Elselijn Kingma argues that Christopher Boorse’s biostatistical theory does not show how the reference classes it uses—namely, age groups of a sex of a species—are objective and naturalistic. Boorse has replied that this objection is of no concern, because there are no examples of clinicians’ choosing to use reference classes other than the ones he suggests. Boorse argues that clinicians use the reference classes they do because these reflect the natural classes of organisms to which their patients belong. Drawing on (...) a thorough exploration of how the disease osteoporosis is defined in adults, I argue that clinicians do indeed make choices about which reference classes to use in diagnosis. Clinicians use young adult reference classes to diagnose osteoporosis in elderly patients. They also use young female reference classes to diagnose osteoporosis in elderly males. Clinicians adjust their reference classes so that the diagnosis of osteoporosis reflects a person’s risk of sustaining a fragility fracture. The ethical intuition that people with the same risk of fracture should receive the same diagnosis overwhelms the naturalistic intuition that reference classes should reflect natural classes of organisms of uniform functional design. Clinicians construct a variety of reference class types, including pathological reference classes and epidemiological population-specific reference classes, to serve this ethical intuition. I show how clinicians use several reference classes at once so that they can more accurately predict risk of fracture. Ultimately, the reference classes chosen and used in medical practice are quite different from those proposed in naturalistic philosophy of medicine. (shrink)

Osteoporosis is characterized by reduced bone density and strength. Bone mass peaks between age 30 and 40 and then declines. This can be accelerated by factors including menopause and insufficient dietary calcium. Hormone replacement therapy (HRT) is currently the standard treatment for osteoporosis. However, growing concern over potential side effects of HRT has driven a search for alternative therapies. A recent report1 reveals a potential alternative to HRT: a gender‐neutral synthetic steroid that increases bone mass and strength without (...) affecting reproductive organs. This compound acts via a novel extranuclear sex steroid receptor signaling mechanism that has important implications for nuclear receptor biology and human health. BioEssays 25:195–199, 2003. © 2003 Wiley Periodicals, Inc. (shrink)

Osteoporosis (OP) is a bone disease which affects a number of post‐menopausal females and puts many at risk for fractures. A large number of patients are taking bisphosphonates (BPs) to treat their OP and a rare complication is the development of atypical femoral fractures (AFF). No real explanations for the mechanisms underlying the basis for development of where AFF develop while on BPs has emerged. The present hypothesis will discuss the possibility that part of the risk for an AFF (...) is a secondary effect of BPs on a subset of vascular cells in a genetically at‐risk population, leading to localized deregulation of the endothelial cell (EC)‐bone cell‐matrix units in nutrient channels/canals of the femur and increased risk for AFF. This concept of targeting ECs is consistent with location of AFF in the femur, the bilateral risk for occurrence of AFF, and the requirement for long term exposure to the drugs. (shrink)

Rationale At the request of a Dutch governmental organization, a multidisciplinary group of osteoporosis experts in the Netherlands published in 2002 a guideline on case finding, diagnosis, prevention and treatment of osteoporosis. These guidelines were evaluated for their validity and applicability. Methods Analysis by 5 external osteoporosis experts using the 'Appraisal of Guidelines for Research & Evaluation' ('AGREE') instrument. Results The score for the 6 domains of AGREE was 88% for the scope and purpose domain, 76% for (...) stakeholder involvement, 81% for rigour of development, 84% for clarity and presentation, 77% for applicability and 73% for editorial independence. For single components of the domains of AGREE, highest scores were found for systematic methods used to search for evidence (100%), inclusion of individuals from all the relevant professional groups (95%) and ease of identifying key recommendations (95%). Lowest scores to single components of the several domains were given for piloting among target users (44%). All experts recommended the guidelines for use in practice. Conclusions The AGREE instrument scored high for development, clarity and presentation but low for piloting among target users and implementation. Based on the guideline, algorithms from case finding to treatment were constructed that could be tested for piloting among target users and for implementation of the guideline. (shrink)

At the dawn of the twenty-first century, osteoporosis is described as a major public health problem of pandemic proportions, affecting millions of people, and women in particular, around the globe. This situation is frequently described as a result of an aging population, but it is also a consequence of a substantial transformation of the medical understanding and definition of osteoporosis in the latter half of the twentieth century. In this article, the authors trace the transformation of a biologically (...) based understanding of the condition involving a few patients, to the current statistically based definition of osteoporosis from which only a few remain untouched. At the center of this development is the measurement of bone mineral density through densitometrics, combining the use of imaging techniques and statistical epidemiology. (shrink)

Osteoporosis, a disease of bone loss associated with aging and estrogen loss, can be crippling but is 'silent' prior to bone fracture. Osteoporosis lacked a universally accepted definition until 1992. In the 1980s, the development of more accurate medical imaging technologies to measure bone density spurred the medical community's need and demand for a common definition. The medical community tried, and failed, to resolve these differing definitions several times at consensus conferences and through published articles. These experts finally (...) accepted a standard definition at an international consensus conference convened by the World Health Organization in 1992. The construction of osteoporosis as a disease of quantifiable risk diagnosed by medical imaging machines reflects contemporary trends in medicine, including the quantification of disease, the risk factor model, medical disciplinary boundaries, and global standardization of medical knowledge. (shrink)

Osteoporosis, a disease of bone loss associated with aging and estrogen loss, can be crippling but is ‘silent’ prior to bone fracture. Despite its disastrous health effects, high prevalence, and enormous associated health care costs, osteoporosis lacked a universally accepted definition until 1992. In the 1980s, the development of more accurate medical imaging technologies to measure bone density spurred the medical community’s need and demand for a common definition. The medical community tried, and failed, to resolve these differing (...) definitions several times at consensus conferences and through published articles. These experts finally accepted a standard definition at an international consensus conference convened by the World Health Organization in 1992. The construction of osteoporosis as a disease of quantifiable risk diagnosed by medical imaging machines reflects contemporary trends in medicine, including the quantification of disease, the risk factor model, medical disciplinary boundaries, and global standardization of medical knowledge. (shrink)

Most people know precious little about the risks and benefits of participating in a clinical trial--a medical research study involving some innovative treatment for a medical problem. Yet millions of people each year participate anyway. Patients at Risk explains the reality: that our current system intentionally hides much of the information people need to make the right choice about whether to participate. Witness the following scenarios: -Hundreds of patients with colon cancer undergo a new form of keyhole surgery at leading (...) cancer centersnever -Tens of thousands of women at high risk of developing breast cancer are asked to participate in a major research study. They are told about the option of having both breasts surgically removed but not told about the option of taking a standard osteoporosis pill that might cut the risk of getting breast cancer by one-half or more. Patients at Risk written by two nationally prominent experts, is the first book to reveal the secrets that many in the research establishment have fought long and hard to keep from patients. It shows why options not commonly knownincluding getting a new treatment outside of a research studycan often be the best choice. It explains how patients can make good decisions even if there is only limited information about a treatments effect. And it does this through the eye-opening stories of what is happening daily to thousands of people. Day after day, we are learning how little we know about what really works. Headlines regularly announce that a previously unquestioned treatmenthormone replacement therapy, drugs such as Vioxx or Celebrexmay now be much riskier than we thought. The latest book in a surge of recent books criticizing the medical establishment (but the first to look at clinical trials specifically), Patients at Risk helps to empower patients to survive in a world of medical uncertainty, and makes positive recommendations for systemic reform. (shrink)

The US FDA currently encourages the addition of vitamin D to milk and cereals, with the aim of reducing rickets in children and osteoporosis in adults. However, vitamin D not only regulates the expression of genes associated with calcium homeostasis, but also genes associated with cancers, autoimmune disease, and infection. It does this by controlling the activation of the vitamin D receptor (VDR), a type 1 nuclear receptor and DNA transcription factor. Molecular biology is rapidly coming to an understanding (...) of the multiplicity of roles played by the VDR, but clinical medicine is having difficulty keeping up with the pace of change. For example, the FDA recently proposed a rule change that will encourage high levels of vitamin D to be added to even more foods, so that the manufacturers can claim those foods “reduce the risk of osteoporosis”. The FDA docket does not review one single paper detailing the transcriptional activity of vitamin D, even though, on average, one new paper a day is being published on that topic. Nor do they review whether widespread supplementation with vitamin D, an immunomodulatory secosteroid, might predispose the population to immune dysfunction. This BioEssay explores how lifelong supplementation of the food chain with vitamin D might well be contributing to the current epidemics of obesity and chronic disease. BioEssays 30:173–182, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

This article argues that the early Christian ?order of widows? provides a fruitful model for Christian ethicists struggling to address the medical and social problems of elderly women today. After outlining the precarious state of the ?almanah? - or widow - in biblical times, it describes the emergence of the order of widows in the early Church. Turning to the contemporary situation, it argues that demographics both in the United States and around the globe suggest that meeting the needs of (...) elderly women will become an enormous challenge in the years to come. The order of widows illustrates a three-fold conception of solidarity that has immediate implications today. That conception of solidarity encourages us: 1) to identify the unique medical needs of elderly women (e.g., osteoporosis); 2) to find ways of overcoming their societal isolation, which can increase their risk of medical and psychological problems; and 3) to develop strategies for enabling them to remain contributing members of the community for as long as possible. This essay is a slightly revised version of a keynote address given by the author at a conference on ?Women?s Health and Human Rights? held in Rome, Italy in February 1998 and sponsored by the Vatican, Georgetown University, and the Università Cattolica del Sacro Cuore. The proceedings of that conference were published in Italy by the Società Editrice Universo-Roma in a volume entitled Women?s Health Issues, edited by Spagnolo and Gambino (2003). (shrink)

Hedgehog is an important morphogenic signal that directs pattern formation during embryogenesis, but its activity also remains present through adult life. It is now becoming increasingly clear that during the reproductive phase of life and beyond it continues to direct cell renewal (which is essential to combat the chronic environmental stress to which the body is constantly exposed) and counteracts vascular, osteolytic and sometimes oncological insults to the body. Conversely, down‐regulation of hedgehog signalling is associated with ageing‐related diseases such as (...) type 2 diabetes, neurodegeneration, atherosclerosis and osteoporosis. Hence, in this essay we argue that hedgehog signalling is not only important at the start of life, but also constitutes an important anti‐geriatric influence, and that enhanced understanding of its properties may contribute to developing rational strategies for healthy ageing and prevention of ageing‐related diseases.Also watch the Video Abstract. (shrink)

The use of aggregated quality of life estimatesin the formation of public policy and practiceguidelines raises concerns about the moralrelevance of variability in values inpreferences for health care. This variabilitymay reflect unique and deeply held beliefs thatmay be lost when averaged with the preferencesof other individuals. Feminist moral theorieswhich argue for attention to context andparticularity underline the importance ofascertaining the extent to which differences inpreferences for health states revealinformation which is morally relevant toclinicians and policymakers. To facilitatethese considerations, we present (...) an empiricalstudy of preferences for the timing andoccurrence of health states associated withhormone replacement therapy (HRT). Sixteenwomen between the ages of 45 and 55 wereenrolled in this pilot study. Theirpreferences regarding five health statesassociated with HRT (menopausal symptoms, sideeffects of HRT, breast cancer, myocardialinfarction, and osteoporosis) were assessed inquantitative terms known as utilities. Twostandard methods, the visual analog scale (VAS) and the standard gamble (SG), were used toassess utility and time preference (calculatedas a discount rate). The wide variability ofresponses underlines the importance oftailoring health care to individual women'spreferences. Policy guidelines whichincorporate utility analysis must recognize thenormative limitations of aggregatedpreferences, and the moral relevance ofindividual conceptions of health. (shrink)

Aldehyde dehydrogenase 2 (ALDH2) deficiency constitutes one of the most common hereditary enzyme deficiencies, affecting 35% to 40% of East Asians and 8% of the world population. It causes the well-known Asian Alcohol Flush Syndrome, characterized by facial flushing, palpitation, tachycardia, nausea, and other unpleasant feelings when alcohol is consumed. It is also associated with a marked increase in the risk of a variety of serious disorders, including esophageal cancer and osteoporosis. Our recent studies with murine models have demonstrated (...) that a one-time administration of an adeno-associated virus (AAV) gene transfer vector expressing the human ALDH2 coding sequence (AAVrh.10hALDH2) will correct the deficiency state and prevent alcohol-induced abnormalities of the esophagus and bone. If successful in humans, such strategy would reduce the increased risk-associated disorders such as esophageal cancer and osteoporosis, but also prevent the Asian Alcohol Flush Syndrome. This treatment thus raises ethical concerns: although it would potentially prevent fatal disease, it could also allow affected individuals to drink alcohol without suffering the Asian Alcohol Flush Syndrome and, hence, potentially enable personal destructive behavior. Here we explore the ethical arguments against the development of a gene therapy for ALDH2 deficiency and we find them wanting. We contend that development of such treatments is ethically appropriate and should be part and parcel of the solutions offered against the condition. (shrink)

Introduction: Globally, vitamin D deficiency is one of the most common deficiencies, affecting nearly half the world's population. The objective of this survey was to assess and compare the knowledge about vitamin D and the perceived state of health in Emirati and international tourist female students in Dubai, UAE. Methods: This is a cross-sectional study that took place in universities in Dubai, UAE. This survey consisted of 17 multiple choice questions. The first part of the survey assessed levels of supplementation, (...) diet and UV exposure. Another section evaluated the participants’ self-assessed state of health regarding vitamin D testing, symptoms related to vitamin D deficiency and general welbeing. The collected data were statistically analyzed using SPSS statistics for windows version 26.0 (SPSS Inc., Chicago, IL). Statistical significance was set at P<0.05. Results: 105 respondents were Emiratis and 65 were international students. The average age was 21, with an average BMI 23.3. Almost one-third of each group reported using Vitamin D supplements once weekly. The majority of both groups reported rarely getting tanned. Almost all participants reported regular consumption of Vitamin-D rich foods. In both groups, more than half reported consuming milk and cheese regularly and up to one-third reported consuming fish in a regular manner. Although more than half of the students rated their health as good; more than two-thirds reported experiencing muscle pain; only half reported having their blood Vitamin D levels measured once; half reported experiencing problems with concentration and more than three-quarters reported experiencing bad mood in the past month. The prevalence of these symptoms was almost similar across different categories of vitamin D supplementation, tanning habits, dietary intake, or nationality. No statistically significant differences were noted between the 2 groups. Conclusion: more Emirati students were aware of the association between vitamin D and osteoporosis than International tourist students (40% vs. 21.9%, respectively; p<0.05). On the other hand, both groups had lower knowledge about the relationship between vitamin D deficiency and depression, Rheumatoid Arthritis and Hypertension, and the optimal vitamin D level; however, no statistically significant differences were noted regarding this knowledge of Emiratis and international students. (shrink)

Bisphosphonates are a class of drugs which have shown good efficacy in the treatment of post‐menopausal osteoporosis, as well as a good safety profile. However, side‐effects such as risk for atypical femoral fractures (AFF) have appeared, leading to a decline in use of the drugs by many patients who would benefit from the treatment. While patient characteristics have contributed to improved understanding of risk factors, the mechanisms involved that explain AFF risk have not appeared. Recently, the possibility that the (...) mechanism(s) involved drug‐induced modification of cells of the nutrient canals of the femur and subsequent compromise in the bone matrix has been published. The present Hypothesis article builds on the concept presented earlier and expands into biomechanical considerations. An analogy of the mechanisms involved to a real‐life scenario is also presented. While this analogy has limitations, consideration of the biomechanical implications of progressive alterations to defects presented by compromised nutrient canal‐bone matrix also presents potential relationships with AFF risk. (shrink)

Mrs. P is a seventy‐six‐year old woman with osteoporosis and a failed left hip prosthesis. In addition, she has severe chronic asthmatic bronchitis. The management of her lung disease has been hampered by her allergy to theophylline, which is one of the mainstays of treatment. As a result, she has had increasing difficulty walking and confinement to a wheelchair is imminent. When surgery to replace the prosthesis was recommended, Mrs. P expressed concern about the possibility of ending up after (...) the operation dependent on a ventilator, possibly comatose. She feared that her resources would be depleted for medical expenses. Little or nothing would be left to pass on to her children. She was willing to have an operation only if she could prepare a legal document that, in the event of prolonged ventilator dependence, would require her physician to remove her from the ventilator after a specified time (for example, two weeks). Should the surgeon agree to be bound by Mrs. P's instructions, or should he refuse her request even if doing so means that she will not have the surgery that might prevent increasing disability? (shrink)

Although we are likely unaware of it, in one troubling respect nearly all of us today wear the ring of Gyges. Because we are “invisible,” we use the ring to harm others with impunity. What is our ring of Gyges? It is our use/release of epigenetically toxic environmental pollutants (ETEP), such as endocrine disruptors, metals, and some pesticides. For developmentally/pre- and-postnatally-exposed children, ETEP often cause heritable gene-expression changes, developmental toxicity (DT) that increases later-life disease/dysfunction/death, including asthma/allergy, cancer, cardiovascular disease, depression, (...) diabetes, hypertension, immune/precocious autoimmune diseases, infertility, neuro-developmental/neuro-degenerative diseases, obesity, osteoporosis, puberty, and schizophrenia.Yet, like Gyges, we offenders are “invisible” in at least two senses: (i) invisible before the law, because current regulations do not prohibit ETEP exposures able to cause DT; (ii) invisible as perpetrators, because most child-DT harms appear later in life. This paper (1) uses ETEP and DT to explain how we cause severe, hidden, pollution harms to children and future generations, (2) argues that no major ethical theory can justify allowing avoidable ETEP, and (3) shows that we have justice-based duties to help stop avoidable ETEP exposures, because, to varying degrees, we help cause ETEP and profit from them. Finally, the paper (4) answers objections to (3). (shrink)

Many clinicians are experiencing consumer resistance to the prescription of equine HRT (that is hormone replacement therapy which has been manufactured from mare's urine). In this paper I consider the ethical implications of prescribing these preparations. I decide that patients should have a right to refuse such treatment but also ask whether a prescribing doctor should choose one preparation over another on moral grounds. I determine that there is prima facie evidence to suggest that mares may suffer and that prescription (...) of equine HRT (instead of synthetic oestrogen-oestriol) would therefore have to be justified in terms of either offering greater benefits to the women or offering greater value for money to the health service. I find that there is no substantial evidence to suggest that equine HRT offers unique advantages over and above oestriol. I conclude that it would be preferable for a doctor to recommend the synthetic oestrogen to women who want relief from the symptoms of the menopause and protection from osteoporosis and cardiovascular disease. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Experiences of an Obese PatientChristine R. BrassIn the middle of an annual pelvic exam, the gynecologist said to me, “You should apply to be on ‘The Biggest Loser.’” I was too stunned and embarrassed to mutter anything more than a [End Page 88] comment that I didn’t think that, being quite introverted, I was a good candidate for a reality TV show. She argued with me about that. I (...) felt blindsided, intensely vulnerable, and dumbstruck—completely unable to respond—and later, when the shock wore off, incandescent with impotent rage.Four years later, I still don’t have words to adequately describe my outrage at this comment. It was only the second time I’d see this medical professional. The first time was the previous year, when she had been filling in for my regular doctor who was on maternity leave. At neither appointment did this physician ask me any questions about my lifestyle, whether or not I saw a primary care physician, or even if I had any concerns that day. She was very brisk, efficient and did not engage in conversation. Such a statement coming from a health care provider, who did not seek to understand or gather more information, surprised and dismayed me.Other incidents where physicians’ statements were not helpful:• Pediatrician: “Well, my wife has had great success with Weight Watchers.”—I was age 12, about 5’5 and weighted about 145 lbs. at that time. If you look at photos of me at the time, you would see I was not overweight.• Orthopedic Surgeon: “If you want her to look better, make her lose weight.”—This was directed to my mother. I was 19, weighed about 200 lbs., and in his office as per his directions to come back in seven years to see if the surgery he had done on my neck needed more attention.• Internist: “How did you get all those stretch marks?”—I was age 24, weighed approximately 220 lbs., and had lost and gained 50 or so pounds several times as a teenager and in college.• Gynecologist: “Lose weight and your periods will be regular.”—I was age 27, weighed 227 lbs. and my periods, which started at age 15, had never been regular.• Another Orthopedic Surgeon: “You don’t have to worry about osteoporosis; everything you do is a weight–bearing exercise.”—I was age 42 and weighed 300 lbs. This was after follow up surgery to remove pins from a broken ankle that had healed and I had asked about whether or not I should have a bone density test.Coming from a genetic heritage of predominately tall, large–boned people, I was tall and proportionally large compared to other girls my age until high school, when the others caught up. I was told I had to “watch my weight” by family members from my pre–teen years. Enforced dieting ensued, with little result because I wasn’t fat. I did not begin to be overweight until my junior and senior years of high school. I was 5’7” when I graduated from high school and weighed 187. By the time I graduated from college, I was no taller but 50 lbs. heavier. Now, nearing my 40th high school reunion, I am 120 lbs heavier than that. During the intervening years, I have done Weight Watchers®, TOPS®, medically–supervised programs (group and individual), and other popular diets, with periodic but temporary success, and hypnosis and aversion therapy, with no success at all.Over the years, I have been insulted, verbally abused, even bullied, because of my weight. I have been treated as though I am invisible, worthless, and stupid—a pariah. As a result, I have felt invisible, worthless, and stupid, even though I know I am none of those things. I have experienced and been treated for clinical depression. The descent into depression began in my late teen years, which was the time when I started gaining excess weight.In 2004, under medical supervision, I lost 70 lbs. over four–month period. I was delighted to finally lose a substantial amount of weight and feel physical lighter. My diabetes medications were significantly reduced, and... (shrink)

Tumor necrosis factor (TNF) receptor associated factor 6 (TRAF6) is a crucial signaling molecule regulating a diverse array of physiological processes, including adaptive immunity, innate immunity, bone metabolism and the development of several tissues including lymph nodes, mammary glands, skin and the central nervous system. It is a member of a group of six closely related TRAF proteins, which serve as adapter molecules, coupling the TNF receptor (TNFR) superfamily to intracellular signaling events. Among the TRAF proteins, TRAF6 is unique in (...) that, in addition to mediating TNFR family signaling, it is also essential for signaling downstream of an unrelated family of receptors, the interleukin‐1 (IL‐1) receptor/Toll‐like receptor (IL‐1R/TLR) superfamily. Gene targeting experiments have identified several indispensable physiological functions of TRAF6, and structural and biochemical studies have revealed the potential mechanisms of its action. By virtue of its many signaling roles, TRAF6 represents an important target in the regulation of many disease processes, including immunity, inflammation and osteoporosis. BioEssays 25:1096–1105, 2003. © 2003 Wiley Periodicals, Inc. (shrink)