tetracycline and Calcinosis

This review of the histomorphometry of bone outlines methods of biopsy and processing of specimens in the laboratory, the basic principles of morphometry, and the measurements made in order to obtain estimates of the proportional volumes and surfaces occupied by different components of bone. Variability such as that between methods, observers and laboratories is discussed and a brief outline of automatic and semiautomatic methods of image analysis also given.

Topics: Adolescent; Adult; Aged; Anthropometry; Biopsy; Bone and Bones; Calcinosis; Child; Female; Fluorescent Dyes; Humans; Male; Middle Aged; Minerals; Osteoblasts; Tetracycline

In young growing rats, fed the lathyrogenic agent aminoacetonitrile for 3 weeks, characteristic skeletal changes developed resembling the chronic state of osteolathyrism. In both lathyritic and untreated control rats, the femoral head, the distal end of the femur, the proximal tibial end, the thalocalcanean joint and the first lumbar vertebra were investigated using undecalcified thin sections and ground sections. The following methods were employed: quantitative morphometrical analysis of bone structure and bone remodelling of the lumbar vertebra, histochemical demonstration of the composition of polysaccharides, detection of the course of collagenous fibres in cartilage and bone by the polarizing microscope, tetracycline-labelling and fluorescence microscopical determination of epiphyseal longitudinal growth and bone formation activity, photometrical quantification of microradiographies and computer-aided determination of the mineral content of bone.

Topics: Aminoacetonitrile; Animals; Bone Diseases; Bone Resorption; Calcinosis; Disease Models, Animal; Exostoses, Multiple Hereditary; Femur Head; Male; Osteoblasts; Osteoclasts; Rats; Spine; Tetracycline; Tibia

This work was aimed at synthesizing novel bisphosphonates (BPs) and examining them in comparison to clinically used BPs such as pamidronate and alendronate, and to tetracycline, in order to evaluate their potential as anticalcification and antiresorption agents. The correlation between the various models was examined in order to establish facile experimental models for pre-screening of potential compounds.. Nitrogen-containing heterocyclic, novel BPs such as 2-(3-methylimidazolio) ethylidene-1,1-bisphosphonic acid betaine (VS-5b), 2-(2-dimethylamino-4-pyrazinio)ethylidene-1,1-bisphosphonic acid betaine (VS-6b), and 2-(2-alpha-pyridylethylthio) ethylidene-1,1-bisphosphonic acid (ISA-225), were synthesized and evaluated in comparison to clinically used BPs, in various experimental models of resorption and calcification.. The physicochemical properties of the novel compounds are slightly different than the BPs in clinical use: the pKa values are lower, the affinity for hydroxyapatite is lower and the solubilities of the calcium salts are higher. The anticalcification potencies of the novel compounds were high and ranked as follows: alendronate = pamidronate > VS-6b = VS-5b = ISA-225 > tetracycline. The in vivo antiresorption activity of VS-5b and VS-6b in comparison to that of the clinically employed, pamidronate, was shown to be similar and higher, respectively.. The anticalcification activity of the novel compounds as well as that of tetracycline was lower than that of alendronate. The antiresorption activity of VS-6b was similar to that of pamidronate. A good correlation between the different models was found, enabling the facile screening of novel compounds. The activities of tetracycline and EDTA highlight the distinct behavior of BPs as "crystal poison." In addition, tetracycline was found to be a potent anticalcification agent in the ectopic calcification model.

Topics: Alendronate; Animals; Anti-Inflammatory Agents; Betaine; Bone and Bones; Bone Resorption; Calcinosis; Chelating Agents; Diphosphonates; Edetic Acid; Hindlimb; Hydroxyapatites; Male; Pamidronate; Protein Synthesis Inhibitors; Rats; Structure-Activity Relationship; Tetracycline

Alkaline phosphatase (ALP) activity is a new histomorphometric index of the extent of osteoblastic surfaces involved in mineralization. To assess its validity in the evaluation of bone formation, we carried out a comparative study between histomorphometric values obtained on the basis of the extent of tetracycline labeling and of the length of ALP-positive endosteal surfaces. The following variables were compared (indicated by ALP when based on the extent of ALP positivity): trabecular mineralizing surface (MS/BS vs. ALP.S/BS); osteoid mineralizing surface (MS/OS vs. ALP.S/OS); bone formation rate (BFR/BS vs. ALP.BFR/BS); and adjusted appositional rate (Aj.AR vs. ALP.Aj.AR). Bone biopsies from 39 patients with chronic renal failure and different types of renal osteodystrophy were considered (48 +/- 12 years of age; 19 men and 20 women). Patients were double labeled with tetracycline and biopsies were embedded in glycol-methacrylate at +4 degrees C. Patients showed various types of renal osteodystrophy and were assigned to different groups of pathologies. Although it differed in incidence according to the different groups, ALP activity was found in typical plump osteoblasts bordering osteoid seams and in flat cells, either in contact with osteoid or along the quiescent surfaces of bone in continuity with it. Tetracycline codistributed with all these features to variable extents, according to groups. In all patients, however, ALP.S/BS and ALP.S/OS respectively exceeded MS/BS and MS/OS. In consequence of this, ALP.BFR/BS and ALP.Aj.AR were greater than BFR/BS and Aj.AR, respectively. For each of the variable considered, differences among groups of patients with different types of renal osteodystrophy were highly significant. Good correlations were found between the variables measured with the two methods.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Alkaline Phosphatase; Biopsy; Bone Development; Calcification, Physiologic; Calcinosis; Calcium; Chronic Kidney Disease-Mineral and Bone Disorder; Female; Histocytochemistry; Humans; Hyperparathyroidism, Secondary; Ilium; Image Processing, Computer-Assisted; Kidney Failure, Chronic; Male; Middle Aged; Osteoblasts; Osteocalcin; Osteomalacia; Parathyroid Hormone; Phosphates; Tetracycline

Clinical studies in thyrotoxicosis reveal a state of high bone turnover leading, eventually, to osteoporosis. Recently there has been concern that thyroxine (T4) treatment may have a similar effect on bone. Rat models have been used to study the effects of T4 on bone, but the majority of studies have looked at the effects of T4 after only 3 weeks of treatment. The aim of this study was to evaluate histomorphometric changes in rats after 12 weeks of thyroxine overtreatment or 12 weeks of hypothyroidism compared with untreated control animals. Animals received either T4 200 micrograms/kg per day, 0.1% propylthiouracil, or vehicle for 12 weeks. Tetracycline was administered 1 week and 3 weeks prior to killing. Iliac crest bone was used for histomorphometry. Serum T4 measurements (taken at killing) confirmed hyper- and hypothyroidism in the appropriate animal groups (between group difference p < 0.001 by ANOVA). In hyperthyroid animals there was an increase in mineral apposition rate (MAR; 0.94 vs. 0.59 microns/day, p < 0.001) and mineral formation rate (MFR/BS; 0.24 vs. 0.12 x 10(-2) micron3/micron2 per day, p < 0.001) and a slight increase in eroded surfaces (ES/BS%; 1.54 vs. 1.36, p < 0.05) compared with controls, consistent with previous in vitro and in vivo observations. In hypothyroid rats there was a marked reduction in osteoid surfaces (OS/BS%; 1.7 vs. 24.8, p < 0.001) and MAR (0.3 vs. 0.59 micrograms/day, p < 0.001), a reduction in ES/BS% (0.51 vs. 1.36, p < 0.05), and an increase in cancellous bone volume (BV/TV%; 30.29 vs. 19.6, p < 0.05), suggesting that thyroid hormones are a requirement for normal bone turnover.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Analysis of Variance; Animals; Body Weight; Calcinosis; Disease Models, Animal; Drug Overdose; Hyperthyroidism; Hypothyroidism; Ilium; Male; Propylthiouracil; Radioimmunoassay; Rats; Rats, Wistar; Tetracycline; Thyroid Function Tests; Thyroxine

In patients with chronic renal failure estimations of the extent of calcification fronts delineated by in vivo tetracycline labelling correlated well with estimates obtained after staining the fronts with haematoxylin dye (Raina method). Similarly there was a good correlation between the Raina method and the demonstration of calcification fronts with ultraviolet (UV) light fluorescence after immersion of the bone tissue in fixative containing a freshly prepared solution of 1% tetracycline. These studies indicate that this latter is a valid and useful technique for demonstrating calcification fronts in a situation where tetracycline cannot be administered systemically.

Topics: Bone and Bones; Calcinosis; Doxycycline; Eosine Yellowish-(YS); Hematoxylin; Humans; Kidney Failure, Chronic; Staining and Labeling; Tetracycline

Five spine specimens obtained at autopsy and five biopsies of sacroiliac joints from subjects with ankylosing spondylitis were submitted to microradiography and to fluorescence microscopy for detection of tetracycline. Decalcified histological sections were also prepared. Microradiography provides a link between the clinical X-ray picture and the classical decalcified section; it enables calcified cartilage, and hence the early stage of most syndesmophytes to be recognised more easily and accurately; It revealed a peculiar calcification of elastic fibers of the ligamentum flavum. Tetracycline labels showed that: in an early case of sacro-iliac arthritis, calcification of the articular cartilage might partly explain the desification of the X-ray picture; syndesmophytes were thickening at both their superficial and deep faces; thickening, lengthening and internal remodelling of the intervertebral bridges occurred together; and calcium was deposited at the end-plates as well.

Topics: Adult; Calcinosis; Cartilage, Articular; Humans; Intervertebral Disc; Ligaments; Male; Microradiography; Microscopy, Fluorescence; Middle Aged; Sacroiliac Joint; Spondylitis, Ankylosing; Tetracycline

Blue nodules developed in the skin of a patient with acne concomitant with the start of tetracycline therapy. When removed, these nodules were brown and histologic examination revealed a lamellate structure compatible with bone. Under ultraviolet light, these osteomas fluoresced yellow, indicating the presence of tetracycline. This suggests that tetracycline, combined with new bone formation, causes pigmentation of osteoma cutis.

Topics: Acne Vulgaris; Adult; Calcinosis; Female; Humans; Osteogenesis; Skin Diseases; Skin Pigmentation; Tetracycline

Bone biopsies were performed after tetracycline double-labelling by transfixing the right iliac crest in forty hyperthyroid patients. The bone changes in cortical and trabecular bone were determined by simple measurement and point counting on decalcified and undecalcified stained sections. A slight decrease in the amount of cancellous bone was found. The mean cortical width was normal. The amount of osteoid and the length of the osteoid seams were increased, whereas the mean width of osteoid seams was decreased. The cortical osteoclastic activity and porosity were markedly increased. The trabecular osteoclasic activity was moderately increased and the mean size of periosteocytic lacunae was slightly increased. The calcification rate in cancellous bone was increased as were the active calcification surfaces (tetracycline-labelled). The osteoclastic activity in cortical bone was positively correlated to the free thyroxine index and to the urinary calcium and phosphorus excretion. The findings indicate that the bone changes in hyperthyroidism are specific and that thyroid hormone(s) stimulates both bone formation and resorption followed by increased porosity in cortical bone and by mobilization of bone mineral.

Topics: Adolescent; Adult; Age Factors; Aged; Biopsy; Bone and Bones; Bone Resorption; Calcinosis; Calcium; Female; Humans; Hyperthyroidism; Male; Middle Aged; Phosphorus; Tetracycline

Topics: Adolescent; Adult; Autopsy; Biopsy; Bone and Bones; Calcification, Physiologic; Calcinosis; Cartilage, Articular; Decalcification Technique; Female; Femur; Fluorescent Dyes; Humans; Joint Diseases; Male; Microradiography; Middle Aged; Patella; Staining and Labeling; Tetracycline

Topics: Adult; Bone and Bones; Calcinosis; Ehlers-Danlos Syndrome; Female; Fluorescence; Humans; Hydroxyproline; Male; Osteoporosis; Radiography; Tetracycline

Topics: Adenocarcinoma; Animals; Calcinosis; Calcium; Cricetinae; Cytoplasm; Fluorescence; Humans; Neoplasm Transplantation; Neoplasms, Experimental; Tetracycline

Topics: Anti-Bacterial Agents; Calcinosis; Humans; Tetracycline

Topics: Calcification, Physiologic; Calcinosis; Chlortetracycline; Cholecalciferol; Connective Tissue; Dihydrotachysterol; Fluorescence; Gastric Mucosa; Kidney; Lung; Microradiography; Microscopy; Microscopy, Fluorescence; Muscle, Smooth; Parathyroid Hormone; Rats; Research; Stomach; Tetracycline; Toxicology

Topics: Bone and Bones; Calcification, Physiologic; Calcinosis; Fluorescence; Protein Synthesis Inhibitors; Tetracycline

Topics: Animals; Anti-Bacterial Agents; Calcification, Physiologic; Calcinosis; Cortisone; Desoxycorticosterone; Desoxycorticosterone Acetate; Dihydrotachysterol; Protein Synthesis Inhibitors; Rats; Tetracycline