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