Scientists Questioning and my response...
"The negative correlation between BMD and fracture rate has been proven a thousand times”
"What little evidence we have in any single racial and ethnic group is that low calcium and low vitamin D can increase fractures"
"A 40% reduction in mineral intake did not affect age-associated diseases"
"We did not find any bone problems among the milk-drinking swiss"
"I do not agree that a high calcium intake leads to an increased activity of osteoblasts (data show opposite)"
"I dont agree that intermittent PTH enhances fracture risk (opposite is true)"
"The differences among countries might be attributed to several other factors"
"Comparing different populations with different genetics , lifestyle and longevity is not really useful"
"there is no basis for the claim that a high BMD is bad"
"low BMD predisposes to fracture"
"there is no suggestion from the data that low calcium in the diet is better than high calcium"
"Excess of calcium cannot be stored, ...is simply excreted"
"with advancing age, ability to adapt to low calcium intake largely disappears"
Current very low net calcium absorption rates are proof that human prehistoric diet was very high in calcium
"The idea that we may “wear out” bone health is certainly a novel one"
"It's not true that an increase in calcium intake will lead to a proportional increase in osteoblast exposure"
"To link calcium intake to an increase in apoptosis may be taking the argument too far."
"One gets the feeling that you are guiding the literature to proof your point rather than the other way around"
"...hip fracture incidence is a reflection of the socio-economic level and longevity..."
"I find this a rather confused set of thoughts"
"Why did you not refer to article
(29),(30) and (31)? , and their perspectives should have been addressed"
"To age may partially be about a decrease in cell-line viability
So, what is the difference between low BMD in osteoporosis and healthy young people? We know that in elderly high bone turnover rates correlate with low BMD, when osteoblasts can no longer keep up with osteoclasts. Opposingly, in healthy young people high BMD correlates with high bone turnover rates (osteoblasts can easily keep up with osteoclasts), and is low BMD not caused by osteoblasts not being able to keep up with osteoclasts, but by low calcium intakes and low bone turnover rates. Osteoblasts are subject to aging phenomena, and high bone turnover rates may prematurely exhaust osteoblast replicative capacity. Osteoporosis may therefore be prevented by preventing lifetime high bone turnover rates. In healthy young people low bone turnover rates correlate with low calcium intake and low BMD, which do not predispose them to fracture. This is supported by the fact that in countries where average BMD is lowest, age adjusted fracture rates are lowest. Only in elderly low BMD predisposes to fracture. In young people low BMD (low bone turnover rates) may save bone formation capacity.
"In our study (J. Gerontol. 43: B13-B21, 1998) in which the intake of minerals (and not other component of the diet) was restricted, we found that neither longevity nor age-associated disease processes were affected by a 40% reduction in mineral intake"
Phyto-estrogens are predominantly present in soy. Yes, in China relatively much soy is consumed, but in other countries with extremely low age adjusted osteoporosis incidence, such as Congo, Guinea and Togo, hardly any soy is consumed (FAO database). In Japan over 2-fold more soy is consumed (per capita) than in China, but osteoporosis incidence is far higher (and so is calcium intake).
Also: Estrogen is protective for decreasing bone turnover. Estrogen administration decreased bone turnover in rats, but a 22% soybean protein diet did not (25). Phyto-oestrogens may replace normal (protective) estrogen. In women consuming 400 mL of soymilk daily during 3 months, estrone and estradiol levels were decreased by 23% and 27%, respectively. (26) Genisteine is the main phyto-estrogen in soy. Unlike estrogen (estrogen inhibits osteoblast activity; see article), genisteine increases osteoblast activity (27), partly due to increased intestinal calcium absorption (28). So, the effects of genisteine oppose the effects of estrogen on bone metabolism, while estrogen is known to be protective against osteoporosis.
"In the arguments about BMD and hip fracture with different ethnicities, this could also
be explained by a number of factors such as differences in bone size and differences in
physical activity patterns."
"Comparing different populations with different genetics, lifestyle and longevity is not really useful"
Longevity has nothing to do with it, since these fracture rates have been adjusted for age. And studies (see article) have shown that despite the different genetics, a similar diet eliminates the differences in BMD and fracture risk. So, only lifestyle remains. Physical activity cannot explain lower average BMD in low fracture risk countries. Calcium intake can.
"What little evidence we have in any single racial and ethnic group is that low calcium and low
vitamin D can increase fractures"
In young people low calcium intakes are accompanied by low bone turnover rates. In young people consuming little (but sufficient) calcium may slow down the decrease in the age related osteoblast replicative capacity, and therefore, by lifetime effects, eventually (at old age) be protective regarding fracture risk because more osteoblast capacity remains. In young people maintaining high BMD is not essential to prevent fractures, whereas keeping bone turnover rates low may be the key to osteoporosis prevention. In elderly, bone formation capacity may already have decreased, and therefore high bone turnover rates decrease BMD (because bone formation can no longer keep up with bone resorption).
In countries with lifetime low bone turnover rates, and therefore low average BMD, due to low calcium intakes, age adjusted fracture rates are low as well. Low bone turnover rates save bone formation capacity.
"We did not find any bone problems among the milk-drinking swiss"
"I do not agree that a high calcium intake leads to an increased activity of osteoblasts (data show opposite)"
Yes, calcium supplementation may indeed decrease bone formation in elderly (1)(2)(3) (or have no influence (4)(5)(6)(7)(8), or even increase bone formation (9)), but that is not of importance here. This
theory is about the lifetime effects of calcium intake, not about the effects of
calcium once bone metabolism already has been affected by aging.
"I
dont agree that intermittent PTH enhances fracture risk (opposite is true)"
For too
long we have been looking at BMD and short term fracture risk without taking
into account bone health (ARORC) and eventual fracture risk.
"I do not agree with you that countries with high BMD also have a high
fracture rate... As far as I know only one paper has really tried to address this in a proper
manner. this is the Evos-paper, which showed that the nordic countries had a
very low level of BMD compared to southern Europe. (Lunt M, Felsenberg D, Adams J, Benevolenskaya L, Cannata J, Dequeker J et al. Population-based
geographic variations in DXA bone density in Europe: The EVOS study.
OSTEOPOROSIS.INT. 1997;7:175-89. )."
"The problem is the issue of the causal relationship. There are data showing that hip
fracture incidence is proportional to the number of books in the public libraries in each country. Thus a reflection of the socio-economic level and of the longevity of the
population"
Honestly, I don't find it convincing... Why did you not refer to any of the articles attached here? [(29),(30),(31) and (35)] They do conclude a benefit of calcium, and their perspectives should have been addressed
Extra calcium is 'beneficial', and helps to strengthen bone until osteoblast replicative capacity is exhausted, in as much as a tan helps to make your skin look young and healthy, until all that sun exposure has made your skin look way too old for your age. The Heaney article is interesting indeed, because it addresses factors of bone metabolism that actually support my hypothesis.
Heaney (30) argues that there is no such thing as higher BMD than required / biologically functional. That all the calcium retained in bone is always required. Subsequently, everybody with a not so very high BMD either fails to ingest, or fails to absorb sufficient calcium. Heaney assumes that net calcium absorption rate is more or less fixed at a very low level (about 10% at intakes in the range of current recommendations), and that this proves that our human prehistoric diet was very high in calcium.
Net calcium absorption rate however, is not fixed at all. It very much depends on, and changes with current dietary habits. The more calcium is consumed, the lower absorption rates, and the lower calcium intake, the higher absorption rates (which both plateau, of course).
In Chinese women consuming little calcium fractional calcium absorption was approximately 61%, and increased to 71% (osteoporotic women), 69% (age-matched control women) and 68% (young women) when dietary calcium was reduced to 300 mg/d.
In
11 girls aged 11.6 +/- 2.4 y, "during a low calcium intake, fractional calcium absorption was significantly greater (0.582 +/- 0.087 compared with 0.260 +/- 0.068, P < 0.0001) and urinary calcium excretion was significantly lower (1.30 +/- 0.83 compared with 3.08 +/- 1.98 mmol/d, P < 0.004) than values obtained during a high calcium
intake". (33)
We therefore must conclude that net calcium absorption rate is not a fixed 'mistake', inhereted from our ancestors, but meant to regulate calcium uptake; to be able to take up the required amount, and to protect us against taking up too much calcium. This is supported by the fact that during space flight intestinal calcium absorption is decreased (34) because at that time there is no need to maintain bone mass.
Heaney speculates that "with advancing age, ability to adapt to low calcium intake largely disappears", while however this low absorption rate is a necessity if excessive calcium can no longer sufficiently be temporarily stored in bone, due to a decrease in osteoblast capacity to form new matrix upon which all this calcium can precipitate (subject to the coupling phenomenon). Thus elderly do not have a higher calcium requirement, but absorption rates are low to compensate for the decreased capacity to cope with high calcium intakes. Assuming that bone mass cannot be manipulated beyond biologically functional, is as assuming that one cannot build muscle mass beyond biologically functional (as if bodybuilders are athletically build instead of overly pumped up).
Heaney also assumes that excess calcium "cannot be stored"; is never temporarily stored in our bones, and is always immediately excreted. That bone metabolism and the system that safeguards serum calcium level are only coupled regarding maintaining serum calcium levels sufficiently high, but not to prevent it from increasing too much. Excessively high serum calcium levels would be lethal, for blocking muscle cell functioning. The system that controls serum calcium level therefore comprises all tools available to up- and downregulate serum calcium levels, including those hormones that co-regulate calcium absorption and excretion. Naturally, maintaining healthy serum calcium levels at all times dominates maintaining biologically functional BMD levels, not just to keep serum calcium levels sufficiently high, but also to keep it prevent from increasing too much. When calcium intake is very high, calcium excretion cannot keep up (Heaney: "urine calcium is in itself only weakly regulated"), and the extra calcium is temporarily 'stored' in the bones, until serum calcium levels have sufficiently decreased, and this extra calcium can be gradually excreted. That is why one can very well manipulate BMD beyond biologically functional levels by keeping calcium intakes high. Keeping calcium intakes high accelerates the age related decrease in osteoblast replicative capacity, eventually prematurely exhausting bone capacity to maintain BMD and repair microfractures.
What Heaney sees as evidence for his conclusions, is actually only evidence for the relationship between calcium intake, BMD and bone strength (until osteoblast replicative capacity has been exhausted). Heaney, nor the studies he quotes, never address the effects of lifetime high calcium intake on osteoblast replicative capacity, and thus bone health. If Heaney's theory was correct, osteoporosis would be synonym to a lack of calcium, and extra calcium would be the cure. We all know that this is not true.
Regarding the Brown et al (29) and the Papadimitropoulos et al (31) articles. I don't dispute that in elderly a low BMD is a key risk factor for fractures, and that a high calcium intake helps to maintain high BMD and momentary bone strenght. Brown et al not just conclude that low BMD is a key risk factor for fractures, but that calcium and vitamin D are essential for the prevention of osteoporosis, and essential adjuncts to treatment. Yes, the short term (up to years) effects of extra calcium may be beneficial regarding momentary bone strength. But what are the lifetime effects of high calcium intake on eventual bone health? Brown et al and Papadimitropoulos et al have not addressed this in their papers, while this is what my theory is about. Yes, BMD represents momentary bone strength, but not bone health; BMD does not tell us to what extend the age related osteoblast replicative capacity has already decreased; how long bone capacity to fully repair and form new bone will remain; the essence of bone health.
The Peacock article
(35) focuses on the short term (4 yr) effects of supplementary calcium and vitamin D on bone strength. Yes, treatment may
indeed increase momentary bone strength, but unfortunately, we all know that there still is no cure for osteoporosis. The funny thing is that also Peacock thinks that reducing bone turnover in elderly is a good thing. Why wouldn't the same be true for people of all ages, in order to prevent osteoporosis? Maybe because in young people you need a low calcium diet to achieve this.
"The body has a unique ability to use the amount of calcium that is needs for optimal
bone strength and can not absorb the remainder"
"there is no basis for the claim that a high BMD is bad!"
"low BMD predisposes to fracture"
Yes, but this low BMD is the result (symptom) of decreased osteoblast replicative capacity, not the cause. In
young people low BMD correlates with low bone turnover rates, and lifetime low
bone turnover rates might prevent osteoporosis, saving bone formation capacity.
"while there is currently some controversy about how much calcium is required for bone health there is no suggestion from the data that low calcium in the diet is better than high calcium"
If we talk about momentary bone strength and fracture risk, no there is not.
"I find this a rather confused set of thoughts... It is good to be controversial and thought provoking, but in order to do so one needs a very good appreciation of the published literature"
My hypothesis is not the result of compiling other's conclusions, but of combining 'small' facts that have emerged from published literature with different conclusions than mine. Proper investigation requires gathering facts, not conclusions.
"The idea that we may “wear out” bone health is certainly a novel one."
"One of the fundamental hypotheses in the argument here is that an increase in calcium
intake will lead to a proportional increase in osteoblast exposure, which is likely untrue."
"To link calcium intake to an increase in apoptosis or to exhaustive age-related
osteoblast replicative capacity may be taking the argument too far."
"One gets the feeling that
you are guiding the literature to proof your point rather than the other way around."
"I think that the decline in bone strength with age is a
multifactorial one and that perhaps a decrease in cell-line viability and an increase in apoptosis is partially to
blame. Certainly these things are all about what it is to age."
REFERENCES
(1) Goemaere S, Van Pottelbergh I, Zmierczak H et al, Inverse association between bone turnover rate and bone mineral density in community-dwelling men >70 years of age: no major role of sex steroid status. Bone. 2001 Sep;29(3):286-91
(25) Harrison E, Adjei A, Ameho C, Yamamoto S, Kono S. The effect of soybean protein on bone loss in a rat model of postmenopausal osteoporosis. J Nutr Sci Vitaminol (Tokyo). 1998 Apr;44(2):257-68. (26)
Nagata C, Takatsuka N, Inaba S, Kawakami N, Shimizu H. Effect of soymilk consumption on serum estrogen concentrations in premenopausal Japanese women. J Natl Cancer Inst. 1998 Dec 2;90(23):1830-5. (30) Heaney, R.P., The importance of calcium intake for lifelong skeletal health. Calcif. Tissue Int. (2002) 70/ 70-73. (31) Papadimitropoulos E, Wells G, Shea B et al, VIII: Meta-analysis of the eficacy of vitamin D treatment in preventing osteoporosis in postmenopausal women. Endocr. Rev. 23 (4): 560-569. (32) Kung AW, Luk KD, Chu LW, Chiu PK. Age-related osteoporosis in Chinese: an evaluation of the response of intestinal calcium absorption and calcitropic hormones to dietary calcium deprivation. Am J Clin Nutr. 1998 Dec;68(6):1291-7. (33) O'Brien KO, Abrams SA, Liang LK, Ellis KJ, Gagel RF. Increased efficiency of calcium absorption during short periods of inadequate calcium intake in girls. Am J Clin Nutr. 1996 Apr;63(4):579-83. (34) Smith SM, Wastney ME, O'Brien KO et al, Bone markers, calcium metabolism, and calcium kinetics during extended-duration space flight on the mir space station. J Bone Miner Res. 2005 Feb;20(2):208-18. Epub 2004 Nov 8. (35) Peacock M, Liu G, Carey M, McClintock R, Ambrosius W, Hui S, Johnston CC. effect of calcium or 25OH vitamin D3 dietary supplementation on bone loss at the hip in men and women over the age of 60. J. Clin. Endocrin. Metab. 2000, 85 (9): 3011-19.
(36)
Karlsson MK, Gardsell P, Johnell O, Nilsson BE, Akesson K, Obrant KJ., Bone mineral normative data in Malmo, Sweden. Comparison with reference data and hip fracture incidence in other ethnic groups. Acta Orthop Scand. 1993 Apr;64(2):168-72.
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