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Biomedical subjects

M Kleerekoper

Publications and source records attributed to M Kleerekoper.

At least 73 records · Page 4Linked to original sources

Hypophosphatemic rickets with hypocalciuria following long-term treatment with aluminum-containing antacid.

We present what we believe is the first case of rickets following prolonged treatment with aluminum containing antacids that bind phosphate, in an 18-year-old mentally retarded boy with cerebral palsy and spastic quadriplegia. As expected, serum calcitriol was increased and urinary phosphate excretion was very low. However, in contrast to all published cases of antacid induced hypophosphatemic osteomalacia in adults, despite a substantial increase in bone resorption reflected by urinary total hydroxyproline excretion, urinary calcium excretion was low rather than high, and significant hypocalcemia occurred after antacids were ceased and a phosphate salt administered. We suggest that the skeleton was so under-mineralized because of growth during prolonged phosphate deficiency, possibly augmented by anticonvulsant administration and immobilization, that increased bone resorption did not release enough calcium to cause hypercalciuria, or to prevent hypocalcemia during resumption of normal mineralization.

Adolescent↗

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↗

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↗

Measurement of vertebral area on spine x-rays in osteoporosis: reliability of digitizing techniques.

Much of the clinical research in osteoporosis is directed toward documenting a reduction in vertebral fracture rate, but there is considerable disagreement about defining and quantifying vertebral fractures. We have evaluated the technique of digitizing landmarks identified on lateral radiographs of thoracic and lumbar vertebrae and computing vertebral body area. Reduction in area indicates that fractures occurred. Radiographs from 10 patients with osteoporosis and vertebral fractures were obtained from each of two centers. Henry Ford Hospital (HFH) and Mayo Clinic (MC), and vertebral area for each individual in the complete set of 20 radiographs was calculated at each center. Measurements at the two centers differed by a multiplicative constant related to the method of recording landmarks on the radiographs that was estimated using 300 x-rays from HFH. After adjusting the MC areas for this multiplicative relationship, the average ratio of the HFH areas to the transformed MC areas of individual vertebrae (T4-L5) ranged from 0.98 to 1.06. The correlation between HFH and transformed MC areas for individual vertebrae averaged 0.85, with slopes between 0.87 and 1.00, intercept average -0.57. Within-patient rank correlation averaged 0.97. We conclude that radiographic digitization is a reliable and reproducible method of determining vertebral body dimensions that is suitable for evaluating radiographs obtained at different clinical sites and for comparison with normal data. This technique should prove useful for documenting the presence of a vertebral fracture that may not be readily apparent on visual inspection of radiographs and for monitoring serial changes in vertebral body dimensions in long-term epidemiologic and therapeutic studies.

Aged↗

Osteoporosis in men: diagnosis, pathophysiology, and prevention.

Osteoporosis in men is a significant problem in clinical medicine and in society in general. Systematic consideration of the differential diagnosis of osteopenia and osteoporosis in men is appropriate in every affected patient. Dynamic bone histomorphometry has diagnostic usefulness in some patients and has provided important pathogenetic implications by study of bone remodeling and turnover. Review of the multifactorial pathophysiology of age-related bone loss in men suggests that routine maintenance of adequate calcium and vitamin D intake, exercise, early recognition and treatment of testosterone deficiency, and modification of other osteoporotic risk factors may have prophylactic value. Future basic research on the cellular biology of bone in health and disease and clinical trials assessing the effects of long-term prophylactic and treatment regimens on bone mass and fracture occurrence will expand the understanding of osteoporosis in men.

Anabolic Agents↗

The direct examination of three-dimensional bone architecture in vitro by computed tomography.

We describe a new method for the direct examination of three-dimensional bone structure in vitro based on high-resolution computed tomography (CT). Unlike clinical CT, a three-dimensional reconstruction array is created directly, rather than a series of two-dimensional slices. All structural indices commonly determined from two-dimensional histologic sections can be obtained nondestructively from a large number of slices in each of three orthogonal directions. This permits a comprehensive description of structural variation within a specimen and greatly facilitates the study of structural anisotropy. A measure of three-dimensional connectivity (Euler number/tissue volume) has been determined for the first time in human cancellous bone and shown to correlate with several two-dimensional histomorphometric indices. The method has the potential for overcoming many of the limitations of current approaches to the study of bone architecture at the microscopic level.

Bone and Bones↗

Identification of women at risk for developing postmenopausal osteoporosis with vertebral fractures: role of history and single photon absorptiometry.

Putative risk factors for the development of postmenopausal osteoporosis (PMO) with vertebral fractures were examined in a retrospective study of 663 postmenopausal white females aged 45-75 years (266 women with non-traumatic vertebral compression fractures (VF+), 134 non-fractured women from a general medicine clinic (controls) and 263 non-fractured women who were evaluated when they presented specifically for osteoporosis screening (VF-]. The VF+ women differed from control women in several respects. The VF+ group reported a higher prevalence of a positive family history of osteoporosis, and a higher prevalence of a history of medical or surgical conditions known to be independently associated with metabolic bone disease, had fewer children, were smaller (weight, height) and were slightly older. The two groups, VF+ and controls, did not differ with respect to cigarette smoking, alcohol consumption, exercise habits, menstrual or menopausal history, dietary intake of milk and cheese or in amount taking calcium supplements during pregnancy. The VF+ group also differed in certain respects from the VF- group. The VF+ group were smaller (weight, height) and were older. The VF+ group had lower cortical bone mass (measured by single photon absorptiometry of the non-dominant forearm) than either the control or VF- groups. The latter two groups did not differ from each other with respect to this measurement. These markers demonstrated limited sensitivity and specificity as estimated from a confirmatory data set, particularly for the historical and anthropometric variables. We conclude that an assessment of the risk of developing PMO with vertebral fractures cannot be based on the putative risk factors as measured in our study, but must be based on measurement of bone mass.

Absorptiometry, Photon↗

Ulceroglandular tularemia: a typical case of relapse.

Tularemia is an infectious disease that continues to occur sporadically and in epidemics in the United States. It is characterized as an acute febrile illness with constitutional symptoms associated with skin, glandular, respiratory, or gastrointestinal involvement. Tularemia usually can be treated effectively with streptomycin. Relapse most often occurs when patients are treated with bacteriostatic agents such as chloramphenicol or tetracycline. We present a case of ulceroglandular tularemia distinguished by its relapse after initial streptomycin/doxycycline therapy and subsequent slow response to additional streptomycin.

Adult↗

Disorders of bone metabolism in severely handicapped children and young adults.

There is a high prevalence of vitamin D deficiency in the severely handicapped pediatric population. Because many of these patients have growth deficiencies, they may not demonstrate wide growth plates commonly seen with vitamin D deficiency. There is also a high prevalence of anticonvulsant use in these patients, and its exact impact is not clear because of the variety of its effects and presentations. Calcium, phosphate, and alkaline phosphatase are not useful as indicators of vitamin D deficiency, and vitamin D metabolites must be measured directly. Patients with low vitamin D levels respond to treatment, including nutritional support and added sunlight exposure. The overall nutritional status of this population may be reflected in their metabolic bone disease and small stature.

Adolescent↗

Mild asymptomatic primary hyperparathyroidism is not a risk factor for vertebral fractures.

STUDY OBJECTIVE: To determine the prevalence of vertebral fractures in patients with mild asymptomatic primary hyperparathyroidism and to ascertain whether this prevalence is increased in comparison with the rate in a retrospective control group previously studied at the same institution or with current estimates of the risk for vertebral fractures in subjects of similar age. DESIGN: Prospectively collected data were retrospectively analyzed and compared with data from a historical control group at the same institution and with published data. SETTING: The outpatient department of a bone and mineral metabolism clinic. PATIENTS: A consecutive series of patients with mild asymptomatic primary hyperparathyroidism diagnosed between 1 January 1976 and 31 December 1985. Criteria for inclusion in the study were the absence of symptoms due to hyperparathyroidism, no current kidney stone disease, no radiographic evidence of osteitis fibrosa, a serum calcium level of less than 3.00 mmol/L, a serum creatinine level of less than 133 mumol/L, and a forearm bone density value not more than 2.5 standard deviations below the age-, sex-, and race-adjusted normal value. INTERVENTIONS: A conservative nonintervention study. MEASUREMENTS AND MAIN RESULTS: The prevalence of vertebral fractures in 174 patients (mean age, 62 years) with mild asymptomatic primary hyperparathyroidism was 1.7%; in a subset of white women, the prevalence was 2.8%. These rates were not higher than those expected, by comparison with the rate in a retrospective control group or with the risk for vertebral fractures in subjects of similar age, and may even be lower. CONCLUSIONS: The risk for vertebral fractures is not increased in patients with mild asymptomatic primary hyperparathyroidism and is not a reason to recommend surgical intervention in asymptomatic patients. The increased rates of vertebral fractures that occurred in other series are probably due to the use of inappropriate controls and the influence of referral or selection bias, the inclusion of patients with severer disease, and the effect of geographic differences in vitamin D nutrition on the expression of disease. Possible differences between lateral spine and lateral chest radiographs for determining vertebral body shape need further study.

Aged↗

Lack of biochemical progression or continuation of accelerated bone loss in mild asymptomatic primary hyperparathyroidism: evidence for biphasic disease course.

We studied the natural history of primary hyperparathyroidism in patients in whom the disease was discovered fortuitously by multichannel biochemical screening and who were selected for conservative management because they were asymptomatic, had no renal stone disease or radiographic osteitis fibrosa, and had serum calcium values below 3.00 mmol/L, serum creatinine levels below 133 mumol/L, and forearm bone density not more than 2.5 SD below the mean expected for age, sex, and race. One hundred and seventy-four patients meeting these criteria were encountered during a 10-yr period, of whom 80 (mean age, 61 yr) had adequate follow-up; they did not differ significantly in any initial characteristic from the remaining 94 patients. These 80 patients were followed for 1-11 yr (mean, 46 months; median, 38 months), during which there was no change, mean or individual, in any index of PTH secretion or any of its biochemical effects and no decline in forearm bone density apart from that expected from increased age. There were 4 deaths from causes unrelated to hyperparathyroidism, and the overall death rate was not increased. The data suggest that no change occurred in either the number of parathyroid cells or secretory set-point, the 2 principal determinants of basal PTH secretion. This implies a biphasic course, with a short period of disease progression followed by a long period of disease stability. Our data support the decision to withhold surgical intervention in such patients, but to establish this as the correct policy for all asymptomatic patients will require a controlled clinical trial.

Aged↗

Bone mass, skin color and body size among black and white women.

We investigated the relationship between bone mass and two variables, skin color and body size, that may contribute to the higher prevalence of osteoporosis among white than among black populations. From a sample of 36 black and 99 white women were obtained measurements of height, weight, skin color (Photovolt 670 reflectometer) and radial bone mineral content (BMC) and bone width (BW) (single photon absorptiometry). There was no significant correlation between skin reflectance and age-adjusted BMC in either population. Multiple regression models of BMC and BMC/BW on age, weight/height and skin reflectance yielded significant correlations ranging from 0.62 to 0.77, but the partial coefficients for skin reflectance were not significant. BMC and age were negatively correlated in both groups, with a significantly steeper slope for the whites. Weight was positively correlated with BMC in both populations, but differences in weight did not explain the differences in bone mass between the blacks and whites.

Adult↗