tetracycline and Osteoporosis

Topics: Adolescent; Adult; Aged; Biopsy; Bone and Bones; Bone Development; Bone Diseases, Metabolic; Bone Resorption; Child; Child, Preschool; Female; Humans; Hyperparathyroidism; Hyperthyroidism; Infant; Male; Middle Aged; Osteogenesis; Osteoporosis; Tetracycline

Topics: Absorptiometry, Photon; Adult; Aged; Aging; Bone Diseases; Bone Resorption; Calcium; Child; Estrogens; Female; Humans; Hydroxyproline; Hyperparathyroidism; Joint Diseases; Male; Microradiography; Middle Aged; Osteitis Deformans; Osteomalacia; Osteoporosis; Parathyroid Glands; Physical Therapy Modalities; Spine; Tetracycline

Osteoporosis is a global chronic disease characterized by severe bone loss and high susceptibility to fragile fracture. It is widely accepted that the origin acidified microenvironment created by excessive osteoclasts causes irreversible bone mineral dissolution and organic degradation during osteoclastic resorption. However, current clinically available approaches are mainly developed from the perspective of osteoclast biology rather than the critical acidified niche. Here, we developed a smart "nanosacrificial layer" consisting of sodium bicarbonate (NaHCO

Topics: Animals; Bone and Bones; Bone Resorption; Carbon Dioxide; Cholesterol; Female; Humans; Lecithins; Mice, Inbred C57BL; Nanostructures; NF-kappa B; Osteoclasts; Osteoporosis; Phosphatidylethanolamines; Polyethylene Glycols; RANK Ligand; Sodium Bicarbonate; Surface Properties; Tetracycline

A number of previous studies have indicated that the genetic variation at the collage type I alpha 1 (COLIA1) gene locus influences susceptibility to osteoporosis. However, seldom have studies reported the effect of gene delivery using an adenovirus vector carrying human recombinant COLIA1 cDNA on stimulating osteogenic activity of osteoblasts and enhancing fracture healing of ovariectomized rats. The current study was performed to demonstrate whether direct gene delivery using an adenovirus vector carrying human recombinant COLIA1 cDNA could stimulate osteogenic activity of osteoblast in vitro and enhance fracture healing of ovariectomized rats in vivo. In vitro, the tet-on system regulated COLIA1 gene adenovirus was constructed and transfected to osteoblasts. COLIA1 mRNA and collagen type I levels were assessed by reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay to determine whether adenovirus transfected successfully. Osteogenic activity of the osteoblasts was assessed by alkaline phosphatase activity, immunohistochemical staining, immunofluorescent staining, mineralized matrix formation, and extracellular calcium levels. In vivo, adenovirus-delivered COLIA1 gene was injected into the fracture site of the tibia in an ovariectomized rat model of osteoporosis, and bone callus condition was assessed to determine whether the COLIA1 gene could accelerate osteoporotic fracture healing. In vitro, the results showed that COLIA1 gene adenovirus transfection could increase osteoblast COLIA1 gene expression and collagen type I protein synthesis, increase alkaline phosphatase activity, and stimulate calcium nodules formation, which exhibited a direct osteogenic effect on the osteoblasts. In vivo, local injection of COLIA1 gene adenovirus increased collagen type I expression, restored bone mineral density, and accelerated fracture healing in ovariectomized rats, without increasing serum collagen type I and liver COLIA1 mRNA levels. This study suggests direct gene delivery using an adenovirus carrying human COLIA1 cDNA can stimulate the osteogenic activity of osteoblasts in vitro and enhance bone fracture healing in vivo. The tet-on system is an ideal gene regulatory system for effective and safe regulation of the therapeutic gene.

Topics: Adenoviridae; Animals; Bone Density; Cell Differentiation; Collagen Type I; Collagen Type I, alpha 1 Chain; Disease Models, Animal; Genetic Therapy; Humans; Osteoblasts; Osteoporosis; Osteoporotic Fractures; Rats; Recombinant Proteins; Tetracycline; Transfection

This study aimed to investigate the improved therapeutic efficacy and pharmacokinetic profiles of simvastatin (SIM) with imparted bone targeting potential using tetracycline-mediated PEG-PLGA (TC-PEG-PLGA) micelles in osteoporotic rats. The SIM-loaded TC-PEG-PLGA (TC-PEG-PLGA/SIM) micelles were evaluated for particle size, morphology, stability, loading efficiency, cell viability, bone mineral binding ability in vitro, mineralization, pharmacokinetics, and pharmacodynamics. TC-PEG-PLGA conjugates were successfully and could self-assembly form micelles in aqueous medium with a 19.4 μg/mL critical micelle concentration. Then, TC-PEG-PLGA/SIM micelles were prepared with solvent diffusion method, and the obtained micelles (56.21 ± 7.39 nm average size; 81.8 ± 3.1% encapsulation efficiency; and 7.56 ± 0.27% drug loading) led to the prolonged release of SIM from micelles. Cellular uptake test indicated that TC had no effects on micellar internalization and micellar internalization was mainly involved with clathrin-mediated endocytic pathway. In vivo pharmacokinetic results indicated that TC-PEG-PLGA/SIM micelles exhibited a significantly prolonged time in systemic circulation and were preferentially accumulated in bone tissue. TC-PEG-PLGA/SIM micelles showed better therapeutic effects, as reflected by the improved bone mineral density, bone mineral content, and bone mechanical strength. Overall, these results suggested that TC-PEG-PLGA/SIM micelles provide several advantages, including prolonged systemic circulation, enhanced bone tissue distribution, and improved therapeutic outcomes in osteoporotic rats.

Topics: Animals; Bone and Bones; Disease Models, Animal; Drug Carriers; Drug Compounding; Human Umbilical Vein Endothelial Cells; Humans; Micelles; Osteoporosis; Particle Size; Polyesters; Polyethylene Glycols; Rats; Simvastatin; Tetracycline

Bisphosphonate, tetracycline and spironolactone use has been shown to increase gastro-oesophageal inflammation, an accepted risk factor for cancer. However, evidence of the effect of these medications on gastro-oesophageal cancer risk are mixed or missing entirely. Therefore, we conducted a nested case-control study using the Primary Care Clinical Information Unit Research (PCCIUR) database from Scotland. Cases with oesophageal or gastric cancer between 1999 and 2011 were matched to up to five controls based on age, gender, year of diagnosis and general practice. Medication use was ascertained using electronic prescribing records. Conditional logistic regression was used to calculate odds ratios (ORs) for the association between medication use and cancer risk after adjustment for comorbidities and other medication use. A similar proportion of gastro-oesophageal cancer cases received bisphosphonates (3.9% vs. 3.5%), tetracycline (6.0% vs. 6.0%) and spironolactone (1.4% vs. 1.1%) compared with the controls. The adjusted ORs for the association between gastro-oesophageal cancer and bisphosphonates, tetracycline and spironolactone were 1.05 (95% CI: 0.85, 1.31), 0.99 (95% CI: 0.84, 1.17) and 1.04 (95% CI: 0.73, 1.49). Further analysis revealed bisphosphonates were associated with increased oesophageal cancer risk (1.34, 95% CI: 1.03, 1.74) but reduced gastric cancer risk (0.71, 95% CI: 0.49, 1.03), although there was no obvious dose-response relationship. Overall, there is little evidence that the use of bisphosphonate, tetracycline or spironolactone is associated with increased risk of gastro-oesophageal cancer. Our findings should reassure GPs and patients that these widely-used medications are safe with respect to gastro-oesophageal cancer risk.

Topics: Adult; Aged; Aged, 80 and over; Diphosphonates; Esophageal Neoplasms; Female; Humans; Inflammation; Logistic Models; Male; Middle Aged; Osteoporosis; Risk Factors; Scotland; Spironolactone; Stomach; Stomach Neoplasms; Tetracycline

Nanoparticles (NPs) that target bone tissue were developed using poly(lactic-co-glycolic acid) (PLGA) copolymers and tetracycline (TC)-based bone-targeting moieties. These NPs are expected to enable the transport of drugs, such as simvastatin (SIM), for the treatment of osteoporosis.. The molecular structures of TC-PLGA were validated by (1)H-NMR, and the SIM-loaded NPs were prepared using the solvent emulsification method. The surface properties, cytotoxicity, cellular uptake, cell mineralization, bone targeting potential, and animal pharmacodynamics of the TC-PLGA NPs were evaluated and compared to those of PLGA NPs.. It was confirmed that the average particle size of the NPs was approximately 220 nm. In phosphate-buffered saline (PBS, pH 7.4), the SIM-loaded NPs exhibited a cumulative release of up to 80% within 72 hours. An in vitro cell evaluation indicated that the NPs had an excellent cellular uptake capacity and showed great biocompatibility with MC3T3-E1 cells, thereby reducing the cytotoxic effects of SIM. The cell mineralization assay showed that the SIM-loaded NPs induced osteogenic differentiation and mineralized nodule formation in MC3T3-E1 cells, thereby achieving the same effect as SIM. Preliminary findings from in vitro and in vivo bone affinity assays indicated that the TC-PLGA NPs may display increased bone-targeting efficiency compared to PLGA NPs lacking a TC moiety. The use of SIM-loaded TC-PLGA NPs in treating osteoporosis was tested through animal pharmacodynamics analyses performed in ovariectomized rats, and the results suggested that the SIM-loaded TC-PLGA NPs can improve the curative effects of SIM on the recovery of bone mineral density compared to either SIM-loaded PLGA NPs or SIM alone.. Bone-targeting NPs, which were based on the conjugation of TC to PLGA copolymers, have the ability to target bone. These NPs may be developed as a delivery system for hydrophobic drugs, and they are expected to improve the curative effects of drugs, reduce the administered drug doses, and reduce side effects in other organs.

Topics: 3T3 Cells; Animals; Bone and Bones; Cell Differentiation; Chromatography, High Pressure Liquid; Drug Delivery Systems; Female; Fluorescein; Lactic Acid; Magnetic Resonance Spectroscopy; Mice; Mice, Inbred ICR; Nanoparticles; Osteogenesis; Osteoporosis; Particle Size; Polyglycolic Acid; Polylactic Acid-Polyglycolic Acid Copolymer; Rats; Rats, Sprague-Dawley; Simvastatin; Solvents; Surface Properties; Tetracycline

This study evaluated whether growing rats were appropriate animal models of glucocorticoid-induced osteoporosis. The 3-month-old male rats were treated with either vehicle or prednisone acetate at 1.5, 3.0, and 6.0 mg/kg/day by oral gavage, respectively. All rats were injected with tetracycline and calcein before sacrificed for the purpose of double in vivo labeling. Biochemistry, histomorphometry, mechanical test, densitometry, micro-CT, histology, and component analysis were performed. We found that prednisone treatments dose dependently decreased body weight, serum biomarkers, biomechanical markers, bone formation, and bone resorption parameters in both tibial and femoral trabecular bone without trabecular bone loss. We also found that significant bone loss happened in femoral cortical bone in the glucocorticoid-treated rats. The results suggested that prednisone not only inhibited bone formation, but also inhibited bone resorption which resulted in poor bone strength but with no cancellous bone loss in growing rats. These data also suggested that the effects of glucocorticoid on bone metabolism were different between cortical bone and trabecular bone, and different between tibia and femur. Growing rats may be a glucocorticoid-induced osteoporosis animal model when evaluated the effects of drugs upon juvenile patients exposed to GC for a long time.

Topics: Acetates; Animals; Biomarkers; Biomechanical Phenomena; Body Weight; Bone Resorption; Densitometry; Disease Models, Animal; Dose-Response Relationship, Drug; Fluoresceins; Glucocorticoids; Male; Osteoporosis; Prednisone; Principal Component Analysis; Rats; Rats, Sprague-Dawley; Stress, Mechanical; Tetracycline; Time Factors; X-Ray Microtomography

Idiopathic osteoporosis (IOP) in premenopausal women is characterized by fragility fractures at low or normal bone mineral density (BMD) in otherwise healthy women with normal gonadal function. Histomorphometric analysis of transiliac bone biopsy samples has revealed microarchitectural deterioration of cancellous bone and thinner cortices. To examine bone material quality, we measured the bone mineralization density distribution (BMDD) in biopsy samples by quantitative backscattered electron imaging (qBEI), and mineral/matrix ratio, mineral crystallinity/maturity, relative proteoglycan content, and collagen cross-link ratio at actively bone forming trabecular surfaces by Raman microspectroscopy and Fourier transform infrared microspectroscopy (FTIRM) techniques. The study groups included: premenopausal women with idiopathic fractures (IOP, n = 45), or idiopathic low BMD (Z-score ≤ -2.0 at spine and/or hip) but no fractures (ILBMD, n = 19), and healthy controls (CONTROL, n = 38). BMDD of cancellous bone showed slightly lower mineral content in IOP (both the average degree of mineralization of cancellous bone [Cn.Ca(Mean) ] and mode calcium concentration [Cn.Ca(Peak) ] are 1.4% lower) and in ILBMD (both are 1.6% lower, p < 0.05) versus CONTROL, but no difference between IOP and ILBMD. Similar differences were found when affected groups were combined versus CONTROL. The differences remained significant after adjustment for cancellous mineralizing surface (MS/BS), suggesting that the reduced mineralization of bone matrix cannot be completely accounted for by differences in bone turnover. Raman microspectroscopy and FTIRM analysis at forming bone surfaces showed no differences between combined IOP/ILBMD groups versus CONTROL, with the exceptions of increased proteoglycan content per mineral content and increased collagen cross-link ratio. When the two affected subgroups were considered individually, mineral/matrix ratio and collagen cross-link ratio were higher in IOP than ILBMD. In conclusion, our findings suggest that bone material properties differ between premenopausal women with IOP/ILBMD and normal controls. In particular, the altered collagen properties at sites of active bone formation support the hypothesis that affected women have osteoblast dysfunction that may play a role in bone fragility.

Topics: Adult; Bone and Bones; Bone Density; Bone Matrix; Female; Fractures, Bone; Humans; Microspectrophotometry; Middle Aged; Osteoblasts; Osteogenesis; Osteoporosis; Premenopause; Prospective Studies; Spectroscopy, Fourier Transform Infrared; Spectrum Analysis, Raman; Tetracycline

Bone-specific compounds have been used effectively for the detection of bone mineralization, growth, and morphological changes. These agents typically contain iminodiacetic acid groups that can form complexes with apatite and fluoresce in the visible spectrum. We exploited a subset of these chemical chelators to produce a near-infrared (NIR) optical bone marker for preclinical animal imaging. By conjugating target compounds to IRDye 800CW, we extended the effective fluorescence signal detection to the NIR region without affecting the compound's ability to function as a marker of the mineralization process. Calcein and a tetracycline derivative (BoneTag agent [BT]) bound specifically to differentiated mineralized osteoblast cultures, with the latter exhibiting 6-fold higher signal intensities. Subsequent in vivo testing demonstrated effective skeletal labeling with IRDye 800CW BT. We were able to identify a changing mineralization front in bone sections from (i) normal growing mice injected with IRDye 800CW BT 6weeks prior to the administration of IRDye 680 BT and (ii) an osteoporosis mouse model comparing cortical bone in sham-treated and ovariectomized mice. These results provide evidence that the NIR-labeled BT is effective as a general marker of skeletal features and an indicator of the bone mineralization and remodeling processes.

Topics: Animals; Biomarkers; Bone Remodeling; Calcification, Physiologic; Cell Line; Disease Models, Animal; Fluoresceins; Indoles; Mice; Mice, Nude; Microscopy, Fluorescence; Osteoporosis; Spectroscopy, Near-Infrared; Tetracycline; Whole Body Imaging

In this study a novel bone-targeting agent containing elements of the tricarbonylmethane system of ring A of tetracycline was developed and was shown to bind to the mineral constituent of bone, hydroxyapatite. Conjugation of this bone-targeting agent to estradiol resulted in a bone-targeted estrogen (BTE(2)-A1) with an enhanced ability to bind to hydroxyapatite. In an ovariectomized rat model of osteoporosis a partial separation of the skeletal effects of estradiol from the uterine effects was observed following subcutaneous administration of BTE(2)-A1. This novel bone-targeting estradiol delivery system has the potential to improve the safety profile of estradiol in the treatment of osteoporosis.

Topics: Animals; Bone and Bones; Bone Density; Chemistry, Pharmaceutical; Drug Design; Durapatite; Estradiol; Estrogens; Female; Osteoporosis; Ovariectomy; Protein Synthesis Inhibitors; Rats; Rats, Sprague-Dawley; Tetracycline

Low vitamin D levels are common. Bone biopsies taken from 121 ambulant patients were therefore reviewed. Seasonal changes in mineralization correlated inversely with serum 25-hydroxyvitamin D but not the more active metabolite, 1,25-dihydroxyvitamin D. This implies that the latter is produced in bone.. It has been 30 yr since a seasonal variation in osteoid surfaces and calcification fronts was noted in bone biopsies from hip fracture patients in Leeds and attributed to vitamin D status. It was suggested at that time that mild vitamin D deficiency might cause osteoporosis from malabsorption of calcium and more severe deficiency osteomalacia, but little has been published on this subject since.. We examined bone biopsies, calcium absorption data, and serum vitamin D metabolites in 121 patients attending our osteoporosis clinics in Adelaide. Biopsies were collected from the anterior iliac crest with a Jamshidi needle after two stat oral doses of 1 g of tetracycline 10 days apart, processed into plastic without demineralization, and all parameters were measured by point counting using a Weibel II graticule. Calcium absorption was measured after an oral dose of 5 microCi of (45)Ca in 250 ml of water with 20 mg of calcium carrier. Serum 25-hydroxyvitamin D [25(OH)D] was measured by radioimmunoassay and 1,25-dihydroxyvitamin D [1,25(OH)(2)D] by radioimmunoassay after high-performance liquid chromatography (HPLC).. 25(OH)D levels were lower from late autumn to early spring (April to September) than from late spring to early autumn (October to March) (51 +/- 23 versus 61 +/- 27 [SD] nM; p=0.040). None of the biopsies yielded a diagnosis of osteomalacia, but osteoid thickness (O.Th.) was greater in the winter than the summer months (8.5 +/- 3.6 versus 7.1 +/- 2.8 microm; p=0.015) as was mineralization lag time (MLT; 11.9 +/- 5.2 versus 9.5 +/- 3.6; p=0.005). O.Th and log MLT were both inversely related to serum 25(OH)D (p=0.014 and 0.036) but not serum 1,25(OH)(2)D. Calcium absorption was related to serum 1,25(OH)(2)D but not serum 25(OH)D.. We conclude that circulating 25(OH)D affects the mineralization process, whereas circulating 1,25(OH)(2)D affects bone indirectly through its effect on calcium absorption.

Topics: Absorption; Administration, Oral; Aged; Aged, 80 and over; Anti-Bacterial Agents; Australia; Bone Density; Calcification, Physiologic; Calcitriol; Calcium; Female; Humans; Ilium; Male; Middle Aged; Osteoporosis; Outpatients; Seasons; Tetracycline; White People

To investigate the distribution of tetracycline-arginine-glycine-aspartate-tyrosine (T-RGDY) in mice and its effect on bone.. 125-labeled T-RGDY was studied for its distribution in mice and for its effects on bone by histomorphometry in ovariectomized rats.. The 125I-labeled T-RGDY was more concentrated in the osteoporotic bone than in the normal bone. Compared with ovariectomy group, the morphologic index such as trabecular bone volume/total tissue volume (TBV/TTV), TBV/sponge bone volume (SBV), and mean trabecular plate thickness (MTPT) in T-RGDY group significantly increased (P < 0.05). As compared with sham operation group, MTPT significantly increased in T-RGDY group (P < 0.05), while TBV/SBV and mean trabecular plate density significantly decreased (P < 0.05), and TBV/TYV and mean trabecular plate spacing were almost the same as those in sham operation group (P > 0.05).. T-RGDY may concentrate in bone tissue to a certain degree, which is closely related with the status of bone remodeling. T-RGDY may inhibit the bone loss caused by ovariectomy.

Topics: Animals; Bone Density; Bone Remodeling; Female; Mice; Oligopeptides; Osteoporosis; Ovariectomy; Rats; Rats, Sprague-Dawley; Tetracycline; Tissue Distribution; Tyrosine

The effect of calcium supplementation on the bone dynamics in the hard palate of the molar region (maxilla), mandible and proximal tibia in experimental osteoporotic rats was examined. Ninety ovariectomized (OVX) and 45 sham-OVX Wistar female rats were used in this study. All the rats received surgical operation at 6 weeks of age. Ovariectomized rats were fed on a low calcium diet (0.02%) for 12 weeks post-operation, and then randomly divided into the two following groups. One group was fed on high calcium diet (2.30%) (OVX-HCa) and the other group was remained on the low calcium diet (OVX-LCa). Sham-OVX rats were fed on regular calcium diet (1.15%) during the experimental period (Sham-OVX). Histomorphological analysis was carried out from 12 to 32 weeks post-operation. On undecalcified thin section, bone volume, eroded surface, osteoid surface and bone formation rate were calculated for cortical bone of the maxilla, and for cancellous bone of the mandible and proximal tibia. In the OVX-LCa group, compared with the Sham-OVX group, decrease of the bone volume and increase of the bone resorption and formation parameters were detected throughout the observation periods. In the OVX-HCa group, compared with the OVX-LCa group, increase of the bone volume and temporarily increased parameters of bone formation at 1 week after feeding on high calcium diet were observed in the maxilla, but these changes were not observed in the mandible and proximal tibia. Moreover, the bone resorption and formation parameters in the maxilla, mandible and proximal tibia in the OVX-HCa group became equivalent to the Sham-OVX levels with the passage of time.

Topics: Analysis of Variance; Animals; Body Weight; Bone Matrix; Bone Resorption; Calcium, Dietary; Dietary Supplements; Disease Models, Animal; Female; Fluoresceins; Fluorescent Dyes; Image Processing, Computer-Assisted; Mandible; Maxilla; Osteogenesis; Osteoporosis; Ovariectomy; Palate, Hard; Random Allocation; Rats; Rats, Wistar; Statistics as Topic; Tetracycline; Tibia

Our aim was to estimate the rate of osteogenesis by using tetracycline double labeling and to correlate it with the radiological grading of osteoporosis in patients of intertrochanteric fracture of the femur in different age groups. Thirty-two cases of intertrochanteric fracture of the femur of either sex, without any associated osteopenic conditions, who were admitted for surgery constituted the clinical material. The cases were divided into three age groups: group I, <45 years; group II, 45-60 years; and group III, >60 years. Osteoporosis was graded in all groups on plain X-rays by Singh's index (SI) and metacarpal index (MI). The patients were labeled with a single large dose (1.5 g) of tetracycline orally on day 1 and day 8. An iliac crest bone biopsy specimen was obtained from each of the patients during surgical intervention. Thin undecalcified sections were made by the hand grinding technique. The sections were studied under UV light for presence of fluorescence, and rate of osteogenesis (mineral appositional rate, MAR) was calculated for each of the groups. Only 7 patients were found to have radiological osteoporosis (by Singh's index). The average MI and MAR were found to be 46.5% and 1.48 microm/day, respectively. The single-dose labeling schedule has shown good fluorescent bands, comparable to the conventional dose schedule. No correlation was found between Singh's index and metacarpal index in group I and III, whereas in group II it was significant. There is no significant correlation between the rate of new bone formation and the radiological grading of osteoporosis.

Topics: Adult; Aged; Bone and Bones; Female; Femoral Fractures; Humans; Male; Middle Aged; Osteogenesis; Osteoporosis; Radiography; Staining and Labeling; Tetracycline

An association between postmenopausal osteoporosis and tooth loss has been proposed. However, histomorphometrical changes in alveolar bone following estrogen deficiency are rarely reported with data on microtrabecular structural changes. To clarify the relationship between estrogen deficiency and tooth loss, we histomorphometrically analyzed the trabecular structural changes of mandibular alveolar bone in ovariectomized rats. Twenty-four adult female Fischer rats were used. Eight rats were sacrificed on day 0 (baseline). The remaining 16 rats were divided into two groups. One group was ovariectomized bilaterally (OVX) and the other group was subjected to sham surgery (Sham). After administration of tetracycline and calcein, the animals were sacrificed 60 days after surgery. Bone histomorphometry, node-strut analysis and measurement of thickness of alveolar bone proper were performed on the interradicular septum of the first molar on the sagittal surface. The trabecular bone volume and trabecular number of the OVX group were significantly lower than those of the baseline and Sham groups. All of the bone resorptive and formative parameters of the OVX group were significantly higher (about one-and-a-half times) than those of the Sham group. Several osteoclasts were seen lining the irregular, eroded surface facing the bone marrow in the OVX group. Furthermore, the OVX group tended to have low microtrabecular stiffness and showed significantly thinner distal alveolar bone proper than in the baseline and Sham groups. In summary, estrogen deficiency caused osteoporotic changes and thin alveolar bone proper in the interradicular septum of rat first molar. This phenomenon might accelerate destruction of alveolar bone and tooth loss, especially in elderly women affected by periodontal disease.

Topics: Alveolar Process; Analysis of Variance; Animals; Bone Density; Bone Marrow; Bone Remodeling; Bone Resorption; Disease Models, Animal; Estrogens; Female; Fluoresceins; Fluorescent Dyes; Mandible; Microscopy, Confocal; Molar; Osteoclasts; Osteoporosis; Ovariectomy; Ovary; Rats; Rats, Inbred F344; Statistics as Topic; Tetracycline

The study aimed at investigating the effects of a new anti-osteoporotic drug, XW630 on promoting the osteogenic activity of bone tissue in ovariectomized rats.. Thirty-six female SD rats, three months old, were randomly divided into four groups: sham-operated group (sham), the ovariectomized group (OVX), the esterone-therapy group (OVX + CFT) and the XW630-therapy group (OVX + XW630). Three rats in each group were killed on the 30th, 60th, and 90th day after the operation. The femur of one side was taken for the three-point bending resistance test, and the bilateral tibias were taken for the HE stain and scanning electronic microscopy (SEM) examination.. The HE and SEM results indicated that the bone loss appeared in the OVX group 30 days after the operation, which lasted for the whole observing period. While after application of ester-one and XW630, there were different degrees of bone repairing around the trabeculae, and the osteogenic activity was obviously active in the XW630 group than that in the esterone group. During the experimental period, the three-point bending resistance of the OVX group gradually decreased and there was a significant difference compared with that of the sham group (P < 0.01), while the three-point bending resistance of the two therapy group gradually increased and there was significant difference between the OVX group and the XW630 group (P < 0.05 and P < 0.01).. XW630 can effectively promote osteogenic action and prevent osteoporostic fracture in ovariectomized rats.

Topics: Animals; Estrogens; Female; Femur; Osteogenesis; Osteoporosis; Ovariectomy; Piperazines; Random Allocation; Rats; Rats, Sprague-Dawley; Tetracycline; Tetracyclines; Tibia

Female rats were ovariectomized (Ovx) or sham-operated (control) at 18 weeks and the entire skeleton obtained at 24 weeks (baseline) or after an additional 31 day (28 week) interval on a normal (1.0%) or deficient (0.02%) calcium diet. Ovx rats showed a 42% increase in whole body bone resorption (3H-tetracycline loss) in the absence of calcium stress (1.0% calcium diet) and a 70% increase in resorption with morphological evidence of dramatic loss of cancellous bone mass when placed on calcium-deficient (0.02%) diets. Ovx rats kept on the 1.0% calcium diet showed a significant increase in both their body weight (30.2%) and total bone mass (11.6%) compared to baseline sham-operated controls. However, the total skeleton mass of these animals was significantly reduced (-20%) from that predicted by calculations based on body weight. Maintaining animals on calcium-deficient diets had no significant effect on the total skeleton mass of either control or Ovx rats in comparison with age-matched controls on 1.0% diets. It was further determined that an increase in bone mass between 24 and 28 weeks in rats receiving 1.0% dietary calcium occurred in both the axial and appendicular skeleton and was proportionately similar between control and Ovx groups. However, in animals subjected to dietary calcium stress during this interval, the decreased skeletal growth noted was confined primarily to the axial skeleton. The data indicate that ovariectomy or ovariectomy plus calcium stress does not result in loss of total bone mass during the interval of dramatically increased resorption and rapid loss of cancellous bone. The results suggest that the deterioration in individual bone structural and mechanical integrity due to ovariectomy or dietary calcium deficiency may not be attributed to overt loss in total bone mass but may involve a redistribution of bone mass.

Topics: Animals; Body Weight; Bone and Bones; Bone Density; Bone Development; Bone Resorption; Calcium; Calcium, Dietary; Female; Femur Head; Femur Neck; Linear Models; Osteoporosis; Ovariectomy; Rats; Rats, Sprague-Dawley; Tetracycline

Differences in trabecular and cortical bone loss have been demonstrated clinically, but differences in bone loss at different skeletal sites remain unclear. We examined regional variations in bone loss histomorphometrically in two strains of mice in which osteopenia progresses spontaneously: tiptoe-walking Yoshimura (twy) mice (from 4 to 37 weeks of age) and senescent ICR mice (from 4 to 88 weeks of age). Morphometrical measurements were obtained to investigate the changes with age in trabecular bone area and anterior cortical bone width in the lumbar vertebral body, trabecular bone area in the tibia, bone area in the parietal bone, and the cortical index in the humerus. Results showed that, in twy mice, trabecular turnover was higher than in ICR mice, and bone loss progressed in the following order: tibial trabecular bone, lumbar trabecular bone, parietal bone, lumbar anterior cortical bone, and the humerus. In ICR mice, bone formation declined after 60 weeks. Bone loss progressed in tibial trabecular bone and the parietal bone at 60 weeks of age, followed by lumbar trabecular bone, lumbar anterior cortical bone, and the humerus at 88 weeks of age. Bone loss varied at each site and between the two mouse strains, with different bone turnover rates. The findings of the present study indicate that special attention should be paid to regional variations in the progression of bone loss associated with differences in pathologic features.

Topics: Aging; Animals; Body Weight; Bone Development; Bone Diseases, Metabolic; Disease Progression; Female; Fluoresceins; Humerus; Mice; Mice, Inbred ICR; Mice, Mutant Strains; Osteoporosis; Parietal Bone; Spine; Tetracycline; Tibia

2-[3-Estrone-N-ethyl-piperazine-methyl] tetracycline (XW630) showing anti-osteoporosis activity is a new compound with piperazine-tetracycline in the steroid structure of estrone. The affinity of XW630 with uterine estrogen receptor and its estrogenic activity were studied in this paper. The relative affinities of estrone, estradiol and XW630 with estrogen receptor (ER) of the uterine myoma tissues were found to be 0.325, 1.000 and 0.011, respectively, by the competitive assay. The estrogenic activity index of estrone, estradiol and XW630 were shown to be 9.70, 10.30 and 6.90, respectively, by the uterine weight assay using immature mice. These indexes indicate that: the estrogenic activity of XW630 is about 1/1960 that of estrone and 1/7742 that of estradiol. The vaginal smear assay of oophorectomized mice also showed that the estrogenic activity of XW630 is less than that of estrone and estradiol.

Topics: Animals; Binding, Competitive; Estradiol; Estrogens; Estrone; Female; Humans; Mice; Osteoporosis; Piperazines; Receptors, Estrogen; Tetracycline; Tetracyclines; Uterus

Long-term heparin treatment causes osteoporosis through an as yet undefined mechanism. To investigate this phenomenon, we treated rats with once daily subcutaneous injections of heparin (in doses ranging from 0.25 to 1.0 U/g) or saline for 8 to 32 days and monitored the effects on bone both histomorphometrically and by serial measurements of urinary type 1 collagen cross linked-pyridinoline (PYD) and serum alkaline phosphatase, markers of bone resorption and formation, respectively. Histomorphometric analysis of the distal third of the right femur in the region proximal to the epiphyseal growth plate showed that heparin induces both a time- and dose-dependent decreased in trabecular bone volume, with the majority of trabecular bone loss occurring within the first 8 days of treatment. Thus, heparin doses of 1.0 U/g/d resulted in a 32% loss of trabecular bone. Heparin-treated rats also showed a 37% decrease in osteoblast surface as well as a 75% decrease in osteoid surface. In contrast, heparin treatment had the opposite effect on osteoclast surface, which was 43% higher in heparin-treated rats, as compared with that in control rats. Biochemical markers of bone turnover showed that heparin treatment produced a dose-dependent decrease in serum alkaline phosphatase and a transient increase in urinary PYD, thus confirming the histomorphometric data. Based on these observations, we conclude that heparin decreases trabecular bone volume both by decreasing the rate of bone formation and increasing the rate of bone resorption.

Topics: Alkaline Phosphatase; Amino Acids; Animals; Bone and Bones; Bone Resorption; Collagen; Epiphyses; Female; Heparin; Osteoblasts; Osteoclasts; Osteoporosis; Rats; Rats, Sprague-Dawley; Tetracycline

The loss of trabecular bone in the ovariectomized (OVX) rat provides a useful experimental model of postmenopausal osteoporosis. In this study, two bone-modulating compounds, an NSAID (flurbiprofen: FBP) and a chemically modified nonantimicrobial tetracycline (CMT), were tested either individually or in combination in this model. Ninety days after OVX, 6-month-old female rats were distributed into the following groups: sham-operated controls, untreated OVX, CMT-treated OVX (5 mg P.O./day), FBP-treated OVX (0.3 mg P.O./day), and combination (CMT plus FBP)-treated OVX (COMBO) groups. Untreated 3-month-old rats were used as pretreatment group. After 21 days of therapy, the dissected distal femurs were processed for light and fluorescence microscopic and backscattered electron microscopic examinations. Net trabecular bone values showed that all the treatment groups lost trabecular bone over the 111 day protocol compared to pretreatment group. In the untreated OVX rats, trabecular bone volume/unit area was reduced by 56% compared to that in the sham-operated controls, this bone loss associated with increased numbers of osteoclasts (p < 0.05). Cortical bone volume was, however, not significantly reduced in OVX rats. Both FBP-alone and COMBO therapy showed marginal, but significant, (p < 0.05, p < 0.01, respectively) inhibition of trabecular bone loss, and osteoclast numbers were also decreased (p < 0.05). Both CMT alone and COMBO therapy appeared to increase bone deposition (p < 0.01) at the endosteal surfaces of cortical bone. These results suggest that, in this animal model, (a) cortical bone volume increases by CMT; (b) FBP inhibits osteoclastic bone resorption in the trabecular area, and (c) a combination of these drugs may synergistically prevent bone loss.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Bone and Bones; Bone Remodeling; Drug Therapy, Combination; Female; Femur; Flurbiprofen; Microscopy, Electron, Scanning; Osteoporosis; Ovariectomy; Protein Synthesis Inhibitors; Rats; Rats, Sprague-Dawley; Tetracycline

To evaluate the effect of 17 beta-estradiol replacement (10 micrograms, twice a week) (E2) and treadmill exercise (18 m/min, 45 min/day) (EX) on long bone and vertebral bone mass and density, 10-month-old rats were ovariectomized (OV) and divided into four groups: OV, OV + E2, OV + EX, OV + EX + E2 2 months after surgery. After 7 weeks intervention, the calcium content and the density of lumbar-5 were higher in both OV + E2 and OV + EX + E2 groups than in the OV group, but, only the OV + EX + E2 group had a significantly higher femoral bone weight and density than the OV group. After 16 weeks intervention, the bone-conserving effects of E2 and EX were significant on lumbar-5 and femoral dry weight and density. The effect of E2 on both two sides of bones was due to the suppression of the bone turnover rate, while EX suppressed bone turnover rate primarily on the femur. We conclude that the effect of the two interventions on lumbar-5 and femoral bone mass were additive and independent.

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Bone and Bones; Bone Density; Bone Remodeling; Calcium; Estradiol; Female; Femur; Lumbar Vertebrae; Organ Size; Osteocalcin; Osteoporosis; Ovariectomy; Physical Exertion; Rats; Rats, Sprague-Dawley; Tetracycline; Tritium

SAMP6 is a recently developed strain of osteoporotic mice, and SAMP2 is a control for SAMP6 and has a higher peak bone mass. The bone mass of SAMP6 was increased until 2 months of age when a lysate of cells derived from the bone marrow of SAMP2 was injected at 1 or 4 days of age, but it was not increased when the lysate was injected at 21 days of age. No effect on bone mass was observed when lysates of other cells, bovine serum albumin or heat-inactivated lysate of bone marrow-derived cells of SAMP2, were injected. The ability to increase bone mass was not in the supernatant but in the pellet obtained by ultracentrifugation (105,000 g) of the lysate of bone marrow-derived cells of SAMP2. The lysate did not change the osteoclast surface but changed the appositional bone formation. In conclusion, the lysate of cells derived from the bone marrow of SAMP2 contains factors which can increase the bone mass of SAMP6, and these factors are present in the pellet obtained by ultracentrifugation.

Topics: Animals; Animals, Newborn; Bone Density; Bone Development; Bone Marrow; Bone Marrow Cells; Densitometry; Femur; Male; Mice; Mice, Mutant Strains; Osteoclasts; Osteoporosis; Species Specificity; Tetracycline

Streptozotocin-induced, insulin-deficient diabetic rats were administrated either minocycline (MC) or a chemically modified non-antimicrobial tetracycline (CMT) by oral gavage for a 3-week period; untreated diabetic and nondiabetic rats served as controls. On day 21, all rats received an intravenous injection of 3H-proline followed by perfusion fixation with an aldehyde mixture at 20 minutes and 4 hours after isotope injection. The parietal bones of these rats were dissected and processed for quantitative electron microscopic autoradiography to study 3H-proline utilization by osteoblasts. At 20 minutes after 3H-proline injection, radioprecursor was incorporated by the Golgi-RER system of the osteoblasts in the periosteal surface of the control rats. At the 4-hour time period, most of the label was present over the collagen fibers of the osteoid. In contrast, the flattened bone-lining cells in the untreated diabetic rats showed minimal uptake (20 minutes) and secretion (4 hours) of labeled proline. In both MC and CMT-treated diabetic rats, the radioprecursor was localized in the osteoblasts and osteoid matrix in a pattern similar to that seen in the control rats at both 20 minutes and 4 hours after isotope injection. Labeling of the osteoid by the radioprecursor was greater as a result of CMT treatment than during minocycline treatment. These results suggest that the diabetes-induced suppression of synthesis and secretion of protein (presumably collagen and its precursor) by osteoblasts can be restored to near-normal levels by administration of tetracycline(s) and that this effect is mediated by a non-antimicrobial property of these antibiotics.

Topics: Animals; Autoradiography; Collagen; Diabetes Mellitus, Experimental; Male; Microscopy, Electron; Osteoblasts; Osteoporosis; Procollagen; Proline; Rats; Rats, Inbred Strains; Streptozocin; Tetracycline; Tritium

In 28 patients with idiopathic or postmenopausal type 1 (spinal crush fracture) osteoporosis, resorption indices and dynamic measurements of trabecular bone formation based on in vivo tetracycline labeling in 7.5 mm transiliac biopsies have been compared with trends in radial cortical and trabecular bone density measured with computed tomography. Positive correlations were observed between trabecular bone density trends in the radius and indices of bone formation in the ilium. These were improved when one of the two resorption indices was included with a formation index in bivariate regressions. Marked interindividual variations in radial bone density trends were also seen in cortical bone. These correlated poorly with trends in trabecular bone. Weak negative relationships between cortical bone trends and indices relating to bone formation and resorption were observed, but a positive association was seen with single-labeled surfaces on iliac trabeculae. If, as has been suggested, there are periodic variations in bone formation, the results suggest that axial and peripheral trabecular bone density trends are synchronized in osteoporosis, perhaps in response to systemic factors, such as circulating hormones.

Topics: Aged; Bone and Bones; Bone Density; Bone Development; Bone Resorption; Female; Humans; Ilium; Male; Middle Aged; Osteoporosis; Osteoporosis, Postmenopausal; Regression Analysis; Tetracycline

Twenty of 22 consecutive British patients with crush fracture osteoporosis had transiliac bone biopsies following double in vivo tetracycline labeling synchronized with the collection of serum for the measurement of vitamin D metabolites. A significant but direct (rather than inverse) relationship was found between 25-hydroxyvitamin D (calcidiol) levels and the fraction of cancellous surfaces covered with osteoid not taking either tetracycline label (r = 0.53, P less than 0.02). There was no correlation with 1,25-dihydroxyvitamin D levels. No patient had frankly thickened osteoid seams although 3 had reduced but measurable calcidiol levels. These results make it unlikely that the majority of patients with osteoporosis who have osteoid of normal thickness but reduced uptake of tetracycline have a mineralization defect secondary to vitamin D deficiency. The pathophysiological significance of unlabeled osteoid in osteoporosis requires further investigation.

Topics: Aged; Calcifediol; Calcitriol; Female; Humans; Male; Middle Aged; Osteogenesis; Osteoporosis; Tetracycline; Vitamin D

Experimental osteoporosis was induced in the rat by a combination of ovariectomy and immobilization by hemicordotomy. (Asu1,7)-eel calcitonin (CT) was administered at doses of 0.1, 0.5, 1.0, 2.5, and 5.0 MRC unit/kg, and its preventive effect on bone loss was examined. Significant bone loss was observed in the untreated control group by photo-densitometry and measurement of bone mass. CT at doses of above 1.0 MRC unit/kg significantly increased femur scores and at doses of above 2.5 MRC unit/kg resulted in significantly higher photodensity. Dry weight and ash weight were significantly higher in the 2.5 and 5.0 MRC unit/kg CT-treated groups. Administration of CT had a nearly dose-dependent effect on bone mass. Histomorphometry revealed significantly lower fractional formation surface and fractional resorption surface in the 5.0 MRC unit/kg CT-treated group. Bone mineralization was studied by the quantitative analysis of tetracycline incorporation. Tetracycline uptake was significantly lower in the groups treated with CT at doses above 1.0 MRC unit/kg. The kinetic bone formation activity studied by 45Ca and 14C-proline tracer examination, in the 5.0 MRC unit/kg CT-treated group was significantly lower than that in the control group, but not lower than that in the sham-operated group.

Topics: Animals; Bone and Bones; Calcitonin; Densitometry; Dose-Response Relationship, Drug; Female; Immobilization; Osteogenesis; Osteoporosis; Ovariectomy; Rats; Rats, Inbred Strains; Tetracycline

Bone formation and resorption have been measured in patients with idiopathic osteoporosis by histomorphometry of 7.5-mm trephine biopsies and in the whole body by 85Sr radiotracer methodology and calcium balances. The studies were synchronized and most were preceded by double in vivo tetracycline labeling. Correlations between histological and kinetic bone formation indices were better when better when based on the extent of double tetracycline labels than on measurements of osteoid by visible light microscopy. Correction of the kinetic data for long-term exchange, using 5 months' serial whole body counting of retained 85Sr, improved the fit of the kinetic to the histological data. A statistical analysis of the measurement uncertainties showed that the residual scatter in the best correlations (between exchange-corrected bone formation rates and double-labeled osteoid surface indices) could be attributed to measurement imprecision alone. The exchange-corrected resorption rate correlated fairly well with iliac trabecular resorption surfaces, and using a volume referent rather than a surface referent for the histological index improved the statistical fit when patients with therapeutically accelerated bone turnover were included. A much better correlation was obtained by including osteoid volume acting as an independent predictor of bone resorption in a bivariate regression with a resorption surface index. The residual errors could then be accounted for by known measurement uncertainties. Whereas osteoid taking a double label closely predicted the kinetic rate of bone formation, further analysis suggested that osteoid that took no label or a single label was more closely related to bone resorption, presumably as a secondary result of the coupling of bone formation to bone resorption. The idea that continued bone loss in some patients is associated with defective osteoblastic bone formation is supported by the low rates found in some patients by both techniques. Heuristically these studies validate both in vivo tetracycline labeling for dynamic histomorphometry and corrections for long-term exchange in kinetic studies of bone formation, providing a quantitative framework for the design and analysis of future studies of bone remodeling in the osteoporoses.

Topics: Adult; Aged; Bone Development; Bone Resorption; Female; Humans; Male; Middle Aged; Osteoporosis; Strontium Radioisotopes; Tetracycline

On theoretical grounds, it seemed plausible that the apparent distance between two fluorescent labels can surpass the actual distance between them by a percentage that is related to the true distance: section thickness ratio. For similar reasons, the percentage of double labels discernible as such would be influenced by the same ratio. These assumptions were tested in a series of doubly labeled biopsies in which a large variation of appositional rates had been found. The apparent mean distance between labels and, hence, the appositional rate as measured in 20 microns sections was significantly lower than in the 5 microns sections from the same biopsies. Yet, 20 microns sections cannot be used to counteract distortion by oblique sectioning because of the bias obscuring the lower range of true interlabel distances. The percentage of doubly labeled surfaces was from 13 to over 50% lower in the 20 microns sections. Thus, overlap of double labels by geometrical projection in 20 microns sections causes a considerable reduction of formation rates derived from the parameters investigated. The problem is resolved, to a large extent, by using sections as thin as possible.

Topics: Bone and Bones; Chronic Kidney Disease-Mineral and Bone Disorder; Histological Techniques; Humans; Microscopy, Fluorescence; Minerals; Models, Biological; Osteogenesis; Osteoporosis; Tetracycline

Thirty-four normal Caucasian women and 69 patients with osteoporosis were given two bone-labeling agents. Transilial biopsies were obtained and embedded undecalcified. Fractional surfaces covered by double label and single label were determined, along with total surface and double label width by fluorescent microscopy. Mean wall thickness was measured on toluidine blue-stained sections. The mathematical model for predicting the amount of single-labeled surface was compared to the actual amount of surface covered by single label. We found an excess of single labels compared to the model in both groups, more so in the normals, and suggest the explanation is that bone-formation pauses at formation sites in both groups but tends not to resume in the patients. This results in a shortened functional life span of the osteoblast and bone loss. Further, the data suggest that for accurate expression of bone formation rates in trabecular bone using a volume referent, one should use the whole bone tissue including bone and marrow and should express the bone-forming surface as the double-labeled surface plus one-half the measured single-labeled surface.

Topics: Aged; Biopsy, Needle; Bone and Bones; Demeclocycline; Female; Humans; Middle Aged; Models, Biological; Osteoporosis; Tetracycline

Although this paper has dealt with well-established diagnostic procedures, I have attempted to present a practical summary based on experience with over 400 cases. A complete and modern approach to the evaluation of the bone biopsy for metabolic bone disease may be summarized as follows: Preoperative double labeling with tetracycline (two 3-day courses of tetracycline separated by 12 days); Full-thickness iliac bone biopsy yielding a 5- to 6-mm diameter specimen; Undecalcified sectioning (5-10 mu) processed in glycol or methyl methacrylate; Histomorphometric analysis with light microscope and planimeter; Tetracycline analysis with fluorescent microscope.

Topics: Biopsy; Bone and Bones; Histological Techniques; Humans; Microscopy, Fluorescence; Minerals; Osteoclasts; Osteomalacia; Osteoporosis; Tetracycline

In this article, an explanation and definition of basic terms used in metabolic bone disease are presented, with a review of histomorphometric findings in osteoporosis, osteomalacia, Paget's disease, and hyperparathyroidism. An appropriate bone biopsy protocol for diagnostic purposes is also presented.

Topics: Biopsy; Bone and Bones; Bone Diseases, Metabolic; Bone Marrow; Humans; Hyperparathyroidism; Microscopy, Fluorescence; Minerals; Osteitis Deformans; Osteoblasts; Osteoclasts; Osteomalacia; Osteoporosis; Tetracycline

The acute effects of immobilization on cortical and trabecular bone formation were studied in juvenile male rhesus monkeys (Macaca mulatta). Four animals were immobilized for two weeks by application of total body casts. Two control monkeys were housed in separate metabolic cages under similar environmental and dietary conditions. Tetracycline derivatives were administered on three separate occasions to label sites of bone formation. The tetracycline-labeling frequency and mineral apposition rate of osteons and trabecular bone surfaces in the humerus and femur were determined. The inhibition of bone formation induced by immobilization was more pronounced in trabecular bone. Immobilized monkeys exhibited a moderate, but statistically nonsignificant, reduction in the percentage of osteons forming bone. Conversely, the dramatic decline in the percentage of trabecular surfaces undergoing bone formation in immobilized monkeys was found to be highly significant. The diminished rate of mineral apposition in osteons suggested that osteoblastic activity was impaired in cortical bone during immobilization. The mineral apposition rate in trabecular bone could not be determined reliably due to minimal tetracycline deposition, which indicated that osteoblastic activity and/or recruitment almost ceased in the metaphyseal tissue of immobilized monkeys.

Topics: Animals; Bone and Bones; Bone Regeneration; Bone Resorption; Demeclocycline; Femur; Humerus; Immobilization; Macaca mulatta; Male; Minerals; Osteoblasts; Osteoporosis; Oxytetracycline; Tetracycline

Twenty-six women with untreated postmenopausal osteoporosis underwent iliac crest biopsy following tetracycline-labeling and mineral metabolism studies. Histomorphometric assessment of their bone remodeling rates, including formation determined by the tetracycline-labeling technique, revealed considerable variation. Eight women had no evidence of active bone formation (inactive remodeling osteoporosis), whereas the others showed a spectrum of bone formation rates (active remodeling osteoporosis). Clinical and biochemical studies failed to predict the histomorphometric findings. Postmenopausal osteoporosis is a histologically heterogeneous disorder with morphologic expression in bone that cannot be predicted by single or combined routine clinical and laboratory parameters. Bone biopsy, necessary to identify the histologic lesion and assess skeletal dynamics, may prove to be important for optimal therapy of osteoporosis, as a variety of agents--with different effects on bone remodeling--are available.

Topics: Aged; Bone Development; Bone Resorption; Calcification, Physiologic; Female; Humans; Ilium; Menopause; Middle Aged; Osteoporosis; Parathyroid Hormone; Tetracycline

The influence of immobilisation on the number and function of osteoblasts was determined by morphological examination of normal rabbit bone and that that had been inactivated through surgery. Contrary to earlier supposition, after inactivation not only the osteoclasts but also the osteoblasts increase distinctly. Even retardation of the parathyroid gland by magnesium does not lead to decrease of the osseous structure. Therefore, it can be concluded that disuse osteoporosis is normally produced in its first weeks by a considerable activity decrease of even more osteoblasts and less by increased function of osteoclasts. The increase in number of osteoblasts and their decreased activity after immobilisation indicate that the mechanical stimulus gives the essential impulse for full osteoblast function.

Topics: Animals; Cell Count; Femur; Immobilization; Magnesium; Osteoblasts; Osteoclasts; Osteoporosis; Parathyroid Glands; Rabbits; Tetracycline

The mean wall thickness (MWT) and duration of formation periods (sigma f) of trabecular bone packets have been measured in iliac crest biopsies following double tetracycline labeling from 9 women having primary osteoporosis, with vertebral crush fractures and reduced trabecular bone volume (TBV), and 9 age- and sex-matched controls. The MWT of the osteoporotic biopsies was significantly less than that of the controls and was negatively correlated with age in the latter. There was also a positive correlation between MWT and TBV in the controls but not in the osteoporotics. Sigma f, in days, showed a tendency to decline with age in the control biopsies and was further decreased in the osteoporotic patients. These results suggest that a major contribution to the negative skeletal balance existing in both primary osteoporosis and physiological osteopenia is a decrease in bone formation, caused by a reduction in the life span of the osteoblastic population at the basic multicellular unit (BMU) level.

Topics: Adult; Age Factors; Aged; Bone and Bones; Humans; Ilium; Male; Middle Aged; Minerals; Osteogenesis; Osteoporosis; Tetracycline

The ration of late to early uptake of several radionuclides was examined as a method for distinguishing states of abnormal bone metabolism. Nutritional osteoporosis (secondary hyperparathyroidism) and osteomalacia were produced in young rats and compared to a control group. The ratio of early (3-6 hrs.) to late (4-6 days) uptake of barium-131, nitrate, indium-111 EDTMP, and lead-203 were studied, as was that of strontium-85 chloride, a calcium analogue. Ratios of late to early uptake were found to distinguish osteomalacia from osteoporosis in the models when strontium-85 or barium-131 were used. Barium-131 may be a clinically useful alternative to strontium-85 in the evaluation of metabolic bone disease due to its shorter half-life and lower radiation dose.

Topics: Animals; Barium; Diagnosis, Differential; Indium; Lead; Osteomalacia; Osteoporosis; Radiation Dosage; Radioisotopes; Radionuclide Imaging; Rats; Strontium Radioisotopes; Tetracycline; Time Factors

Involutional osteopenia is the most common metabolic bone disorder affecting the elderly population. Improved diagnostic techniques now allow for earlier detection of a decrease in bone mass than is possible with routine skeletal roentgenograms. Methods developed for quantitating bone remodeling have given new insight to the mechanisms involved in age-related skeletal loss. Theories of pathogenesis include [1] inadequate skeletal acquisition during youth, [2] dietary deficiencies of calcium and vitamin D, [3] hormonal imbalance, and [4] local factors influencing skeletal remodeling, particularly at the endosteal envelope. Numerous agents affecting bone remodeling have been used to treat involutional osteopenia, but none has been proved to restore bone mass. New programs involving combinations of agents give promise for increasing bone mineral content and, it is hoped, reducing fracture rate.

Topics: Absorptiometry, Photon; Age Factors; Aged; Bone and Bones; Bone Development; Ergocalciferols; Estrogens; Female; Humans; Male; Middle Aged; Osteoporosis; Tetracycline

Topics: Calcium; Drug Combinations; Fluorides; Humans; Microscopy, Fluorescence; Osteoporosis; Ribs; Tetracycline

This paper presents an experimental study of rabbits immobilized in plaster of paris casts. By means of Tetracycline and 45Ca-labelling an immobilisation over 12 weeks showed a significant diminuition of bone formation. In the first stages of remobilisation the bone formation was found to be increased and became normally in a later stage. The lower dorsal spine was not sufficiently immobilized in our experiments. Therefore significant changes of bone turnover could not be observed.

Topics: Animals; Bone and Bones; Calcium Radioisotopes; Calcium Sulfate; Femur; Immobilization; Osteoporosis; Rabbits; Tetracycline; Thoracic Vertebrae; Time Factors

Topics: Animals; Bone and Bones; Dose-Response Relationship, Drug; Methods; Microscopy, Fluorescence; Osteoporosis; Oxytetracycline; Parathyroid Hormone; Rats; Tetracycline; Time Factors; Tissue Preservation

Topics: Animals; Body Weight; Bone and Bones; Bone Development; Bone Resorption; Crystallization; Dosage Forms; Dose-Response Relationship, Drug; Femur; Hydrocortisone; Male; Microscopy, Fluorescence; Osteoporosis; Rabbits; Radiography; Ribs; Solutions; Tetracycline; Time Factors

Topics: Adult; Age Factors; Aged; Biopsy; Bone and Bones; Bone Development; Bone Resorption; Female; Humans; Ilium; Male; Middle Aged; Osteoblasts; Osteomalacia; Osteoporosis; Tetracycline

Topics: Amines; Animals; Disease Models, Animal; Femur Head; Lathyrism; Male; Microscopy, Fluorescence; Nitriles; Osteoporosis; Rats; Rats, Inbred Strains; Tetracycline

Topics: Adult; Aged; Bone Diseases; Calcium; Calcium Isotopes; Calcium Metabolism Disorders; Child, Preschool; Demeclocycline; Diet Therapy; Dietary Proteins; Female; Glutens; Humans; Hydrochlorothiazide; Infant; Kinetics; Male; Methandrostenolone; Middle Aged; Osteoporosis; Rickets; Tetracycline; Vitamin D

Topics: Animals; Bone and Bones; Calcium; Dextrans; Female; Femur; Forelimb; Hindlimb; Hypocalcemia; Male; Osteoporosis; Parathyroid Glands; Phosphorus; Radiography; Rats; Tetracycline; Tibia

Topics: Adult; Aged; Biopsy; Bone Resorption; Female; Fractures, Spontaneous; Haversian System; Humans; Male; Middle Aged; Osteoporosis; Phenylbutazone; Radiotherapy; Ribs; Salicylates; Spinal Diseases; Spondylitis, Ankylosing; Tetracycline

Topics: Adult; Aged; Arthritis, Rheumatoid; Cartilage, Articular; Female; Humans; Male; Metatarsus; Microradiography; Microscopy, Fluorescence; Middle Aged; Osteoporosis; Rheumatoid Factor; Tetracycline; Time Factors

Topics: Adult; Age Factors; Aged; Biopsy; Histological Techniques; Humans; Microradiography; Middle Aged; Osteoporosis; Tetracycline

Topics: Achilles Tendon; Animals; Bone Regeneration; Bone Resorption; Calcaneus; Fluorescence; Immobilization; Methods; Microradiography; Osteoporosis; Rabbits; Sciatic Nerve; Tetracycline; Ultraviolet Rays

Topics: Adult; Aged; Biopsy; Bone and Bones; Female; Haversian System; Humans; Male; Middle Aged; Osteogenesis; Osteoporosis; Ribs; Tetracycline

Topics: Alkaline Phosphatase; Animals; Bone Resorption; Calcitonin; Calcium; Calcium, Dietary; Cats; Depression, Chemical; Epiphyses; Femur; Fluorescence; Microradiography; Osteogenesis; Osteoporosis; Phosphates; Swine; Tetracycline; Time Factors; Ulna

Topics: Aminosalicylic Acids; Antitubercular Agents; Cortisone; Drug Hypersensitivity; Ethambutol; Fludrocortisone; Humans; Hypotension; Isoniazid; Male; Middle Aged; Osteoporosis; Prednisone; Streptomycin; Tetracycline; Tuberculosis, Pulmonary

Topics: Adult; Biopsy; Bone Regeneration; Bone Resorption; Calcitonin; Calcium; Gluconates; Humans; Infusions, Parenteral; Intestinal Absorption; Kinetics; Male; Middle Aged; Osteoporosis; Parathyroid Hormone; Phosphorus; Ribs; Tetracycline

Topics: Adult; Aged; Biopsy; Bone and Bones; Bone Development; Female; Fluorides; Humans; Ilium; Male; Microradiography; Middle Aged; Osteoporosis; Ribs; Sodium; Tetracycline; Vitamin D

Topics: Animals; Biological Assay; Bone and Bones; Dogs; Glycosaminoglycans; Heparin; Osteoblasts; Osteogenesis; Osteoporosis; Tetracycline

Topics: Animals; Body Weight; Bone and Bones; Bone Development; Haplorhini; Hydroxyproline; Male; Osteoporosis; Protein Deficiency; Tetracycline

Topics: Aged; Animals; Bone and Bones; Bone Diseases; Bone Resorption; Cortisone; Female; Fluorides; Fractures, Bone; Heparin; Humans; Male; Osteitis Deformans; Osteoporosis; Otosclerosis; Phosphates; Rats; Sodium; Tetracycline

Topics: Animals; Animals, Newborn; Bone Resorption; Epiphyses; Femur Head; Fluorescence; Hip Dislocation; Microradiography; Osteogenesis; Osteoporosis; Rabbits; Radioisotopes; Tetracycline

Topics: Adult; Aged; Arthritis, Rheumatoid; Bone Development; Bone Resorption; Female; Humans; Male; Middle Aged; Osteoporosis; Prednisone; Ribs; Tetracycline

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

Topics: Adolescent; Adult; Biopsy; Bone and Bones; Bone Resorption; Collagen; Cushing Syndrome; Glucocorticoids; Humans; Hydroxyproline; Osteoblasts; Osteoclasts; Osteoporosis; Phosphorus; Tetracycline

Topics: Acromegaly; Adrenal Cortex Hormones; Adult; Aged; Bone Development; Female; Humans; Male; Methods; Middle Aged; Osteogenesis Imperfecta; Osteoporosis; Radioisotopes; Tetracycline

Topics: Arthritis, Rheumatoid; Biopsy; Bone Resorption; Fluorescence; Humans; In Vitro Techniques; Osteoporosis; Ribs; Tetracycline

Topics: Blood Chemical Analysis; Calcium, Dietary; Femur; Microradiography; Osteoporosis; Parathyroid Glands; Research; Skeleton; Tetracycline

Topics: Arteriovenous Fistula; Bone and Bones; Chlortetracycline; Femoral Artery; Femur; Humans; Leg; Osteoporosis; Tetracycline; Tibia

Topics: Aging; Allergy and Immunology; Bone and Bones; Bone Transplantation; Calcification, Physiologic; Calciphylaxis; Calcium; Dihydrotachysterol; Fluorescence; Growth Hormone; Humans; Metabolism; Microscopy; Microscopy, Fluorescence; Myositis Ossificans; Osteoporosis; Physiology; Regeneration; Tetracycline

Topics: Biopsy; Bone and Bones; Fluorescence; Humans; Microscopy; Microscopy, Fluorescence; Osteoporosis; Physiology; Tetracycline; Tetracyclines