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Biomedical subjects

F Cosman

Publications and source records attributed to F Cosman.

52 records · Page 3Linked to original sources
PubMed1993

Urinary hydroxypyridinium crosslinks of collagen as markers of bone resorption and estrogen efficacy in postmenopausal osteoporosis.

Estrogen deficiency-induced bone loss has been associated with accelerated bone turnover. Levels of some biochemical markers, such as serum osteocalcin (BGP), tartrate-resistant acid phosphatase (TRAP), and urinary hydroxyproline (OHP), have been shown to be related to the rate of bone turnover. They may therefore be useful in identifying the individual at risk for osteoporosis and monitoring the efficacy of the treatment. Two recently discovered markers, urinary pyridinoline (PYD) and deoxypyridinoline (DPD), are apparently directly related to bone matrix degradation and may be more accurate markers of bone resorption than OHP or TRAP. To evaluate the effects of menopause, osteoporosis, and estrogen replacement on the excretion of these new markers, we measured the levels of PYD and DPD and other biochemical markers of bone turnover in four groups of women, premenopausal healthy (PRE), postmenopausal healthy (POST), postmenopausal osteoporotic (UTO), and postmenopausal osteoporotic with estrogen treatment (ETO). Significant increases in PYD, DPD, BGP, TRAP, and OHP were found in POST and UTO groups compared with PRE. These increases were blunted by estrogen treatment when the levels of each of the markers returned to PRE levels. When comparing POST and UTO groups, significant increases were observed in UTO only for PYD, DPD, and urinary calcium but not for OHP, BGP, or TRAP. With subgroups matched for age and years from menopause, only DPD discriminated between POST and UTO. Indices of bone formation covaried with markers of bone resorption in the total population.(ABSTRACT TRUNCATED AT 250 WORDS)

Acid Phosphatase↗
PubMed1993

Calcium homeostasis of an elderly population upon admission to a nursing home.

OBJECTIVE: To evaluate the skeletal health, calcium, and vitamin D homeostasis of patients upon their entry to a long-term-care facility. Factors that could contribute to the risk of future osteoporotic fractures were also evaluated. DESIGN: Cross-sectional study. PATIENTS: Two hundred eighty-seven consecutive admissions were invited to participate; 109 patients were recruited into the study. MEASUREMENTS: A high prevalence of low to low-normal circulating levels of 25(OH)D was found in nursing home residents upon their admission to the nursing home, with 86% of the patients having circulating 25(OH)D levels of less than 50 nmol/L and 41% having levels below 25 nmol/L. Frankly elevated parathyroid hormone levels were found in 16% of the patients. Additionally, alkaline phosphatase and osteocalcin levels were elevated in 23% and 13% of the patients, respectively. Bone mineral measurements were in the osteoporotic range for 85% of the nursing home residents. Bone density results for females with a history of any classic osteoporotic fracture were significantly lower than for those with no fracture history (68.5 arbitrary units (AU) for those with no fracture history, 58.8 AU in those with history of hip fracture; P < 0.05). The bone mineral measurements were higher in women with adequate 25(OH)D compared with women with deficient or borderline 25(OH)D with and without fracture history. Levels of 25(OH)D were positively correlated with urine calcium/creatinine (r = .24; P = 0.03) and 1,25(OH)2D (r = .28; P = 0.01) and were negatively correlated with 1-84 PTH (r = -.24; P = 0.02). CONCLUSION: Hypovitaminosis D is prevalent among elderly patients entering a nursing home with secondary hyperparathyroidism and apparently increased bone turnover present in patients with circulating 25(OH)D levels below 50 nmol/L. Bone density measurements showed that a majority of the individuals entering a nursing home are osteoporotic. There is a positive association between 25(OH)D levels and bone mass and a negative association between 25(OH)D levels and a history of fracture.

Activities of Daily Living↗
PubMed1993

Subcutaneous administration of the amino-terminal fragment of human parathyroid hormone-(1-34): kinetics and biochemical response in estrogenized osteoporotic patients.

A standard dose (400 U or 25 micrograms) of human (h) PTH-(1-34) was administered sc in 11 estrogen-treated patients with postmenopausal osteoporosis. Increments in circulating hPTH-(1-34) were brisk, peaking at 30 min, with variable peak levels averaging 10 times normal. Clearance of the peptide from the circulation followed an expontential pattern, with a mean t1/2 of 75 min. Peptide administration was followed by an immediate decline in serum concentrations of PTH-(1-84), which remained suppressed at about 65% of the basal value for the duration of the study (4 h). Serum calcium did not increase until 120 min, thus occurring after the diminution in PTH-(1-84). Serum phosphorus declined promptly as urinary phosphate excretion increased. There were no clear changes in urinary calcium excretion, but urinary cAMP excretion increased within 120 min. In 9 of 11 patients, the serum concentration of 1,25-dihydroxyvitamin D increased, with mean levels increasing progressively after 90 min to approximately 30% above baseline (P < 0.05). In conclusion, sc administration of 25 micrograms hPTH-(1-34) produces significant short term changes in mineral homeostasis that appear to be mediated by the kidney, parathyroid gland, and skeleton, with the latter displaying the most delayed response.

Calcitriol↗
PubMed1992

Bone mass and body composition in normal women.

The interrelationships between measurements of bone mass and total-body bone mineral were examined in a cross-sectional study of normal healthy women aged 17-82 years. In addition we evaluated the relationship between measures of body composition, estimated by four independent techniques, and bone mass in the same population. Considering the group as a whole, bone mass at all sites correlated with each other and with total-body bone mineral (TBBM). Cancellous and cortical sites could predict TBBM equally well. As expected, all measurements of bone mass were significantly lower in postmenopausal women in comparison to premenopausal women. Declines in bone mass were only seen in premenopausal women in the femoral neck and Ward's triangle, not in lumbar spine, radius, or skeleton as a whole. In postmenopausal women bone mass correlated negatively with age and years from menopause equally at all sites. TBBM was significantly related to height and weight in both premenopausal and postmenopausal women. In premenopausal and postmenopausal women TBBM also correlated with fat mass, but TBBM was much better correlated with percentage body fat in premenopausal than postmenopausal women. TBBM was a constant proportion of lean body mass in premenopausal women, but the fraction of lean mass occupied by the skeleton declined with age in postmenopausal women. Correction of TBBM for lean mass did not change the relationship between TBBM and percentage fat in premenopausal women but eliminated the relationship in postmenopausal women. Regional measurements, which are at least partially corrected for body size by dividing mass by area, correlated less well with height and weight and with any index of obesity, especially in postmenopausal women.

Adolescent↗
PubMed1992

Comparative assessment of bone mineral density of the forearm using single photon and dual X-ray absorptiometry.

Forearm bone mineral density (BMD) was measured at proximal and distal sites by 125I single photon absorptiometry (SPA) and by dual energy X-ray absorptiometry (DXA) in 67 consecutive subjects, aged 18-75 years. Correlations and regression equations between these two techniques were determined. All forearm measurements were significantly correlated with each other (r = 0.599-0.926; P < or = 0.0001). Although SPA and DXA correct for fat in different ways, we found similar correlation and regression equations in women with body mass index measurements above and below the mean. In addition, forearm measurements by both techniques were moderately correlated with vertebral spine and hip BMD. We conclude that overall, SPA forearm measurements in a population can be calibrated to DXA measurements if necessary, and that DXA forearm measurements are as predictive of the remainder of the skeleton as SPA measurements.

Absorptiometry, Photon↗
PubMed1992

Relationships between quantitative histological measurements and noninvasive assessments of bone mass.

We performed a comprehensive analysis of the relationships between histologic indices in the iliac crest (cancellous bone volume, trabecular structural indices, cortical width, and core width) and bone density in the spine, hip, and wrist in 81 patients with various metabolic bone diseases including osteoporosis, osteomalacia, hyperparathyroidism, and Paget's disease. In the whole group, all of the histologic indices correlated significantly with bone mineral density (BMD) of the spine and the three regions of the hip (r = 0.28-0.73), with the exception of cortical width which correlated with the hip but not the spine (r = 0.21). There was no relationship between the histologic variables and either the distal or proximal radius. When the osteoporotic subgroup was considered separately, the relationships between BMD and both cancellous bone volume and the structural indices (trabecular number, separation, and thickness) were lost. In contrast, cortical width correlated more strongly with both spine and hip BMD. The relationship between core width and the spine was lost but persisted in the hip region. In female osteoporotic patients alone, only cortical width remained significantly correlated with spine or hip BMD. We conclude that the relationships between bone densities in the axial and peripheral regions and histomorphometric variables in iliac crest are not constant. In addition, cancellous bone volume and the trabecular structural indices relate well to noninvasive axial BMD measurements only in a heterogenous group with a large variance in both parameters. In the more homogeneous group with osteoporosis, cortical width appears to be a more powerful predictor of BMD at the important sites of osteoporotic fracture.

Bone Density↗
PubMed1991

Radiographic absorptiometry: a simple method for determination of bone mass.

Bone mass measurements have been shown to be useful determinants of the risk of development of osteoporotic fractures and may help identify individuals who are most likely to benefit from both primary and secondary prevention of osteoporosis. As standard bone density measurements are not available to all physicians, there is a need for a fast, inexpensive, and widely available technique to measure bone mass. Radiographic absorptiometry of the phalanges requires only routine radiography with processing of the films done at a special off-site laboratory. We performed a preliminary investigation to see whether this simple technique could be used to predict a low bone mass as defined by dual- and single-photon absorptiometry. Correlations between radiographic absorptiometry. Correlations between radiographic absorptiometry and the standard techniques were as good as those among the standard techniques themselves (r = 0.58-0.9). Radiographic absorptiometry measurements predicted low bone mass of the lumbar spine and femoral neck with 90% and 82% sensitivity respectively. If further evaluation supports these initial conclusions, radiographic absorptiometry may be useful as a screening technique for primary care physicians and in research settings where dual-photon or dual-energy X-ray absorptiometry are impossible.

Absorptiometry, Photon↗
PubMed1991

Response of the parathyroid gland to infusion of human parathyroid hormone-(1-34) [PTH-(1-34)]: demonstration of suppression of endogenous secretion using immunoradiometric intact PTH-(1-84) assay.

Alterations in the sensitivity of the parathyroid gland to both stimulative and suppressive stimuli may be partially responsible for skeletal changes that occur with age, estrogen deficiency, osteoporosis, and estrogen treatment of osteoporosis. We sought to define the changes in intact PTH-(1-84) secretion in normal premenopausal and postmenopausal, osteoporotic and estrogen-treated osteoporotic women during the infusion of human (h) PTH-(1-34). hPTH-(1-34) was infused at 0.55 U/kg.h for 24 h, with serum sampling every 4 h. Serum was analyzed for calcium (ionized and total), hPTH-(1-34), and PTH-(1-84). Basal chemistries were no different among groups, except for serum phosphorus, which was highest in osteoporotic women (1.31 vs. 1.07 mmol/L in premenopausal; P less than 0.02), and hPTH-(1-34), which was slightly higher in normal postmenopausal women (19.31 vs. 13.24 ng/L in estrogen treated; P less than 0.02). No differences in PTH-(1-84) were found among groups. hPTH-(1-34) rose similarly in all patient groups, while the calcemic response was somewhat more sluggish in estrogen-treated women, although statistically significant differences were not found. PTH-(1-84) declined rapidly in all patient groups, although estrogen-treated women had a smaller maximal decrease in PTH-(1-84), and the slope of the decremental change in PTH-(1-84) was lower in estrogen-treated women than in osteoporotic or normal postmenopausal women. Untreated osteoporotic women had less suppression of PTH-(1-84) than normal postmenopausal women at every calcium level. Estrogen treatment decreases the calcemic effects of infused hPTH-(1-34) and at the same time reduces calcium-induced suppression of parathyroid secretion. It is possible that such changes in the set-point of the gland contribute to the alterations in bone turnover that result in osteoporosis and the mechanisms by which estrogen prevents bone loss.

Calcium↗
PubMed1990

Body composition studies in premenopausal healthy women.

Body composition studies of healthy premenopausal women were performed using dual photon absorptiometry and the results compared with fat estimates obtained from skinfold measurements, body mass index, and bioelectrical impedance. Total body bone mineral did not decline with age nor did the fraction of lean body mass occupied by the skeleton, which ranged from 4-10%. DPA values for fat were significantly higher than those obtained by other techniques, in part because of calibration but also because of apparent inadequate correction for the fraction of lean body mass occupied by bone in the assumptions made for the other techniques.

Absorptiometry, Photon↗
PubMed1990

Estrogen in prevention and treatment of osteoporosis.

Estrogen has clearly been shown to decrease bone loss and frequency of osteoporotic fractures. Calcitonin has been shown in several studies to reduce the rate of bone loss, although no data are yet available demonstrating a reduction in fracture frequency. Studies of osteoporosis intrinsically assume that prevention of further loss, or increments in bone mass, will be associated with declines in fracture recurrence. That may not always be the case. Recent controlled studies in which fluoride was used to increase bone mass in vertebral bodies resulted in no significant decline in fracture recurrence, and there was even a suggestion of increased fracture risk at some sites. Thus further data on calcitonin will be important, even though calcitonin is not expected to alter bone quality as does fluoride. Alternative therapies to calcitonin and estrogen are being investigated in clinical studies since both are currently limited in their use. Because calcitonin currently requires nearly daily injections, estrogen remains the principal agent available for both prevention and treatment in spite of its wide effect on multiple body systems. Bisphosphonates, given continuously or intermittently, appear to be relatively safe oral alternatives to calcitonin. The long-term effects of these agents need to be evaluated in greater detail before they can be recommended for prevention, but a role in therapy of the established disorder seems likely. The skeletal effect of bisphosphonates is also inhibition of bone remodeling and therefore prevention of further bone loss. Thus, they add nothing to the other therapeutic regimens from this perspective and as with calcitonin therapy, documentation of decreased frequency of fracture is lacking. Agents to increase bone mass are purely investigational at this time and many years may elapse before efficacy can be shown for such interventions.

Estrogen Replacement Therapy↗
PubMed1989

Stimulation of inositol phosphate formation in ROS 17/2.8 cell membranes by guanine nucleotide, calcium, and parathyroid hormone.

In addition to stimulation of cyclic AMP, parathyroid hormone (PTH) may influence cellular events by utilizing other pathways of hormone action, such as the generation of inositol phosphates (IPs). We sought to examine this potential action of PTH by assessing the formation of inositol phosphates in PTH-sensitive ROS 17/2.8 cells. The polyphosphoinositides were labeled by growing the cells with [3H]inositol following which cell homogenates were prepared. The nonhydrolyzable guanine nucleotide, GTP gamma S, and calcium ion, alone and together, stimulated all three IPs, IP1, IP2, and IP3. IP1 formation was linear over 30 minutes but IP2 and IP3 accumulated more rapidly peaking by 5 minutes for all agonist conditions. The proportion of total P as IP3 was enhanced when the cells were grown with retinoic acid (1 microM) or when the assay was conducted at pH 4.5. In addition, the lower pH was associated with much more enzyme activity. PTH agonists, bPTH-(1-84) and bPTH-(1-34), both caused a small but significant stimulation of IP3 formation. When bPTH-(1-84), and the analog bPTH-(3-34)amide, that inhibits PTH-mediated adenylate cyclase activity were present together, there was additive stimulation of IP3 formation compared with that with either agent alone. The results demonstrate that inositol phosphate formation can be stimulated directly in a membrane preparation of ROS cells by GTP gamma S, calcium ion, and PTH and that the enzyme mediating this activity, phospholipase C, is regulated by a guanine nucleotide binding protein.

Calcium↗
PubMed1989

Lymphocytic hypophysitis. Report of 3 new cases and review of the literature.

Lymphocytic hypophysitis is an uncommon but increasingly recognized disorder characterized by chronic inflammation and destruction of the anterior pituitary. Three new cases are presented here with a review of the 27 previously reported cases. The disease affects primarily young women in late pregnancy or in the postpartum period but also has been described in postmenopausal women and in one man. It presents as an expanding intrasellar mass or as partial or panhypopituitarism. The etiology may be autoimmune. The natural history of this entity begins with enlargement of the pituitary secondary to inflammatory infiltration and progresses to atrophy of the gland with destruction of pituitary tissue and replacement with fibrosis. At least 1 patient had documented recovery of pituitary function, and the overall potential incidence of recoverable function is unknown. Our improved understanding of this disease has led us to conclude that surgical intervention is not always necessary.

Adolescent↗
PubMedDate not supplied

Hypercalcaemia causing declining cognitive function in a head injured patient.

Although hypercalcaemia in young children or adolescents immobilized by fractures or spinal cord injury is well recognized, hypercalcaemia in adult immobilized patients is rare without a pre-existing bone disease. To our knowledge, hypercalcaemia in a head-injured, immobilized patient has not been previously reported. We report here a case where a previously normocalcaemic, immobilized, head-injured adult patient developed cognitive decline secondary to hypercalcaemia five months after injury, when transient interruption of enteral feedings led to mild dehydration. Indices of bone turnover were elevated and parathyroid hormone was appropriately suppressed. Possible predisposing factors in our patient included a severe degree of immobilization and a very high level of athletic activity prior to injury. Careful fluid management and specific monitoring of calcium levels, even several months post-injury, should be performed to avoid the added complications of hypercalcaemia in head-injured patients.

Adult↗