Showing papers in "Calcified Tissue International in 1980"
TL;DR: The hypothesis that structurally incorporated H2O is the principal cause of the enlargement of thea lattice parameter of TE compared to hydroxyapatite is allowed, and an interconnectedness of the A and B sites which may be significant in vivo is suggested.
Abstract: Further insight into human tooth enamel, dense fraction (TE), has been obtained by following the change and loss of CO3
2−, OH−, structurally incorporated H2O, Cl−, and, indirectly, HPO4
2− after TE had been heated in N2 or vacuum in the range 25–1000°C. Quantitative infrared spectroscopic, lattice parameter, and thermogravimetric measures were used. Loss of the CO3
2− components begins at much lower temperature (e.g., 100°C) than previously recognized, which has implications for treatments in vitro and possibly in vivo. CO3
2− in B sites is lost continuously from the outset; the amount in A sites first decreases and then increases above 200° to a maximum at ∼800°C (>10% of the possible A sites filled), where it is responsible for an increase ina lattice parameter. A substantial fraction of the CO3
2− in B sites moves to A sites before being evolved, apparently via a CO2 intermediary. This implies an interconnectedness of the A and B sites which may be significant in vivo. No loss of Cl− was observed at temperatures below 700–800°C. Structural OH− content increases ∼70% to a maximum near 400°C. Structurally incorporated water is lost continuously up to ∼800°C with a sharp loss at 250–300°C. The “sudden”a lattice parameter contraction, ∼0.014A, occurs at a kinetics-dependent temperature in the 250–300°C range and is accompanied by reordering and the “sharp” loss of ∼1/3 of the structurally incorporated H2O. The hypothesis that structurally incorporated H2O is the principal cause of the enlargement of thea lattice parameter of TE compared to hydroxyapatite (9.44 vs 9.42A) is thus allowed by these experimental results.
241 citations
TL;DR: Age-related changes in femoral cortical bone were quantified in an age-graded series of human cadavers to define the role of increasing Haversian canal number and mean canal size per unit area of cortical bone as a factor in the reduction of bone mass as a function of age.
Abstract: Age-related changes in femoral cortical bone were quantified in an age-graded series of human cadavers. Variables included in this study were cortical thickness, bone mineral content, cortical bone density, summed Haversian canal area, Haversian canal number, and mean Haversian canal area. Females showed significant (P<0.05) decreases in cortical thickness, bone mineral content, and cortical bone density when plotted against age. Males exhibited slight nonsignificant declines for cortical thickness, bone mineral content, and cortical bone density. Both males and females exhibited significant (P<0.05) age-related increases in summed Haversian canal area values and Haversian canal number. Females as a group were found to exhibit significantly (P<0.05) larger mean Haversian canal area values compared with males, but the male group exhibited more Haversian canals per unit area of cortical bone compared with females.
155 citations
TL;DR: It is concluded that the lower doses of APD inhibited resorption of bone and cartilage, possibly by physicochemical stabilization of bone mineral, whereas the effect on bone apposition was due to a cellular homeostatic mechanism.
Abstract: Dose-related effects of APD on bone metabolism and Ca homeostasis were studied in rats. The experimental approach consisted of longitudinal and cross-sectional observations, aiming at a kinetic interpretation. Bone and cartilage resorption was inhibited within 2–8 days at doses between 0.16 and 16 µmol/kg body weight/day. This was followed by changes in bone apposition that needed at least 23 days for a maximal effect. The time lag created a transient dissociation between resorption and apposition resulting in excess Ca and P retention, adding to increased metaphyseal bone mass. At high doses of APD (≥40 µmol/kg/day) the mineral content of new matrix decreased, associated with impairment of longitudinal growth of long bones. It is concluded that the lower doses of APD inhibited resorption of bone and cartilage, possibly by physicochemical stabilization of bone mineral, whereas the effect on bone apposition was due to a cellular homeostatic mechanism. Inhibition of growth and of matrix calcification, requiring much higher doses, may be due to a direct, toxic effect on bone cells. The modes of action of APD are discussed in relation to EHDP and Cl2MDP.
154 citations
TL;DR: A structural mechanism for the incorporation of impurities during hydrolysis of octacalcium phosphate is presented, of particular importance since the presence of carbonate in human enamel appears to be related to caries susceptibility.
Abstract: Octacalcium phosphate (Ca8H2(PO4)6·5H2O) is considered to be a precursor in the formation of apatite in bones and teeth; a crucial step for incorporation of impurities appears to occur during its hydrolysis. The present study examines the role that octacalcium phosphate plays in the process of incorporation of carbonate into apatite. Chemical, X-ray diffraction, and infrared techniques were used.
147 citations
TL;DR: The results indicate that the year-old castrate male rat may be a valuable experimental model for studies of the treatment of osteoporosis.
Abstract: Forty young (23-day-old) and thirty old (1-year-old) male rats were castrated and sacrificed with controls at intervals up to 18 months of age. No differences were observed between femurs or mandibles of rats castrated at 23 days and those of controls. Year-old castrate rats developed femoral osteoporosis after 2 months, which became more pronounced 4 months after castration. This was characterized by reductions in femoral density, dry weight, dry weight per unit length, and ash weight, and by the appearance of resorption cavities in diaphyseal walls and a sparsity of trabeculae in metaphyses and epiphyses of castrate femurs. These results indicate that the year-old castrate male rat may be a valuable experimental model for studies of the treatment of osteoporosis.
144 citations
TL;DR: It is argued that both cell distribution and tissue distribution in the metaphysis support the concept that osteoblasts and osteoclasts, rather than osteocytes, are responsible for the maturation of the metaphys.
Abstract: The purpose of this work was to analyze the proximal tibial metaphysis of the 170 g rat in a quantitative histologic fashion which would allow some relation to tissue age to be established. Stained 3 µm thick tissue sections were analyzed with the aid of a Merz grid on an eyepiece reticule and a light microscope. Tissue mass and cell distribution were studied in all areas. The rate of change in tissue mass during aging of the metaphysis was calculated. Two regions of the metaphysis were identified. One, corresponding to the primary spongiosa, less than 4.45 days of age, is a region of high turnover of hard tissue and high numbers of osteoblasts and osteoprogenitor cells. The other, corresponding to the secondary spongiosa, is a region of relatively low net tissue turnover and low numbers of osteoblasts and osteoprogenitor cells. Osteoclasts were found relatively more uniformly distributed through the metaphysis than were osteoblasts and osteoprogenitor cells. The rate of bone formation in the primary spongiosa is 50 times that found in the Haversian bone of the rib of 5-year-old humans and about 500 times that found at the cortical-endosteal surface of ribs of 5-year-old humans. It is argued that both cell distribution and tissue distribution in the metaphysis support the concept that osteoblasts and osteoclasts, rather than osteocytes, are responsible for the maturation of the metaphysis. The inhomogeneous distribution of both cells and tissue in the metaphysis has definite meaning for the interpretation of findings concerning the incorporation of radionuclides into the skeleton.
138 citations
TL;DR: Normal rat bone maturation has been studied using biochemical methods and hydrazine separation of matrix and mineral for X-ray diffraction and growth in mean crystal size appears to be the determinant of the changing ratios of calcium, magnesium, carbonate, and phosphorus.
Abstract: Normal rat bone maturation has been studied using biochemical methods and hydrazine separation of matrix and mineral for X-ray diffraction In the bone, the amount of mineral increases between 4 and 22 weeks of age, while in the matrix, the ratio of noncollagenous protein to collagen progressively decreases In mineral, in the absence of serum ion changes, growth in mean crystal size appears to be the determinant of the changing ratios of calcium, magnesium, carbonate, and phosphorus, and of the increasing mineral density
133 citations
TL;DR: A potential regulatory role for phosphoproteins in dentin mineralization is suggested after several phosphoprotein preparations all inhibit apatite growth/replication from pre-existing crystal seeds in metastable solutions.
Abstract: Several phosphoprotein preparations (phosvitin, rat incisor and fetal calf molar dentin phosphoproteins) all inhibit apatite growth/replication from pre-existing crystal seeds in metastable solutions. Two stages of the crystal growth process were inhibited by these phosphoproteins. First an initial lag period was induced, probably associated with seed surface phenomena. This period was prolonged indefinitely when a combination of phosphoprotein precoated seeds was used together with soluble phosphoproteins in the crystal growth reaction. Second, the phosphoproteins prolonged that stage of the reaction where octacalcium phosphate is the predominant mineral phase present prior to its conversion to the final apatite product. Pre-treatment of the phosphoproteins with calcium diminished their inhibitory activity to seeded crystal growth as well as towards de novo apatite formation in synthetic extracellular fluids. The presence of collagen diminished the inhibitory activity of the phosphoproteins towards de novo precipitation but had no effect on phosphoprotein-modulated apatite crystal growth in the seeded systems. These results suggest a potential regulatory role for phosphoproteins in dentin mineralization.
122 citations
TL;DR: Cell populations derived from adult rat bone were grown in cell culture and characterized with respect to their morphology and response to hormones, including an initial positive cAMP response to PTH and PGE2, but not to TCT.
Abstract: Cell populations derived from adult rat bone were grown in cell culture and characterized with respect to their morphology and response to hormones. The cells were isolated from adult rat calvaria by mechanical rather than enzymatic methods. Cultures were initiated in modified BGJb medium supplemented with fetal bovine serum. These cultures and several cloned populations derived from them retained the ability to mineralize in vitro even after extended serial passage.
112 citations
TL;DR: Flow is different in different regions of a long bone because of different proportions of cortical and cancellous bone, probably because of interrelationships of function (surfaces undergoing remodeling) and, therefore, of energy metabolism and blood flow.
Abstract: Blood flow was measured in mature and immature dogs by means of tracer microspheres. Microspheres of 15 µm were found to be the most suitable size in the dog. Total body nonentrapment in the awake, standing dog is likely to be less than 10%. Cortical bone flood flow, devoid of periosteum and marrow, is 2.5 ml/100 g/min in mature dogs and 7.0 ml/100 g/min in immature dogs,P<0.005. Blood flow in cancellous bone is greater than that in cortical bone in mature (P<0.001) and immature (P<0.02) dogs. Flow is different in different regions of a long bone because of different proportions of cortical and cancellous bone, probably because of interrelationships of function (surfaces undergoing remodeling) and, therefore, of energy metabolism and blood flow.
99 citations
TL;DR: The results suggest that the receptor for 1α25(OH)2D3 in both bone resorbing and bone forming cells has similar affinities for several vitamin D metabolites.
Abstract: We compared the effects of four vitamin D metabolites, 1α,25 dihydroxy vitamin D3 (1α,25(OH)2D3), 1α hydroxy vitamin D3 (1αOH D3), 25 hydroxy vitamin D3 (25 OH D3), and 24R,25 dihydroxy vitamin D (24R,25(OH)2D3) on resorption and collagen synthesis in fetal rat bone maintained in organ culture. Resorption was quantitated by measuring the release of previously incorporated45Ca from long bone shafts of 19-day fetal rats, and collagen synthesis was assessed by measuring the incorporation of3H-proline into collagenase digestible protein (CDP) in calvaria from 21-day fetal rats. All four compounds stimulated bone resorption and inhibited collagen synthesis, but 1α,25(OH)2D3 was approximately 1000 times more potent in both organ culture systems. Although the differences were small among the other three compounds, the order of potency was 1αOH D3>25 OH D3≧24R,25(OH)2D3. These results suggest that the receptor for 1α25(OH)2D3 in both bone resorbing and bone forming cells has similar affinities for several vitamin D metabolites.
TL;DR: Dermestid beetles are useful as a technique to clean bones, especially for the parts of the skeleton which are difficult to dissect by hand, when the bones were cleaned by dermestes maculatus beetles or manually.
Abstract: Various parts of the skeleton of normal and osteoporotic rats were compared with respect to their dry weight, ash weight, and calcium content when the bones were cleaned byDermestes maculatus beetles or manually. Both techniques gave similar results. This was also true when whole body calcium measured by neutron activation and total skeletal calcium from bones cleaned by the beetles were compared. Thus dermestid beetles are useful as a technique to clean bones, especially for the parts of the skeleton which are difficult to dissect by hand.
TL;DR: It is suggested that monocytes stimulate osteoclastic bone resorption by prostaglandin production, which may play an important role in physiologic bone remodeling and in bone destruction that occurs in chronic inflammatory diseases such as rheumatoid arthritis and periodontal disease.
Abstract: Monocytes are frequently found adjacent to active bone resorption surfaces in both physiological and pathological situations and may play a key role in bone resorption. There is strong circumstantial evidence that monocytes are precursors for osteoclasts in vivo, and recently they have been shown to resorb devitalized bone directly. The present study shows that monocytes can also resorb bone by stimulation of osteoclasts.
TL;DR: X-ray diffraction studies on calcified tissues (teeth and/or scales) of fish and of shark showed that the presence of fluoride affects the crystallite size and lattice parameters of the apatite phase, suggesting that in some fish, a fluoride-concentrating mechanism is operative during the formation of the enameloid but not during theformation of the dentine.
Abstract: X-ray diffraction studies on calcified tissues (teeth and/or scales) of fish and of shark showed that the presence of fluoride affects the crystallite size and lattice parameters of the apatite phase. An inverse correlation between F contents (ranging from 0.2 to 3.8 wt% F) anda-axis dimensions (9.441 to 9.375±0.003A) exists for both synthetic and enameloid apatites and is consistent with the F-for-OH substitution in the apatite, idealized as Ca10(PO4)6(OH)2 and Ca10(PO4)6F2, for fluoride-free and maximum fluoride-substituted apatite, respectively. In synthetic systems, the incorporation of F is found to be dependent on the F concentration of the media from which the apatite formed. This dependency is also observed between F content of the dentine apatites and the F concentration of the water from which the fish came (i.e., less than 0.08 ppmF in fresh water, about 1.3 ppm in seawater). However, no such dependency was observed between the F incorporation in fish enameloid apatite and the F concentration in the water of origin. In some cases, the F incorporated in the enameloid apatite is much in excess of what can be expected from the F concentration of water. These observations suggest that in some fish, a fluoride-concentrating mechanism is operative during the formation of the enameloid but not during the formation of the dentine, and this mechanism appears to be specie-related.
TL;DR: Purified matrix vesicle alkaline phosphatase from bovine fetal epiphyseal cartilage hydrolyzes a variety of phosphate esters as well as ATP and PPi, and is inhibited irreversibly by Be2+ ion, EDTA, EGTA, ethane-l-hydroxydiphosphonate, dichloromethanediphosph onate, L-cysteine, and N-ethylmaleimide.
Abstract: Purified matrix vesicle alkaline phosphatase from bovine fetal epiphyseal cartilage hydrolyzes a variety of phosphate esters as well as ATP and PPi. Optimal activities forp-nitrophenyl phosphate, ATP, and PPi are found at pH 10.5, 10.0, and 8.5, respectively. The latter two substrates exhibit substrate inhibition at high concentrations.p-Nitrophenyl phosphate demonstrates decreasing pH optima with decreasing substrate concentration. Heat inactivation studies indicate that both phosphorohydrolytic and pyrophosphorolytic cleavage occur at the same site on the enzyme. Mg2+ and Hg2+ ions inhibit thep-nitrophenyl phosphatase activity at pH 10.5 while Mn2+ ions show no effect. Pi, levamisole, CN−, Zn2+, Ca2+ ions, and L-phenylalanine are reversible inhibitors of the phosphomonoesterase activity. Pi is a linear noncompetitive inhibitor with a Ki of 8.0 mM. Levamisole and L-phenylalanine are uncompetitive inhibitors with inhibition constants of 0.02 and 39.4 mM, respectively. Ca2+ ions inhibit noncompetitively with a Ki of 9.3 mM. Zn2+ ion is a potent noncompetitive inhibitor with an inhibition constant of 0.026 mM. The enzyme is inhibited irreversibly by Be2+ ion, EDTA, EGTA, ethane-l-hydroxydiphosphonate, dichloromethanediphosphonate, L-cysteine, and N-ethylmaleimide. NaCl, KCl, and Na2SO4 at 0.5–1.0 M inhibit the enzyme.
TL;DR: The existence of two kinetically different, as well as ultrastructurally different, members of the metaphyseal osteoprogenitor cells population is postulated and a cell cycle time of 39±18 h was found for the osteoprogensitor cell population, but has limited meaning.
Abstract: The purpose of this work was to provide futher knowledge about bone cell kinetics in the metaphysis of the growing long bone. Seventy rats were sacrificed from 1 to 120 h after injection of tritiated thymidine. Autoradiographs of 3 micrometers thick sections of the proximal tibial metaphysis were studied in a manner which allowed evaluation of labeled cell nuclei as a function of increasing age of metaphyseal tissue. A cell cycle duration study for osteoprogenitor cells was done. Labeled osteoprogenitor cells and osteoblasts first appeared at 1 h post-injection. The great majority of all labeled osteoprogenitor cells and osteoblasts was found within 1 mm of the growth cartilage-metaphyseal junction (GCMJ) at all times, apparently migrating with the moving GCMJ. In contrast, labeled osteoclast nuclei first appeared at 24 h post-injection within 0.3 mm of the GCMJ and remained always with the area of bone surface with which they were first associated, even as the GCMJ migrated away. By 5 days post-injection, the source of new labeled osteoclast nuclei in the metaphysis near the GCMJ was depleted, whereas that for the osteoblasts remained. The existence of two kinetically different, as well as ultrastructurally different, members of the metaphyseal osteoprogenitor cells population is postulated. A cell cycle time of 39 +/- 18 h was found for the osteoprogenitor cell population, but has limited meaning. A schema for metaphyseal bone cell movements during longitudinal bone growth is presented.
TL;DR: Electro microscopic investigations on young bone tissue and on de novo bone formation found variations in the number and appearance of nuclei, Golgi, RER, and lysosomes could be an indication of altered activity of the osteoclast.
Abstract: Stimulated by the rather sparse information in the literature on cellular changes induced by EHDP, we carried out electron microscopic investigations on young bone tissue and on de novo bone formation. Cellular changes could be observed during continuous administration of EHDP. The osteoblasts demonstrated temporary storing of crystalloid structures in the mitochondria, and atypical osteocytes showed persistent changes indicative of hyperactivity. The osteoclasts exhibited varying ultrastructural features with respect to the number and appearance of nuclei, Golgi, RER, and lysosomes. These changes under the influence of EHDP could be an indication of altered activity of the osteoclast. The possible interference of EHDP with bone cell metabolism is discussed.
TL;DR: The present data suggest that when the priority of the cell population is the synthesis of structural proteins, the inhibitor, in addition to preventing the hydrolysis of newly synthesized peptides, also maintains matrix degradation at normal turnover levels.
Abstract: The application of a continuous tensile mechanical stress (30g) to explants of coronal sutures from newborn rabbits (1–2 days) produced increases in enzyme activity of 33.7% for collagenase, 95.2% for gelatinase, and 35.9% for NMP III over a 4-day culture period. All three activities were in latent form and required activation with either 4-APMA or trypsin. The increases in enzyme activities were not accompanied by an alteration in the degradation of structural proteins. This was due to the ability of the cells to synthesize an inhibitor (mol wt 29,000 daltons) which complexed the increased quantities of enzyme. This necessitated a substantial stimulation of inhibitor production because there was still a residue of free inhibitory activity in the media of stressed cultures after 4 days. We previously showed using the same model system that coronal sutures respond to tensile mechanical stress by a two-fold increase in collagen synthesis. The present data suggest that when the priority of the cell population is the synthesis of structural proteins, the inhibitor, in addition to preventing the hydrolysis of newly synthesized peptides, also maintains matrix degradation at normal turnover levels.
TL;DR: It is concluded that the increase in urinary calcium excretion, and presumably the negative calcium balance, produced by a 2-week administration of oxazacort is significantly less pronounced than that produced by an equivalent dose of prednisone.
Abstract: Prolonged therapeutic administration of prednisone or other corticosteroids frequently produces severe osteopenia with an increased incidence of bone fractures. Recent efforts to decrease the severity of corticosteroid-induced osteopenia have included the development of corticosteroid analogues designed to possess diminished bone-wasting effects relative to their anti-inflammatory activity. We compared the effects of an oxazoline derivative of prednisolone, oxazacort (azacortinol), with those of prednisone on mineral metabolism in man. After a 12-day equilibration period on a 600 mg/day calcium diet, normal volunteers were studied for 15 days during treatment with either prednisone (20 mg/day, 12 subjects) or oxazacort (25 mg/day, 10 subjects). There was no difference between the two groups with regard to the effects of each corticosteroid on serum ionized calcium, phosphate, alkaline phosphatase, immunoreactive parathyroid hormone (iPTH), and 25-hydroxyvitamin D (25OHD) concentrations. Both corticosteroids suppressed intestinal47Ca absorption to a similar degree after 15 days of treatment (prednisone: −28.5±7.5, oxazacort: −30.2±4.4% of initial values). Although both corticosteroids increased 24-h urinary calcium excretion significantly above pretreatment values, this effect was less marked in the oxazacort-treated subjects. The mean cumulative 15-day increase in urinary calcium excretion in the prednisone-treated group (+326 ± 54 mg/g creatinine/24 h) was more than twice as great as that in the oxazacort-treated group (+146 ± 48 mg/g creatinine/24 h), a difference significant atP<0.001. It is concluded that the increase in urinary calcium excretion, and presumably the negative calcium balance, produced by a 2-week administration of oxazacort is significantly less pronounced than that produced by an equivalent dose of prednisone.
TL;DR: The ability of Ca-PL-P complexes and lipid fractions of B. matruchotii to initiate apatite formation from metastable calcium phosphate solution was compared and the yield of hydroxyapatite decreased, explaining the failure to detect protein in Ca- PL-P preparations.
Abstract: Calcium-phospholipid-phosphate complexes (Ca-PL-P) were isolated from calcified and uncalcified Bacterionema matruchotii and its calcified lipid extracts. Similar complexes were absent from the noncalcifying bacterium Actinomyces naeslundii. The majority of the Ca-PL-P complexes were associated with the proteolipid acidic phospholipid component. Ca-PL-P complexes isolated from B. matruchotii and from calcified proteolipid contained phosphatidylinositol, phosphatidylinositol-4-phosphate, phosphatidylinositol-4,5-diphosphate, and phosphatidylserine. They consisted of approximately 52 mole % Ca, 32 mole % organic P, and 15 mole % Pi. During Ca-PL-P extraction from B. matruchotii or its proteolipid-containing calcified lipid extracts, the proteolipid was dissociated and the apoprotein precipitated as fluff at the aqueous-organic solvent interface, thus explaining the failure to detect protein in Ca-PL-P preparations. When the ability of Ca-PL-P complexes and lipid fractions of B. matruchotii to initiate apatite formation from metastable calcium phosphate solution was compared, the yield of hydroxyapatite decreased as follows: Ca-PL-P greater than proteolipid acidic phospholipids greater than proteolipid greater than crude phospholipid greater than total lipids greater than whole cells.
TL;DR: It is suggested that the presence of Mg does affect in vivo calcification and that the initiation of calcification by means of a Ca-PL-PO4 complex may be dependent on the Mg/Ca ratio in the calcifying tissue.
Abstract: The effect of Mg on hydroxyapatite proliferation induced by phosphatidyl serine, phosphatidyl inositol, and calcium-acidic phospholipidphosphate complexes has been studied in metastable calcium phosphate solutions of constant ionic strength and variable Mg/Ca ratio. Mg inhibits formation of the Ca-acidic phospholipid phosphate complexes, probably by competing with Ca for sites on the phospholipid molecules. Once the complexed acidic phospholipids are present, Mg has no effect on the proliferation of hydroxyapatite. This is shown by the invariant first-order rate constant for the disappearance of Ca during hydroxyapatite proliferation (kCa=0.0037 h−1) in solutions with Mg/Ca weight ratios ranging 0/1 to 10/1. These studies suggest that the presence of Mg does affect in vivo calcification and that the initiation of calcification by means of a Ca-PL-PO4 complex may be dependent on the Mg/Ca ratio in the calcifying tissue.
TL;DR: It is demonstrated that oxytetracycline has no effect on the bone apposition rate when used in the concentrations indicated, and it is found that at labeling intervals of 96 h or more, periods of osteoblastic inactivity are likely to be included in measurements at individual sites and the instantaneousapposition rate is underestimated at these long time intervals.
Abstract: We have analyzed various aspects of tetracycline labeling technique for the measurement of bone apposition rate in vivo. Our efforts were restricted to those aspects that are frequently questioned when data obtained using this technique are interpreted as representing the rate of bone apposition. Rat bone was labeled in vivo by sequential injections of oxytetracycline at a dose range of 3 to 24 mg/kg body weight and at intervals ranging from 24 to 72 h. The bone apposition rate was calculated by measuring the distance from the first dose of label to the subsequent ones. As these distances are by far too small to be determined accurately by any available micrometer eyepiece, we have used a scanning microscope photometer which allows measurements on slow-forming sites that otherwise would have been considered nongrowing sites. Using these techniques, we have demonstrated that oxytetracycline has no effect on the bone apposition rate when used in the concentrations indicated. In addition, we found that at labeling intervals of 96 h or more, periods of osteoblastic inactivity are likely to be included in measurements at individual sites. The instantaneous apposition rate is thus underestimated at these long time intervals.
TL;DR: It is suggested that because preosteoclasts are morphologically distinctive and relatively abundant, it should be feasible to separate these cells from a heterogeneous cell isolate.
Abstract: This is a study of the fine structure of cells of the 20-day fetal rat calvarium. Special attention is given to identifying and characterizing preosteoclasts. These cells are relatively common and located largely, but not exclusively, at the endocranial bone surface. The preosteoclasts are characterized by abundant mitochondria, an incomplete perinuclear Golgi apparatus, and variable-shaped dense granules. The dense granules are unique in appearance in that they contain an internal dense matrix surrounded by a clear halo. Most granules are circular in shape but some are elongate or tubular in form. Granules with identical appearance are observed in osteoclasts. The preosteoclasts are mononucleate, or occasionally binucleate. It is suggested that because preosteoclasts are morphologically distinctive and relatively abundant, it should be feasible to separate these cells from a heterogeneous cell isolate.
TL;DR: Diabetic rat femurs were more fragile and required less force to break in contrast to those from diabetic rats treated with insulin or normal rats, and daily insulin treatment significantly improved the bone cortical thickness and enhanced their capacity to withstand pressure.
Abstract: A simple instrument is described which measures the breaking strength of rat bones. The apparatus yields reproducible results and is suitable for use in measuring the strength of bones from both large and small animals. Diabetic rat femurs were more fragile and required less force to break in contrast to those from diabetic rats treated with insulin or normal rats. Daily insulin treatment significantly improved the bone cortical thickness and enhanced their capacity to withstand pressure, although these did not reach the level of the normal controls. The amount of force required to break the bone appears to be related to its cortical thickness and mass.
TL;DR: The results suggest that the initial effect of mechanical perturbation on relatively quiescent adult bone progenitor cells is a generalized, transient release of G1 and G2 blocked cells, which may correlate clinically with the regional acceleration phenomenon (RAP), which follows bone trauma, fracture, or surgical injury.
Abstract: Initial cell kinetics (15 min-20 h) of mechanically induced osteogenesis was studied with3H-thymidine (3H-Tdr) autoradiography. Continuous orthodontic force elicited a three-stage cell proliferative reaction within rat molar periodontal ligament (PDL): (a) brief, generalized response, characterized by a burst of mitotic activity from 75 min to 2 h and a cyclic change (decrease, increase and return to control levels) in percent labeled cells from 15 min to 2 h; (b) transient, generalized response, involving an increased mitotic index (MI) from 2 to 13 h, associated with elevated labeling index (LI) from 6 to 12 h; and (c) sustained, localized osteogenic response (12 h to several days) in which cell proliferation was confined primarily to the immediate area of new bone formation. These results suggest that the initial effect of mechanical perturbation on relatively quiescent adult bone progenitor cells is a generalized, transient release of G1 and G2 blocked cells. This response may correlate clinically with the regional acceleration phenomenon (RAP), which follows bone trauma, fracture, or surgical injury.
TL;DR: It is suggested that calcium and sulfur deposition (representing mineral and glycosaminoglycan deposition, respectively) are not simply inversely proportional, and that the hematoxylin-stained structural increments did not solely reflect differences in the distribution of the mineral components in dentin.
Abstract: We have identified a variety of biological rhythms involved in the apposition and mineralization of dentin in the rabbit incisor.
TL;DR: It is postulate that bone magnesium depletion has a direct negative effect on osteoblastic and osteocytic activity, and may explain, in part, the decreased responsiveness of bone to parathyroid hormone (PTH) that has been observed in magnesium-deficient animals.
Abstract: Calcium homeostasis and bone pathology were studied in weanling rats fed a low (70 ppm) magnesium diet for 2–21 days. The rats developed significant, progressive hypercalcemia after 6 days on the diet. The increase in blood calcium was accompanied by progressive hypoactivity of the parathyroid gland (PTG), as determined by histologic and morphometric analyses. Thus hyperactivity of the PTG could not have been responsible for the hypercalcemia observed. Histologic examination of femora and humeri from magnesium-deficient rats showed progressive subperiosteal hyperplasia, consisting of undifferentiated osteoprogenitor cells and fibrous tissue, after 7 days of deficiency. The presence of unmineralized osteoid tissue in the metaphyses indicated that mineralization was not proceeding normally. The alterations in differentiation of osteoprogenitor cells, together with the failure of mineralization, resulted in significantly lower rates of bone formation (as measured by fluorochrome labeling) in the magnesium-deficient rats. Basophilic cementing lines and inactive osteocytes in the cortices of bones from magnesium-deficient rats indicated that bone resorption was also severely reduced in magnesium deficiency. We postulate that bone magnesium depletion (66% by day 21) has a direct negative effect on osteoblastic and osteocytic activity, and may explain, in part, the decreased responsiveness of bone to parathyroid hormone (PTH) that has been observed in magnesium-deficient animals.
TL;DR: Kinetic analysis demonstrated that WBR provided overestimate of the skeletal retention by an average of 16%, the retention in the “extravascular space” being greater in patients with chronic renal failure, which shows significant promise for a quantitative approach to the skeletal turnover in metabolic bone disease.
Abstract: The blood clearance and the urinary excretion of the bone scanning complex technetium-tin-methylene-diphosphonate (99mTc-Sn-MDP) administered intravenously have been measured in 27 normal subjects and 104 patients with post-menopausal osteoporosis, osteomalacia, primary hyperparathyroidism, Paget's disease, pagetoid metastases of prostatic cancer, osteolyses, chronic renal failure, and liver cirrhosis to quantitate the skeletal uptake of the radiopharmaceutical.
TL;DR: The results suggest that beta agonists and low Ca have separate but related mechanisms for stimulating PTH release and may affect different pools of hormone.
Abstract: An in vitro perifusion system was used to study parathyroid hormone (PTH) secretion in response to calcium (Ca) and beta-adrenergic agents. Perifused parathyroid tissue responded to changes in Ca within the physiologic range during experiments up to 5 h. There was rapid secretory stimulation after exposure to low Ca, with the maximum response being observed at 20 min. Normal bovine glands showed a Ca-independent nonsuppressible component of PTH release at concentrations of Ca above physiologic. 1-isoproterenol produced rapid stimulation of PTH release, the response being blocked by a beta antagonist. The maximum secretory response to either low Ca (0.5 mM) or 1-isoproterenol (10−5 M) was enhanced when the two stimuli were applied simultaneously. The response to isoproterenol was blocked by raising Ca to 2.5 mM. Although d,l-propranolol (10−4 M) caused mild suppression of PTH release at a Ca of 1.25 mM, it did not cause additional suppression at 2.5 mM Ca nor did it decrease the response to 0.5 mM Ca stimulation. The secretory response of the gland to low Ca was sustained at a level more than double the baseline rate. The response to isoproterenol was more transient, with a return to or toward baseline secretion within 60 min. These results suggest that beta agonists and low Ca have separate but related mechanisms for stimulating PTH release and may affect different pools of hormone. The perifusion system described is a relatively simple technique for assessing the kinetics and interactions of various stimulators of PTH secretion.
TL;DR: A 50-year-old Latin American man with tumoral calcinosis presented with hyperphosphatemia (6.62±1.04 SD mg/dl), elevated renal threshold phosphorus concentration (TmP) (7.3 mg/GFR), and 1,25-dihydroxyvitamin D [1,25-(OH)2D] (69 pg/ml) hypercalciuria (239 mg/day), and a high fractional intestinal calcium (Ca) absorption (0.91±0.74) as mentioned in this paper.
Abstract: A 50-year-old Latin American man with tumoral calcinosis presented with hyperphosphatemia (6.62±1.04 SD mg/dl), elevated renal threshold phosphorus concentration (TmP) (7.3 mg/GFR), and 1,25-dihydroxyvitamin D [1,25-(OH)2D] (69 pg/ml) hypercalciuria (239 mg/day), and a high fractional intestinal calcium (Ca) absorption (0.74). Sodium cellulose phosphate therapy (20 g/day) lowered urinary Ca, and partially reduced serum phosphorus (P) and TmP to 5.91±0.63 mg/dl and 6.2 mg/GFR, respectively. Serum 1,25-(OH)120D remained elevated at 58–64 pg/ml. Amphojel therapy (4 oz/day) decreased urinary P to 23±21 mg/day and lowered serum P to 5.75±0.36 mg/dl (P<0.05). TmP increased to a value of 8.0 mg/GFR while serum 1,25-(OH)2D continued to remain elevated at 53 pg/ml.