Search results for Fred Nelson

A New Venue for Dr. Nelson’s Basic Science Tips

Based on page-view data, the monthly basic science posts from Fred Nelson, MD have been hugely popular on OrthoBuzz over the last 4-plus years.

Now, OrthoBuzz readers can sign up to receive Dr. Nelson’s insights on a weekly basis. The “ORS Connects” e-newsletter, a publication of the Orthopaedic Research Society, has kindly agreed to email OrthoBuzz readers Dr. Nelson’s weekly basic science tips. If you are interested, please email Amber Blake at blake@ors.org with your first and last name and email address.

Because Dr. Nelson’s tips are now available to a wider audience on a more frequent basis, we will no longer be including them in OrthoBuzz. The OrthoBuzz team has thoroughly enjoyed engaging with Dr. Nelson and his fascinating basic-science content. We thank him for his outstanding contributions.

Trimming the Fat (Pad) in Knee OA

This post 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. It has been sent to >3,000 members of the Orthopaedic Research Society (ORS). For more information about the ORS, visit http://www.ors.org

The knee joint is comprised of cartilage, fibrocartilage, bone, synovium, ligaments, a fibrous capsule, and adipose tissue, the last of which includes the large anterior infrapatellar fat pad (IFP). The role of synovial inflammatory cells and cytokines in knee osteoarthritis (OA) has been well studied. The IFP is also rich in stem cells and inflammatory cells. Because Hartley guinea pigs naturally develop a form of knee OA that is similar to human disease, researchers recently used them as a model for elucidating a possible role of the IFP in knee OA.1

Ten 3-month-old guinea pigs had a unilateral IFP excision from one knee, with sham surgery performed on the opposite knee. Hartley guinea pigs typically develop OA after three months, and this intervention sought to determine whether IFP excision protected against OA. Gait analysis data were collected prior to surgery and then monthly until the animals were harvested at 7 months of age, at which point researchers performed microcomputed tomography (microCT) and histopathology on all 20 knee joints.

In knees with IFP resection, fibrous connective tissue replaced the adipose tissue. Stride length was not statistically different for either hindlimb throughout the study. Joints with resected IFPs had a decreased microCT score compared to contralateral intact knees (p <0.0001), indicating healthier cartilage. Histopathologically, the mean modified Mankin score of knees with IFPs removed was 2.556 versus 12.56 in contralateral knees (p <0.0004).

Surgeons commonly resect the fat pad during reconstructive knee surgery in humans, with no known reports of adverse effects beyond decreased range of motion due to local fibrosis. A recent review of the contribution of the IFP and synovium to knee OA pain2 suggests that synovial tissue and adipose tissue may act as a “functional unit” and have a combined effect on OA pathogenesis and, in all probability, OA pain and progression.

References

  1. Afzali MF, Radakovich LB, Pixler ZC, Campbell MA, Sanford JL, Marolf AJ, Donahue T, Santangelo, Kelly S. Early removal of the infrapatellar fat pad beneficially alters the pathogenesis of primary osteoarthritis in the Hartley guinea pig ORS 2020 Annual Meeting Paper No.0166
  2. Belluzzi E, Stocco E, Pozzuoli A, Granzotto M, Porzionato A, Vettor R, De Caro R, Ruggieri P, Ramonda R, Rossato M, Favero M, Macchi V. Contribution of Infrapatellar Fat Pad and Synovial Membrane to Knee Osteoarthritis Pain. Biomed Res Int. 2019 Mar 31;2019:6390182. doi: 10.1155/2019/6390182. eCollection 2019.PMID: 31049352

T-Scores for Diagnosing Osteoporosis: 3 Are Better Than 1

This post 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.

The World Health Organization (WHO) and the International Society for Clinical Densitometry (ISCD) define osteoporosis based on (DXA) measures of bone mineral density that are translated into T-scores. A T-score ≤ -2.5 at any 1 of the 3 commonly measured sites (lumbar vertebrae, femoral neck, and total hip) is considered diagnostic for osteoporosis, and a T-score between -2.5 and -1 is indicative of osteopenia. University of Pennsylvania investigators1 proposed that combining all 3 T-scores in a multivariate analysis would be “potentially more informative” than the common practice of using the single lowest T-score.

The investigators applied multivariate statistical theory to T-scores from a sample of 1,000 65-year-old white women. When both real data and simulation models were analyzed, the researchers found that more patients were diagnosed with osteoporosis using the multivariate version of the WHO/ISCD guidelines than with the current WHO/ISCD guidelines. The diagnoses of osteoporosis using this method were also associated with higher Fracture Risk Assessment Tool (FRAX) probabilities of major osteoporotic fractures (P=0.001) and hip fractures (P=2.2×10−6). The FRAX tool combines a patient’s history of fracture with age, sex, race, height, weight, and social habits such as smoking and drinking to determine the risk of a major facture in the next 10 years.

This study shows that statistically considering all 3 T-scores may reveal more cases of osteoporosis than using the single lowest T-score. The trick will be getting this insight into the hands—and minds—of those making radiologic interpretations of DXA findings.

Reference 

  1. Sebro R, Ashok S. A Statistical Approach regarding the Diagnosis of Osteoporosis and Osteopenia from DXA: Are we underdiagnosing osteoporosis? J. Bone Mineral Res Plus. In press

Knee OA: Does It Start with Stiff Menisci or Soft Cartilage?

This post 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.

As an orthopaedic surgeon, I often noticed the rigidity of the meniscus as I excised it during a total knee replacement. Focused on the job at hand, however, I never closely considered the involvement of menisci in degenerative joint disease. But German researchers recently hypothesized that early biomechanical changes in meniscal tissue occur before articular cartilage changes in knee osteoarthritis.1

To test their hypothesis, they dissected 12 cadaver knees with Kellgren-Lawrence (KL) scores between 1 and 2 and 12 knees with KL scores between 3 and 4. The menisci were carefully embedded in a cast of polymethylmethacrylate using bony attachments to hold the specimens for Einst testing at the anterior horn, pars intermedia, and posterior horn. (Instantaneous modulus of elasticity [Einst] is the measure of the initial response of a viscoelastic material to an initial load before long-term deformity occurs.)  The exposed tibial surface was then cut 10 mm below the joint for Einst testing at the same zones, and the researchers also measured the articular cartilage-to-cartilage contact area.

Mann-Whitney U-testing revealed higher meniscal Einst values with increasing degeneration for both lateral and medial menisci, while the underlying tibial articular cartilage showed a decrease in Einst in the medial compartment. These findings suggest that knee joint degeneration might very well begin with a stiffening of the menisci, followed by articular cartilage softening.

The wide variation in Einst values uncovered in this study leaves open the possibility there is more than one pathway by which the biochemical response to meniscal cytokine expression would lead to subsequent articular cartilage breakdown. Nevertheless, the authors suggest that their findings might prompt the treatment and diagnostic paradigms of knee osteoarthritis to change, “focusing on the degeneration detection of the menisci instead of the articular cartilage.”

Reference 

  1. Seitz AM, Osthaus F, Ignatius A, Dürselen L. Degeneration alters first the biomechanical properties of human menisci before affecting the tibial cartilage. ORS 2020 Annual Meeting Paper No.0687

Big Data Needs Big Progress

This post 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.

The broad term “big data,” when applied to health care, refers to the mining of large databases to find information that might predict and improve clinical outcomes on a national scale. A recent article in AAOSNow cites one example of the merging of big data with artificial intelligence (AI) as the 10-year partnership between the Mayo Clinic and Google to leverage cloud technologies, machine learning, and AI to accelerate change in healthcare delivery. The American Joint Replacement Registry (AJRR) is also using big data to help hospitals make more efficient supply-chain decisions and lower costs.

However, there are limitations and potential flaws in the use of big data. One is the high cost, making it unaffordable for some institutions. In addition, variations in how the data is collected and reported may lead to flawed analyses. Also, data collection may vary in completeness by region, which makes nationwide registries with consistent data collection so important. Big data can also be contaminated by bias. Even large datasets may over- or underrepresent certain groups of people, thereby skewing any analysis made with those data.

There are several solutions to improve the use of big data in orthopaedics. One is the development of registries with uniform and consistent data collection methods to ensure equity. Participation in registries by orthopaedic surgeons is critical. The authors of the AAOSNow article also emphasize that if patient data were linked longitudinally, researchers would have a powerful tool with which to study health outcomes and monitor public health trends. However, current HIPAA rules prevent clearinghouses from linking data that way. To update the law to match our data-driven reality, in 2017 US Rep. Cathy McMorris Rodgers (D-Ore.) introduced the Ensuring Patient Access to Health Records Act (H.R. 4613), which would allow greater access to big data for the purpose of research, public health, and personal patient use. The bill has been tied up in committee since December 15, 2017. The ultimate objective of using big data in medicine is to provide health care that is “predictive, preventive, personalized, and participatory,” conclude the authors.

A Genetic Basis for Adhesive Capsulitis?

This post 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.

Adhesive capsulitis (AC), colloquially known as frozen shoulder, is associated with conditions such as diabetes, cardiopulmonary disorders, stroke, Parkinsonism, and injury. However, many cases are idiopathic. Given the inflammatory nature of the condition, clinicians often administer intra-articular steroid injections in recalcitrant cases where physical therapy alone is too painful or nonproductive. Some cases, particularly in patients with diabetes, may require manipulation, brisement, or arthroscopic release.

To better understand the genetic basis of AC, investigators obtained punch tissue samples from the middle glenohumeral ligament and rotator cuff interval from AC patients undergoing arthroscopic release surgery (mean age of 53 years) and from a comparative group of patients undergoing arthroscopic surgery for shoulder instability (mean age of 24 years).1 The researchers performed RNA sequencing-based transcriptomics on the samples and, after identifying differentially expressed genes, they applied real-time reverse transcription polymerase chain reaction (RT-PCR) to obtain more detailed genetic data.

A total of 545 genes were differentially expressed. The top 50 were associated with extracellular matrix remodeling. Patient age and sex did not have a major influence on gene expression. The genes marked by overexpression (not necessarily protein expression) were genes for matrix metallopeptidase 13 and platelet-derived growth factor subunit B. Other suspects included the gene for metalloprotease 9 and COL18A1.

In the discussion, the authors comment on the association between AC and protein tyrosine kinase 2 (PTK2), also known as focal adhesion kinase (FAK). FAK activation is particularly sensitive to fibronectin and other integrins. Activated FAK also controls cell migration and focal adhesion assembly. These interesting associations may also shine light onto the etiology of other musculoskeletal diseases.

Reference

  1. Kamal N, McGee SL, Eng K, Brown G, Beattie S, Collier F, Gill S, Page RS.
    Transcriptomic analysis of adhesive capsulitis of the shoulder.
    J Orthop Res. 2020 Oct;38(10):2280-2289. doi: 10.1002/jor.24686. Epub 2020 Apr 17. PMID: 32270543

The Importance of a “Well-Rounded” Hip

This post 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.

Fifty years ago, the precise etiology of hip osteoarthritis (OA) was not clear. In 1976, Solomon proposed 3 potential causes of osteoarthritis in general:1

  1. Failure of essentially normal cartilage subjected to abnormal or incongruous loading for long periods
  2. Damaged or defective cartilage failing under normal conditions of loading
  3. Breakup of articular cartilage due to defective subchondral bone

In 1986, Harris expanded on this concept by noting that mild acetabular dysplasia and/or pistol grip deformity were associated with 90% of patients who had “so-called primary or idiopathic” hip OA.2 Harris further claimed that “when these abnormalities are taken in conjunction with the detection of other metabolic abnormalities that can lead to osteoarthritis of the hip,…it seems clear that either osteoarthritis of the hip does not exist at all as a primary disease entity or, if it does, is extraordinarily rare.”

Subsequently, acetabular dysplasia was defined as an acetabular shape where the lateral center edge angle (LCEA) was <25°, and the cam and pincer deformities were introduced as forms of acetabular dysplasia. Acetabular retroversion, as detected by the crossover sign seen in anterolateral hip radiographs, was recognized later, and Tonnis used CT imaging to determine acetabular and femoral anteversion.3

In 2020, investigators suspected that zonal-acetabular radius of curvature (ZARC) might play a role in hip-joint shape disorders.4 ZARC is the radius of curvature of the articular contact surface (from the margin of the fovea centralis to the acetabular rim), and the authors analyzed ZARC in anterior, superior, and posterior zones in subjects with normal, borderline, and dysplastic hips. (“Normal” was defined as LCEA of 25° to <40°; “borderline” as LCEA of 20° to <25°; and “dysplastic” as LCEA of <20°.) The 3-zone ZARC findings are summarized in the table below.

Mean Zonal-Acetabular Radius of Curvature (ZARC)

ZARC Zone Borderline Normal Dysplasia
Anterior 29.8 +/- 2.6 mm 28.0 +/- 2.2 mm 31.5 +/- 2.7 mm *
Superior 25.7 +/- 3.0 mm 25.9 +/- 2.2 mm 25.8 +/- 2.5 mm
Posterior 27.2 +/- 2.5 mm 26.4 +/- 1.9 mm 30.4 +/- 3.3 mm *

* P < 0.01

In this study, the severity of lateral undercoverage affected the anterior and/or posterior zonal-acetabular curvature. The take home message is that, absent metabolic abnormalities, acetabular and femoral head congruity and orientation are the driving forces in hip OA.

References

  1. Solomon L. Patterns of osteoarthritis of the hip. J Bone Joint Surg Br. 1976;58(2):176-83. Epub 1976/05/01. PubMed PMID: 932079.
  2. Harris WH. Etiology of osteoarthritis of the hip. Clinical orthopaedics and related research. 1986(213):20-33. Epub 1986/12/01. PubMed PMID: 3780093.
  3. Tonnis D, Heinecke A. Acetabular and femoral anteversion: relationship with osteoarthritis of the hip. J Bone Joint Surg Am. 1999;81(12):1747-70. Epub 1999/12/23. PubMed PMID: 10608388.
  4. Irie T, Espinoza Orias AA, Irie TY, Nho SJ, Takahashi D, Iwasaki N, et al. Three-dimensional hip joint congruity evaluation of the borderline dysplasia: Zonal-acetabular radius of curvature. J Orthop Res. 2020;38(10):2197-205. Epub 2020/02/20. doi: 10.1002/jor.24631. PubMed PMID: 32073168.

Hydrogel + Stem Cells Improve Disc Conditions in Goats

This post 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.

One of the key changes leading to intervertebral disc degeneration is the loss of complex proteoglycans in the nucleus pulposus (NP), which leads to a loss of water avidity, physiologic dysfunction, NP tissue rigidity, and disruption of surrounding disc tissues. In humans, these changes can begin as early as the second decade of life. One of the difficulties in developing cellular therapies to address these changes is creating a hydrogel that can support effective delivery of mesenchymal stem cells (MSCs).

University of Pennsylvania researchers chemically induced degeneration in lumbar discs in adult male goats. After 12 weeks, some of the degenerating discs were injected with either a hydrogel alone (n=9 discs) or hydrogel with 10 million mesenchymal stem cells per ml (n=10 discs). The remaining discs received neither injection. Two weeks later, researchers analyzed disc height, hydrogel distribution, and MSC localization using green fluorescent protein (GFP) immunostaining.

After 12 weeks of disc degeneration, disc height was approximately 66% of pre-intervention levels. After 2 weeks of the treatment phase, researchers found an insignificant increase in height in the hydrogel-alone discs, and a significant 7.6% height increase in the hydrogel-with-MSCs discs. Imaging revealed that the majority of hydrogel was located in the NPs of the treated discs.

Treated discs exhibited improved overall histological grade compared to untreated discs, but the improvement was significant only in discs treated with hydrogel + MSCs. The fact that GFP-positive MSCs were identified both in the hydrogel itself and in the surrounding NP tissue suggests that MSCs migrated beyond the injection site.

The question remains whether we can similarly improve physiology in the wide spectrum of degenerative disc disease experienced by humans. Let’s hope that future investigations yield positive findings.

Owning the Bone in Spine Surgery

This post 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.

Approximately 20% of patients who undergo spine surgery have osteoporosis, which has a significant impact on spine-surgery complications such as failure of fixation devices and collapse fractures following fusion procedures. In a recent critical analysis review, authors focus on improving outcomes by identifying and optimizing patients with osteoporosis prior to spine surgery. The multidisciplinary team involved in that process should include primary care providers, endocrinologists, physical therapists, and orthopaedic surgeons.

The predominant tool for assessing bone mineral density (BMD) is dual x-ray absorptiometry. The diagnosis is based on a T score, which represents the number of standard deviations between the patient’s BMD and that of a healthy 30-year-old woman. Standard deviations  ≤─2.5 define osteoporosis. The Z score is similar to the T score but compares the patient to an age- and sex-matched individual.

A history of low-energy fracture, such as a wrist fracture following a fall from a standing height, is considered a sentinel event for suspicion of fragility fractures. The combination of a fragility fracture and low BMD is considered to be severe osteoporosis. The most common form of osteoporosis is associated with a postmenopausal decrease in mineralization, but there are other causes. These include advanced kidney disease, hypogonadism, Cushing disease, vitamin D deficiency, anorexia and/or bulimia, rheumatoid arthritis, hyperthyroidism, primary hyperparathyroidism, and some medications (e.g., anticonvulsants, corticosteroids, heparin, and proton pump inhibitors).

Forty-seven percent of patients undergoing spine deformity surgery and 64% of cervical spine surgery patients have low vitamin D levels. Postoperative bone health can be enhanced in women ≥51 years old with daily intake of 800 to 1,000 units of vitamin D and 1,200 mg of daily calcium. There is no solid evidence that pre- or postoperative bisphosphonates have a positive impact on bone healing. Conversely, some series have shown that teriparatide, an anabolic parathyroid hormone, may improve time-to-fusion and help reduce screw pull-out after lumbar fusion in postmenopausal women.

Calcitonin has been shown to reduce the incidence of vertebral compression fracture, but there is no concrete evidence that it supports spine-fusion healing. Similarly, there is no strong evidence for the use of estrogen or selective estrogen receptor modulators in this surgical scenario. There is evidence that when the human monoclonal antibody denosumab is combined with teriparatide, spine-fusion healing may be improved relative to the use of teriparatide alone. Finally, the review article identifies screw size, screw position, and other surgical considerations that can improve fixation strength.

Using the “Own the Bone” practices promulgated by the American Orthopaedic Association and the technical considerations described in this review, we should be able to mitigate osteoporosis-related postoperative complications in spine-surgery patients.

COVID-19’s Musculoskeletal Manifestations

This post 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.

The SARS-CoV-2 coronavirus that causes COVID-19 induces the expression of several cytokines and signaling molecules. The impact of these inflammatory mediators on the lungs is the most lethal effect and thus has drawn the most attention. However, COVID-19 can have potentially longer-lasting (but less deadly) musculoskeletal effects.

COVID-19 has not been affecting people long enough to study its effects completely, but we do know that the virus predominantly infects type-II pneumocytes that line the respiratory epithelium. These cells express angiotensin converting enzyme-2 (ACE2) and transmembrane protease, serine 2 (TMPRSS2). Disser et al. note that TMPRSS2 is also expressed in muscle tissue, while only smooth muscle cells and pericytes express ACE2. They add that either ACE2 or TMPRSS2 is expressed in cartilage, menisci, bone, and synovium.

Myalgia has been reported to occur in COVID-19 patients 25% to 50% of the time. The effect on muscle can be severe, with more seriously ill patients having higher levels of creatine kinase. After recovery, patients often show decreased strength and endurance, but it is not clear how much of that is due to deconditioning or to persisting muscle effects. Although arthralgia can also occur, it is hard to separate those symptoms from myalgia, and both may exist at the same time.

Examination of muscle specimens from autopsies of COVID-19 patients shows significant muscle destruction. It is not clear whether the osteoporosis and osteonecrosis sometimes seen with SARS-CoV-2 is due to the virus’s direct effect on bone or to the steroids used to treat patients with more severe cases.

Because it is probable that inflammation associated with cytokine release has an impact on musculoskeletal tissues, orthopaedic surgeons are likely to be faced with a variety of musculoskeletal symptoms in post COVID-19 patients. Preliminary data suggest that rehabilitation for both strength and endurance is effective among patients who recover from COVID-19, but it is not clear whether return to former conditioning levels occurs. The use of immunotherapies, such as IL-1 and IL-6 inhibitors, may have a positive impact on initial treatment in these patients.