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
3D-Printed Endoprosthesis Yields Promising Early Results
Tumor resections from the pelvic girdle often pose daunting reconstruction challenges for orthopaedic surgeons. In the September 2, 2020 issue of The Journal of Bone & Joint Surgery, Ji et al. report early results from a series of 80 bone-tumor patients who underwent pelvic reconstruction using a 3D-printed modular hemipelvic endoprosthesis. The 3D-printed interconnected porous component was generated from an electron beam melting process, and the design allowed for the main iliosacral fixation screws to be oriented parallel to the loading axis of the trunk.
The authors detected no acetabular component instability or implant loosening or migration after a mean follow-up of 32.5 months. The mean acetabular tilt on the reconstructed side immediately after surgery was 46.9o, and it was 47.1o at the most recent follow-up. The mean function score (84%, as measured by the Musculoskeletal Tumor Society 93 tool) was higher than the previously reported range of 55% to 72% from recent studies, and the authors say that the 3-month dislocation rate in this series (2.5%) “seems to be the lowest ever reported.” Moreover, histological analysis of specimens from 2 patients who experienced tumor recurrence revealed bone trabeculae extending toward the implant and bone ingrowth within the porous network.
Still, complications occurred in 16 (20%) of the patients, with wound dehiscence being the most prevalent one. Deep infections, relatively common after pelvic reconstruction surgery, occurred in 5 (6.3%) of the patients, which is a lower deep-infection rate than those reported in previous studies.
Despite the stable fixation and “satisfying early functional and radiographic outcomes” with this 3D-printed modular prosthesis, the authors caution that their short-term results “may prove to be insufficient for the assessment of implant viability.” Nevertheless, any innovation that helps address the many surgical challenges in this population of orthopaedic patients is welcome.
What Affects Symptoms in Kids with Flatfoot?
Pes planovalgus (flatfoot) is a common condition seen in the pediatric orthopaedic clinic. We who help manage this condition differentiate it from adult acquired flatfoot deformity, primarily in that most child and adolescent patients remain asymptomatic or minimally symptomatic and rarely require surgical intervention. However, it would be nice to have data to share with young patients and their parents regarding factors associated with flatfoot symptoms.
Min et al. provide some of that data in the September 2, 2020 issue of The Journal. The authors retrospectively evaluated factors affecting the symptoms of idiopathic pes planovalgus among 123 patients (mean age of 10.1 ± 3.2 years) using the 4-domain Oxford Ankle Foot Questionnaire (OxAFQ) administered to patients and their parents. They compared questionnaire scores to 3 radiographic measurements─anteroposterior (AP) talo-first metatarsal angle, lateral talo-first metatarsal angle, and hallux valgus angles. They also analyzed the scores in relation to patient age and sex.
Min et al. found that the physical domain score for the child-reported OxAFQ decreased by 0.74 with each 1° increase in the AP talo-first metatarsal angle. Because that angle is a surrogate for forefoot abduction, this finding portends worse patient-reported outcomes in kids with greater severity of that component of flatfoot. Female sex was also associated with lower physical domain scores, with the authors postulating that this might be attributable to culturally influenced sex differences.
In addition, age was a significant factor in 3 domains of the OxAFQ. Compared with scores from younger kids, children ≥10 years old and their parents reported statistically worse outcomes with regard to school/play, emotional well-being, and footwear. In other words, at or beyond the age of 10, flatfoot deformity seems to significantly affect the patient’s choice of footwear, interferes with the ability to participate in sports and play, and may cause personal distress, such as that which comes from being teased about foot appearance.
Orthopaedists can help manage most cases of pediatric flatfoot with sound footwear recommendations and reassurance. But it appears that in the setting of increased forefoot abduction, female sex, and symptoms that persist past the age of 10 years, further investigation may be warranted. Although this study has weaknesses, it shows that there may be detriments─both physical and emotional─associated with pes planovalgus in pediatric patients that should not be ignored.
Matthew R. Schmitz, MD
JBJS Deputy Editor for Social Media
New Surgical Approaches Still Welcome
JBJS has long promoted the use of high-level studies to facilitate evidence-based decision making. Still, each year only approximately 10% to 12% of published articles provide Level-I evidence. Although that percentage is increasing, the slope of the upward curve is gentle, largely because of the difficulty in designing and conducting randomized controlled trials (RCTs), and in gathering enough data from existing RCTs to conduct Level-I meta-analyses. The challenge of designing and conducting Level-I studies in orthopaedic surgery is compounded by our need to treat many conditions that are not common enough to make a controlled trial feasible. Consequently, there will always be room for Level-III and Level-IV research in the pages of The Journal (see related JBJS Editorial).
A Level-IV study that focuses on a surgical approach is rare, but in the September 2, 2020 issue of JBJS, Liu et al. describe preliminary results from a new concealed-incision, extrapelvic surgical approach to the anterior pelvic ring. This so-called “Fu-Liu approach” was investigated to treat pubic symphysis diastasis and parasymphyseal fractures, including those of the anterior column. Among the advantages of this approach over the more traditional Pfannenstiel approach are the following:
- Easier protection of the spermatic cord in males and the round ligament of the uterus in females
- Less risk to peritoneal internal organs, iliac blood vessels, and femoral nerves
- Improved aesthetic outcomes (The 2 small incisions are ultimately covered under perineal hair.)
- Relatively short learning curve
As our field continues to innovate toward less-invasive surgical interventions, such creative approaches are welcome. What we need now are comparative trials focused on this surgical approach versus the time-honored Pfannenstiel approach to convince surgeons and assure patients that the Fu-Liu approach yields limited complications and equal or better radiographic and patient-reported functional outcomes.
Because the conditions to which this approach can be applied are quite variable, such a trial would likely have to be multicenter and focused on pure, open-book, isolated pelvic fractures. We look forward to receiving and reviewing the manuscript describing an adequately powered trial that directly compares these two approaches.
Marc Swiontkowski, MD
JBJS Editor-in-Chief
Teamwork Necessary When Treating Patients with Syringomyelia + Scoliosis
Most orthopaedic spine surgeons and neurosurgeons have come to understand that syringomyelia plays a role in some cases of scoliosis, and that the spinal-cord condition may increase the risk of cord injury during deformity-correction surgery. In the August 19, 2020 issue of JBJS, Tan et al. investigate whether radiographic and clinical outcomes after 1-stage posterior spinal fusion to correct scoliosis secondary to syringomyelia differ between patients with syringomyelia related to Chiairi-I malformation (CIM) and those with idiopathic syringomyelia.
The short answer is “no.” Although researchers found larger preoperative syringeal parameters in the CIM group, up through 2 years after scoliosis-correction surgery, they detected no significant between-group differences in coronal/sagittal parameters or in scores from the 5 domains of the Scoliosis Research Society-22 questionnaire. Moreover, the preoperative neurological status and intraoperative neuromonitoring signals were similar in both groups.
In commenting on these findings, Kent A. Reinker, MD, points out that patients who had received preoperative neurological treatment for the syrinx were excluded from the study, so “the results … do not necessarily apply to patients who have had neurological intervention prior to scoliosis surgery.” He strongly recommends that all patients with a syrinx be referred to a neurosurgeon for evaluation prior to any scoliosis surgery, concluding that “a working partnership between orthopaedic surgeons and their neurological colleagues is important when assessing these patients.”
What’s New in Limb Lengthening and Deformity Correction 2020
Every month, JBJS delivers 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, Andrew G. Georgiadis, MD, co-author of the August 19, 2020 “What’s New in Limb Lengthening and Deformity Correction,” selected the five most clinically compelling findings from among the more than 50 noteworthy studies summarized in the article.
Congenital Limb Deficiencies
–A study of 42 children with severe fibular hemimelia found that levels of psychosocial adjustment and health-related quality of life were comparable among those who underwent staged reconstruction and those who underwent amputation, at a minimum of 2 years after treatment.
Congenital Dysplasia
–A study evaluating long-term outcomes of 34 patients who were treated with the Charnley-Williams procedure for congenital pseudarthrosis of the tibia found high rates of refracture after initial union, and that failure to operate on the fibula at the time of index surgery resulted in poor outcomes. On a more positive note, 10 of the 13 refractures healed upon retreatment.
Trauma
–A series of 14 patients with aseptic nonunion of the femur or tibia underwent long-bone compression with magnetic lengthening nails programmed “in reverse.”1 The nails shortened by 6.7 mm and the bones shortened by an average of 3.1 mm. Union was achieved in 13 of 14 cases.
Limb Lengthening
–In a study comparing motorized internal lengthening with external fixation for humeral lengthening,2 ultimate lengthening parameters were comparable, but motorized lengthening mitigated pin-site complications and allowed for reuse of the implant.
Pin-Site Management
–A randomized trial of 114 patients with external fixators concluded that there is no role for antiseptic preparations in routine pin care.3 Neither the antiseptic preparation used nor daily dressing changes affected the pin-site infection rate.
References
- Fragomen AT, Wellman D, Rozbruch SR. The PRECICE magnetic IM compression nail for long bone nonunions: a preliminary report. Arch Orthop Trauma Surg. 2019 Nov;139(11):1551-60. Epub 2019 Jun 19.
- Morrison SG, Georgiadis AG, Dahl MT. Lengthening of the humerus using a motorized lengthening nail: a retrospective comparative series. J Pediatr Orthop. 2019 Sep 23. Epub 2019 Sep 23.
- Subramanyam KN, Mundargi AV, Potarlanka R, Khanchandani P. No role for antiseptics in routine pin site care in Ilizarov fixators: a randomised prospective single blinded control study. Injury. 2019 Mar;50(3):770-6. Epub 2019 Jan 23.
Sustained Fevers After Spinal Fusion: A Sentinel for Infection?
Postoperative fevers occur frequently. During the first 2 to 3 days after surgery, these fevers are often due to atelectasis or the increased inflammatory response that arises from tissue injury during surgery. However, persistent postoperative fevers should be cause for concern. In the August 19, 2020 issue of The Journal, Hwang et al. examine the relationship between sustained fevers after spine instrumentation and postoperative surgical site infection.
The authors retrospectively reviewed 598 consecutive patients who underwent lumbar or thoracic spinal instrumentation. They excluded patients who underwent surgery to treat tumors or infections and those with other identified causes of fever, such as a urinary tract infection or pneumonia. Sustained fevers were defined as those that began on or after postoperative day (POD) 4 and those that started on POD 1 to 3 if they persisted until or beyond POD 5.
Sixty-eight patients (11.4%) met the criteria for a sustained fever after spinal instrumentation. Nine of those 68 (13.2%) were diagnosed with a surgical site infection. Of the 530 patients who did not have a sustained fever, only 5 (0.9%) developed a surgical site infection (p<0.001 for the between-group difference).
Further analysis revealed 3 diagnostic clues for surgical site infections among the patients with sustained fevers:
- Continuous fever (rather than cyclic or intermittent)
- Levels of C-reactive protein (CRP) >4 mg/dL after POD 7
- Increasing or stationary patterns of CRP level and neutrophil differential
In addition, the authors found that CRP levels >4 mg/dL between PODs 7 and 10 had much greater sensitivity for discriminating surgical site infection than gadolinium-enhanced magnetic resonance imaging data obtained within 1 month of the surgical procedure.
Although a vast majority (87%) of patients with sustained postoperative fevers in this study did not develop an infection, persistent fever after spine instrumentation surgery is something to be mindful of. The authors describe their findings as “tentative” and advise readers to interpret them with caution. Those caveats notwithstanding, I consider this information to be valuable because it might help prevent delays in the diagnosis of a potentially serious perioperative complication.
Matthew R. Schmitz, MD
JBJS Deputy Editor for Social Media
Drug to Improve Tibial Shaft Fracture Healing Fizzles
In our ongoing attempt to identify pharmacologic interventions that improve fracture healing, the sclerostin inhibitor romosozumab is a logical candidate, as it has been shown to decrease bone resorption, improve bone healing in animal and human studies, and reduce the prevalence of some fragility fractures in postmenopausal women. In the August 19, 2020 issue of The Journal, Bhandari et al. present the results of a randomized trial comparing romosozumab to placebo in the healing of tibial diaphyseal fractures treated with intramedullary (IM) nails. Tibial shaft fractures are common in adults, but even after IM nail fixation there is a significant rate of healing failure and subpar functional outcomes with this fracture type.
The study by Bhandari et al. was very well designed and conducted with high-quality data collection. In terms of the primary outcome—median time to radiographic healing—there was no significant difference between the placebo group (n=100) and 9 romosozumab groups (n=293 total, testing 3 different dose levels and 3 different frequencies). Additionally, analysis revealed no differences between placebo and romosozumab groups in median time to clinical healing or in changes in physical function from baseline. (See related OrthoBuzz post about a recent randomized trial investigating romosozumab for hip fractures.)
Kudos to Amgen for funding the trial and for allowing the 66-center, international academic consortium that conducted it to publish the results, warts and all. Such negative findings appropriately inform decisions about which compounds to investigate and about study designs for retesting the same compounds. For example, Bhandari et al. encourage further study of romosozumab in tibial-fracture patients at high risk of poor fracture healing, such as those with diabetes or patients undergoing treatment with corticosteroids.
We are likely to see many such “failures” in the search for pharmacological adjuncts to improve fracture healing, but it seems our orthopaedic community has laid out a clear roadmap for studying this important question further.
Marc Swiontkowski, MD
JBJS Editor-in-Chief
Treating Developmental Hip Dislocations Diagnosed after Walking Age
There is a wry saying in academic medicine that “nothing ruins good results like long-term follow-up.” But long-term follow-up helps us truly understand how our orthopaedic interventions affect patients. This is especially important with procedures on children, and the orthopaedic surgeons at the University of Iowa have been masterful with long-term outcome analysis in pediatric orthopaedics. They demonstrate that again in the August 5, 2020 issue of The Journal, as Scott et al. present their results comparing outcomes among 2 cohorts of patients who underwent treatment for developmental hip dislocations between the ages of 18 months and 5 years—and who were followed for a minimum of 40 years.
Seventy-eight hips in 58 patients underwent open reduction with Salter innominate osteotomy, and 58 hips in 45 patients were treated with closed reduction. At 48 years after reduction, 29 (50%) of the hips in the closed reduction cohort had undergone total hip arthroplasty (THA), compared to 24 (31%) of hips in the open reduction + osteotomy group. This rate of progression to THA nearly doubled compared to previously reported results at 40 years of follow-up, when 29% of hips in the closed reduction group and 14% of hips in the open reduction group had been replaced.
In addition, the authors found that patient age at the time of reduction and presence of unilateral or bilateral disease affected outcomes. Patients with bilateral disease who were treated at 18 months of age had a much lower rate of progression to THA when treated with closed reduction, compared to those treated with open reduction—but the opposite was true among patients with bilateral disease treated at 36 months of age. Treatment type and age did not seem to substantially affect hip survival among those with unilateral disease.
I commend the authors for their dedication to analyzing truly long-term follow-up data to help us understand treatment outcomes among late-diagnosed developmental hip dislocations in kids. Long-term follow-up may “ruin” good results, but it gives us more accurate and useful results. And, in this case, the findings reminded us how important it is to diagnose and treat developmental hip dislocations as early in a child’s life as possible.
Read the JBJS Clinical Summary about this topic.
Matthew R. Schmitz, MD
JBJS Deputy Editor for Social Media
Electronic Portal Usage among Orthopaedic Patients
Physician groups and hospitals have come to rely on electronic patient portals (EPPs) for many things, including appointment scheduling and reminders, delivery of test results, and pre- and post-visit information gathering from patients. Most of the research into the clinical efficacy and cost-effectiveness of EPPs has taken place in primary care and internal medicine settings. But in the August 5, 2020 issue of The Journal of Bone & Joint Surgery, Varady et al. examine the benefits of EPP use among patients undergoing orthopaedic procedures of various types. In the process, they also uncover racial and socioeconomic disparities in the use of EPPs.
The retrospective review of >18,000 patients (average age of 56.9 years) undergoing an orthopaedic procedure at 2 Boston-area academic hospitals found a veritable 50-50 split between those who used the EPP and those who did not. Relative to white patients, African-American and Hispanic patients were significantly less likely to use the EPP. Other demographic factors associated with portal nonuse were non-English speaking, male sex, low income, and having less than a college education.
Multivariable regression analysis demonstrated that, relative to EPP nonuse, EPP use was associated with significantly lower no-show rates, increased odds of completing one or more patient-reported outcome measures (PROMs), and improved overall patient satisfaction. The degree of after-surgery functional improvements measured with PROMs was the same among EPP users and nonusers.
The authors home in on the benefits of the 27% reduction in missed appointments this study divulged. First and foremost, missed appointments have been shown to negatively affect patient outcomes. On the provider side, no-shows increase staff frustration and cost time and money. (The 2 hospitals realized a combined estimated $200,000 in savings over 1 year from the reduction in no-shows.) Consequently, Varady et al. say that “the benefit of reducing missed appointments alone may be sufficiently strong to warrant efforts to increase EPP enrollment.”
Increased efforts among orthopaedic office staff and clinicians to enroll patients in portal usage during their hospital stay or during pre- or postoperative visits could also help address the disparity issue. “These results have important implications for the orthopaedic surgery community in…achieving more equitable care,” the authors conclude.
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