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Biomedical subjects

F Melsen

Publications and source records attributed to F Melsen.

At least 73 records · Page 4Linked to original sources
PubMed1989

Effects of sodium fluoride, vitamin D, and calcium on cortical bone remodeling in osteoporotic patients.

The purpose of this histomorphometric study of iliac bone biopsies from 10 postmenopausal osteoporotic patients was to describe the effects of sodium fluoride (combined with calcium and vitamin D) on remodeling in cortical bone after 6 months and after 5 years of treatment. Biopsies had been fixed in absolute methanol, embedded undecalcified in methylmetacrylate, and cut on a heavyduty microtome. The therapy had no effect on the thickness of cortical bone in the iliac crest but increased the porosity slightly. It had no statistically significant effect on depth of resorption or thickness of new walls formed at remodeling sites but treatment increased the fraction of osteons undergoing remodeling in cortical bone. After 6 months of treatment, the increase was due to an enhanced activation of new remodeling sites, but in biopsies taken after 5 years of treatment, some degree of mineralization defect was observed and the duration of the remodeling cycle appeared to be prolonged. The mechanism underlying this qualitative change in the response to treatment is unknown, and it is unclear whether the mineralization defect may be prevented by, e.g., an altered supplementation of vitamin D or calcium.

Aged↗
PubMed1989

A randomized study on the effects of estrogen/gestagen or high dose oral calcium on trabecular bone remodeling in postmenopausal osteoporosis.

Thirty-seven patients with postmenopausal crush fracture osteoporosis were randomized to oral cyclic estrogen/gestagen (n = 20) or oral calcium (2000 mg elemental calcium per day) (n = 17). Fourteen in each group completed 1 year of treatment. Iliac crest bone biopsies were obtained after intravital double labeling with tetracycline before and after treatment in 10 patients on estrogen/gestagen and 11 patients on calcium. In the estrogen/gestagen group the activation frequency in trabecular bone decreased from 0.52 + 0.11 (SEM) year-1 to 0.27 + 0.08 year-1 (p less than 0.01). No significant changes were found in resorption or formation periods. The osteoid surfaces and the mineralizing surfaces decreased (p less than 0.05), whereas the decrease in eroded surfaces was insignificant. Furthermore, no significant changes were observed in final resorption depth, wall thickness or bone balance per remodeling cycle. Serum alkaline phosphatase and renal hydroxyproline excretion decreased during treatment (p less than 0.002), whereas the lumbar bone mineral content (BMC) increased (p less than 0.01). In the calcium group the extent and thickness of osteoid surfaces decreased (p less than 0.05) without significant changes in activation frequency. Serum alkaline phosphatase and renal hydroxyproline excretion decreased during treatment (p less than 0.02). No significant changes were observed in lumbar BMC or the other histomorphometric parameters. The study supports that the positive effect of estrogen/gestagen on BMC can be explained by a reduction in the activation frequency of new remodeling cycles leading to a decreased remodeling space and an increase in mean bone age. There is no evidence of a positive balance per remodeling cycle.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1989

Normal postmenopausal women show iliac crest trabecular thickening on vertical sections.

Trabecular thickness and the trabecular star volume were estimated in 49 normal individuals (20 males and 29 females) using an unbiased sampling procedure consisting of anisotropic, vertical sections, and a corresponding anisotropic test system. Eight-microns-thick undecalcified stained vertical sections were obtained from iliac crest specimens. Implying a trabecular plate model mean trabecular thickness (Tb.Th., microns) was estimated by different methods: (a) the ratio between bone volume and bone surface (Tb.Th.ratio); (b) the mean of the orthogonal intercepts multiplied with pi/4 (Tb.Th.l0); and (c) the mean of random linear intercepts divided by 2 (Tb.Th.l1). Trabecular star volume (Vtr*, mm3), a true three-dimensional size parameter independent on any model, was estimated using linear intercepts in random directions. Significant (2p less than 0.001) correlations were found between the different methods with coefficients of correlation ranging from 0.71 to 0.89. The Tb.Th. ratio was overall higher (155 +/- 31 microns, (X, SD), 2p less than 0.001) than the other linear estimates, Tb.Th.l0: 144 +/- 26 microns and Tb.Th.l1: 135 +/- 27 microns. Estimates based on orthogonal intercepts (l0) were slightly higher (2p less than 0.001) than those from random linear intercepts (l1). Among all the individuals no significant age-related changes were seen in the measured parameters. However, postmenopausal women (greater than 50 years of age) had more thick trabeculae than younger women (2p = 0.03). Intra-individual distribution analysis disclosed that this finding could not be explained by preferential perforation and loss of thinner trabeculae during bone remodeling. Therefore, normal postmenopausal women do increase trabecular thickness with age.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Star volume of marrow space and trabeculae of the first lumbar vertebra: sampling efficiency and biological variation.

The decrease in the amount of trabecular bone which is seen with age cannot solely be explained by thinning of trabeculae but must also be due to a loss of structural trabecular bone leading to a discontinuity in the trabecular network. Due to the complex architecture and the anisotropy of bone it is difficult to demonstrate this structural change by conventional histomorphometry. Unbiased stereological estimators can however be obtained from anisotropic structures when using vertical sections and a specially designed anisotropic test system. This combined with a new and unbiased stereological parameter for bone structure the star volume can be of major importance in clarifying histological changes of bone structure. The star volume is defined as the mean volume of all the parts of an object which can be seen unobscured in all directions from a particular point with the mean value taken over all points inside the object. It is defined for any type of objects including cavities like marrow space and networks like the trabecular system. Measurements are performed using a frame and a grid with points and lines. The material investigated was the first lumbar vertebra obtained from two females and six males with ages 26 to 75 years without malignant or metabolic bone diseases. The sampling procedure was as required for vertical sections. Results did show a highly significant, five-fold increase in the star volume of the marrow space with age; no such age correlation was found for the star volume of the trabeculae. The only explanation for such an increase in the size of the marrow space is by removing or perforating trabecular bone.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Structural and histomorphometric studies of iliac crest trabecular and cortical bone in autosomal dominant osteopetrosis: a study of two radiological types.

Cylindrical iliac crest biopsies were obtained from 16 patients with autosomal dominant osteopetrosis after intravital double labeling with tetracycline, and compared with normal age- and sex-matched controls. Ten patients had the radiological type I (5 women, 5 men, aged 17-62 years, mean 42) characterized by diffuse, symmetrical osteosclerosis and enlarged thickness of the cranial vault. Six patients had type II (2 women, 4 men, aged 22-44 years, mean 36), where "Rugger Jersey Spine" and endobone are characteristic findings. Structural studies of cortical and trabecular bone were performed, and trabecular bone resorption and formation rates were studied using dynamic histomorphometry. The total biopsy length (C. Wi) were increased in type I (p less than 0.05), and unchanged in type II. Both types showed increased cortical width (Ct. Wi) (p less than 0.01 and p less than 0.05, respectively), and decreased fractional width of cancellous bone (Cn.Wi/C.Wi) (p less than 0.01 and p less than 0.05). The fractional trabecular bone volume (BV/TV) and trabecular thickness (Tb. Th) were both significantly increased in type I (p less than 0.05), while resorptive and formative indices of trabecular bone remodeling were normal. No difference was found in trabecular bone balance, which was slightly positive in both patients and controls. In type II osteopetrosis the eroded surfaces (OS/BS) were significantly increased (p less than 0.01), as was the total resorptive period RP) (p less than 0.05). The resorption depth (R.D.) was normal, while the resorption rate (MRR) was insignificantly decreased. Many big multinucleated osteoclasts were seen in this type suggesting defective resorptive function.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1989

Cortical bone cross-sectional osteon size in chronic pulmonary insufficiency and regional ischemic states.

Cross sectional osteon diameter (D) and Haversian canal diameter (d) were measured in undecalcified, unstained sections from the mid-diaphysis of femoral bones from 13 patients with long lasting chronic pulmonary insufficiency, 10 patients with unilateral thrombosis of the femoral artery and from sex- and age-matched normal controls. The cross sectional osteon radius (R = the distance travelled by osteoclats), the mean wall thickness (MWT = (D-d)/2 = distance travelled by osteoblasts) and the structural unit balance (B = R/MWT) were calculated. No significant differences were found in R, MWT og B between chronic pulmonary insufficiency patients and normal controls. Furthermore, no significant differences were found between thrombotic or non-thrombotic legs or between thrombotic legs and their normal controls. This part of the study does not support the concept that the distance travelled by the osteoclasts (R) depends on local supply of nutrients and/or removal of waste products. However, in all patients and controls R was larger in the inner zone than in the outer zone (p less than 0.01). This could be explained by the anatomy of the arterial supply to cortical bone supporting the above hypothesis.

Adult↗
PubMed1989

Histomorphometric analysis of bone in idiopathic hypercalciuria before and after treatment with thiazide.

Twenty-seven normocalcemic patients aged 11-69 yrs with recurrent renal stone formation and idiopathic hypercalciuria were studied before and after treatment with hydrochlorthiazide (TD) 50 mg twice a day for 6 months. Hypercalciuria was defined as a 24 h renal calcium excretion of more than 7.5 mmol for males and 6.3 mmol for females. Quantitative histomorphometric analysis of iliac crest bone biopsies were performed before and after treatment. TD treatment increased the adjusted serum calcium level (p less than 0.01), whereas no significant effects on the serum levels of phosphorous, alkaline phosphatase or iPTH were found. The urinary calcium/creatinine ratio decreased (p less than 0.01) during TD treatment, whereas no change in the urinary phosphorous/creatinine ratio was found. The histomorphometric analysis revealed a reduction in the extent of eroded surfaces (p less than 0.05) and bone formation rate (p less than 0.05) as well as a decrease in the osteoid thickness (p less than 0.05) during TD treatment. No effect on the trabecular bone volume was found. A reduction in the activation frequency of new remodeling sites and thereby a reduced bone turnover during TD treatment can explain the observed histomorphometric changes. The decrease in osteoid thickness may be related to the increased serum calcium concentration leading to better conditions for mineralization.

Adult↗
PubMed1989

A histomorphometric determination of iliac bone remodeling in patients with recurrent renal stone formation and idiopathic hypercalciuria.

33 normocalcemic patients (22 males and 11 females) aged 20-68 years with recurrent renal stone formation and idiopathic hypercalciuria were compared to 33 approximately sex- and age-matched normal controls. Quantitative histomorphometric analysis of iliac crest biopsies were performed after intravital tetracycline double labeling in the patients and in 30 sex- and age-matched normal controls. No difference was found between patients and controls in albumin adjusted serum calcium levels. Serum phosphorus was significantly reduced (p less than 0.01) in the patient group whereas the urinary phosphorus/creatinine ratio was increased (p less than 0.01). The serum calcium phosphate product (S-CaxS-P) was significantly reduced in the patients (p less than 0.05). As expected, the urinary calcium/creatinine ratio was higher in the patient group than in the controls (p less than 0.001). Serum parathyroid hormone was normal. The histomorphometric analysis revealed signs of a moderate mineralization defect (reduced adjusted appositional rate (p less than 0.05), prolonged mineralization lag time (p less than 0.05) and prolonged formation (p less than 0.05)), and an increased extension of eroded surfaces (P less than 0.05) in the patients. The amount of trabecular bone and the balance between the thickness of bone resorbed and later formed per remodeling cycle and all other histomorphometric parameters were found normal in the patients. The combined histomorphometric and biochemical data are best explained by a primary renal phosphate leak leading to hypophosphataemia and a slight mineralization defect. The hypercalciuria may be explained by an enhanced renal production of 1.25-dihydroxyvitamin D secondary to the reduced serum levels of phosphorus. No signs of secondary or primary hyperparathyroidism were observed.

Adult↗
PubMed1989

Navicular bone disease: a comparative histomorphometric study.

Twelve horses suffering from navicular bone disease were examined in a prospective, controlled histomorphometric study for six months. The objective was to compare the histology of navicular bones from untreated animals to those treated with the egg-bar shoeing technique. These data were compared to similar sections from three normal animals. The current investigation provided quantitative support to previous findings concerning clinical improvement. Detailed histology, changes in bone morphometry and pathophysiological reactions are discussed.

Animals↗
PubMed1989

Indomethacin and bone remodeling. Effect on cortical bone after osteotomy in rabbits.

Remodeling in cortical bone close to a plated tibial midshaft osteotomy was histomorphometrically evaluated in 32 rabbits. The animals were divided into two groups, one being treated with indomethacin (10 mg/kg per day) and the other receiving placebo. In the placebo-treated group, the remodeling activity was higher in the osteotomized leg compared with the intact leg. Two and 6 weeks after osteotomy, the number of resorptive and formative foci was reduced in the indomethacin-treated group compared with the placebo group. Porosity did not differ between the groups after 2 weeks; but after 6 weeks, it was reduced in the indomethacin-treated animals. Throughout the study, the bone formation rate did not differ between the two groups. This study demonstrates that indomethacin inhibits the remodeling of traumatized bone.

Animals↗
PubMed1989

Urinary cytology in the detection of bladder tumours. Influence of concomitant urothelial atypia.

The role of urinary cytology in detection and follow-up of urinary bladder tumours is still evolving. However, considerable variations in the accuracy of detecting bladder tumours exist in published work on the subject. In this study the influence of concomitant urothelial atypia on urinary cytology was investigated. Further, the correlation of grading between cytology and tumour histology was examined, and finally the role of urinary cytology as a prognostic factor was investigated. 102 comparative studies of simultaneously achieved precystoscopic voided urine samples, tumour histology and 8 pre-selected site biopsies were available from patients having a Ta, T1 or T2 bladder tumour. The overall numbers of positive cytology were found to be 64%, but correcting for false positives caused by concomitant urothelial atypia the numbers were reduced to 55% (p less than 0.01). A considerable higher ability to detect high-grade than low-grade tumours was found. Correlation between grading of tumour histology and cytology was found to be only 50%. Patients were followed for 3 years. From the results of pre-cystoscopic cytology it was possible to define a low-risk group and a high-risk group. Patients with negative cytology had very low risk of future invasive tumour recurrence whereas all patients with grade III-IV cytologic changes were found to harbour either a grade III tumour or carcinoma in situ, both conditions predictive of aggressive tumour course.

Carcinoma in Situ↗
PubMed1989

Histomorphometric analysis of bone in metabolic bone disease.

Most of the tools necessary for a detailed study of bone remodeling are now available. These methods will enable us to substitute simple surface-based histomorphometry with pertinent derived variables that reveal more information about the processes going on. Because of the inherent variability of the methods, bone histomorphometry is less well suited for investigations in single individuals. However, in terms of basic investigations of cell and tissue activity in grouped materials of patients with metabolic bone disease and the evaluation of treatment regimens in these materials, bone histomorphometric investigations still yield the most detailed analyses.

Animals↗
PubMed1989

[Hormonal regulation of bone remodeling].

In the adult skeleton a continuous turnover of bone matrix and mineral takes place at discrete foci throughout life (bone remodeling). This process ensures the mechanical integrity of the skeleton and plays an important role in calcium homeostasis. It constitutes a very complex sequence of events, involving activation of several different stem cell populations and rigid regulation of two contrasting processes: bone resorption and bone formation. The study of factors involved in the control of bone remodeling is complicated by the involvement of local factors (growth factors, prostaglandins, inorganic ions) and systemic factors (calcitropic hormones), that interact at several different levels (cellular, tissue, and organ-levels). Most metabolic bone diseases, including osteoporosis, are caused by disturbances in the regulation of bone remodeling leading to an imbalance between resorption and formation. To understand these disturbances fully, it is necessary to study the different levels of skeletal organization, and the effect of different hormones and local factors on bone resorption and formation. In this review are described the effects of calcitropic hormones on bone cells at the cellular and tissue levels, and their interaction with local factors.

Bone and Bones↗
PubMed1988

Positive urinary cytology after tumor resection: an indicator for concomitant carcinoma in situ.

Concomitant urothelial atypia (grade II atypia or carcinoma in situ) is predictive of new tumor growth after transurethral tumor resection. Concomitant urothelial atypia can be demonstrated by pre-selected site mucosal biopsies. However, a number of patients have new tumors despite normal pre-selected site biopsies. To investigate whether urinary cytology is a better indicator for concomitant urothelial atypia than pre-selected site biopsies, we studied in bladder tumor patients the correlation between the findings of pre-selected site biopsies (8 per patient) at tumor resection and urinary cytology (2 per patient) after successful resection. Concomitant urothelial atypia was demonstrated by biopsies in 52 per cent of the patients, of whom 60 per cent had grade II atypia and 40 per cent had carcinoma in situ. All patients with concomitant carcinoma in situ in biopsies had positive cytology findings. Of the patients with concomitant grade II atypia in biopsies 15 per cent had negative cytology studies. In 48 per cent of the patients no urothelial atypia in pre-selected site biopsies was demonstrable. However, cytology was positive, that is neoplastic cells were present, in 64 per cent of these specimens (19 patients). Of the 19 patients 16 currently have had demonstrable urothelial atypia in pre-selected site mucosal biopsies at a later occasion. We conclude that urinary cytology seems to be a better indicator for the presence of concomitant urothelial atypia than pre-selected site mucosal biopsies and, therefore, it can be used as a screening procedure for patients without demonstrable concomitant carcinoma in situ at tumor resection.

Carcinoma in Situ↗
PubMed1987

Bone turnover and balance evaluated by a combined calcium balance and 47calcium kinetic study and dynamic histomorphometry.

Bone resorption and formation rates were evaluated at the organ level using calcium kinetic methods and at the trabecular bone tissue level using dynamic histomorphometry in 20 patients with various metabolic bone diseases (primary hyperparathyroidism (N = 9), hyperthyroidism (N = 6), and hypothyroidism (N = 5). Highly significant correlations were demonstrated between resorption and formation rates at organ level (r = .90, P less than .001) and at tissue level (volume referent) (r = .93, P less than .001), indicating a high degree of coupling between resorption and formation within the three disease states. Tissue level resorption rates (surface referent, as well as volume referent) both correlated significantly (P less than .01) to organ level resorption rate (r = .60 and r = .63, respectively). Fractional active resorption surface and cellular level resorption rate did not reveal significant correlations to calcium kinetic estimates. No correlation could be demonstrated between organ level mineralization rate and formative or labeled trabecular surfaces. However, all tetracycline based tissue level formation rates revealed highly significant correlations (P less than .01) to organ level mineralization rate (calcification rate, r = .71; surface referent bone formation rate, r = .59; volume referent bone formation rate, r = .68). Based on histomorphometric parameters for resorption and formation, actual and predicted tissue level trabecular bone balances were calculated. Both the actual and predicted bone balance correlated significantly to the organ level calcium balance (P less than .05). Correction for skeletal size based on BMC measurements did not improve any of the correlations significantly.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Unbiased stereological estimation of osteoid and resorption fractional surfaces in trabecular bone using vertical sections: sampling efficiency and biological variation.

The conventional stereological procedure for estimating bone surface densities in iliac crest biopsies provides biased estimates because bone substructure is anisotropic and the sectioning of the biopsies is intended to be parallel to the cylindrical axis of the iliac crest biopsy. It has recently been shown that random anisotropic sections with an identifiable axis or direction which is arbitrary but fixed can be used for unbiased estimates of surface areas. The arbitrary axis is called "vertical," a denomination which does not imply anything about its relation to directions in the world's field of gravity. Sampling efficiency and biological variation of fractional osteoid and resorptive surfaces were investigated in 14 paired bone specimens obtained from two females and five males (mean age 64) using an integral anisotropic test system constructed of cycloids. Results obtained at direct microscopy were compared to results obtained with projection onto the table. Mean fractional osteoid and resorption surfaces were 6.2 and 1.4% using direct microscopy and 5.6 and 1.7% using projection. Estimation of variance at each level of sampling showed that the majority of the total observed variance was due to true variance between individuals; for fractional osteoid surface the unavoidable biological variation was 80.5% of the observed variation and for fractional resorption surfaces it was 57%. The efficiency of the estimation procedure is therefore close to optimal and the only way to improve the precision in groups of patients and controls would be to include more individuals in the study.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1987

Unbiased stereologic estimation of surface density in bone using vertical sections.

The conventional stereologic procedure for estimating bone surface densities in iliac crest biopsies gives biased estimates because bone substructure is anisotropic and the sectioning of the biopsies is intended to be parallel to the cylindrical axis of the iliac crest biopsy. It has recently been shown that random anisotropic sections with an identifiable axis or direction that is arbitrary but fixed can be used for unbiased estimates of surface areas. The arbitrary axis is called "vertical," which does not imply anything about its relation to direction of gravity. To describe the methodology and the practical sampling procedure for vertical sections, surface density of trabecular bone was estimated in 16 bone samples obtained at autopsy from eight persons (mean age 64 years) using an anisotropic cycloid test system designed for vertical sections. In addition, variation in the estimation procedure was quantitated. The average surface density of trabecular bone was 2.8 +/- 0.4 mm-1 (+/- SD). No systematic difference was observed between the two bone specimens from each of the eight persons. Estimation of the variance at each level of sampling showed that the majority of the total observed variance was due to true variance between individuals. Vertical section is, in general, the method of choice when dealing with surfaces not known to have an isotropic orientation distribution. The cycloid test system is easy and fast to use, and the estimate is truely unbiased. The requirements are all sections must be parallel to the vertical axis, the rotation around this axis must be random, the position of the section or of the biopsy must be random, and the vertical axis must be identified in the section.

Aged↗