Author Interviews, Hip Fractures, Orthopedics, Osteoporosis / 14.05.2018

MedicalResearch.com Interview with: “Just a hairline fracture...” by Gloria Bell is licensed under CC BY 2.0Brittany Bindon, MD Department of Internal Medicine University of Chicago Chicago, Illinois MedicalResearch.com: What is the background for this study? Response: Bisphosphonates are commonly used in the treatment of osteoporosis, however, they have been associated with rare, severe side effects such as osteonecrosis of the jaw and atypical femoral fractures. As a result, bisphosphonate drug holidays have become common in clinical practice though currently, there are minimal data on the safe duration of these drug holidays. We sought to further characterize the clinical and laboratory parameters associated with increased fracture risk in patients on bisphosphonate drug holiday. (more…)
Author Interviews, Biomarkers, Brigham & Women's - Harvard, Orthopedics, Pain Research / 11.05.2018

MedicalResearch.com Interview with: “osteopathic treatment for sciatica” by betterhealthosteopathy is licensed under PDM 3.0Daniel Albrecht, PhD Research Fellow in Radiology, Harvard Medical School Research Fellow, Massachusetts General Hospital MedicalResearch.com: What is the background for this study? What are the main findings? Response: A great deal of preclinical work in animal models of pain has established that activation of peripheral immune cells or, in the central nervous system (brain and spinal cord), immune cells called “glia” (microglia and astrocytes) play a key role in the establishment and/or maintenance of persistent pain. For instance, if you pharmacologically block activation of these cells in the nervous system, you are able to reduce/inhibit/prevent pain behaviors, e.g. in animals who have received a nerve injury. This observation is very exciting, because it suggests that blocking neuroinflammation may be a viable way of treating pain. However, the evidence linking human chronic pain with neuroinflammation has so far been limited. In this study we show, for the first time, that patients with chronic sciatica (that is, back pain that shoots down the leg) demonstrate elevations in the levels of a protein called the translocator protein (TSPO) in the spinal cord and in the nerve roots. Because TSPO is a marker of neuroinflammation, our results suggest that sciatica is associated with neuroinflammation. While on average patients do show elevations in the levels of the TSPO, we also saw significant variability across individuals. Importantly, patients that show stronger elevations (in the nerve roots) were those who benefit the most from receiving a local anti-inflammatory treatment (epidural spinal injection). This makes sense: patients whose nerve roots are inflamed benefit from an anti-inflammatory treatment. Those whose nerve roots aren’t inflamed, don’t receive the same benefit. In the latter case, the source of the inflammation and pain may not be the nerve roots, but may be the spinal cord, or, as we showed in a previous paper (Loggia et al., Brain 2015), the brain.  (more…)
Author Interviews, Breast Cancer, Osteoporosis / 05.05.2018

MedicalResearch.com Interview with: Chenfang Dong, Ph.D & M.D. Professor Department of Pathology and Pathophysiology Zhejiang University School of Medicine,  MedicalResearch.com: What is the background for this study? What are the main findings?  Response: Basal-like breast cancer (BLBC), which generally falls into the triple-negative breast cancer subtype, is associated with a poor clinical outcome due to few treatment options and poor therapeutic response; thus there is a pressing need to elucidate the determinants of aggressiveness in BLBC and identify potential therapeutic targets for this challenging disease. By analyzing gene expression profiles of breast cancer in multiple publicly available datasets that contain over 5000 cases, we have identified that UDP-galactose ceramide galactosyltransferase (UGT8), a key enzyme in the sulfatide biosynthetic pathway, promotes BLBC progression by activating sulfatide-αVβ5 axis. Importantly, we identify that zoledronic acid (ZA), a marketed drug for treating osteoporosis and bone metastasis, is a direct inhibitor of UGT8, which has the potential to become a valuable targeted drug for treating Basal-like breast cancer.  (more…)
Author Interviews, Orthopedics, Pain Research, Rheumatology / 02.05.2018

MedicalResearch.com Interview with: “dog” by Neil Mullins is licensed under CC BY 2.0Deborah S. Cummins, PhD Director, Research, Quality and Scientific Affairs American Academy of Orthopaedic Surgeons On behalf of the researchers: David Jevsevar, MD, MBA; Gregory A. Brown, MD, PHD, and Deborah S. Cummins, PhD MedicalResearch.com: What is the background for this study? What are the main findings? Response: It is estimated that individuals have a 45% risk of developing knee osteoarthritis (OA) in their lifetime. As a result of the shifting demographics of the US, where an increasing percentage of the population is older than 65, the burden of knee OA will continue to increase. To help deal with this burden, effective nonsurgical treatments are needed to manage knee OA symptoms associated with pain and function before surgical intervention becomes necessary. To determine which non-surgical options are best, we performed a network meta-analysis exploring mixed treatment comparisons for nonsurgical treatment of knee osteoarthritis in order to effectively rank the various nonsurgical treatment options from best to worst. Our network meta-analysis suggests that the single most effective nonsurgical treatment for improving knee function is function is naproxen, followed by diclofenac, celecoxib, and ibuprofen. When considering pain and function together, our data suggest that naproxen is the most effective treatment followed by IA corticosteroid injection. The single most effective short-term (4-6 weeks) treatment for decreasing pain is intra-articular (IA) corticosteroid injection, followed by ibuprofen, IA platelet rich plasma, and naproxen. Additionally, intra-articular hyaluronic acid injections never achieved a rank in the top five treatments for pain, function, or combined pain and function. An analysis of 12 articles also found that HA is not significantly different than IA placebo in effect. (more…)
Author Interviews, Exercise - Fitness, Orthopedics, Pediatrics / 02.05.2018

MedicalResearch.com Interview with: “Pitching Crop” by slgckgc is licensed under CC BY 2.0Jason L. Zaremski, MD, CAQSM, FACSM, FAAPMR Assistant Professor│Divisions of PM&R, Sports Medicine, & Research Department of Orthopaedics and Rehabilitation Co-Medical Director Adolescent & High School Outreach Program University of Florida College of Medicine MedicalResearch.com: What is the background for this study? What are the main findings? Response: Throwing injuries are common in baseball and can be caused by excessive pitch counts, year-round pitching, and pitching with arm pain and fatigue. Despite the evidence, pitching injuries among high school players have not decreased. With a multitude of research in overhead throwers, yet the volume of overuse throwing injuries not decreasing, our team suspected there was a missing workload factor in baseball pitchers. Therefore, our team conducted research to determine whether an important factor was being overlooked: volume of pitches thrown during warm-up between innings and bullpen activity in high school varsity baseball pitchers. In the study, our team counted all pitches thrown off a mound during varsity high school baseball games played by 34 different high schools in North Central Florida during the 2017 season. After counting nearly 14,000 pitches in 115 pitch outings, our team found that 42% of the pitches thrown off a mound were not accounted for in the pitch counts, and that there is a large variability of bullpen pitches being thrown from pitcher to pitcher. Even with a greater focus on pitch counts as a way to prevent injuries, a substantial number of pitches are going unaccounted for in high school players as part of warm-up and bullpen activity. (more…)
Author Interviews, Emory, Infections, JACC, Orthopedics / 26.04.2018

MedicalResearch.com Interview with: Robert Taylor, MD, PhD Marcus Chair in Vascular Medicine Executive Vice Chair, Medicine Director, Division of Cardiology Professor of Medicine and Biomedical Engineering Emory University School of Medicine MedicalResearch.com: What is the background for this study? What are the main findings? Response: The early identification and localization of bacterial infections is a critical step for initiating effective treatment.   This is particularly challenging in the setting of infections associated with implanted medical devices.  We have developed a highly specific probe for bacteria that is based on the fact that bacteria have a specific system for taking up maltodextrins which are polysaccharides that mammalian cells cannot take up directly.  We can label this probe with either a fluorescent of radioactive tag that allows visualization of the bacteria. In the current article, we have used an animal model of implantable cardiac devices to demonstrate that our probe is very specific and sensitive for detecting bacterial infections.  It is worth noting that these are subclinical infections that could not be detected by any other means except for surgical removal. (more…)
Author Interviews, Infections, Orthopedics, Surgical Research / 09.04.2018

MedicalResearch.com Interview with: Dr Setor Kunutsor PhD Research Fellow Musculoskeletal Research Unit Bristol Medical School MedicalResearch.com: What is the background for this study? Response: Hip replacement is a very common operation that is effective at providing pain relief and improving mobility. Infection is a fortunately infrequent but devastating complication that can occur following joint replacement. Currently, two main types of surgical procedures are used in treating these infections – one-stage and two-stage revision strategies. In the two-stage procedure, the existing artificial joint is removed in one operation and the patient is treated for several months with antibiotics. A new joint is then inserted in a second operation. In the one-stage procedure, the artificial joint is removed along with all infected tissue and a new one inserted in the same operation. The two-stage procedure has been in use for decades and was regarded as the most effective treatment. There has been an increase in the use of the one-stage procedure as it has also been claimed to be very effective at treating infection. There has been a lot of controversy among orthopaedic surgeons as to which is the best way to treat infected hip replacements. Several studies have been conducted on the topic, but the findings have been inconsistent. Some claim the two-stage to be more effective and others claim the one-stage procedure is. Currently the majority of studies claim the two-stage is better; but no study has been conducted that compares these procedures head-to-head to decide if one is better or if they achieve the same results. Due to the lack of evidence, some surgeons are reluctant to use the one-stage strategy. There was therefore a need to compare the effectiveness of the two surgical strategies using an appropriate study design. We conducted a study which involved collecting and bringing all previous data together under one umbrella. The process is known as “Individual Participant Data meta-analysis”. It involved communicating with surgeons in different countries all over the world and inviting them to contribute data. We called the name of the group “The Global Infection Orthopaedic Management (INFORM) Collaboration”. (more…)
Author Interviews, Orthopedics, UCSF / 19.03.2018

MedicalResearch.com Interview with: Terence J. Gioe, MD American Joint Replacement Registry, Rosemont, IL UCSF School of Medicine, San Francisco VA Health Care System  MedicalResearch.com: What is the background for this study? What are the main findings?  Response: Hospital-based or regional registries are typically limited in their catchment area, making loss to follow-up a major concern when patients move out of the area or otherwise receive subsequent medical care outside of the original hospital network. The American Joint Replacement Registry (AJRR), a part of the American Academy of Orthopaedic Surgeons’ (AAOS) registries portfolio, has the goal of tracking total joint arthroplasty (TJA) patients nationally across the US, but currently captures only approximately 28% of annual TJA procedures. Until a nationwide network of reporting hospitals is established that covers at least 90% of all TJA procedures, loss to follow-up due to migration will be a key potential limitation of large-scale studies on implant performance in the US. Assessment of loss to follow-up can provide an essential understanding of the migration patterns of TJA patients, and help to improve recruitment and enrollment efforts of the AJRR. The magnitude and characteristics of patient migration following TJA have not previously been studied in the US.  (more…)
Author Interviews, Orthopedics, Pediatrics / 19.03.2018

MedicalResearch.com Interview with: Baron  Lonner, MD Professor of Orthopaedics Icahn School of Medicine at Mount Sinai  MedicalResearch.com: What is the background for this study? What are the main findings? Response: 2-3% of adolescents have idiopathic scoliosis and 1 in 10 of these individuals will require surgery to correct severe scoliosis which if left untreated can lead to back pain and disability as well as pulmonary (breathing) problems later in life. For the adolescent with curvatures that require surgical treatment, body image and self esteem are big issues as they are for all adolescents going through their developmental stages. Scoliosis has an impact on body shape, which is seen by the affected individual looking in the mirror as well as by their peers and those around them. This can lead to self esteem and body image disturbance issues. We set out to explore the body shape distortions that occur with scoliosis, that are not depicted by x-rays that are standardly used to assess curvatures of the spine, and the improvements in parameters of body shape that occur with corrective surgery. We can assess body shape directly through surface topography imaging, that is light-based, thus, not involving x-ray exposure. This technology (Diers Formetrics) uses the same scientific methodology that is used to create modern topographical maps through satellite imagery. We found dramatic improvements in body shape asymmetry with surgery that correlated with some improvements in quality of life for the adolescent in this cohort of 23 patients as well as with the improvements in curvatures evaluated by x-rays.  (more…)
Author Interviews, Orthopedics / 08.03.2018

MedicalResearch.com Interview with: Dr. Charles A. Popkin, MD Orthopedic Surgeon NewYork-Presbyterian/Columbia University Medical Center MedicalResearch.com: What is the background for this study? What are the main findings? CAP: Sports participation offers multiple benefits for children and adolescents, but there is growing concern about the rise of early sports specialization (ESS). ESS is defined as intense, sport specific training for greater than 8 months a year at the exclusion of other sports and activities in children younger than 12 years of age (pre-pubescent). ESS has been linked with decreased enjoyment, burnout, injury risk and the impact of specialization on long term athletic success is unknown. The extent to which parents exert influence, both directly and indirectly on the phenomenon of ESS was the major focus of the study. (more…)
Author Interviews, Hematology, NEJM, Orthopedics, Thromboembolism / 22.02.2018

MedicalResearch.com Interview with: Dr. David R. Anderson, MD, FRCPC, FACP Faculty of Medicine Dean, Professor Dean, Faculty of Medicine Division of Hematology, Department of Medicine & Nova Scotia Health Authority MedicalResearch.com: What is the background for this study? What are the main findings? Response: Blood clots in the lungs (pulmonary embolism) and veins of the legs (deep vein thrombosis) are well recognized complications following total hip and knee arthroplasty surgeries.  Prior to the routine use of antithrombotic prophylaxis, pulmonary embolism was the most common cause of death following these procedures.  Oral anticoagulants such as rivaroxaban are commonly prescribed for the indication of preventing blood clots following total hip or knee arthroplasty.  For maximal benefit these agents are continued following surgery for up to five weeks following total hip arthroplasty and for two weeks following total knee arthroplasty. There is evidence that aspirin has some benefit for the prevention of deep vein thrombosis and pulmonary embolism following total hip or knee arthroplasty.  However there is less evidence for its benefit than for oral anticoagulants.  We reasoned that aspirin would potentially be an attractive alternative for extended out of hospital prophylaxis following total hip or knee arthroplasty for patients who received a short course (5 days )of rivaroxaban following surgery.  Aspirin would be attractive for this indication because of its low cost, ease of use, and low rates of side effects. Our study demonstrated that in a randomized controlled trial involving a large group (over 3400) of patients undergoing total hip or knee arthroplasty that extended therapy with aspirin was comparable to rivaroxaban for the prevention of deep vein thrombosis and pulmonary embolism following surgery.  Low rates of complications (< 1%) were observed with both treatment arms.  We also found that rates of clinically important bleeding complications (the most common side effect with antithrombotic drugs) were uncommon and similar with the two agents. (more…)
Accidents & Violence, Author Interviews, Orthopedics / 16.01.2018

MedicalResearch.com Interview with: “First day of snowboarding” by kaolin fire is licensed under CC BY 2.0Dr. Brett D Owens, MD Dr. Owens is currently Team Physician for the US Lacrosse National Men’s Team, and Team Physician for Brown University Professor at Uniformed Services University and Professor at Brown University Alpert School of Medicine MedicalResearch.com: What is the background for this study? What are the main findings? Response: This study is a review of the literature on ski and snowboarding injuries. We summarize findings by our group and others on the injuries seen with these snow sports and report an overall increase in injuries as participation continues to increase. Snowboarders have a higher injury rate and there are different injury patterns with skiers experiencing more lower extremity injuries (knee) and snowboarders experiencing more upper extremity injuries (wrist, shoulder, etc.).  (more…)
Author Interviews, Bone Density, Dermatology, Endocrinology, Osteoporosis, Pediatrics / 03.12.2017

MedicalResearch.com Interview with: Diana L. Cousminer, PhD Division of Human Genetics Children's Hospital of Philadelphia Philadelphia, PA 19104 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Osteoporosis is a significant public health burden, with origins early in life. Later puberty and lower adolescent bone mineral density are both risk factors for osteoporosis. Geneticists have identified hundreds of genetic variants across the genome that impact pubertal timing, and we found that collectively this variation also plays a role in bone mineralization during adolescence. Additionally, we found that later puberty caused lower adult bone density. (more…)
Asthma, Author Interviews, JAMA, Orthopedics, Pediatrics / 14.11.2017

MedicalResearch.com Interview with: “Asthma” by Michael Havens is licensed under CC BY 2.0Teresa To, PhD Biostatistics, Design and Analysis Scientific Director The Hospital for Sick Children Dalla Lana School of Public Health, University of Toronto Institute for Clinical Evaluative Sciences Toronto, Ontario, Canada MedicalResearch.com: What is the background for this study? What are the main findings? Response: We studied asthma prescription drug use in Ontario children aged 2 to 18 years with physician diagnosed asthma between 2003 and 2014. We found that:
  1. Currently in Ontario, nearly 50% of children with asthma did not fill a prescription for an inhaled corticosteroid during the study period, despite these medications being considered the gold-standard for asthma management.
  2. Our findings did not show clinically important association between inhaled corticosteroids and fracture among children with asthma.
  3. However, systemic corticosteroids (oral or injection) are associated with higher fracture risk in children with asthma (17% higher risk).
(more…)
Author Interviews, Cancer Research, Orthopedics, Pharmacology / 13.11.2017

MedicalResearch.com Interview with: Charles L.Shapiro MD Professor of Medicine Director of Translational Breast Cancer Research Director of Cancer Survivorship Division of Hematology/Oncology Tisch Cancer Institute New York, NY MedicalResearch.com: What is the background for this study? What are the main findings? Response: The new 2017 ASCO guidelines for the use bone-modifying in individuals with bone metastases recently endorsed every 3-month zoledronic, because of high level evidence from three randomized trials, including our trial (published in Jama in Jan 2017, first author Himelstein et al) that giving zoledronic acid every 3-months was non-inferior to the standard of monthly zoledronic. The guidelines also concluded that there was not one preferred bone modifying agent of the other, despite the fact the comparing monthly zoledronic to monthly denosumab in women with bone metastases, denosumab delayed the time to first skeletal-related event (pathological fractures, necessity for radiation or surgery, and spinal cord compression) and subsequent events by 23% (or in absolute terms about 3 months) . Zoledronic acid became generic in 2013, whereas monthly denosumab is still patented until 2022-25. (more…)
Author Interviews, Orthopedics, Rheumatology, Social Issues / 07.11.2017

MedicalResearch.com Interview with: Susan M. Goodman, MD Director of the Integrative Rheumatology and Orthopedics Center of Excellence Hospital for Special Surgery  MedicalResearch.com: What is the background for this study? What are the main findings? Response: We have previously reported that African Americans who have poorer health outcomes, may be disproportionately impacted by community factors. For African Americans undergoing knee replacement, no difference in pain and function was seen compared to whites in communities with little poverty, while in poor communities, African Americans had poorer outcomes. We wondered if this was generally true or if this only applied to knee replacements. We found similar results; African Americans in richer neighborhoods have comparable outcomes to whites, but as poverty increases- in this study measured as percent with Medicaid coverage- outcomes worsen in a step wise fashion. (more…)
Accidents & Violence, Author Interviews, Exercise - Fitness, Frailty, Geriatrics, JAMA, Osteoporosis / 07.11.2017

MedicalResearch.com Interview with: Andrea C. Tricco PhD, MSc Scientist and Lead of the Knowledge Synthesis Team Associate Professor Dalla Lana School of Public Health, University of Toronto Associate Editor Journal of Clinical Epidemiology, BMC Medical Research Methodology, Systematic Reviews MedicalResearch.com: What is the background for this study? Response: Falls are the leading cause of injury among older adults and account for $2 billion in direct health-care costs annually ($31 billion in costs to Medicare in the United States in 2012). We aimed to determine which types of fall-prevention programs may be effective for reducing falls in older people. MedicalResearch.com: What are the main findings? Response: Exercise, along with vision assessment and treatment, as well as an assessment and possible modification of a person’s living environment, reduced the risk of injurious falls by 23% compared to usual care. (more…)
Author Interviews, Exercise - Fitness, NEJM, Orthopedics / 04.10.2017

MedicalResearch.com Interview with: Monika Bayer PhD. Institute of Sports Medicine Copenhagen Bispebjerg Hospital Denmark MedicalResearch.com: What is the background for this study? What are the main findings? Response: Acute muscle strain injuries display a major clinical problem with a high incidence rate for both professional and amateur athletes and are associated with substantial risk for recurrence. Common clinical practice advices to follow the RICE (Rest – Ice – Compression – Elevation) principle after strain injuries but it has not been investigated whether patients really benefit from a period of rest or whether an early of loading following the injury would improve recovery. In this study, amateur athletes were divided into two groups: one group started rehabilitation two days after the trauma, the other group waited for one week and began rehabilitation after nine days. All athletes had a clear structural defect of the muscle-connective tissue unit following explosive movements. We found that protraction of rehabilitation onset caused a three-week delay in pain-free recovery. In all athletes included, only one suffered from a re-injury. (more…)
Author Interviews, Columbia, Heart Disease, Orthopedics / 28.09.2017

MedicalResearch.com Interview with: Dr. Mathew Maurer, Medical Director The Hypertrophic Cardiomyopathy Center NewYork-Presbyterian/Columbia University Medical Center. MedicalResearch.com: What is the background for this study? Response: Transthryretin cardiac amyloidosis (TTR-CA) is an underdiagnosed type of cardiomyopathy in which TTR (transthyretin, also known as prealbumin), a protein that forms amyloid fibrils, deposits in the heart. The deposits cause thickening of the ventricular wall and diastolic as well as systolic dysfunction. It is usually discovered around age 75 and presents more commonly in men than in women. With advances in non-invasive diagnostic modalities and growing awareness, TTR-CA is being diagnosed increasingly more frequently. Additionally, there are several emerging treatments that are under active investigation. Most of these therapies prevent disease progression and don’t address the amyloid already deposited in the heart. Accordingly, it is imperative that we diagnose TTR-CA before patients develop significant amyloid heart disease. However, this presents a great challenge since there are few known clinical predictors that might alert even the most astute physician that a patient is at such risk. With identification of predictors that may appropriately raise the index of clinical suspicion, clinicians may begin to pick up more subtle (and perhaps not yet clinically significant) forms of TTR-CA and initiate treatment before significant damage occurs. The few known clinical predictors of TTR-CA include bilateral carpal tunnel syndrome and lumbar spinal stenosis, and numerous studies found TTR on biopsies and autopsies of other musculoskeletal sites, particularly in hip and knee joints. (Just last week, and also discussed here on MedicalResearch.com, biceps tendon rupture was also shown to occur more frequently in TTR-CA!) We suspected that patients who ultimately develop TTR-CA may first develop clinically significant hip and knee disease, enough to even warrant a hip (THA) or knee (TKA) replacement. (more…)
Author Interviews, Brigham & Women's - Harvard, Heart Disease, JAMA, Orthopedics / 22.09.2017

MedicalResearch.com Interview with: Avinainder Singh, M.B.B.S. Research Fellow Cardiovascular Medicine Brigham & Women's Hospital Harvard Medical School Boston, MA MedicalResearch.com: What is the background for this study? Response: Amyloidosis due to aberrant folding of proteins. These misfolded proteins can deposit in various parts of the body and lead to organ dysfunction. The two most common types of amyloidosis affecting the heart include transthyretin and light chain amyloidosis. Transthyretin is a protein produced by the liver which supports the transport of thyroxine and retinol. Wild-type transthyretin amyloidosis (ATTRwt, previously known as senile amyloidosis) occurs due to deposition of misfolded fibrils derived from transthyretin and primarily affects elderly men. Once considered a rare disease, it is now reported to be responsible for nearly 13% of heart failure with preserved ejected fraction and increased wall thickness. Rupture of the biceps tendon is a rare occurrence in the general population (<1 per 1000). We noticed a ruptured biceps tendon in several patients with wild-type transthyretin amyloidosis and performed this study to further evaluate this finding in a group of patients with wild-type transthyretin amyloidosis and in a control group of age-matched patients with non-amyloid heart failure. (more…)
Author Interviews, Osteoporosis, Pharmacology / 30.08.2017

MedicalResearch.com Interview with: Dieter Bromme, Ph.D. Professor and Canada Research Chair The University of British Columbia Faculty of Dentistry Vancouver, BC MedicalResearch.com: What is the background for this study? What are the main findings? Response: Every three seconds somebody will fracture a bone because of osteoporosis. Several treatments are available to slow down bone loss but all of them have shortcomings ranging from poor bone quality to various side effects. Thus new treatment strategies and novel drug targets are needed that promise efficacy without significant adverse reactions. One of the novel promising targets was cathepsin K, a protease solely responsible for the degradation of our organic bone matrix. Major efforts and funds were spent by the pharmaceutical industry to develop potent and selective cathepsin K inhibitors. These inhibitors were highly effective in preserving bone in clinical trials. Despite the good news, cathepsin K inhibitors were never approved because of various non-skeletal side effects. We hypothesized that these side effects are not caused by off-target effects (drugs react with undesired targets) but by on-target effects. Most drugs that target enzymes are active site-directed compounds and thus will stop the entire activity of the target enzyme. If the target is a multifunctional enzyme, safety problems are preprogrammed. Based on our studies to understand the molecular mechanism of collagen degradation by cathepsin K, we developed the concept of ectosteric enzyme inhibition, which allowed us to identify highly selective collagenase inhibitors of this protease. In our study, we used a red sage-derived small molecule that selectively blocked the collagenase activity of cathepsin K and thus consequently bone degradation in an osteoporosis mouse model without affecting other known functions of the protease. The crucial difference might be that the red sage inhibitor did not block the cathepsin K-mediated degradation of TGF-ß1, a growth factor involved in fibrotic pathologies described in the clinical trials. TGF-ß1 degradation is blocked by these inhibitors and thus accumulates in tissues, causing fibrosis. (more…)
Author Interviews, Opiods, Orthopedics, Pain Research, Stanford / 21.08.2017

MedicalResearch.com Interview with: Tina Hernandez-Boussard, PhD MPH, MS Associate Professor of Medicine, Biomedical Data Science, and Surgery Stanford School of Medicine Stanford, CA 94305-5479 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Opioid addiction is a national crisis.  As surgery is thought to be a gateway to opioid misuse, opioid-sparing approaches for pain management following surgery are a top priority. We conducted a meta-analysis of 39 randomized clinical trials of common non-pharmalogical interventions used for postoperative pain management. We found that acupuncture and electrotherapy following total knee replacement reduced or delayed patients’ opioid use. (more…)
Author Interviews, Cleveland Clinic, Orthopedics, Pain Research, Surgical Research / 01.08.2017

MedicalResearch.com Interview with: Michael A. Mont, MD Department of Orthopaedic Surgery Cleveland Clinic Cleveland, OH  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Postoperative pain after total knee arthroplasty (TKA) is a major hurdle for both the patients and the orthopaedists. Many analgesic modalities are currently in use, and can be used alone or in combination in order to augment their effect. Addition of local anesthetic analgesia has been shown to improve pain control and reduce opioid consumption during postoperative period. However, the effects of this analgesia tend to dissipate with time, with the longest duration of action (bupivacaine) of approximately 12 hours. Therefore, long acting local anesthetic (liposomal bupivacaine) has been developed in order to expand the duration of effectiveness of pain relief for up to 96 hours. Many studies evaluated the effectiveness of this anesthetic and demonstrated contradictory results, however, they did not use the same methods and infiltration technique. Therefore, we conducted a prospective, randomized, double-blind, controlled study at 16 hospitals using optimal infiltration techniques. Our study demonstrated significant improvement in pain, decreased opioid consumption, increased time to first opioid rescue, more opioid free patients in liposomal bupivacaine cohort. In addition, there were no unexpected safety concerns. (more…)
Author Interviews, JAMA, Orthopedics / 11.07.2017

MedicalResearch.com Interview with: Mattias Lorentzon, PhD Professor, Senior Physician Head of Geriatric Medicine, Institute of Medicine, Sahlgrenska Academy Sahlgrenska University Hospital, Mölndal Mölndal, Sweden MedicalResearch.com: What is the background for this study? What are the main findings? Response: It was previously known that alendronate reduces the risk of vertebral fractures in patients using oral glucocorticoids, but there were no studies regarding hip fractures, which are the most severe osteoporotic fractures, often resulting in disability and mortality. We found that older patients prescribed alendronate after starting medium to high doses of oral prednisolone had a much lower risk of hip fracture than patients not taking alendronate. (more…)
Author Interviews, Exercise - Fitness, Orthopedics, Pediatrics / 31.05.2017

MedicalResearch.com Interview with: Jacqueline Pasulka, OMS II Des Moines University College of Osteopathic Medicine , Des Moines , IA Division of Pediatric Orthopaedic Surgery & Sports Medicine, Ann & Robert H. Lurie Children's Hospital of Chicago , Chicago , IL MedicalResearch.com: What is the background for this study? What are the main findings? Response: In this study young athletes were recruited from both sports medicine and general practice clinics and were asked to complete surveys reporting on their sports participation, training patterns, and any sports-related injuries they had over the previous six months. We focused this study on the subset of athletes who met the criteria for being a single-sport specialized athlete based on their reported participation in only one sport and training for eight months or more during the year for that sport. Athletes participating in individual sports were more likely to be single-sport specialized than their team sport peers, and they also reported an earlier age at which they began specializing in their sport. Additionally, injury types differed among these two groups as single-sport specialized athletes in individual sport athletes had a greater proportion of overuse injuries, while single-sport specialized athletes in team sport athletes had a greater proportion of acute injuries. (more…)
Author Interviews, BMJ, Osteoporosis / 23.05.2017

MedicalResearch.com Interview with: Jean-Yves Reginster M.D.,PH.D. Professor of Epidemiology, Public Health and Health Economics Head of the Bone and Cartilage Metabolism Unit University of Liège MedicalResearch.com: What is the background for this study? What are the main findings? Response: Whereas several recommendations, issued by scientific societies, recommend to use Symptom-Modifying Slow Acting Drugs (SYSADOAs) for the symptomatic and structural management of osteoarthritis, no medication is currently registered, in this particular indication, by the European Medicines Agency (EMA) or by the Food and Drug Administration (FDA). This study is the first study, conducted, with a SYSADOA which fully complies with the requirements of the EMA for the assessment of drugs to be used in the treatment of osteoarthritis, i.e. a six-month duration, two co-primary endpoints (pain and function) and a three-arm design, with a placebo and an active comparator. The main findings are that pharmaceutical grade chondroitin sulfate provides an improvement in pain and function, which is greater than placebo and not distinguishable from celecoxib, a non-steroidal anti-inflammatory drug currently licensed for the symptomatic management of osteoarthritis. (more…)
Author Interviews, Dermatology, Orthopedics, Stem Cells / 22.04.2017

MedicalResearch.com with: Lee Buckler, CEO RepliCel Life Sciences MedicalResearch.com: What is the background for this your company, RepliCel.com? Response: RepliCel Life Sciences is a Canadian regenerative medicine company based in Vancouver, British Columbia that was founded in 2006. The company focuses on the development of cell therapies using a patient's own cells (autologous cell therapy). It is developing treatments targeted at healing chronic tendon injuries that have failed to heal properly, hair restoration, and the treatment of damaged and aged skin. (more…)
Author Interviews, Hip Fractures, Mineral Metabolism / 17.04.2017

MedicalResearch.com Interview with: Dr Setor Kunutsor Ba(Legon), MBChB(Legon), MA(Cantab), PhD(Cantab) Research Fellow Musculoskeletal Research Unit University of Bristol MedicalResearch.com: What is the background for this study? Response: Bone fractures are one of the leading causes of disability and ill health especially among the ageing population and are a burden to health care systems. There is established evidence that calcium and vitamin D play an important role in bone health. Magnesium is an essential trace element, being the second most abundant intracellular cation after potassium and the fourth most abundant cation in the body. It serves several important functions in the body, which include protein synthesis, nucleic acid synthesis, enzymatic reactions, and has also been shown to be cardio-protective. It is also an important component of bone, with majority (67 percent) of total body magnesium known to be found in the bone tissue. There have been suggestions from both human and animal experiments that magnesium may have a beneficial effect on bone health; however, its relationship with fractures is not very certain. (more…)
Author Interviews, Orthopedics / 11.04.2017

MedicalResearch.com Interview with: Christopher M. Larson, M.D. Minnesota Orthopedic Sports Medicine Institute Twin Cities Orthopedics Edina, MN   MedicalResearch.com: What is the background for this study? What are the main findings? Response: Until recently Athletic Hip and Pelvis disorders and the appropriate treatment strategies have not received the same attention as other sports related disorders.  There is significant overlap between intra-articular and extra-articular hip disorders that make this a challenging area of sports medicine from a diagnosis and treatment standpoint. (more…)