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S L Teitelbaum

Publications and source records attributed to S L Teitelbaum.

At least 163 records · Page 9Linked to original sources
PubMed1983

Mast-cell proliferation in postmenopausal osteoporosis.

Because mast cell proliferation has been reported in disorders of abnormal bone remodeling, we quantitated the number of mast cells in undecalcified section of iliac crest bone from 16 untreated women with postmenopausal osteoporosis and contrasted the findings to values from 10 normal women and 12 normal men. The mean number of marrow mast cells was greater in normal women than men (1.17 vs 0.40 cells per mm2, P less than 0.05). Compared to the normal women, osteoporotic women had a greater number of mast cells in the marrow (3.38 vs 1.17 cells per mm2, P less than 0.01). However, there was no statistically significant correlation between the number of marrow mast cells and either the patient's age or the severity of the bone lesions, as assessed by histomorphometry. Our findings confirm the association between increased numbers of mast cells and postmenopausal osteoporosis.

Aged↗
PubMed1983

Induction of monocytic differentiation and bone resorption by 1,25-dihydroxyvitamin D3.

1,25-Dihydroxyvitamin D3 [1,25(OH)2D3] stimulates bone resorption in man and other vertebrates, in part, by increasing the number of osteoclasts, the principal resorbing cells of bone. Because osteoclasts are very likely derived from a member(s) of the mononuclear phagocyte family, we determined if 1,25(OH)2D3 promotes maturation of these cells by studying its effects on the human promyelocytic leukemia cell line HL-60. Of the vitamin D3 metabolites tested, only 1,25(OH)2D3, at 10(-10) to 10(-7) M, induces the differentiation of HL60 into mono- and multinucleated macrophage-like cells. Phenotypic change is evident within 24 hr and reaches a plateau between 72 and 96 hr of incubation. The changes are metabolite-specific and include (i) adherence to substrate, (ii) acquisition of the morphological features of mature monocytes, (iii) a 4- to 6-fold enhancement in lysozyme synthesis and secretion, (iv) increase in the fraction of alpha-naphthyl acetate esterase-positive cells from approximately 2% to 100% of the population, and (v) the acquisition of several monocyte-associated cell surface antigens. More importantly, treated HL-60 cells acquire the capacity to bind and degrade bone matrix, two of the essential, functional characteristics of osteoclasts and related bone-resorbing cells. These results, considered together with the reported action of 1,25(OH)2D3 on nontransformed mononuclear cells, are consistent with the view that vitamin D3 enhances bone resorption and osteoclastogenesis in vivo by promoting the differentiation of precursor cells.

Animals↗
PubMed1983

Saccharides mediate the attachment of rat macrophages to bone in vitro.

Macrophages (M phi) are multipotential cells capable of giving rise to osteoclasts and of resorbing bone. Since both of these processes are ultimately dependent upon the attachment of cells to a mineralized bone surface, we have examined in this study the mechanism by which such attachment is achieved. The data show that elicited rat peritoneal M phi bind to bone in a temperature-dependent and -saturable manner with half-maximal attachment occurring within 10 min at 37 degrees C and reaching a plateau by approximately 60 min. The kinetics of binding are essentially the same whether devitalized bone particles or viable calvaria are used as a substrate. The attachment of M phi to bone is inhibited by some sugars (e.g., N-acetyl-galactosamine, thiogalactoside, beta-lactose), fetuin and asialofetuin, and by pretreating the bone with periodate. Binding is also significantly reduced when M phi are preincubated with tunicamycin and swainsonine at nontoxic concentrations sufficient to inhibit or alter glycosylation. On the other hand, exposing the cells to neuraminidase increases the capacity of M phi to bind to bone. Collectively, our observations indicate that the attachment of M phi to bone is a highly regulated process and is mediated, at least in part, by saccharides located on both the cell and the bone surface.

Animals↗
PubMed1983

Defective binding of macrophages to bone in rodent osteomalacia and vitamin D deficiency. In vitro evidence for a cellular defect and altered saccharides in the bone matrix.

In the osteomalacic as well as normal skeleton, few osteoclasts are associated with osteoid-covered bone surfaces. The reason for this particular cellular deficit is not clear, but may relate to the inability of osteoclasts and/or osteoclast precursors (monocyte-macrophages) to attach to immature, unmineralized bone matrix, a step apparently essential for normal resorptive activity and osteoclast differentiation. In this study, we have examined cell-bone binding using macrophages (M phi) and bone isolated from vitamin D-deficient rats and hypophosphatemic, osteomalacic mice and from their normal counterparts. The data show that M phi-bone attachment is greatly reduced (P less than 0.001) in both vitamin D deficiency and hypophosphatemia, but that the mechanisms responsible for this reduction are apparently different in the two disorders. In hypophosphatemia, the reduction in binding appears solely attributable to the absence or inaccessibility of bone matrix oligosaccharides or glycoproteins essential to the attachment process. In vitamin D deficiency, on the other hand, not only is the bone matrix defective as a binding substrate, but the M phi, per se, is limited in its capacity to attach to normal, vitamin D-deficient, and hypophosphatemic bone.

Animals↗
PubMed1983

Calcitonin response in circulating human lymphocytes.

The concentration of cAMP increases in human mononuclear leukocytes after exposure to salmon calcitonin (SCT). This response is lost when the cells are separated into adherent (monocytic) and nonadherent (lymphocytic) cells, although the appropriate response to prostaglandin E2 remains in both groups. Adherent and nonadherent cells, each cultured alone for 16 h, do not regain the SCT response. Coculturing adherent and nonadherent cells together for 16 h restores the SCT response in the lymphocytes. The addition of a cyclooxygenase inhibitor to this culture system prevents development of the SCT response. The SCT response may be induced in nonadherent cells by culturing them for 16 h in medium previously conditioned by the growth of mixed mononuclear leukocytes.

Calcitonin↗
PubMed1983

Sclerosteosis: neurogenetic and pathophysiologic analysis of an American kinship.

We studied an American kinship with sclerosteosis, an autosomal-recessive disorder of bone remodeling and bone overgrowth of the calvaria, skull base, and tubular bones. Unlike osteopetrosis, which is attributed to abnormal immune and osteoclast function as well as bone resorption, sclerosteosis appears to be primarily a disorder of osteoblast (bone formation) hyperactivity. Related to cranial vascular and neural foraminal narrowing and reduced intracranial volume, affected patients with sclerosteosis demonstrate frequent seventh nerve palsy, progressive optic and cranial neuropathies, mixed hearing loss, brainstem compression, intracranial hypertension with increased elastance, and sudden, premature death. Management should involve early childhood identification of homozygotes, monitoring and aggressive treatment of intracranial hypertension, and extensive bone removal from skull, posterior fossa, and cervical spine.

Adult↗
PubMed1983

Symptomatic osteomalacia after jejunoileal bypass surgery in a patient with primary hyperparathyroidism. A study of the change in bone morphology and vitamin D metabolites before and during treatment.

A 48-year-old woman underwent jejunoileal bypass surgery for obesity while hypercalcemic. Three years later, she developed symptomatic osteomalacia impairing her daily activities. Bone biopsy confirmed the clinical diagnosis of osteomalacia, and treatment with 8000 U daily of vitamin D and milk resulted in striking improvement of clinical symptoms and resolution of her osteomalacia both chemically and histologically. The patient, however, again became hypercalcemic and a parathyroid adenoma was subsequently removed with restoration of serum calcium values to normal. Neither the occurrence and successful treatment of gross symptomatic osteomalacia consequent to jejunoileal bypass surgery, nor the obscuration of primary hyperparathyroidism by osteomalacia has been hitherto well documented in the United States.

25-Hydroxyvitamin D 2↗
PubMed1983

Exogenous hyperthyroidism with osteoporosis.

Symptomatic osteopenia accompanied by subclinical hyperthyroidism developed in three women who were receiving excess thyroid hormone medication. Excessive thyroid replacement therapy resulted in mild hypercalcemia, hyperphosphatemia, and hyperphosphatasemia associated with diffuse skeletal demineralization and multiple fractures. Nondecalcified sections of double tetracycline-labeled iliac crest bone showed an accelerated rate of bone turnover with marked osteoclastosis and resorption of the cortical as well as the trabecular bone, typical of endogenous hyperthyroidism. Since thyroid hormones are among the most frequently prescribed medications, bone loss caused by exogenous hyperthyroidism may be more common than previously recognized.

Aged↗
PubMed1983

Multinucleation enhances macrophage-mediated bone resorption.

The degradation of mineralized connective tissues in vivo is a function of multinucleated giant cells ('clasts) derived from and belonging to the mononuclear phagocyte family. However, it is not known whether the attainment of the multinucleated state is causally or only coincidentally related to 'clast degradative activity. To address this issue, 'clast-like polykaryons were produced by exposing elicited rat macrophages to human serum (10% for 7 to 14 days). Pure populations (90%) of multinucleated cells and their mononuclear macrophage counterparts were then assessed for their ability to bind and degrade 45Ca-labeled, devitalized bone particles in vitro. Macrophage polykaryons bind bone particles significantly more effectively than ordinary elicited mononuclear macrophages (approximately 40% attachment versus approximately 25%; p less than 0.001). Similarly, 'clast-like polykaryons resorb both large (24 to 43 microns diameter) and small (less than or equal to 24 microns) particles more efficiently than age- and culture condition-matched mononuclear cells (treated to control ratios, 1.3 to 4.2:1, p less than 0.001). This difference in degradative activity remains highly significant whether resorption (45Ca release) is expressed per microgram of DNA, per 100 micrograms of protein, or per total cell surface area. We conclude that multinucleation produces qualitative changes in the resorptive capacity of macrophagic cells. The data suggest that the formation of polykaryons is a physiologically important event in 'clast development.

Animals↗
PubMed1982

An improved method for the retrieval of cultured macrophages.

We report a simple procedure for the maintenance and retrieval of rodent peritoneal macrophages on dialysis membrane supports. Culture units are easily constructed from plastic petri dishes and dialysis membranes. Macrophages adhere readily but are detached easily from the dialysis membrane by mild mechanical agitation. Cell viability remains high and the morphologic and functional characteristics of the macrophages are maintained.

Animals↗
PubMed1982

Postmenopausal osteoporosis. A heterogeneous disorder as assessed by histomorphometric analysis of Iliac crest bone from untreated patients.

Twenty-six women with untreated postmenopausal osteoporosis underwent iliac crest biopsy following tetracycline-labeling and mineral metabolism studies. Histomorphometric assessment of their bone remodeling rates, including formation determined by the tetracycline-labeling technique, revealed considerable variation. Eight women had no evidence of active bone formation (inactive remodeling osteoporosis), whereas the others showed a spectrum of bone formation rates (active remodeling osteoporosis). Clinical and biochemical studies failed to predict the histomorphometric findings. Postmenopausal osteoporosis is a histologically heterogeneous disorder with morphologic expression in bone that cannot be predicted by single or combined routine clinical and laboratory parameters. Bone biopsy, necessary to identify the histologic lesion and assess skeletal dynamics, may prove to be important for optimal therapy of osteoporosis, as a variety of agents--with different effects on bone remodeling--are available.

Aged↗
PubMed1982

Meningeal osteomas and chronic renal failure.

Osteomas, although usually found in the frontal and ethmoid sinuses or the mandible, may be located on the inner table of the skull. We report the incidence, distribution, histologic features, and clinical correlates of intracranial osteomas arising in the dura mater and the falx cerebri in 200 consecutive adult autopsies. Ten patients (5 per cent of autopsies) were found to have meningeal osteomas. The tumors were usually located at the dural-falx junction at the superior longitudinal sinus. Histologically, they resembled osteomas arising from other sites, but undecalcified sections generally demonstrated histologic features of active bone remodeling--namely, the presence of abundant osteoid and numerous osteoclasts, and, in some instances, osteitis fibrosa. The age and sex distributions were similar among autopsied patients with meningeal osteomas (mean age, 66 years; 60 per cent female) and those without (mean age, 64 years; 58 per cent female). Although the incidence of uremia in the general autopsy population was only 13 per cent, 60 per cent of patients with osteomas died with concomitant renal failure. The authors consider these cases of meningeal ossifications and reports of meningeal calcifications to represent osteomas arising from the dura mater and the falx cerebri. Thus, intracranial osteomas may be more common than was previously recognized. In some instances, the abnormal biochemical state accompanying chronic renal failure may stimulate new bone formation in the osteogenic tissue of the dura mater.

Aged↗
PubMed1982

Recruitment of osteoclast precursors by purified bone matrix constituents.

The osteoclast, the multinucleated giant cell of bone, is derived from circulating blood cells, most likely monocytes. Evidence has accrued that is consistent with the hypothesis that the recruitment of monocytes for osteoclast development occurs by chemotaxis. In the present study, we have examined the chemotactic response of human peripheral blood monocytes and related polymorphonuclear leucocytes to three constituents of bone matrix: peptides from Type I collagen, alpha 2-HS glycoprotein, and osteocalcin (bone gla protein). The latter two substances are among the major noncollagenous proteins of bone and are uniquely associated with calcified connective tissue. In chemotaxis assays using modified Boyden chambers, Type I collagen peptides, alpha 2HS glycoprotein, and osteocalcin evoke a dose-dependent chemotactic response in human monocytes. No chemotaxis is observed on PMNs despite their ontogenetic relationship to monocytes and their documented sensitivity to a broad range of other chemical substances. Our observations are consistent with the view that osteoclast precursors (monocytes) are mobilized by chemotaxis, and suggest that the chemoattractants responsible for this activity are derived from the bone matrix or, in the case of collagen and osteocalcin; directly from the osteoblasts which produce them.

Bone Matrix↗