PubMed Health⌕ Search

Biomedical subjects

M Kleerekoper

Publications and source records attributed to M Kleerekoper.

At least 19 recordsLinked to original sources
PubMed1992

Borderline-low serum thyrotropin level is correlated with increased fasting urinary hydroxyproline excretion.

BACKGROUND: Recent studies suggest that even mildly supraphysiologic thyroid hormonal status accelerates bone loss. In hyperthyroidism, increased bone resorption is the predominant mechanism for bone loss. We postulated that the changes in thyroid hormone status as reflected by low-normal and minimally subnormal serum thyrotropin level would have an effect on bone turnover and could be detected by a simple, noninvasive marker of bone resorption, fasting urinary total hydroxyproline-creatinine excretion (THP/Cr). METHODS: We retrospectively identified ambulatory patients with a restricted range of diagnoses who had had measurements of thyrotropin and THP/Cr performed within +/- 21 days. RESULTS: Of the 86 patients, 47 had thyrotropin levels greater than 1.0 mU/L. In these patients, no correlation was evident for thyrotropin and THP/Cr. Of the other 39 patients, 11 had suppressed thyrotropin levels (less than 0.1 mU/L) and showed clearly elevated values for THP/Cr, as expected from previous studies of hyperthyroidism. For 28 patients with thyrotropin in the borderline and low-normal range of 0.1 to 1.0 mU/L, a significant negative correlation with THP/Cr was found. The THP/Cr was positively correlated with serum alkaline phosphatase level, as expected with increased bone turnover. CONCLUSIONS: These results add further support to the hypothesis that even a minimal excess of thyroid hormones increases bone turnover and may contribute to accelerated bone loss.

Aged↗
PubMed1992

Comparison of single-photon and dual-energy x-ray absorptiometry of the radius.

We compared dual-energy x-ray absorptiometry (DXA) for measurement of the radius with the conventional single-photon absorptiometry (SPA) method. To evaluate reproducibility, 34 healthy male and female subjects were measured twice each by both methods. While the instruments measured bone mineral content (BMC) similarly, projected area was consistently lower by SPA and therefore bone mineral density (BMD) was higher by an average of 10%. We report similar coefficients of variation for the two methods, which are 0.8% (SPA) and 0.7% (DXA) for BMC (P = 0.71) and 0.8% (SPA) and 1.4% (DXA) for BMD (P = 0.02). We also evaluated the relationship between the methods with data from 196 clinic patients who were measured once each on both instruments. The BMD measurements from the two instruments were highly correlated (r = 0.97) in these patients, which permits the conversion of databases from SPA to DXA-equivalents. We conclude that DXA can replace SPA for radial bone densitometry.

Absorptiometry, Photon↗
PubMed1992

Mucin-producing parathyroid carcinoma.

A 67-year-old white male presented with symptomatic hypercalcemia (15.6 mg/dl) in December 1989. He had undergone thyroidectomy for removal of a mucin-producing adenocarcinoma of the thyroid in 1967, and after eight years of follow-up during which time no other neoplasms were detected, he was reported as a unique case of this syndrome. Mild hypercalcemia (less than 11.0 mg/dl) was first noted in 1987, and this had remained stable until shortly before the acute presentation. Multiple lung nodules were observed radiographically and presumed to be granulomatous until increased size was observed shortly before presentation. Serum intact PTH was 190 pg/ml (n 10-55), but at neck exploration no parathyroid tissue was found and surgery did not resolve the hypercalcemia. Serum PTHrP was undetectable. Biopsies from all three lobes of the right lung revealed numerous nodules of metastatic adenocarcinoma with cords of tumor cells surrounded by mucin. The histology was similar to that obtained 23 years earlier. Following left upper lobe resection with removal of a 3-cm nodule, hypercalcemia resolved. The tumor stained strongly positive with a peroxidase stain for PTH using a polyclonal antibody. Northern blot hybridization of total RNA from the tumor confirmed the presence of message for PTH but not PTHrP. The original diagnosis has been revised to that of a unique case of mucin-producing parathyroid cancer with an extraordinarily long latency period before recurrence.

Adenocarcinoma↗
PubMed1992

Outcome variables in osteoporosis trials.

The conduct of controlled clinical trials examining the anti-fracture efficacy of potential therapies for osteoporosis is a relatively new and developing science. We have reviewed several aspects of data acquisition, emphasizing that bone mass measurement and, similarly, back pain can only be regarded as ancillary outcome variables. Serial measurement of stature when performed in a precise manner may be an inexpensive, quick, and convenient surrogate outcome variable, most applicable to large multi-center studies. The only true end-point of such trials is the radiographic documentation of new vertebral fracture occurrence. Techniques for obtaining serial radiographs and assessing vertebral morphometry with good quality control have been described. Important questions still need to be resolved concerning the most appropriate criteria for defining incident fractures and for calculating fracture frequency. Implications regarding trial sample size requirements are discussed.

Body Height↗
PubMed1992

Fluorides and osteoporosis.

Sodium fluoride has clearly been shown to have pronounced effects on the skeleton, probably more than any other currently available therapeutic agent. Unfortunately, these effects appear to be both beneficial and potentially toxic at the same time. A more clear understanding is needed of the basic mechanisms whereby these effects (both beneficial and detrimental) are exerted. When such data are forthcoming, it may be possible to modify the therapeutic use of fluoride in osteoporosis and other brittle bone diseases such that the beneficial effects outweigh the toxic effects much more completely than is currently the case. Until such time, and despite thirty years of meaningful clinical investigation, we must conclude that sodium fluoride has no role in clinical medicine outside the confines of properly conducted clinical research studies.

Bone and Bones↗
PubMed1992

Parathyroid stimulation after bleeding in man.

A role for the PTH-calcium axis in the normal bone-marrow response to bleeding or erythropoietin administration has been demonstrated in rats. We studied 20 autologous blood donors, each donating two units of blood, who served as a human bleeding model. Fifteen patients completed the study. Blood donations were followed by a significant increase in serum intact PTH (2.15 +/- 0.67 to 2.81 +/- 0.84 pmol/l; p = 0.0003) and protein-corrected total calcium (2.43 +/- 0.09 to 2.49 +/- 0.08 mmol/l; p = 0.2). All the individual values remained within the normal range. PTH weakly correlated with the reticulocyte count, but not with the corrected serum calcium. We conclude that moderate bleeding in humans is followed by a physiological increase in serum PTH and calcium.

Adolescent↗
PubMed1991

Structural and geometric changes in iliac bone: relationship to normal aging and osteoporosis.

We measured indices of bone volume (cancellous and cortical) and bone surface (cancellous, endocortical, and intracortical) in intact, full-thickness transiliac bone biopsies obtained from 47 healthy white women (23 premenopausal and 24 postmenopausal) and 82 patients with postmenopausal osteoporosis. In the normal subjects there was the expected loss of cancellous bone with age, best shown by a reduction in bone surface/tissue volume, but no fall in cortical thickness with age despite a significant reduction in forearm bone density measured by single-photon absorptiometry. Bone surface/bone volume was about four times higher in cancellous than in cortical bone, and cancellous bone contributed about one-third of the total bone volume and about two-thirds of the bone surface when related to the core volume referent. In the osteoporotic patients, core width, an index of iliac bone thickness at the biopsy site, was reduced by 10%, but we could not determine whether this was the result of compaction of the core or of bone slenderness. All indices of bone volume, cortical as well as cancellous, were significantly smaller, as were the values for forearm bone densitometry; the relative deficits at different sites depended on whether they were expressed as percentages or as zeta scores. Bone surface/bone volume was increased in both cancellous and cortical bone, but bone surface/tissue volume was reduced in cancellous bone and increased in cortical bone. The proportions of total bone volume and surface contributed by cancellous and cortical bone were almost the same as in normal postmenopausal women.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Asymptomatic primary hyperparathyroidism discovered by multichannel biochemical screening: clinical course and considerations bearing on the need for surgical intervention.

The sustained effects of biochemical screening to increase both apparent incidence and age at diagnosis indicate that, without screening, most patients with primary hyperparathyroidism would would never be diagnosed. This suggests that asymptomatic patients discovered as a result of screening have a nonprogressive form of the disease, with adverse health effects that are few or nontraditional, for which treatment policies validated only in symptomatic patients may be inappropriate. Accordingly, in 1975 we formulated criteria for withholding surgical treatment from such patients. Of 174 who were eligible for study over a 10 year period, clinical, biochemical, and densitometric assessment was repeated after at least 1 year (mean 52 months) in 106 patients who did not differ in any initial characteristic from 68 patients in whom follow-up was inadequate. There was no change in symptoms, no disease complications, and no change in any index of hormone secretion or disease severity. In 30 patients, individual regression slopes against time were not significant for any serum measurement. In these patients the disease appeared to have stopped progressing by the time the diagnosis was made, most likely because of cessation of tumor growth. There was a significant deficit in appendicular cortical bone at the time of diagnosis but no further acceleration of bone loss thereafter. In an earlier study, surgical cure was followed by a modest increase in forearm bone density for the first 6 months, but even after 3 years only about 20% of the deficit was corrected. The deficit in bone density is smaller in the spine than in the forearm and is not accompanied by any increase in vertebral fracture risk.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

A randomized trial of sodium fluoride as a treatment for postmenopausal osteoporosis.

The anti-fracture efficacy of sodium fluoride (NaF) was evaluated in 84 postmenopausal white women with spinal osteoporosis. The dose of NaF used was 75 mg/day and all patients in this prospective, randomized, double-blind, placebo-controlled clinical trial received calcium supplements (carbonate salt) 1500 mg/day in addition to participating in a structured physical therapy program. For each of the outcome measures (change in stature, change in cortical bone mass in the forearm and development of new vertebral fractures determined by change in vertebral morphometry and by scintigraphy) there was no significant difference between the fluoride or placebo treated groups. Side effects, predominantly gastrointestinal symptoms and the development of the painful lower extremity syndrome, occurred significantly more frequently in the fluoride group (P less than 0.05). Peripheral fractures were not more frequent in the fluoride group. We conclude that, in the dose and manner used in this study, NaF is no more effective than placebo in retarding the progression of spinal osteoporosis. There is no role for NaF in the treatment of osteoporosis outside the confines of clinical research.

Aged↗
PubMed1991

Fluorides and osteoporosis.

Sodium fluoride has clearly been shown to have pronounced effects on the skeleton, probably more than any other currently available therapeutic agent. Unfortunately, these effects appear to be both beneficial and potentially toxic at the same time. A more clear understanding is needed of the basic mechanisms whereby these effects (both beneficial and detrimental) are exerted. When such data are forthcoming, it may be possible to modify the therapeutic use of fluoride in osteoporosis and other brittle bone diseases such that the beneficial effects outweigh the toxic effects much more completely than is currently the case. Until such time, and despite thirty years of meaningful clinical investigation, we must conclude that sodium fluoride has no role in clinical medicine outside the confines of properly conducted clinical research studies.

Bone and Bones↗
PubMed1991

Oral contraceptive use may protect against low bone mass. Henry Ford Hospital Osteoporosis Cooperative Research Group.

This cross-sectional retrospective epidemiologic study investigated risk factors for low bone mineral density (BMD) in a group of 2297 women, 76% of whom were postmenopausal. Reproductive information, history of oral contraceptive use, BMD measurements, and other data were available from women presenting to 12 osteoporosis screening centers in 1986 and 1987. Each woman was classified into a BMD category based on the range of BMD measurements at her respective center. Menopause, increasing age and years since menopause, and decreasing body mass index were associated with low BMD. A history of oral contraceptive use was protective against low BMD (odds ratio = 0.35, 95% confidence interval = 0.23 to 0.53). Multivariate analyses confirmed this result and further demonstrated that increasing duration of use was protective. These data suggest that prior use of oral contraceptive agents is associated with higher levels of BMD and that the degree of protection from lower BMD is related to duration of exposure.

Adolescent↗
PubMed1978

Idiopathic multicentric osteolysis. Report of an affected father and son.

Genetic, rheumatologic, immunologic, metabolic, and renal studies of a father and son with idiopathic multicentric osteolysis are reported. The disorder appeared through mutation. The father developed symptoms as an infant, his son at age 4 years and 9 months. Both have micrognathia and hypotelorism and were exceptionally tall during the symptomatic phase of their disease. Biopsies of the son's wrist showed normal synovium, encroachment on cartilage by fibrocellular tissue, and both osteoclastic resorption and repair of affected bone. Hydroxyproline in his urine was increased. No immunologic, renal, or other metabolic abnormalities were identified.

Adult↗
PubMed1977

Hypercalcemic hyperparathyroidism in hypophosphatemic rickets.

A 25-year-old white woman with sporadic hypophosphatemic rickets presented with a 7 year history of chronic mild hypercalcemia, osteitis fibrosa cystic and hypercalcemic nephropathy. Serum immunoreactive parathyroid hormone was elevated by greater than 100-fold and a 3.5 g parathyroid tumor was found at operation. Survey of the literature reveals that of 9 previous cases in which hypercalcemic hyperparathyroidism occurred in association with hypophosphatemic rickets, only two had classical x-linked familial hypophosphatemic rickets. It appears more than likely that this unusual combination of skeletal diseases represents the chance occurrence of primary hyperparathyroidism in patients with underlying x-linked familial hypophosphatemic rickets rather than a complication of phosphate therapy.

Adolescent↗