Osteopetrosis is a metabolic bone disease characterized by excessive accumulation of skeletal mass due to a reduction in bone resorption. The pathogenesis of osteopetrosis is reduced osteoclast function. Reports of osteoclast numbers in several mammalian mutations exhibiting osteopetrosis have shown them to be increased, decreased, or normal in numbers. The present investigation quantitated the osteoclast populations and examined the cytology of osteoclasts by light microscopy in calvarial and tibial sites in one rabbit and two mouse mutations and compared them with their normal littermates.
Quantitative bone histology was carried out in five osteosclerotic adults. The bone was extremely hard in all patients, and open biopsy was usually required. One patient, aged 18 years, presented with hypoplastic anemia, and the most probable explanation for the osteosclerosis is a marrow stem cell defect leading to defective osteoclasts. Another had the dominant form of osteopetrosis. Her bone contained cartilage remnants, and there were many large, morphologically abnormal osteoclasts, which lacked normal cytoplasmic acid phosphatase activity. The third patient had chronic renal failure and osteomalacia; here the increased bone mass might have resulted from an inability of normal osteoclasts to resorb bone, due to the surface coating of osteoid, though an earlier increase of bone formation cannot be excluded. The fourth patient, who suffered from systemic mastocytosis, had high turnover bone, with greatly increased bone formation. The fifth patient, with fluorosis of bone, also had increased bone formation and resorption, the process being much more pronounced in the head of her pathologically fractured femur than it was in the iliac crest. In this patient some osteoclasts had reduced acid phosphatase activity and long cytoplasmic extensions, both changes similar to those observed in diphosphonate-treated animals. Very diverse processes can result in the increased cancellous bone mass producing the radiographic appearance of diffuse osteosclerosis.
Extracellular matrix vesicles from bone and epiphyseal cartilage of femur and tibia of rats were isolated by collagenase digestion (crude vesicles) and further purified by sucrose gradient centrifugation. Fractions containing cells and membranes were also isolated from the two tissues. The alkaline and acid phosphatase and ATPase activities, as well as protein content of all fractions including crude and purified matrix vesicles, were assayed. The crude vesicles from both tissues demonstrated a high alkaline phosphatase specific activity (5-20 times higher than in the cell fraction). The total enzyme activities and protein content were significantly higher in all fractions from cartilage than those from bone. A major peak of alkaline phosphatase activity and protein content was obtained following the sucrose gradient centrifugation. The position of this peak was similar for both tissues. The specific activity of alkaline phosphatase of purified matrix vesicles was significantly higher in bone than in cartilage. The phosphatase activities from cartilage and bone showed a similar pH dependence and a similar response to metal ions. Of the metal ions tested (Na+, Mg2+, Zn2+, and Ca2+) only Zn2+ (at 5 mM concentration) inhibited significantly the alkaline phosphatase activity of purified matrix vesicles. The electrophoretic profile of purified matrix vesicles showed eight major protein bands common for both tissues. In addition, cartilage vesicles appeared to possess two peptides not found in bone.
Transilial biopsies from postmenopausal osteoporotic patients showed that static features and remodeling activity tended tended to form a pattern, with the area midway between the cortices having less bone and lower remodeling activity than the area closer to the inner boundary of the cortex. The appearance, enlargement, and coalescence of the resorption cavities within the subendosteai area of the cortex lead to negative bone balance and a progressive trabeculation of the cortex, resulting in the formation of a transitional zone. Therefore, in most cases we can distinguish two different zones, transitional and trabecular zones, within the area usually known as the trabecular bone area. The transitional zone undergoes more active remodeling than the trabecular zone and has an important role in evaluation of the traditional trabecular bone volume and remodeling dynamics depending on the field selection for this evaluation, i.e., the proportion between transitional and trabecular zones within the selected fields.
Testosterone cypionate and Stanozolol are Anabolic-Androgenic Steroids (AAS) which are synthetic substances that possess functions similar to testosterone. The use of these substances has increased considerably among youngsters and sports practitioners aiming better performance of with aesthetic purposes. The major concern is the effects caused by the inappropriate use of the substances, such as hypertension, myocardial ischemia, and left ventricle hypertrophy. The objective of the present research was to measure the diameter of the left ventricle lumen and the thickness of the left ventricle myocardium in mice submitted to supraphysiological doses of AAS. A total of 30 female Swiss mice were used in the experiments. The animals received supraphysiological doses of the AAS for 30 days, and during the treatment period, they were put to swim in intercalated days. After treatment animals were euthanized and slides were made from the hearts for measurements. Results demonstrated that both AAS changed significantly the heart morphology: Testosterone cypionate led to an increase in the ventricular lumen and stanozolol increased left ventricle myocardium thickness. In conclusion, the use of AAS in supraphysiological doses can change the heart morphology and can lead to serious health consequences.
The anatomy of the remodeling sites in bone is only partly reflected by random histologic sections. This study is aimed at reconstructing the three-dimensional morphology of the osteons in human trabecular bone from serial sections of decalcified tissue. The osteons resembled broad bands, which were made up of parallel lamellae, bounded on one side by the marrow surface and on the other side by an irregular cement plane. The mean thickness was much less (<0.2) than the mean extent in the other dimensions. The plate may, therefore, be used as the morphologic model for stereologic studies. The plates were curved and irregular. One three-dimensional osteon can, therefore, give rise to a varying number of profiles in a single random section. The two-dimensional profiles, which are of unequal surface extent, are thus not appropriate sampling units for morphometric studies of, e.g., osteon thickness, osteoid thickness, or calcification rate in trabecular bone. When estimating thickness the number of measuring sites should be sampled proportional to the surface extent of the profiles.
The thickness of the bone walls formed at completed remodeling sites was estimated by morphometry in iliac trabecular bone from 85 normal individuals (48 women and 37 men) aged 18-90 years. The mean three-dimensional (3-D) wall thickness was 59.4 +/- 5.9 micron. No sex difference was observed. The wall thickness decreased with age: Thickness (micron) = 65.56 micron - 0.14 micron/yr X age (yr). This reduction may lead to a loss of bone with increasing age. The coefficient of variation in completed wall thickness between individuals of the same age was 7%. The factors controlling the thickness are largely unknown, but it was noted that the intraindividual distributions of linear 3-D wall thickness (proportional to the mass of the wall) were symmetric, while distributions of reciprocal 3-D thickness (proportional to the conductivity for oxygen and waste products) were markedly rightskewed. A subgroup comprising 42 individuals aged 18-56 years had been double labeled with tetracycline. The average 3-D calcification rate was 0.63 +/- 0.11 micron/day. No relationship to age or sex was demonstrated. Based on the estimates of completed wall thickness and calcification rate, the mean duration of calcification at remodeling sites was calculated to be approximately 100 days.
The application of x-ray microtomography (computerized axial tomography) to the histomorphometry of bone at a resolution of approximately 15 μm is described. Serial sections (obtained without physically cutting the sample) separated by 25 μm were made from an 0.8 mm square rod of human femoral bone. These showed several haversian canals and changes in mineralization within individual sections. The results obtained are quantitative in terms of the x-ray linear absorption coefficient, which is closely related to the degree of mineralization. Thus x-ray microtomography has the potential for the nondestructive determination of the fractional bone volume, with the ability to select the degree of mineralization of the bone used to determine the fraction.
A 19-year-old Indian girl presenting with intermittent tetany, enamel hypoplasia, bilateral cataracts, and calcification of the basal ganglia is described. Dental evidence suggested a calcification defect had been present from the age of 2-3 years. Hypocalcemia, hyperphosphatemia, and low levels of immunoassayable parathyroid hormone (iPTH), urinary cAMP, 25-hydroxyvitamin D, and 1,25-dihydroxyvitamin D were documented, suggesting hypoparathyroidism with vitamin D deficiency. A bone biopsy showed osteomalacia. Following ultraviolet irradiation and oral calciferol therapy, a symptomatic and biochemical response typical of privational vitamin D deficiency occurred. iPTH levels rose to normal and remained normal following withdrawal of treatment, indicating that the clinical features were entirely due to long-standing vitamin D deficiency.
Although PTH inhibits bone collagen synthesis acutely, prolonged administration of PTH increases trabecular bone mass. The objectives of this study were to develop a simple method to quantitate the anabolic response of cortical and trabecular bone, to determine if the trabecular bone response is at the expense of cortical bone, and to correlate the bone response with changes in serum calcium or phosphate. Subcutaneous injections of 2 to 16 micrograms/100 g body weight hPTH(1-34) were given daily to weanling rats for 12 days. The trabecular and cortical bone were manually separated from the distal femur, and calcium, hydroxyproline, and extracted dry weight were measured. Growth and renal function were not impaired. Serum calcium (range: 8.9-9.5 mg%) and serum phosphate (range: 7.7-8.5 mg%) did not differ significantly from control serum calcium, 9.1 mg%, or serum phosphate, 8.1 mg%. A dose-related anabolic response was observed in calcium, hydroxyproline, and dry weight of trabecular bone. At the highest dose of hPTH for 12 days, these values were increased above control by 26%, 33%, and 26%, respectively (P less than .01). While cortical bone values increased over 12 days, only the dry weight increase was significant (P less than .01). Our method showed an increase in trabecular bone mass after daily subcutaneous injections of hPTH (1-34) at doses that were neither toxic nor hypercalcemic. Although the absolute change of cortical bone mass was greater than that of trabecular bone, it was more variable and not statistically significant. Nevertheless, these results indicate that trabecular bone mass did not increase at the expense of cortical bone.
This report describes the staining reactions of decalcified dentine and the microradiographic appearance of undecalcified and decalcified dentine after it had been covered with four different materials. Young premolars were employed, and the observation periods extended up to 117 days. Marked changes could be observed with microradiography of undecalcified sections. Apart from the alterations described previously as a result of cavity preparations (Mjör, 1967), the two other methods only revealed changes in the dentine-predentine region.Different patterns of dentine reactions were observed depending on the material used and it was concluded that the dentine is capable of reacting in different ways under varying experimental conditions. On the basis of the observations made, it is suggested that the testing of operative procedures and filling materials should include detailed studies of the dentine as well as of the pulp.Les réactions colorées de la dentine décalcifiée ainsi que l'aspect microradiographique de la dentine décalcifiée et non décalcifiée sont décrits après mise en contact avec 4 produits différents. Des prémolaires sont utilisées pendant une période de 117 jours. Des changements nets sont observés sur les microradiographies de coupes non décalcifiées. A part les lésions provoquées par la taille des cavités, décrites antérieurement (Mjör, 1967), les deux autres méthodes ne montrent que des changements dans la région dentine-prédentine.Différents types de réactions dentinaires sont observés en fonction du matériel utilisé et il apparaît ainsi que la dentine est capable de réagir de différentes façons, selon les conditions expérimentales utilisées. L'essai de méthodes opératoires et de produits d'obturation devrait inclure l'étude détaillée de la dentine et de la pulpe.Diese Arbeit beschreibt die Färbereaktionen entkalkten Dentins und das mikroradiographische Erscheinungsbild unentkalkten und entkalkten Dentins, nachdem es mit 4 verschiedenen Materialien bedeckt worden war. Junge Prämolaren wurden während Untersuchungszeiträumen bis zu 117 Tagen untersucht. Bemerkenswerte Unterschiede konnten durch Mikroradiographie unentkalkter Schliffe festgestellt werden. Von früher beschriebenen Veränderungen als Ergebnis der Kavitätenpräparation abgesehen (Mjör, 1967), lieβen die anderen beiden Methoden lediglich Veränderungen im Bereich der Dentin-Prädentin-Region erkennen.Abhängig vom benutzten Material wurden unterschiedliche Dentinreaktionen beobachtet; daraus wurde geschlossen, daβ das Dentin in der Lage ist, unter verschiedenen experimentellen Bedingungen in unterschiedlicher Weise zu reagieren. Auf der Grundlage dieser Beobachtungen wird vorgeschlagen, daβ die Prüfung von Behanglungsmethoden und Füllungsmaterialien sorgfältige Untersuchungen des Dentins wie auch der Pulpa einbeziehen sollte.
