In multicellular organisms, homeostasis is maintained through a balance between cell proliferation and cell death. Although much is known about the control of cell proliferation, less is known about the control of cell death. Physiologic cell death occurs primarily through an evolutionarily conserved form of cell suicide termed apoptosis. The decision of a cell to undergo apoptosis can be influenced by a wide variety of regulatory stimuli. Recent evidence suggests that alterations in cell survival contribute to the pathogenesis of a number of human diseases, including cancer, viral infections, autoimmune diseases, neurodegenerative disorders, and AIDS (acquired immunodeficiency syndrome). Treatments designed to specifically alter the apoptotic threshold may have the potential to change the natural progression of some of these diseases.

https://science.sciencemag.org/content/sci/267/5203/1456.full.pdf

Apoptosis in the pathogenesis and treatment of disease

RACTITIONERS OF BONE HISTOMORPHOMETRY communicate P with each other in a variety of arcane languages, which in general are unintelligible to those outside the field. Many in the bone and mineral scientific community would like to keep abreast of the contributions of histology to their subject, but are dismayed by the semantic barriers they must overcome. The need for standardization has been recognized for many years,(') during which there has been much talk but no action. To meet the needs of ASBMR members, Dr. B.L. Riggs (President, 19851986) asked the senior author to convene a committee of the Society to develop a unified system of termnology, suitable for adoption by the Journal of Bone and Mineral Research as part of its Instructions to Authors. The committee includes members from Europe and Canada as well as the U.S., and represents most existing systems of nomenclature. A circular letter seeking suggestions and information on current usage was sent to several hundred persons, with names drawn from the Society membership roster and lists of attendees at various recent conferences, to which approximately 40 replies were obtained. These confirmed the magnitude of the semantic problem (for some measurements as many as nine different terms were in use) and suggested a range of solutions likely to be generally acceptable. In formulating the new system. the committee kept in mind certain agreed general principles. First, the primary reason for change was to help other scientists understand bone histomorphometry, not to help bone histomorphometrists undcntand each other. Second. names should be self-explanatory and dcscriptive, without implicit assumptions. Third. symbols should consist mainly of abbreviations that included the first letter of each word in the same order as in the name. without subscripts or superscripts. Fourth. each symbol component should have one and only one meaning, and so eliminate ambiguity. Fifth, primary measurements should be clearly distinguished from derived indices. Finally, the chosen system should be sufficiently flexible to apply to all surfaces and all types of bone, and to accommodate any new primary measurement or derived index. The recommended system shares common elements with. but also differs substantially from. all those in current usc. was tested in practice for several months before the final forniat was chosen, and is as complex and conceptually difficult ;I\\ the field with which it deals. For those within the field we hope that increased readership of their papers will be adequate conipensation for the inconvcnicncc of learning a new systcm. For those outside the field, mastering the new system will be hard work, but if we are able to secure its acceptance by all journals with an interest in bone and mineral metabolism, the effort will only have to be expended once rather than. as at present. rcpeated many times. To this end we give the reasons for our decisions in the areas of controversy and, as well as definitions, provide methods for calculation of derived indices and

Bone histomorphometry: Standardization of nomenclature, symbols, and units: Report of the asbmr histomorphometry nomenclature committee

https://courses.washington.edu/bonephys/ASBMRHisto.pdf

Bone Histomorphometry : Standardization of Nomenclature, Symbols, and Units

Before publication of the original version of this report in 1987, practitioners of bone histomorphometry communicated with each other in a variety of arcane languages, which in general were unintelligible to those outside the field. The need for standardization of nomenclature had been recognized for many years,(1) during which there had been much talk but no action. To satisfy this need, B Lawrence Riggs (ASBMR President, 1985 to 1986) asked A Michael Parfitt to convene an ASBMR committee to develop a new and unified system of terminology, suitable for adoption by the Journal of Bone and Mineral Research (JBMR) as part of its Instructions to Authors. The resulting recommendations were published in 1987(2) and were quickly adopted not only by JBMR but also by all respected journals in the bone field. The recommendations improved markedly the ability of histomorphometrists to communicate with each other and with nonhistomorphometrists, leading to a broader understanding and appreciation of histomorphometric data.

In 2012, 25 years after the development of the standardized nomenclature system, Thomas L Clemens (Editor in Chief of JBMR) felt that it was time to revise and update the recommendations. The original committee was reconvened by David W Dempster, who appointed one new member, Juliet E Compston. The original document was circulated to the committee members and was extensively revised according to their current recommendations. The key revisions include omission of terminology used before 1987, recommendations regarding the parameters and technical information that should be included in all histomorphometry articles, recommendations on how to handle dynamic parameters of bone formation in settings of low bone turnover, and updating of references.

/pdf/standardized-nomenclature-symbols-and-units-for-bone-gah33fyb68.pdf

Standardized nomenclature, symbols, and units for bone histomorphometry: A 2012 update of the report of the ASBMR Histomorphometry Nomenclature Committee

Vitamin D deficiency is common in the elderly, especially in the housebound and in geriatric patients. The establishment of strict diagnostic criteria is hampered by differences in assay methods for 25-hydroxyvitamin D. The synthesis of vitamin D3 in the skin under influence of UV light decreases with aging due to insufficient sunlight exposure, and a decreased functional capacity of the skin. The diet contains a minor part of the vitamin D requirement. Vitamin D deficiency in the elderly is less common in the United States than elsewhere due to the fortification of milk and use of supplements. Deficiency in vitamin D causes secondary hyperparathyroidism, high bone turnover, bone loss, mineralization defects, and hip and other fractures. Less certain consequences include myopathy and falls. A diet low in calcium may cause an increased turnover of vitamin D metabolites and thereby aggravate vitamin D deficiency. Prevention is feasible by UV light exposure, food fortification, and supplements. Vitamin D3 supplementation causes a decrease of the serum PTH concentration, a decrease of bone turnover, and an increase of bone mineral density. Vitamin D3 and calcium may decrease the incidence of hip and other peripheral fractures in nursing home residents. Vitamin D3 is recommended in housebound elderly, and it may be cost-effective in hip fracture prevention in selected risk groups. (Endocrine Reviews 22: 477–501, 2001)

Vitamin D Deficiency and Secondary Hyperparathyroidism in the Elderly: Consequences for Bone Loss and Fractures and Therapeutic Implications

Study Objective:To determine whether the failure to attain normal bone mass in young adulthood contributes to the later development of osteoporotic fractures. Design:Case-control study. Se...

Bone mass is low in relatives of osteoporotic patients.

Bone loss after liver transplantation.

The reversibility of steroid-induced osteoporosis, a major complication of Cushing syndrome and long-term use of exogenous corticosteroids, is not well documented. We measured the bone mineral density of lumbar vertebras and the femoral neck by dual-photon absorptiometry and determined the biochemical variables of bone turnover in two patients successfully treated for Cushing syndrome who were followed for the next 24 months. Our data are the first to show marked increases in bone density (up to 20%) during the recovery period. The accompanying biochemical changes, particularly the marked increase in serum osteocalcin levels, confirm that enhanced bone formation occurred during the recovery phase. These findings suggest that steroid-induced osteoporosis can be reversed at least in young persons.

Recovery from Steroid-Induced Osteoporosis

The viability of osteocytes can be demonstrated in sawn decalcified sections of bone by their lactate dehydrogenase activity. In the cancellous bone of the femoral head, the proportion of lacunae containing viable osteocytes decreased from 88 +/- 7% (mean +/- SD) at 10-29 years to 58 +/- 12% (P < 0.001) by 70-89 years. Viability in the second lumbar vertebra was 88 +/- 3% in subjects aged 25-90 years and did not decrease with age. Mean osteocyte viability in the femoral head of 21 hip fracture patients aged 72-94 years was 58 +/- 21%, similar to controls of a similar age, though there was greater variation and, in five patients, osteocyte viability was less than 25%. In hip fracture patients, microfracture callus incidence correlated positively with osteocyte viability, with little or no fracture callus observed if the bone viability was low. Ultimate compressive strength did not correlate with osteocyte viability. In the femoral head there is gradual, age-related reduction in osteocyte viability that can be more pronounced in hip fracture. Osteocyte death may affect bone quality by impairing repair of fatigue damage.

Osteocyte death and hip fracture.

The effects of intraperitoneal aluminum chloride (1.5 mg aluminum/kg/day for 9 weeks) were studied in normal and uremic rats. Parameters measured included tissue aluminum, serum vitamin D metabolites, and quantitative bone histology.

Richard A. Evans

Papers

Bone mass is low in relatives of osteoporotic patients.

Bone loss after liver transplantation.

Recovery from Steroid-Induced Osteoporosis

Osteocyte death and hip fracture.

Effect of aluminum on normal and uremic rats: tissue distribution, vitamin D metabolites, and quantitative bone histology.