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Biomedical subjects

F Melsen

Publications and source records attributed to F Melsen.

At least 91 records · Page 5Linked to original sources

The rhythmic relation between antler and bone porosity in Danish deer.

The interrelationship between porosity of antlers and metacarpal bones and annual physiologic osteopenia has been investigated in mature Danish male Roe deer (Capreolus capreolus). The study shows a highly significant inverse correlation between porosity in the antlers and porosity in the metacarpal bones, indicating a necessary calcium mobilization from the bones for the mineralization of the antlers. The investigation further suggests that the decreasing porosity of the antlers throughout the antler period, reaching very low values, may be the cause of antler shedding.

Animals↗

Safety of osteoporosis treatment with sodium fluoride, calcium phosphate and vitamin D.

During an 8-year period, 163 consecutive patients with spinal crush fracture osteoporosis started a 5-year treatment with a combination of sodium fluoride (60 mg/day), calcium phosphate (45 mmol/day) and vitamin D2 (18,000 IU/day), and were followed in the outpatient clinic every 3 months. Fourty-three patients completed the 5-year treatment. Mean observation time was 2.8 years, totalling 460 patient-years. Fifty-one percent of the patients experienced joint-related (37%) or gastrointestinal (25%) side effects at one time or another. All side effects subsided after a median 6-week withdrawal of fluoride. Six percent of the patients withdrew from treatment due to side effects. Mean serum calcium values slightly decreased during treatment and no hypercalcemic episodes were seen. Urinary excretion of calcium did not change during treatment. No changes in renal, bone marrow or thyroid functions could be detected. The liver function might be slightly affected as indicated by minute increases in serum bilirubin and decreases in serum coagulation factors and albumin, but no other changes in liver function were observed.

Adolescent↗

Trabecular bone remodeling and balance in primary hyperparathyroidism.

The total remodeling sequences in 19 primary hyperparathyroid patients and 16 approximately age-matched and sex-matched controls were reconstructed from histomorphometric analyses of bone specimens obtained after intravital tetracycline double labeling. In the primary hyperparathyroid group the total amount of work performed by resorptive cells was reduced, as indicated by the significantly lower three-dimensional mononuclear and preosteoblast-like cell resorption depths (35.8 microns vs 44.5 microns in normals, P less than 0.01 and 45.3 microns vs 56.6 microns in normals, P less than 0.01, respectively). The active resorption period (i.e., the function period for osteoclasts and mononuclear cells) was reduced to 19 days compared to 29 days in normals (P less than 0.05), but no difference with respect to bone resorption rates could be demonstrated between the two groups. The median bone formation period (Sigmaf) in primary hyperparathyroid patients was not different from the value obtained in normals (172 days vs 134 days, respectively), and the matrix appositional rate (Ama), as well as the mineralization lag time (tm), were also unchanged. The initial mineralization rate (Ami(i)) was not significantly different from the value obtained in normals, but averaged over the total bone formation period, a reduced mineralization rate could be demonstrated (0.32 micron3/micron2 per day vs 0.46 micron3/micron2 per day in normals, P less than 0.01). The measured final three-dimensional thickness of bone formed during Sigmaf (mcwTm) was reduced in the primary hyperparathyroid group (51.1 microns vs 55.9 microns in normals, P less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

A histomorphometric determination of iliac bone structure and remodeling in obese subjects.

Quantitative histomorphometric analyses of iliac crest biopsies were performed after tetracycline double labeling in 24 patients with morbid obesity and in 30 age- and sex-matched controls. The amount and structure of bone were determined from measurements of total biopsy length, fractional length of medullary space, fractional trabecular bone volume, trabecular thickness, and the intertrabecular distance. Static and dynamic variables of bone resorption and formation were determined, and the balance of the BMU level was estimated from final resorption depth and mean wall thickness of trabecular structural units. In the obese patients the total biopsy length was increased, with a normal proportion of medullary space to total biopsy length. The mean fractional trabecular bone volume was reduced due to an increased distance between trabeculae of normal mean thickness. The total biopsy length in the obese patients was found to be positively related to the intertrabecular distance and inversely related to the fractional trabecular bone volume. The remaining histomorphometric variables describing bone formation rate at tissue, BMU, and cellular levels, the amount of bone formed, the mineralization process, mineralization lag time, bone resorption, and the balance between resorption and formation were all normal in the obese group.

Adult↗

Kinetics of trabecular bone resorption and formation in hypothyroidism: evidence for a positive balance per remodeling cycle.

Using a recently described model for reconstruction of the entire remodeling sequence in trabecular bone after tetracycline double labeling, bone remodeling was investigated in 18 hypothyroid female patients and 11 age- and sex-matched controls. In the hypothyroid group, the final resorption depth was reduced to 42 microns vs 53 microns in the control group (P less than 0.01). The total resorption period was increased to 76 days vs 32 days in the control group (P less than 0.001), and the resorption rate was lowered to 0.8 micron/day vs 2.1 microns/day in the control group (P less than 0.001). The function period for preosteoblast-like cells was 22 days compared to 14 days in normals (P less than 0.05). The total bone formation period was prolonged to 620 days in the hypothyroid group compared to 151 days in the control group (P less than 0.001), and the matrix and mineral appositional rates were lowered to 0.7 and 0.5 micron3/micron2 per day compared to 1.8 (P less than 0.001) and 1.4 (P less than 0.001) micron3/micron2 per day, respectively. The mineralization lag time in the hypothyroid group was 48 days vs 25 days in the control group (P less than 0.001), and at the start of bone formation this difference was even more pronounced (63 and 16 days, respectively, P less than 0.001). The mean completed wall thickness was increased in the hypothyroid group to 59.5 microns compared to 54 micron in the control group (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Nuclear uptake of 1,25-dihydroxy[3H]-cholecalciferol in peripheral blood monocytes.

The active vitamin D metabolite, 1,25-dihydroxycholecalciferol induces differentiation of monocytes into macrophages. The pharmacological induction of differentiation of primitive, rapidly proliferating cell lines into more mature cells with lower proliferative potential is a new dimension in the treatment of myeloproliferative disorders, which may prove to be an important alternative to more traditional regimens. Furthermore, the cell primarily engaged in bone resorption--the osteoclast--represents another differentiated form of mononuclear phagocytes, and 1,25-dihydroxycholecalciferol increases the number of osteoclasts. Since the cellular action of 1,25-dihydroxycholecalciferol is exerted mainly through its binding to nuclear receptors, a detailed knowledge of ligand-receptor interactions is mandatory for future work in this area. In order to investigate the interaction between 1,25-dihydroxycholecalciferol and its receptor in mononuclear cells, the nuclear uptake of the hormone was studied using a whole cell assay. The nuclear uptake of 1,25-dihydroxy[3H]cholecalciferol in human monocytes at physiological temperature and pH was saturable, specific, and fully reversible. When eight normal individuals were investigated, the maximal binding capacity (Bmax) was 0.4-8.4 fmol/10(6) cells and the dissociation constants (Kd) were 0.12-0.45 nmol/l. The characterization of the nuclear uptake of 1,25-dihydroxy[3H]cholecalciferol in intact human monocytes shows that it is mediated by binding of the ligand to a specific nuclear receptor. The binding to the nuclear receptor is the result of the passage of ligand across the cytoplasmic membrane and of the cytoplasmic transport of ligand. In contrast to conventional receptor assays in hypertonic cellular extracts, this system provides information on the role of the cytoplasmic membrane in relation to the nuclear uptake of 1,25-dihydroxycholecalciferol, which may be closer to in vivo cellular conditions.

Binding, Competitive↗

An experimental study of the healing process of equine chondral and osteochondral defects.

Four full thickness cartilage defects, two linear and two elliptical, and four subchondral cavity defects were created at the point of weightbearing of the medial femoral condyle in four experimental ponies. This study showed that subchondral bone cysts can develop following full thickness (cartilage only) linear cartilage defects at a weightbearing location. Subchondral bone cysts did not develop following the removal of an elliptical piece of cartilage, exposing the subchondral bone. Primary subchondral defects created in communication with the joint cavity did not heal by replacement with bone over a six-month period. Fibrous and cartilaginous repair occurred which appeared to be unrelated to the size or depth of the subchondral defect. Irrespective of the size of the defects, the surrounding bone showed marked woven bone formation with remodelling of existing and newly formed bone. The resulting osteosclerosis indicated a positive balance and a natural limitation of cavity expansion. The positive balance affected only the surrounding bone and did not lead to re-establishment of the bone within the cavity during the period studied.

Animals↗

Bone mineral loss, bone histomorphometry and vitamin D metabolism in patients with rheumatoid arthritis on long-term glucocorticoid treatment.

Long-term glucocorticoid treatment might interfere with the vitamin D metabolism. The serum concentrations of 25-OHD were significantly reduced whereas the circulating levels of 1,25-(OH)2D were normal in 50 patients with rheumatoid arthritis on long-term treatment with small doses of prednisone. The bone mineral content of the forearm was significantly reduced, but the degree of bone loss did not correlate with duration of treatment or dose of prednisone given. Quantitative bone histomorphometry was performed in 18 patients. Apart from a significant correlation between serum 25-OHD and the fractional trabecular bone volume, no relationships were observed between bone histomorphometry and vitamin D metabolites or serum iPTH. The results indicate that the bone loss was due to a decreased osteoblastic activity rather than to an impaired vitamin D metabolism.

Adult↗

Changes in vitamin D metabolites and bone histology in rats during recovery from rickets.

The relative roles of 25-hydroxyvitamin D (25-OHD), 1,25-dihydroxyvitamin D (1,25-(OH)2D) and 24,25-dihydroxyvitamin D (24,25-(OH)2D) in bone mineralization are largely unknown. Young vitamin D depleted rats were fed increasing amounts of vitamin D and grouped radiologically in accordance with the rat line test. They ranged from severely rachitic to normal. Radiology was correlated with serum levels of 25-OHD, 1,25-(OH)2D, 24,25-(OH)2D, ionized calcium, magnesium, and phosphate, with bone histology, and with the total mineral content of the animals. Serum 1,25-(OH)2D rose in a linear fashion to supranormal values during bone healing and correlated with the radiological degree of rickets. Serum 25-OHD was below detection limit in the most rachitic and low in the radiologically normal rats, whereas 24,25-(OH)2D was low in all groups. These two metabolites showed no correlation with the radiologic, histologic or biochemical parameters. In rachitic rats, 1,25-(OH)2D appears to play a major role in bone healing and possibly exerts a direct effect on bone cells. It cannot be ruled out, however, that the effect is mediated through a rise in serum levels of calcium and phosphorus, although signs of bone healing were seen in the presence of a subnormal calcium X phosphorus product. Initiation of mineralization can take place with unmeasurable 25-OHD, and 24,25-(OH)2D seems to be without importance.

Animals↗

Trabecular bone resorption depth decreases with age: differences between normal males and females.

The resorption depth below osteoclasts, mononuclear cells, and preosteoblast-like cells can be estimated by counting the number of lamellae of known thickness eroded below the three cell types. In a previous study on bone resorption in young normal individuals, we demonstrated that the mean depth below osteoclasts was smaller than the mean depth below mononuclear cells, which again was smaller than the mean depth below preosteoblast-like cells, the last taken as the final depth reached. In order to investigate the variation in resorption depth with age in both sexes, we examined bone biopsy specimens from 42 normal females and 34 normal males aged 17-90 years. For each patient the mean osteoclastic, mononuclear, and preosteoblast-like cell resorption depths were calculated, and the surface extensions of the three types of resorption lacunae were determined. The surface extent of preosteoblast-like cell lacunae increased with age in females (p less than 0.05). Osteoclastic resorption depth was constant throughout the ages in females as well as in males. Mononuclear and preosteoblast-like cell resorption depths decreased significantly with age in females (p less than 0.01 and p less than 0.05, respectively) as well as in males (p less than 0.05 and p less than 0.01, respectively). The mean depth of lacunae where resorption had terminated (i.e., preosteoblast-like cell resorption depth) was larger in females aged 30-60 years than in men of the same age (p less than 0.05). The reduction in final resorption depth with age is parallel to the decrease in mean thickness of completed walls previously described.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Trabecular bone remodeling and bone balance in hyperthyroidism.

In vivo tetracycline double-labeled iliac crest bone biopsies from 15 hyperthyroid patients were used for the reconstruction of curves describing the variation of resorption depth and formation thickness with time. The curves emerging were compared to curves reconstructed from 13 age- and sex-matched normal individuals (mean age 44 years). The median function period for resorptive cells in hyperthyroid patients (16 days) was about one-third the resorptive period in normals (51 days). No significant difference between the osteoclast-, mononuclear-, or preosteoblast-like cell resorption depths could be demonstrated between the two groups. Consequently, the median resorption rate in hyperthyroid patients (3.8 microns/day) was more than 3 times higher than the value in the control group (1.1 micron/day). Median Sigma, was shorter in the hyperthyroid group (109 days) than in the control group (151 days, P less than 0.05), as was the median initial mineralization lag time (5 and 16 days, respectively, P less than 0.01). No significant difference between the measured mean completed wall thickness (mcwT) values in the hyperthyroid groups and the control group could be demonstrated (58.1 and 60.5 micron respectively). Median initial mineralization rate in the hyperthyroid group (1.2 micron3/micron2 per day) was not significantly higher than the value calculated in the control group (0.9 micron3/micron2 per day), but median initial matrix appositional rate in hyperthyroid (4.8 microns3/micron2 per day) was 3 times higher than the value calculated for normals (1.6 micron3/micron2 per day) (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Relationships between calcium and phosphorus homeostasis, parathyroid hormone levels, bone aluminum, and bone histomorphometry in patients on maintenance hemodialysis.

Serum biochemistry related to calcium and phosphorus homeostasis and parathyroid function was studied together with bone histomorphometry after double-labeling with tetracycline and staining for aluminum in 17 patients without symptoms of bone disease, treated with maintenance hemodialysis for at least 6 months. A close correlation was found between the serum level of parathyroid hormone (PTH) and bone resorption surfaces and bone formation rates, both at tissue and basic multicellular unit (BMU) levels. The patients could be divided into a high turnover group with a normal mineralization process and a low turnover group with markedly defective mineralization. The second group was further characterized by lower PTH and higher fractional aluminum-stained trabecular bone surfaces. For the whole patient material, the fractional aluminum-stained surfaces related inversely to tetracycline-labeled surfaces and to bone formation rates at both BMU and tissue levels, but not to the time on dialysis or to the cumulative ingested amount of aluminum hydroxide. The data provide evidence that PTH or PTH-related factors, besides activating bone remodeling, directly enhance bone formation in dialysis patients and that aluminum incorporation into bone is associated with a progressive disturbance of bone mineralization.

Adult↗

Histopathology of the stapes in osteogenesis imperfecta.

Conventional histological studies of stapes footplates from patients with osteogenesis imperfecta revealed, in nine out of 15 stapes examined, an otospongiotic-like lesion. Although the morphology of the stapedial lesion was comparable to the early otosclerotic focus, a greater structural disorganization and larger resorption spaces in osteogenesis imperfecta distinguished the two conditions. The histopathology of the stapes was related to the morphology of cortical and trabecular bone from the iliac crest. Various degrees of immature, osteogenic bony tissue were found in the iliac crest, showing no resemblance to the otospongiotic-like focus in the footplate. Even though the histologic appearance of the stapes footplates differed from the findings in peripheral bone, the present study indicates that the stapedial lesion in osteogenesis imperfecta is most likely a manifestation of the generalized bone and connective tissue disorder. The study further supports the view that osteogenesis imperfecta and otosclerosis are of different aetiology.

Adolescent↗

Prostaglandin E2 receptors on human peripheral blood monocytes.

The prostaglandin E2 (PGE2) receptor on human peripheral blood monocytes is characterized. The receptor binding at physiological temperature and pH was saturable, specific, and reversible. Scatchard analysis of binding data revealed a linear plot giving a Kd = 1.1 X 10(-9) mol/l and Bmax = 4.1 fmol/10(7) cells, equal to 240 binding sites per cell. PGE2 increased intracellular cyclic adenosine 5'-monophosphate by a maximal factor of 3. PGF2 alpha and arachidonic acid had no stimulatory effects on adenyl cyclase, in accordance with their low binding to the cells. The characterization of the PGE2 receptor on human monocytes creates a basis for the study of the clinical significance of changes in PGE2-receptor binding in disease states involving PGE2-monocyte interactions such as various immunological disorders and bone resorption.

Arachidonic Acid↗