determinants of osteoporosis

Determinants of Determinants of OsteoporosisOsteoporosis

• Dr.Uma Gupta MD,FICMCH. Professor,Dept of Obstetrics &

Gynecology Era’s Lucknow Medical College.Lucknow

[email protected]

Dr.N.K.Gupta,MS,M.Ch. Professor,Dept of Surgery,Era’s Lucknow

Medical [email protected]

DefinitionDefinitionOsteoporosis is defined as “a

disease characterized by low bone mass and microarchitectural deterioration of bone tissue leading to enhanced bone fragility and a consequent increase in fracture risk”

Simon S. Lee. Osteoporosis. Clin Geriatr Med 2005; 21: 603-629

04/11/23 2uma gupta nk gupta

Magnitude of problemMagnitude of problem

It is a global problem affecting 150 million men and women worldwide.

In USA over 10 million individuals are affected by osteoporosis and 18 million have osteopenia

Osteoporosis prevention, diagnosis and therapy. NIH consensus statement 2000; 17(1): 1-36.


Magnitude of problemMagnitude of problem

Osteoporosis is emerging as a major health problem in view of the increasing number of older people in India. It is estimated that in India 61 million people are affected by osteoporosis out of which 80% are female

Joshi VR, Mangat, G, Balakrishnan C and Mittal G. Osteoporosis approach to Indian scenario. J Assoc Physicians India 1998; 46(11): 965-967.


Magnitude of problemMagnitude of problemAbove 65 years of age, 50% of

females are affected by osteoporosis. One in every third post-menopausal woman is at risk of fracture. Projections in Asia for the year 2050 indicate that this figure will rise from 26% in 1990 to 45%.

Consensus statement of the expert group meeting convened by the Osteoporosis Society of India at All India Institute of Medical Sciences, New Delhi on 10th February, 2003 President Dr. A.B. Dey., Secretary General- Dr. Rohini Handa.


Due to morbid consequences, prevention of osteoporosis is considered essential. Post menopausal osteoporosis is common and is preventable. It’s worldwide health concern & economic burden of osteoporosis is likely to increase with improvement in life expectancy.WHO scientific group on the assessment of osteoporosis at

primary health care level. Summary Meeting Report. Brussels, Belgium, 5-7 May 2004.


WHO definition of osteoporosis is based on BMD levels :

Normal bone mass: T score greater than, equal to -1.0.BMD is above 1 standard deviation below the average young adult value.

Osteopenia:T score between -1.0 and -2.5

BMD is between 1 and 2.5 standard deviation below the average young

adult value.04/11/23 8uma gupta nk gupta

Osteoporosis:T score less than -2.5 BMD more than 2.5 standard

deviation below the average young value.

Severe osteoporosis: T score less than -

2.5or established osteoporosis BMD more than 2.5 standard deviation

below the average young adult value and at least one osteoporotic fracture.

World Health Organ Tech Rep Ser 1994; 843: 1-129.


Pathophysiology - Pathophysiology - osteoporosisosteoporosisBone is a dynamic organ which

remodels itself throughout life. This process involves removal or resorption of bone. Factors that participate in modulating these processes include systemic hormones and local paracrine factors

Simon S. Lee. Osteoporosis. Clin Geriatr Med 2005; 21: 603-629


Pathophysiology - Pathophysiology - osteoporosisosteoporosisThe specialized cells that perform

remodeling include osteoblasts and osteoclasts. The osteoblasts are the cells that form bone. The organic matrix synthesized by osteoblasts includes proteins in addition to type I collagen. There are also noncollagenous proteins within the organic structure

Heinegard D, Hultenby K, Oldberg A et al. Macromolecules in bone matrix. Connect Tissue Res 1989; 21: 3.


Pathophysiology - Pathophysiology - osteoporosisosteoporosisThe osteoclasts are the bone

resorbing cells. Macrophages also participate- through phagocytosis and by producing cytokines. The cytokines participate in increased osteoclast recruitment, differentiation, and function. Systemic hormones and local factors regulate osteoblasts and the osteoclasts.

Raisz LG, Kream BE. Regulation of bone formation. N Engl J Med 1983; 309: 29.04/11/23 12uma gupta nk gupta

Pathophysiology - osteoporosisPathophysiology - osteoporosis

The remodeling process in the adult skeleton is continuous throughout life, peak bone mass is reached in the middle of the third decade of life, a plateau period –

Following this plateau phase there begins, a period of net bone loss equivalent to about 0.3% to 0.5% per yearSimon S. Lee. Osteoporosis. Clin Geriatr Med 2005; 21: 603-629


Pathophysiology - osteoporosisPathophysiology - osteoporosis

Accelerated bone loss is the dominant effect in postmenopausal osteoporosis. With the progressive loss of estrogen, levels of these cytokines rise and enhance bone resorption by increasing the recruitment, differentiation and activation of osteoclast cells

Hurwitz MC. Cytokines and estrogen in bone: anti-osteoporotic effects. Science 1993; 260: 623.


TYPES OF TYPES OF OSTEOPOROSIS:OSTEOPOROSIS:

A. Primary Osteoporosis:(i) Type I osteoporosis: It occurs in hypogonadal individuals. Postmenopausal women and women with oligo-menorrhoea, develop net bone loss directly related to the loss of gonadal function. Patients present with fractures of skeleton where trabecular bone is predominant; e.g.,distal forearm and vertebral bodies.

Prior JC, Vigna YM, Schechler MT et al. Spinal bone loss and ovulatory disturbances. N Engl J Med 1990; 323: 1221.


(ii) Type II osteoporosis: It is associated with the normal aging process and is seen in individuals typically after the age of 60 to 70 years. Normal aging is associated with a progressive decline in the supply of osteoblasts and a decrease in their activity. This results in net loss of bone. Fractures of cortical bone, such as in the femur, femoral neck, proximal tibia, and pelvis, are more common in this group.


Secondary Osteoporosis: It can occur due to endocrine

diseases (hyperparathyroidism, hypothyroidism, chronic renal failure, diabetes mellitus), hypervitaminosis A, immobilization, malignancy, rheumatoid arthritis and drug induced (corticosteroid, ethanol, barbiturates, etc.).

Shah Rashmi S, Savardekar Lalita S. Postmenopausal osteoporosis in India: Growing Public Health Concern. National Institute for Research in Reproductive Health, (ICMR). Presentation made at Forum 9, Mumbai, India, September 2005; 12-16.


DIAGNOSTIC MODALITIES FOR TESTING BMD:

Dual Energy X-ray Absorptiometry (DEXA)

Quantitative Computerized Tomography Quantitative Ultrasonography (QUS)


IMPORTANT RISK FACTORS IMPORTANT RISK FACTORS AFFECTING BONE MINERAL AFFECTING BONE MINERAL DENSITY:DENSITY:

Increasing Age - Perimenopause and Menopause: Oestrogen deficiency is important factor in the pathogenesis of bone fragility.

Prior to menopause, bone loss occurs at the rate of 0.5% to 1.0% per year which accelerates at the rate of 2% to 5% per year due to decline in estrogen levels and is maximum in the first 3-6 years after menopause.

Riggs BL, Kholsa S and Melton LJ III. A unitary model for involutional osteoporosis: estrogen deficiency causes both type-1 and type-2 osteoporosis in postmenopausal women and contributes to bone loss in aging men. J Bone Miner Res 1998; 13: 763-773. 04/11/23 19uma gupta nk gupta

Weight : Low body weight is associated with low BMD.

In obesity, there are several mechanisms that produce higher bone mass including the weight bearing effect of excess soft tissue on skeleton, the association of fat mass with the secretion of bone active hormones i.e. estrogens, leptins and adiponectin from the adipocytes, and the secretion of bone active hormones from other organs such as the gut and the pancreas.

It is suggested that improved vitamin D status due to storage of vitamin D in fatty tissues also improves bone mass.

Kroger H, Tuppurainen M, Honkanen R. et al. Bone mineral density and risk factors for osteoporosis – a population based study of 1600 perimenopausal women. Calcif Tissue Int 1994; 55: 1-7.


Parity and Lactation : Parity and Lactation :

Pregnancy and lactation - predisposing factors for osteoporosis.

During pregnancy, mineralization of fetal skeleton requires approximately 30 g of calcium from maternal sources. Furthermore, abundant calcium is lost from the mother during lactation.

BMD may change during and after pregnancy. Lactation causes bone loss of upto 5%.Sowers MF. Pregnancy and lactation as risk factors for subsequent bone loss and osteoporosis. J Bone Miner Res 1996; 2: 1052-1060.


Menstrual Function Menstrual Function Age at menarche and menopause

seem to be of important in determining endogenous estrogen.

Onset of hypothalamic amenorrhoea is extremely important in determining its impact on bone density. Estrogen deficiency in puberty is -devasting b’s adolescence is a crucial time for bone formation and for eventful attainment of peak bone density. Miller KK and Klibanski. Amenorrhoea bone loss. Journal of Clinical Endocrinology and Metabolism 1999; 84(6): 1775-1783.


Menstrual Function Menstrual Function

Delayed menarche and amenorrhoea during adolescence are associated with decreased peak bone mass.

Untreated hypothalamic amenorrhoea is associated with progressive bone loss during first 5 years of amenorrhoea after which bone loss may significantly decline.

Miller KK and Klibanski. Amenorrhoea bone loss. Journal of Clinical Endocrinology and Metabolism 1999; 84(6): 1775-1783.


DietDietNutrition is an important factor in the

development and maintenance of bone mass. Approximately 80-90% of content is comprised of calcium and phosphorous.

Other dietary components - protein, magnesium, zinc, copper, iron, fluoride, vitamin D, A, C and K .

Ilich JZ, Kerstetler JE. Nutrition in bone health revised: a study beyond calcium. Journal of American College of Nutrition 2002; 19: 715-737.


Calcium SupplementationCalcium Supplementation

The adult human body contains about 1000 to 1500 gm of calcium of which 99% is found in the bone.

Dietary calcium requirements are determined mostly by skeletal needs. Skeletal response occurs only when calcium is increased from the deficiency level to a threshold zone.

Ilich JZ, Kerstetler JE. Nutrition in bone health revised: a study beyond calcium. Journal of American College of Nutrition 2002; 19: 715-737.


Intake of MagnesiumIntake of Magnesium

There is approximately 25 mg of Magnesium in human body.

Magnesium plays an important role in calcium and bone metabolism. Magnesium deficiency alters calcium metabolism resulting in hypocalcemia.


Genetic Factors affecting BMD :

Race and familial predisposition are non modifiable risk factors for osteoporosis10.


Effect of lifestyle on bone massEffect of lifestyle on bone mass

Low physical activity leads to increased bone loss, decreased BMD and increased fracture risk.

Osteoclasts are sensitive to mechanical loading and reduced loading as in immobility leads to bone loss.

Moderate exercise of 5-10 hours per week or high exercise of 10 hours per week produces a better improvement in BMD.


BIOCHEMICAL PARAMETERS BIOCHEMICAL PARAMETERS AFFECTING BMD AFFECTING BMD

Markers of bone formation include – serum calcium, serum inorganic phosphate, serum alkaline phosphatase (total and bone specific), serum osteocalcin, serum procollagen I carboxy-terminal extension peptide.


FSHFSH

Sowers et al performed a longitudinal , Study of Women Health Across the Nations (SWAN).

Participants were 2311 premenopausal or early postmenopausal women.

Baseline FSH values were > 35-45 mIU/ml and lower follow up of FSH (40-50 mIU/ml) predicted a 0.05 gm/cm2 four year spine BMD loss.

The study results gave evidence that FSH may have direct effect on bone.Sowers M, Jannausch M, McConnell D, Little R, Greendle G, Finkelstein J, Neer R, Johnston J and Ettinger B. Hormone predictors of bone mineral density changes during the menopausal transition: Journal of Clinical Endocrinology & Metabolism 2006; 91(4): 1261-1267.


Take home messageTake home message

Bone mineral density and biochemical parameters measurement is helpful in assessing bone health in women. Timely intervention can prevent bone loss and its associated complications


determinants of osteoporosis

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