PRAMUDJI HASTUTI

DEPARTMENT OF BIOCHEMISTRY
FACULTY OF MEDICINE, UGM
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SUB TOPICS

1. Function of bone
2. Composition of bone
3. Bone related with age
4. Hormones affected bone turnover
5. Diet related with bone
6. Physical activity
7. Biochemical markers
8. Menopause
9. Osteoporosis

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 Fragile osteoporotic bone
Strong dense bone
FUNCTION of BONE
= Supporting the body weight

= Protection internal organs

Rib cage = protection for organs located in the
thoracic region :
heart, lungs, abdominal organs, liver, kidneys.
Skull = protect brain

= Primary site of hemopoiesis : formation blood cells

(in the adult)
red marrow long bones, flat bones (sternum, ribs, ileum,
vertebral bodies)

= Storage minerals

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COMPOSITION of BONE
• Matrix
– 40% organic
• Type 1 collagen
• Proteoglycans, osteopintin, thrombopondin
• Osteocalcin/Osteonectin
• Growth factors/Cytokines/Osteoid

– 60% inorganic
• Calcium hydroxyapatite[Ca10(PO4) 6(OH) 2]
• CaCO3, citrate, F, Mg, Na, Mn (impurities)

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Three types of cells in mature bone tissue:
osteoblasts
osteocytes
osteoclasts

Osteoblasts and osteocytes :

involved in deposition bone matrix
produce - collagen type I then calcified
- non-collagenous proteins

Osteoclasts involved in the resorption bone

tissue.

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Development of osteoblasts and osteoclasts from bone marrow progenitors

GH: growth hormone, IGF: insulin like growth factors, PTH: parathyroid hormone
Source : Valsamis et al. Nutrition & Metabolism 2006 3:36 doi:10.1186/1743-7075-3-36 7
BONE RELATED WITH AGE

Bone : dynamic tissue

remodeled continuously throughout the life

Bone density is determined by the dynamic balance

between bone formation and bone resorption.

Increased sex hormone production at puberty is crucial

for achievement of peak bone mass.

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Between 10 and 20 Years : peak bone mass

Girl
begin puberty : 10
start menstrual :12 sufficient estrogen improves
calcium absorption in the kidneys and intestines  fastest
grow in height
stops growing :14 and 15 years
peak bone mass in 20

Boy
fastest rate of growth in height :13 – 14
stops growing :17 -18
Peak bone mass :9 -12 months after the peak rate in height
growth.

Late puberty less bone mass

Obesity boy  delays start puberty
Obesity girls  accelerate puberty 9
Between 20 and 30 Years of Age

- no longer forming new bone

- bones reach peak strength
- get adequate calcium, vitamin D & exercise
Exercise

during teen years essential to reach maximum bone

strength

Exercise excessively in young women lose weight

hormonal changes stop menstrual periods
(amenorrhea) loss estrogen bone loss
Bone mineral density (BMD) : measure bone mass and
strength.

Childhood  adolescence  adulthood

Increase: skeletal mass and BMD, peak in early adulthood

After 30–45 years : bone resorption > bone formation

and BMD begins to decrease.
Decrease in peak bone mass with age
Increase in fracture risk with increasing age.
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Valsamis et al. Nutrition & Metabolism 2006 3:36 doi:10.1186/1743-7075-3-36
HORMONES AFFECTING BONE TURNOVER
• Oestrogen/androgen/GH
– gut - increased absorption Calcium
– bone - decreased reabsorbtion Calcium

• Glucocorticoids
– gut - decrease absorption Calcium
– bone - increased resorption Calcium

• Thyroxine
– Stimulates resorption Calcium

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 Vitamin D (cholecalciferol /Calcitriol)
Help to synthesis of osteocalcin (bone protein)

Deficiency of vitamin D :

- demineralization of bone matrix

- risk factor for low bone mass and fracture
- Severe deficiency defective mineralization skeleton
 rickets in children
 osteomalacia in adults

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 Vitamin D
• Sources :
– Diet
– u.v. light on precursors in skin

• Requirement : 400IU/day

• Target organs
– Gut - increased Ca absorption
– Kidney : increase Ca & Phosphate
reabsorption

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 Metabolism of vitamin D

7-dehydrocholesterol (Skin)
- UV light

25-OH-Vitamin D (Liver)

Ca/PTH
1,25-(OH)2-Vitamin D 24,25-(OH)2-Vitamin D
(Kidney) (Kidney)

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 PARATHYROID HORMONE

Target organs
• bone - increased Ca/PO4 release
• kidneys
– increased reabsorption of Ca
– increased excretion of PO4
• gut - indirect increase calcium absorption by
stimulate activation vitamin D metabolism

Elevated PTH levels

- response to hypocalcemia
- activate bone resorption to maintain normocalcemia

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 CALCITONIN

• increased when serum Ca increase

• Target organs
– Bone - suppresses resorption
– Kidney - increases excretion Ca & Phosphate

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Beneficial factors Potentially detrimental factors
Calcium Excess alcohol
Copper Excess caffeine
Zinc Excess sodium
Fluoride Excess fluoride
Magnesium Excess/insufficient protein
Phosphorus Excess phosphorus
Potassium Excess/insufficient vitamin A
Vitamin C Excess n-6 PUFA
Vitamin D
Vitamin K
B vitamins
n-3 Fatty acid
Protein DIET RELATED WITH BONE
Phytoestrogens
Nondigestible oligo-
saccharides (inulin)
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=Potassium and Magnesium : reduce acidity in
the blood.
= High dietary salt intake  increase renal calcium
excretion  risk of osteoporosis
= Vitamin K for carboxylation of osteocalcin

=Homocysteine : interfer collagen formation

Intake B6, B2, folic acid vitamine inadequate 
increase level of homocysteine

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VITAMIN A
Very high vitamin A have adverse effects on bone

MAGNESIUM
Involved in calcium homeostasis & formation of
hydroxyapatite , if deficient  abnormal bone structure
and function

POTASSIUM
- Reduce : acidity, calcium excretion, bone resorption
- improves calcium balance

-increase bone formation

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ZINC

= Constituent of hydroxyapatite
= needed for functioning of alkaline phosphatase
= needed for functioning IGF-I
= stimulate bone formation

Protein

Poor protein status :

reduced IGF-I  muscle mass and strength low 
risk factor for falls & fracture
High protein diet decrease absorption of Calcium

Phytoestrogens :
soy isoflavones = weak estrogens
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 PHYSICAL ACTIVITY

• increase bone mass

• at least 30 minutes/day
• 3 x a week
- walking
- dancing
- stair climbing
- gardening
- weight-lifting
- Running
- rope jumping
- Hiking
- Tennis
- Volleyball

- Swimming – less helpful

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BIOCHEMICAL MARKERS :

BONE FORMATION : elevated in

Osteoblast activity
serum alkaline phosphatase & osteocalcin
receptors for PTH and vitamin D3
type I procollagen C-terminal peptide(PICP)

BONE RESORPTION : degraded products of

osteoclastic activity in urine :
hydroxyproline
hydroxylysine
hydroxypyridinium collagen cross links

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Increased acidity  dissolve hydroxyapatite crystals
= Organic portion in matrix dissolved by proteolysis
 forms pits on the surface of bones

Bone loss higher in

Women after menopause
Pathologically
Hypogonadism
Medications :steroid & anti-epileptic drug
low bone density and increased risk
fractures.

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Menopause

estrogen level drop rapid bone loss

10 years after menopause lose 40% spongy, inner
bone
10% hard, outer bone

Estrogen replacement therapy increased risk :

- Blood clots
- Stroke
- Heart attack
- Breast and ovarian cancers
- Gall bladder disease
- Dementia.
 Osteoporosis

Clinically :presence fragility fracture & low bone mass

Decrease bone mass per unit volume

Osteoporosis : >- 2.5 SD below the mean peak BMD

(bone mass density)

Osteopenia : BMD -1to -2.5 SD below the mean peak

value (T score <-1 & > -2.5)

Normal : BMD > -1 SD

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Risk factors for osteoporosis

= factors that cannot be modified: gender, age, body

(frame) size, genetics and ethnicity

= factors can be modified:

hormonal status (sex and calciotropic hormone)
lifestyle :physical activity, smoking, alcohol, diet

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REFERENCES

Cashman K.D., Diet, Nutrition and Bone Health, J Nutr., 2007, 137
(11): 2507S-2512S

Zand J, Healthy Bones

BCW819_Nutrition for Healthy Bones (for Adults with or at risk of

Osteoporosis_2011_Mar.pdf

DHBNFBone.htm

Healthy bones June 2011 final.pdf

Healthy Bones at every Age.orthoinfo-AAOS-

Robinson C.M., Student bone metabolism

Valsamis HA , Arora SK , Labban B and McFarlane SI : Nutrition &

metabolism

Indrojit Roy : Bone development 30