Hartmut H. Malluche

A new semiautomatic method for quantitative static and dynamic bone histology

SummaryA new semiautomatic technique combining advantages of the manual and fully automatic methods is described for obtaining quantitative static and dynamic histologic data of bone. The hardware consists of a photomicroscope, digitizing platen, digitizer, plotter/printer, floppy disc drive, and computer. The microscope is equipped with a drawing tube through which the image of the digitizing platen is projected over the optical field. The investigator selects and traces all histologic structures to be measured by moving a cursor on the digitizing platen which is visible by its projection over the histologic field. The results on accuracy and static and dynamic precision of this method show that static and dynamic parameters of bone are obtained with a degree of error (<20%) well within the acceptable range for biologic measurements. Comparison of this method with the grid technique according to Merz and Schenck showed that for almost all micromorphometric parameters comparable absolute data are obtained. Due to the higher precision of our method, however, the number of optical fields evaluated in obtaining these comparable data could be reduced to 25% of the number of fields evaluated by the Merz and Schenck technique. The time requirements for quantitative evaluation of a histologic slide of bone by our technique are 40–50 min; 20–25 min is needed for quantitative evaluation of osteocytes.

Quantitative bone histology in 84 normal American subjects. Micromorphometric analysis and evaluation of variance in iliac bone.

SummaryQuantitative bone histology was done in undecalcified sections of iliac crest bone specimens obtained from 84 normal American individuals. Samples were obtained within 12 h after death in a vertical and horizontal manner from both the right and left iliac crests. In addition to the determination of normal values of micromorphometric parameters of bone in these healthy American subjects, the following studies were carried out: (a) comparison of variance of micromorphometric parameters of bone obtained from the right versus left iliac bone (40 pairs), (b) comparison of micromorphometric parameters of bone obtained in a vertical versus horizontal manner (12 pairs), (c) evaluation of variance with increasing distance from the compact zone in bone samples obtained in a vertical manner (44 pairs), (d) analysis of variation between bone samples obtained more anteriorly versus posteriorly along the iliac crest (N=40), (e) comparison of differences in micromorphometric parameters obtained from age-matched men versus premenopausal women (N=12), and (f) plotting of histograms for assessment of distribution of micromorphometric parameters. The results show that histomorphometric data of bone cannot be easily compared when different techniques are employed for obtaining bone samples. Sampling variations are kept smaller when bone specimens are obtained in a vertical manner. Anterior/posterior variation does not cause major sampling error. If ranges of variation are taken into account, quantitative bone histology is a valuable tool for assessment of bone structure and bone cells.

Prevention of p.o. clotting of av. cimino fistulae with Acetylsalicyl acid results of a prospective double blind study

SummaryIn a prospective double blind study prophylactic administration of Acetylsalicylic acid (ASA) in low doses decreased significantly the rate of fistula clotting in the immediately p.o. period in uremic patients. The risk of fistula clotting was related to poor arterial blood flow, female sex and number of unsuccessful previous fistula operations. The incidence of side effects (g.i. and non g.i. bleeding) was acceptable with low doses of ASA and prophylactic administration of antacids.ZusammenfassungIn einer prospektiven Doppelblindstudie wurde der Einfluß von Acetylsalicylsäure auf die Häufigkeit von Cimino-Fistelthrombosen in der ersten p.o. Phase untersucht. Durch prophylaktische Gabe von Acetylsalicylsäure ließ sich der thrombotische Fistelverschluß auf 4% senken (Placebogruppe: 23%). Ein erhöhtes Thromboserisiko bestand bei schlechtem arteriellen Blutfluß, weiblichem Geschlecht und vorausgegangenen erfolglosen Fisteloperationen. Die Nebenwirkungen von Acetylsalicylsäure waren vertretbar, sofern Aspirin in niedriger Dosierung und in Verbindung mit Antacida verabreicht wurde.

24R,25-dihydroxyvitamin D3 and 1α,25-dihydroxyvitamin D3 are both indispensable for calcium and phosphorus homeostasis

Abstract The essential role of vitamin D throughout the life of most mammals and birds as a mediator of calcium homeostasis is well established. In view of the complex endocrine system existent for the regulated metabolism of vitamin D 3 to both 1α,25-dihydroxyvitamin D 3 [1,25(OH) 2 D 3 ] and 24R,25-dihydroxyvitamin D 3 [24R,25-(OH) 2 D 3 ] (both produced by the kidney), an intriguing problem is to elucidate whether only one or both of these dihydroxyvitamin D 3 metabolites is required for the generation of all the biological responses mediated by the parent vitamin D 3 . In contrast to the accumulated knowledge concerning the short term actions of 1,25(OH) 2 -D 3 on stimulating intestinal calcium absorption and bone calcium reabsorption, relatively little is known of the biological function of 24,25(OH) 2 D 3 . We report now the results of a nine month study in which chicks were raised on a vitamin D-deficient diet from hatching to sexual maturity and received as their sole source of “vitamin D” either 24,25(OH) 2 D 3 or 1,25(OH) 2 D 3 singly or in combination. Specifically we are describing the integrated operation of the vitamin D endocrine system as quantitated by the individual measurement in all birds of 22 variables related to “vitamin D status” and as evaluated by the statistical procedure of multivariate discriminant analysis. Twelve of these variables involved detailed analysis of the bone including quantitative histology and the other 10 variables reflect various manifestations of vitamin D action, e.g. serum Ca 2+ and Pi levels, vitamin D-dependent calcium binding protein (CaBP) in the intestine and kidney, egg productivity etc. As evaluated by the multivariate analysis, it is clear that 24,25(OH) 2 D 3 and 1,25(OH) 2 D 3 are simultaneously required for normalization of calcium homeostasis.

A program package for quantitative analysis of histologic structure and remodeling dynamics of bone.

Quantitative bone histology has become an increasingly valuable tool for the management and diagnosis of metabolic bone disease. A new computer-assisted method for quantitative analysis of bone histology which combines the advantages of discriminatory input by the investigator with a significant reduction of evaluation time is presented. These programs allow the analysis of a sufficient number of subjects from different populations for the establishment of normative data, and are useful in the diagnosis and documentation of the treatment of metabolic bone disease.

The role of vitamin D metabolites in the management of bone abnormalities in renal disease.

Considerable progress has been made in recent years in the field of vitamin D metabolism (1–7). There is better understanding of the factors controlling the formation of the various metabolites of the vitamin and the role of these metabolites in calcium and phosphorus homeostasis. In addition, methods have been developed for the measurement of blood levels of the various vitamin D analogs (8–13). These advances have permitted us to better understand the role of vitamin D in the pathogenesis of bone abnormalities in renal disease and the requirement of the various compounds for the management of these derangements. Therefore, the indications for, and the optimal time for the initiation of therapy with the various vitamin D metabolites for the management of renal osteodystrophy should be reconsidered. Bone abnormalities occur in patients with renal disease and normal renal function (14), in those with mild to moderate renal insufficiency (15), as well as in patients with advanced renal failure (16–20). Although the severity of the bone disease may vary among these groups of patients, the nature and characteristics of bone pathology are similar.

Disturbed Terminal Mineralization of Bone in Idiopathic Hypercalciuria

Hypercalciuric renal stone-formers are commonly divided into 3 different groups: Resorptive hypercalciuria, hyperabsorptive and renal hypercalciuria1–4. Patients with hyperabsorptive hypercalciuria have normal or low serum parathyroid hormone activities and normal to low urinary excretion of cAMP. In renal hypercalciuria elevated serum PTH levels and increased renal excretion of cAMP has been reported4–6. Bordier et al.6 published elevated immunoreactive parathyroid hormone levels and increased numbers of osteoclasts in bone biopsies obtained from patients with renal hypercalciuria. No information is available on bone histology in patients with hypercalciuria of the hyperabsorptive type. The present study evaluates quantitatively bone sections in 15 patients with hyperabsorptive hypercalciuria and recurrent stone-formation.