Histomorphometric analysis of resorption and formation in osteoporotics and controls with a mean age of 61 years.
Explore the source record for details and available documents.
Biopsy↗
Biomedical subjects
F Melsen
Publications and source records attributed to F Melsen.
Reconstruction of the formative site in trabecular bone by a new, quick, and easy method.
Ordinary measurements of the wall thickness (the end result of the osteoblastic work) of trabecular bone packets (completed remodeling sites) describe the average thickness of walls formed during the previous two to three years. If the bone biopsy is obtained shortly after onset of disease or initiation of treatment, only a few of the measured sites will represent walls formed under the new conditions. With a reconstruction of the formative site true information of the performed osteoblastic work can be obtained, since it is based upon observations of the actual formative events and not the end result (completed walls). Previously published methods have the disadvantage of being time consuming and technically difficult. Furthermore, the method by Eriksen et al. includes rather complicated mathematical calculations. In the present study a new method for reconstruction of the formative phase is presented, which can be performed from measurements normally obtained in a routine histomorphometric analysis and from paired values of osteoid thicknesses and uncompleted wall thickness. The method does not introduce a new time consuming step in the histomorphometric analyses of the bone biopsy. Furthermore, calculations needed to reconstruct the events of the formative phase can easily be performed using a personal computer and a spread-sheet. The new method for reconstruction presented in this paper gives growth curves for matrix and bone mineral, which are virtually identical with the growth curves previously published by Eriksen et al. for the same 20 normal individuals.
Adult↗
Primary hyperparathyroidism: iliac crest trabecular bone volume, structure, remodeling, and balance evaluated by histomorphometric methods.
Iliac bone biopsies from 69 patients (48 females, 21 males; median age 58 years; range 17-79 years) with primary hyperparathyroidism (PHP) were examined, and static histomorphometric parameters compared to 30 age- and sex-matched normal controls. The control group for the dynamic parameters constituted 20 sex-matched younger normal controls. Fractional volume of trabecular bone was normal, but the trabeculae were thinner (p less than 0.05) in PHP. The structural parameters marrow space star volume, intertrabecular distance, and mean trabecular plate density were not significantly different in PHP patients compared to normal controls, but the age-related increase, for females, in marrow space star volume and decrease, for both sexes, in mean plate density observed in the controls were not noticed in the PHP group. Trabecular bone remodeling was found significantly increased in the PHP patients reflected by increased extension of eroded (p less than 0.001), osteoid (p less than 0.001), and labeled surfaces (p less than 0.05). The activation frequency was increased by approximately 50% (p less than 0.001). Neither PHP patients nor controls showed age-related decrease in trabecular thickness, and accordingly in both groups the bone balance per remodeling cycle was very close to and not significantly different from zero. Normal postmenopausal women (age greater than or equal to 50 yr) had lower trabecular bone volume (p less than 0.001) and higher intertrabecular distance than normal pre-menopausal women (age less than 50 yr).(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
A reconstruction of the remodelling cycle in normal human cortical iliac bone.
This paper describes the reconstruction of the remodelling cycle in normal iliac crest cortical bone from static and dynamic variables after double labelling with tetracycline in 10 young normal individuals. The average duration of the resorptive period was 27 days during which the average rate of resorption was 4.7 microns/day. The final resorption depth was 76 microns. The diameter of osteoclast containing cutting cones was significantly smaller (P less than 0.05) than cutting cones containing mononuclear cells, indicating an initial osteoclastic resorption phase preceding a mononuclear resorption phase. The average mineralization lag-time was 8 days and the formative period 89 days. Osteoid thickness during this period averaged 5.8 microns. The seam thickness varied with the underlying uncompleted wall thickness, i.e., during the course of the formative period, with matrix deposition initially exceeding, later equalling and finally lower than the rate of mineralization. The mineral appositional rate (MAR) was 1.2 microns/day and the adjusted mineral appositional rate (Aj.AR) 0.9 micron/day. Both MAR and Aj.AR decreased during the formative period. A completed wall thickness of 62 microns left a Haversian canal with a diameter of 29 microns. After a quiescent period of 438 days the osteon (or parts of it) was reactivated. The average activation frequency was 0.93 per year.
Adult↗
The effects of etidronate on trabecular bone remodeling in postmenopausal spinal osteoporosis: a randomized study comparing intermittent treatment and an ADFR regime.
Thirty-seven patients were randomized to receive intermittent cyclic etidronate (400 mg/day oral for 2 weeks, followed by 13 weeks off treatment) or an ADFR treatment (100 micrograms/day oral triiodothyronine for 7 days, followed by 400 mg/day etidronate for 2 weeks and 12 weeks off treatment). Supplemental calcium (120 mg/day) and vitamin D3 (400 IU/day) were given throughout the study period to all patients. Biochemical analyses, iliac-crest bone biopsies, and lumbar bone mineral content (BMC) measurements were performed before and during 60 weeks of treatment. Sixteen patients in the intermittent cyclic etidronate group and 15 in the ADFR group completed 60 weeks of treatment. Serum alkaline phosphatase decreased from 185 (43) (mean, (SD] to 144 (35) (p less than 0.001) and from 221 (69) to 156 (43) (p less than 0.002) during intermittent cyclic etidronate treatment and ADFR treatment, respectively, without any significant changes in renal hydroxyproline excretion. Final resorption depth, trabecular bone activation frequency, and bone formation rate decreased significantly from 51.5 (48.4/60.0) microns (median (25%/75% quartiles] to 44.0 (39.6/46.2) microns (p less than 0.04), from 0.30 (0.17/0.62) year-1 to 0.10 (0.02/0.19) year-1 (p less than 0.03) and from 0.035 (0.020/0.081) microns3/microns2/day to 0.015 (0.002/0.025) microns3/microns2/day, p less than 0.03 respectively, during intermittent cyclic etidronate treatment, but were unchanged during ADFR treatment. No significant changes in trabecular bone volume, bone balance per remodeling cycle, or BMC were noted in either treatment group; no evidence of osteomalacia was found. Intermittent cyclic etidronate treatment may be effective in preventing bone loss and in decreasing the risk of trabecular plate perforation, and thereby maintaining the integrity of bone architecture, in postmenopausal osteoporosis.(ABSTRACT TRUNCATED AT 250 WORDS)
Aged↗
Biologically meaningful determinants of the in vitro strength of lumbar vertebrae.
Applying unbiased stereological methods and a new stereological parameter, star volume of cancellous bone, the bone structure of the first vertebral body was examined and compared with the compressive strength of the second lumbar vertebra. The material came from eight males, aged 33-69 years (mean 49 years) and seven women, aged 22-87 years (mean 52 years) without malignant or metabolic bone disease. From these individuals, first and second lumbar vertebral body were obtained at autopsy. The heights and weights of the individuals were recorded. The following structural parameters were estimated on undecalcified, seven-microns, Goldner-Trichrome stained vertical sections: fractional volume of trabecular bone (BV/TV%), mean trabecular thickness (Tb.Th.l1 microns), trabecular star volume (V*tr mm3), marrow space star volume (V* m.space mm3), and mean thickness of the lateral cortical ring (microns). The compressive strength of whole vertebral body, mean cross sectional area (cm2), and ash density (g/cm3) were estimated and the data were compared to bone histomorphometric estimates. A significant decrease with age for all parameters was found except for marrow space star volume, which increased. With compressive strength as the dependent variable and all other parameters as independent variables, it was shown by standard multiple regression analysis that the in vitro tested compressive strength could be predicted from mean cortical thickness, mean cross sectional area, and marrow space star volume or ash density with a multiple, squared coefficient of regression (r2) of 0.95 when the height and sex of the individual were known.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Marrow space star volume in the iliac crest decreases in osteoporotic patients after continuous treatment with fluoride, calcium, and vitamin D2 for five years.
Iliac crest biopsies in osteoporotic patients were obtained before and after five years of continuous treatment with sodium fluoride (40-60 mg/d), vitamin D2 (18,000 IE/d), and calcium phosphate (45 mmol/d). Star volume of marrow space and trabeculae, mean trabecular thickness, and fractional amount of trabecular bone were estimated on so-called vertical sections before and after treatment. Results showed a significant decrease in marrow space star volume after five years of treatment (35 mm3 versus 19 mm3) (2p less than 0.02). No significant changes were observed in trabecular star volume (0.149 mm3 versus 0.104 mm3) (2p greater than 0.50) or mean trabecular thickness (85 microns versus 79 microns, 2p greater than 0.30). A slight but insignificant increase in the fractional amount of trabecular bone was found (9.7% versus 10.4%, 2p greater than 0.50). A rather close inverse correlation was obtained, however, between individual changes in trabecular bone volume fraction and marrow space star volume (r = -0.72, 2p = 0.011). The findings suggest that the large marrow "cavities" had been split into two or more "cavities" by some newly generated trabecular structures leading to increased trabecular connectivity. The strength of trabecular bone may be increased due to this beneficial effect of fluoride on trabecular bone structure.
Aged↗
Antacid-induced osteomalacia: a case report with a histomorphometric analysis.
The case of a 75-year-old woman with severe osteomalacia secondary to ingestion of large amounts of an aluminum-containing antacid is reported. Biochemical analysis revealed signs of phosphate malabsorption and increased levels of bone markers (S-alkaline phosphatase and U-hydroxyproline). A 99mTc-bone scan revealed multiple areas of increased uptake. The patient was normocalcaemic, with normal serum levels of intact parathyroid hormone and 25-hydroxyvitamin D. Serum 1,25-dihydroxyvitamin D was high normal. A transiliac bone biopsy from the patient showed severe osteomalacia. Symptoms, biochemical parameters, bone scan and bone morphology were all normalized 1 year after stoppage of antacid ingestion and treatment with vitamin D2. calcium phosphate and sodium fluoride because of severe osteopeni. The characteristics of this condition and the role of phosphate depletion and aluminum in the pathogenesis of bone lesions are discussed.
Aged↗
Bone biopsy in the horse. 1. Method using the wing of ilium.
Two hundred and five bone biopsies from the wing of ilium were taken from 52 growing and 70 older horses. The method was initially evaluated in 4 horses at post mortem and then performed in 26 horses under general anaesthesia. The technique was later developed for biopsying horses in the standing position under local anaesthesia (n = 70 adults; n = 22 foals). The core of the bone biopsy consisted of a central cancellous portion between two cortices. This type of sample allowed a complete histomorphometrical analysis. An integral part of the procedure was intravital bone labelling using fluorochromes with a known interval between labels. Potential hazards associated with the use of oxytetracycline labels included the onset of diarrhoea and laminitis in some foals. The method was simple, safe and efficient for both anaesthetised and standing horses. The only difficulties encountered were minor and were associated with blunting of the drill bit, scoring of the internal surface of the drill bit guide and occasional loss of the distal part of the biopsy core. Post operative complications included haematoma formation and skin infections. It was concluded that this technique offered a quick and effective method of collecting bone biopsies in horses, which facilitated the quantitative assessment of skeletal changes.
Animals↗
Bone biopsy in the horse. 2. Evaluation of histomorphometric examination.
The histomorphometrical examination of a series of bone biopsies from the wing of ilium of foals and older horses is reported. Biopsies were obtained from 20 clinically normal horses, which had previously been infused with tetracycline intravenously twice at a 7 day interval at a dose rate of 10 to 15 mg kg-1. The horses were divided into 2 groups. Group 1 consisted of 10 foals (mean age: 4 +/- 1 months) which were biopsied at 3 different sites in the wing of ilium. Group 2 comprised 10 older horses (mean age: 91 +/- 63 months) which were biopsied from only one site in the left ilium. A systematic evaluation of intra-observer, intra-core, intra-bone and inter-bone errors was made to investigate parameter variations that might affect interpretation of bone biopsies. The measurements carried out included cancellous bone volume (Cn-BV/TV), osteoid surface (OS/BS), eroded surface (ES/BS), mean wall thickness (W.Th), mean osteoid thickness (O.Th), distance between labels (Ir.L.Th) and mineralizing surface (MS/BS). The intra-observer variance, the variance between sections, the variance between adjacent biopsies and that between right and left sides proved to be smaller than the inter-individual variance. The estimate of errors associated with the histomorphometrical analysis of bone biopsies is important for correct interpretations of changes due to disease.
Animals↗
Bone biopsy in the horse. 3. Normal histomorphometric data according to age and sex.
Histomorphometrical analysis of bone biopsies from the wing of ilium in 35 clinically normal horses are reported according to age. The biopsies were collected from 20 mixed-bred foals (mean age 6 +/- 1 months) and 15 older horses (mean age 73 +/- 62 months). No gender differences were found in the group of foals examined, but a significant difference (p less than 0.001) in a number of the primary measurements occurred between them and the older horses. The parameters which altered with age were the extent of osteoid surface (OS/BS), the extent of resorption (erosion) surface (ES/BS), the osteoid thickness (O. Th), the mineral appositional rate (MAR), which corresponds to the rate of matrix mineralisation and, if no mineralisation defects exist reflects the amount of bone laid down per day, and the extent of labelled surfaces (MS/BS). These data indicate a much greater rate of bone remodelling in the foals. This was also reflected in a number of the derived parameters (i.e. the extent of quiescent surfaces [QS/BS] and the activation frequency [Ac.f]).
Age Factors↗
Formation of osteoclasts and osteoblast-like cells in long-term human bone marrow cultures.
A culture system for human osteoclasts is described. It is based on incubation of mononuclear marrow cells for three weeks in the presence of 1,25 dihydroxyvitamin D3. The resulting cells exhibited all the classic characteristics of osteoclasts. They formed a true syncytium with up to 25 nuclei per cell. The cells revealed a strong positive reaction for tartrate-resistant acid phosphatase and a ruffled border. When these cells were cultured on 100 microns thick human dentine slices for three weeks, typical resorption pits were formed. In the culture, alkaline phosphatase-positive osteoblast-like cells were formed in the vicinity of osteoclasts. This culture system permits studies of human osteoclasts and their interaction with osteoblast cell precursors in the human bone marrow.
Acid Phosphatase↗
Formation of osteoblast-like cells from human mononuclear bone marrow cultures.
Osteoblast-like cells are commonly found in the vicinity of osteoclasts formed in long-term human bone marrow cultures, and they are believed to be derived from osteogenic cell precursors belonging to the stromal cell system. This paper describes a new culture method for human osteoblasts from the adherent cell population of long-term human mononuclear bone marrow cultures. The cells obtained exhibited all the classic characteristics of osteoblasts. They contained high intracellular concentrations of alkaline phosphatase and they secreted the osteoblast-specific marker bone Gla protein. Collagen production was mainly (95-98%) procollagen type I propeptide and only minute quantities of procollagen type III propeptide were detectable by radioimmunoassay in the conditioned medium. After eight weeks the cells formed a mineralized matrix on exposure to beta-glycerophosphate and ascorbic acid. This system provides a model for the study of osteoblast differentiation in vitro and may form the basis for the use of defined media in bone cell cultures due to the presence of high concentrations of osteoblast precursors.
Adult↗
Osteopenia and osteomalacia after gastrectomy: interrelations between biochemical markers of bone remodelling, vitamin D metabolites, and bone histomorphometry.
The prevalence of metabolic disease in a population of 68 postgastrectomy patients was assessed using histomorphometric evaluation of transiliac bone biopsy specimens after tetracycline double labelling. Trabecular bone volume was significantly lower in the postgastrectomy group (p less than 0.01): 62% of the patients had increased osteoid surface, 56% increased osteoid thickness, and 24% increased mineralisation lag time. Only 18%, however, fulfilled the diagnostic criteria for osteomalacia--increased osteoid thickness and increased mineralisation lag time. Postgastrectomy patients had reduced serum concentrations of calcium (p less than 0.01), phosphate (p less than 0.01), and 25-hydroxyvitamin D, while levels of alkaline phosphatase and 1,25 dihydroxyvitamin D were high (p less than 0.01). The severity of the mineralisation defect as reflected by mineralisation lag time was positively correlated to serum 25-hydroxyvitamin D, but unrelated to serum 1,25-dihydroxyvitamin D. Multiple linear regression analysis showed that serum 25-hydroxyvitamin D, age, and the duration of postoperative follow up were significant determinants of the mineralisation defect in a given patient. The limited value of serum markers in the diagnosis of osteomalacia was emphasised by the fact that six of the eight patients with osteomalacia had normal serum levels of calcium and alkaline phosphatase, and five of the eight had values for 25-hydroxyvitamin D in the normal range for healthy control subjects. The results clearly show the need for vitamin D supplementation and regular control after gastric resection.
Adult↗
Primary hyperparathyroidism: changes in trabecular bone remodeling following surgical treatment--evaluated by histomorphometric methods.
Iliac bone biopsies from 11 patients who underwent successful surgery for primary hyperparathyroidism were examined before and median 7 months after surgical treatment. Trabecular bone volume increased (p less than 0.05) and eroded (p less than 0.005) and osteoid covered surfaces decreased (p less than 0.005) in the postoperative period. Also, a decline in tetracycline labeled surfaces was noticed (p less than 0.02). Osteoid thickness, mineral appositional rate and mineralization lag time were unchanged. Bone formation rate at the level of the basic multicellular unit (BMU) was unaffected, but at the tissue level bone formation rate diminished (p less than 0.02). The surgical cure of primary hyperparathyroidism was found accompanied by a change in bone metabolism as the trabecular bone remodeling decreased from a high turnover to a low turnover state. The spongy bone mass increased after parathyroidectomy but the clinical significance of this finding was not clear.
Aged↗
A direct method for fast three-dimensional serial reconstruction.
A method for accurate three-dimensional reconstruction of openly connected porous structures is described. The method is based on embedding of a specimen in a contrast coloured epoxy resin and serial sectioning in a standard hard tissue microtome. A PC-based image processing system is used for direct digitization of the cut surface, and by thresholding two-phase images are obtained. The process is fully automated, and about 170 sections can be produced, digitized, dichotomized, and stored per hour. As an example of its applications, the method is used on trabecular bone, which is an anisotropic porous structure.
Bone and Bones↗
Indomethacin and bone trauma. Effects on remodeling of rabbit bone.
The influence of indomethacin on remodeling activity in normal trabecular and cortical bone and its influence on cortical bone close to a midtibial drill hole, 2 mm in diameter were histomorphometrically evaluated. Eight rabbits were treated with indomethacin (12.5 mg/kg/day), and another 8 rabbits served as controls. After 3 days, the mean plasma indomethacin level was 542 ng/mL, resulting in an almost complete inhibition of prostaglandin synthesis as reflected by the serum levels. In the control rabbits the remodeling activity after 6 weeks was increased 1 mm away from the drill hole but not at 3 and 8 mm. In conclusion, indomethacin had no effect on the activated remodeling process in cortical bone neighboring a small drill hole or on remodeling in nontraumatized cortical and cancellous bone. This suggests that the inhibitory effect of indomethacin on the remodeling process following local trauma to bone depends on the extent of the trauma.
Animals↗
[Animal experimental testing of the irritant properties of a multimineral solution on veins].
Explore the source record for details and available documents.
Animals↗