OSTEOPOROSIS & DIETBy V.S. Deepika

M.Sc. I year (Applied nutrition)Reg. No. 15MSAN16

IntroductionOSTEOPOROSIS = “porus bones”

Definition of osteoporosisOsteoporosis is a multifactorial, complex disorder characterized by an asymptomatic reduction in the quantity of bone mass per unit volume. When bone mass becomes too low, structural integrity and mechanical support are not maintained and fractures occur with minimal trauma.

Sites affected by Osteoporosis

Distal radiusvertebrae

humerus

pelvis

ribs

Types of OsteoporosisThere are various types of osteoporosis such as,1. Idiopathic juvenile osteoporosis - pre-pubertal children2. Idiopathic osteoporosis - young adults (30 to 50 years) with no obvious

cause 3. Age related osteoporosis - in people above 50 years etc.

most frequently seen in post menopausal women & elderly of both sexes.

Normal spine at age 40 and osteoporotic changes at ages 60 and 70. These changes can cause a loss of as much as 6 to 9 inches in height and result in so called Dowager’s hump (far right) in the upper thoracic vertebrae.

Bone Composition

Bone

Organic30%

Cells, collagen

(95%)

Non collagenous proteins &

mucopolysaccharides (5%)

Inorganic70%

Hydroxyapatite [Ca10(PO4)6OH2]

Bone Structure

Types of Bone & Bone cells

Bone modeling and remodeling

1. Activation step2. Resorption phase3. Reversal phase4. Formation

Peak bone mass & Turn over

Age (years)

Attainment of Peak Bone Mass

Consolidation Age Related Bone Loss

Men

Women

Menopause

0 10 20 30 40 50 60

Fracturethreshold

0.2 to 0.5% per year

2 to 5% per year

Diagnosis of osteoporosis

BMC – bone accumulated before end of growth cessationgm of mineral / cm of bone.

BMD – bone mass after development period is completegm of mineral / cm squared of bone.

Techniques for assessment :1.Bone biochemical markers - can be measured in blood stream or urine.

Matrix markers – collagen molecules Bone cell markers – enzymes alkaline phosphatase, serum PTH, 25 (OH) D.

2. Bone densitometry - single x- ray absorptiometry, DEXA, quantitative CT, bone histomorphometry.

X-Rays Insensitive, Detect loss >30-50%

SPA / DPA Requires Radionuclide photon source

DEXA Gold standard

QCT Spine & Peripheral sites, High radiation

US Cannot be used for diagnosis, Used for assessment of # risk

MRI No direct information on BMD

World Health Organization (WHO) criteria for diagnosis of Osteoporosis

T score – number of SDs a patient’s BMD deviates from a reference population of normal young adults.

WHO, Guidelines for Preclinical Evaluation and Clinical Trials in Osteoporosis, 1998.

Osteoporosis association with Non- Dietary factors

1. Age and Sex2. Body weight and body composition – Body wt. α bone density3. Race / ethnicity – e.g. Africans vs. Asians4. Physical activity – weight bearing exercises5. Reproductive history - high parity & long lactation periods6. Genetics and Familial factors – genetic polymorphisms - BMD7. Estrogen depletion – menopause, early oophorectomy8. Other medical conditions – type- 1 DM, hyperthyroidism, CRF9. Use of other medications – Al- antacids, tetracyclines,

anticonvulsants, exogenous thyroid etc.10. Cigarette smoking- alterations in estrogen metabolism

Osteoporosis association with Dietary factors

Calcium : -ve balance in osteoporosis Ca balance depends on Ca content in diet, efficiency of Ca

absorption by intestine etc.Pre menopausal women, post menopausal women – Increase Ca intake decrease in rate of bone loss.

Phosphorous : P depletion occurs before the Ca is locally depletedOsteoblast function is severely compromised

Indians usually meet RDA for phosphate so depletion is not common.

Vitamin D : commonest cause of osteoporosis.Vit- D supplementation in elderly (800 IU/day) is beneficial for

optimal bone health and reduces the risk of fractures.

Contd…Vitamin K : Vitamin K is a co- factor for gamma carboxylation of 3 bone matrix proteins.Osteocalcin is the best studied of these which is a bone specific protein.

Vitamin K may reduce urinary Ca loss in patients with Osteoporosis

Contd…Vitamin C : Is necessary for collagen cross linking. Leveille et al have found that the long term use of vit- C supplements - higher BMD in women aged 55 to 64 yrs vs. those who had never used estrogen.

Vitamin A : Excess vitamin A seems to stimulate osteoclasts and suppress osteoblasts. Bone has receptors for vitamin A and vitamin D, hence high intakes of vit –A interfere with vit – D activity.

Protein : Excess of purified protein- contributor of osteoporosis riskCalciuric effect

Most protein rich foods contain many other nutrients that could counteract Calciuric effect of protein.

Contd…Fiber : It chelates Ca (and other minerals) in G.I tract.

High fiber diets (taken as staple foods) increase osteoporotic risk.

Other micronutrients : several dietary components affect dietary Ca absorption. Manganese, copper, and znic are necessary cofactors for enzymes involved in bone metabolism.Some evidences showed their supplementation to have some benefit when added to a supplementation regimen.

Alcohol : Moderate alcohol is beneficial.Alcohol stimulates the conversion of androstenedione to estrone,

an estrogenic compound with bone preserving properties.But,

Bone formation is decreased in patients who abuse alcohol.

Contd…Phytoestrogens : confer estrogen like effects.

these have both estrogenic and anti – estrogenic activity and seem to achieve these properties by binding to estrogen receptors.e.g. present in sprouts, beans, and soybeans.Isoflavones have most potent estrogenic activity when compared to other phytoestrogens. – prevent bone loss.

Sodium and caffeine are also said to cause increase in Ca excretion.

Medical therapies for osteoporosis1. ERT / HRT : Administration of estrogen molecules to replace the menstrual hormone.

Approved by FDA. But now only used for treating menopausal symptoms because of its adverse effects.

2. Biphosphonates : inhibition of bone resorption through a direct dose related effect on osteoclasts. Approved by FDA.

3. Calcitonin: inhibits bone resorption.salmon calcitonin is a more potent inhibitor of bone resorption than human calcitonin.

4. Selective estrogen receptor modulator (SERM) : these act on estrogen receptors in osteoblasts to promote the maintenance of bone

tissue.5. Intermittent therapy of PTH : it is the first anabolic agent to be FDA approved for the treatment of osteoporosis.

SCIENTIFIC REPORT – 1:Chennaiah S, Vijayalakshmi V, Suresh C

Effect of supplementation of dietary rich phytoestrogens in alternating the vitamin D levels in diet induced osteoporotic rat model.J Steroid Biochem Mol Biol.121:268-272, (1.F2.866), March 2010.

Aim of the study : was to elucidate whether supplementation of Isoflavones (daidzein and genistein) rich Cow pea is capable of preventing rapid bone loss occuring after diet induced OSP in rats.

Animals and conditions maintained:Female weanling WNIN rats (30-35g) were selected and maintained

at an ambient temperature (20±20C) and relative humidity of 50 to 80%. Rats were allowed for illumination 12 hour light and 12 hour dark.It was approved by institute’s animal ethical committee.

Contd…Study design and conduct: Total of 68 rats.

Firstly they are fed semisynthetic diet with low Ca (O.15%) & low VD (0.1IU/day/rat) as proposed by suda et al. In combination with low (10mg/kg) or high (25mg/kg) concentration of PE’s derived from CPIF. The study groups are

1. Normal Ca (0.47%) & normal VD (25 IU/day/rat) - 6 rats – control diet.2. Low Ca & low VD – 38 rats3. Low Ca & low VD & low CPIF (10mg/kg diet) – 8 rats4. Low Ca & low VD & high CPIF (25mg/kg diet) – 8 rats5. Low Ca & Low VD & 17- β – estradiol (3.2mg/kg diet) – 8 rats

They had an access to deionized water and food intake was recorded every alternative. Body weight was checked for every 4 days.

After as rats developed OSP after 6 weeks as indicated by BMD, BMC and biochemical analysis, the group 2 was sub grouped intoSG 1 continued on low Ca & VD – 8 ratsSG 2 low CPIF – 8 ratsSG 3 high CPIF – 8 ratsSG 4 17- β – estradiol – 8 ratsSG 5 normal Ca & VD – 6 rats.

Contd…After 90 days the rats were sacrificed and investigations were

carried out to find the protective and therapeutic effects of CP.BMD and BMC noted by DEXA, serum 25 (OH) D- RIA, serum ALP- Walter-schult-enzyme activity, serum Ca –atomic absorption spectrophotometry.Inference from the results:• Improved BMD, BMC of whole body, Ca, P and ALP levels. In

addition 25-VD also found to play a role in partially reversing the clinical manifestation of the osteoporotic situation in the rats.

• CPIF diet alone was not sufficient to reverse the loss in the whole body BMD due to diet induced OSP but can provide additive effect in terms of bone density; BMD was maintained normally in the control diet group.

• Low BMD and BMC levels improved in SG 2, 3 & 5 of group 2, after OSP + supplementation of CPIF.

Contd…• Daidzein and genistein, improved BMD by suppressing the bone

turnover increase.• CPIF might have suppressed osteoclastic activity through tyrosine

kinase inhibition and the bone loss preventive effects of IF resulted from suppression in bone turnover increase and could be due to mechanism similar to that of estrogens.

• IF inhibitory effects on osteoclasts as inhibitors of Ca- dependent signaling molecules calmodulin and protein kinase which antagonizes the reduction in osteoclast no. induced by these compounds.

• 25 – VD levels were found to be altered in a significant way in SG 2, 3 and 5 of group 2 indicating the fact that CPIF and VD metabolism involvement in bone mineralization.

Conclusion of the study

CPIF had a convincing effect in protecting the bone mineralization in the critical situation like OSP in terms of improving BMD, BMC, Ca, ALP and 25 VD levels. It is inconclusive whether IF had a therapeutic effect and needs to be further investigated.

SCIENTIFIC REPORT - 2:Bharati kulkarni, Anjali Ganpule- Rao, Urmila Deshmukh and Chittaranjan Yajnik.

Maternal influences on bone health in Indian children: Appraisal of the evidence.Asia- Pacific journal of endocrinology, 2009.

Aim of the study:The study was on the impact of maternal factors on offspring bone health review and it suggested that the “Developmental Origins of Health and Disease” (DoHaD; or the life cycle) approach is the best available model to curtail the epidemic of osteoporosis and related conditions.

Proving by the evidence from Pune maternal nutrition study – 1993 – carried out in 6 villages near to Pune.PMNS cohort was established to test and elaborate the fetal origins hypothesis. That study data provided the data needed to prove the maternal influence on offspring bone heath.

Contd…Details of the study:

1. House to house study.2. 1675 young women registered.3. All aged < 35 years and not sterilized.4. Menstrual dates were recorded every month.5. Detailed anthropometry done for every 3 months.6. Age of mother’s = 21.5 (+3.4) years, weight= 46.7(+6.5)kg,

height= 1.52 (+0.05)m, BMI= 18.1 (+2.5)kg/m2.7. All ate approximately 1700 kcal/day. 45 g of protein,

physically active worked both at home and farm.8. During the study 824 women became preganant.9. 770 women delivered single live baby.10. LBW registered is 28%.

Contd…Conduct of the study:The PMNS collects data serially at different time points of study material and from data we draw the developmental influences on offspring bone health.

Maternal factorsSize and body composition,

Dietary intake, Physical activity,

supplements.

Fetal skeleton development

Birth size

Lactation

Childhood &

adolescent growth

Peak bone mass

OsteoporosisFracture risk

DoHaD concept of skeletal development, Growth and its relationship to bone health and Disease.

Contd…Observations from the study:1. They suggest that modifications in maternal nutritional factors may influence

bone health in offspring. Paternal influence might operate through genetic mechanism or through a shared environment.

2. Preterm infants had lower total body BMC than term infants and are at increased risk of osteopenia, rickets and fracture.

3. Impact of childhood nutrition on the accumulation of peak bone mass may contribute to osteoporosis.

4. Suboptimal peak bone mass resulting from early life factors may be difficult to compensate for by optimal nutrition in later years.

5. A beneficial effect of maternal calcium supplementation on neonatal bone health has been reported from India.

Conclusion from the study:This study report states that the available evidence to achieve optimum offspring

bone health points towards modifiable maternal factors including nutrition and physical activity. The life style factors including nutrition and environment during growing years also need equal attention. The DoHaD model emphasizes the need to start early in life to prevent the rising epidemic of osteoporosis.

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