Acid base, calcium, protein and vitamin D: Key nutrients for bone health
Key health outcome- osteoporosis
calcium and bone health
acid-base balance and the skeleton
vitamin D and health
Define osteoporosis?
What is the process of bone turnover
what are the Royal College of Physician (RCP) guidelines on osteoporosis? IN 2000
what are Ca requirementS?
what are current controversies regarding ca?
UK clinical guideline for the prevention and treatment of osteoporosis= calcium (diet focus, inclusion of supplements only if needed), vitamin D supplementation, protein (need to avoid low intake) [Royal College of Physicians Guidelines, 2000)
what was the early research ?
what are the mechanisms for acid-base balance and bone?
What does the APOSS data say?
Dietary acidity and bone resorption
how is protein involved in the skeleton ?
potassium and salts meta- analysis
What are the vitamin D requirements?
DEFINITION: Progressive, systemic skeletal disease where there is low bone mass and micro architectural deterioration of bone tissue, with consequent increase in bone fragility and susceptibility of fracture (WHO, 1991) Usually measure proxy for bone fracture (expensvie) so use bone mass/density (DEXA scan)
vertebrae/trabecular turnover of bone occurs much quicker than hip bone /cortical = reason why vertebral fracture occurs earlier due to turnover
Osteoclast responsible for resorbing bone= aim to reduce activity of this
THE CONTINUED CYCLE of bone turnover: osteoclasts migrate to bone surface and resorb bone/ bone cavity. Osteoblasts then reverse this by forming new bone matrix which is mineralised, filling the cavity
What drives bone turnover? Osteoclasts become hyperactive when deficiency in Oestrogen e.g. This is why in menopause, when oestrogen drops, you see more bone loss or females with amenorrhea
Why does bone turnover occur? Adapt to mechanical loading, repaire damage, regulate Ca levels, contribute to acid base balance
Why/ how to slow down resorption? Want to have as high bone mass as possible so that when resorption occurs at old age, less affected. Bisphosphates slow down resorption by targeting osteoclast activity. very effective more than diet but still need to achieve vitamin D/ calcium needs
difficult to adhere to bisphosphate medication as side effects, take daily and need to take on empty stomach, sitting up with water
Can bisphosphates be replaced with diet? Dietary means not as effective at stopping resorption
What are the markers of bone turnover? there are markers of bone resorption and bone formation AND regulators of bone turnover (medications target these regulators).
body uses bone to balance acid/base homeostasis in an environment of systemic metabolic acidosis. Diet high in fruit and veg (alkaline diet) can reduce osteoclastic activity (as much as bisphosphinates)
PYD/DPD are main markers of bone resorption.
How does bone mass change with ageing? Regardless of gender, have age related bone loss after 40 years. Bone loss more advanced in women once menopause reached.(drop in oestrogen increasing osteoclasts) Big increase in bone mass in puberty. Late menarche correlates with late menopause which is good as conserves bone
genetics controls peak bone mass around 75% but 25% controlled by other controllable factors e.g. diet and exercise
present to GP with risk factors, then bone density (DEXA) scan taken. Lifestyle advice give and/or pharmaceutical treatment. If frail and housebound, calcium and vitamin D supplement
Calcium influences of bone health/ calcium homeostasis
Can we measure serum calcium? Is this a good indicator of Ca status? Yes, can measure if hyper or hypo calcaemic not a nutritional marker of calcium status as when blood Ca rises, calciotrophic hormones balance levels (homeostastically controlled)
UK RNI Calcium = 700mg 19+ for all. Americna have higher levels but studies do not show significant risk (10000/1200 females as Uk just to minimise bone loss). SACN (UK) basis around avoiding deficiency whereas US for optimal health
LRNI= 400mg/d much better marker of concern (below sees increase in menopausal bone loss and inadequate calcium retention in bone skeleton
inadequate calcium will result in not achieving peak bone mass and will also lead to more bone loss later on
Researcher found cardiovascular complications with calcium supplements but study not powered to look at this. Media storm 'calcium supplements cause heart disease'
HOWEVER: UK biobank cohort trial found no evdience of detrimental effect of calcium or vitamin d on ischaemi cheart disease (Harvey et al 2018)
Aberdeen Prospective Osteoporosis Screening Study (APOSS)-
When body has excess H2 ions from diet, employs several strategies to maintain normal blood pH (7.4) / acid-base homeostasis
WHAT EARLY WORK SHOWED: importance of alkaline bone mineral in defence of organism against acid loading and acidosis. Acid loading and acidosis associated with hypercalciuria and negative Ca balance)
STUDY 1969: Animals on a regular diet and low calcium diet = ingestion of NH4CI increased bone resorption and NaHC03 and KHC03 prevented it. Low calcium diet increased bone resorption
Wachman and Bernstein 1968- an alkaline diet high in fruits and veg and portein (moderate milk) may be beneficial to stave off bone resoprtion as increased incidence of osteoporosis with age may represeent, in part, results of life long utilisation of buffering capacity off basic salts of bone for ph acidity
Look at food intake and adjusted for total energy intake/ nutrient density and effect on bone mineral density
positive link between fruit and veg consumption and bone health and K+, Mg2+ and fruits and veg intakes associated with > bone mineral density in elderly men and women
Phosphoric acid in cola drinks / fizzy drinks high = ? associated with bone resorption. For every litre consumed of cola, need 2000mg calcium to neutralise acidity
What does the early work show about extent of loss of bone mass? Assuming total body Ca content 1kg, need 2 mEq of Ca/kg/kday to buffer 1 mEq/kg/day of fixed acid/day = over 10 years, account for 15% loss of inorganic bone mass in an average individual
if big cola consumer and low dairy intake, then at risk as calcium low
=direct enhancement of osteoclastic activity - via simple passive physicochemical exchange rather than cell mediated
tiny changes in extracellular pH close to physiological range- results in large (but independent) alterations in osteoclastic and osteoblastic activity
If bone put in acid environment, osteoclasts become hyperactive
Sebatsian et al 1994- age plotted aginst Ph in blood and bicarbonate . As age increases, pH increases whilst bicarbonate reduces = more acidic plasma
critics- diet not high in acidic foods so not an issue as kidneys can buffer against. (except coke). People with kidney dysfunction/ elderly with reduced function at risk
Evidence of acid-base / fruit and veg effect in human trials (DASH)= IINCREASING fruit and veg intake reduced urinary Ca significantly . Reduction in acid load which shuts off urinary acid secretion. Bone resoprtion reduction showed in further sutdy of DASH -intervention study RCT but short term (STILL NEED LONG TERM STUDY)
Differing view on acid-base and skeletal integrity= Fenton et al 2011: Systematic review showed no effect but made far-reaching unsupported judgements, excluded key cohort populations and disregarded >30 years of work
Altohugh some negative evdience, many trials show postive effect of K+ bicarbonate lowering Ca excretiona d bone resorption
Protein and potassium important for bone health and subjects in lowest qurtile of NEAP had protein intakes well above RNI
META-ANALYSIS SHOWS EFFECT OF SUPPLEMENTATION WITH ALKALINE POTASSIUM SALTS ON BONE METABOLISM
NEED LONGER TERM STUDIES TO PROVE IF WE NEED TO TAKE A FOOD FIRST APPROACH
Early work on vitamin D: Found Cod liver oil and sunlight prevented Ricketts (Dr Chick, 1922)
Vitamin D converting enzymes involved in VITAMIN D PATHWAY: Vitamin D precursor absorbed by UVB and converted to pre-vitamin D3 (NEEDS TO BE DIRECT EFFECT OF SUNLIGHT and not hidden by clothing or windows)
converted to Vitamin D3 (cholecalciferol)
converted to 25-hydroxy vitamin D3 in liver
converted to active hormone vitamin D3 (calcitriol) in kidneys
Cannot get toxic levels of vitamin D by sun exposure as excess converted to inactive form (threshold for metabolic pathway is 25/30 mins sunlight)
Vitamin D toxicity can be achieved through supplement (unlikely with diet)
Vitamin D is needed to prevent rickets, adult osteomalacia (Adult ricketts), osteoporosis (weather effect vitamin D, only absorb in UK April till September). When shadow is longer than height, you make no vitamin D (Holloway, 1990 in Lancet)
Symptoms of mild osteomalacia - tiredness, bone ache (require SACN reccomended 10ug/day vitamin D)
Vitamin D3 foods: salmon , egg yolks, cereal, fortified milk or Vitamin D2: mushrooms and leave in sunlight and UV radiated mushrooms
25OHD levels: 10ug will achieve levels 25 (SACN) for avoiding deficiency
50nmol/l by American FSA , set higher for optimum levels for health
endocrine society suggests 75nmol/l but some debate. No evidence for this
Can go for higher levels but at a population level, want to avoid deficiency first
UK PHE recommendations changed in 2016 (previously assumed achieved enough in summer but half life is 28 days) to 10ug/day
VITAMIN D AND ETHNICITYD-FNIES STUDY, 2012: extensive vitamin D issues in white Caucasian and South Asian populations (Informed DoH and PHE reccomendations for 10 ug/day)
25(OH)D nmol/L lower in Asian women throughout the year than cuacasian women and asian women extremely deficient throughout the year. Therefore, need higher levels.
UK Biobank study of serum 25(OG)D - Vitamin D defcieincy is almost universal in UK south asian women with 92% <50nmol/L and 55% <25nmol/l and 20% <15 . 10% below detection limit. Supplement use also low
Vitamin D cycling: high levels seen in summer and much lower in winter- is this beneficial? About 30% vitamin D deficient in summer so recommendations of 10ug/day for WHOLE YEAR but best to stop from April to september if outside
Some studies show detrimental associations of high vitamin D levels- could be due to slow adaption of vitamin D hydroxylase enzymes to fluctuating levels so high levels may be detrimental.
Study showed those who cycled seasonally the most, had increased bone resorption= want to keep levels steady).
Superior muscular pwoer and aerboic fitness associated with higher vitamin D status
FOOD SOURCE OF VITAMIN D: Vitamin D2 (plant source) vs D3 from food (animals source)- vitamin D3 50% better at raising vitamin D levels in white caucasian and south asian women- infomred DoH and PHE and food industry.
when lose weight, vitamin D rises as vitamin D stored in fat cells. People who are overweight or obese will have lower levels as weight loss releases more vitamin D
Vitamin D and immune homeostasis vitamind D receptors and enzymes found in immune cells. Meta-analysis of RCT show supplement of Vit D show lower mortality in elderly deficient.
Vit D and respiratory tract infections: SACN recommend supplementation for prevention of respiratory tract infections in addition to muscular-skeletal health
Lower vitamin D levels in North of UK
Rain fall of preceeding summer makes no difference in vitamin D levels of year after
See slide 9- royal osteoprorosis society : puberty is critical period of bone mass attainment . late puberty results in later menopause (beneficial for bone health, exercise can delay puberty)
Calcium homeostasis: If Ca drops in blood, PTH stimulates Ca uptke in intestines and PTH and calciotriol work together to act on osteoclasts to release Ca from bone to balance out levels in blood to return to homeostatic levels 10mg/100mL
Low Vit D (active hormone calciotriol) , which works with PTH, will result in low circulation in blood and more bone lost as PTH rises= AVOID LOW VIT D ACROSS LIFE SPAN
REVERSE: Calcitonin takes Ca from blood to bone and increases Ca losses in urine
Active hormone Vit D important in absorption of calcium from food through production of CBP (Calcium Binding Protein) so low vitamin D will result in LOW CALCIUM ABSORPTION AND HIGH BONE LOSS
Systematic review from Ian Reid et al: Trials on calcium and vitamin D for fracture prevention sub -analyses found > risk of CVD risk (not powered to look at this though)