Biomedical subjects
Publications and source records attributed to B P Lukert.
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The effect of severe ascorbic acid deficiency on bone remodeling and collagen synthesis was evaluated in a 21 day experiment, using the scorbutic guinea pig model. Animals (n = 6-7/group) were assigned to one of three groups: scorbutic, pair-fed ascorbic acid-replete, or ad libitum ascorbic acid-replete groups. After 2 weeks, scorbutic animals started voluntarily decreasing food intake and losing weight. By day 19-21, at which time bone and tissue samples were collected and analyzed, scorbutic animals decreased food intake to 46% of usual and lost 9% body weight. Serum 25OHD3, 1,25(OH)2D3, calcium, and albumin were significantly lower (p < 0.05) in the scorbutic animals than in the other groups. Bone mineral density and bone mineral content of the proximal and central femur were significantly lower in the scorbutic group than in the other groups (p < 0.05). Morphometric analysis of tibia indicated significantly lower bone volume, fewer and thinner trabeculae, and a thinner growth plate in the scorbutic group, compared to the pair-fed and ad libitum groups (p < 0.05). Osteoclast surface was about 60% higher in the scorbutic group than in the pair-fed and ad libitum control groups (0.05 < p < 0.10). Mechanical strength of the femur and lumbar vertebral body tended to be lower when bone mass was altered in the same group. Collagen synthesis of articular cartilage and tendons was lower in the scorbutic group than in the pair-fed or ad libitum groups (p < 0.05). In conclusion, scurvy but not food restriction, per se, results in alterations in bone mass and tissue collagen synthesis.
The effect of long-term (1 y) low to excess ascorbic acid (AA) intake on bone mass was evaluated using guinea pigs that were 12-14 d old at the start of the experiment. Dietary AA was low (0.15 g/ kg diet) (n = 7), normal (0.50 g/kg) (n = 8) or excess (10 g/kg) (n = 8). After 12 mo, total body bone mineral density (BMD, mg/cm2) and bone mineral content (BMC, g) were determined by dual energy X-ray absorptiometry. Histomorphometric analysis of the cancellous bone of the proximal tibial metaphysis was completed after in vivo dual fluorochrome labeling. Total body BMD of the low AA group was 4.9% lower (P < 0.05), and total body BMC was 12.4% lower (P < 0.05) than in the normal AA group. Total body BMD and BMC were similar in normal and excess AA groups and in the low and excess AA groups. Histomorphometric analysis indicated significantly greater (P < 0.05) double-labeled bone surface, mineralizing surface, and bone formation rate in the low AA guinea pigs compared with the normal AA animals. Thus, there was greater bone turnover in the low AA group than in the normal AA guinea pigs. No differences in histomorphometric endpoints existed between the normal AA and excess AA groups. Long-term AA deficiency, during the period of rapid growth and slower phases of skeletal maturation, resulted in bone abnormalities in adult guinea pig skeletons. Long-term dietary AA excess caused no such abnormalities.
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Glucocorticoids are important in the management of rheumatic diseases. Bone loss is one of the most devastating side effects of glucocorticoids because they inhibit calcium transport, cause secondary hyperparathyroidism, hypogonadism, and impairment of osteoblast function. Efforts to control these side effects minimize bone loss.
OBJECTIVE: Because children with rheumatic disease receiving longterm corticosteroids are at high risk for developing osteoporosis, we attempted to determine whether nutritional supplementation would improve bone status in this group of children. METHODS: In a crossover design study, 10 corticosteroid treated children with rheumatic disease and osteoporosis received calcium and vitamin D supplementation for 6 months to determine their effect on bone density. They were then studied for 6 months without added nutrition supplements. The mean age was 13.1 years with a mean duration of disease of 4.2 years. Six patients had juvenile rheumatoid arthritis, 2 had systemic lupus erythematosus and 2 had mixed connective tissue disease. These children obtained a minimum of 1 g of calcium and 400 IU of vitamin D daily from diet and added supplements. Dual photon absorptiometry, laboratory and dietary data were obtained at baseline, 6 months, and one year. RESULTS: Spinal bone density significantly improved with supplementation. Osteocalcin values remained low throughout the study. CONCLUSION: Our results suggest some children with rheumatic disease receiving corticosteroids would benefit from calcium and vitamin D supplementation.
About 25% of U.S. women over age 50 will suffer one or more vertebral compression fractures related to osteoporosis. Vertebral fractures may be biconcave, anterior wedge, or crush deformities. A fracture is most often precipitated by putting a load on outstretched arms (eg, while raising a window). Back pain is usually incapacitating for a few weeks, then diminishes in severity but remains intense for 2 to 3 months. Acute complications include transient ileus, urinary retention, or (rarely) cord compression. Long-term effects include kyphosis, deconditioning, insomnia, and depression. Initial treatment includes bed rest, pain management with local and systemic analgesia, bracing to improve comfort, and patient reassurance. Long-term management includes spinal stretching exercises, walking, and treatment of underlying osteoporosis with calcitonin or estrogen in selected patients.
This is a retrospective study of 15 postmenopausal or amenorrheic women aged 34-78 years who had taken prednisone for 6-108 months and were followed for 1 year while continuing to take doses of 5-15 mg/day. A total of 8 patients were treated with 0.6256 mg Premarin daily for 25 days and 5 mg/day of medroxyprogesterone on days 15-25 (ERT, group 2); 7 were followed without ERT (group 1). A group of 17 women, matched for age, were randomly selected from our computerized data base to serve as a control group (group 3), and 10 women of similar age who were taking ERT only (group 4) were selected to compare the response to ERT to that of group 2. Bone density (BD) was measured in the lumbar spine baseline and at 1 year using dual-photon or dual-energy x-ray absorptiometry. Spine density did not change significantly during the year of observation in group 1. Although BD decreased in 5 of 7 patients, the change was not significant (-0.034 +/- 0.018 g/cm2, p = 0.10). In group 2 BD increased significantly, with 7 of 8 patients showing an increase (0.037 +/- 0.011 g/cm2, p = 0.008). BD did not change significantly in the control group (0.013 +/- 0.008 g/cm2, p = 0.16). Loss of bone from the spine was significantly greater in group 1 than in controls (p = 0.02), but changes in group 2 were similar to those in the control group (p = 0.66).(ABSTRACT TRUNCATED AT 250 WORDS)
The role consultants play in detecting disease coincidental to the reason for consultation is unclear. We sought to elucidate this function in the setting of a specialty clinic for osteoporosis. Making no specific attempt to screen for general conditions, we evaluated 760 women; any new diagnosis was found in the course of thoroughly examining the patient for osteoporosis. A total of 274 new diagnoses were counted, encompassing 68 conditions. There were 211 women (28%) in whom a new diagnosis was detected; a higher percentage of older women than younger women had a new diagnosis. A diagnosis severity grouping scheme was devised, groups C and D being those in which further evaluation was clearly indicated. The diagnoses in groups C and D accounted for 70% of all new diagnoses made, suggesting that trivial conditions were not overrepresented. The history and physical examination alone was responsible for 50% of the various conditions diagnosed and 64% of the total number of new diagnoses. The consultant has an excellent opportunity to detect disease while performing a specialty consultation.
The incidence of osteoporosis in patients receiving long-term glucocorticoid therapy is 30% to 50%. Trabecular bone is lost more rapidly than cortical. The cause of glucocorticoid-induced bone loss is multifactorial. Gastrointestinal absorption of calcium falls and urinary excretion rises, production of gonadal hormones decreases, and bone formation is inhibited in the presence of glucocorticoids. Bone loss can be minimized by using the lowest effective dose of a glucocorticoid with a short half-life, maintaining good nutritional status and physical activity, limiting sodium intake and giving a thiazide diuretic, maintaining serum 25-OHD at the upper limits of the normal range, giving estrogen replacement therapy to postmenopausal and amenorrheic women, and giving testosterone to men with low serum testosterone levels. The use of calcitonin or bisphosphonates should be considered.
PURPOSE: To review the clinical picture, pathogenesis, and management of glucocorticoid-induced osteoporosis. DATA IDENTIFICATION: Studies published since 1970 were identified from a MEDLINE search, articles accumulated by the authors, and through bibliographies of identified articles. STUDY SELECTION: Information for review was taken from 160 of the more than 200 articles examined. DATA EXTRACTION: Pertinent studies were selected; the relative strengths and weaknesses of these studies are discussed. RESULTS OF DATA SYNTHESIS: Studies in tissue and organ cultures suggest that glucocorticoids have a direct effect on bone, causing inhibition of bone formation and enhancing bone resorption. Glucocorticoids decrease calcium absorption from the intestine and increase renal excretion. Osteoporosis occurs in at least 50% of persons who require long-term glucocorticoid therapy. Long-term trials of therapy for the prevention of glucocorticoid-induced osteoporosis have not been done, but reasonable recommendations include the use of a glucocorticoid with a short half-life in the lowest dose possible, maintenance of physical activity, adequate calcium and vitamin D intake, sodium restriction and use of thiazide diuretics, and gonadal hormone replacement. In refractory cases, the use of calcitonin, bisphosphonates, sodium fluoride, or anabolic steroids should be considered. CONCLUSIONS: Osteoporosis is common in patients requiring long-term treatment with glucocorticoids. Careful attention to preventive management may minimize the severity of this serious complication.
A 59-year-old male presented with systemic mastocytosis with extensive skeletal involvement resulting in vertebral compression fractures and bone pain. Histomorphometric analysis of bone revealed increased mast cells, elevated static parameters of bone resorption, and low bone formation. Serum calcium, phosphorus, and alkaline phosphatase were normal; however, serum 1,25-dihydroxyvitamin D3 and osteocalcin levels were low. Histamine levels in plasma and urine were elevated. Following therapy with ketotifen, the patient had resolution of bone pain along with decreased flushing and pruritus. Elevated plasma and urine histamine levels normalized, as did 1,25-dihydroxyvitamin D3 and osteocalcin levels. Indices of low bone formation improved on therapy. Eroded surfaces improved but remained elevated. This case is the first demonstration that bone symptoms and histomorphometric change in systemic mastocytosis are reversed with inhibition of mast cell degranulation. The role of mast cells and their products in bone metabolism is poorly understood, but the therapy of bone disease in systemic mastocytosis should include inhibition of the release of mast cell products along with the use of histamine antagonist.
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Two women, ages 53 and 46, presented with multiple spontaneous vertebral fractures. Serum calcium, 25OHD, 1,25-(OH)2D, PTH, and 24-h urinary calcium were all normal. Bone mineral analysis (BMA) was performed at the junction of the distal third of the radius by single photon absorptiometry. BMA on Patient 1 was 0.68 g/cm2 and on Patient 2 was 0.58 g/cm2, with the normal being 0.70 g/cm2 and 0.77 g/cm2, respectively. In addition to vertebral fractures, x rays of Patient 2 revealed lytic lesions of the tibia and ulna. Bone biopsies revealed osteopenia associated with generalized eosinophilic fibromastocytosis and increased resorption without evidence of increased numbers of osteoclasts. There was no evidence of extraskeletal mast cell involvement. Our observations contribute to the increasing evidence that mast cells play a direct role in the etiology of osteoporosis in certain patients. Possible pathophysiologic mechanisms include mast cell release of heparin, histamine, prostaglandin D2 or other osteolytic substances.
Osteoporosis often occurs as a consequence of, or is accelerated by, many medical diseases, drug exposures, or other conditions. We called these conditions contributing diagnoses. Although technological advances permit the accurate measurement of bone density, identifying osteoporosis without searching for contributing diagnoses may result in remediable diseases being missed or in the initiation of inadvisable therapy. The value of comprehensive medical evaluation in conjunction with appropriate diagnostic studies was demonstrated in an osteoporosis referral center. We studied 300 consecutive persons who presented to an osteoporosis clinic. Using strict criteria, 180 patients (60%) had osteoporosis. Of these 180 patients, 83 (46%) had one or more contributing diagnosis, ie, a condition thought to accelerate bone loss. The largest single group was composed of persons with past or present exposure to glucocorticoids; the second largest group consisted of women who had undergone premature menopause. In all, 27 different contributing diagnoses were identified. Additionally, in 19 (11%) of the 180 patients with osteoporosis, a contributing diagnosis new to those patients was made. The evaluation of osteoporosis does not only entail measurement of bone density but must also take into consideration a patient's entire medical milieu.
A prospective study of thoracic and lumbar spinal fracture distribution and its relationship to thoracic kyphosis was performed in 87 women with osteoporosis. Anterior wedge fractures were most commonly seen in the midthoracic spine and about the thoracolumbar junction, whereas central compression fractures were most common from the first to the fourth lumbar levels. Solitary wedge fractures did not occur above the seventh thoracic vertebra, suggesting that a cause other than osteoporosis must be suspected in any patient with an isolated high thoracic fracture. Analysis of the spinal radiographs obtained in an additional 16 women without osteoporosis revealed that both forms of fracture were unusual in this small group with normal spinal mineralization. The number of anterior wedge fractures in the thoracic spine correlated (r = .546) with the degree of thoracic kyphosis. However, 19% of the women with no thoracic fractures still had thoracic hyperkyphosis. The authors conclude that the hyperkyphosis of osteoporotic women is related to anterior compression fractures but also has contributing nonskeletal factors.
UNLABELLED: The relationships between nutritional factors, calcium regulating hormones, and bone density were evaluated in three groups of normal subjects in rural southeast Kansas. Dietary intake of calcium (Ca), phosphorous (P), protein, and vitamin D; and serum 25OHD, Ca, P, parathyroid hormone (iPTH), and bone density (distal 1/3 radius) were measured in 29 elderly women, 35 elderly men, and 50 perimenopausal women. Measurements were repeated 5 years and 4 years later respectively in 16 elderly women and 15 elderly men. The r values for significant regression correlations for each group were as follows: perimenopausal: bone density and dietary Ca:P--r = .29, iPTH and 25OHD--r = -.38; elderly women: 25OHD and dietary Vitamin D(D)--r = .58, change in bone density (delta BD) and initial bone density (BDI)--r = -.71, delta BD and serum 25OHD--r = -.60, serum calcium and age--r = -.42; elderly men: Serum 25OHD and D--r = .61, iPTH and 25OHD--r = -.43, iPTH and serum phosphorous--r = .59. CONCLUSIONS: The more adequate the state of vitamin D nutriture, the lower the serum iPTH in perimenopausal women and elderly men and the less bone loss in elderly women. The Ca:P ratio in the diet may be important in maintaining bone density in perimenopausal women.