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Biomedical subjects

M Kleerekoper

Publications and source records attributed to M Kleerekoper.

At least 37 records · Page 2Linked to original sources
PubMed1994

Non-dental tissue effects of fluoride.

The anti-caries effects of water fluoridation are well-established. The non-dental tissue effects of fluoride in drinking water, either naturally occurring or as an additive, have been too poorly studied to permit definitive conclusions to be drawn. Claims have been made that fluoride results in an increased occurrence of malignancies, particularly osteogenic sarcoma. Experimental rat data have not resolved this issue, and epidemiologic studies are equally unclear. Initial claims that fluoride offers protection against atherosclerosis remain viable, but here too, much more directed research is needed. Early studies suggested that a water fluoride content greater than 1 ppm resulted in a lower prevalence of osteoporotic fractures. Recent epidemiologic data seriously question this conclusion and raise the possibility that even this relatively low level may increase the prevalence of osteoporotic hip fractures. Other elements, including calcium and magnesium, also vary in amount as water fluoride content varies, and it has proved difficult to distinguish the independent effects of the various nutrients in water from each other. Therapeutic use of fluoride has been largely restricted to studies of its effect on the osteoporotic study, this important issue remains unresolved. This review provides an overview of these issues, focusing on the uncertainties alluded to, and attempting to develop strategies for future research.

Arteriosclerosis↗
PubMed1994

Body composition and gonadal steroids in older white and black women.

Obesity offers protection against osteoporosis in older women. The mechanisms are not well understood, but relate in part to increased aromatization of adrenal androgens to estrone in peripheral fat and muscle tissue. Two hundred and one white and 77 black women previously reported to be free of skeletal disease and to have normal bone mass had measurements of total body bone mineral (TBBM), fat mass (TBFM), and lean mass (TBLM) performed by dual energy x-ray absorptiometry. Serum estrone, androstenedione, and dihydroepiandrostenedione sulfate were measured on the same day. Body weight, body mass index, TBFM, and TBLM were all significantly higher in the black women. However, proportionately, there were no differences in body composition between the two groups. This suggests that the black women were not more obese despite their greater body mass index, and that future studies on the health impact of obesity in older black women should take this into consideration. Despite the greater TBFM and TBLM in the black women and no difference in serum androstenedione levels, the serum estrone level was not higher in the black women, and the higher bone mass in blacks was not related to serum estrone. In both ethnic groups, TBBM was significantly related to body weight (white, r = 0.80; black, r = 0.85; P < 0.001 for both). Both TBFM and TBLM were significantly related to TBBM in both ethnic groups. Serum estrone was significantly related to all measures of body mass in the white women, but to no measures of body mass in the black women, indicating apparent differences in the metabolism of estrone between older white and black women.

Adipose Tissue↗
PubMed1993

Skin color and body size as risk factors for osteoporosis.

We compared skin color, body size and bone mineral density (BMD) among three groups of postmenopausal women: 104 healthy black women, 45 healthy white women, and 52 osteoporotic white women with vertebral fractures. Skin color was measured by reflectometry, stature with a Harpenden stadiometer, weight with digital scales, and radial BMD by single photon absorptiometry. There were no significant differences in mean skin color (age-adjusted) between the healthy and osteoporotic white women, although both white groups differed from the black group. There was no significant correlation between skin color and BMD (age- and weight/height-adjusted) in any of the groups. All three groups differed significantly in age-adjusted BMD, although there was less difference between the healthy blacks and whites when covariates (body size, age) were taken into account. We further investigated body size differences by estimating stature at age 55 in all three groups based on our observations that osteoporotic women with vertebral fractures lose height at a rate that is 2.6 times faster than that of healthy aging women. Our analyses indicate that the osteoporotics were not shorter than the normals before the onset of their disease (based on estimated height), and do not have a significantly smaller body mass (weight/height and weight/height 2) than the normal white women. Additionally, the osteoporotics are above the ideal body mass index recommended by the National Institutes of Health. We conclude that fair skin is not a risk factor for osteoporosis and that large body size is not protective against the development of osteoporosis, although it may have a salutary effect on BMD in both blacks and whites.

Aged↗
PubMed1993

Sodium fluoride therapy of postmenopausal osteoporosis.

More than 30 yr of research has clearly established sodium fluoride as the most potent agent currently available for increasing spinal bone mass. The increase is dose-dependent and linear with time for at least 6 yr, probably as long as 10 yr. This is in keeping with observed pharmacological actions of fluoride to enhance recruitment of osteoblasts and matrix deposition without any consistent effect on bone resorption. Unfortunately this has not translated into therapeutic efficacy in terms of preventing the VFR in patients who are already fractured at the initiation of therapy. Whether fluoride will be effective in preventing the first fracture is currently being investigated. If successful in this regard it will not only be extremely useful as prophylaxis against osteoporotic vertebral fractures, but will also provide substantial insight into the pathogenesis of these fractures and the management of patients seen after the first or subsequent fracture. We predict that fluoride will turn out to be extremely useful for prophylaxis. Whether or not lower doses or intermittent fluoride therapy will prove to be effective in patients who have already sustained fractures, is also being actively investigated in controlled clinical trials. Given the difficulty in demonstrating therapeutic efficacy over the past 30 yr, with favorable outcomes only reported from uncontrolled studies, we are not as optimistic about these investigations. Side-effects of NaF are becoming more clearly understood and easier to manage. The gastrointestinal symptoms are short-lived and dependent on the dose and formulation. These symptoms infrequently prohibit the use of the drug. The painful lower extremity syndrome appears to us to represent a 'positive' response to NaF, reflecting abundant formation of new bone that is poorly mineralized. If detected on the basis of symptoms, therapy should be interrupted for 6-8 weeks, then restarted at a lower dose. This syndrome, while clearly related to NaF, appears to be idiosyncratic and not dose or formulation dependent. The data relating NaF to hip fractures cannot be completely ignored because of the major community health problem posed by hip fractures. However, the data are largely anecdotal. Putting all this together, we feel that there may be an important role for NaF in osteoporosis treatment but, for now, its use should be restricted to properly conducted controlled clinical trials.

Aged↗
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↗