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Biomedical subjects

M A Bergfeld

Publications and source records attributed to M A Bergfeld.

16 recordsLinked to original sources
PubMed1991

X-linked hypophosphatemia: skeletal mass in adults assessed by histomorphometry, computed tomography, and absorptiometry.

PURPOSE AND PATIENTS AND METHODS: X-linked hypophosphatemia (XLH) is the most common inherited form of rickets, yet its influence on skeletal mass in adulthood is controversial and incompletely characterized. Accordingly, we measured bone mass at several skeletal sites using histomorphometric and radiographic techniques in 19 adults (four men) with XLH (age range 20 to 66 years). Most subjects had not received medical therapy for XLH since puberty. RESULTS: Eight of 14 subjects who underwent transiliac bone biopsy had an elevated cancellous bone volume (osteoid and calcified bone), and the group's mean value was supranormal (p less than 0.01). Mineralized bone volume, however, was above normal in only three subjects (NS). Another measure of trabecular bone density, vertebral mineral density by computed tomography, was elevated in three of 13 subjects, and the mean value of the group was increased (p = 0.05). Integral spine bone mineral density (BMD) assessed by dual photon absorptiometry (DPA) was elevated in six of 16 subjects, and the mean was also above normal (p less than 0.01). However, total body calcium, total body BMD (both by DPA), and forearm bone mineral content assessed by single photon absorptiometry (predominantly cortical bone) were normal in almost all subjects, as were the group means for these parameters. Mean regional BMD (by DPA) was below normal in the upper and lower limbs (p less than 0.001) and above normal in the spine (p less than 0.005) and ribs (p less than 0.01). There was no relationship between these indices of bone mass and either biochemical or clinical parameters of disease severity, although men tended to have higher z-scores for axial bone density than premenopausal women whose values, in turn, tended to be higher than those in postmenopausal women (NS). CONCLUSION: We conclude that axial bone mass tends to be increased in adults with XLH, sometimes dramatically so, and this is only partially attributable to hyperosteoidosis. Peripheral bone mass, however, tends to be diminished. Despite these group trends, most adults with untreated XLH have normal indices of bone mass as assessed by a variety of techniques at the commonly used measurement sites. These findings suggest that "osteoporotic" fractures are unlikely to develop as a late complication of XLH in adults.

Absorptiometry, Photon↗
PubMed1989

X-linked hypophosphatemia: a clinical, biochemical, and histopathologic assessment of morbidity in adults.

Research and management of XLH have concentrated on the disease in childhood, and the natural history and morbidity of XLH in adult life are thus poorly understood. We have studied 22 adults (6 men) with XLH to clarify these aspects of this most common inherited form of rickets and osteomalacia. Most study participants had presented with rickets in early childhood and had undergone tibial osteotomies on at least 1 occasion. Seventeen individuals had genu varum, 1 had genu valgum, and 4 had straight legs, attributable to successful osteotomies in 2. Five subjects reported increasing lower limb deformity in the late teens or subsequently. Eight subjects complained of bone pain, 6 of whom had radiologic evidence of pseudofractures; pseudofractures were found in 4 additional asymptomatic individuals. None of 16 subjects who underwent transiliac bone biopsy had normal double tetracycline labeling; accordingly, all were considered to have osteomalacia. Bone pain was associated with a relative osteoid volume in excess of 25%. Relative osteoid volume was inversely related to serum 1,25(OH)2D concentration (r = -0.74, p less than 0.02), but unrelated to serum concentrations of calcium and phosphate or their product. Eighteen participants complained of joint pain, predominantly in the knees and ankles. The severity of joint pain correlated with the degree of lower limb deformity (p = 0.011) which, in turn, was related to fasting serum phosphate concentration (r = -0.56, p less than 0.025) and TmP/GFR (r = -0.70, p less than 0.005). Enthesopathy affected 33% of those younger than 30 years, and all those above this age. Nineteen individuals had experienced significant dental problems, most commonly abscess formation. Eight had required complete dental clearance. Twelve women from the group had a total of 22 live births. Fifteen of these were by cesarean section, although radiologic evidence of pelvic narrowing was not found in any subject. Serum ALP was elevated in all but 3 of the 18 untreated subjects. Levels correlated with those of other indices of bone turnover (BGP r = 0.82, p less than 0.005; urine total HP r = 0.60, p less than 0.025; urine free HPr = 0.78, p less than 0.005), but were not related to the degree of osteomalacia found on bone biopsy. Serum levels of iPTH, 25(OH)D, 1,25(OH)2D, and thyroid hormones were generally normal in the untreated patients. We conclude that adults with untreated XLH have osteomalacia that is frequently symptomatic. Even greater morbidity is caused by degenerative joint disease arising from lower limb deformities.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1988

Assessment of calcitriol and inorganic phosphate therapy before cure of oncogenous osteomalacia by resection of a mixed mesenchymal tumor.

A 57 year old white male with oncogenous osteomalacia due to a mixed mesenchymal tumor was evaluated by sequential histologic and metabolic studies over a period of 33 mos prior to identifying the location of the tumor. On the basis of these studies we conclude: (i) disorders of the enterohepatic circulation and/or acceleration of metabolism of calcitriol are not responsible for its diminished level in oncogenous osteomalacia, (ii) the Von Kossa stain is preferred to the modified Masson in evaluating osteomalacia, (iii) avascular necrosis of the femoral head may be part of the syndrome, (iv) heterogeneity may be the hallmark of the responsible mesenchymal tumor and account for the different histological interpretations in the literature, (v) in compliant patients with oncogenous osteomalacia, calcitriol and Pi therapy may be effective.

Bone Neoplasms↗
PubMed1988

Effects of hypervitaminosis A on the bone and mineral metabolism of the rat.

Vitamin A toxicity has been associated with alterations in mineral metabolism and may result in osteopenia, fractures, deformities, and growth arrest. The pathogenesis of the bone lesions that occur in vitamin A toxicity is, however, ill defined and was examined in the present study. The administration of pharmacological doses of vitamin A to growing male rats resulted in weakness and spontaneous fractures. Undecalcified bone histology of vitamin A toxic animals was characterized by increased bone resorption, osteoclastosis, a paucity of trabecular surfaces covered with osteoid, and lesions which appear to be pathognomonic of hypervitaminosis A. The serum calcium and magnesium levels of vitamin A-toxic animals were unremarkable, but serum phosphate levels were significantly higher than control values. Urinary hydroxyproline excretion reflected bone histology and was significantly increased in experimental rats. Circulating levels of the potent bone resorbers, PTH, 1,25-dihydroxyvitamin D, and 25-hydroxyvitamin D, were, however, comparable in vitamin A-toxic and control animals, suggesting a possible direct effect of vitamin A on bone. Subsequently, the effects of vitamin A (retinol) on in vitro collagen synthesis (incorporation of [3H]proline into collagen) and bone resorption (45Ca release from bone) were examined using a fetal rat calvarial culture. Retinol added to the culture medium for 20-24 h in concentrations ranging from 0.5-10 micrograms/ml selectively inhibited collagen synthesis in a dose-dependent fashion. Higher concentrations of retinol were toxic and resulted in a general inhibition of protein synthesis. Bone resorption was stimulated by 0.5 and 2.5 micrograms/ml retinol. We conclude that vitamin A toxicity in rats causes bone lesions, the genesis of which can be explained, at least in part, by a direct effect of the vitamin on skeletal tissue.

Alkaline Phosphatase↗
PubMed1986

Continuous ambulatory peritoneal dialysis and bone.

We studied the effects of continuous ambulatory peritoneal dialysis (CAPD) on the histological manifestations of uremic bone disease. Twelve patients underwent bone biopsy immediately prior to and after one year of such treatment. Those with larger quantities of non-mineralized bone matrix (osteoid) experienced a reduction in relative osteoid volume, mean osteoid seam width, and total osteoid surface. Moreover, the use of time-spaced kinetic markers of mineralization (tetracycline) enabled us to demonstrate that CAPD usually decreased the amount of non-mineralized bone matrix by shortening mineralization lag time (that is, the interval from organic matrix deposition to its mineralization). The changes in the histomorphology appeared to occur independently of bone aluminum. These data indicate that CAPD generally enhances the mineralizing capacity of individual osteoblasts and suggests that such therapy is beneficial to the uremic skeleton.

Biopsy↗
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↗
PubMed1981

Isolated skeletal involvement in Cushing's syndrome: response to therapy.

A 38-yr-old male presented with severe symptomatic osteopenia secondary to adrenal hyperfunction without any clinical expression of Cushing's syndrome. The predominantly axial distribution of his osteopenia and the presence of rib fractures healing with abundant callus formation, despite insignificant elevations in serum alkaline phosphatase, were characteristic of glucocorticoid excess syndromes. The histological features of the pretreatment bone biopsy were typical of those associated with excess glucocorticoids, namely decreased quantities of nonmineralized bone matrix, reflecting sites of bone formation, and an increase in the number of osteoclasts, indicating enhanced bone resorption. Six weeks after adrenalectomy, repeat bone biopsy revealed a marked increase in bone matrix synthesis and a significant decrease in bone resorption. These observations suggest that stimulators of skeletal turnover, like sodium fluoride, may be inappropriate in the initial treatment of steroid-induced osteopenia after surgical cure and that vitamin D and calcium therapy offers a more rational approach. Furthermore, the importance of the routine evaluation of adrenal function in any patient presenting with osteopenia is stressed, as well as the fact that relatively isolated skeletal involvement, classically described in micronodular adrenal disease, is not necessarily peculiar to a specific subset of the syndrome but may potentially attend any cause of glucocorticoid excess.

Adrenal Cortex Function Tests↗
PubMed1981

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↗
PubMed1980

Effect of alcohol ingestion on bone and mineral metabolism in rats.

Chronic ethanol administration to growing rats for 56 days resulted in circulating levels of 140 mg/dl, approximating concentrations that characterize alcoholic intoxication in man. This degree of alcohol ingestion, although without gross or histological effect on the liver or testicles, was attended by decreased trabecular bone volume despite a normal rate of skeletal mineralization as measured by time-spaced tetracycline labeling. Concomitant serum levels of calcium, phosphate, magnesium, creatinine, glutamic oxalacetic transaminase, alkaline phosphatase, testosterone, and 25-hydroxyvitamin D were normal. Although alcohol treatment was associated with a significant decrease in urinary calcium excretion, it had no effect on phosphate excretion nor on its renal tubular reabsorption. The data reveal that circulating levels of alcohol that do not result in hepatic or testicular injury are toxic for bone.

Alcohol Drinking↗
PubMed1980

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↗
PubMed1979

Adult hypophosphatasia. Clinical, laboratory, and genetic investigation of a large kindred with review of the literature.

Investigation of the kindred of a 58-year-old woman with all of the features of "adult" hypophosphatasia revealed 12 individuals in 3 generations with subnormal circulating total alkaline phosphatase (AP) activity. The pattern of inheritance suggested autosomal dominant transmission, with incomplete penetrance of the trait particularly in the young males. Hypophosphatasic individuals other than the proposita were clinically well but had loss of permanent teeth, showing that dental abnormalities could be the only clinical manifestation of the disorder. Radiographic investigation of the proposita revealed that completion of stress fractures was necessary for healing; maturation of incomplete fractures resulted in stable Looser zones. Skeletal survey and radionuclide bone imaging were unremarkable in hypophosphatasic individuals without fracture. Subclinical osteopenia was found in several affected women by metacarpal cortical width and bone densitometric measurements. Laboratory studies showed increased plasma and urinary phosphoethanolamine levels in affected individuals. Phosphoethanolamine and phosphoserine appeared to be natural subtrates for AP since a negative correlation existed between each substrate and circulating total AP activity. Phosphoethanolamine and phosphoserine levels were greatest in the clinically affected proposita; furthermore, only she showed absence of leukocyte AP activity. Heat fractionation of her total circulating AP activity suggested severe reduction in the bone isoenzyme. Hypophosphatasic children had higher levels of total circulating AP than affected adults; the increase was apparently secondary to increased bone isoenzyme. Iliac crest bone biopsies showed greater abnormality in affected women. Osteoidosis was particularly pronounced in the proposita's younger affected sister and hypophosphatasic daughter. Histomorphometric analyses of the biopsies revealed a paucity of osteoblasts despite increased quantities of unmineralized matrix. The finding that hypophosphatasic children in this kindred had higher circulating total AP activity than adults and were able to model their skeleton normally, together with observations that the bone biopsy in adults had a paucity of osteoblasts, suggests that some factor(s) during growth is able to induce both AP activity and osteoblast function, or, that this disorder is an "abiotrophy" with deficient osteoblastic formation and/or accelerated destruction in adult life.

Adolescent↗
PubMed1978

Effect of testosterone therapy on bone formation in an osteoporotic hypogonadal male.

Osteoporosis has been reported to complicate androgen deficiency in males. Accordingly, we have evaluated an osteoporotic hypogonadal male with bone histomorphometry before and after 6 months of testosterone replacement. Androgen therapy resulted in increases in relative osteoid volum, total osteoid surface, linear extent of bone formation, and bone mineralization. The dramatic histological response to hormonal replacement confirms the importance of androgens in bone modeling and remodeling.

Adult↗
PubMed1978

Lithium inhibition of bone mineralization and osteoid formation.

Lithium chloride administration to growing rats, which resulted in circulating lithium levels of 1.4 meq/liter, was attended by significant suppression of bone mineralization and organic matrix synthesis as assessed by tetracycline labeling and histological quantitation of osteoid, respectively. These effects of lithium were not associated with changes in animal behavior, nor were there any significant differences in blood levels of calcium, phosphorus, alkaline phosphatase, creatinine, pH, or parathyroid hormone. The data suggest that lithium inhibition of bone mineralization is secondary to suppression of osteoid formation.

Animals↗