Life Extension Final Clerance Sale


Table of Contents
image Calcium regulation of androgen receptor expression in the human prostate cancer cell line LNCaP
image The role of calcium, pH, and cell proliferation in the programmed (apoptotic) death of androgen-independent prostatic cancer cells induced by thapsigarin
image Programmed cell death as a new target for prostatic cancer therapy
image Hypercalcemia in carcinoma of the prostate: Case report and review of the literature
image Calcium excretion in metastatic prostatic carcinoma
image Chemoprevention of colorectal tumors: role of lactulose and of other agents.
image [Overview--suppression effect of essential trace elements on arteriosclerotic development and it's mechanism]
image Different effects of PTH on erythrocyte calcium influx
image Hypercalcemia due to constitutive activity of the parathyroid hormone (PTH)/PTH-related peptide receptor: Comparison with primary hyperparathyroidism
image Osteoclast cytomorphometry in patients with femoral neck fracture
image The PTH-calcium relationship curve in secondary hyperparathyroidism, an index of sensitivity and suppressibility of parathyroid glands
image Role of parathyroid hormone-related peptide (PTHrP) in hypercalcemia of malignancy and the development of osteolytic metastases
image Experimental study of glucocorticoid-induced rabbit osteoporosis
image 24,25 dihydroxyvitamin D supplementation corrects Intradialytic calcium balances with different calcium dialysate levels. Effects on cardiovascular stability and parathyroid function
image Biochemical effects of calcium and vitamin D supplementation in elderly, institutionalized, vitamin D-deficient patients
image Calcium, phosphate, vitamin D, and the parathyroid
image The BsmI vitamin D receptor restriction fragment length polymorphism (bb) influences the effect of calcium intake on bone mineral density
image Bone mineral density changes during lactation: Maternal, dietary, and biochemical correlates
image Postprandial parathyroid hormone response to four calcium-rich foodstuffs
image Complementary medical treatment for Colles' fracture: A comparative, randomized, longitudinal study
image Treatment of postmenopausal osteoporosis: Spoilt for choice? Part 1 - Foundations for an individually adapted management concept
image Calcium and vitamin D in the prevention and treatment of osteoporosis
image Calcium intake and fracture risk: Results from the study of osteoporotic fractures
image Bone loss and turnover after cardiac transplantation
image What's hip in diet and osteoporosis?
image A high dietary calcium intake is needed for a positive effect on bone density in Swedish postmenopausal women
image Amelioration of hemiplegia-associated osteopenia more than 4 years after stroke by 1alpha-hydroxyvitamin D3 and calcium supplementation
image The usefulness of bone turnover in predicting the response to transdermal estrogen therapy in postmenopausal osteoporosis
image Osteoporotic vertebral fractures in postmenopausal women
image Proteins and bone health
image Osteoporosis: Prevention, diagnosis, and management
image Connections between phospho-calcium metabolism and bone turnover. Epidemiologic study on osteoporosis (second part)
image Calcium regulation and bone mass loss after total gastrectomy in pigs
image Management of osteoporosis in the elderly
image Effect of measuring bone mineral density on calcium intake
image Osteoporosis: Its pediatric causes and prevention opportunities
image Estimated dietary calcium intake and food sources for adolescent females: 1980-92
image The pathogenesis of age-related osteoporotic fracture: Effects of dietary calcium deprivation
image Osteoporosis prevention and treatment. Pharmacological management and treatment implications
image Calcium metabolism in the elderly
image Therapy of osteoporosis: Calcium, vitamin D, and exercise
image Pathophysiology of osteoporosis
image Risk for osteoporosis in black women
image Age considerations in nutrient needs for bone health: Older adults
image Dietary calcium intake and its relation to bone mineral density in patients with inflammatory bowel disease
image Harmonization of clinical practice guidelines for the prevention and treatment of osteoporosis and osteopenia in Europe: A difficult challenge
image Clinical practice guidelines for the diagnosis and management of osteoporosis
image Current and potential future drug treatments for osteoporosis
image Calcium nutrition and osteoporosis
image Osteoporosis of Crohn's disease: A critical review
image The preparation and stability of compound active calcium tablets
image Immunosuppression: Tightrope walk between iatrogenic side effects and therapy
image Secondary osteoporosis in rheumatic diseases
image Does lactose intolerance predispose to low bone density? A population-based study of perimenopausal Finnish women
image Glucocorticoid-induced osteoporosis
image Current treatment options for osteoporosis
image Treatments for oestoporosis
image Estrogen replacement may be an alternative to parathyroid surgery for the treatment of osteoporosis in elderly postmenopausal women presenting with primary hyperparathyroidism: A preliminary report
image The effect of calcium supplementation and Tanner Stage on bone density, content and area in teenage women
image Osteoporosis
image Osteoporosis and calcium ingest
image Vitamin D and calcium in the prevention of corticosteroid induced osteoporosis: A 3 year followup
image Novelties and issues in the drug market 1995
image Influence of life style in the MEDOS study
image Roles of diet and physical activity in the prevention of osteoporosis
image The problem: Health impact of osteoporosis
image Prophylaxis of osteoporosis with calcium, estrogens and/or eelcatonin: Comparative longitudinal study of bone mass
image Nutritional prevention of aging osteoporosis
image Osteoporotic fractures: Background and prevention strategies
image Energy and nutrient intake in patients with CF
image Current and future nonhormonal approaches to the treatment of osteoporosis
image Transient osteoporosis of the hip. Case report and review of the literature
image Osteomalacia and osteoporosis in a woman with ankylosing spondylitis
image Calcium and vitamin D nutritional needs of elderly women
image Heated oyster shell-seaweed calcium (AAA Ca) on osteoporosis
image Calcium deficiency in fluoride-treated osteoporotic patients despite calcium supplementation
image Endocrinology
image Axial bone mass in older women
image Bone mineral density in mother-daughter pairs: Relations to lifetime exercise, lifetime milk consumption, and calcium supplements
image Reduced bone mass in women with premenstrual syndrome
image Calcium-regulating hormones across the menstrual cycle: Evidence of a secondary hyperparathyroidism in women with PMS
image Calcium supplementation in premenstrual syndrome: A randomized crossover trial
image Multiple sclerosis: vitamin D and calcium as environmental determinants of prevalence (a viewpoint). I.: Sunlight, dietary factors and epidemiology
image Calcium, phosphorus and magnesium intakes correlate with bone mineral content in postmenopausal women
image Effect of glucocorticoids and calcium intake on bone density and bone, liver and plasma minerals in guinea pigs
image Relationship between liver cirrhosis death rate and nutritional factors in 38 countries
image Prophylaxis of recurring urinary stones: hard or soft mineral water
image Prospective study of nutritional factors, blood pressure, and hypertension among US women.
image Association of macronutrients and energy intake with hypertension.
image Relations between magnesium, calcium, and plasma renin activity in black and white hypertensive patients
image Effect of renal perfusion pressure on excretion of calcium, magnesium, and phosphate in the rat.
image Nonpharmacologic treatment of hypertension.
image Micronutrient effects on blood pressure regulation.
image Role of magnesium and calcium in alcohol-induced hypertension and strokes as probed by in vivo television microscopy, digital image microscopy, optical spectroscopy, 31P-NMR, spectroscopy and a unique magnesium ion-selective electrode.
image Consequences of magnesium deficiency on the enhancement of stress reactions; preventive and therapeutic implications (a review).
image Effect of dietary magnesium supplementation on intralymphocytic free calcium and magnesium in stroke-prone spontaneously hypertensive rats.
image Impact of increasing calcium in the diet on nutrient consumption, plasma lipids, and lipoproteins in humans
image Electrolytes and hypertension: results from recent studies.
image Augmentation of the renal tubular dopaminergic activity by oral calcium supplementation in patients with essential hypertension.
image The pathogenesis of eclampsia: the 'magnesium ischaemia' hypothesis.
image Intracellular Mg2+, Ca2+, Na2+ and K+ in platelets and erythrocytes of essential hypertension patients: relation to blood pressure.
image A prospective study of nutritional factors and hypertension among US men
image Electrolytes in the epidemiology, pathophysiology, and treatment of hypertension.
image Minerals and blood pressure.
image The effect of Ca and Mg supplementation and the role of the opioidergic system on the development of DOCA-salt hypertension.
image Dietary modulators of blood pressure in hypertension
image Daily intake of macro and trace elements in the diet. 4. Sodium, potassium, calcium, and magnesium
image Calcium intake: covariates and confounders
image Nutrition and the elderly: a general overview.
image Blood pressure and nutrient intake in the United States.
image Serum calcium, magnesium, copper and zinc and risk of cardiovascular death.
image Endothelial function in deoxycorticosterone-NaCl hypertension: effect of calcium supplementation.
image Prevention of preeclampsia with calcium supplementation and its relation with the L-arginine:nitric oxide pathway.
image [Guidelines on treatment of hypertension in the elderly, 1995--a tentative plan for comprehensive research projects on aging and health-- Members of the Research Group for "Guidelines on Treatment of Hypertension in the Elderly", Comprehensive Research Projects on Aging and Health, the Ministry of Health and Welfare of Japan]
image Management of acute myocardial infarction in the elderly
image Supraventricular tachycardia after coronary artery bypass grafting surgery and fluid and electrolyte variables
image The effects of calcium channel blockers on blood fluidity.
image Concentrations of magnesium, calcium, potassium, and sodium in human heart muscle after acute myocardial infarction.
image Nutrient intake and food use in an Ojibwa-Cree community in Northern Ontario assessed by 24h dietary recall
image Mgsup 2sup +-Casup 2sup + interaction in contractility of vascular smooth muscle: Mgsup 2sup + versus organic calcium channel blockers on myogenic tone and agonist-induced responsiveness of blood vessels
image Antacids drugs: Multiple but too often unknown pharmacological properties
image Trace elements in prognosis of myocardial infarction and sudden coronary death
image Intakes of vitamins and minerals by pregnant women with selected clinical symptoms.
image [Amyotrophic lateral sclerosis--causative role of trace elements]
image Aluminum Deposition in Central Nervous System of Patients with Amyotrophic Lateral Sclerosis From the Kii Peninsula of Japan
image [Deficiency of certain trace elements in children with hyperactivity]
image Augmented Ca2+ in-flux is involved in the mechanism of enhanced proliferation of cultured vascular smooth muscle cells from spontaneously diabetic Goto-Kakizaki rats
image The central role of calcium in the pathogenesis of cardiovascular disease
image Dietary calcium, vitamin D, and the risk of colorectal cancer in Stockholm, Sweden
image Natural products and their derivatives as cancer chemopreventive agents
image New agents for cancer chemoprevention
image Frequently nebulized beta-agonists for asthma: effects on serum electrolytes.
image Effect of nebulized albuterol on serum potassium and cardiac rhythm in patients with asthma or chronic obstructive pulmonary disease.
image Long-term treatment with calcium-alpha-ketoglutarate corrects secondary hyperparathyroidism
image Oral vitamin D or calcium carbonate in the prevention of renal bone disease?
image Comparison of effects of calcitriol and calcium carbonate on secretion of interleukin-1beta and tumour necrosis factor-alpha by uraemic peripheral blood mononuclear cells
image Effect of dietary calcium on urinary oxalate excretion after oxalate loads
image The lack of influence of long-term potassium citrate and calcium citrate treatment in total body aluminum burden in patients with functioning kidneys


Calcium regulation of androgen receptor expression in the human prostate cancer cell line LNCaP

Endocrinology (USA), 1995, 136/5 (2172-2178)

Elevation of intracellular calcium levels in the presence of normal androgen levels has been implicated in apoptotic prostate cell death. Since the androgen receptor (AR) plays a critical role in the regulation of growth and differentiation of the prostate, it was of interest to determine whether Ca2+ would affect the expression of androgen receptor messenger RNA (mRNA) and protein, thus affecting the ability of androgens to control prostate function. AR-positive human prostate cancer cells, LNCaP, were incubated with either the calcium ionophore A23187 or the intracellular endoplasmic reticulum Ca2+-ATPase inhibitor thapsigargin. Subsequently, AR mRNA and protein levels were assessed by Northern and Western blot analysis. Both A23187 and thapsigargin were found to down-regulate steady state AR mRNA levels in a time- and dose-dependent manner. AR mRNA began to decrease after 6-8 h of incubation with 10-6 M A23187 or 10-7 M thapsigargin, reaching a nadir at 16 and 10 h of incubation, respectively. In contrast, control mRNA (glyceraldehyde 3-phosphate dehydrogenase) did not change significantly during the treatments with either A23187 or thapsigargin. AR protein levels were found to be decreased after 12 h of incubation with either 10-6 M A23187 or 10-7 M thapsigargin. The decrease in AR mRNA and protein seemed to precede apoptosis, since neither A23187 (24 h) nor thapsigargin (30 h) was found to alter cell morphology within the treatment time. Cycloheximide and actinomycin D were unable to change the calcium-mediated decrease in AR mRNA, ruling out the necessity for de novo protein synthesis or a change in mRNA stability. Moreover, the decrease in AR mRNA induced by calcium does not seem to involve protein kinase C- or calmodulin-dependent pathways, since inhibitors of these cellular components had no effect. Nuclear run-on assays demonstrated little or no effects of either A23187 or thapsigargin treatment on AR gene transcription (8 h and 10 h). In conclusion, these studies show that intracellular calcium seems to be a potent regulator of AR gene expression in LNCaP cells.

The role of calcium, pH, and cell proliferation in the programmed (apoptotic) death of androgen-independent prostatic cancer cells induced by thapsigarin

CANCER RES. (USA), 1994, 54/23 (6167-6175)

Calcium (Ca2+) accumulates within the endoplasmic reticulum of cells through function of the sarcoplasmic reticulum and endoplasmic reticulum Ca2+-dependent ATPase family of intracellular Ca2+-pumping ATPases. The resulting pools have important signaling functions. Thapsigargin (TG) is a sesquiterpene gamma-lactone which selectively inhibits the sarcoplasmic reticulum and endoplasmic reticulum Ca2+-dependent ATPase pumps with a 50% inhibitory concentration of approximately 30 microM. Treatment of androgen- independent prostate cancer cells of both rat and human origin with TG inhibits their endoplasmic reticulum Ca2+-dependent ATPase activity, resulting in a 3-4-fold elevation in the level of intracellular free Ca2+ (Ca(i)) within minutes of exposure. Due to a secondary influx of extracellular Ca2+, this increase in Ca(i) is sustained, resulting in morphological (cell rounding) and biochemical changes within 6-12 h (enhanced calmodulin, glucose regulated protein, and tissue transglutaminase expression, and decreased expression of the G(i) cyclins). Within 24 h of exposure, androgen-independent prostatic cancer cells stop progression through the cell cycle, arrest out of cycle in G0, and irreversibly lose their ability to proliferate with a median effective concentration value of 31 nM TG. During the next 24-48 h, the genomic DNA of the G0-arrested cells undergoes double-strand fragmentation. This is followed by the loss of plasma membrane integrity and fragmentation of the cell into apoptotic bodies. During this process, there is no acidification in the intracellular pH. Using cells transfected with the avian M(r) 28,000 calbindin D Ca2+-buffering protein, it was demonstrated that the programmed death initiated by TG is critically dependent upon an adequate (i.e., 3-4-fold) sustained (>1 h) elevation in Ca(i) and not depletion of the endoplasmic reticulum pools of Ca2+. These results demonstrate that TG induces programmed cell in androgen-independent prostatic cancer cells in a dose-dependent manner and that this death does not require proliferation or intracellular acidification but is critically dependent upon an adequate, sustained (i.e., >1 h) elevation in Ca(i).

Programmed cell death as a new target for prostatic cancer therapy

CANCER SURV. (USA), 1991, 11/- (265-277):

To increase survival of men with metastatic prostatic cancer, a modality that can effectively eliminate androgen independent cancer cells is desperately needed. By combining such an effective modality with androgen ablation, all of the heterogeneous populations of tumour cells within a prostatic cancer patient can be affected, thus optimizing the chances of cure. Unfortunately, such effective therapy for the androgen independent prostatic cancer cell is not yet available. This therapy will probably require two types of agents, one having antiproliferative activity affecting the small number of dividing androgen independent cells, and the other able to increase the low rate of cell death among the majority of non- proliferating (ie interphase) androgen independent prostatic cancer cells present. Androgen dependent prostatic epithelial cells can be made to undergo programmed death by means of androgen ablation, even if the cells are not in the proliferative cell cycle. Androgen independent prostatic cancer cells retain the major portion of this programmed cell death pathway, only there is a defect in the pathway such that it is no longer activated by androgen ablation. If the intracellular free Ca2+ is sustained at an elevated level for a sufficient time, androgen independent cells can be induced to undergo programmed death. The long term goal is therefore to develop some type of non-androgen ablative method that can be used in vivo to induce a sustained elevation in Ca2+ in androgen independent prostatic cancer cells. To accomplish this task, a more complete understanding of the biochemical pathways involved in programmed cell death is urgently needed. At present, studies are focusing on the mechanism involved in the Ca2+ elevation in the normal and malignant androgen dependent cell induced following androgen ablation and the role of the TRPM-2 protein in this process.

Hypercalcemia in carcinoma of the prostate: Case report and review of the literature

J. UROL. (BALTIMORE) (USA), 1987, 137/2 (309-311)

Hypercalcemia developed in a man with recurrent adenocarcinoma of the prostate. Serum calcium became normal soon after bilateral orchiectomy and the patient was free of disease 18 months later. The absence of radiographically detectable bone metastases in this patient suggested a humoral mechanism for the hypercalcemia. Orchiectomy may be an effective treatment for hypercalcemia complicating prostatic carcinoma.

Calcium excretion in metastatic prostatic carcinoma

BR. J. UROL. (ENGLAND), 1984, 56/6 (687-689)

In 64 men with prostatic carcinoma, calcium excretion per litre of glomerular filtrate (Ca(e)) was persistently lower in those with bone secondaries than in those with soft tissue involvement only, despite a normal range of serum calcium in both groups. In three patients who showed an improvement in their bony metastases on bone scan 6 months after starting treatment, the Ca(e) values had increased slightly but still remained in the low range. In a further five who showed no improvement on bone scan, Ca(e) values were lower than before. In patients with prostatic carcinoma, Ca(e) is an indicator of early changes in calcium homeostasis. It may also provide an objective indication of progression of bone secondaries.

Chemoprevention of colorectal tumors: role of lactulose and of other agents.

Ponz de Leon M; Roncucci L

Dept. of Internal Medicine, University of Modena, Italy.

Scand J Gastroenterol Suppl (NORWAY) 1997, 222 p72-5

Chemoprevention can be defined as an attempt at cancer control in which the occurrence of the disease is prevented by the administration of one (or more) chemical compounds. Main problems in chemoprevention studies are the choice of a suitable drug, the choice of an appropriate intermediate or definitive end point, and the definition of the population which should be investigated. Main classes of chemopreventive agents include vitamins, non-steroid antinflammatory drugs, minerals such as calcium or selenium, and other antioxidants such as N-acetylcysteine. Chemoprevention is particularly appealing in colorectal cancer, either because these lesions develop through a multistep process, or owing to the concept of "field carcinogenesis'. Between 1985 and 1990 we carried out a controlled study in which antioxidant vitamins or lactulose were used in an attempt to prevent the recurrence of colorectal polyps after their endoscopic removal. Among the 209 patients who could be evaluated, polyps recurred in 5.7% of the individuals who were given vitamins (A, C and E), 14.7% of patients given lactulose and 35.9% of untreated controls (chi 2 = 17.1, P < 0.001). The study suggested that either antioxidant vitamins or lactulose could be effective in reducing the recurrence rate of adenomatous polyps. In a subsequent on-going study, lower doses of the same vitamins were tested versus N-acetylcysteine (60a 40% reduction of the recurrence of polyps (ver sus controls) in individuals given N-acetylcysteine, while the effect of lower doses of vitamins was less appreciable. Definitive results of the study should be available by the end of 1998.

[Overview--suppression effect of essential trace elements on arteriosclerotic development and it's mechanism]

Saito N

Nippon Rinsho (JAPAN) Jan 1996, 54 (1) p59-66

It is known that the peroxidation of LDL is a trigger for developing arteriosclerosis. The oxidized LDL is produced by either oxidative stress or a few oxidant. Selenium decreased in serum and some organs of stroke-prone spontaneously hypertensive rats (SHRSP), which is a cofactor of glutamine peroxidase. Serum magnesium decreased in patients with diabetes mellitus, with ischemic heart disease, with essential hypertension and with cerebral vascular lesions. Calcium to magnesium ratio was higher in some organs of SHRSP as compared to Wistar Kyoto rats (WKY). These changes accelerated vascular lesions in SHRSP. (21 Refs.)

Different effects of PTH on erythrocyte calcium influx

Italian Journal of Mineral and Electrolyte Metabolism (Italy), 1996, 10/3-4 (149-152)

Since Ca ions mediate cellular response to parathyroid hormone (PTH), the effect of PTH on cell membrane Ca influx was studied by measuring erythrocyte passive Sr influx. Two different experiments have been performed: 1) Sr influx was determined in erythrocytes from 10 patients with primary hyperparathyroidism and 14 controls either in the absence and in the presence of nitrendipine, a dihydropiridine (DHP) Ca channel blocker; the results were compared in the two patient groups; 2) Sr influx was measured in erythrocytes from 4 normal subjects after incubation with and without PTH and the results in the presence of the hormone were compared with those in its absence. In the first experiment erythrocyte Sr influx was lower in patients with primary hyperparathyroidism when measured without nitrendipine (total Sr influx), but did not differ with controls when measured in presence of the inhibitor (DHP- independent Sr influx), Erythrocyte Sr uptake inhibited by nitrendipine (DHP- dependent Sr influx) was calculated by the difference between total and DHP- independent Sr influx values and was decreased in hyperparathyroid patients. In the second experiment Sr influx was increased after incubation of erythrocytes with PTH. We hypothesize that in primary hyperparathyroidism the high plasma levels of PTH may induce a downregulation of the erythrocyte Ca influx, mediated by the increase in cellular Ca content. These events may sustain the desensitization to physiological effects of PTH that has been reported in patients with primary hyperparathyroidism and after prolonged PTH infusion.

Hypercalcemia due to constitutive activity of the parathyroid hormone (PTH)/PTH-related peptide receptor: Comparison with primary hyperparathyroidism

Journal of Clinical Endocrinology and Metabolism (USA), 1996, 81/10 (3584-3588)

In Jansen's disease (JD), the hypercalcemia found in about half the cases is the result of a mutant, constitutively overactive, form of the PTH/PTHrP receptor, which in these cases also causes the skeletal dysplasia. The subject of the present report was first seen in 1956 and is still under treatment at the same medical center. We report the clinical course and a detailed study of calcium and bone metabolism carried out in 1976 and compare the results with those of six typical patients with mild primary hyperparathyroidism in whom exactly the same studies were carried out. In the patient with JD, the hypercalcemia was of early onset; chronic and nonprogressive; refractory to the administration of phosphate, glucocorticoid, and calcitonin; and accompanied by suppressed PTH levels as determined by two different immunoassays, an undetectable PTHrP level, increased excretion of nephrogenous cAMP (an in vivo bioassay of endogenous PTH production), decreased tubular reabsorption of phosphate, increased tubular reabsorption of calcium, increased biochemical indexes of bone turnover, and increased histological indexes of bone turnover on iliac bone histomorphometry after double tetracycline labeling. There was exaggerated loss of cortical bone and preservation of cancellous bone. All the results in JD relating to renal or skeletal effects of PTH excess were within or close to the ranges found in the hyperparathyroid patients, except that tubular reabsorption of phosphate was more depressed. Because PTH secretion was suppressed, any effects mediated by putative alternative receptors would have been diminished. We conclude that 1) the hypercalcemia due to constitutive overactivity of the PTH/PTHrP receptor is indistinguishable from that of mild primary hyperparathyroidism in clinical characteristics and renal tubular and skeletal features; and 2) the classic laboratory manifestations of primary hyperparathyroidism, with the possible exception of osteitis fibrosa cystica, can all be accounted for by overactivity of a single receptor.

Osteoclast cytomorphometry in patients with femoral neck fracture

Pathology Research and Practice (Germany), 1996, 192/6 (573-578)

In patients with femoral neck fracture, nutritional deficiencies have been shown to be common. A low calcium diet and/or a reduced vitamin D intake have been suspected to cause secondary hyperparathyroidism responsible for increased bone turn over and bone loss. Parathyroid hormone (PTH) levels are increased in these patients, data which are in accordance with the pronounced changes observed on bone biopsies reflecting a true hyperparathyroidism. We have used a cytomorphometrical approach to characterize PTH-induced changes on the osteoclastic population. Osteoclasts were detected histochemically (by tartrate resistant acid phosphatase staining) on bone biopsies from 10 control subjects, 8 patients with primary hyperparathyroidism and 10 patients with a femoral neck fracture of osteoporotic origin. The maximum Feret's diameter of each osteoclast (Oc.Le) was determined with a semiautomatic image analyzer. In all groups, the frequency distribution of Oc.Le appeared positively skewed. In both hip fractured patients and primary hyperparathyroid patients, the mode of the distribution was higher (25-30 microm) than in controls (20-25 microm). When graphically converted on a probability graph, the osteoclastic populations appeared homogeneous and well described by a lognormal distribution in the three groups. However osteoclasts appeared similarly enlarged in the groups of patients with primary hyperparathyroidism and with femoral neck fracture. PTH has been shown to increase both the recruitment of mononucleated precursors and their fusion into larger osteoclasts than controls. In the present study, a cytomorphometric method appeared able to identify the border line hyperparathyroidism in the hip fractured patients.

The PTH-calcium relationship curve in secondary hyperparathyroidism, an index of sensitivity and suppressibility of parathyroid glands

Nephrology Dialysis Transplantation (United Kingdom), 1996, 11/SUPPL. 3 (136-141)

A sigmoidal relationship, fitting a four-parameter model, has been demonstrated in in who and in vitro studies to link the parathyroid hormone (PTH) secretion rate and calcium concentration changes. In uraemic patients different patterns of calcium-mediated PTH secretion were reported in different types of renal bone diseases and a shift to the right and a steeper slope has been observed in secondary hyperparathyroidism. To gain more information that could predict indexes for successful medical therapy we investigated the calcium-PTH sigmoidal relationship in 42 hyperparathyroid patients with different degrees of secondary hyperparathyroidism; we classified as moderate those patients presenting basal PTH (PTH(bas)) < 600 pg/ml and bone alkaline phosphatase (AP)< 500 U/l, and severe those with a PTH(bas) less than or equal to 600 pg/ml and bone AP less than or equal to 500 U/l. Changes in ionized calcium (iCa) were induced by calcium-free dialysis on the first day, to induce hypocalcaemia up to serum iCa 3.5 mEq/l, and calcium 8 mEq/l dialysis on the third day, to induce hypercalcaemia. The moderate hyperparathyroidism patients had PTH(max), PTH(min) and slope, calculated in absolute values and relative values, lower than severe hyperparathyroidism patients but they did not differ in the minimal to maximal PTH ratio. In the moderate group the PTH(bas) correlated with all the curve parameters except PTH(min), calculated both in absolute and percentage values, while in the severe group PTH(min) was the only parameter correlating to the PTH(bas). In conclusion, by performing the dynamic test, we found that some glands were not suppressible among moderate hyperparathyroidism patients.

Role of parathyroid hormone-related peptide (PTHrP) in hypercalcemia of malignancy and the development of osteolytic metastases

Journal of Clinical Rheumatology (USA), 1997, 3/2 SUPPL. (S109-S113)

Hypercalcemia of malignancy carries an extremely grim prognosis. The most common mechanism underlying hypercalcemia of malignancy is production by the tumor cells of cytokines responsible for osteoclastic differentiation and, therefore, lysis of the bone adjacent to the tumor. A minority of cases are attributable to increased renal reabsorption of calcium caused by a humoral factor, termed parathyroid hormone-related peptide, which is produced by some primary tumors. These two mechanisms can be involved in conjunction, particularly in patients with breast cancer. The development of osteolytic metastases initiates a vicious cycle in which bone degradation products, especially growth factors, stimulate the growth of the tumor cells located at the bone-tumor interface. Parathyroid hormone-related peptide is produced by many malignant tumors, most notably those of the breast. In addition to its endocrine effect on the kidney, it may have a paracrine effect consisting of enhancement of osteoclastic differentiation with osteolysis of the bone adjacent to the tumor. Other factors produced by primary tumor cells, such as proteases, intercellular adhesion molecules, or bone matrix proteins, may influence the propensity for the tumor to produce bone metastases. Bisphosphonates are usually effective in inducing a remission of hypercalcemia of malignancy and in improving the clinical manifestations of osteolytic metastases. Elucidation of the factors that influence the propensity for malignancies to metastasize to bone would improve our ability to use bisphosphonates optimally as adjuncts to tumor therapy.

Experimental study of glucocorticoid-induced rabbit osteoporosis

Chinese Pharmacological Bulletin (China), 1996, 12/6 (540-542)

To study the effect of variant administration and cumulative dose of glucocorticoid on the skeleton, thirty male rabbits were divided into 5 groups, serum calcium, phosphorus, alkaline phosphatase and N-terminal fragment of parathyroid hormone (PTH) and bone mineral content (BMC) were determined, The results showed no significant differences were observed between supplement calcium group and control group at the level of BMC and PTH (P > 0.05), but there were significantly decreased BMC and elevated PTH in other groups (P < 0.01), especially in the high-dose group. The results indicated that glucocorticoid-induced osteoporosis is associated with the steroid dose, and the pathogenesis is concerned with the development of secondary hyperparathyroidism. Alternate-day therapy can't prevent bone loss. Supplementation of calcium and vitamin D is an effective method for the prevention and treatment.

24,25 dihydroxyvitamin D supplementation corrects Intradialytic calcium balances with different calcium dialysate levels. Effects on cardiovascular stability and parathyroid function

Nephron (Switzerland), 1996, 72/4 (530-535)

It has been shown that calcium carbonate (CaCO3) is an effective phosphate binder which is less toxic than Al(OH)3. However, given that its use with standard calcium dialysate (CaD) levels may lead to hypercalcemia, a decrease in CaD levels has been proposed. The aim of the present study was to evaluate the acute clinical and biochemical consequences of a lowering of CaD in HD patients. Dialysate composition was otherwise the same. (1) Blood pressure levels (BP) during short hemodialysis were measured in a group of 12 patients who underwent alternate hemodialyses with dialysate calcium of 1.75 and 1.25 mmol/l. (2) Ca2+ and PTH kinetics during short hemodialysis were studied in a group of 6 patients who were sequentially treated with 1.75 and 1.25 mmol/l CaD. The results show: (1) that cardiovascular stability in chronic HD patients during short HD sessions with low CaD (LCaD) may be good; (2) that a single treatment with standard CaD (SCaD) produces positive calcium balances (JCa2+) with Ca2+ plasma increase and PTHi inhibition at the end of HD sessions; during HD with LCaD there were neutral mean JCa2+ and no changes in post-dialysis mean Ca2+ and PTHi plasma levels; furthermore 2 patients showed a small PTHi increase during HD with LCaD and neutral JCa2+ because of a high positive bicarbonate balance during HD. In conclusion, as with several aspects of dialysis treatment, dialysate calcium levels should also be individualized to avoid hypercalcemic crises or PTHi stimulation.

Biochemical effects of calcium and vitamin D supplementation in elderly, institutionalized, vitamin D-deficient patients

Revue du Rhumatisme (English Edition) (France), 1996, 63/2 (135-140)

Forty-five subjects (41 women and 4 men) in long-stay and medium-stay facilities, aged 74 to 95 years (mean 86.4 years), with 25-hydroxy-vitamin D levels less than 12 ng/ml, were treated for six consecutive months with two tablets per day of a preparation containing vitamin D3 (800 IU/day) and calcium carbonate (1 g elemental calcium/day). Serum levels of 25-hydroxy-vitamin D were very low at baseline (5.6 plus or minus 0.4 ng/ml) and rose significantly under treatment, to normal values, 33.2 plus or minus 1.2 and 40.9 plus or minus 2.1 ng/ml after three and six months, respectively (p < 0.001 for both comparisons). Serum calcium increased significantly, by 4.5% (p < 0.001) during the first three months, and remained at a plateau thereafter. Corrected serum calcium rose by 8.9% (p < 0.001) during the trial. No patient developed hypercalcemia. Serum parathyroid hormone levels, which were elevated at baseline (71.6 plus or minus 5.8 pg/ml; normal, 12 to 54 pg/ml), decreased gradually and significantly throughout the treatment period, by 43.0% and 67.1% after three and six months, respectively (p < 0.001 for both comparisons). Serum alkaline phosphatase activity fell concomitantly, by 9.9% after three months (p < 0.01) and 36.5% after six months (p < 0.001). In conclusion, the preparation used in our study is effective in correcting both the vitamin D deficiency that is prevalent in elderly institutionalized patients and the resultant increase in bone turnover.

Calcium, phosphate, vitamin D, and the parathyroid

Pediatric Nephrology (Germany), 1996, 10/3 (364-367)

The main factors which regulate parathyroid hormone (PTH) production are calcium, phosphate, vitamin D, and estrogens. Hypocalcemia leads to increased PTH secretion in seconds and minutes, gene expression in hours, and parathyroid (PT) cell number in weeks and months. Hypercalcemia leads to a decrease in PTH secretion by its action on the PT cell calcium receptor and no decrease in PTH mRNA levels. There is now convincing evidence that phosphate regulates the PT, independent of its effect on serum calcium and 1,25-dihydroxyvitamin D3 (1,25(OH)2D3). In vivo in rats hypophosphatemia markedly decreases PTH mRNA and serum intact PTH levels, independent of its effect on serum calcium and 1,25(OH)2D3. Clinical studies also indicate that phosphate regulates the PT independent of its effect on calcium and 1,25(OH)2D3; 1,25(OH)2D3 itself has a marked effect on the PT, where it decreases PTH gene transcription by a direct action on the PT. The application of basic science findings of how calcium, phosphate, and 1,25(OH)2D3 regulate the PT has led to an efficient and safe prescription for the management of the secondary hyperparathyroidism of chronic renal failure, which is the maintenance of a normal serum calcium and phosphate and the careful use of 1,25(OH)2D3.

The BsmI vitamin D receptor restriction fragment length polymorphism (bb) influences the effect of calcium intake on bone mineral density

Journal of Bone and Mineral Research (USA), 1997, 12/7 (1049-1057)

Previous studies of the vitamin D receptor (VDR) polymorphisms and bone mineral density (BMD) have suggested that there may be differences in calcium absorption among groups of women with different VDR genotypes, and that the association may be stronger in younger women. To investigate the association between the VDR polymorphisms and BMD, this study was undertaken in the Framingham Study Cohort and a group of younger volunteers. Subjects from the Framingham Study (ages 69-90 years) included those who underwent BMD testing and who had genotyping for the VDR alleles (n = 328) using polymerase chain reaction methods and restriction fragment length polymorphisms with BsmI (B absence, b presence of cut site). A group of younger volunteer subjects (ages 18-68) also underwent BMD testing and VDR genotyping (n = 94). In Framingham Cohort subjects with the bb genotype, but not the Bb or BB genotypes, there were significant associations between calcium intake and BMD at five of six skeletal sites, such that BMD was 7-12% higher in those with dietary calcium intakes greater than 800 mg/day compared with those with intakes <500 mg/day. The data also suggested that BMD was higher in persons with the bb genotype only in the group with calcium intakes above 800 mg/day. No significant differences were found in the Framingham Cohort for age-, sex-, and weight-adjusted BMD at any skeletal site between those with the BB genotype and those with the bb genotype regardless of 25-hydroxyvitamin D levels or country of origin. In the younger volunteers, BMD of the femoral neck was 5.4% higher (p < 0.05) in the bb genotype group compared with the BB group and 11% higher (p < 0.05) in males with the bb genotype compared with the BB group. There were no significant differences at the lumbar spine. In this study, the association between calcium intake and BMD appeared to be dependent upon VDR genotype. The finding of an association between dietary calcium intake and BMD only in the bb genotype group suggests that the VDR genotype may play a role in the absorption of dietary calcium. Studies that do not consider calcium intake may not detect associations between VDR genotype and BMD. In addition, the association between VDR alleles and BMD may become less evident in older subjects.

Bone mineral density changes during lactation: Maternal, dietary, and biochemical correlates

American Journal of Clinical Nutrition (USA), 1997, 65/6 (1738-1746)

The objectives of this study were to characterize the effects of lactation and weaning on maternal bone mineral density (BMD) and on biochemical markers of bone turnover, and to determine the effects of dietary intake,milk output,and other maternal factors on changes in BMD. Twenty-six fully lactating and eight nonlactating women were followed longitudinally through 7 me postpartum; the lactating women were followed through postweaning. Maternal dietary and supplement intake data, infant milk intake measurements, blood and urine samples, and midradius and L2-L4 vertebral BMD measurements were obtained 0.5, 3, 5, and 7 mo postpartum. Biochemical analyses included measurements of calciotropic hormones, 24-h urinary excretion of calcium, markers of bone formation and resorption, estradiol, and prolactin. Estimated maternal demands for calcium excretion in milk were met by a combination of high calcium intake (from diet and supplements, 1500 plus or minus 460 mg/d at 0.5 mo for lactating women) and a decline of similar4% in vertebral BMD between 0.5 and 3 mo postpartum. Postweaning BMD (n = 15) at this site approximated initial values. Two factors were positively associated with vertebral BMD, estradiol (P < 0.001) and calcium intake (P = 0.03), whereas two factors were negatively associated, parity (P = 0.03) and protein intake (P = 0.01). In these well- nourished women, the results suggest that the extent of bone loss associated with lactation and its recovery postweaning are negatively influenced by parity. The results also suggest that the bone loss may be attenuated by a generous dietary ratio of calcium to protein.

Postprandial parathyroid hormone response to four calcium-rich foodstuffs

American Journal of Clinical Nutrition (USA), 1997, 65/6 (1726-1730)

We studied the effects of four calcium-rich foodstuffs on postprandial parathyroid hormone secretion. Four hundred milligrams calcium from either Emmental cheese, milk, sesame seeds, spinach, or calcium salt (calcium lactate gluconate + calcium carbonate) or no additional calcium (control session) were given to nine female volunteers immediately after a first blood sample (at 0900) in random order with a light standardized meal containing 37 mg Ca. Blood samples were taken at 0900 (before the calcium load), 1000, 1100, 1300, and 1500 at every study session. Urine was collected during the sessions. Serum ionized calcium, phosphate, magnesium, intact parathyroid hormone, and urinary calcium excretion were measured. The serum ionized calcium concentration increased significantly after ingesting cheese (P=0.004, contrast analysis) or calcium salt (P=0.05, contrast analysis) compared with the control session. Compared with the control session, the serum phosphate concentration increased after the cheese session (P=0.004, contrast analysis) and after the milk session (P=0.02, contrast analysis). Calcium salt (P=0.007, contrast analysis) and cheese (P=0.002, contrast analysis) caused a significant decline in serum intact parathyroid hormone compared with the control session. The urinary calcium excretion with cheese was 141% (P=0.001), with milk was 107% (P=0.004), and with calcium salt was 75% (P= 0.02) above that of the control session. Our results show that calcium from sesame seeds and spinach does not cause an acute response in calcium metabolism. Our results indicate that fermented cheese could be a better dietary source of calcium than milk when the metabolic effects of the foodstuffs are considered.

Complementary medical treatment for Colles' fracture: A comparative, randomized, longitudinal study

Calcified Tissue International (USA), 1997, 60/6 (567-570)

In 45 women with Colles' fracture, two types of complementary medical treatment (calcitonin with calcium (SCT+Ca) and calcium alone (Ca)) were compared with placebo. Consecutive patients were assigned randomly to one of the three study groups at the time of inclusion in the study: 15 women (68.6 +/- 5.7 years) were given 100IU/day IM of SCT plus 1200 mg of elemental Ca for 10 successive days each month; 15 women (71.7 +/- 6.1 years) were given only 1200 mg of elemental Ca for 10 days each month; and 15 women (66.9 +/-7.9 years) were treated with placebo. Biochemical and radiogrammetric studies were made at baseline and after 1 year of treatment. In the SCT+Ca group tartrate-resistant acid phosphatase decreased (Wilcoxon test, P =0.014) and the metacarpal index and the cortical and total area (CA/TA) ratio increased (both P =0.001). In the group treated with Ca alone, no changes were observed. In the placebo group, the metacarpal index and CA/TA decreased (P = 0.015 and P = 0.007, respectively). Ca alone, at the dosage used here, inhibited bone loss after Colles' fracture. The addition of SCT to Ca administration not only impeded bone loss but significantly increased cortical bone mass.

Treatment of postmenopausal osteoporosis: Spoilt for choice? Part 1 - Foundations for an individually adapted management concept

Munchener Medizinische Wochenschrift (Germany), 1997, 139/20 (33-34+37-38)

The number of agents for the treatment of osteoporosis has increased over the past few years allowing more and more differentiated therapy. Concerning the specific indications of vitamin D metabolites and bisphosphonates, up to now there is only little therapeutic experience in Germany. Furthermore, osteoporosis per se is not a homogeneous nosological entity. Primary and secondary forms must be distinguished. These are further modified by age, sex, accompanying diseases, risk factors, and life style, leading to individually different manifestations. Therefore, today the therapeutic strategy should be adapted to the individual case. Calcium and vitamin D supplementation and avoidance of risk factors can be recommended as a basic treatment for all forms of osteoporosis. Anti-resorption therapy with hormone replacement or bisphosphonates should be considered in younger postmenopausal women with assumed or proved high bone turnover. In accordance with the existing international literature, this therapy may also be used in elderly women, but in cases with advanced osteopenia of the spine, fluoride/calcium therapy with the aim of continuously increasing bone mass may be preferable. The latter may be also combined with hormone replacement therapy. Further aspects of individually adapted therapeutic regimens will be explained on the basis of individual case reports (cf. part 2).

Calcium and vitamin D in the prevention and treatment of osteoporosis

Journal of Clinical Rheumatology (USA), 1997, 3/2 SUPPL. (S52-S56)

An increasing prevalence of calcium and/or vitamin Ddeficiency in the general population (especially, but not only, in elderly subjects) has been emphasized in recent epidemiologic studies. These deficiencies could be responsible for accelerated bone loss mediated by secondary hyperparathyroidism and increased bone turnover and could explain the dramatic increase of the incidence of osteoporotic fractures with age. High calcium intake in prepubertal girls seems to be associated with higher peak bone mass in late adolescence. Calcium supplementation could slow bone turnover and bone loss in particular subsets of patients, including calcium- deficient postmenopausal women and elderly patients. A specific antifracture effect of calcium supplementation in postmenopausal osteoporotic patients has not been established, but a calcium-plus-low-dose-vitamin D3 supplementation has been suggested to decrease the peripheral fracture incidence (especially hip fracture) in elderly institutionalized women. After a critical review of these data, some practical recommendations are suggested.

Calcium intake and fracture risk: Results from the study of osteoporotic fractures

American Journal of Epidemiology (USA), 1997, 145/10 (926-934)

The relation between dietary calcium, calcium, and vitamin D supplements and the risk of fractures of the hip (n = 332), ankle (n = 210), proximal humerus (n = 241), wrist (n = 467), and vertebrae (n = 389) was investigated in a cohort study involving 9,704 US white women aged 65 years or older. Baseline assessments took place in 1986-1988 in four US metropolitan areas. Dietary calcium intake was assessed at baseline with a validated food frequency questionnaire. Data on new nonvertebral fractures were collected every 4 months during a mean of 6.6 years of follow-up; identification of new vertebral fractures was based on comparison of baseline and follow-up radiographs of the spine done a mean of 3.7 years apart. Results were adjusted for numerous potential confounders, including weight, physical activity, estrogen use, protein intake, and history of falls, osteoporosis, and fractures. There were no important associations between dietary calcium intake and the risk of any of the fractures studied. Current use of calcium supplements was associated with increased risk of hip (relative risk = 1.5, 95% confidence interval 1.1-2.0) and vertebral (relative risk = 1.4, 95% confidence interval 1.1-1.9) fractures; current use of Tums antacid tablets was associated with increased risk of fractures of the proximal humerus (relative risk = 1.7, 95% confidence interval 1.3-2.4). There was no evidence of a protective effect of vitamin D supplements. Although a true adverse effect of calcium supplements on fracture risk cannot be ruled out, it is more likely that our findings are due to inadequately controlled confounding by indications for use of supplements. In conclusion, this study did not find a substantial beneficial effect of calcium on fracture risk.

Bone loss and turnover after cardiac transplantation

Journal of Clinical Endocrinology and Metabolism (USA), 1997, 82/5 (1497-1506)

Cardiac transplantation is associated with increased prevalence and incidence of fracture, and rapid bone loss has been reported during the first rat posttransplant year. To define further the pattern and etiology of bone loss after cardiac transplantation, we enrolled 70 patients (52 men and 18 women) in a prospective 3-yr study. Bone densitometry (BMD) and biochemical indexes of mineral metabolism were performed before and at defined times after transplantation. Despite supplementation with elemental calcium (1000 mg/day) and vitamin D (400 IU/day), the mean rate of bone loss during the first year was 7.3 plus or minus 0.9% (plus or minusSEM) at the lumbar spine and 10.5 plus or minus 1.1% at the femoral neck. The rate of bone loss slowed (P < 0.001 compared to year 1) at both sites (0.9 plus or minus 0.9% and 0.1 plus or minus 1.0%, respectively) during the second year. During the third year, lumbar spine BMD increased at a rate of 2.4 plus or minus 0.8%/yr (P < 0.02 compared to year 2), but femoral neck BMD did not change. At the radius, the rate of decline in BMD was negligible during the first year (0.9 plus or minus 0.5%), but was significant during the second (2.1 plus or minus 0.6%; P < 0.01) and third (2.9 plus or minus 0.8%; P < 0.03) years. Evaluation of the pattern of bone loss during the first year demonstrated that mean lumbar spine BMD decreased rapidly during the first 6 months, after which there was no further decline. In contrast, femoral neck BMD continued to fall at an annualized rate of 8.2 plus or minus 1.3% during the second half of the year. The pattern and rates of bone loss were similar in men and women. Biochemistries revealed decreases in serum testosterone and osteocalcin and increases in all bone resorption markers 1 and 3 months after transplantation, with a return to baseline by 6 months. Higher rates of bone loss were associated with greater exposure to prednisone, lower serum concentrations of vitamin D metabolites, greater suppression of osteocalcin, higher levels of bone resortion markers, and, in men, lower serum testosterone concentrations. We conclude that rapid bone loss is primarily confined to the initial year after transplantation. During the first 6 months, bone loss is accompanied by alterations in markers of bone turnover consistent with biochemical uncoupling of bone formation and resorption. Greater exposure to glucocorticoids, lower serum concentrations of vitamin D metabolites and testosterone, and higher bone turnover were associated with more rapid bone loss.

What's hip in diet and osteoporosis?

Scandinavian Journal of Nutrition/Naringsforskning (Sweden), 1997, 41/1 (2-8+12)

Many nutritional causes of osteoporosis have been suggested, but the one that has been and that is still most debated is the possible role of a low calcium intake. In our analysis of published papers we have found convincing evidence, mostly from several clinical trials completed in the last few years, that an increase in the current Nordic calcium recommendations for postmenopausal women should lead to decreased bone loss among these women in the future, although the effect is probably modest. We therefore recommend a calcium intake level above 1,200 mg/day for women over the age of 50 years. We have also found compelling evidence of a need for vitamin D supplementation among elderly individuals not regularly spending time out of doors. Further research in the area of diet and osteoporosis is strongly needed.

A high dietary calcium intake is needed for a positive effect on bone density in Swedish postmenopausal women

Osteoporosis International (United Kingdom), 1997, 7/2 (155-161)

The importance of dietary calcium for bone health is unclear, partly since most investigations have dealt only with a fairly narrow range of calcium intake. In the present population-based observational study with longitudinal dietary assessment, we investigated women with a mean age of 60 years and with a consistently high (range 1417-2417, mean 1645 mg, n = 40), intermediate (80-1200, mean 1006 mg, n = 35) or low (400-550, mean 465 mg, n = 40) estimated daily consumption of calcium. Measurements of bone mineral density (BMD) of the lumbar spine, femoral neck and total body were performed by dual-energy X-ray absorptiometry, as well as ultrasound of the heel. In a multivariate analysis, with adjustment for energy intake the risk factors for osteoporosis (age, body mass index, physical activity, menopausal age, use of estrogens, smoking and former athletic activity), the group with the highest calcium intake had higher values for BMD than the others at all measured sites. The average mean difference compared with the low and the intermediate calcium group was 11% for the femoral neck, 8-11% for the lumbar spine and 5-6% for total body BMDs. In univariate analyses and multivariate models which did not include energy intake, the differences between the groups were less pronounced. The women in the intermediate calcium group had approximately the same mean BMD values as those in the low calcium group. These findings support the view that only a high calcium intake (3% highest percentiles in the studied population) protects against osteoporosis in Swedish postmenopausal women.

Amelioration of hemiplegia-associated osteopenia more than 4 years after stroke by 1alpha-hydroxyvitamin D3 and calcium supplementation

Stroke (USA), 1997, 28/4 (736-739)

Background and Purpose: It has been demonstrated that bone mass was significantly reduced on the hemiplegic side of stroke patients, which might increase their risk of hip fracture. We evaluated the efficacy of 1alpha- hydroxyvitamin D3 (1alpha(OH)D3) and supplemental elemental calcium in maintaining bone mass and decreasing the incidence of hip fractures after hemiplegic stroke. Methods: In a randomized study, 64 patients with hemiplegia after stroke with a mean duration of illness of 4.8 years received either 1 microg 1alpha(OH)D3 daily (treatment group, n=30) or an inactive placebo (placebo group, n=34) for 6 months and were observed for this duration. Both groups received 300 mg of elemental calcium daily. The bone mineral density (BMD) and metacarpal index (MCI) in the second metacarpals were determined by computed x-ray densitometry. The incidence of hip fractures in these patients was recorded. Results: BMD on the hemiplegic side decreased by 2.4% in the treatment group and 8.9% in the placebo group (P=.0021), while BMD on the intact side increased by 3.5% and decreased by 6.3% in the treated and placebo groups, respectively (P=.0177). In the treatment group, the difference in BMD between hemiplegic and nonhemiplegic sides decreased significantly compared with that before randomization. This difference increased in the placebo group. We observed a similar improvement in MCI in the treatment group but not in the placebo group. Four patients in the placebo group suffered a hip fracture compared with none in the treatment group (P=.0362). Conclusions: Treatment with 1alpha(OH)D3 and supplemental elemental calcium can reduce the risk of hip fractures and can prevent further decreases in BMD and MCI on the hemiplegic side of patients with a long-standing stroke. Treatment also may improve these indices on the intact side.

The usefulness of bone turnover in predicting the response to transdermal estrogen therapy in postmenopausal osteoporosis

Journal of Bone and Mineral Research (USA), 1997, 12/4 (624-631)

Transdermal estrogen therapy is now an accepted form of treatment for postmenopausal osteoporosis. Ninety postmenopausal osteoporotic women were randomized to receive either transdermal estrogen (0.05 mg/day 17beta- estradiol) and calcium (n = 45) or calcium alone (n = 45). The study period was 2 years. Bone mineral density (BMD) at the lumbar spine (by dual-energy X-ray absorptiometry (DXA)) and markers of bone turnover (alkaline phosphatase, osteocalcin, hydroxyproline, pyridinoline cross-links) were assessed at baseline and after I and 2 years. In the estrogen-treated group, BMD showed a significant increase (p < 0.001) both after I and 2 years, with a reduction in biochemical markers. To investigate the effectiveness of estrogen treatment of postmenopausal osteoporosis in relation to bone turnover, we also divided the patients on the basis of bone turnover, as assessed by measurement of whole body retention (WBR) of 99mTc-methylene diphosphonate. WBR revealed that 26 patients had high bone turnover (HT) and 55 had low bone turnover (LT). The response to estrogen was greater in the HT patients than in the LT patients; in fact BMD increased by 5.7 and 6.6% in HT patients and by 2.6 and 2.7% in LT patients after 1 and 2 years, respectively. In conclusion, the present study demonstrates that, while the BMD decreases in the patients treated with calcium alone, 2-year treatment with transdermal estrogen increases axial BMD and that the response to estrogen treatment is influenced by bone turnover. Therefore, the evaluation of bone turnover may be useful to identify those postmenopausal osteoporotic women who may especially benefit from treatment with estrogen.

Osteoporotic vertebral fractures in postmenopausal women

American Family Physician (USA), 1997, 55/4 (1315-1322)

Back pain is a common symptom in post-menopausal women. As in younger age groups, most cases of back pain in post-menopausal women do not represent serious disease and resolve spontaneously within four weeks. However, acute back pain in postmenopausal women may be caused by vertebral fracture, and 'red flags' in the history and physical examination can help clinicians decide on the appropriate work-up. When findings suggest vertebral fracture, anteroposterior and lateral radiographs of the thoracolumbar spine should be obtained. The diagnosis of existing vertebral fractures is critical because the probability of sustaining new spine and hip fractures is increased in women with one vertebral fracture, and the presence of multiple fractures puts the patient at risk for chronic debilitation. Acute fractures should be treated supportively, and a further work-up should be performed to assess the degree of osteoporosis and to exclude secondary causes. Evaluation of bone mineral density is a helpful guide to further management. Treatment may include calcium and vitamin D, hormone replacement therapy, bisphosphonates and/or calcitonin.

Proteins and bone health

Pathologie Biologie (France), 1997, 45/1 (57-59)

Hip fracture consecutive to osteoporosis represents a major health problem in terms of both morbidity and financial burden for the community. Deficiency in nutritional elements appear to play a major role in the pathogenesis of osteoporosis and of fractures in elderly. Correction of an inadequate supply in both calcium and vitamin D can reduce bone loss and fracture incidence in elderly subjects. In addition, low protein intake could be particularly detrimental for the conservation of bone integrity with aging. Thus, in hospitalized elderly patients reduced protein intake is associated with lower femoral neck bone mineral density (BMD) and poor physical performance. Furthermore, state of malnutrition or undernutrition is often observed in elderly patients with hip fracture. In these patients, in whom we detected very low femoral neck BMD at the level of the proximal femur, the self-selected intake of protein and energy was insufficient during their hospitalization. Interestingly, the clinical outcome after hip fracture was significantly improved by daily oral nutritional supplement normalizing the protein intake, documented as a reduction in both complication rate and median duration of hospital stay. Further studies showed that normalization of the protein intake, independently of that of energy, calcium and vitamin D, was responsible for this more favorable outcome, and could prevent further bone loss, at least at the level of weight-bearing cortical bone. In undernourished elderly subjects an increase in the protein intake, from low to normal, could be beneficial for bone integrity. This could act through an increase in the growth factor IGF-1 which has been found to decrease with aging.

Osteoporosis: Prevention, diagnosis, and management

American Journal of Medicine (USA), 1997, 102/1 A (35S-39S)

Osteoporosis is a public health scourge that is usually eminently preventable. Some risk factors, such as low calcium intake, vitamin D deficiency, and physical inactivity, are amenable to early interventions that will help maximize peak bone density. Other risk factors subject to modification are cigarette smoking and excessive consumption of protein, caffeine, and alcohol. Hip fractures are the most serious outcome of osteoporosis, with enormous personal and public health consequences. The ongoing Study of Osteoporotic Fractures has identified additional independent predictors of hip fracture risk, including maternal hip fracture, absence of significant weight gain since age 25, height, hyperthyroldism, use of long- acting benzodiazepines or anticonvulsants, spending <4 hours a day on one's feet, inability to rise from a chair without using one's arms, poor visual depth perception and contrast sensitivity, and tachycardia. In an individual perimenopausal woman, the risk of osteoporotic fracture and the urgency of estrogen replacement therapy can be best estimated on the basis of bone mineral density, as measured by dual-energy x-ray absorptiometry, coupled with the presence or absence of existing fractures and clinical risk factors evident from the history and physical examination. Estrogen, calcitonin, and bisphosphonates have all been proved effective in retarding postmenopausal bone loss and therefore reducing the risk of fracture. The use of sodium fluoride is more controversial, although a recent study has suggested a possible role for slow-release fluoride combined with high-dose calcium supplementation.

Connections between phospho-calcium metabolism and bone turnover. Epidemiologic study on osteoporosis (second part)

Minerva Medica (Italy), 1996, 87/12 (565-576)

Background. The recent development of highly accurate and precise osseous mass quantitative evaluation methodology, permits the conduction, in the sphere of osteoporosis, of epidemiologic investigations no longer limited solely to fracture complications, but also based on the definition of osseous mass. Fractures being only complications, possible but not certain, of the advanced stages of the disease, the studies based on their incidence allow one to underestimate the global entity of prevalence and incidence, besides building only a partially useful reference in view of primary and secondary prevention. Methods. The main points of our study are the following: 1) evaluation of the incidence of the primary risk factors for osteoporosis as they appear in the literature, on the bone mass values of examined subjects, utilizing static mineralometric data as a reference standard; 2) study of biohumoral data relative to phospho-calcium metabolism and to sexual function, to show the possibility of their use as early identifying markers of subjects at risk; reference values represented by dynamic mineralometric data. The principal conclusions that emerged in the course of the study are the following. Results.In relation to the use of phospho-calcium metabolic biohumoral and hormonal variables, as a predictive function on the variations of bone turnover, the variables:osteocalcin, alkaline phosphatase, alkaline phos-phatase bone isoenzyme, hydroxyprolinuria/creatininuria, have resulted significantly different in the comparison between high and low turnover subjects. The degree of quantitative correlation of such variables with the entity of percentage decrement of bone mass has been modest. The overall value of R-square of the predictive model, besides the variables mentioned the value of bone mass at 1degreecontrol visit, was 0.38(osteocalcin:0 .27; osteocalcin+hydroxyprolinuria /creatininuria: 0.33; preceding variables + bone mass at 1st control: 0.36; preceding variables + alkaline phosph-atase:0.37; preceding variables +alkaline phosphatase bone isoenzyme:0.38). Conclusions.The single value osteocalcin may furnish indications on the future variations of bone turnover and consequently on the early identification of the subjects at risk for osteoporosis at high turnover; the addition of the other variables indicated in our predictive model allows an increase of the possibilities of individualizing of these subjects.