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Dr. Joseph Lorenzo

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  1. Calcium consumption in the diet is essential for bone health. However, the type and amount of calcium that must be consumed to prevent skeletal disease and maintain overall health is controversial. A series of studies have recently reported that consumption of supplemental calcium, but not calcium in foods, was associated with an increased risk of cardiovascular events, including myocardial infarction (1, 2). In contrast, other studies failed to demonstrate that calcium supplements caused an increased risk of cardiovascular events (3, 4). Clearly, this field is controversial and has genera
  2. Bone research, like other forms of science, occurs because dedicated individuals believe that scientific discovery is a noble calling that will reward society with new insights into normal and pathologic bone physiology and new therapies for bone diseases. However, even the most committed scientist would be helpless without funding agencies, which provide the resources that are the mother’s milk of all research. There are many sources of research support. These include philanthropic organizations, industry, local and state governments and the support of one’s own academic institution. Howe
  3. Biologic science is in the middle of a revolution, which is providing researchers with amazing tools to understand gene functions. Foremost among these are the rapidly evolving developments in genetic engineering. It is now commonplace for scientists to examine mice with global or targeted deletion of specific genes. It is also now possible to develop inducible and targeted gene deletion models that allow controlled temporal removal of genes. These models are almost always developed in mice because of the availability of appropriate reagents and their lower costs compared to larger mammals
  4. Like many of you, I spent last week writing and editing scientific abstracts for the next ASBMR annual meeting in September, which were due on Wednesday April 13th. It is always a challenge for me to organize all the experiments of a project and integrate them into a compelling story. Abstract writing is an art unto itself. To do it well, one basically needs to reduce the content of an entire scientific manuscript into 2500 characters. For even the best scientist this is often difficult. Having reviewed my fair share of abstracts, I know from a reviewer’s standpoint that the best abstracts
  5. My younger (and much better-looking) sister was interviewed for the New York Times Business Section this weekend (1). For the last ten years or so she has run a growing industrial design firm. Her company specializes in creating "new media", which is a term that describes web pages and the interfaces that are commonly used by household gadgets to interact with the computers they almost ubiquitously contain. As Chief Executive Officer of her company, Doreen supervises designers and multiple other creative people in studios around the world. In the article she describes the methods that she
  6. Over the last few days I have watched the events transpiring in northern Japan with great sadness. Like many of you, I have spent my career studying the mechanisms that govern cellular function at a molecular scale. However, every once in a while events transpire, which remind us that nature can also generate enormous forces that produce dire consequences. Such an event occurred on March 11, 2011 in northern Japan. For many of us who do not live in earthquake-prone regions, the whole concept of an unstable earth may be somewhat abstract. My own limited experience with earthquakes occurred
  7. Bisphosphonates are the principal class of medications that are used to treat and prevent osteoporosis. They are effective therapies, which significantly decrease the rate of osteoporotic fractures. However, they also may produce untoward effects. Recently, an increased incidence of subtrochanteric and mid-shaft femoral fractures was identified as a potential risk of these medications. This is a significant problem, which is associated with substantial morbidity and often requires surgical intervention. The ASBMR recently commissioned a Task Force to study this issue (1). In their final r
  8. In a series of papers in the 1940s Fuller Albright demonstrated that bone loss accelerates after menopause and estrogens have beneficial effects on the skeleton (1, 2). Since then, numerous studies have identified multiple potential mechanisms by which estrogens regulate skeletal mass (3). It is now known that estrogens influence the function and the rate of apoptosis of osteoblasts, osteocytes and osteoclasts, skeletal responses to parathyroid hormone, the immune system and its production of cytokines that affect bone cells and oxidative stress in the bone microenvironment. As a consequenc
  9. A recent New York Times (1) article commented about a paper in The New England Journal of Medicine (2), which described the anxiety and behavioral effects that subjects experienced after undergoing a genome-wide genetic analysis that determined their risks for developing a number of common diseases. In the study more than 2000 subjects were recruited to send saliva samples to a commercial lab that performed a genome-wide SNP analysis on their DNA. Participants received a discounted price for this service, which varied from 0 to $470. Each participant received a 90-page report that outlined
  10. Last weekend I had the opportunity to attend the Consumer Electronics Show in Las Vegas. I had always wanted to go to this event because, like a lot of people, I am fascinated by technology and being there allowed me to learn, first hand, which new electronic gadgets would be available in the next year or so. I had many impressions of the event. The number of people who attended (approximately 140,000) was overwhelming. All of the venues were very crowded. The most notable theme of the show was the integration of the Internet with almost every electronic device. This was most apparent
  11. Since this will be my last blog of 2010, I thought that it would be appropriate for me to review this year's events in skeletal biology research as reflected in previous blogs. First of all, I would like to say that it has been my honor to be able to write this blog. I thank the member of the Society for allowing me to have this forum. I hope that my contributions have been kindly received and provide some clarification about important issues. I started the blog in March and this is now my thirtieth entry. Over that time I have written about a variety of topics. As I look back on the t
  12. An interesting article appeared in this week's New Yorker magazine by Jonah Lehrer entitled "The Truth Wears Off" (1). The article is about proving scientific truth. In it the author describes how the magnitude of the differences between groups in scientific studies, which appear to be rigorously performed, often become less dramatic or disappear in latter studies. There are a number of reasons for why this might occur. The most obvious is that even though difference between experimental groups may achieve some level of statistical significance (typically p0.05), additional testing with a
  13. "The message is that there are known "knowns." There are things we know that we know. There are known unknowns. That is to say there are things that we now know we don't know. But there are also unknown unknowns. There are things we do not know we don't know." Donald Rumsfeld, former United States Secretary of Defense Over the last 10 to 15 years there has been a growing trend by health care providers to be concerned about deficiencies in vitamin D and calcium. It has long been established that these nutrients are vital for bone health. However, a large body of data has also demonstrated
  14. Money is viewed in a variety of different ways, ranging from a necessary evil to a highly prized goal. In the hit play "Cabaret", the character known only as "The Emcee" sang about how it "makes the world go round" (1). In our field it is the "mothers milk" of all research activities since without it investigations are usually impossible. Hence, many of us spend great amounts of time looking for ways to generate money or worrying about how to stretch the funds that we have to achieve the research that we want to perform. Because it is both the medium by which science can progress and a pot
  15. This past week's Annual Meeting of the ASBMR was marked by some great science and a number of controversies. There were at least two sessions, which I am aware of, where investigative teams, who had proposed paradigm-shifting hypotheses, had their theories challenged by the results of subsequent experiments. In both cases another group, either failed to reproduce the original data upon which the novel paradigm was based or produced results that directly challenged the conclusions of the novel paradigm. As might be expected, these presentations generated some heated discussions and much pass
  16. Receptor Activator of NF kB Ligand (RANKL) is a cytokine that is probably best known to the members of the ASBMR for its role as a stimulator of the terminal differentiation of osteoclast progenitor cells and the maintenance of bone resorption by mature osteoclasts. Proof of its critical role in bone resorption comes from studies demonstrating that osteoclasts do not form in mice, lacking either RANKL (1) or its receptor RANK (2). The unique ability of RANKL to stimulate osteoclast formation and bone resorption in most physiologic and pathologic states is the basis for the development of dru
  17. Last week the ASBMR Task Force on Atypical Femoral Fractures released its report (1). This group found that the long-term use of bisphosphonates may be related to unusual but serious atypical femur fractures. The task force reviewed 310 cases of "atypical femur fractures," and found that 94 percent (291) of patients with this condition had taken a bisphosphonate. Furthermore, most had taken one of these drugs for more than five years. There are many problems with this type of analysis and the Task Force was well aware of this. Their primary recommendation was for the development of better
  18. This week a report by Green et al (1) finds that the risk of esophageal but not stomach or colorectal cancer was significantly increased in individuals who were given prescriptions for oral bisphosphonates between 1995 and 2005. The study comes from a nested case-controlled analysis of patients in the United Kingdom who were treated with any of a number of oral bisphosphonates and enrolled in the General Practice Research Database. Each patient with a diagnosis of esophageal, stomach or colorectal caner was paired with five control patients who were matched for age, gender, participa
  19. There continues to be concern in the bone community about whether calcium supplements cause an increased risk of cardiovascular events. My two previous blogs on this topic remain popular, with the first having had over 1500 “hits” and the second over 425. There have also been many comments by readers about the first of my blogs on this topic, which was written in response to an article by Bolland et al (1). These represent a mix of views concerning whether Bolland et al made a convincing argument that calcium supplements increased the risk of myocardial infarction. In the absence of a cons
  20. Lawrence Gideon Raisz, my friend, mentor and colleague died on August 25th, 2010. He was 84 years old. It is not an exaggeration to state that there are few of us in this field who were not touched in some way by the life and career of this remarkable man. Larry's achievements are numerous. After graduating from Harvard College and Harvard Medical School in 1947, he did his internship and residency training on the Harvard service of the Boston City Hospital and the Boston VA hospital. His initial research training in nephrology was in the Department of Physiology at New York University
  21. Last week my blog described the results of a meta-analysis by Bolland et al that was published in the British Medical Journal (1). This paper examined the effects that calcium supplements had on the risks for cardiovascular events and concluded that there was approximately a 30% increase in myocardial infarction in those individuals consuming calcium compared to those consuming placebo. As many of you are aware, this is a topic that has generated much controversy. It is widely believed that calcium intake is inadequate for many people. The National Institutes of Health in the United State
  22. A recent article by Bolland MJ, et al in the British Medical Journal (http://www.ncbi.nlm.nih.gov/pubmed/20671013) suggests that the use of calcium supplements is associated with an increased risk of cardiovascular events. These authors performed a meta-analysis of 11 studies, containing a total of about 12,000 participants. All the included studies compared the effects of calcium supplementation to those of placebo in a blinded prospective manner. Analysis was restricted to studies that did not also add vitamin D to the regimens of the treatment or placebo groups. Results in which patient
  23. I make my living as a physician-scientist. Superficially, it would seem that these two worlds are vastly different. However, this is not necessarily the case. Ultimately, success at both comes down to mastering the same fundamental skills. I thought that I would list some of these this week. 1) Develop and prioritize clear and testable hypotheses to explain observed phenomena. I cannot overemphasize how important it is to focus one's thinking when approaching a scientific or medical question. The world is full of interesting potential mechanisms for how an observed phenomenon might
  24. Someone called me an expert in bone biology the other day, which always makes me feel uncomfortable. My definition of an expert is someone who is less ignorant about a topic than most others. In truth, there are too many questions about our field that remain unanswered for me to think of anyone as an expert. Despite the tremendous advances in both clinical and basic bone biology that have been achieved, we have far from a complete understanding of how the skeleton forms and what signals cause it to be diseased. Therefore, I thought that this week I would list some of the important question
  25. There are now a large number of articles, which have compiled statistics for the annual incidence of hip fractures in a variety of countries including the United States (http://www.ncbi.nlm.nih.gov/pubmed/20484751, http://www.ncbi.nlm.nih.gov/pubmed/19826027, http://www.ncbi.nlm.nih.gov/pubmed/19484169), Canada (http://www.ncbi.nlm.nih.gov/pubmed/19706862), Denmark (http://www.ncbi.nlm.nih.gov/pubmed/19436931) and Finland (http://www.ncbi.nlm.nih.gov/pubmed/17002578). The studies examined the rate that patients were admitted to hospitals with the diagnosis of a hip fracture and, for the most
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