Category: Medicine

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Statins & Osteoporosis

   The protective effect of statin therapy on bone health that has been demonstrated in some studies may be dose-related, and although low doses are associated with a reduced risk for osteoporosis, high doses were linked to an increased risk of the bone disease in new research.

   “To the best of our knowledge, this is the first study which shows that it is important to consider the different kinds of substances and dosages when investigating the relationship of osteoporosis and statin therapy,” say Michael Leutner, MD, of the Clinical Division of Endocrinology and Metabolism, Unit of Gender Medicine, Medical University of Vienna, Austria, and colleagues in an article published online in the Annals of the Rheumatic Diseases.

   “The results were surprising for us,” senior author Alexandra Kautzky-Willer, Dr Med, also of the Medical University of Vienna, told Medscape Medical News.

   “We propose that monitoring high-risk patients, that is, postmenopausal female patients under high-dosage statin therapy, might be useful in order to offer an individual therapy to prevent or treat osteoporosis,” she said.

   Asked to comment, Ching-Lung Cheung, PhD, assistant professor in the Department of Pharmacology and Pharmacy and investigator with the Center for Genomic Sciences at the University of Hong Kong, said key caveats to consider in the study include the role of high cholesterol, which prompts the need for higher doses of statins.

   “Elevated serum low-density lipoprotein (LDL) cholesterol is associated with reduced bone mineral density (BMD); thus, it is possible that those patients receiving high-dose statins had a lower baseline BMD compared to those receiving low-dose statins, which confound the observed association,” Cheung, who is also involved in research on the relationship between statins and bone health, told Medscape Medical News.

Large Study in Austrian Population

   For the large population study, Leutner and colleagues reviewed data on all Austrians younger than 90 years, nearly 8 million, from January 2006 to December 2007.

   They identified 353,502 patients who had been taking one of the seven statins available at the time for at least 1 year, including simvastatin, lovastatin, pravastatin, fluvastatin, atorvastatin, cerivastatin and rosuvastatin. The patients were approximately evenly divided among males and females.

   Among them, 11,701 patients, including 1765 males and 9936 females, were diagnosed with osteoporosis, according to International Classification of Diseases, 10th Revision (ICD10) codes.

   They were compared with a control group of about 7.5 million patients who were not treated with statins. About 3.5 million were male and 4 million were female. Among them, 68,699 were diagnosed with osteoporosis, including 10,410 males and 58,289 females.

   Overall, treatment with statins was associated with more than threefold greater odds of having osteoporosis compared to nonstatin use among control persons (odds ratio [OR], 3.62; P < .01).

   However, low-dose statin therapy (0 – 10 mg/day) was associated with a lower risk for osteoporosis.

   The effects were similar for the different drugs, including lovastatin (OR, 0.39; P < .05), pravastatin (OR, 0.68; P < .01), simvastatin (OR, 0.70; P < .01), and rosuvastatin (OR, 0.69; P < .01).

   However, risk for osteoporosis increased among those taking higher doses of statins, defined as doses exceeding 40 mg for simvastatin (OR, 1.64; P < .01) and exceeding 20 mg for atorvastatin (OR, 1.78; P < .01) and rosuvastatin (OR, 2.04; P < .01), compared to control persons.

   The study controlled for other prescribed drugs and for comorbidities that included diabetes and diseases typically treated with corticosteroids that are known risk factors for the development of osteoporosis.

Could Higher Doses of Statins Affect Sex Hormones?

   Kautzky-Willer explained, “In mouse models and in vitro, statins have been shown to enhance bone formation ― for example, by increasing the expression of bone morphogenic protein (BMP-2), which is an osteoprotective protein. However, statin dosages were insufficiently considered in existing studies.

   “In lower dosages of statins, this osteoprotective effect of BMP-2 could be a major reason for the lower rates of diagnosed osteoporosis,” she said.

   However, estrogen, which plays a crucial role in the maintenance of BMD, is derived from cholesterol.

   Therefore, the strong cholesterol-lowering effects of stains at high doses could also lower estrogen and have an effect on the bones similar to that of menopause, which is a leading cause of osteoporosis.

   “Our hypothesis is that in higher dosages of statins, the possible inhibiting effect of statins on sex hormones could overrule the osteoprotective effect,” Kautzky-Willer said.

   Likewise, statin use has been associated with reduced levels of testosterone in some research. One study showed that higher levels of non–sex hormone–binding globulin-bound testosterone were associated with a decrease in BMD in Korean men.

   “Taken together, these findings suggest a connection between sex hormone levels and statins in the pathogenesis of osteoporosis,” the Austrian authors conclude.

Whether Statins Affect Levels of Sex Hormones Requires Further Study

   Cheung and some of his colleagues focused on the roles of LDL cholesterol and statins in bone health in research reported as a poster at last month’s annual meeting of the American Society for Bone and Mineral Research.

   Using a US cohort from NHANES III (n = 3638) and another from the Hong Kong Osteoporosis Study (n = 1128), they found that reductions in LDL cholesterol were significantly associated with increases in femoral neck and lumbar spine BMD.

   Furthermore, statins’ LDL cholesterol–lowering proxies were associated with increased total body BMD.

   These findings “suggest that statin use was associated with increased BMD,” Cheung said.

   In further commenting on the Austrian study, Cheung agreed that the potential effect of high-dose statins on sex hormones is noteworthy.

   “This is an interesting hypothesis,” he said. “Although the authors mention a few studies showing a significant association between statins and sex hormones, there [are also] a few studies showing null association of statins with sex hormones.

   “Thus, whether statins use affects sex hormone requires further study,” he commented.

   Cheung also underscored the fact that the use of ICD codes to define osteoporosis is a “major limitation” of the Austrian study.

   “The authors should validate the accuracy of the coding, as this is extremely important in a pharmacoepidemiology study, especially [because] BMD is not routinely measured. [Therefore,] accuracy of the coding of osteoporosis is doubtful,” he said.

Courtesy : Medscape

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Blood : A Significant Unmet Need

   The World Health Organization (WHO) recently added blood and its components to the Model List of Essential Medicines, underscoring the importance of an adequate blood supply to optimize patient care.

   However, a new analysis finds that many countries are critically short of blood and that current targets for blood collection are often inadequate to meet local needs. These findings, based on data from 195 countries, were published online today in the journal The Lancet Haematology.

   For the study, Christina Fitzmaurice, MD, MPH, from the University of Washington, Seattle, and colleagues estimated blood availability from the WHO Global Status Report on Blood Safety and Availability between 2011 and 2013. The authors then calculated disease-specific transfusion needs for 20 medical conditions using United States data collected between 2000 and 2014 for the Healthcare Cost and Utilization Project.

   They then used data from the 2017 Global Burden of Disease study to determine disease prevalence in each of the 195 countries and estimate how much blood would be needed to treat every patient requiring a blood transfusion.

   The researchers estimate that in 2017 the global blood supply was approximately 272 million units; however, the global demand was approximately 304 million units, resulting in a deficit of over 30 million units.

   However, the supply gap was unevenly distributed among countries. Specifically, when the authors considered just the 119 countries where need outstripped supply, they uncovered a shortage of over 100 million units, equal to 1849 units per 100,000 population. Countries in sub-Saharan Africa, Oceania, as well as South Asia and Southeast Asia, had the greatest unmet need despite having relatively small blood needs across all causes.

   The WHO suggests that 10 to 20 donations for every 1000 people is sufficient to provide adequate blood component supplies. The authors propose, however, that this target may underestimate actual blood needs, noting that all countries included in this study were above this goal. Assuming a ratio of five units of components for every unit of whole blood donated, 40 countries required more than 30 donations per 1000 people and four countries required more than 40 donations per 1000 people.

   The authors acknowledge that the ideal blood usage rates by cause are unknown and transfusion recommendations outside of the US will differ based on disease severity. Further, estimates of blood need also assumed a standard of care similar to what is available in the United States and acknowledge that this may not be the case in middle- and low-income countries.  

   The causes for blood transfusion also varied greatly among countries. Injuries and cardiovascular disease were the primary causes for blood transfusion in high-income countries, whereas respiratory diseases (eg, tuberculosis) and nutritional deficiencies were the more common causes in low-income countries.

   “Many countries face critical undersupply of transfusions, which will become more pronounced as access to care improves,” Fitzmaurice and colleagues write.

   “A more detailed understanding of a country’s blood needs will allow stakeholders such as ministries of health, non-governmental entities that focus on global health, and national transfusion services and blood banks to better predict the needed supply and plan for adequate transfusion services,” the authors write.

   “This study is a reminder that a safe and sufficient blood supply is needed to manufacture unique cell based or protein therapeutic products,” writes Thierry Burnouf, PhD, from the Taipei Medical University, Taiwan, in an accompanying editorial.

   “Comprehensive strategies, through national and regional commitment, international cooperation, and transfer of technologies to blood establishments, can help fill the gap and strengthen local blood systems so that patient access to life-saving blood therapies gradually improves,” he concludes.

Courtesy : Medscape

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Vegetarians = Higher Risk for Stroke + Lower Heart Disease Risk

   People who follow vegetarian or vegan diets may have lower odds for heart disease but higher chances of having a stroke, compared to meat eaters, a large UK study suggests.

 

   Vegetarians – including vegans – were 22% less likely to develop coronary artery disease than meat eaters. This is the equivalent of 10 fewer cases of artery disease per 1,000 people over a decade among vegetarians compared to meat eaters, researchers calculated.

   However, vegetarians and vegans were 20% more likely than others to have a stroke – particularly a hemorrhagic stroke. This translates over 10 years to roughly three more strokes per 1,000 people in vegetarians than in meat eaters.

 

   “The reason for higher risk of stroke in vegetarians is less clear, but some recent evidence has suggested that while low cholesterol levels (are) protective against both heart disease and ischemic stroke, very low cholesterol levels might be linked to a higher risk of hemorrhagic stroke, the subtype that was found to be higher in the vegetarians,” Tong said by email.

   The elevated stroke risk among vegetarians and vegans was due to 43% increased odds of a hemorrhagic stroke; there was no meaningful difference in ischemic stroke rates between this group and meat eaters.

   There also was no meaningful difference in risk of heart attacks based on eating habits, researchers reported September 4 online in The BMJ.

   Researchers assessed eating habits with questionnaires at the start of the study. Some participants completed questionnaires again an average of 14 years later.
 

   People who ate meat – regardless of whether they also ate fish, dairy, or eggs – were classified as meat eaters. Their ranks totaled 24,428 at the start of the study and 96% remained meat eaters based on the follow-up dietary questionnaires.

   Another 7,506 people ate fish, but no meat at the start of the study, and 57% of these participants who completed the second dietary questionnaires remained fish eaters.

   An additional 16,254 people started out as vegetarians or vegans, eating no meat or fish, and 73% still abstained based on the follow-up dietary questionnaires.

   “Dietary guidelines recommend increasing our intake of whole nutritious foods such as fruits and vegetables and reducing intake of ultra-processed foods and beverages,” said Mark Lawrence, a public health and nutrition researcher at Deakin University in Melbourne, Australia, who co-authored an editorial accompanying the study.
 
   “Increasingly, national dietary guidelines around the world are recognizing plant-based diets for their environmental sustainability as well as health benefits,” Lawrence said by email. “Though, shifting towards plant-based dietary patterns for reasons of personal or planetary health does not necessarily mean becoming a vegetarian.”
 
Courtesy : Medscape
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‘Game Changer’ for Spinal Cord Injury – Nerve Transfer Surgery

   A new technique in which working nerves are rerouted to paralyzed sites in patients with spinal cord injury provides patients with significant functional improvement in upper limb and hand function and is being described as “a game changer.”

   A prospective case series of 16 patients undergoing this nerve transfer surgery at an Australian hospital has shown meaningful improvements in elbow extension and grasp-and-pinch hand functions. In some cases, the nerve transfer surgery was successfully combined with tendon transfers to maximize functional benefits. The current report — the largest prospective, consecutive case series of nerve transfers done at a single center in the tetraplegic population — was published online July 4 in The Lancet.

   “Our results show that nerve transfer gives particularly good results for hand function. This includes grasping and pinching, and the open hand position needed for using a computer or smartphone. This gives patients a whole new realm of independence,” lead author Natasha van Zyl, MBBS, Austin Health, Melbourne, Australia, told Medscape Medical News.

   “The improvements in hand function we have achieved with nerve transfer have allowed patients to do their own personal care, handle money, feed themselves with normal utensils, hold a cup or glass and drink independently, and go to the toilet themselves. The ability to use their hands for functions like this is what spinal cord injury patients want most — more so than being able to walk,” she added.

“Expendable” Nerves

   Van Zyl explained that the procedure involves taking a nerve that is working but is expendable (it is supplying a muscle that is also supported by other working nerves) and rerouting it to a muscle that is paralyzed.

   “Many spinal cord injury patients still have the ability to move their shoulders, bend their elbows and expand their wrists — this means we have the nerves to these muscles at our disposal,” she said. “It’s like unplugging the power source to the toaster and plugging it into the kettle instead.”

   She explained that nerve transfer is not a new concept. “We have been doing this for peripheral nerve and brachial plexus injuries for many years, but its use in spinal cord injury only started recently, and before this publication there have only been single cases reported.”

   Van Zyl has been pioneer in this area. “I was doing a lot of brachial plexus nerve transfer surgeries and I thought it might work in spinal cord injury so we started doing it and found good results.; Here we are reporting a case series with careful documentation of methodology and outcomes so that other surgeons can learn about the techniques that work best,” she said.

   She notes that tendon transfer is already an established technique for patients with spinal cord injury, but nerve transfer gives different benefits. “‘Tendon transfer generally gives more strength to a muscle but nerve transfer gives more natural subtle movements better for fine motor control,” Van Zyl said. The two techniques can be complementary and are sometimes performed in opposite limbs.

   “We often do tendon transfer in one arm and nerve transfer in the other. The patient then has one strong hand and one more suited to the intricate actions needed for everyday life,” Van Zyl explained. “If they have to pick something up from the floor, patients say they would use their tendon-transfer hand to hold the wheel and stabilize their wheelchair and their nerve-transfer hand to pick up the object.”

   Nerve transfer can also allow elbow extension so patients can reach out to perform tasks such as propel their wheelchair, turn off lights, or wash their hair, Van Zyl reported. “It is very important for people in a wheelchair to be able to reach up in a world designed for individuals standing up,” she said.

   The authors note that cervical spinal cord injury is a devastating, life-changing injury, which affects 250,000–500,000 people worldwide each year, with more than 50% of these injuries resulting in tetraplegia. They point out that nerve transfers are an attractive option: the procedure can reanimate more than one muscle at a time and multiple nerve transfers can be completed simultaneously. The procedure also requires a smaller operative incision and a shorter recovery than tendon transfer.

   The Lancet article describes a case series of 16 patients with early (<18 months post-injury) cervical spinal cord injury of motor level C5 and below who underwent single or multiple nerve transfers in one or both upper limbs, sometimes combined with tendon transfers, for restoration of elbow extension, grasp, pinch, and hand opening. A total of 59 nerve transfers were performed in 27 limbs.

   Results at 24 months showed clinically significant improvements from baseline in median Action Research Arm Test total score (16.5 to 34.0) and Grasp Release Test (35.0 to 125.2). Mean Spinal Cord Independence Measure (SCIM) also showed clinically meaningful improvements. “There isn’t a measure for open-hand action but actually that is where I think the maximum benefit is to be had,” Van Zyl said.


A “Huge” Advantage

   In an accompanying commentary, Elspeth J. R. Hill, MBChB, and Ida K. Fox, MD, surgeons from Washington University in St. Louis, Missouri, who also perform this procedure, note that nerve transfers “represent a huge advance in reconstruction to restore hand function following spinal cord injury.”

   “Nerve transfers are a cost-effective way to harness the body’s innate capability to restore movement in a paralyzed limb,” they write. Reached for comment, Fox described the results shown in the current report as “phenomenal for patients.”

   “They can go from not being able to use their hands at all to being able to conduct everyday tasks needing fine motor control such as making a drink, holding onto a cup, using a computer keyboard, smartphone, and television remote control. That is a real game changer,” she told Medscape Medical News.

   Fox said the current article was “ground breaking” as it “diligently documents the benefits, which can take several years to become apparent.” “The nerves take time to re-innervate the target muscles, but also time is needed for motor re-education and cortical remodeling. The brain has to figure out how to use the rewired muscles again. “This paper documents the largest series and longest follow-up so far reported. I think this publication will make a difference and this option will be now be considered more widely.

   “Too often desperate patients pay for procedures that have not been proven, but this approach now has good data behind it. This is compelling work — people can see clearly that it works and has a good success rate,” said Fox. However, she added, It’s important to select the right patients, the right surgeon, the right nerves to transfer, and make sure the patient gets the right aftercare — with dedicated physiotherapy a crucial part of the process.”


Not All Patients Are Candidates

   Van Zyl pointed out that the technique is not applicable to all patients with spinal cord injury. “The patients we describe here had C5 or C6 injuries. It probably would not work in those with injuries further up — if there is no movement in the shoulder then the functioning nerves will not be available. But C5 and C6 are the most common type of spinal cord injuries.”

   “Patients need to have some nerve function to steal,” said Fox. As for the timing of the surgery, Van Zyl said earlier is probably better.

   “Around 6 months post-injury is thought to be optimum, but I have some patients for whom this technique has been successful many years after injury,” she said. “If the muscle can be stimulated by an electrode then the nerve junction with the muscle is still functioning and we can transfer into that.”

   This technique is only offered at a few centers worldwide. Van Zyl’s team has been doing it the longest. She advises surgeons considering it to start with rerouting the nerve supplying the supinator muscle to the posterior interosseous nerve to restore hand opening. “We have gotten incredible results with this procedure and hand opening cannot be achieved with tendon transfer. Some centers are just offering this one procedure.”

   Van Zyl said her hope is that this study will encourage more surgeons to do these procedures and raise awareness of the whole area of both nerve and tendon transfer.

   “Many people think that there is nothing that can be done to improve hand function for patients with tetraplegia,” she said, “but actually great results are achievable with these techniques.”

Courtesy : Medscape