Nontraumatic Osteonecrosis: An Early Target for Gene Therapy
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
JBJS Editor-in-Chief
Where Does the Blood Flow in the Femoral Head?
Osseous vascular anatomy has always been clinically relevant to orthopaedists, but its importance is sometimes overlooked. In the July 19, 2017 issue of The Journal, Rego et al. provide a precise topographic map of arterial anatomy in and around the femoral head.
Ever since Trueta’s classic work published in the British volume of JBJS in 1953, we’ve known that the terminal branches of the medial femoral circumflex system (also known as the lateral epiphyseal artery complex) supply blood to the majority of the femoral head. This information has proved critical in supporting treatment decisions for the management of femoral head and neck fractures. In those cases, surgeons typically perform ORIF through an anterior approach because it is remote from this posterior vascular supply.
The details in the Rego et al. study will help today’s and tomorrow’s arthroscopists more safely manage acetabular labral tears associated with cam deformities. In those settings, when increasing the “offset” across the femoral neck to decrease impingement, surgeons should limit the depth of bone removal to avoid injury to this important vascular network. Thanks to this study, operating surgeons now have precise anatomic information (albeit derived from non-deformed cadaver hips) with which to limit the risks of increasing the femoral head offset.
Marc Swiontkowski, MD
JBJS Editor-in-Chief
Don’t Delay DDH Treatment to Wait for Ossific Nucleus
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.
Reperfusion Patterns in Legg-Calve-Perthes Disease
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.
Plusses and Minuses of Capital Femoral Growth Plate Extension
Femoroacetabular impingement (FAI), especially in adolescent athletes, has received a lot of attention from orthopaedists in the last 15 years. In the May 18, 2016 edition of The Journal of Bone & Joint Surgery, a longitudinal radiographic study by Morris et al. sheds light on how a measurement called the epiphyseal extension ratio (EER) delivers excellent diagnostic accuracy for predicting cam morphology of the femoral head, one of the main causes of FAI.
The authors carefully analyzed at least five consecutive annual hip radiographs from 96 healthy adolescents. Specifically, they measured changes in the anteroposterior alpha angle and the superior EER (the superior epiphyseal extension divided by the femoral head diameter). They found a mean increase in alpha angle and EER between Oxford bone age (OBA) stages 5 and 7/8. The mean EER increased significantly at each stage, with the greatest increase occurring between OBA stages 6 and 7/8.
In this study, the EER showed excellent diagnostic accuracy for predicting a final alpha angle of ≥78, which prior research has suggested is a threshold that predicts an increased risk for developing end-stage hip osteoarthritis. However, as commentator John H. Wedge, MD emphasizes, Morris et al. “do not recommend radiographic screening for this marker.”
Dr. Wedge adds that this study lends credence to the hypothesis that cam deformity develops from chronic impingement before rather than after proximal femoral physeal closure. But perhaps the most interesting messages are in the discussion section, where Morris et al. state that “epiphyseal extension may be a physiologic, protective response to increased physeal shear forces that decreases the risk of progression to SCFE [slipped capital femoral epiphysis].” The authors describe the cam-morphology downside of epiphyseal extension as “the unfortunate long-term consequence of a short-term adaptive response.”
Reducing the Risk of Ceramic Femoral-Head Fractures
JBJS Case Connector has issued a “Watch” regarding the rare but potentially catastrophic fracture of ceramic femoral heads used in hip replacements.
Ceramic hip components are often chosen for younger patients to minimize long-term wear. Ceramic femoral head fractures arise mainly from trauma; non-compatible, damaged, or contaminated femoral head/stem taper connections; or material or manufacturing defects.
Because c
eramic head fractures are more likely to occur from insults during or after implantation than from manufacturing defects, the Watch includes four “golden rules” surgeons can follow to reduce the risk of these events, including making sure that the tapers on both the head and stem are compatible in all dimensions. The Watch also emphasizes the importance of patient education, during which patients should be encouraged to promptly report any and all postsurgical irregularities.
This Watch was prompted by a case report by Pomeroy et al. in the December 23, 2015 JBJS Case Connector, and a report by Heiner and Mahoney in the October 22, 2014 JBJS Case Connector.
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