pregnancy, a woman's ability to retain dietary calcium and iron increases,
and the baby seems to be susceptible to overloading. A normal baby doesn't
need dietary iron for several months, as it uses the iron stored in
its tissue, and recently it has been reported that normal fetuses and
babies may have calcified pituitary glands. Pituitary cell death is
sometimes seen with the concretions. (Groisman, et al.) Presumably,
the calcification is resorbed as the baby grows. This is reminiscent
of the "age pigment" that can be found in newborns, representing
fetal stress from hypoxia, since that too disappears shortly after birth.
Iron overload, age pigment, and calcification of soft tissues are so
commonly associated with old age, that it is important to recognize
that the same cluster occurs at the other extreme of (young) age, and
that respiratory limitations characterize both of these periods of life.
is probably the most popular element in physiological research, since
it functions as a regulatory trigger in many cell processes, including
cell stimulation and cell death. Its tendency to be deposited with iron
in damaged tissue has often been mentioned. In hot weather, chickens
pant to cool themselves, and this can lead to the production of thin
egg shells. Carbonated water provides enough carbon dioxide to replace
that lost in panting, and allows normal calcification of the shells.
[Science 82, May, 1982] The deposition of calcium is the last phase
of the "tertiary coat" of the egg, to which the oviduct glands
successively add albumin, "egg membrane," and the shell, containing
matrix proteins (including some albumin; Hincke, 1995) and calcium crystals.
Albumin is the best understood of these layers, but it is still complex
and mysterious; its unusual affinity for metal ions has invited comparisons
with proteins of the immune system. It is known to be able to bind iron
strongly, and this is considered to have an "immunological"
function, preventing the invasion of organisms that depend on iron.
Maria de Sousa ("Iron and the lymphomyeloid system: A growing knowledge,"
Iron in Immunity, Cancer and Inflammation, ed. by M. de Sousa and J.
H. Brock, Wiley & Sons, 1989) has argued that the oxygen delivery
system and the immune system evolved together, recycling iron in a tightly
role of macrophages in the massive turnover of hemoglobin, and as osteoclasts,
gives us a perspective in which iron and calcium are handled in analogous
ways. Mechnikov's view of the immune system, growing from his observations
of the "phagocytes," similarly gave it a central role in the
organism as a form-giving/ nutrition-related process. In a family with
"marble-bone disease," or osteopetrosis, it was found that
their red blood cells lacked one form of the carbonic anhydrase enzyme,
and that as a result, their body fluids retained abnormally high concentrations
of carbon dioxide. Until these people were studied, it had been assumed
that an excess of carbon dioxide would have the opposite effect, dissolving
bones and causing osteoporosis or osteopenia, instead of osteopetrosis.
The thyroid hormone is responsible for the carbon dioxide produced in
respiration. Chronic hypothyroidism causes osteopenia, and in this connection,
it is significant that women (as a result of estrogen's effects on the
thyroid) are much more likely than men to be hypothyroid, and that,
relative to men, women in general are "osteopenic," that is,
they have more delicate skeletons than men do.
an experiment, rats were given a standard diet, to which had been added
1% Armour thyroid, that is, they were made extremely hyperthyroid. Since
their diet was inadequate (later experiments showed that this amount
of thyroid didn't cause growth retardation when liver was added to the
diet) for their high metabolic rate, they died prematurely, in an apparently
undernourished state, weighing much less than normal rats. Their bones,
however, were larger and heavier than the bones of normal rats. A few
incompetent medical "studies" have made people fear that "taking
thyroid can cause osteoporosis." Recognizing that hypothyroid women
are likely to have small bones and excessive cortisol production, the
inadequate treatment of hypothyroidism with thyroxin (the thyroid-suppressive
precursor material), is likely to be associated with relative osteoporosis,
simply because it doesn't correct hypothyroidism. Similar misinterpretations
have led people to see an association between "thyroid use"
(generally thyroxin) and breast cancer--hypothyroid women are likely
to have cancer, osteoporosis, obesity, etc., and are also likely to
have been inadequately treated for hypothyroidism. T3, the active form
of thyroid hormone, does contribute to bone formation. (For example,
M. Alini, et al.)
the same time (early 1940s) that the effects of thyroid on bone development
were being demonstrated, progesterone was found to prevent age-related
changes in bones, and "excessive" seeming doses of thyroid
were found to prevent age-related joint diseases in rats.
A logical course of events, building on these and subsequent discoveries, would have been to observe that the glucocorticoids cause a negative calcium balance, leading to osteoporosis, and that thyroid and progesterone oppose those hormones, protecting against osteoporosis. But the drug industry had discovered the profits in estrogen ("the female hormone") and the cortisone-class of drugs. Estrogen was promoted to prevent miscarriages, to stop girls (and boys) from growing too tall, to cure prostate and breast cancer, to remedy baldness, and 200 other absurdities. As all of those frauds gradually became untenable, even in the commercial medical culture, the estrogen industry began to concentrate on osteoporosis and femininity. Heart disease and Alzheimer's disease back those up.
"If estrogen causes arthritis,
prescribe prednisone for the inflammation. If prednisone causes osteoporosis,
increase the dose of estrogen to retard the bone-loss. People are tough,
and physiological therapies aren't very profitable."
years ago I noted in a newsletter that hip fractures most often occur
in frail, underweight old women, and that heavier, more robust women
seem to be able to bear more weight with less risk of fracture. Although
I hadn't read it at the time, a 1980 article (Weiss, et al.) compared
patients with a broken hip or arm with a control group made up of hospitalized
orthopedic patients with problems other than hip or arm fractures. The
fracture cases' weight averaged 19 pounds lighter than that of the other
patients. They were more than 3.6 times as likely to be alcoholic or
epileptic. It would be fair to describe them as a less robust group.
the use of estrogen has become so common in the U.S., it is reasonable
to ask whether the incidence of hip fractures in women over 70 has declined
in recent decades. If estrogen protects against hip fractures, then
we should see a large decrease in their incidence in the relevant population.
fractures, like cancer, strokes, and heart disease, are strongly associated
with old age. Because of the baby-boom, 1945 to 1960, our population
has a bulge, a disproportion in people between the ages of 35 and 50,
and those older. Increasingly, we will be exposed to publicity about
the declining incidence of disease, fraudulently derived from the actually
declining proportion of old people. For example, analyzing claims based
on the pretense that the population bulge doesn't exist, I have seen
great publicity given to studies that would imply that our life-expectancy
is now 100 years, or more.
the number of hip fractures, per 1000 75 year old women, in 1996, with
the rate in 1950, we would have a basis for judging whether estrogen
is having the effect claimed for it.
x-ray data seem to convince many people estrogen is improving bone health,
by comparing measurements in the same person before and after treatment.
Does estrogen cause water retention? Yes. Does tissue water content
increase measured bone density? Yes. Are patients informed that their
"bone scans" don't have a scientific basis? No. The calcification
of soft tissues under the influence of estrogen must also be taken into
account in interpreting x-ray evidence. (Hoshino, 1996) Granted that
woman who are overweight have fewer hip fractures (and more cancer and
diabetes), what factors are involved? Insulin is the main factor promoting
fat storage, and it is anabolic for bone. (Rude and Singer, "Hormonal
modifiers of mineral metabolism.") The greatest decrease in bone
mass resulting from insulin deficiency was seen in white females, and
after five years of insulin treatment, there was a lower incidence of
decreased bone mass (Rosenbloom, et al., 1977). McNair, et al. (1978
and 1979) found that the loss of bone mass coincided with the onset
of clinical diabetes. Since excess cortisol can cause both high blood
sugar and bone loss, when diabetes is defined on the basis of high blood
sugar, it will often involve high blood sugar caused by excess cortisol,
and there will be calcium loss. Elsewhere, I have pointed out some of
the similarities between menopause and Cushing's syndrome; a deficiency
of thyroid and progesterone can account for many of these changes. Nencioni
and Polvani have observed the onset of progesterone deficiency coinciding
with bone loss, and have emphasized the importance of progesterone's
antagonism to cortisol.
(1979) found that progesterone (but not estrone, estradiol, testosterone,
or androstenedione) was significantly lower in those losing bone mass
the age of 50, when bone loss is increasing, progesterone and thyroid
are likely to be deficient, and cortisol and prolactin are likely to
be increased. Prolactin contributes directly to bone loss, and is likely
to be one of the factors that contributes to decreased progesterone
tends to cause increased secretion of prolactin and the glucocorticoids,
which cause bone loss, but it also promotes insulin secretion, which
tends to prevent bone loss. All of these factors are associated with
increased cancer risk.
and progesterone, unlike estrogen, stimulate bone-building, and are
associated with a decreased risk of cancer. It seems sensible to use
thyroid and progesterone for their general anti-degenerative effects,
protecting the bones, joints, brain, immune system, heart, blood vessels,
the issue of calcification/decalcification is so general, we mustn't
lose interest just because the practical problem of osteoporosis is
example, healthy high energy metabolism requires the exclusion of most
calcium from cells, and when calcium enters the stimulated or deenergized
cell, it is likely to trigger a series of reactions that lower energy
production, interfering with oxidative metabolism. During aging, both
calcium and iron tend to accumulate and they both seem to have an affinity
for similar locations, and they both tend to displace copper. (Compare
K. Sato, et al., on the calcification of copper-containing paints.)
Elastin is a protein, the units of which are probably bound together
by copper atoms. In old age, elastin is one of the first substances
to calcify, for example in the elastic layers of arteries, causing them
to lose elasticity, and to harden into almost bone-like tubes. In the
heart and kidneys, the mitochondria (rich in copper-enzymes) are often
the location showing the earliest calcification, for example when magnesium
certain proteins have higher than average affinity for copper, iron,
and calcium. For example, egg-white's unusual behavior with copper can
be seen if you make a meringue in a copper pan--the froth is unusually
firm. My guess is that copper atoms bind the protein molecules into
relatively elastic systems. In many systems, calcium forms the link
between adhesive proteins.
brain degeneration, the regions that sometimes accumulate aluminum,
will accumulate other metals instead, if they predominate in the environment;
calcium is found in this part of the brain in some of the Pacific regions
studied by Gajdusek. Certain cells in the brain used to be called "metalophils,"
because they could be stained intensely with silver and other metals;
I suppose these are part of the immune system, handling iron as described
by Maria de Sousa. Macrophages have been proposed as an important factor
in producing atherosclerotic plaques (Carpenter, et al.). There is evidence
that they (and not smooth muscle cells) are the characteristic foam
cells, and their conversion of polyunsaturated oils into age pigment
accounts for the depletion of those fats in the plaques. The same evidence
could be interpreted as a defensive reaction, binding iron and destroying
unsaturated fatty acids, and by this detoxifying action, possibly protecting
against calcification and destruction of elastin. (This isn't the first
suggestion that atherosclerosis might represent a protective process;
see S. M. Plotnikov, et al., 1994.)
carbon dioxide and bicarbonate are formed in the mitochondria, it is
reasonable to suppose that the steady outward flow of the bicarbonate
anion would facilitate the elimination of calcium from the mitochondria.
Since damaged mitochondria are known to start the process of pathological
calcification in the heart and kidneys, it probably occurs in other
tissues that are respiratorily stressed. And if healthy respiration,
producing carbon dioxide, is needed to keep calcium outside the cell,
an efficient defense system could also facilitate the deposition of
calcium in suitable places--depending on specific protein binding. The
over-grown bones in the hyperthyroid rats and the women with osteopetrosis
suggest that an abundance of carbon dioxide facilitates bone formation.
Since no ordinary inorganic process of precipitation/crystallization
has been identified that could account for this, we should consider
the possibility that the protein matrix is regulated in a way that promotes
(or resists) calcification. The affinity of carbon dioxide for the amine
groups on proteins (as in the formation of carbamino hemoglobin, which
changes the shape of the protein) could change the affinity of collagen
or other proteins for calcium. Normally, ATP is considered to be the
most important substance governing such changes of protein conformation
or binding properties, but ordinarily, ATP and CO2 are closely associated,
because both are produced in respiration. Gilbert Ling has suggested
that hormones such as progesterone also act as cardinal adsorbants,
regulating the affinity of proteins for salts and other molecules.
have many proteins with variable affinity for calcium; for example in
muscle, a system called the endoplasmic reticulum, releases and then
sequesters calcium to control contraction and relaxation. (This calcium-binding
system is backed up by--and is spatially in close association with--that
of the mitochondrion.) Ion-exchange resins can be chemically modified
to change their affinity for specific ions, and molecules capable of
reacting strongly with proteins can change the affinities of the proteins
for minerals. What evidence is there that carbon dioxide could influence
calcium binding? The earliest deposition of crystals on implanted material
is calcium carbonate. (J. Vuola, et al, 1996.) In newly formed bone,
the phosphate content is low, and increases with maturity. While mature
bone has an apatite-like ratio of calcium and phosphate, newly calcified
bone is very deficient in phosphate (according to Dallemagne, the initial
calcium to phosphorus ratio is 1.29, and it increases to 2.20.) (G.
Bourne, 1972; Dallemagne.)
carbonate content of bone is often ignored, but in newly formed bone,
it is probably the pioneer. Normally, "nucleation" of crystals
is thought of as a physical event in a supersaturated solution, but
the chemical interaction between carbon dioxide and amino groups (amino
acids, protein, or ammonia, for example) removes the carbon dioxide
from solution, and the carbamino acid formed becomes a bound anion with
which calcium can form a salt. With normal physiological buffering,
the divalent calcium (Ca2+) should form a link between the monovalent
carbamino acid and another anion. Linking with carbonate (CO32-), one
valence would be free to continue the salt-chain. This sort of chemistry
is compatible with the known conditions of bone formation.
Klein, et al. (1996), think of uncoupled oxidative phosphorylation in terms of "subtle thermogenesis," which isn't demonstrated in their experiment, but their experiment actually suggests that stimulated production of carbon dioxide is the factor that stimulates calcification. Their experiment seems to be the in vitro equivalent of the various observations mentioned above. DHEA, which powerfully stimulates bone formation, is (like thyroid and progesterone) thermogenic, but in these cases, the relevant event is probably the stimulation of respiration, not the heat production. In pigs (Landrace strain) susceptible to malignant hyperthermia, there is slow removal of calcium from the contractile apparatus of their muscles. Recent evidence shows that an extramitochondrial NADH-oxidase is functioning. This indicates that carbon dioxide production is limited. I think this is responsible for the cells' sluggishness in expelling calcium.
Stress-susceptible pigs show abnormalities
of muscle metabolism (e.g., high lactate formation) that are consistent
with hypothyroidism. (T. E. Nelson, et al., "Porcine malignant
hyperthermia: Observations on the occurrence of pale, soft, exudative
musculature among susceptible pigs," Am. J. Vet. Res. 35, 347-350,
1974; M. D. Judge, et al., "Adrenal and thyroid function in stress-susceptible
pigs (Sus domesticus)," Am. J. Physiol. 214(1), 146-151, 1968.)
hyperthermia during surgery is usually blamed on genetic susceptibility
and sensitivity to anesthetics. (R. D. Wilson, et al., "Malignant
hyperpyrexia with anesthesia," JAMA 202, 183-186, 1967; B.A Britt
and W. Kalow, "Malignant hyperthermia: aetiology unknown,"
Canad. Anaesth. Soc. J. 17, 316-330, 1970.) Hypertonicity of muscles,
various degrees of myopathy and rigidity, and uncoupling of oxidative
phosphorylation occur in these people, as in pigs. Lactic acidosis suggests
that mitochondrial respiration is defective in the people, as in the
pigs. Besides the sensitivity to anesthetics, the muscles of these people
are abnormally sensitive to caffeine and elevated extracellular potassium.
During surgery, artificial ventilation, combined with stress, toxic
anesthetics, and any extramitochondrial oxidation that might be occurring
(such as NADH-oxidase, which produces no CO2), make relative hyperventilation
a plausible explanation for the development of hyperthermia. Hyperventilation
can cause muscle contraction. Panting causes a tendency for fingers
and toes to cramp. Free intracellular calcium is the trigger for muscle
contraction (and magnesium is an important factor in relaxation.) Capillary
tone, similarly, is increased by hyperventilation, and relaxed by carbon
dioxide. The muscle-relaxing effect of carbon dioxide shows that the
binding of intracellular calcium is promoted by carbon dioxide, as well
as by ATP. The binding of calcium in a way that makes it unable to interfere
with cellular metabolism is, in a sense, a variant of simple extrusion
of calcium, and the binding of calcium to extracellular materials. A
relaxed muscle and a strong bone are characterized by bound calcium.
of the sympathetic nervous system promotes hyperventilation. This means
that hypothyroidism, with high adrenalin (resulting from a tendency
toward hypoglycemia because of inefficient use of glucose and oxygen),
predisposes to hyperventilation.
stiffness, muscle soreness and weakness, and osteoporosis all seem to
be consequences of inadequate respiration, allowing lactic acid to be
produced instead of carbon dioxide. Insomnia, hyperactivity, anxiety,
and many chronic brain conditions also show evidence of defective respiration,
for example, either slow consumption of glucose or the formation of
lactic acid, both of which are common consequences of low thyroid function.
Several studies (e.g., Jacono and Robertson, 1987) suggest that abnormal
calcium regulation is involved in epilepsy. The combination of supplements
of thyroid (emphasizing T3), magnesium, progesterone and pregnenolone
can usually restore normal respiration, and it seems clear that this
should normalize calcium metabolism, decreasing the calcification of
soft tissues, increasing the calcification of bones, and improving the
efficiency of muscles and nerves. (Magnesium, like carbonate, is a component
of newly formed bone.) The avoidance of polyunsaturated vegetable oils
is important for protecting respiration; some of the prostaglandins
they produce have been implicated in osteoporosis, but more generally,
they antagonize thyroid function and they can interfere with calcium
control. The presence of the "Mead acid" (the omega-9 unsaturated
fat our enzymes synthesize) in cartilage suggests a new line of investigation
regarding the bone-toxicity of the polyunsaturated dietary oils.
G. R. Sauer, et al., "A facilitating role for carbonic anhydrase activity in matrix vesicle mineralization," Bone and Mineral 26(1), 69-79, 1994. T. R. Anellet, "Effects of medium acidification by alteration of carbon dioxide or bicarbonate concentration on the resorptive action of rat osteoclasts," J. Bone and Mineral Res. 9(3), 375-379, 1994. (...resorption was almost abolished in the presence of 2.5% CO2 at pH 7.61 but increased in a stepwise manner up to 1.3 pits per osteoclast when dentin slices were cultured with 10% CO2 at pH 6.97.")
D. A. Bushinsky, et al., "Acidosis and bone," Min. & Electrolyte Metab. 20(1-2), 40-52, 1994. ("During acute respiratory acidosis there is no measurable influx of protons in bone and during chronic studies there is no measurable calcium efflux.")
D. A. Bushinsky, et al., "Decreased bone carbonate content in response to metabolic but not respiratory acidosis," Amer. J. Physiol. 265(4, part 2), F530-F536, 1993. ("...elevated pCO2 doesn't allow bone carbonate dissolution despite reduced pH.")
J. Vuola, et al., "Bone marrow induced osteogenesis in hydroxyapatite and calcium carbonate implants," Biomaterials 17(18), 1761-1766, 1996. A. H. Knell, I. J. Fairchild, and K. Swett, Palaios 8, 512-525, 1993. (Late proterozoic ocean was supersaturated with calcium carbonate.) F. Marin, et al., "Sudden appearance of calcified skeletons at precambrian-cambrian transition," Proc. Nat. Acad. Sci. U.S. 93(4), 1554-1559, 1996.
M. J. Dallemagne, Acta Physiother. Rheumatol. Belg.3, 77, 1947; Nature (London) 161, 115, 1948; Annu. Rev. Physiol. 12, 101, 1950; J. Physiol. (Paris) 43, 425, 1951.
G. H. Bourne, ed., The Biochemistry and Physiology of Bone; Physiology and Pathology, Academic Press, 1972.
J. A. Schlechte, et al., "Bone density in amenorrheic women with and without hyperprolactinemia," J. Clin. Endocrinol. & Metabolism 56, 1120, 1983. (Evidence for a direct effect of prolactin on bone.) P. S. Dannies, "Control of prolactin production by estrogen," chapter 9, p. 289, in Biochemical Actions of Hormones XII, Academic Press, 1985. J.-J. Body, et al., "Calcitonin deficiency in primary hypothyroidism," J. Clin. Endocrinology and Metabolism 62(4), 700, 1986. ("We conclude that the process that causes hypothyroidism in patients with autoimmune thyroid disease can also cause marked CT deficiency.") T. Nencioni and F. Polvani, "Rationale for the use of calcitonin in the prevention of post-menopausal osteoporosis," in Calcitonin, A. Pecile, editor, Elsevier Science Publ., 1985.
C. C. Johnston, et al., "Age-related bone loss," pages 91-100 in U. S. Barrel, editor, Osteoporosis II, Grune and Stratton, N. Y., 1979. E. I. Barengolts, et al., "Progesterone antagonist RU 486 has bone-sparing effects in ovariectomized rats," Bone 17(1), 21-25, 1995. "...progesterone prevents ovariectomy-induced bone loss." M. Kasra and M. D. Grynpas, "The effects of androgens on the mechanical properties of primnate bone," Bone 17(3), 265-270, 1995. D. J. Rickard, et al., "Importance of 1,25-dihydroxyvitamin D-3 and the nonadherent cells of marrow for osteoblast differentiation from rat marrow stromal cells," Bone 16(6), 671-678, 1995. ("...growth could be stimulated by...1,25-dihydroxyvitamin D-3, but not dexamethasone, 17 beta-estradiol, or retinoic acid...." D-3 and glucocorticoids "may regulate osteogenesis from the bone marrow but a similar role for estrogen is not supported.") P. W. Stacpoole, "Lactic acidosis and other mitochondrial disorders," Metabolism 46(3), 306-321, 1997.
L. M. Banks, et al., "Effect of degenerative spinal and aortic calcification on bone density measurements in post-menopausal women: Links betwwen osteoporosis and cardiovascular disease?" Eur. J. of Clin. Investigation 24(12), 813-817, 1994. ("Women with spinal degenerative calcification had higher spine bone density when measured by dual photon absorptionmetry compared to those without calcification." "Women with aortic calcification had significantly lower quantitative computer tomography and proximal femur bone density compared to those without calcification."
S. E. Wendelaar Bonga and G. Flik, "Prolactin and calcium metabolism in a teleost fish, Sarotherodon mossambicus," Gen. Compar. Endocrinol. 46, 21-26, 1982.
U.S. Barzel, "The skeleton as an ion exchange system: Implications for the role of acid-base imbalance in the genesis of osteoporosis," J. of Bone and Mineral Res. 10(10), 1431-1436, 1995.
P. Schneider and C. Reiners, Letter, JAMA 277(1), 23, Jan. 1, 1997. Dual-energy x-ray absorptiometry for bone density can lead to false conclusions about bone mineral content, because of alterations in tissue fat or water content. "The influence of fat distribution on bone mass measurements with DEXA can be of considerable magnitude and ranges up to 10% error per 2 cm of fat."
J. Pearson, et al, Osteoporosis
5, 174-184, 1995 J. Dequeker, et al, "Dual X-ray absorptiometry--cross-calibrati
M. Silberberg and R. Silberberg, Arch. Path. 31(1), 85-92, 1941. (Progesterone counteracts aging of bone in guinea pig.) M. Silberberg and R. Silberberg, Growth 4(3), 1305-14, 1940. (Decreased severity and incidence of old-age changes in the joints of normal mice.) G. Coryn, "Recherche experimentale sur l'influence des glands endocrines sur l'histologie du cartilage de conjugaison," Annales d'anatomie pathol. 16, 27, 1939.
O. Rahn, "Protozoa need carbon dioxide for growth," Growth 5, 197-199, 1941. "On page 113 of this volume, the statement of Valley and Rettger that all bacteria need carbon dioxide for growth had been shown to apply to young as well as old cells." "...it is possible...to remove it as rapidly as it is produced, and under these circumstances, bacteria cannot multiply." K. L. H. Carpenter, et al., "Production of ceroid and oxidised lipids by macrophages in vitro," Lipofuscin--1987: State of the Art, I. Zs.-Nagy, editor, pp. 245-268, 1988.
A. Schlemmer, et al., "Posture, age, menopause, and osteopenia do not influence the circadian variation in the urinary excretion of pyridinium crosslinks," J. Bone Miner. Res. 9(12), 1883-1888, 1994. N. S. Weiss, et al., "Decreased risk of fractures of the hip and lower forearm with postmenopausal use of estrogen,:" N. Engl. J. Med. 303, 1195-1198, 1980.
S. M. Plotnikov, et al., "Anxiety, atherogenesis, and antioxidant protection: Clinico-pathogenetic relationships," Bull. Exp. Biol. & Medicine 117(2), 221, 1994.
G. M. Groisman, et al., "Calcified concretions in the anterior pituitary gland of the fetus and the newborn: A light and electron microscopic study," Human Pathology 27(11), 1139-1143, 1996. (...calcified concretions represent a normal finding in the anterior pituitary gland of fetuses and young infants.")
K. S. G. Jie. "Vitamin K status and bone mass in women with and without aortic atherosclerosis: A population-based study," Calc. Tiss. Intern. 59(5), 352-356, 1996. ("The finding that in atherosclerotic women vitamin K status is associated with bone mass supports our hypothesis that vitamin K status affects the mineralization processes in both bone and in atherosclerotic plaques."
B. Y. Klein, et al., "Cell-mediated mineralization in culture at low temperature associated with subtle thermogenic response," J. of Cellular Biochemistry 63(2), 229-238, 1996. "...cell-mediated mineralization is preceded by characteristics of anaerobic and low efficiency energy metabolism." "Modulation of mitochondrial membrane potential and energy metabolism could be linked to regulation of mineralization by the uncoupling of oxidative phosphorylation. This uncoupling should be associated with thermogenesis in cells that induce mineralization." C. R. Heath, B.S.C. Leadbeater, and M. E. Callow, "The control of calcification of antifouling paints in hard waters using a phosphonate inhibitor," Biofouling 9(4), 317-325, 1996. ("All paints contained cuprous oxide....)
C. D. Yee, et al., "The relationship of nutritional copper to the development of postmenopausal osteoporosis in rats," Biol. Trace Element Res. 48(1), 1-11, 1995.
H Hoshino, et al., "The influence of aortic calcification on spinal bone mineral density in vitro," Calc. Tiss. Intern 59(1), 21-23, 1996. ("...changes over time in a patient could falsely elevate values.") E. Toussirot, et , "Giant calcification in soft tissue after shoulder corticosteroid injection, J. of Rheumatology 23(1), 181-182, 1996, "Such periarticular calcifications are rarely observed and generally after triamcinolone hexacetonide injection."
M. Alini, et al., "In serum-free culture thyroid hormones can induce full expression of chondrocyte hypertrophy leading to matrix calcification," J. of Bone and Mineral Res. 11(1), 105-113, 1996. ("...we compared the capacity of T3 with T4 to stimulate expression of the hypertrophic phenotype and matrix calcification in three . . . prehypertrophic chondrocyte subpopulations." "...T3 was at least 50-fold more potent than T4. The effects of T3 were most pronounced with the most immature cells." "...matrix calcification, measured by the incorporation of Ca45(2+) into the cell layer, always occurred earlier in cells cultured with T3 compared with T4."
M. T. Hincke, "Ovalbumin is a component of the chicken eggshell matrix," Connective Tissue Research 31(3), 227-233, 1995. (Immunochemically demonstrated in the mammillary bodies of decalcified shell. "These results indicate that ovalbumin is present during the initial phase of shell formation and becomes incorporated into the protein matrix of the mammillary bodies.")
A. L. Boskey, et al., "Persistence of complexed acidic phospholipids in rapidly mineralizing tissues is due to affinity for mineral and resistance to hydrolytic attack: In vitro data," Calc. Tiss. Intern. 58(1), 45-51, 1996. (Complexed acidic phospholipids may persist in the growth plate and facilitate initial mineral deposition.)
A.L. Boskey, et al., "Viable cells are a requirement for in vitro cartilage calcification," Calc. Tiss. Intern. 58(3), 177-185, 1996. (Challenges dogma that chondrocyte death must precede calcification in the growth plate.) K. Sekino, et , role of coccoliths in the utilization of inorganic carbon by a marine unicellular coccolithophorid, Plant and Cell Physiol 37(2), 123-127, 1996.
Y. Seyama, et al., "Effect of vitamin K2 on experimental calcinosis induced by vitamin D2 in rat soft tissue," Intern. J. for Vitamin and Nutr. Res. 66(1), 36-38, 1996.
R. Danielsen, et, "Predominance of aortic calcification as an atherosclerotic manifestation in women: The Reykjavik study," J. of Clin. Epidemiology 49(3), 383-387, 1996. (...a potential relation to pulse pressure; associated with blood sugar, use of antidiabetic drugs, serum cholesterol, smoking; much more frequent in women.) F. Etcharry, et al., Fahr's disease and mitochondrial myopathy," Revue Neurologique 151(12), 731-733, 1995. (Calcification of the basal ganglia, Fahr's disease, associated with mitochondrial myopathy.) J. J. Jacono and J. M. Robertson, "The effects of estrogen, progesterone, and ionized calcium on seizures during the menstrual cycle of epileptic women," Epilepsia 28(5), 571-577, 1987.
J. E. Sojka and C. M. Weaver, "Magnesium supplementation and osteoporosis," Nutrition Reviews 53(3), 71-74, 1995. ("...magnesium therapy appears to have prevented fractures and resulted in a significant increase in bone density.")
R. Eastell, "Management of corticosteroid-induced osteoporosis," J. Internal Medicine 237(5), 439-447, 1995. "Corticosteroid therapy results in osteoporosis." "The most important mechanism for the bone loss is a decrease in osteoblastic activity."
J. P. Bonjour and R. Rizzoli, "Inadequate protein intake and osteoporosis: Possible involvement of the IGF system,:" Nutritional Aspects of Osteoporosis '84, Challenges of Mod. Med. 7, 399-406, 1995. H. Pedersen, et al, "Skin thickness in patients with osteoporosis..." Skin Pharmacology 8(4), 207-210, 1995.
K. E. Schaefer, et al., "Phasic changes in bone CO2 fractions, calcium, and phosphorus during chronic hypercapnia," J. Applied Physiol. 48(5), 802-811, 1980.
F. C. Driessens, "Probable phase composition of the mineral in bone," Z. Naturforsch (C) 35(5-6), 357-362, 1980.
G. R. Sauer, et al., "A facilitative role for carbonic anhydrase activity in matrix vesicle mineralization," Bone Miner. 26(1), 69-71, 1994, E. Reichart, et al., "CO2 storage in various organs during chronic experimental hypercapnia," Bull. Eur. Physiopathol. Respir. 12(1), 19-32, 1976. ("During a four week hypercapnia, this CO2 increase is very inmportant in bone and brain compared with that of other organs.... ...the bone CO2 content is still increasing after four weeks.") H. Nitta, et al., "Effects of hot environments and carbonated drinking water on bone characteristics of eight-week-old broiler chicks," Poult. Sci. 65(3), 469-473, 1986.
W. G. Bottje and P. C. Harrison, "Effect of carbonated water on growth performance of cockerels subjected to constant and cyclic heat stress termperatures," Poult. Sci. 64(7), 1285-92, 1985. P. Quint, et al., "Characteristic molar ratios of magnesium, carbon dioxide, calcium and phosphorus in the mineralizing fracture callus and predentine," Calcif. Tissue Int.32(3), 257-261, 1980. ("It was found that the Mg and CO2-contents are high in relation to Ca and P values during the prestages and early stages of mineralization.") M. F. Gulyi, "Role of carbonic acid and ammonium nitrogen in regulation of metabolism and physiological function in heterotrophic organisms," Ukr. Biokhim. Zh. 52(2), 141-145, 1980.
K. E. Schaefer, et al., "Effect of intermittent exposure to 3% CO2 on respiration, acid-base balance, and calcium-phosphorus metabolism," Undersea Biomed. Res. 6 Suppl, S115-34, 1979. ("The known renal response to hypercapnia, consisting of an increased excretion of titratable acidity, ammonia, and hydrogen ion excretion, occurred but was interrupted after the first day....")
U. F. Rasmussen, et al., "Characterization of mitochondria from pig muscle:
Higher activity of exo-NADH-oxidase in animals suffering from malignant hyperthermia," Biochem. J. 315(Pt. 2), 659-663, 1996. R. K. Rude and F. R. Singer, "Hormone modifiers of mineral metabolism," in Disorders of Mineral Metabolism, vol. II: Calcium Physiology, Ed. by F. Bronner and J. W. Coburn, Academic Press, 1982.
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