An article published in The Lancet today reports that apixaban is a more convenient and effective anticoagulant than enoxaparin. It is better at preventing venous thromboembolism after knee replacement surgery. Also, apixaban does not increase the risk of bleeding. This is an essential concern with anticoagulants since this can hinder recovery and predispose patients to infections that could damage the prosthesis.

Presently, the existing prophylactics such as heparins (like enoxaparin) or other drugs (such as fondaparinux) need regular injections. Furthermore, the use of warfarin has various disadvantages in routine practice, and mechanical methods are burdensome.

Michael Rud Lassen, Department of Orthopaedics, Horsholm Hospital, University of Copenhagen, Denmark, and colleagues investigated to determine whether apixaban would be better than enoxaparin in both keeping thromboembolism and bleeding to a minimum. They undertook a randomized controlled phase 3 trial. The patients either received 2.5 mg of apixaban twice daily or 40 mg enoxaparin once daily. The primary outcome was a composite of deep vein thrombosis, non-fatal pulmonary embolism, and death from any cause.

A total of 147 patients (15 percent of 976) on apixaban and 243 (24 percent of 997) on enoxaparin had a primary outcome event. This showed a statistically significant difference. There was no noteworthy disparity between the groups in the bleeding during treatment.

The authors explain: “2•5 mg apixaban twice daily, starting on the morning after total knee replacement, offers a convenient and more effective orally administered alternative to 40 mg per day enoxaparin, without increased bleeding.”

They say in closing: “These favourable results might help surgeons to resolve their clinical dilemma when considering anticoagulant prophylaxis for total knee replacement. Bleeding can delay recovery and can predispose to infections that endanger the prosthesis. The small but occasionally important increase in surgical bleeding that is attributed to enoxaparin can contribute to underuse of effective prophylaxis.”

In an associated note, Dr Jawed Fareed, Department of Pathology, Loyola University Medical Center, Maywood, IL, USA, and Dr Russell Hull, University of Calgary, Calgary, Canada comment: “we are potentially a step closer to the unmet need of oral antithrombotic therapy without need for monitoring.”

They write in conclude: “The ideal prophylactic drug would reduce the frequency of postoperative venous thromboembolism without causing bleeding and other complications in patients postoperatively. An ideal drug does not yet exist. The balance is fairly simple: a stronger anticoagulant effect is associated with fewer thrombotic events, but with a cost of increased occurrence of bleeding.”

“Apixaban versus enoxaparin for thromboprophylaxis after knee replacement (ADVANCE-2): a randomized double-blind trial”

To monitor the real-time performance of bone implants is the challenge of “Smart Hip”, an innovative medical device that aims to reduce the number of surgical interventions in the hip area and regenerate bone tissue by using non-evasive methods. The concept’s validation unique in the world and developed by a PHD from the Faculty of Engineering of the University of Porto, has already been successfully tested on animals.

It is estimated that there are about a million surgeries in Europe and USA in the hip joint, and that 5% to 10% of these surgeries eventually generates further health problems, which usually demands a new surgery for review. But the solution to this problem may now be closer.

Clara Frias a 29-year-old PhD in Engineering Sciences from the Faculty of Engineering of University of Porto (FEUP) and researcher at the Institute of Mechanical Engineering and Industrial Management (INEGI) has just created an “intelligent” hip. This worldwide innovative device is able to detect eventual implant’s problems through the application of capsules and hip sensors. This will help to stimulate the bone growth and, therefore, improve the quality of life for patients, reducing the risk surgery.

The “Smart Hip” is a network of capsules, measuring sensors and actuators that are placed on the hip implant. Once activated by the doctor trough a computer connected to a Bluetooth device the “Smart Hip” components send information that will prevent eventual problems after the surgery and the actuators stimulate the needed bone growth. At this point, the device looks or the implant’s validation and development, that monitors its performance in real-time and, additionally, works directly in the bone growth.

In addition, says Clara Frias, “a network of actuators capable of stimulating bone growth at the implant’s surface is being developed”. This network, as well as the network of sensors, will be externally controlled, trough a wireless system, by a physician. The concept has been validated in a study cell and was recently tested in animals, with “very encouraging results” adds the researcher.

According to a new study accepted for publication in The Endocrine Society’s Journal of Clinical Endocrinology & Metabolism (JCEM), obese teenage girls with a greater ratio of visceral fat (fat around internal organs) to subcutaneous fat (fat found just beneath the skin) are likely to have lower bone density than peers with a lower ratio of visceral to subcutaneous fat.

“Visceral fat is known to increase the risk of diabetes and heart disease in obese people,” said Madhusmita Misra, MD, of Massachusetts General Hospital and senior author of the study. “Our study suggests that visceral fat may also have an impact on bone health. This finding is particularly relevant given the rising prevalence of obesity and recent studies suggesting a higher risk of fractures in some obese individuals.”

In this study, researchers examined 30 adolescent girls (15 obese/15 normal weight) between the ages of 12 and 18 years. After measuring weight and height, researchers used magnetic resonance imaging (MRI) to measure subcutaneous and visceral fat tissue and dual energy x-ray absorptiometry (DXA) to assess bone density at the spine, hip and whole body. They found that subcutaneous fat and visceral fat had reciprocal associations with bone density measures, with subcutaneous fat demonstrating positive associations and visceral fat demonstrating inverse associations.

“We do not yet fully understand the chemical mediators of the associations between regional fat and bone health,” said Misra. “It is possible that inflammatory cytokines, types of signaling molecules used in cellular communication, or hormones like adiponectin or leptin are potential mediators of these associations between fat and bone, but further studies are needed to determine their true impact on bone metabolism.”

Bones, muscles and tendons work together to provide the perfect balance between stability and movement in the skeleton. Now, Weizmann Institute scientists show that this partnership begins in the embryo, when the bones are still taking shape. The study, published in a recent issue of Developmental Cell, describes a previously unrecognized interaction between tendons and bones that drives the development of a strong skeletal system.

‘Our skeleton, with its bones, joints and muscle connections serves us so well in our daily lives that we hardly pay attention to this extraordinary system,’ says Dr. Elazar Zelzer of the Weizmann Institute’s Molecular Genetics Department. ‘Although previous research has uncovered mechanisms that contribute to the development and growth of each component of this complex and wonderfully adaptable organ system, specific interactions between bones, muscles and tendons that drive the assembly of the musculoskeletal system are not fully understood.’

Zelzer, research student Einat Blitz, Sergey Viukov and colleagues, were interested in uncovering the molecular mechanisms that regulate the formation of bone ridges – bony protuberances that provide a stable anchoring point for the tendons that connect muscles with bones. Bone ridges are critical for the skeleton’s ability to cope with the considerable mechanical stresses exerted by the muscles. The researchers used embryonic mouse skeletons to study a bone ridge called the deltoid tuberosity, located on the humerus bone in the arm.

They discovered, to their surprise, that rather than being shaped by processes within the skeleton, bone-ridge formation was directly regulated by tendons and muscles in a two-phase procedure. First, the embryonic tendons initiated bone-ridge formation by attaching to the skeleton. This interaction induced the tendon cells to express a specific protein called scleraxis, which in turn, led to the production of another protein, BMP4 – a molecule involved in the onset of bone formation. Blocking BMP4 production in tendon cells prevented deltoid tuberosity bone ridge formation. In the second phase, the subsequent growth and ultimate size of the deltoid tuberosity was directly regulated by muscle activity.

The results demonstrate that tendons play an active role in initiating bone ridge patterning. Zelzer: ‘These findings provide a new perspective on the regulation of skeletogenesis in the context of the musculoskeletal system, and they shed light on an important mechanism that underlies the assembly of this system.’

Treatments for osteoporosis (a disease characterized by reduced bone density, which leads to an increased risk of fracture) need to increase the amount and/or quality of bone. As bone formation is tightly coupled to bone destruction, researchers looking to develop new approaches to build bone in individuals with osteoporosis need to identify ways to separate the two processes. Natalie Sims and colleagues, at St. Vincent’s Institute, Melbourne, Australia, have now identified one way to do this in mice.

In the study, the molecule oncostatin M (OSM) was found to induce distinct functions in mice upon binding to two different cell surface proteins. When OSM bound OSMR it stimulated the production of cells that destroy bone. Consistent with this, mice lacking OSMR were found to have increased bone density. However, when OSM bound LIFR it blocked production of a protein that inhibits bone formation. Importantly, OSM acting via LIFR did not stimulate the production of cells that destroy bone. These data indicate the existence of a pathway by which bone formation can be stimulated independently of bone destruction.

Holiday shopping and holiday feasting may make you a prime candidate for a case of plantar fasciitis. Prolonged walking or standing and an increase in body weight are two leading causes of plantar fasciitis, a painful overuse injury affecting the sole of the foot, warns the American Orthopaedic Foot & Ankle Society (AOFAS).

According to the AOFAS, plantar fasciitis typically starts gradually with mild heel pain. The pain classically occurs with the first step in the morning. Treatment options include stretching exercises, and modifying activities until the initial inflammation goes away. Ice application to the sore area for 20 minutes three or four times a day may also relieve symptoms. Your orthopaedic surgeon may also prescribe a non-steroidal anti-inflammatory medication. But your best course of action is a routine of home exercises to stretch the Achilles tendon and plantar fascia.

Benedict DiGiovanni, MD, Associate Professor, Department of Orthopaedics at the University of Rochester Medical Center (NY) and active AOFAS member, treats many patients with plantar fasciitis. He offers the following suggestions on treatment options. “A key component of a plantar fascia specific stretching program is when it is performed and how often. Based on findings from our research work, I instruct patients to perform the stretch prior to the first step in the morning and prior to weight bearing after periods of inactivity, such as sitting for lunch or driving in the car. Most patients will perform the stretch 4 – 5 times per day for the first month of treatment, and then as needed based on symptoms. Patients are also instructed to stretch the Achilles tendon twice a day, morning and evening. In addition to stretching exercises, we suggest ice, over the counter anti-inflammatory medicine, and inexpensive over the counter soft arch supports.”

Plantar fasciitis has been known to side-line major league athletes such as the recent case with New York Giants quarterback Eli Manning. Ninety percent of people with plantar fasciitis improve significantly after two months of initial treatment. Shoes with shock-absorbing soles or over the counter arch supporting inserts may help alleviate pain. Another treatment protocol is taping the foot to support the arch and plantar fascia. If heel pain continues after a few months of conservative treatment, your orthopaedic surgeon may suggest heel injections with steroidal anti-inflammatory medications. Walking casts or positional splints are other options for treatment of plantar fasciitis.

Treatment of plantar fasciitis is important because it has the potential of turning into a chronic condition. Plantar fasciitis may prevent you from keeping up with your current level of activity and you may also develop symptoms of foot, knee, hip and back problems because of the way plantar fasciitis changes the way you walk.

Nearly half of women using depot medroxyprogesterone acetate (DMPA), commonly known as the birth control shot, will experience high bone mineral density (BMD) loss in the hip or lower spine within two years of beginning the contraceptive, according to researchers at the University of Texas Medical Branch at Galveston.

The study, reported in the January 2010 issue of Obstetrics and Gynecology, was the first to show that women on DMPA who smoke, have low levels of calcium intake and never gave birth are at the highest risk for BMD loss. The researchers also found that high risk women continued to experience significant losses in BMD during the third year of DMPA use, especially in the hip – the most common facture site in elderly women.

DMPA is an injected contraceptive administered to patients every three months. According to the American College of Obstetricians and Gynecologists, more than two million American women use DMPA, including approximately 400,000 teens. DMPA is relatively inexpensive compared with some other forms of birth control, has a low failure rate and doesn’t need to be administered daily, which contributes to the contraceptive’s popularity.

“Bone mineral density loss is not a significant concern for all women who choose DMPA,” says senior author Dr. Abbey Berenson, professor in the department of obstetrics and gynecology and director of the Center for Interdisciplinary Research in Women’s Health at UTMB.

According to Berenson, over the last several years there’s been a fair amount of confusion about how to counsel patients. “Based on these findings, clinicians have the information they need to recommend basic behavior changes for high risk women to minimize BMD loss,” she said.

The study followed 95 DMPA users for two years. In that time, 45 women had at least five percent BMD loss in the lower back or hip. A total of 50 women had less than five percent bone loss at both sites during the same period.

By and large, BMD loss was higher in women who were current smokers, had never given birth and had a daily calcium intake of 600 mg or less – far below the recommended amounts. Moreover, BMD loss substantially increased among the women with all three risk factors. Age, race or ethnicity, previous contraceptive use and body mass index were not associated with higher BMD loss.

The researchers followed 27 of the women for an additional year and found that those who experienced significant BMD loss in the first two years continued to lose bone mass.

“These losses, especially among women using DMPA for many years, are likely to take an extended period of time to reverse,” says first author Dr. Mahburbur Rahman, assistant professor in the department of obstetrics and gynecology and Center for Interdisciplinary Research in Women’s Health.

New research from the US has discovered that women who used bisphosphonates, commonly-prescribed bone-strengthening drugs, had significantly fewer invasive breast cancers than women who did not use them.

The study is the work of lead investigator Dr Rowan Chlebowski, medical oncologist at the Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center (LA BioMed), and colleagues, and the findings are being presented at the 32nd San Antonio Breast Cancer Symposium in Texas this week from 9 – 13 December. The symposium is presented by the CTRC (Cancer Therapy & Research Center), AARC (American Association for Cancer Research), and the Baylor College of Medicine.

“The idea that bisphosphonates could reduce breast cancer incidence is very exciting because there are about 30 million prescriptions for these agents written annually in the US targeting bone health, and more could easily be used to counteract both osteoporosis and breast cancer,” Chlebowski told the media.

For the study, Chlebowski and colleagues re-analyzed data from the Women’s Health Initiative (WHI), a large observational study set up by the National Institutes of Health (NIH) in 1991 to examine the most common causes of death, disability and impaired quality of life in postmenopausal women. The WHI collected information on cardiovascular disease, cancer, and osteoporosis.

In the 150,000-plus cohort of generally healthy postmenopausal women, the researchers found 32 per cent fewer cases of invasive breast cancer among women who used bisphosphonates (mostly alendronate, marketed as Fosamax by Merck), compared to women who did not use such drugs.

What prompted the study were the findings of a report from a breast cancer trial that suggested bisphosphonate zoledronic acid given intravenously every 6 months resulted in fewer cancers in the other breast.

Chlebowski said that:

“It appeared to make bone less hospitable to breast cancer.”

In deciding how to devise the study, the researchers had to find a way to control for bone density, since that in itself is a risk factor for breast cancer. In other words they had to devise a way to control for potential differences between the women prescribed bisphosphonate and those not prescribed bisphosphonate, because those on the bone-strengthening drugs were on it because they had low bone mineral density, which is linked to lower breast cancer incidence.

They found that about 10,000 of the cohort had their bone mineral density analyzed as part of the WHI study, and for the others, including those prescribed bisphosphonates, the researchers used a 10-item hip fracture predictive score to measure bone density.

Thus they were able to correlate the results of bone mineral density tests in the 10,000 who had the tests with the predictive score in order to correct for any potential difference in bone density in women using bisphosphonates compared to those who did not use them.

Thus prepared, Chlebowski and colleagues then studied data on 2,216 women who were using bisphosphonates when they entered the WHI study.

The results showed that:

* Only 64 of the bisphosphonate users developed breast cancer, and most of the cases, (50 of them), were estrogen-receptor positive.

* Overall there was an average of 32 per cent fewer breast cancers among bisphosphonate users compared to non-users.

* There were 30 per cent fewer estrogen-receptor positive cancers and 34 per cent fewer entry-receptor negative cancers among bisphosphonate users, although the latter finding was not statistically significant due to low numbers.

Speculating on what effect bisphosphonates might have to cause fewer breast cancers, Chlebowski said it could be because the drugs discourage blood vessel formation (which tumors rely on to grow), and help the immune system:

“Bisphosphonates reduce angiogenesis and stimulate immune cells responsible for tumor cell surveillance as potential mediators,” explained Chlebowski.

He said we need to study this link in more detail, because “while we currently have several options for reducing receptor positive breast cancers, none are available for receptor negative cancers”.

Other studies presented at the symposium pointed to a similar link between bisphosphonate use and lower breast cancer risk, and a number of breast cancer trials evaluating oral and intravenous uses of the drug are about to report randomized clinical trial evidence on it.

A virus that in nature infects only rabbits could become a cancer-fighting tool for humans. Myxoma virus kills cancerous blood-precursor cells in human bone marrow while sparing normal blood stem cells, a multidisciplinary team at the University of Florida College of Medicine has found. The findings are now online and will appear in an upcoming issue of the journal Leukemia.

The discovery could help make more cancer patients eligible for bone marrow self-transplant therapy and reduce disease relapse rates after transplantation.

“This is a new strategy to remove cancer cells before the transplant,” said virologist Grant McFadden, Ph.D., senior author of the paper and a member of the UF Genetics Institute. “This is the first time anyone has shown in a living animal that a virus can distinguish normal bone marrow stem cells from cancerous stem cells.”

The major therapeutic applications will likely be for blood cancers such as leukemia, lymphoma and bone marrow cancers, the researchers say.

In mouse studies, myxoma virus was used to purge cancerous cells from leukemia patient bone marrow samples before they were infused into the test animals. The technique was effective against an aggressive form of leukemia that is resistant to conventional chemotherapy.

Microorganisms have been used to fight cancer before. More than 100 years ago, physicians treating patients who had bone and head and neck cancers used mixtures of bacteria to jumpstart the immune system, which also happened to attack the cancer. While the approach helped some people it sometimes also caused harm.

Today, patients who have certain types of cancer such as acute myelogenous leukemia are usually treated with using high doses of chemotherapy. But that can destroy the patient’s own immune system unless he or she receives a transplant of blood stem cells, which can be from the patient’s own marrow samples or from a donor.

Although reinfusion of a patient’s own bone marrow stem cells is generally safer in the short run, those patients are at high risk of dying from return of disease because of leukemia contaminating the infused bone marrow.

“That’s one of the major frustrations, so we’re looking for ways to clean these stem cells before putting them back into patients,” said Christopher R. Cogle, M.D., an assistant professor in the division of hematology and oncology and a leader of the research team.

A new study using solid-state NMR spectroscopy to analyze intact bone paves the way for atomic-level explorations of how disease and aging affect bone.

The research by scientists at the University of Michigan is reported in the Dec. 2 issue of the Journal of the American Chemical Society.

“If people think of bone at all—and they usually don’t, until they have a fracture—they think of it as an inert material,” said Ayyalusamy Ramamoorthy, professor of chemistry and of biophysics. “But like everything else, bone is also made up of molecules whose behavior is reflected in its structure, toughness and mechanical strength, making bone really exciting in terms of its chemistry and its contribution to health and well-being,”

As scientists strive to understand the human body and its diseases in terms of molecular behavior, bone presents a challenge to most analytical techniques. “However, solid-state NMR spectroscopy is an ideal tool for exploring what goes on inside bone at nanoscopic resolution,” Ramamoorthy said. “It is possible to probe the structure and dynamics of individual molecules that constitute bone without any physical damage or chemical modification.”

But while solid-state NMR spectroscopy is capable of revealing complete nanoscopic details of molecular events from most samples, it often provides so many details that they’re difficult to tease apart and analyze. Ramamoorthy, whose children are fans of the Magic School Bus science series, challenged his lab group to find ways of “driving around” to explore the interior of bone, just as characters on the series might in their imaginary world. The researchers’ real-world approach involved a different kind of magic.

Ramamoorthy and colleagues used a variation of solid-state NMR (nuclear magnetic resonance) spectroscopy called magic-angle spinning, a non-invasive technique that makes solid material as amenable to analysis as solutions are. Previous NMR studies have used pulverized bone, but the U-M group’s instruments and methods made it possible to analyze a sample of intact cow bone. The bone sample was shaped to just fit the rotor that is spun at the so-called magic angle inside the probe of a solid-state NMR spectrometer.

With this technique, the researchers examined changes that occur in bone with water loss. The water content of bone tissue decreases with age, which—by affecting both collagen and minerals—reduces bone’s strength and toughness.

“We were able to see dynamical structural changes with the main protein, collagen,” Ramamoorthy said. “Its characteristic triple helix structure was not completely damaged, but its mobility was altered, in addition to a disorder in the structure.”

The success of the study makes possible future research into how bone’s constituents behave under different conditions.

“We’d like to look at how bone changes at the atomic level, as a function of aging,” Ramamoorthy said, “and to make comparisons between diseased and healthy bone.” Such studies may provide insights into the susceptibility of bone to fracture, especially in the osteoporotic tissues of many elderly people.