Metabolic bone disease & related research最新文献

Transilial biopsies from postmenopausal osteoporotic patients showed that static features and remodeling activity tended tended to form a pattern, with the area midway between the cortices having less bone and lower remodeling activity than the area closer to the inner boundary of the cortex. The appearance, enlargement, and coalescence of the resorption cavities within the subendosteai area of the cortex lead to negative bone balance and a progressive trabeculation of the cortex, resulting in the formation of a transitional zone. Therefore, in most cases we can distinguish two different zones, transitional and trabecular zones, within the area usually known as the trabecular bone area. The transitional zone undergoes more active remodeling than the trabecular zone and has an important role in evaluation of the traditional trabecular bone volume and remodeling dynamics depending on the field selection for this evaluation, i.e., the proportion between transitional and trabecular zones within the selected fields.

We postulate that the appearance of resorption cavities in the subendosteal area of the cortex depends on osteoclast work, and bone loss in the resulting transitional zone depends on a combination of excessive osteoclast work and defective osteoblast work, with the osteoclast excessive work predominating.

The concentrations of elements in avian growth cartilage were studied by electron probe x-ray emission microanalysis (EDX). The cartilage was prepared for analysis by freezing, freeze-fracturing, freeze-drying, and carbon coating techniques. Cells and matrix fragments were removed from the tissue by microdissection with a tungsten needle in a scanning electron microscope (SEM) equipped with a real-time stereoscopic viewing facility. The samples were analyzed in the same SEM by EDX. Elemental analyses were performed on each fragment at a distance from the tissue sample, and hence background radiation due to the sample was eliminated. An important finding was that the intracellular potassium concentration of chondrocytes in calcified cartilage was similar to the levels in the premineralized zones. This observation supports the view that chondrocytes do not die in the process of, or as a consequence of, mineralization of the surrounding matrix. Calcium peaks were seen in the matrix at all levels and in chondrocytes immediately prior to mineralization. In contrast, phosphorus levels were always high in cells and low or absent from the premineralized matrix. At the mineralization front the appearance of a phosphorus peak in the matrix just preceded the deposition of mineral. We propose that the transfer of phosphorus from cell to matrix is a rate-limiting step in mineralization. Finally, when rachitic and normal cartilage were compared, little difference was seen in the profile of either intracellular or extracellular elements. However, in rickets the mineralized matrix remained soft in consistency. We suggest that this may reflect a phosphorus-related calcification defect that prevents growth and interlocking of the apatite crystallites.

Osteoblastic and osteoclastic activity was studied in avian medullary bone in vivo. During the active period of eggshell calcification, medullary bone active resorption surface increased ninefold. This correlated with a sevenfold increase in the percentage of active osteoclasts. Osteoblast activity is also increased during the active period, as demonstrated by a twofold increase in the active osteoblastic surface. These findings and our observation that the medullary bone volume remains the same (± 13%) whether the eggshell is being formed (active period) or not (inactive period) led to the conclusion that the activities of osteoblasts and osteoclasts rapidly return to balance.

Effects of 1,25(OH)₂D₃ or 24,25(OH)₂D₃ on plasma PTH were examined following induced hypocalcemia with EGTA. EGTA infusions caused an elevation of plasma PTH within 10 min. Sixty min after the start of EGTA infusions, 1,25(OH)₂D₃ or 24,25(OH)₂D₃ were IV administered. Transient (within 5 min) elevations in plasma PTH were observed in two of five animals following the administration of 1,25(OH)₂D₃ or of 24,25(OH)₂D₃. Neither secosterol had an effect on the induced elevations in plasma PTH during the remaining 60 min of the EGTA infusions. Twenty-two hr following 24,25(OH)₂D₃ administration, plasma PTH, ionized and total calcium, inorganic phosphate, and magnesium were normal, while plasma 24,25(OH)₂D was elevated. The plasma PTH response to EGTA-induced hypocalcemia was not significantly altered from that observed prior to the administration of 24,25(OH)₂D₃. Animals, which were IV injected with 1,25(OH)₂D₃ received the same amount IM 60 min later. Twenty-two h following IM 1,25(OH)₂D₃, plasma 1,25(OH)₂D, ionized and total calcium, and plasma inorganic phosphate were elevated. Plasma PTH and magnesium were lowered. The PTH response to EGTA-induced hypocalcemia was significantly reduced in these animals. A similar reduction in the PTH response to induced hypocalcemia was observed in animals receiving 7 hr IV infusions of calcium chloride. The findings suggest that the blunted response was, in part, the consequence of the preceding hypercalcemia. These results indicate that 1,25(OH)₂D₃ does not directly regulate plasma PTH secretion and that 24,25(OH)₂D₃ has no effect on plasma PTH during induced hypocalcemia in the bovine species.

Dichloromethylene diphosphonate (CI₂MDP), a powerful inhibitor of bone resorption, was given (daily dose: 500 mg i.v. for 2 months and then 1600 mg p.o.) to five patients with Paget's disease after 8 months treatment with 50–100 MRC u/day of human calcitonin (CT).

During treatment with CT plasma alkaline phosphatase (ALP) and urinary hydroxyproline (HOP) levels fell to about 60% of pretreatment values within the first 2 months in all the patients. CI₂MDP therapy resulted in a further drop of urinary HOP to 20% of baseline values, while serum ALP rose impressively during the first 2 weeks of therapy and then slowly fell to 25% of baseline values. We conclude that Cl₂MDP can induce a further biochemical response after the so-called plateau phenomenon to CT and that it may represent the therapy of choice for severe Paget's disease.

In Paget's disease of bone, quantitation of skeletal uptake of radiolabeled diphosphonate has been proposed as a means of monitoring response to therapy. However, the validity of such techniques has been questioned during oral diphosphonate therapy because of possible interaction between oral and radiolabeled diphosphonate.

In the present study 18 patients with Paget's disease received a 6 month course of oral diphosphonate therapy. Measurements of 24 h whole body retention (WBR) of ^99mTc-labeled hydroxyethylidene diphosphonate (HEDP), serum alkaline phosphatase (SAP), and urinary hydroxyproline excretion were obtained before, during, and after treatment. WBR correlated well with SAP and urinary hydroxyproline throughout the course of therapy. In addition, the relationship between WBR and SAP was maintained aftercessation of oral diphosphonate.

It would thus appear that in Paget's disease 24 h WBR of HEDP, a quantitative measure of skeletal uptake of diphosphonate, will reflect disease activity even in the presence of an oral diphosphonate load.