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Biomedical subjects

J A Kanis

Publications and source records attributed to J A Kanis.

At least 19 recordsLinked to original sources
PubMed1992

Evidence for efficacy of drugs affecting bone metabolism in preventing hip fracture.

OBJECTIVE: To examine the effects of taking drugs affecting bone metabolism on the risk of hip fracture in women aged over 50 years. DESIGN: Retrospective, population based, case-control study by questionnaire. SETTING: 14 centres in six countries in southern Europe. SUBJECTS: 2086 women with hip fracture and 3532 control women matched for age. MAIN OUTCOME MEASURES: Number of drugs affecting bone metabolism taken and length taken for. RESULTS: Women taking drugs affecting bone metabolism had a significantly decreased risk of hip fracture. After adjustment for differences in other risk factors, the relative risk of hip fractures was 0.55 (95% confidence interval 0.31 to 0.85) in women taking oestrogens, 0.75 (0.60 to 0.94) in those taking calcium, and 0.69 (0.51 to 0.92) in those taking calcitonin. The fall in risk was not significant for anabolic steroids (0.6 (0.29 to 1.22)). Neither vitamin D nor fluorides were associated with a significant decrease in the risk of hip fracture. The effect on hip fracture risk increased significantly with increasing duration of exposure (risk ratio 0.8 (0.61 to 1.05) for less than median exposure v 0.66 (0.5 to 0.88) for greater than median exposure). Drugs were equally effective in older and younger women, with the exception of oestrogen. CONCLUSIONS: Oestrogen, calcium, and calcitonins significantly decrease the risk of hip fracture. Short term intervention late in the natural course of osteoporosis may have significant effects on the incidence of hip fracture.

Aged↗
PubMed1992

Paleohistology of Paget's disease in two medieval skeletons.

Paget's disease has been ascribed several times to specimens of archeological bone but, in the absence of microscopic examination, the evidence remains insubstantial. Suspected metabolic bone disease is described here in the archeological remains of a skeleton from a 16th century burial ground at Wells Cathedral, England and from a single medieval sacrum recovered from a large deposit of disarticulated bones from a churchyard at Barton-on-Humber, England. Radiographs showed apparent structural abnormality in one femoral shaft and calcaneus and in the isolated sacrum. Histomorphometry on undecalcified bone cores confirmed the regions of abnormality and showed not only increased trabecular width but also areas of "mosaic" woven bone together with extensive resorption cavities; these features contrasted with the normal structure and organized lamellar bone from sites elsewhere. Despite post-interment changes in surrounding tissues, the morphological stability of some of the osteocytes was remarkable. Preservation of the histology was sufficient to permit the assignment of a metabolic bone disorder and the nature of the sclerosis was consistent with Paget's disease.

England↗
PubMed1992

Effects of five daily 1 h infusions of alendronate in Paget's disease of bone.

We report a randomized placebo-controlled double-blind study of amino-hydroxybutylidene bisphosphonate (alendronate), infused over 1 h, in 15 patients with Paget's disease of bone. Alendronate, 10 mg/day for 5 days, suppressed urinary hydroxyproline to 44.9 +/- 4.8% and serum alkaline phosphatase to 74.6 +/- 5.4% of their pretreatment values within 1 month of the start of treatment. Within 5 months of the start of treatment serum alkaline phosphatase fell to 47.9 +/- 6.3% of pretreatment values. These effects were associated with a decrease in serum calcium and phosphate and in urinary calcium excretion and with a rise in serum iPTH values. A transient fever was observed in 3 of 10 patients who received alendronate during the course of the infusions, and this was associated with a decrease in the total and differential white cell count. No adverse effects were noted on renal function as judged by glomerular filtration rate and indices of proximal and distal tubular function. This regimen may simplify the management of patients with Paget's disease of bone.

Aged↗
PubMed1992

The apparent incidence of hip fracture in Europe: a study of national register sources.

The objective of this study was to examine the apparent incidence of hip fracture from discharge rates in European countries. A request was sent to the Ministries of Health in all European countries, asking for the number of hip fracture patients by age and sex, between the years 1983 and 1985. Seventeen countries responded. As expected, hip fracture was most frequently found amongst the elderly, particularly women. The incidence of hip fracture rose exponentially with age in both sexes. It was higher in women than men and there was a three-fold range between countries in the female to male sex ratio. There was an eleven-fold range in apparent incidence amongst women and a seven-fold range amongst men between the various countries. The highest incidence was found in the northern part of Europe and the lowest in the Mediterranean area. There was a significant positive correlation between the age-standardized incidence rates reported in men from each country and that in women. There was a larger difference in incidence between countries than between sexes, which suggests important genetic or environmental factors in the causation of hip fracture. The extent to which this reflects imperfect capture of data is uncertain but will be important to determine in order to identify reasons for differences and to enable confident projections of the future magnitude of this disorder.

Adult↗
PubMed1992

An automated method for the analysis of trabecular bone structure.

Trabecular structure as well as bone mass is important in studies of bone disease and fracture. An automated method for the direct analysis of two-dimensional trabecular micro-anatomy and its application to human iliac crest bone biopsies is described. Compared with established methods which require expensive equipment and complex software, costs have been reduced and availability increased by using an image analyzer driven by a microcomputer. Routine histological sections are accepted and an editing function enables the removal of artifacts. An elastic window allows field expansion for large specimens. The program enables the rapid assessment of the bone volume and trabecular surface from the intact image, followed by image skeletonization and the deduction of the trabecular length, number, character, and spacing together with the number of trabecular junctions and discontinuities; the trabecular width is calculated indirectly. Images may be stored to disk or printed as permanent records for diagnostic or research purposes.

Biopsy↗
PubMed1992

Bone hypertrophy and trabecular generation in Paget's disease and in fluoride-treated osteoporosis.

The replacement of lost trabeculae characteristic of postmenopausal osteoporosis is problematic, since a biological pathway has not been established for trabecular regeneration de novo in the healthy, intact, mature skeleton. Possible pathways for trabecular replacement may occur under pathological conditions, in particular those associated with bone hypertrophy. The topography of trabecular hypertrophy was compared in two groups of subjects with disease- or treatment-induced osteosclerosis following a period of atrophy. In Paget's disease and fluoride-treated osteoporosis a thickening of rarefied trabeculae in both was associated in Paget's disease only with an increase in the trabecular number and the transformation of a discontinuous arrangement into a more continuous network. The sequence seems to be a progression of intratrabecular resorption normally attendant upon a period of trabecular thickening. The failure of fluoride-treated bone in this respect, due to the unusual stability of the fluorotic skeleton, may provide insight to more effective anabolic regimens.

Adult↗
PubMed1992

Osteoporotic fractures: an unusual presentation of haemochromatosis.

The association of haemochromatosis and osteoporosis is well established, but it is unclear whether this is due to iron overload, hypogonadism, liver disease, or diabetes mellitus. We describe a young eugonadal male patient with osteoporotic fractures as a presenting feature of haemochromatosis, suggesting that factors other than hypogonadism contribute to osteoporosis.

Adult↗
PubMed1992

Epidemiology of vertebral osteoporosis.

Whereas the extent, morbidity and costs of hip and Colles' fracture are well recognised from epidemiological studies, those arising from vertebral fracture are less secure. Reasons relate to the uncertain definition of vertebral fracture and its variable clinical expression, and hence its incidence is not known. Utilising radiological criteria 50% or more of vertebral fractures may be asymptomatic. In the remainder morbidity is significant, particularly in the presence of multiple vertebral fractures. Although the true incidence of vertebral fracture is unknown there is evidence that it increases exponentially with age in much the same way as for hip fracture. Between the ages of 60 and 90 years the apparent incidence rises approximately 20-fold in women compared to a 50-fold increase in risk of hip fracture. The incidence of vertebral osteoporosis is two-fold lower in men than in women at all ages, comparable to the pattern observed with other osteoporotic fractures. However, there is a relatively high incidence of vertebral fracture in men during middle adult-life (probably due to trauma), so that the prevalence of vertebral fracture in the male community is not two-fold less than in women.

Adult↗
PubMed1992

Epidemiology of osteoporosis.

Fragility fractures are now recognised as a major problem of public health. Although the prevalence of all fractures is similar among men and women, the vast majority of osteoporotic fractures occur in elderly women. These comprise vertebral compression fractures, Colles fractures at the wrist, and hip fracture, and to a lesser extent fractures at other sites. The incidence of vertebral and hip fracture increases exponentially with age. The reasons for this relate in part to the lower bone density of women at the time of maturity (peak bone density), and the accelerated bone loss that occurs after the menopause. Women live significantly longer than men, so that the prevalence of osteoporosis amongst elderly women is six-fold that of men. The age- and sex-specific incidence of osteoporotic fracture is rising in many countries, and if the current trends in the United Kingdom continue, then the number of hip fractures each year will more than double over the next 20 years. There is a marked geographic distribution in the incidence of hip fracture, and probably of other osteoporotic fractures. Indeed, the difference in incidence between communities is greater than the difference in incidence between sexes within communities. This suggests that the importance of gonadal insufficiency in women has been over-emphasised and that other factors, probably relating to life-style factors affecting peak bone density, account for ecological differences in incidence between communities and secular trends within communities.

Colles' Fracture↗
PubMed1992

Abnormal bone remodelling in patients with myelomatosis and normal biochemical indices of bone resorption.

We studied bone biopsies from 26 patients with myelomatosis with apparently normal skeletal metabolism. Quantitative histomorphometric measurements suggested that skeletal disease was progressive despite normocalcaemia and normal urinary excretion rates of calcium and hydroxyproline. When biopsies were divided according to the involvement of marrow by plasma cells, bone resorption--as judged by the eroded surface--increased significantly the greater plasma cell burden. Osteoclasts were frequent with moderate tumour burdens, but there was no further increase in the number of osteoclasts when plasma cell infiltration increased by more than 50% of bone marrow. Contrary to expectation, the numbers of osteoblasts and bone formation rates were increased with bone biopsies with moderate tumour burden, but were markedly lower when plasma cell infiltration occupied more than 50% of bone marrow, due to a decreased functional capacity of osteoblasts. We conclude that skeletal bone disease in myeloma is commonly progressive despite apparently stable bone disease as judged by biochemical measurements. The major mechanism of bone loss in myelomatosis is increased osteoclastic resorption but decreased bone formation contributes to bone loss with heavy plasma cell burdens. Urinary excretion of calcium and hydroxyproline provide insensitive indices of bone resorption in myelomatosis.

Alkaline Phosphatase↗
PubMed1991

1,25(OH)2D3 induces differentiation of osteoclast-like cells from human bone marrow cultures.

Multinucleated cells were generated from human bone marrow cultured in the presence of 10(-6)M 1,25(OH)2D3 and 10(-6)M all-trans-retinoic acid for 3-4 weeks. These multinucleated cells have the phenotypic and functional characteristics of osteoclasts as judged by (a) immunostaining with osteoclast specific monoclonal antibodies 13C2 and 23C6 (b) expression of tartrate resistant acid phosphatase, an enzyme marker of osteoclast differentiation; and (c) the ability to resorb bone in vitro. The multinucleated cells appeared to form by fusion of large mononuclear cells. The monoclonal antibodies 13C2 and 23C6 stained 60-90% of the multinucleated cells, and 40-60% of the large mononuclear cells. Tartrate resistant acid phosphatase activity was expressed by 80-95% of the multinucleated cells and 60-80% of the large mononuclear cells. Scanning electron microscopy of bone wafers co-incubated with the multinucleated cells, for 7 days, revealed resorption pits. These findings suggest that in the presence of 1,25(OH)2D3 the marrow cells differentiated into multinucleated and large mononucleated cells in which a proportion of them expressed osteoclast phenotype and resorbed bone.

Bone Marrow Cells↗
PubMed1991

Immunoreactivity and proliferative actions of beta 2 microglobulin on human bone-derived cells in vitro.

Recent studies have demonstrated homology between bone-derived growth factor and beta 2 microglobulin. We have shown that beta 2 microglobulin has proliferative actions on human bone-derived cells in vitro and that these cells also show immunogenicity for beta 2 microglobulin. beta 2 microglobulin stimulated the incorporation of 3H-thymidine into DNA of human bone cells in a dose-dependent manner. In contrast to this stimulatory action, beta 2 microglobulin had no detectable activity with the same concentration on the production of osteocalcin, alkaline phosphatase activity or prostaglandin E2 synthesis. The possibility that the human bone-derived cells could also produce beta 2 microglobulin was examined. Under basal conditions these cells exhibit immunoreactivity for beta 2 microglobulin, the expression of which could be enhanced following treatment with interferon gamma in a dose-dependent manner. The co-localization of staining for beta 2 microglobulin and alkaline phosphatase, a marker of the osteoblast phenotype, indicate that human osteoblast-like cells represent a source of activity of this factor. The production of beta 2 microglobulin by human osteoblast-like cells and the subsequent action of this factor on cells within the bone microenvironment may indicate a role for beta 2 microglobulin as a local regulator of bone metabolism.

Alkaline Phosphatase↗
PubMed1991

A double-blind study of deflazacort and prednisone in patients with chronic inflammatory disorders.

Deflazacort and prednisone were given to 26 patients with rheumatoid arthritis, polymyalgia rheumatica, or other chronic inflammatory diseases, in a double-blind study. Deflazacort rapidly and effectively suppressed disease activity in a manner supporting its assumed therapeutic potency of 83% that of prednisone. Prednisone induced a rapid increase in the level of daily calcium excretion that was not evident with deflazacort. Cortisol secretion was acutely inhibited by prednisone, but not by deflazacort. Neither corticosteroid had a significant effect on glucose metabolism, at the doses studied. Treatment with deflazacort may be an effective alternative to prednisone treatment, with fewer adverse effects on levels of calcium and cortisol, in patients with severe inflammatory conditions warranting the use of glucocorticoids.

Analysis of Variance↗
PubMed1991

Actions of calcipotriol (MC 903), a novel vitamin D3 analog, on human bone-derived cells: comparison with 1,25-dihydroxyvitamin D3.

The actions of a novel vitamin D3 analog calcipotriol (MC 903), on human bone-derived cells were compared to those of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3]. Both calcipotriol and 1,25-(OH)2D3 inhibited the proliferation of human osteoblast-like cells in a dose-dependent manner (10(-10)-10(-6) M), an effect observed at different cell densities. Lower concentrations of either agent exerted no marked effect on the growth of the cells compared to untreated cultures. Calcipotriol and 1,25-(OH)2D3 were equipotent in stimulating the activity of alkaline phosphatase and the synthesis of osteocalcin in human osteoblast-like cells. The stimulation of alkaline phosphatase activity and osteocalcin synthesis by both compounds was evident by 24 h and was increased progressively up to 96 h in a dose-dependent manner over the concentration range of 10(-10)-10(-6) M. The increment in both proteins was dependent on cell density and was attenuated at higher cell densities. In contrast to these actions, neither calcipotriol nor 1,25-(OH)2D3 (10(-14)-10(-6) M) affected the synthesis of prostaglandin E2. These studies indicate that calcipotriol and 1,25-(OH)2D3 exhibit a similar spectrum of activity on human osteoblast-like cells in vitro.

Alkaline Phosphatase↗