Tag Archive | Infection

Routine Diagnostic Tests for Periprosthetic Joint Infection Demonstrate a High False-Negative Rate

 
Background:
Current guidelines recommend serum erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) as the first-line testing for evaluation of suspected periprosthetic joint infection, in addition to synovial white blood-cell (WBC) count and polymorphonuclear percentage. However, the sensitivity and other diagnostic measures of these tests and the influence of organisms on these inflammatory markers remain inadequately investigated.

What’s New in Musculoskeletal Basic Science 2018

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, Matthew J. Allen, VetMB, PhD, author of the December 5, 2018 Specialty Update on Musculoskeletal Basic Science, focuses on the five most compelling findings from among the more than 60 noteworthy studies summarized in the article.

Gene Editing in Orthopaedics

–Gene-editing tools such as CRISPR-Cas9 have great potential as a means of introducing therapeutic genes into mesenchymal stem cells that can then be targeted to tissues in vivo. These researchers1 reported on genetically modified stem cells that have the potential to differentiate into chondrocytes encoding a natural inhibitor of interleukin-1, providing an opportunity for localized release of immunomodulatory factors.

Managing Orthopaedic Infections

–A novel study2 in which transmission electron microscopy was used to identify viable bacteria deep within the canalicular structure of cortical bone, remote from the site of an infected implant, suggests that effective debridement requires the removal of not just necrotic tissue, but also of adjacent, apparently unaffected bone.

Computational Modeling of Human Movement

–This report3 presented a human musculoskeletal model that provided extremely accurate predictions of ground reaction forces during simulated walking and squatting. As similar models are developed and validated, surgeons will have improved tools for evaluating patients, planning surgery, and making decisions about which procedure/implant is most appropriate for an individual patient.

Sex-Related Differences

–This report4 demonstrated sexually dimorphic regulation of gene-expression profiles in bone marrow osteoprogenitor cells that could partly explain clinical observations in sex differences in peak bone mass, bone remodeling, and immunomodulation.

Biological Enhancement of Ligament Healing

–Among several basic science papers focused on the optimal healing and durable fixation of tendons and ligaments, this notable work5 reported on the translation of bridge-enhanced ligament repair for the anterior cruciate ligament.

References

  1. Brunger JM, Zutshi A, Willard VP, Gersbach CA, Guilak F. CRISPR/Cas9 editing of murine induced pluripotent stem cells for engineering inflammation-resistant tissues. Arthritis Rheumatol.2017 May;69(5):1111-21. Epub 2017 Mar 31.
  2. de Mesy Bentley KL, Trombetta R, Nishitani K, Bello-Irizarry SN, Ninomiya M, Zhang L, Chung HL, McGrath JL, Daiss JL, Awad HA, Kates SL, Schwarz EM. Evidence of Staphylococcus aureus deformation, proliferation, and migration in canaliculi of live cortical bone in murine models of osteomyelitis. J Bone Miner Res.2017 May;32(5):985-90. Epub 2017 Jan 26.
  3. Jung Y, Koo YJ, Koo S. Simultaneous estimation of ground reaction force and knee contact force during walking and squatting. Int J Precis Eng Manuf.2017;18(9):1263-8.
  4. Kot A, Zhong ZA, Zhang H, Lay YE, Lane NE, Yao W. Sex dimorphic regulation of osteoprogenitor progesterone in bone stromal cells. J Mol Endocrinol.2017 Nov;59(4):351-63. Epub 2017 Sep 4.
  5. Perrone GS, Proffen BL, Kiapour AM, Sieker JT, Fleming BC, Murray MM. Bench-to-bedside: bridge-enhanced anterior cruciate ligament repair. J Orthop Res.2017 Dec;35(12):2606-12. Epub 2017 Jul 9.

Physical Parameters Beyond BMI Affect TKA Outcomes

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

JBJS 100: Shoulder Impingement and Distraction Osteogenesis

JBJS 100Under one name or another, The Journal of Bone & Joint Surgery has published quality orthopaedic content spanning three centuries. In 1919, our publication was called the Journal of Orthopaedic Surgery, and the first volume of that journal was Volume 1 of what we know today as JBJS.

Thus, the 24 issues we turn out in 2018 will constitute our 100th volume. To help celebrate this milestone, throughout the year we will be spotlighting 100 of the most influential JBJS articles on OrthoBuzz, making the original content openly accessible for a limited time.

Unlike the scientific rigor of Journal content, the selection of this list was not entirely scientific. About half we picked from “JBJS Classics,” which were chosen previously by current and past JBJS Editors-in-Chief and Deputy Editors. We also selected JBJS articles that have been cited more than 1,000 times in other publications, according to Google Scholar search results. Finally, we considered “activity” on the Web of Science and The Journal’s websites.

We hope you enjoy and benefit from reading these groundbreaking articles from JBJS, as we mark our 100th volume. Here are two more:

Anterior Acromioplasty for Chronic Impingement Syndrome in the Shoulder
C S Neer: JBJS, 1972 January; 54 (1): 41
For many years after its publication, this 1972 JBJS article changed the treatment approach for patients with shoulder disability. But more recently, arthroscopy and magnetic resonance imaging arthrography have identified other painful non-impingement shoulder conditions. Consequently, the liberal use of acromioplasty to treat “impingement” is being replaced by a trend toward making an anatomic diagnosis, such as a partial or complete rotator cuff tear, and performing aggressive rehabilitation prior to corrective surgery.

Use of the Ilizarov Technique for Treatment of Non-union of the Tibia Associated with Infection
G K Dendrinos, S Kontos, E Lyritsis: JBJS, 1995 June; 77 (6): 835
This case series described a technique of bone transport with bridging achieved by distraction osteogenesis. The defects averaged 6 cm, the mean duration of treatment was 10 months, and the mean time to union was 6 months. More recent research has focused on augmenting the osteogenic potential of tissues in the distraction gap with substances such as bone morphogenetic protein, platelet-rich plasma, and mesenchymal stem cells.

JBJS 100: Infection Prevention and Hip Replacement Rates

JBJS 100Under one name or another, The Journal of Bone & Joint Surgery has published quality orthopaedic content spanning three centuries. In 1919, our publication was called the Journal of Orthopaedic Surgery, and the first volume of that journal was Volume 1 of what we know today as JBJS.

Thus, the 24 issues we turn out in 2018 will constitute our 100th volume. To help celebrate this milestone, throughout the year we will be spotlighting 100 of the most influential JBJS articles on OrthoBuzz, making the original content openly accessible for a limited time.

Unlike the scientific rigor of Journal content, the selection of this list was not entirely scientific. About half we picked from “JBJS Classics,” which were chosen previously by current and past JBJS Editors-in-Chief and Deputy Editors. We also selected JBJS articles that have been cited more than 1,000 times in other publications, according to Google Scholar search results. Finally, we considered “activity” on the Web of Science and The Journal’s websites.

We hope you enjoy and benefit from reading these groundbreaking articles from JBJS, as we mark our 100th volume. Here are two more:

Prevention of Infection in Treatment of 1,025 Open Fractures of Long Bones
R B Gustilo and J T Anderson: JBJS, 1976 June; 58 (4): 453
While “best practices” for managing open long-bone fractures have changed since this landmark study was published, the Gustilo-Anderson classification still correlates well with the risk of infection in patients with comorbid medical illnesses and other complications. It remains widely accepted for research and training purposes, and it provides commonly used basic language for communicating about open fractures.

Rates and Outcomes of Primary and Revision Total Hip Replacement in the US Medicare Population
N N Mahomed, J A Barrett, J N Katz, C B Phillips, E Losina, R A Lew, E Guadagnoli, W H Harris, R Poss, J A Baron: JBJS, 2003 January; 85 (1): 27
Analyzing Medicare claims data between July 1, 1995 and June 30, 1996, the authors of this prognostic study claimed it was “the first population-based study of the rates of revision total hip replacement and its short-term outcomes.” In the last 10 years alone, more than 5,000 studies on revision THA have been published in PubMed-indexed journals, including this 2012 JBJS study, which examined THA revision risk in the same Medicare cohort over 12 years.

JBJS 100: Pavlik Harness and the Infected TKA

jbjs_pl_journal_4c_5Under one name or another, The Journal of Bone & Joint Surgery has published quality orthopaedic content spanning three centuries. In 1919, our publication was called the Journal of Orthopaedic Surgery, and the first volume of that journal constituted Volume 1 of what we know today as JBJS.

Thus, the 24 issues we turn out in 2018 will constitute our 100th volume. To help celebrate this milestone, throughout the year we will be spotlighting 100 of the most influential JBJS articles on OrthoBuzz, making the original content openly accessible for a limited time.

Unlike the scientific rigor of Journal content, the selection of this list was not entirely scientific. About half we picked from “JBJS Classics,” which were chosen previously by current and past JBJS Editors-in-Chief and Deputy Editors. We also selected JBJS articles that have been cited more than 1,000 times in other publications, according to Google Scholar search results. Finally, we considered activity on the Web of Science and The Journal’s websites.

We hope you enjoy and benefit from reading these groundbreaking articles from JBJS, as we mark our 100th volume. Here are the first two:

  • Congenital Dislocation of the Hip
    PL Ramsey, S Lasser, GD MacEwen: JBJS, 1976 Oct; 58 (7): 1000
    The introduction of the Pavlik harness revolutionized the treatment of congenital dislocation of the hip in infants. The concept of the “safe zone” was introduced in this article.
  • Two-Stage Reimplantation for the Salvage of Infected Total Knee Arthroplasty
    J N Insall, F M Thompson, B D Brause: JBJS, 1983 Jan; 65 (8): 1087
    This was the first paper to show that a specific reimplantion protocol (debridement of the soft tissues and removal of the prosthesis and all cement, six weeks of parenteral antibiotics, and implantation of a new total knee) could provide predictable results in managing this difficult problem.

What’s New in Musculoskeletal Basic Science 2017

Specialty Update Image for OBuzz

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, Matthew J. Allen, VetMB, PhD, author of the December 6, 2017 Specialty Update on Musculoskeletal Basic Science, summarized the five most compelling findings from among the more than 60 noteworthy studies summarized in the article.

Cartilage Repair

–Deriving induced pluripotent stem cells (iPSCs) from peripheral blood cells1 rather than from dermal fibroblasts obviates the need for in vitro expansion. This method may also serve to boost interest in the use of commercial cell-based therapies with defined potency that are available off-the-shelf and don’t require separate cell-harvesting procedures.

–The FDA recommends that large-animal models be used to corroborate basic-science findings from small-animal models. Recent work has demonstrated the efficacy of insulin-like growth factor (IGF)-1 in supporting mechanically competent repair tissue following chondrocyte implantation in a pig model.2

Infection

–Infection, especially from organisms that have developed antimicrobial resistance and/or that produce biofilms, continues to pose a challenging problem for orthopaedic surgeons. To provide a more rational and stratified approach to managing these complex cases, Getzlaf et al. recommend the use of a multidisciplinary approach in which patient-specific information about individual microorganisms is combined with detailed understandings of the vulnerabilities of candidate bacterial species.3

Aseptic Loosening

–There is a resurgence of interest in the role of subclinical infection in the etiopathogenesis of aseptic loosening. At the same time, molecular diagnostic methods for microbial infection are moving forward.4 Such methods may serve to highlight the relevance of subclinical microbial contamination as a cause of aseptic loosening.

Cartilage Imaging

–While the goal of cartilage imaging is to develop tools that are fast, inexpensive, sensitive, accurate, and noninvasive, there is growing interest in the use of more direct, invasive techniques such as optical coherence tomography (OCT),5 which could be used in vivo at the time of surgery to analyze cartilage damage.

References

  1. Li Y, Liu T, Van Halm-Lutterodt N, Chen J, Su Q, Hai Y. Reprogramming of blood cells into induced pluripotent stem cells as a new cell source for cartilage repair. Stem Cell Res Ther.2016 Feb 17;7:31.
  2. Meppelink AM, Zhao X, Griffin DJ, Erali R, Gill TJ, Bonassar LJ, Redmond RW,Randolph MA. Hyaline articular matrix formed by dynamic self-regenerating cartilage and hydrogels. Tissue Eng Part A.2016 Jul;22(13-14):962-70. Epub 2016 Jul 7.
  3. Getzlaf MA, Lewallen EA, Kremers HM, Jones DL, Bonin CA, Dudakovic A,Thaler R, Cohen RC, Lewallen DG, van Wijnen AJ. Multi-disciplinary antimicrobial strategies for improving orthopaedic implants to prevent prosthetic joint infections in hip and knee. J Orthop Res.2016 Feb;34(2):177-86. Epub 2015 Dec 29.
  4. Palmer MP, Melton-Kreft R, Nistico L, Hiller NL, Kim LH, Altman GT, Altman DT, Sotereanos NG, Hu FZ, De Meo PJ, Ehrlich GD. Polymerase chain reaction-electrospray-time-of-flight mass spectrometry versus culture for bacterial detection in septic arthritis and osteoarthritis. Genet Test Mol Biomarkers.2016 Dec;20(12):721-31. Epub 2016 Oct 17.
  5. Novakofski KD, Pownder SL, Koff MF, Williams RM, Potter HG, Fortier LA. High-resolution methods for diagnosing cartilage damage in vivo. 2016 Jan;7(1):39-51.

Fructosamine Bests HbA1c for Preop Glycemic Screening

Fructosamine for OBuzzPatients with diabetes have an increased risk of postoperative complications following total joint arthroplasty (TJA). Additionally, perioperative hyperglycemia has been identified as a common and independent risk factor for periprosthetic joint infection, even among patients without diabetes. Therefore, knowing a patient’s glycemic status prior to surgery is very helpful.

In the November 15, 2017 edition of The Journal of Bone & Joint Surgery, Shohat et al. demonstrate that serum fructosamine, a measure of glycemic control obtainable via a simple and inexpensive blood test, is a good predictor of adverse outcomes among TJA patients—whether or not they have diabetes.

Researchers screened 829 patients undergoing TJA for serum fructosamine and HbA1c—a common measure, levels of which <7% are typically considered good glycemic control. Patients with fructosamine levels ≥292 µmol/L had a significantly higher risk of postoperative deep infection, readmission, and reoperation, while HbA1c levels ≥7% showed no significant correlations with any of those three adverse outcomes. Among the 51 patients who had fructosamine levels ≥292 µmol/L, 39% did not have HbA1c levels ≥7%, and 35% did not have diabetes.

In addition to being more predictive of postsurgical complications than HbA1c, fructosamine is also a more practical measurement. A high HbA1c level during preop screening could mean postponing surgery for 2 to 3 months, while the patient waits to see whether HbA1c levels come down. Fructosamine levels, on the other hand, change within 14 to 21 days, so patients could be reassessed for glycemic control after only 2 or 3 weeks.

While conceding that the ≥292 µmol/L threshold for fructosamine suggested in this study should not be etched in stone, the authors conclude that “fructosamine could serve as the screening marker of choice” for presurgical glycemic assessment. However, because the study did not examine whether correcting fructosamine levels leads to reduced postoperative complications, a prospective clinical trial to answer that question is needed.

What’s New in Shoulder and Elbow Surgery 2017

Shoulder & elbowEvery 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, Aaron Chamberlain, MD, co-author of the October 18, 2017 Specialty Update on shoulder and elbow surgery, selected the most clinically compelling findings from among the 36 studies summarized in the Specialty Update.

Reverse Shoulder Arthroplasty
With reverse shoulder arthroplasty, surgeons often have difficulty setting expectations for patients due to the lack of long-term outcomes data. Bacle et al. published a study that describes the clinical outcomes in patients with at least 10 years’ follow-up. Medium-term outcomes among  an original cohort of 186 patients had been previously described. Eighty-four of those original patients were available for a mean long-term follow-up of 150 months. The mean overall Constant score fell from 63 at medium-term follow-up to 55 at final follow-up.  Active anterior elevation also decreased from 138° to 131.° Despite the decrease in Constant score and ROM between mid- and long-term follow-up, these two measures remained significantly better than preoperative values. Analysis showed a 93% implant survival probability at 120 months. This study will help surgeons counsel patients regarding long-term expectations after reverse shoulder arthroplasty – especially as younger patients are increasingly indicated for this procedure.

Rotator Cuff Repair
A central focus of studies evaluating rotator cuff repair has been to better understand the biological environment that influences tendon healing. Greater understanding of the genetic influence in rotator cuff pathology may lead to interventions that could improve the healing environment.  Tashjian et al. reported outcomes after arthroscopic rotator cuff repair in 72 patients who were assessed for family history of rotator cuff tears and underwent a genetic analysis looking for variants in the estrogen-related receptor beta (ESRRB) gene.1 Positive family history and tear retraction were associated with a failure of healing, and lateral tendon retears were associated with both family history and the presence of a single nucleotide polymorphism in the ESRRB gene.

In another recent study focused on the biological healing environment after rotator cuff repair, a prospective randomized trial of platelet-rich plasma (PRP) in patients undergoing repair of a medium to large-sized rotator cuff tear2 found that patients who received PRP experienced an increase in vascularity at the repair site up to 3 months postoperatively. The PRP group also demonstrated better Constant-Murley and UCLA scores and lower retear rates than the no-PRP group, but there was no difference in ASES scores. In another recent randomized trial, 120 patients were randomized to either PRP or ropivacaine injection after rotator cuff repair.3 No between-group differences in clinical outcome scores or retear rates were identified. The contrasting results of these two recent randomized studies illustrate the challenge of identifying any conclusive benefit of PRP in the setting of rotator cuff repair.

Prosthetic Shoulder Infection
Accurate diagnosis of prosthetic shoulder infection continues to present a formidable challenge, given the difficulty of detecting Proprionibacterium acnes (P. acnes) and interpreting when positive results are clinically significant. Development of P. acnes tests that are more rapid and precise in identifying clinically significant infections would be of significant value.  Holmes et al. evaluated a PCR restriction fragment length polymorphism (RFLP) technique to identify P. acnes from infected tissue in the shoulder.4 In this study, within 24 hours of sampling, the PCR-RFLP assay detected P. acnes-specific amplicons in as few as 10 bacterial cells.

Clavicle Fractures
Approaches to managing clavicle fractures have evolved significantly over the past several decades. While it was once generally accepted that middle third clavicle fractures should be managed nonoperatively, multiple studies have described concerning rates of nonunions and symptomatic malunions. A multicenter prospective trial that randomized patients to either surgical fixation with a plate or nonoperative management identified a nonunion rate of 23.1% in the nonoperatively managed group, compared with a 2.4% nonunion rate in the surgically treated group (p<0.0001). However, the rate of secondary operations was 27.4% in the operatively treated group (most for plate removal) versus 17.1% in the nonoperative group, although that difference did not reach statistical significance (p=0.18). These results will help inform discussions between providers and patients when considering management options for midshaft clavicle fractures.

References

  1. Tashjian RZ, Granger EK, Zhang Y, Teerlink CC, Cannon-Albright LA. Identification of a genetic variant associated with rotator cuff repair healing. J Shoulder Elb Surg. 2016. doi:10.1016/j.jse.2016.02.019.
  2. Pandey V, Bandi A, Madi S, et al. Does application of moderately concentrated platelet-rich plasma improve clinical and structural outcome after arthroscopic repair of medium-sized to large rotator cuff tear? A randomized controlled trial. J Shoulder Elb Surg. 2016;26(3):e82-e83. doi:10.1016/j.jse.2016.01.036.
  3. Flury M, Rickenbacher D, Schwyzer H-K, et al. Does Pure Platelet-Rich Plasma Affect Postoperative Clinical Outcomes After Arthroscopic Rotator Cuff Repair? Am J Sports Med. 2016. doi:10.1177/0363546516645518.
  4. Holmes S, Pena Diaz AM, Athwal GS, Faber KJ, O’Gorman DB. Neer Award 2017: A rapid method for detecting Propionibacterium acnes in surgical biopsy specimens from the shoulder. J Shoulder Elb Surg. 2017. doi:10.1016/j.jse.2016.10.001.

New Hope for New Bone After Osteomyelitis Debridement

Osteomyelitis Tibia for OBuzzThis 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.

One clinical frustration following osteomyelitis debridement is poor bone healing. Impaired bone homeostasis provokes serious variations in bone remodeling that involve multiple inflammatory cytokines.

The chemokines CCL2, CCL3, and CXCL2 are known to be strong chemoattractants for neutrophils during inflammatory states, and they play a role during osteoclastogenesis. B cells are also activators of osteoclastognesis and are regulated, in part, by tissue inhibitor of metalloprotease 1 (TIMP-1).

Researchers drilled a 1 mm hole into the proximal tibia of 126 mice. In half of the mice (63), a dose of S. aureus was injected into the canal, while the controls had no bacteria injected. At two weeks, all proximal tibiae were debrided; cultures were taken 3 and 7 days after debridement to assure no residual infection. Cytokine assays and Western blots for CCL2, CCL3, CXCL2, TIMP-1, RANKL, and TNF-α were performed in selected mice in each group. Flow cytometry and histology were also done in selected mice in each group.

In the osteomyelitis group, Western blot analysis identified increased levels of CCL2, CCL3, and CXCL2. Histology revealed increased osteoclastogenesis after osteomyelitis debridement, with calcitonin-receptor and RANKL detection via immunohistochemical and fluorescence staining. There was diminished osteogenesis and proliferation in the osteomyelitis group, but TNF-α expression seemed to have no effect on altered bone regeneration after bone infection. Flow cytometry revealed elevated B cell activity in the osteomyelitis group, with subsequent increased osteoclast activity and accelerated bone resorption.

The researchers propose a RANKL-dependent osteoclastogenesis after debridement for osteomyelitis that is associated with elevated B cells and decreased osteogenesis. These findings could lead to new interventions to improve bone healing during the course of osteomyelitis treatment, particularly following debridement.

Reference
Wagner JM, Jaurich H, Wallner C, Abraham S, Becerikli M, Dadras M, Harati K, Duhan V, Khairnar V, Lehnhardt M, Behr B. Diminished bone regeneration after debridement of posttraumatic osteomyelitis is accompanied by altered cytokine levels, elevated B cell activity, and increased osteoclast activity. J Orthop Res. 2017 Mar 6. doi: 10.1002/jor.23555. [Epub ahead of print] PMID: 28263017