The interpretation of fluorescent tetracycline markers in the diagnosis of metabolic bone diseases.
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Biopsy↗
Biomedical subjects
M D Fallon
Publications and source records attributed to M D Fallon.
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↗
Cystic parathyroid gland hyperplasia--hyperparathyroidism presenting as a neck mass.
Hyperparathyroidism may occasionally present as a neck mass resulting from cystic change in a parathyroid adenoma. We report an unusual instance of hyperparathyroidism presenting as a palpable, but asymptomatic hyperplastic parathyroid gland cyst. We conclude that hyperplastic parathyroid glands may undergo cystic degeneration resulting in a palpable neck mass; and that all functional parathyroid gland cysts are not necessarily adenomas. Therefore, during parathyroidectomy procedures, biopsy material from at least one additional parathyroid gland should be obtained.
Aged↗
Mixed-sclerosing-bone-dystrophy: report of a case and review of the literature.
We present clinical, laboratory, radiologic, genetic, and pathologic findings in a 49-year-old man with mixed-sclerosing-bone-dystrophy (MSBD), review the six cases previously reported as "MSBD", and examine the nosology of this rare bone dysplasia. Our asymptomatic patient showed radiographic changes consistent with osteopoikilosis, osteopathia striata, and melorheostosis and had widespread osteosclerosis of the axial skeleton. Several previous reports of combined osteosclerotic disorders suggest the latter finding represents osteopetrosis, however, histologic examination of our patient's iliac crest excluded that diagnosis. Limited radiographic surveys of his eight children were unremarkable except for isolated bone islands in two sons. Literature review revealed that "MSBD" has actually been used generically to describe the association of a variety of osteosclerotic bone dysplasias when they occur together in a single patient.
Bone Diseases↗
A simple procedure for the rapid histologic diagnosis of metabolic bone disease.
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Acrylates↗
Ultrastructure of the rat epiphyseal growth plate following chronic ethanol ingestion.
We have previously demonstrated that ethanol has a direct toxic effect on the rat skeleton characterized by decreased trabecular bone volume. In the present study, we examined the ultrastructure of the distal radial epiphyseal growth plates in these same animals. Eight weeks of ethanol administration to 12 male rats results in serum alcohol levels of 140 mg/dl but did not alter the width or light microscopic appearance of the radial growth plate. Quantitative electron microscopy failed to demonstrate morphologic evidence of toxicity in the skeletal cells. We conclude that although ethanol appears to have a direct effect on rat bone characterized by enhanced resorption, toxicity is not attended by ultrastructural changes in the skeletal cells.
Animals↗
Axial osteomalacia. Clinical, laboratory and genetic investigation of an affected mother and son.
Axial osteomalacia--a rare osteosclerotic bone disorder characterized by axial skeleton pain, coarsening of the trabecular bone pattern on radiographs of the axial but not appendicular skeleton, and osteomalacia on biopsy of a rib or iliac crest--has been reported in 10 apparently sporadic cases, all of which were in middle-aged or elderly Caucasian men. The etiology is unknown but has been postulated to be a bone cell defect. We describe the clinical, laboratory, pathologic and family study of a black mother and son with axial osteomalacia associated with polycystic liver and kidney disease. Investigation of the son suggested that radiographic osteosclerosis can be detected in early adulthood. Limited skeletal survey of his three children revealed no abnormalities. Examination of undecalcified iliac crest bone after in vivo tetracycline labeling revealed severe osteomalacia in the son despite normal circulating calcium, inorganic phosphate and vitamin D metabolite levels and persistently elevated alkaline phosphatase activity. Although osteoblasts appeared flat and inactive, histochemical studies showed intense alkaline phosphatase activity in the osteoblasts along most trabecular bone surfaces. Electron microscopy revealed intact matrix vesicles within unmineralized osteoid. The presence also of unexplained myopathy in the son--characterized by proximal muscle weakness, persistently elevated circulating creatine phosphokinase levels and pathogenic changes of myopathy on biopsy of quadriceps muscle--together with impaired bone mineralization, suggests that a disorder of vitamin D action may be involved in the pathogenesis of this unusual condition. Axial osteomalacia affects blacks as well as Caucasians, women as well as men, may be familial, and may perhaps be a developmental abnormality inherited in association with polycystic kidney and liver disease.
Adolescent↗
Alkaline phosphatase activity in chronic streptozotocin-induced insulin deficiency in the rat: effect of insulin replacement.
Alterations in circulating alkaline phosphatase have been described in both man and the experimental animal with chronic insulin deficiency. We evaluated plasma and tissue alkaline phosphatase levels in freely-fed control, streptozotocin-induced diabetic and insulin-treated diabetic rats, seven weeks after the induction of diabetes. Circulating alkaline phosphatase activity was markedly elevated in the insulin deficient animal (p less than 0.001) and completely normalized following insulin administration. The elevated plasma alkaline phosphatase activity observed in the insulin deficient animals was heat-resistant and phenylalanine-sensitive, a pattern typical of the intestinal isoenzyme. Small intestinal alkaline phosphatase activity was significantly higher (p less than 0.01) in the diabetic animals, but comparable in the insulin-replaced and control rats. The intestinal isoenzyme activity was found to be strikingly insulin-sensitive; withholding insulin therapy for 36 hr prior to sacrifice resulted in an abrupt rise in both plasma and intestinal alkaline phosphatase values comparable to those observed in the insulin-deficient state. In contrast to these observations, skeletal alkaline phosphatase activity was decreased in the insulin deficient animal (p less than 0.01) and this abnormality was corrected by insulin replacement. Neither insulin deficiency nor insulin replacement resulted in any significant changes in the hepatic alkaline phosphatase isoenzyme.
Alkaline Phosphatase↗
Skeletal sarcoidosis with osteopenia.
Diffuse osteopenia is not generally recognized as a radiological manifestation of skeletal sarcoidosis. Furthermore, the pathologic correlates of the skeletal abnormalities in sarcoidosis are poorly characterized. We quantitated the histomorphometric parameters of bone formation and resorption in a transiliac crest biopsy specimen from a patient with sarcoidosis, diffuse osteopenia, hypercalcemia, and hypercalciuria, who was treated only intermittently with corticosteroids and thiazides. Peritrabecular granulomas were associated with the histologic features of accelerated bone remodeling, namely: excess osteoid; increased numbers of osteoclasts and osteoblasts; increased osteoclastic resorbing surfaces; and increased bone formation rate. We conclude that the peritrabecular granulomas of skeletal sarcoidosis may result in rapid bone turnover with diffuse osteopenia which may contribute to the abnormalities of mineral metabolism.
Adult↗
Systemic mastocytosis associated with generalized osteopenia. Histopathological characterization of the skeletal lesion using undecalcified bone from two patients.
Although mast cell proliferation in the bone marrow frequently occurs in systemic mastocytosis and is often associated with radiographically detectable bone lesions, the pathologic correlates of the skeletal abnormalities are poorly characterized. We therefore examined three nondecalcified transiliac crest biopsy specimens from two patients with systemic mastocytosis and diffuse osteopenia with vertebral crush fractures. Marrow involvement included unusual mast cell aggregates, as revealed by metachromatic staining, that mimicked granulomas. Histomorphometric analysis or trabecular bone revealed accelerated bone remodeling or "turn over" characterized by osteoidosis, peritrabecular fibrosis, increased numbers of osteoblasts and osteoclasts, and an increase in osteoclastic resorbing surfaces. Our observations and review of the literature suggest that with the recent development of techniques for assessing undecalcified bone biopsy specimens, mastocytosis will probably be shown to be a more common etiology in "osteoporosis" than previously recognized. Metachromatic staining of the biopsy specimen should be a routine procedure in the investigation of any patient who undergoes diagnostic bone biopsy.
Adult↗
Correction of abnormal bone and mineral metabolism in chronic streptozotocin-induced diabetes mellitus in the rat by insulin therapy.
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Animals↗
The effect of streptozotocin-induced chronic diabetes mellitus on bone and mineral homeostasis in the rat.
Diabetes mellitus was induced in Lewis rats by streptozotocin, and these animals and control rats fed ad lib were studied after 7 weeks. At the time of sacrifice, nondecalcified histological sections of bone were prepared and subsequently quantitated by micromorphometric techniques. In addition, tibial alkaline phosphatase and mineral ash content were determined. The bones obtained from the diabetic animals are characterized by significant decrements in the quantities of osteoid and osteoclasts and by failure to acquire a tetracycline label. These histological features are attended by reduced quantities of urinary hydroxyproline and tibial alkaline phosphatase. As compared with control animals fed ad lib, diabetic rats are hyperphosphatemic and markedly hypercalciuric. Circulating alkaline phosphatase is also elevated and associated with a parallel increase in intestinal content of this enzyme. Although serum corticosterone levels are increased, diabetes is associated with decrements in both circulating immunoreactive parathyroid hormone and 1,25(OH)2D. We conclude that prolonged streptozotocin-induced diabetes mellitus in the rat results in reduced bone turnover. The relative roles that functional caloric deprivation, low circulating levels of 1,25(OH)2D, hypercalciuria, hypercortisolemia, and decreased blood parathyroid hormone levels play in the genesis of these skeletal abnormalities remain to be determined.
Alkaline Phosphatase↗
Pseudotruncus arteriosus: Its occurrence with acquired aortic stenosis in an adult.
Prolonged survival with pseudotruncus arteriosus, an extreme variant of Fallot's tetralogy, is unusual. We studied the clinical and pathological findings in an adult with uncorrected pseudotruncus. Longevity may have been related to the presence of markedly enlarged bronchial arteries that provided collateral circulation to the lungs. However, prolonged survival was accompanied by the development of severe degenerative changes of the aortic valve leaflets that resulted in acquired valvular stenosis.
Adult↗
Osteopetrosis, renal tubular acidosis and basal ganglia calcification in three sisters.
Three adult sisters with osteopetrosis in infancy had spontaneous resolution of bone modeling defects and osteosclerosis. During adolescence, basal ganglia calcification developed in two. Renal tubular acidosis (type I) was diagnosed in each during early adulthood. The disorder was transmitted apparently as a recessive trait--the same mode of inheritance as for the "malignant" form of osteopetrosis which is usually fatal during childhood. Electron microscopy of bone suggested that osteoclasts failed to form "ruffled membranes" characteristic of active bone resorbing cells. Chronic systemic acidosis may have ameliorated the skeletal manifestations of this new syndrome.
Acidosis, Renal Tubular↗
Effects of semistarvation on skeletal homeostasis.
Rats were semistarved over a 7-week period, resulting in a loss of 28.2 +/- 1.6% (SEM) of their initial body weights, while ad libitum fed controls gained 15.1 +/- 1.8% (SEM). Bone loss occurred and skeletal turnover was markedly reduced in the semistarved rats, as evidenced by a paucity of osteoid and osteoclasts, failure of the bone to assume a tetracycline label, and reduced urinary hydroxyproline excretion. Despite these changes, there were no alterations of serum or bone alkaline phosphatase activity with semistarvation, and analysis of tibial mineral content revealed reductions only in magnesium and sodium. The malnourished animals, however, were hypercalciuric and hypophosphatemic. Semistarvation had no effect on circulating levels of immunoreactive parathyroid hormone or 25-hydroxyvitamin D, but did result in reduced serum levels of corticosterone, insulin, and 1,25-dihydroxyvitamin D. Therefore, it appears that the effects of semistarvation on the rat skeleton are osteoporotic rather than osteomalacic, and that the defect is the consequence of reduced bone turnover. The contribution which the abnormalities of bone-regulating hormones play in the genesis of this skeletal lesion remains to be determined.
Animals↗
Stereospecific inhibition of alkaline phosphatase by L-tetramisole prevents in vitro cartilage calcification.
To clarify the role of alkaline phosphatase (ALP) and ATPase in skeletal mineralization, we studied the effect of the anthelmintic drug, l-tetramisole (levamisole), a stereospecific inhibitor of ALP activity, and its inactive isomer, d-tetramisole (dexamisole), on in vitro calcification of rachitic rat cartilage. ALP activity in homogenized rachitic rat proximal tibiae was inhibited by l-tetramisole in a dose-dependent manner. Histochemical and electron microscopic cytochemical analysis of intact epiphyseal plate rachitic rat cartilage showed that 5 x 10(-2) M and greater concentrations of l-tetramisole (1) virtually abolished ALP activity, (2) moderately reduced ATPase activity, and (3) prevented in vitro cartilage calcification, while preserving the structural integrity of the matrix vesicles. Concentrations of d-tetramisole as high as 1 x 10(-1) M failed to inhibit ALP activity in tibial homogenates by more than 10 per cent and did not alter histochemical staining of enzyme activity or calcification in intact cartilage slices. Heating the cartilage slices destroyed ALP activity, prevented calcification, and disrupted matrix vesicle integrity. These data show that there is a close association between ALP activity and in vitro calcification of rachitic rat cartilage. In the absence of ALP activity, intact matrix vesicles do not promote calcification. Our data also suggest that some ATPase activity of rachitic rat cartilage may be distinct from ALP activity.
Adenosine Triphosphatases↗
Progressive diaphyseal dysplasia (Engelmann's disease). Report of a sporadic case of the mild form.
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Adolescent↗
Phenytoin inhibition: failure to inhibit periosteal responses to lathyrogen.
beta-Aminopropionitrile (BAPN) administered to rats has caused exostosis formation at sites of muscle attachment and also caused delay in the healing of soft tissue wounds and of bone fractures. Since phenytoin sodium has an opposite effect on wound healing, bone fractures, and the tensile strength of connective tissues, an experiment was performed to determine whether or not BAPN could produce periosteal exostoses in the presence of phenytoin. Rats that were given both BAPN and phenytoin produced similar exostoses as rats that were given BAPN alone. This indicates that phenytoin does not prevent inhibition of lysyl oxidase by BAPN, does not promote increased tensile strength of connective tissues in the presence of BAPN, and does not facilitate the detoxification of BAPN. Further, no evidence for an increased cellular response with phenytoin was observed. The mechanism by which phenytoin promotes wound healing is still unknown.
Aminopropionitrile↗