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Biomedical subjects

M Kleerekoper

Publications and source records attributed to M Kleerekoper.

At least 19 recordsLinked to original sources
PubMed1995

Hypercalcemic crisis.

Hypercalcemic crisis or severe hypercalcemia represents a life-threatening emergency. The most common cause is hypercalcemia of malignancy, although granulomatous diseases, previously undetected primary hyperparathyroidism, medication-induced hypercalcemia, and a few rarer causes may result in this endocrine emergency as well. The clinical presentation and prognosis depend on the acuity of the development of hypercalcemia, the degree of hypercalcemia, and the underlying cause. Certainly, patients with malignancy who develop hypercalcemia superimposed on their already debilitated state are more likely to have a poor outcome than a previously relatively healthy patient with thiazide-induced hypercalcemia, for example. The clinical presentation of patients with hypercalcemic crisis varies depending once again on the underlying cause and degree and rapidity of the hypercalcemia. Most patients experience some constitutional symptoms, neurologic symptoms, gastrointestinal symptoms, and renal manifestations of hypercalcemia. Immediate and effective therapy directed toward the pathophysiology of hypercalcemia is essential. General measures must be implemented to reverse the dehydration, to promote urinary calcium excretion, to avoid prolonged immobilization, and to identify the underlying cause of hypercalcemia. Specific measures directed at inhibiting bone resorption, increasing renal sodium and calcium excretion, and occasionally at decreasing intestinal absorption of calcium (or more specifically blocking vitamin D metabolism) should also be implemented. Obviously the more reversible the underlying cause of hypercalcemia, the more aggressive one should be with the therapy. The literature was reviewed to compile comparative data that practitioners may use in choosing among the various pharmacologic therapies available for the treatment of acute hypercalcemia. Despite all the advances in the field, hypercalcemic crisis still carries a significant mortality risk, although with appropriate therapy with the aforementioned general and specific measures, the calcium level can effectively be lowered in most patients.

Calcium↗
PubMed1994

Reversal of vertebral deformities in osteoporosis: measurement error or "rebound"?

Digitized morphometry of vertebral bodies on lateral spine films is used to identify and quantify vertebral deformities or fractures. One problem associated with this method is the phenomenon of "disappearing fractures," which results from the apparent increase in vertebral body heights of previously deformed vertebrae on subsequent radiographs. These have been considered biologically implausible and therefore a result of measurement error. Measurement error is unlikely to be unidirectional, so that a proportion of fractures identified by morphometry is also the result of measurement error. Since some vertebral deformities are real events, some disappearances of deformities detected by morphometry may be real events. In this report, we examine the data from our clinical trial of sodium fluoride in spinal osteoporosis to assess critically the plausibility of two hypotheses: (1) The "rebound" phenomenon results from measurement error. If this is the case, then some fractures of the same magnitude as the rebound must also represent measurement error. (2) Some deformed vertebrae in fact rebound toward their original shape and size, displaying an elastic response to deformation. If this occurs, then some vertebral deformities are transient events, not true fractures. We conclude that the variability inherent in morphometric data obtained from serial spine x-rays results in both disappearing fractures and a high false positive fracture rate. The use of more stringent criteria for defining significant deformities, or true fractures, will minimize these problems. We cannot exclude the second hypothesis, that some vertebral deformities may be transient events, but this needs further study.

Aged↗
PubMed1994

Reference data for bone mass, calciotropic hormones, and biochemical markers of bone remodeling in older (55-75) postmenopausal white and black women.

From a random sample of our institution's health maintenance organization (HMO), we recruited 250 white women and 112 black women, aged 55-75, all of whom were 10 or more years postmenospause with minimal estrogen exposure and free of osteoporosis, other metabolic bone disease, and medical, surgical, or therapeutic situations that may influence bone loss. Bone mass was measured in the radius, spine, and femur by DXA and in L1 by QCT. Serum samples were analyzed for parathyroid hormone, calcidiol, calcitriol, osteocalcin, and bone alkaline phosphatase and urine samples analyzed for creatinine, calcium, and hydroxyproline. Mean Z score, based on published reference data for forearm and femoral neck BMD in the white women, was not significantly different from zero, but mean Z score at the lumbar spine was 0.6 (p < 0.001), 17.2% of the individual values being > 2.0. In normal white women (BMI < 27.3, n = 143), Z score was still > 2.0 in 10.3%, suggesting that the upper bound of the published reference interval may be too low. After adjustment for body mass index, BMD was greater in the forearm (9.8%), spine (8.7%), and femoral neck (14.7%) in black women (p < 0.001 at all sites). At L1, adjusted BMC in the black women was 37.4% greater than in the white women (p < 0.001). Serum calcidiol was significantly lower and serum PTH and calcitriol significantly higher in the black women. Despite this, biochemical markers of bone resorption and formation were significantly lower in the black women. We conclude that skeletally healthy older black women have a greater bone mass and lower rates of bone remodeling than a comparable group of white women. These data can serve as reference intervals for the variables measured.

Aged↗
PubMed1994

Comparison of radiographic absorptiometry with dual-energy x-ray absorptiometry and quantitative computed tomography in normal older white and black women.

Bone mineral density (BMD) of the phalanges of the hand was measured by the technique of radiographic absorptiometry (RA) in 199 older postmenopausal women previously determined to have normal BMD by dual-energy x-ray absorptiometry (DXA) and quantitative computed tomography (QCT). The average age of the women was 66.8 +/- 4.9 years, and they were 19.9 +/- 6.7 years postmenopause. In the 54 black women, phalangeal BMD was 11.7% greater than in the 145 white women, a difference comparable to that found using DXA at the radial midshaft, the lumbar spine, and femoral neck. A correlation matrix comparing BMD measured by RA to BMD measured by DXA and QCT indicates that, in general, RA was related to the various DXA and QCT measurement sites as well as these sites were related to each other. When results for RA, DXA, and QCT obtained in our cohort of older women were compared to available reference data for peak adult bone mass, the average difference (SD units) from peak value was greatest for RA (-1.77 radius, -1.24 spine, -2.13 femoral neck, -2.34 QCT spine, and -2.71 phalanges). We conclude that RA is an acceptable measure of phalangeal BMD and that the data in our cohort can serve as reference data for older white and black women aged 55-75 years. Once the ability of RA to predict future fracture occurrence has been demonstrated, it could be rapidly deployed as a low-cost, widely available bone mass measurement technique.

Absorptiometry, Photon↗
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↗