Genetic susceptibility to orthopaedic conditions is of interest to clinicians and patients alike. While the link between genetics and certain pediatric conditions is known, studies of sets of twins are providing new insights into adult issues, such as osteoarthritis, and the impact that genetics may have.
In the current issue of JBJS, Hailer et al. report on an investigation in Sweden in which they analyzed genetic susceptibility to hip and knee osteoarthritis necessitating total hip arthroplasty (THA) or total knee arthroplasty (TKA), and whether body mass index (BMI) moderates the heritability of these outcomes. They linked nearly 30,000 twin pairs with BMI information in the Swedish Twin Registry with the Swedish National Patient Register to identify twins who had undergone THA or TKA with a primary diagnosis of osteoarthritis. Structural equation modeling was then used to calculate the heritability of osteoarthritis treated with THA or TKA and how it related to BMI, age, and sex.
The authors note that, for radiographically defined knee osteoarthritis, previous twin studies have shown that the genetic susceptibility (“the proportion of the variation of a trait that can be attributed to the variation of genetic factors”) is between 0.4 to 0.8. In twin studies using total joint replacement as the outcome, heritability has been estimated to be 0.2 for TKA and 0.5 for THA.
Hailer et al. found that, on average in their cohort, approximately half of the susceptibility to undergo THA or TKA for osteoarthritis was explained by heritability, with similar estimates demonstrated for the 2 procedures: THA, 0.65 (95% CI, 0.59 to 0.70) and TKA, 0.57 (95% CI, 0.50 to 0.64). Of note, heritability decreased with higher BMI in both men and women for THA and in men for TKA. But in women, heritability for TKA increased with higher BMI (0.37 for a BMI of 20 kg/m2 and 0.87 for a BMI of 35 kg/m2).
Although the need for THA or TKA is not a perfect indicator of osteoarthritis (plenty of osteoarthritis does not become symptomatic enough to warrant total joint arthroplasty), this large study offers further data on the question of genetic susceptibility to the development of osteoarthritis. Understanding the influence of obesity (a modifiable risk factor) becomes increasingly important and warrants continued investigation in studies exploring heritability in relation to orthopaedic conditions.
Matthew R. Schmitz, MD
JBJS Deputy Editor for Social Media
The obesity epidemic continues throughout much of the developed world. Among the morbidly obese (BMI ≥40 kg/m2), we have a group of patients in whom arthritis is very likely to develop due to excessive loading of articular cartilage, chronic inflammation, and alignment problems. At the same time, many arthroplasty surgeons are wary of treating morbidly obese patients with surgery because of the increased perioperative risks. Although many of these patients still benefit greatly from joint replacement, in today’s “value-based care” environment, some institutions have implemented BMI cutoff thresholds for performing knee or hip arthroplasty. Others have set weight-loss requirements before they will schedule lower-extremity arthroplasty for morbidly obese patients. One still-unanswered question along these lines is: how much weight does a morbidly obese patient need to lose preoperatively in order to improve the outcome after a knee replacement?
Keeney et al. address that question in the August 21, 2019 issue of The Journal. In a retrospective cohort study, the authors evaluated outcomes among 203 morbidly obese patients who underwent a total knee arthroplasty (TKA). They found that a loss of 20 pounds preoperatively was associated with a shorter length of stay and a lower chance of being discharged to a rehab or skilled nursing facility rather than home. However, a 20-pound weight loss had no impact on surgical time or functional outcomes, as measured with the PROMIS-10 physical component score. Of note, only 14% of the evaluated patients lost at least 20 pounds preoperatively (highlighting the difficulty of losing weight in general and among this patient population in particular). There were no benefits of any kind in patients who lost only 5 or 10 pounds preoperatively.
While this study’s sample size is small, the findings provide evidence surgeons can use to encourage (or insist upon) larger amounts of weight loss before arthroplasty procedures in morbidly obese patients. In this study, the patients who lost at least 20 pounds remained morbidly or severely obese, and all the patients eventually regained most or all of the weight they lost. Still, the conclusion that at least 20 pounds of weight loss is beneficial for morbidly obese patients prior to a TKA remains sound. Because of the magnitude of this public health issue, we need more high-quality outcomes research (preferably using more knee-specific functional measures) on preoperative management of morbidly obese patients who are considering lower-extremity arthroplasty.
Marc Swiontkowski, MD
It is well established that obese patients who undergo total joint arthroplasty have increased risks of complications and infections. But what about folks who are not obese, but are just generally large? Do they also have increased post-arthroplasty complications, compared to their smaller counterparts? That is the question Christensen et al. explored in a registry-based study in the November 7, 2018 edition of JBJS.
In addition to BMI, the authors examined 3 other physical parameters—body surface area, body mass, and height—to determine whether these less-studied characteristics (all contributing to “bigness”) were associated with an increased rate of various adverse outcomes, including mechanical failure and infection, after primary total knee arthroplasty (TKA). They evaluated data from more than 22,000 TKAs performed at a single institution and found that the risk of any revision procedure or revision for a mechanical failure was directly associated with every 1 standard deviation increase in BMI (Hazard Ratio [HR], 1.19 and 1.15, respectively), body surface area (HR, 1.37 and 1.35, respectively), body mass (HR, 1.30 and 1.27, respectively), and height (HR, 1.22 and 1.23, respectively). In this study, 1 standard deviation was equivalent to 6.3 kg/m2 for BMI, 0.3 m2 for body surface area, 20 kg for body mass, and 10.5 cm for height.
These findings, while not all that surprising, are enlightening nonetheless. The study shows that increasing height has a greater negative impact on TKA outcomes than previously thought. While I spend a lot of time counseling patients with high BMIs about the increased risks of undergoing a TKA (and while such patients can take certain actions to lower their BMI prior to surgery), I do not spend nearly as much time counseling patients who are much taller than normal about their increased risks (and height is not a modifiable risk factor). Nor do I spend much time thinking about a patient’s overall body mass or body surface area in addition to their BMI. This study will remind me not to overlook these less commonly examined physical parameters when discussing TKA with patients in the future.
Chad A. Krueger, MD
JBJS Deputy Editor for Social Media
OrthoBuzz occasionally receives posts from guest bloggers. This guest post comes from Matthew Herring, MD, in response to a recent study in the Journal of Orthopaedic Trauma.
With many problems in orthopaedics, the best management options are still being debated. The treatment of femoral neck fractures is one such problem. Surgeons have several available options: cancellous screws (CS), a sliding hip screw (SHS), hemiarthroplasty, and total hip arthroplasty. The recently completed Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) randomized trial sought to offer insight on those treatment modalities.1 The study enrolled 1,079 patients with low-energy femoral neck fractures and randomized them into treatment with CS or SHS.
In a follow-up study published in the May 2018 edition of the Journal of Orthopedic Trauma, Sprague et al. analyzed FAITH data to identify predictors of revision surgery during 24 months after surgical fixation of a femoral neck fracture.2 Based on previously published studies, the authors identified 15 factors a priori that may be associated with revision surgery . Among the more than 800 patients in the FAITH cohort who had complete follow-up data, 191 (23%) underwent revision surgery and were included in the analysis. Proportional hazard modeling identified 5 factors associated with revision surgery: female sex (hazard ratio [HR], 1.79), body mass index (HR, 1.19—a 19% increased risk of revision for every 5-point increase in BMI), displaced fracture (HR, 2.16), Pauwels type III configuration (HR, 2.13 relative to type II), and poor implant positioning (HR, 2.70). In addition, prefracture dependence on assistive devices for ambulation was significantly associated with a risk of conversion to arthroplasty (p = 0.04), although a hazard ratio was not reported.
These important findings may help guide our decision making for the treatment of femoral neck fractures. First, male patients may be better candidates for surgical fixation of neck fractures than female patients, which probably relates to sex differences in bone density. Thinner patients also may be better candidates for femoral neck fixation, while arthroplasty may be the more reliable option for high-BMI patients.
Second, we have to pick the right fractures to fix. As is well described elsewhere in the literature, a more vertical fracture line (>50°) is more likely to fail with fixation. Additionally, patients with displaced fractures face a significantly higher risk of revision surgery and may be poor candidates for fixation.
Arguably, the most important modifiable risk factor for revision surgery is surgical technique. Unfortunately (and fortunately), in the FAITH study there were too few malreductions to investigate this variable in detail. However, poor implant positioning—defined as prominent screws at the lateral cortex, screw penetration, and lag screws positioned too high—was strongly associated with an increased risk of revision surgery.
It goes without saying, but well-placed implants perform better.
Matthew Herring, MD is a senior orthopaedic resident at the University of Minnesota and a member of the JBJS Social Media Advisory Board.
- Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) Investigators. Fracture fixation in the operative management of hip fractures (FAITH): an international, multicentre, randomised controlled trial. Lancet. 2017;389(10078):1519-1527.
- Sprague S, Schemitsch EH, Swiontkowski M, et al. Factors Associated With Revision Surgery After Internal Fixation of Hip Fractures. J Orthop Trauma. 2018;32(5):223-230.
Long-term population-based research has documented associations between high BMI and decreased longevity and increased risk of developing diabetes and cardiac complications. Musculoskeletally speaking, the risk of developing osteoarthritis of the knee has been strongly associated with elevated BMI, although the impact of high BMI on the development of hip osteoarthritis has been less clearly defined.
To detail the impact of increased BMI on the developing hip, in the January 3, 2018 issue of The Journal, Novais et al. painstakingly evaluated 128 pelvic CT images from a group of adolescents presenting with abdominal pain but no prior history of hip pathology. The authors found a significant association between increasing BMI percentiles and femoral head-neck alterations, including:
- Increased alpha angle
- Reduced head-neck offset and epiphyseal extension, and
- More posteriorly tilted epiphyses.
Taken together, these morphological anomalies resemble, in the authors’ words, “a post-slip or mild slipped capital femoral epiphysis [SCFE] deformity.”
While the association between elevated body mass and the risk of SCFE has long been known, the impact of high BMI on the morphology of the “normal” hip had not, until now, been described in detail. It makes intuitive mechanical sense that Novais et al. found no impact of high BMI on acetabular anatomy, but because of the orientation of the proximal femoral growth plate, it does make sense that high BMI affects the growing femoral head-neck junction.
It is my hope that consolidating these data with the abundance of other evidence about the health risks of high BMI in growing children will further coalesce worldwide efforts to lower the intake of sugar and “empty carbs” among growing children, and will further spur investment in programs to increase physical activity among this vulnerable age group.
Marc Swiontkowski, MD
This basic science tip comes from Fred Nelson, MD, an orthopaedic surgeon in the Department of Orthopedics at Henry Ford Hospital and a clinical associate professor at Wayne State Medical School. Some of Dr. Nelson’s tips go out weekly to more than 3,000 members of the Orthopaedic Research Society (ORS), and all are distributed to more than 30 orthopaedic residency programs. Those not sent to the ORS are periodically reposted in OrthoBuzz with the permission of Dr. Nelson.
Early cartilage changes in early-stage osteoarthritis (OA) often exist before symptoms arise. Using MRI, researchers assessed a random sample of 73 subjects, aged 40 to 79 years and without knee pain, for cartilage changes.1 A self-reported BMI at age 25, a current measured BMI, and change in BMI were recorded. Knee cartilage was scored semi-quantitatively (grades 0 to 4) on MRI. In primary analysis, cartilage damage was defined as ≥2 (at least moderate), and in a secondary analysis as ≥3 (severe). Researchers also conducted a sensitivity analysis by dichotomizing current BMI as <25 vs. ≥25. Logistic regression was used to evaluate the association of each BMI variable with prevalent MRI-detected cartilage damage, adjusted for age and sex.
Their abstract states that among the 73 subjects, knee cartilage damage ≥2 and ≥3 was present in 65.4% and 28.7%, respectively. Note the high prevalence. The median current BMI was 26.1, while the median past BMI was 21.6. For cartilage damage ≥2, current BMI had a non-statistically significant odds ratio (OR) of 1.65 per 5-unit increase in BMI (95% CI 0.93-2.92). For cartilage damage ≥3, current BMI showed a trend towards statistical significance with an OR of 1.70 per 5 units (95% CI 0.99-2.92). Past BMI and change in BMI were not significantly associated with cartilage damage. Current BMI ≥ 25 was statistically significantly associated with cartilage damage ≥2 (OR 3.04 [95% CI 1.10-8.42]), but not with damage ≥3 (OR 2.63 [95% CI 0.86-8.03]).
The take-home is that MRI-detected knee cartilage damage is highly prevalent in asymptomatic populations aged 40 to 79 years. There is a trend towards significance in the relationship between rising BMI and cartilage damage severity. (It should be added there are localities where a BMI of 26.1, which is technically in the “overweight” zone, would be considered relatively low.) Although this study lends some support to the relationship between BMI and the pathogenesis of knee cartilage damage in asymptomatic people, the role of BMI in symptomatic OA progression is clearer.
In another study, researchers showed that weight loss over 48 months among obese and overweight individuals is associated with slowed knee cartilage degeneration and improved knee symptoms.2 These results point to a promising approach to disease modification that carries little or no risk.
- Keng A, Sayre EC, Guermazi A, Nicolaou S, Esdaile JM, Thorne A, Singer J, Kopec JA, Cibere J. Association of body mass index with knee cartilage damage in an asymptomatic population-based study. BMC Musculoskelet Disord. 2017 Dec 8;18(1):517. doi: 10.1186/s12891-017-1884-7. PMID: 29221481 PMCID: PMC5723095
- Gersing AS, Solka M, Joseph GB, Schwaiger BJ, Heilmeier U, Feuerriegel G, Nevitt MC, McCulloch CE, Link TM. Progression of cartilage degeneration and clinical symptoms in obese and overweight individuals is dependent on the amount of weight loss: 48-month data from the Osteoarthritis Initiative. Osteoarthritis Cartilage. 2016 Jul;24(7):1126-34. doi: 10.1016/j.joca.2016.01.984. PMID: 26828356 PMCID: PMC4907808
Obesity can negatively affect outcomes after total hip arthroplasty (THA), and an inadvertent reduction in cup anteversion may be one reason why, according to findings from Brodt et al. in the May 4, 2016 edition of The Journal of Bone & Joint Surgery.
The authors retrospectively analyzed postoperative radiographs from 790 THA patients (all of whom were operated on via a direct lateral approach) within three BMI ranges: normal weight (BMI <25 kg/m2), moderately obese (BMI between 25 and 34 kg/m2), and morbidly obese (BMI of ≥35 kg/m2). Reduced cup anteversion significantly correlated with increasing BMI and younger patient age, with the morbidly obese group demonstrating a 3.4° anteversion reduction compared with the normal-weight group. The authors attribute the reduced anteversion to increased pressure applied to dorsal and ventral acetabular rim retractors to ensure adequate visualization during THA surgery in obese patients.
When the authors applied their findings to the Lewinnek “safe zone” for acetabular positioning, only 59% of the morbidly obese patients were in that zone. While this study was not designed to track subsequent dislocations (a common consequence of incorrect cup positioning), the authors claim that these findings are nevertheless clinically important. “Knowledge of a systemic error in obese patients should raise surgeons’ awareness of the need to perform cup implantation with greater attention,” they conclude.
Obesity is one of the most serious public health problems in the 21st century, and body weight is becoming an important consideration in orthopaedic procedures, especially joint arthroplasty. Two new studies in the February 3, 2016 Journal of Bone & Joint Surgery illuminate the relationship between body mass index (BMI) and hip-arthroplasty outcomes.
In a prognostic study based on registry data (21,361 consecutive hip replacements), Wagner et al. analyzed postsurgical complications and reoperations using BMI as a continuous variable. They found strong associations between increasing BMI and increasing rates of reoperation, implant revision or removal, early hip dislocation, and both superficial and deep infections. Although researchers are just starting to examine the efficacy of preoperative interventions to reduce BMI (see related OrthoBuzz post), Wagner et al. suggest that “collaborative interventions between care providers and patients may be undertaken to modify risk factors, such as BMI, before elective procedures.” A commentary on this study lauds the authors for analyzing BMI with a “dose-response” perspective, but the commentators note that “BMI neither remains constant nor follows a predictable trend over time.”
In a separate therapeutic study by Issa et al., clinical and patient-reported outcomes of primary THA were lower in super-obese patients (BMI ≥ 50 kg/m2) than in matched patients with normal BMI (<30 kg/m2). Specifically, after a mean follow-up of six years, compared with the normal-BMI group, the super-obese group had:
- A 4.5 times higher odds ratio (OR) of undergoing a revision
- A 7.7 times higher OR of surgical complications, including superficial and deep infections
- Significantly lower mean values on the Harris hip score, the physical and mental components of the SF-36, and the UCLA activity score.
Despite these between-group findings, super-obese patients still experienced significant clinical improvements compared with their preoperative status. However, they saw an average of 2.5 previous surgeons who refused to perform the procedure prior to being referred to the authors.
The two numbers that you’ll want to remember from the computer model-based cost-effectiveness study by McLawhorn et al. in the January 20, 2016 Journal of Bone & Joint Surgery are $13,910 and $100,000. The first number is an incremental cost-effectiveness ratio (ICER). Here, it’s the estimated added cost per quality-adjusted life year (QALY) for morbidly obese patients (BMI ≥35 kg/m2) with end-stage knee osteoarthritis who undergo bariatric surgery two years prior to total knee arthroplasty (TKA), compared with similar patients who undergo immediate TKA.
The $100,000 is the threshold “willingness to pay” (WTP) that the authors used in their evaluation. Willingness to pay reflects the amount society and healthcare payers such as Medicare and private insurers are willing to pay for a patient to accrue one year lived in perfect health.
Here’s another way to view these findings: Morbidly obese patients who undergo TKA are at increased risk for wound-healing problems, superficial and deep infections, early revision, and poor function. The authors estimated that if bariatric surgery reduces the TKA risks in these patients by at least 16%, on average, the combination of bariatric surgery followed by TKA is more cost-effective than immediate TKA alone.
Because the ICER was much less than the WTP in this model, the authors conclude that “bariatric surgery prior to total knee arthroplasty may be a cost-effective option for improving outcomes in motivated patients with a BMI of ≥35 kg/m2 with end-stage knee osteoarthritis.” However, they are quick to add that “decision modeling cannot simulate reality for every clinical situation.” While this rigorously developed model may provide a decision-making framework for surgeons and policymakers, the authors say, “this approach may be impractical for an individual patient…desiring immediate symptomatic relief from knee osteoarthritis.”
The relationships between body weight and joint replacement are debated often in the orthopaedic community. Some surgeons are so concerned about perioperative complications related to obesity that they recommend delaying arthroplasty in obese patients until weight loss is achieved.
But what are the likelihood and implications of weight changes after joint replacement? For those answers, in the June 3, 2015 edition of JBJS, Ast et al. tracked differences in body mass index (BMI) among nearly 7,000 patients for two years after total hip arthroplasty (THA) or total knee arthroplasty (TKA). Establishing a 5% BMI change as “clinically meaningful,” the researchers found that:
- Most patients (73% of those undergoing THA and 69% of those undergoing TKA) experienced no weight change.
- Female patients, patients with a higher preoperative BMI, and those undergoing TKA were most likely to lose weight after surgery.
- Weight loss was associated with improved clinical outcomes after THA, but not after TKA. However, weight gain in general was associated with inferior clinical outcomes.
- Those with better preoperative functional status were less likely to gain weight after THA or TKA.
Countering conventional wisdom that weight loss after total joint arthroplasty is unlikely, Ast. Et al. emphasize that “obese patients who undergo total joint arthroplasty are more likely than non-obese patients to lose weight after surgery.”