Fish bone‐derived cell lines: an alternative in vitro cell system to study bone biology

Human bone diseases represent a major health problem worldwide and effective therapies have still to be developed. Despite numerous studies using mammalian systems, cellular and molecular processes governing bone and cartilage homeostasis in vertebrates are still not fully understood. Recently, fish have emerged as a suitable model and a promising alternative to the classical mammalian systems to study vertebrate development, in particular skeletogenesis. To complement in vivo developmental studies and identify signalling pathways involved in development processes, fish cell lines have been developed, in particular bone‐derived cells. This work intends to review what is presently known about fish bone‐derived cell lines, focusing on their relevance for bone biology studies.     

Skeletal effects of serotonin (5-hydroxytryptamine) transporter inhibition: evidence from clinical studies

The discovery of a functional serotonin (5-hydroxytryptamine; 5-HT) transporter (5-HTT) in bone has given rise to questions about the physiologic role of 5-HT in bone, and the possible clinical implications for humans. 5-HT is known to play a role in the pathophysiology of depression, and many antidepressant medications function by inhibiting the 5-HTT. Among the antidepressants, those that selectively block the 5-HTT (namely, selective serotonin reuptake inhibitors; SSRIs) appear to have skeletal effects. Several studies have demonstrated lower bone density, increased rates of bone loss at the hip, and increased rates of fracture among older individuals taking SSRIs. However, there remains uncertainty about whether it is the antidepressant medications themselves or the reason for their use (depression) that is responsible for these observed bone changes. This paper reviews the epidemiologic literature that explores the role of the 5-HTT in bone health, by looking at questions about how depression, antidepressant therapy and SSRIs impact bone health in humans. Further research will be important to better understand how these factors interact to influence skeletal status, and to characterize the biochemical mechanism through which 5-HT may mediate bone turnover and metabolism.     

Genetic regulation of osteoclast development and function

Osteoclasts are the principal, if not exclusive, bone-resorbing cells, and their activity has a profound impact on skeletal health. So, disorders of skeletal insufficiency, such as osteoporosis, typically represent enhanced osteoclastic bone resorption relative to bone formation. Prevention of pathological bone loss therefore depends on an appreciation of the mechanisms by which osteoclasts differentiate from their precursors and degrade the skeleton. The past five years have witnessed important insights into osteoclast formation and function. Many of these discoveries have been made through genetic experiments that involved the rare hereditary disorder osteopetrosis.     

The “love–hate” relationship between osteoclasts and bone matrix

Osteoclasts are unique cells that destroy the mineralized matrix of the skeleton. There is a “love–hate” relationship between the osteoclasts and the bone matrix, whereby the osteoclast is stimulated by the contact with the matrix but, at the same time, it disrupts the matrix, which, in turn, counteracts this disruption by some of its components. The balance between these concerted events brings about bone resorption to be controlled and to contribute to bone tissue integrity and skeletal health. The matrix components released by osteoclasts are also involved in the local regulation of other bone cells and in the systemic control of organismal homeostasis. Disruption of this regulatory loop causes bone diseases, which may end up with either reduced or increased bone mass, often associated with poor bone quality. Expanding the knowledge on osteoclast-to-matrix interaction could help to counteract these diseases and improve the human bone health. In this article, we will present evidence of the physical, molecular and regulatory relationships between the osteoclasts and the mineralized matrix, discussing the underlying mechanisms as well as their pathologic alterations and potential targeting.     

Understanding the local actions of lipids in bone physiology

The adult skeleton is a metabolically active organ system that undergoes continuous remodeling to remove old and/or stressed bone (resorption) and replace it with new bone (formation) in order to maintain a constant bone mass and preserve bone strength from micro-damage accumulation. In that remodeling process, cellular balances – adipocytogenesis/osteoblastogenesis and osteoblastogenesis/osteoclastogenesis – are critical and tightly controlled by many factors, including lipids as discussed in the present review.Interest in the bone lipid area has increased as a result of in vivo evidences indicating a reciprocal relationship between bone mass and marrow adiposity. Lipids in bones are usually assumed to be present only in the bone marrow. However, the mineralized bone tissue itself also contains small amounts of lipids which might play an important role in bone physiology. Fatty acids, cholesterol, phospholipids and several endogenous metabolites (i.e., prostaglandins, oxysterols) have been purported to act on bone cell survival and functions, the bone mineralization process, and critical signaling pathways. Thus, they can be regarded as regulatory molecules important in bone health. Recently, several specific lipids derived from membrane phospholipids (i.e., sphingosine-1-phosphate, lysophosphatidic acid and different fatty acid amides) have emerged as important mediators in bone physiology and the number of such molecules will probably increase in the near future. The present paper reviews the current knowledge about: (1°) bone lipid composition in both bone marrow and mineralized tissue compartments, and (2°) local actions of lipids on bone physiology in relation to their metabolism. Understanding the roles of lipids in bone is essential to knowing how an imbalance in their signaling pathways might contribute to bone pathologies, such as osteoporosis.     

Health and cancer prevention: knowledge and beliefs of children and young people.

OBJECTIVE--To collect information from children and young people about their knowledge of and attitudes towards cancer and their understanding of health and health related behaviours to inform future health promotion work. DESIGN--Questionnaire survey of 15-16 year olds, and interviews with play materials with 9-10 year old children. SETTING--Six inner city, suburban, and rural schools. SUBJECTS--226 children aged 15-16 years and 100 aged 9-10 years. MAIN OUTCOME MEASURES--Knowledge about different types of cancer; beliefs about health; sources of information; quality of research data obtainable from young children about cancer and health. RESULTS--Both samples knew most about lung cancer, but there was also some knowledge of breast and skin cancer and leukaemia. Smoking, together with pollution and other environmental factors, were seen as the dominant causes of cancer. Environmental factors were mentioned more often by the inner city samples. Television and the media were the most important sources of information. Young people were more worried about unemployment than about ill health. More than half the young people did not describe their health as good, and most said they did not have a healthy lifestyle. Children were able to provide detailed information about their knowledge and understanding by using drawings as well as interviews. CONCLUSIONS--Children and young people possess considerable knowledge about cancer, especially about lung cancer and smoking, and show considerable awareness of predominant health education messages. Despite this knowledge, many lead less than healthy lifestyles. Health is not seen as the most important goal in life by many young people; the circumstances in which many children and young people live are not experienced as health promoting.     

Climate change and local public health in the United States: preparedness, programs and perceptions of local public health department directors

While climate change is inherently a global problem, its public health impacts will be experienced most acutely at the local and regional level, with some jurisdictions likely to be more burdened than others. The public health infrastructure in the U.S. is organized largely as an interlocking set of public agencies at the federal, state and local level, with lead responsibility for each city or county often residing at the local level. To understand how directors of local public health departments view and are responding to climate change as a public health issue, we conducted a telephone survey with 133 randomly selected local health department directors, representing a 61% response rate. A majority of respondents perceived climate change to be a problem in their jurisdiction, a problem they viewed as likely to become more common or severe over the next 20 years. Only a small minority of respondents, however, had yet made climate change adaptation or prevention a top priority for their health department. This discrepancy between problem recognition and programmatic responses may be due, in part, to several factors: most respondents felt personnel in their health department--and other key stakeholders in their community--had a lack of knowledge about climate change; relatively few respondents felt their own health department, their state health department, or the Centers for Disease Control and Prevention had the necessary expertise to help them create an effective mitigation or adaptation plan for their jurisdiction; and most respondents felt that their health department needed additional funding, staff and staff training to respond effectively to climate change. These data make clear that climate change adaptation and prevention are not currently major activities at most health departments, and that most, if not all, local health departments will require assistance in making this transition. We conclude by making the case that, through their words and actions, local health departments and their staff can and should play a role in alerting members of their community about the prospect of public health impacts from climate change in their jurisdiction.     

Radiological evaluation of bone status in the jaw and in the vertebral column in a group of women

Vertebral bone mineral content was determined in a group of 56 women, ages 30–62. These measurements were compared with the status of supporting bone in the jaws (alveolar, molar and bicuspid) and with gingival health. There was a significant decline in vertebral bone mineral content from the pre- to post-menopausal group. Molar and bicuspid measurements were highly correlated. There was some association between lumbar bone mineral content and molar bone status for postmenopausal women. For postmenopausal women, the cases of greatest percent bone loss in alveolar crest were associated with lower lumbar bone mineral content. Gingival health did not confound the bone status measurements. The 56 subjects did not exhibit the degree of reduction in bone density that is observed in the general population. Further investigation using these radiographic techniques may reveal a link between substantial bone loss in the jaw and moderate to severe bone loss in the lumbar vertebrae.     

Understanding the pathology and mechanisms of type I diabetic bone loss

Type I (T1) diabetes, also called insulin dependent diabetes mellitus (IDDM), is characterized by little or no insulin production and hyperglycemia. One of the less well known complications of T1-diabetes is bone loss which occurs in humans and animal models. This complication is receiving increased attention because T1-diabetics are living longer due to better therapeutics, and are faced with their existing health concerns being compounded by complications associated with aging, such as osteoporosis. Both male and female, endochondrial and intra-membranous, and axial and appendicular bones are susceptible to T1-diabetic bone loss. Exact mechanisms accounting for T1-diabetic bone loss are not known. Existing data indicate that the bone defect in T1-diabetes is anabolic rather than catabolic, suggesting that anabolic therapeutics may be more effective in preventing bone loss. Potential contributors to T1-diabetic suppression of bone formation are discussed in this review and include: increased marrow adiposity, hyperlipidemia, reduced insulin signaling, hyperglycemia, inflammation, altered adipokine and endocrine factors, increased cell death, and altered metabolism. Differences between T1-diabetic- and age-associated bone loss underlie the importance of condition specific, individualized treatments for osteoporosis. Optimizing therapies that prevent bone loss or restore bone density will allow T1-diabetic patients to live longer with strong healthy bones.     

Autoradiographic Studies of the Utilization of Ca45 by the Chick Embryo

Calcium-45 was injected into the dense albumen of fertile hen's eggs, to the extent of 25 µc. per egg. The eggs were incubated under standard conditions and three or more embryos removed daily and fixed in 10 per cent neutral formalin. Stripping-film autoradiograms were prepared from paraffin sections of the tibiofibulae. Exposure varied with the isotope concentration. The tissue sections with their autoradiograms in place were stained with dilute Giemsa, while other sections were stained with hematoxylin-azure-eosin and by von Kossa to demonstrate bone salt. At about 9 days, Ca⁴⁵ is found in the cartilage template both intra- and extracellularly. Between 9 and 11 days, a primary diaphyseal lamella is deposited which is largely acellular. The lamella is eroded by capillaries from the periosteum and a resorption center is established in the cartilage. New lamellae of bone are deposited centrifugally in an imbricated pattern. Bone matrix formation precedes calcification by about 1 to ½ days, and calcification in a particular lamella is not uniform. Endochondral bone formation is described, as well as calcification of the epiphyseal/diaphyseal cartilage. Calcium-45 occurs intracellularly in the osteocyte during bone formation.     

Spurious Case of XX Maleness in A Patient With A History of Wiskott-Aldrich Syndrome

ObjectiveTo alert endocrinologists about the potential for karyotype confusion in patients who have undergone bone marrow transplantation.MethodsClinical, laboratory, and imaging data are reported on a young adult male patient who initially presented because of concerns about short stature.ResultsAn 18-year-old fully virilized male patient with a history of Wiskott-Aldrich syndrome had undergone successful bone marrow transplantation in infancy. The donor was his older sister. Many years later, he underwent evaluation because of short stature and was found to have a 46, XX karyotype. This unexpected finding led to several costly laboratory and imaging studies, as well as a new diagnosis of a disorder of sex development. The patient was referred to our medical center for further evaluation of XX sex reversal. A skin biopsy was eventually performed, which revealed a 46, XY karyotype. This unusual case highlights the fact that a peripheral blood specimen from bone marrow transplant recipients reflects the genetic makeup of the bone marrow donor.ConclusionAlthough the cytogenetic changes that occur in recipients of bone marrow transplants are well known to hematologists and oncologists, they are not commonly recognized by other health care providers. Increased awareness of this potential situation in long-term survivors of bone marrow transplantation is needed. (Endocr Pract. 2011;17:e1-e3)     

Seeing the light in bone metabolism imaging

Conventional in vivo imaging of bone metabolism is dominated by gamma-ray bone scintigraphy: a technique in which gamma-ray emissions from radioactively labeled regions of metabolically active bone are mapped. More recently, however, near-infrared fluorescent probes have been developed that optically emulate these radionuclides. Although still in their infancy, techniques based on the use of such functionally targeted fluorophores might one-day offer improved resolution, sensitivity and speed in bone metabolism imaging -- without any of the health risks posed by the internalization of radioactive sources.     

The relative spatial distribution of erythroid progenitor cells (BFUe and CFUe) in the normal mouse femur

Abstract. Femoral mouse bone marrow cells were separated into axial and marginal fractions, in order to investigate the relative concentration of erythroid progenitor cells (BFUe and CFUe) with respect to their location across the diameter of the femur. Two areas of high incidence of early progenitor cells (BFUe) were identified: one lying near the bone surface with a peak at about 410 μ m radial distance from the axis of the bone; the other nearer the centre of the bone with a peak at about 270 μ m. The more immature BFUe were found in higher proportion in the marginal peak. In contrast, CFUe, apart from very low concentration values in the vicinity of the bone surface, demonstrated a fairly uniform distribution throughout the marrow. The present results indicate that the distribution of erythroid progenitor cells within the bone marrow is not random. The haemopoietic tissue seems to exhibit a well-defined structure that may be relevant in regulating proliferation and differentiation processes.     

Consensus and Controversy Regarding Osteoporosis in the Pediatric Population

ObjectiveTo review current consensus and controversy surrounding the diagnosis and treatment of osteoporosis in childhood and adolescence.MethodsThe medical literature was reviewed with emphasis on the importance of early skeletal health, risk factors for bone fragility, and the diagnosis and management of children at risk for osteoporosis.ResultsChildhood and adolescence are critical periods for optimizing bone growth and mineral accrual. Bone strength is determined by bone size, geometry, quality, and mass—variables that are influenced by genetic factors, activity, nutrition, and hormones. For children with genetic skeletal disorders or chronic disease, bone growth and mineral accrual may be compromised, increasing the lifetime risk of osteoporosis. The goal for the clinician is to identify children at greatest risk for future fragility fracture. Bone densitometry and turnover markers are challenging to interpret in children. Prevention and treatment of bone fragility in children are less well established than in adults. Optimizing nutrition and activity may not restore bone health, but the drug armamentarium is limited. Sex steroid replacement has not proven effective in restoring bone mass in patients with anorexia nervosa or exercise-associated amenorrhea. Bisphosphonates can increase bone mass and may reduce bone pain and fractures, most convincingly in patients with osteogenesis imperfecta. Further studies are needed to establish the safety, efficacy, and optimal drug, duration, and dosage in pediatric patients.ConclusionBone health during the first 2 decades contributes to the lifetime risk of osteoporosis. Further research is needed to develop evidence-based recommendations for the diagnosis and treatment of osteoporosis in childhood. (Endocr Pract. 2007;13:513-520)     

Prevention and treatment of osteoporosis in chronically ill children

Osteoporosis secondary to chronic disease in children has emerged as a major health issue. As the severity of a child's illness increases, so too does the number of factors affecting their bone health. Determinants of bone health in children include level of mobility, exposure to osteotoxic medication, nutritional status, calcium and vitamin D intake, chronic inflammation and pubertal development.     

Cortical bone maintenance in an historic Afro-American cemetery sample from Cedar Grove, Arkansas

The relocation and analysis of 80 skeletons from the Cedar Grove Cemetery, located in southwest Arkansas, provides an opportunity to examine the level of health and nutrition experienced by Afro-Americans in the post-Reconstruction South (1878-1930). The demographic profile lends support to the interpretation that Cedar Grove participated in the nationwide decline in Afro-American health. The high frequencies of skeletal lesions indicative of dietary deficiencies and infectious disease demonstrate that this was a highly stressed population. For this analysis, adult femoral thin sections (15 females and 14 males) are examined histologically. These data provide support to the assertion that the Cedar Grove population experienced poor health. Measures taken from the sections include cortical thickness, percent cortical area, and mean number of resorption spaces and forming osteons per square millimeter of bone. As a group, they demonstrate low percent cortical area compared with well-nourished normals. They also show high rates of resorption to formation, thereby disrupting the balance necessary for normal cortical bone maintenance. The pattern established for bone porosity in this group is not a function of age but rather is due to other factors, most likely nutrition and disease stress. What may be unique about this group is that males, as well as females, experienced problems with calcium homeostasis and normal maintenance and repair of bone. Taken together, these data support the interpretation that diet and health were substandard in the post-Reconstruction South.     

Female Genital Surgeries: The Known, the Unknown, and the Unknowable

This article reviews the literature on female genital surgeries and examines the extent to which available research supports commonly accepted "facts" about the prevalence and harmful effects of these practices, in particular their possible health complications, and their effect on sexuality. While information regarding the prevalence of female genital surgeries is becoming increasingly available, the powerful discourse that depicts these practices as inevitably causing death and serious ill health, and as unequivocally destroying sexual pleasure, is not sufficiently supported by the evidence. The article discusses some of the implications of research on female genital surgeries for the societies that are involved—not merely those where the practices are found, but also those whose gaze has been so intensely focused on the customs of others, [female genital surgeries/mutilation, prevalence, health complications, sexuality]     

Long-term effects of aromatase inhibitors on bone

The risk of fracture in the postmenopausal woman given aromatase inhibitors may be increased by up to 60%. This is likely to be true for all third generation drugs, but the clinical trials did not include sufficient fracture events for certainty on this issue. It would appear that most of the excess fracture risk relates to vertebral fracture and in future studies, more effort should be given to ascertaining these fractures. The likely mechanism for the increase in fracture risk is an increase in bone turnover (of about 20%) and an acceleration of bone loss. There is evidence to suggest that the residual levels of oestradiol present in the postmenopausal woman are important for bone health, and thus, the effect of these drugs is to remove this protective effect. Current clinical practice should include the measurement of bone mineral density in postmenopausal women taking these drugs and commencement of antiresorptive therapy if osteoporosis is already present.