Coupling Of Bone Resorption Research Articles

Hormones in the coupling of bone resorption and formation

Hormones in the coupling of bone resorption and formation

Progesterone as a Bone-Trophic Hormone

Experimental, epidemiological, and clinical data indicate that progesterone is active in bone metabolism. Progesterone appears to act directly on bone by engaging an osteoblast receptor or indirectly through competition for a glucocorticoid osteoblast receptor. Progesterone seems to promote bone formation and/or increase bone turnover. It is possible, through estrogen-stimulated increased progesterone binding to the osteoblast receptor, that progesterone plays a role in the coupling of bone resorption with bone formation. A model of the interdependent actions of progesterone and estrogen on appropriately-"ready" cells in each bone multicellular unit can be tied into the integrated secretions of these hormones within the ovulatory cycle. Figure 5 is an illustration of this concept. It shows the phases of the bone remodeling cycle in parallel with temporal changes in gonadal steroids across a stylized ovulatory cycle. Increasing estrogen production before ovulation may reverse the resorption occurring in a "sensitive" bone multicellular unit while gonadal steroid levels are low at the time of menstrual flow. The bone remodeling unit would then be ready to begin a phase of formation as progesterone levels peaked in the midluteal phase. From this perspective, the normal ovulatory cycle looks like a natural bone-activating, coherence cycle. Critical analysis of the reviewed data indicate that progesterone meets the necessary criteria to play a causal role in mineral metabolism. This review provides the preliminary basis for further molecular, genetic, experimental, and clinical investigation of the role(s) of progesterone in bone remodeling. Much further data are needed about the interrelationships between gonadal steroids and the "life cycle" of bone. Feldman et al., however, may have been prophetic when he commented; "If this anti-glucocorticoid effect of progesterone also holds true in bone, then postmenopausal osteoporosis may be, in part, a progesterone deficiency disease."

Cytochemical studies of the cellular events sequence in bone remodeling: Cytological evidence for a coupling mechanism

In order to elucidate the sequence of the cellular events in the bone remodeling process which may contribute to the coupling mechanism between bone resorption and formation, this study was attempted to observe the cytochemical localization of acid phosphatase (ACPase) and alkaline phosphatase (ALPase) activities in the remodeling bone cells. The ACPase activity in osteoclasts could be demonstrated in the vacuoles, extracellular channels of the ruffled border and spaces between cells and bone. In addition, the reaction product was observed at the resorbed bone surface, which was continued to the cement line resulting in new bone formation. Attached to the resorbed bone surface and newly formed cement line, ALPase-positive osteoblastic cells appeared and formed new bone matrix. These suggest that osteoclasts may move as resorbing bone and form a new cement line, which may be responsible for coupling of bone resorption and formation. Moreover, the ACPase-positive mononuclear cells could be observed on the resorbed bone surface adjacent to the resorbing osteoclast. They were characterized by numerous cytoplasmic extensions, sparse r-ER and mitochondria, and many lysosomes. However, the osteocytes being excavated by osteoclasts also showed the similar appearance. In the cytochemical study, these osteocytes showed ACPase activity in lysosomes in the same way as the mononuclear cells on the resorbed bone surface. Therefore, it is suggested that the ACPase-positive mononuclear cells principally originate from the osteocytes which are excavated by osteoclasts from bone matrix, and these cells are identified with the mononuclear phagocytes in reversal phase which have been postulated.

Effects of heparin, histamine, and salmon calcitonin on mouse calvarial bone resorption.

A quantitative mouse calvarial bone resorption assay was employed to investigate the effects of the mast cell products, heparin and histamine, and of salmon calcitonin. 'Amorphous' heparin, containing a range of molecular weight fractions, inhibited resorption by 15-20% at concentrations of 0.75-5.0 mg/ml. A 'defined' heparin species of mol.wt 13 500 inhibited resorption by 14-28% at 10(-5)-10(-4) mol/l. Histamine inhibited resorption by 19-55% at 10(-3)-10(-2) mol/l. It is proposed that heparin and histamine depress coupled bone resorption and formation and may lead to net loss of bone. Salmon calcitonin inhibited resorption at concentrations as low as 10 pg/ml. 'Amorphous' (but not 'defined') heparin blunted calcitonin induced inhibition of bone resorption and may derepress osteoclasts.

A detailed evaluation of oral phosphate therapy in selected patients with primary hyperparathyroidism.

Recent studies have emphasized the pathophysiological importance of circulating 1,25-dihydroxyvitamin D ((1,25-(OH)2D] in the pathogenesis of hypercalciuria and renal stone formation in primary hyperparathyroidism. Reasoning that phosphate administration might be capable of reducing the plasma concentration of 1,25-(OH)2D in patients with a prominent 1,25-(OH)2D-mediated absorptive component to their disease, 10 carefully selected patients were treated with oral phosphate (1500 mg elemental phosphorus daily) for 1 yr. Phosphate treatment significantly reduced circulating 1,25-(OH)2D levels (84 to 56 pg/ml), the calciuric response to an oral calcium tolerance test (0.30 to 0.21 delta mg calcium/dl GF), and calcium excretion on an unrestricted calcium diet (438-269 mg/day), in essence reversing the absorptive pattern of abnormalities observed before treatment. This response, however, was accompanied by an increase in biochemical hyperparathyroidism, as assessed by circulating immunoreactive PTH and nephrogenous cAMP excretion. In patients with biochemical evidence of an increase in bone resorption before therapy, histomorphometric, radiographic, and biochemical data revealed a trend toward a reduction in bone turnover during phosphorus therapy, with an apparent maintenance of coupled bone resorption and bone formation. This trend, however, was of marginal statistical significance in the patient group as a whole. It is concluded 1) that phosphate therapy represents a viable medical alternative in selected patients with primary hyperparathyroidism, 2) that the net response in treated patients is multifaceted and complex, and 3) that the efficacy of phosphate therapy will ultimately depend upon its long term effects on skeletal homeostasis.