative reduction and delayed open reduction and internal fixation compared with patients who received immediate operative reduction and fixation.
In summary, femoral head fractures are uncommon but severe. After prompt reduction of hip dislocations, a thorough evaluation is required to detect all associated injuries and to formulate an appropriate operative plan. Treatment should be directed toward achieving a stable, concentrically reduced hip with anatomic reduction of the fracture or excision of comminution and removal of articular debris. Arthroplasty should be reserved for patients who are older, those who have degenerative changes of the hip, and those who have complex injuries, the treatment of which would be more detrimental or risky than immediate arthroplasty.
Thomas A. Einhorn, MD
Editor, JBJS Reviews
For decades, researchers have been investigating different methods of cartilage repair, but no approach has yet risen to “gold standard” status. In the June 24, 2015 edition of JBJS Case Connector, “Case Connections” looks at three different restorative/replacement approaches to cartilage defects.
In the springboard case by Ramirez et al., a high school athlete’s full-thickness glenoid osteochondral defect was filled arthroscopically with particulated juvenile cartilage allograft (see image below).
In an earlier case report by Convery et al., the authors recommended placing additional autogenous bone beneath allografts to augment the host bed and enhance incorporation of the allograft’s osseous shell.
Welsch et al. alert surgeons to the possibility of hypertrophic cartilage opposite a defect that’s treated with a matrix-associated autologous chondrocyte transplant (MACT). And finally, Adachi et al. report on osteonecrosis of the femoral condyles that was treated with tissue-engineered cartilage combined with a hydroxyapatite scaffold enhanced with mesenchymal stem cells.
Although prospective studies with suitable control groups will be needed to prove the efficacy of these and other restorative techniques, early intervention with biologic restoration of the articular surface could eventually have a profound influence on patients with cartilage damage.