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A STUDY OF METACARPOCORTICAL INDEX IN CHRONIC

RENAL FAILURE

DISSERTATION SUBMITTED FOR

M.D GENERAL MEDICINE

BRANCH - I

MAY 2018

THE TAMIL NADU

Dr. M G R MEDICAL UNIVERSITY, CHENNAI

TAMIL NADU, INDIA

CERTIFICATE FROM THE DEAN

This is to certify that the dissertation entitled “A STUDY OF

METACARPOCORTICAL INDEX IN CHRONIC RENAL FAILURE”

is the bonafide work of Dr. MANOJ M S in partial fulfilment of the

University regulations of the Tamil Nadu Dr. M.G.R Medical University,

Chennai for M.D General Medicine Branch I examination to be held in MAY

2018.

Prof. Dr. MARUTHUPANDIAN M.S

The Honourable Dean

Madurai Medical College

Govt. Rajaji Hospital

Madurai

CERTIFICATE FROM THE HOD


METACARPOCORTICAL INDEX IN CHRONIC RENAL FAILURE” is

the bonafide work of Dr.MANOJ M S in partial fulfilment of the university

regulations of the Tamil Nadu Dr. M.G.R Medical University, Chennai for M.D

General Medicine Branch I examination to be held in MAY 2018.

Prof. Dr. V. THEOPHILUS PREMKUMAR, M.D.,

H.O.D & Professor of Medicine

Department Of General Medicine,

Government Rajaji Hospital,

Madurai Medical College,

Madurai.

CERTIFICATE FROM THE GUIDE


METACARPOCORTICAL INDEX IN CHRONIC RENAL FAILURE” is

the bonafide work of Dr. MANOJ M S in partial fulfilment of the university

regulations of the Tamil Nadu Dr. M.G.R Medical University,Chennai for M.D

General Medicine Branch I examination to be held in MAY 2018.

Prof Dr. G. BAGIALAKSHMI, M.D.,

Professor of Medicine,

Department Of General Medicine,

Government Rajaji Hospital,

Madurai Medical College,

Madurai.

DECLARATION

I, Dr.MANOJ M S solemnly declare that this dissertation “A STUDY

OF METACARPOCORTICAL INDEX IN CHRONIC RENAL

FAILURE” is a bonafide record of work done by me at the Department of

General Medicine, Govt.Rajaji Hospital, Madurai under the guidance of

Dr.G. BAGIALAKSHMI, MD, Professor. Department of General Medicine,

Madurai Medical College. Madurai. This Dissertation is submitted to the Tamil

Nadu Dr. M.G.R Medical University in partial fulfilment of the rules and

regulations for the award of M.D GENERAL MEDICINE DEGREE

BRANCH–I examination to be held in MAY 2018.

DATE :

PLACE : MADURAI (Dr. MANOJ M S)

ACKNOWLEDGEMENT

I would like to thank our respected dean Dr.MARUTHUPANDIAN M S.,

Madurai Medical college for permitting me to utilize the facilities of Madurai

Medical college and Government Rajaji Hospital for this dissertation. I wish to

express my respect and sincere gratitude to my beloved teacher and Head of the

Department, Prof. Dr. V.THEOPHILUS PREMKUMAR, M.D., Professor of

Medicine for his valuable guidance and encouragement during the study and

also throughout my course period. I would like to express my deep sense of

gratitude, respect and thanks to my beloved Unit Chief and Professor of

Medicine, Prof. Dr G. BAGIALAKSHMI, M.D., for her valuable suggestions,

guidance and support throughout the study and also throughout my course

period.

I am greatly indebted to the Professors, Dr. R. BALAJINATHAN, M.D.,

Dr. M. NATARAJAN, M.D, Dr.J.SANGUMANI, M.D,

Dr.DHARMARAJ M.D. and Dr. Dr. R. PRABHAKARAN, M.D., for their

valuable suggestions throughout the course of the study.

I sincerely thank the Assistant Professors Dr.P.SARAVANAN M.D., and

Dr. S.KRISHNASAMY PRASAD M.D., for their guidance and suggestions in

this dissertation work.

I am extremely thankful to Prof. Dr. ARUL, MD. DM., Head of the

Department of Nephrology for their constant support, guidance, cooperation

and to complete this study.

I am thankful to Prof. Dr. SUMATHI, MD., Head of the Department of

Radiology for their constant support, guidance, cooperation and to complete this

study.

I am thankful to Prof. Dr. MOHANAKUMARESAN, MD., Head of the

Department of Bio-chemistry for their constant support, guidance, cooperation

and to complete this study.

I sincerely thank all the staffs of department of medicine for the timely help

rendered to me whenever and wherever needed.

I am extremely thankful to my beloved father Mr A MOHANRAJ and mother

Mrs C SARASWATHI , my brother and sister for their constant support

throughout my study and course period.

My special thanks and love for my wife Dr. G.V.PREETHI for her constant

support throughout the study and course period.

I extend my thanks to all my friends, batch mates, my juniors and senior

colleagues who have stood by me and supported me throughout my study and

course period.

Finally, I thank all the patients, who form the most vital part of my work, for

their extreme patience and co-operation without whom this project would have

been a distant dream and I pray God for their speedy recovery.

CONTENTS

S.NO TOPICS PAGE.NO.

1. INTRODUCTION 1

2. AIMS AND OBJECTIVES 4

3. REVIEW OF LITERATURE 5

4. MATERIALS AND METHODS 46

5. RESULTS AND INTERPRETATION 49

6. DISCUSSION 71

7. CONCLUSION 74

8 LIMITATIONS OF THE STUDY 75

9 ANNEXURES

PROFORMA i

MASTER CHART iv

BIBLIOGRAPHY v

ETHICAL COMMITTEE APPROVAL LETTER viii

ANTI PLAGIARISM CERTIFICATE ix

1

INTRODUCTION

Chronic renal failure is a pathophysiological process with many

etiologies resulting in the inexorable attrition of nephron number and function

and frequently leading to end stage renal disease. Uremia is a clinical and

laboratory syndrome reflecting dysfunction of all organ systems as a result of

untreated or under treated acute or chronic renal failure. Renal osteodystrophy

is observed in 75-100% of patients with chronic renal failure as the glomerular

filtration rate (GFR) falls below 60 ml/minute. Renal osteodystrophy is an

almost universal consequence of chronic renal insufficiency and is associated

with rickets in child hood and osteomalacia in adults, hyperparathyroidism,

osteosclerosis and osteoporosis. In normal bone, the remodeling process of

removal and replacement is tightly coupled.

Osteoblasts are responsible for the production of bone matrix constituents

such as collagen and ground substances which become mineralized and the

multinucleated osteoclasts which are in contact with calcified bone surfaces

reabsorb bone. End-stage renal disease (ESRD) may result in abnormal

turnover, coupling, and mineralization. As nephron loss causes the glomerular

filtration rate (GFR) to fall below 60 ml/minute, phosphate is retained inducing

a rise in parathyroid hormone (PTH) and a decline in 1,25-dihydroxyvitamin D

levels. As described in 1969 and termed the “trade-off hypothesis.” The PTH

rise reduces renal phosphate reabsorption so that phosphate balance is restored.

2

Calcium levels are maintained by the rise in PTH as is 1, 25-dihydroxyvitamin

D homeostasis, providing adequate renal mass remains. In 50% of patients,

abnormal bone histology is present at this level of renal function. With further

reduction in the GFR to 20-40 ml/minute, 1,25-dihydroxyvitamin D levels fall

below normal and calcium and phosphate homeostasis cannot be maintained.

Skeletal PTH resistance also increases with worsening uremia and in the

immediate predialysis period almost all patients have abnormal bone histology.

Hyperparathyroid (high turnover) bone disease is found most frequently

followed by mixed osteodystrophy, low-turnover bone disease, and

osteomalacia. With advancing renal impairment, “skeletal resistance” to

parathyroid hormone (PTH) occurs. To maintain bone turnover, intact PTH

(iPTH) targets from two to four times the upper normal range have been

suggested, but whole PTH (1-84) assays indicate that amino-terminally

truncated fragments, which accumulate in end-stage renal disease (ESRD),

account for up to one-half of the measured iPTH. PTH levels and bone-specific

alkaline phosphatase (BSAP) provide some information on bone involvement

but bone biopsy and histomorphometry remains the gold standard. Calcitriol

and calcium salts can be used to suppress PTH and improve osteomalacia but

there is growing concern that these agents predispose to the development of

vascular calcification, cardiovascular morbidity, low-turnover bone disease and

fracture. Newer therapeutic options include less calcemic vitamin D analogues,

3

calcimimetics and bisphosphonates for hyperparathyroidism, and sevelamer for

phosphate control. Calcitriol and hormone-replacement therapy (HRT) have

been shown to maintain bone mineral density (BMD) in certain patients with

end-stage renal disease (ESRD). After renal transplantation, renal

osteodystrophy generally improves but BMD often worsens. Bisphosphonate

therapy may be appropriate for some patients at risk of fracture. When renal

bone disease is assessed using a combination of biochemical markers, histology

and bone densitometry, early intervention and the careful use of an increasing

number of effective therapies can reduce the morbidity associated with this

common problem. One of the earliest radiological changes in chronic

renalfailure is metacarpocortical index (MCI).

It is sum of medial +lateral cortical thickness of second metacarpal bone

at mid point divided by total thickness of second metacarpal bone. This study is

conducted to measure bone density by calculating metacarpocortical thickness

of second metacarpal bone by X-ray which is simple and reliable method to

predict bone changes (MCI index) in comparison with biochemical parameters

like serum creatinine, urea, calcium, phosphorus, alkaline phosphatase, uric acid

, vitamin D3 and axial skeletal survey which may help in optimising dosage of

calcium and vitamin D 3 supplements.

4

AIM OF STUDY

1. Early detection of renal osteodystrophy.

2. Calculate metacarpocortical index (MCI) and predict quantitative bone

changes in Chronic renal failure (CRF) patients.

3. Comparison between metacarpocortical index in CRF with biochemical

parameters like blood urea, serum creatinine, serum calcium, serum

phosphorus, serum alkaline phosphatase , serum uric acid , serum vitamin

D3 and survey of axial skeletal region.

5

REVIEW OF LITERATURE

DISEASE BURDEN OF CKD:-

According to the latest published evidence, CKD has resulted in almost

one million deaths worldwide, and is the direct cause of one out of 57 fatal

outcomes. It remains among the few growing causes of mortality which made

CKD the 13th leading cause of death in 2013; this compared to ranking 27th in

1990, signifying a rise of 134% over this period. In past decades, the increase of

CKD-related mortality has remained prominent even after considering changes

in the world’s age structure and population growth. Regarding age-standardised

rates, only a few conditions such as HIV/AIDS, atrial fibrillation, and drug

abuse have increased mortality more than CKD. Kidney disease is closely inter-

related with heart and blood vessel disease, with 7% of all cardiovascular deaths

attributed to the reduced glomerular filtration rate, a principal marker of CKD.

Importantly, CKD also has a strong impact on morbidity and non-fatal

outcomes. Among over 300 causes accounted for in the GBD Study, CKD is the

15th and 20th leading cause of years lived with disability and disability-adjusted

life years.

High-quality epidemiological studies conducted in different parts of the

world revealed that 10–13% of the adult population have markers of

CKD. Moreover, kidney diseases are projected to grow further due to many

factors, including the aging general population and the growing prevalence of

6

diabetes. Widespread kidney disease in child populations is less common, but

requires special precaution, early evaluation and appropriate treatment to

prevent CKD in later life—as highlighted by World Kidney Day 2016.

CKD is widespread but insufficiently recognised, and has a high impact

on mortality and morbidity; this impacts directly kidney diseases, and indirectly

cardiovascular diseases. Thus, the performance of CKD screenings by general

practitioners is badly needed, at least in the designated high-risk populations.

The good news is that modern clinical practice guidelines for CKD are

available, and the appropriate treatment has been developed for protecting

kidneys. Implementing the available cost-effective treatment has already helped

to delay CKD complications in distinct subgroups of patients in the emerging

world. Kidney disease is common and harmful, yet treatable.

The kidney is one of the most highly differentiated organs in the body. At

the conclusion of embryologic development, nearly 30 different cell types form

a multitude of filtering capillaries and segmented nephron enveloped by a

dynamic interstitium. This cellular diversity modulates a variety of complex

physiologic processes. Endocrine functions, the regulation of blood pressure

and intraglomerular hemodynamics, solute and water transport, acid-base

balance, and removal of drug metabolites are all accomplished by intricate

mechanisms of renal response.

7

DIAEASE BURDEN OF CKD IN INDIA:-

There is an epidemiological transition taking place in India, with the

decline in communicable diseases and a growing burden of chronic disease. In a

recent review, Reddy and others noted that 53 per cent of deaths in India in

2005 were due to chronic disease. The principal named categories of chronic

disease in their report were cardiovascular disease, cancer, chronic respiratory

disease and diabetes. Notably, chronic kidney disease (CKD) was not a category

on its own merits but most likely included under the ‘other’ category.

The World Health Organization laid down certain criteria for a major

non-communicable disease (NCD), namely, (i) being a major cause of

morbidity and mortality, (ii) being amenable to prevention by community based

strategies, and (iii) sharing common risk factors with other NCDs . Though

CKD meets these criteria, it does not find a place in this category. There is no

reason to suspect that the global epidemic of CKD does not have its counterpart

in India and epidemiologic indicators suggest that it is likely to be sizeable.

India has been described as the diabetes capital of the world, every fifth diabetic

in the world being Indian .

Hypertension is not far behind – the CURES cohort in Chennai showed

that every fifth individual was hypertensive. The increasing prevalence of

diabetes, hypertension and associated risk factors such as obesity,

hypercholesterolaemia and the metabolic syndrome underscores the potential

8

for sustained and explosive growth of this epidemic. The epidemiology of CKD

in India is very different from the West. Patients are roughly two decades

younger, and a substantial proportion present with small kidneys, so the

aetiology of CKD is unclear. The contribution of less well understood risk

factors toward these epidemiologic differences is unknown - low birth weight

and relationship to diminished nephron , variations in Th1/Th2 regulatory

lymphocyte balance and relationship to glomerulonephritis as postulated by the

‘Hygiene hypothesis’ and the so called ‘Asian Indian Phenotype’ or ‘Thrifty

Phenotype’ of truncal/visceral obesity and insulin resistance, have been poorly

studied in this context. Recent publications have dealt with mainly single centre

reports or regional population based estimates and the definition of CKD has

differed. In the absence of nationwide reporting systems or registries, the true

incidence and prevalence is difficult to determine.

Observational and anecdotal data suggest that the normal ranges of

glomerular filtration rate (GFR) may be lower in the predominantly vegetarian,

less muscular Indian subjects with different creatinine generation rates,

compared to their western counterparts although this issue needs more rigorous

study. In the last decade, there has been a major evolution in the definition and

classification of CKD that is based upon estimated GFR. Application of these

definitions would impact identification of disease. Therefore issues of global

implementation will need to be resolved. Mani, working in Chennai, South

9

India, estimated a prevalence of chronic renal failure of 0.16 per cent in the

community in 2003; applying the Modification in Diet in Renal Disease

(MDRD) equation for GFR estimation in 2005, 0.86 per cent was found to have

a GFR 1.8 mg/dl. Estimates for the United States (US) population extrapolated

from the National Health and Nutrition Examination Survey (NHANES III) data

place the prevalence of CKD stages 4 and 5 (severe decrease in GFR) and CKD

stage 3 (moderate decrease in GFR) at 0.4 percent. However, such direct

comparisons with Western populations are not valid; since the equivalent GFR

for a serum creatinine of 1.8 mg/dl in Indians may place the individual

anywhere between CKD stages 2 to 4 depending upon gender and nutritional

status. Modi and Jha reported from an urban population in the city of Bhopal,

that the crude and age adjusted incidence rates of end stage renal disease

(ESRD) were 151 and 232 per million population, respectively.

ESRD incidence rates lend themselves more easily to international

comparisons as the diagnosis is less susceptible to inaccuracies. These estimates

are roughly similar to the US. However, notwithstanding the actual proportions

of individuals with disease, the one billion population of India makes the

absolute numbers of patients potentially needing specialized and expensive

tertiary care, enormous. Moreover, the socioeconomic implications of a young

population afflicted with a potentially terminal illness are devastating and in the

face of growing epidemics of diabetes and hypertension, the burden of CKD is

10

not likely to ease. On this background, the study in this issue from the Christian

Medical College and Hospital (CMCH) in Vellore, South India, describing the

pre-tertiary care of patients with CKD is timely. Varughese and colleagues

studied 561 patients presenting with CKD stage 5 for the first time to their

institution, over an eight month period. Advanced CKD was the initial

presentation in over half the patients, and CKD was already known in the

remainder for a mean duration of a year, possibly less in a majority. Despite

more than 90 per cent having been under the care of a nephrologist or internist,

the majority were self-referred.

Kidney disease related investigations -proteinuria quantification,

ultrasonography - had been performed in respectively 48 and 86 per cent, viral

screening (hepatitis B, C, HIV) in about a third or less and immunization

against hepatitis B initated in less than a quarter. Blood pressure was

inadequately controlled in 62 per cent, 18 per cent were receiving recombinant

erythropoietin (rEPO), 40 per cent had already been transfused for the

correction of anaemia and about 16 per cent had undergone prior arterio-venous

fistula construction. All these parameters, as well as education and preparation

for future renal replacement therapy (RRT) were more likely to happen under

the care of a nephrologist.

11

DISEASE BURDEN OF RENAL OSTEODYSTROPHY:-

The increasing incidence and prevalence of chronic kidney disease

(CKD), including kidney failure requiring renal replacement therapies (RRT),

have drawn attention to the need for understanding accompanying mineral bone

disorder (CKD-MBD). Individuals with CKD are at increased risk of bone

disorders, vascular abnormalities, and premature mortality due in part to

changes in calcium and phosphate homeostasis. While recent guidelines focus

primarily on treating renal failure populations, work from Levin and colleagues

describes early changes in mineral metabolism, particularly parathyroid

hormone (PTH) concentrations, that are evident in individuals with only

moderate kidney disease. Thus, secondary hyperparathyroidism (SHPT), bone

remodelling, and associated mineral dysfunction have been seen to begin in the

setting of established CKD when individuals are either asymptomatic or

unaware that they have kidney disease.

Because the increased focus on mineral and bone disorders in CKD is

relatively recent, little published information is available regarding the

international burden of SHPT among even renal replacement populations.

Hence, understanding the total burden of SHPT may be feasible only by

understanding the total burden of CKD. Nationwide registries now exist to track

chronic renal failure, with additional publications providing estimates of the

12

population burden of earlier stage disease. An internationally based systematic

review could help estimate this burden.

INCIDENCE AND PREVALANCE OF RENAL OSTEODYSTROPHY:-

The worldwide population is aging. In the United States alone, the

number of persons aged 65 years and over is expected to rise from 32 to 69

million between 1990 and 2050, and the number over the age of 85 years will

increase from 3 to 15 million. The global population is demonstrating similar

trends as the number of persons aged 65 years and over is expected to rise from

323 to 1555 million between 1990 and 2050. These demographic trends have

raised great concern about the burden of several common diseases associated

with aging.

Osteoporosis, defined by the World Health Organization as a disorder of

bone resulting in decreased bone strength, is an extremely common disorder of

aging that currently affects 10–12 million people in the United States alone.

Future projections, based on the aging of the United States population, indicate

that the number of people with osteoporosis will increase exponentially during

the first half of this century. For example, the estimated 7.8 million women and

2.3 million men affected with osteoporosis at the hip today is expected to

increase to 10.5 and 3.3 million, respectively, by 2020.

13

Fractures represent the main clinical manifestation of osteoporosis. Half

of all women over the age of 50 years will suffer an osteoporotic fracture during

their lifetime. Moreover, the increased prevalence of osteoporosis at the hip is

expected to lead to a tripling of the number of hip fractures worldwide by 2050.

The medical and economic burden of fragility fracture is substantial. Burge and

colleagues have recently estimated that the incidence of osteoporotic fractures

will increase by almost 50% from two million fractures in 2005 to three million

fractures in 2025. The associated cost of those fractures is estimated at $25.3

billion. When the impact of hip fracture on the quality of life is considered in

disability-adjusted life years, the global burden of disease (GBD) has been

estimated at 1.75 million years, with approximately one-quarter occurring in

China and India, and 50% occurring in Western countries alone.

Declining kidney function is another extremely common disorder of

aging. Over the past decade, there has been a worldwide epidemic of chronic

kidney disease (CKD). In a recent analysis of the Third National Health and

Nutrition Examination Survey (NHANES III), Coresh et al. found that the

prevalence of significant kidney impairment was remarkably high in the elderly

US population. Of those aged 70 years and above, only 26% had normal kidney

function, whereas 49% had mildly and 25% had moderately decreased kidney

function. Notably, the short-term risk of osteoporotic fracture increases

dramatically after the age of 70 years. However, despite the fact that

14

osteoporotic fracture and mild-to-moderate CKD (Stages 1–4) are highly co-

prevalent in the elderly, relatively few studies have examined the contribution

of impaired kidney function to the risk of fragility fracture.

Given the rapid worldwide growth of an elderly population at risk for

both osteoporosis and CKD, and the many potential mechanisms by which CKD

could decrease bone strength and increase fracture risk, it is imperative that we

develop effective diagnostic strategies to identify patients with CKD who are

also at risk for fracture. It is also essential that we develop effective therapeutic

strategies that decrease fracture risk in patients with CKD.

. FRACTURE RISK IN END-STAGE KIDNEY DISEASE

The risk of fracture is greatly increased in patients with ESKD..Using the

United States Renal Data System, Alem et al demonstrated a four-fold increased

risk of hip fracture in men and women on hemodialysis. Although the risk

exceeded that of the normal population in all age groups of patients with ESKD,

for those less than 65 years old the relative risk ranged between 10- and 100-

fold higher, most likely due to the generally low incidence of hip fracture in

normal men and women below the age of 65 years.

Other studies of patients with ESKD have shown that yearly incidence

rates for fracture by site are about 1% per year for hip fracture and about 2.6%

for any fracture .This compares with the incidence rates of 0.07–0.22% for

15

fracture at the hip in the general population. Risk factors for fracture in patients

with ESKD include, both traditional risk factors for osteoporotic fracture (older

age, female gender, low body weight, postmenopausal status, osteoporosis

history, family history of osteoporosis, previous fracture, propensity to fall, and

the use of psychoactive medications, such as benzodiazepines and selective

serotonin reuptake inhibitors) and also risk factors that are specific to patients

with ESKD, including the duration of kidney replacement therapy, exposure to

glucocorticoids, history of a kidney transplant, and both low and high

parathyroid hormone (PTH) levels. It is noteworthy that fracture rates in

patients with ESKD are similar to fracture incidence rates of non-uremic

individuals who are older by 10–20 years.

FRACTURE RISK IN PRE-DIALYSIS CKD:-

A growing body of literature suggests that patients with CKD who do not

yet require renal replacement therapy are also at an increased risk of fragility

fracture. In a cross-sectional analysis of the NHANES III, we showed that

moderate-to-severe kidney disease was independently associated with more than

a 2-fold increase in history of hip fracture. This association was stronger than

several traditional risk factors for fracture including age, gender, race, body

weight, and bone mineral density (BMD) measured at the hip by dual-energy X-

ray absorptiometry (DXA)..A similar relationship was noted in an analysis of

the Cardiovascular Health Study. After multivariate adjustment for risk factors

16

associated with osteoporotic fracture, there was a statistically significant 16%

increased risk of incident hip fracture for women per standard deviation

increase in cystatin C. Furthermore, in a case–control cohort study that selected

women with either hip (n=149) or vertebral (n=150) fracture from the Study of

Osteoporotic Fractures, the risk of trochanteric fracture was significantly

increased by 5-fold and 3.5-fold with a glomerular filtration rate (GFR) less

than 45 ml/min and between 45 and 59 ml/min, respectively. In a cross-

sectional study of elderly men and women treated for osteoporosis, a creatinine

clearance of less than 65 ml/min was associated with a significant increase in

the risk of hip, spine, and wrist fractures. In summary, these studies are

consistent in demonstrating that fracture risk is increased in patients with

moderate-to-severe CKD.

17

STUDIES OF FRACTURE RISK ASSOCIATED WITH CKD:-

Studies of fracture risk associated with CKD

Study Definition of kidney

function

Fracture

site

Fracture risk (95%

CI)

Dukas et

al. (2005) <65 ml/min Hip

OR 1.57

(1.18–2.09)

Wrist

OR 1.79

(1.39–2.31)

Vertebral

OR 1.31

(1.19–1.55)

Nickolas et


OR 2.32

(1.13–4.74)

Ensrud et

al. (2007) 45–59 ml/min Hip

HR 1.24

(0.60–2.56)

<45 ml/min

HR 1.41

(0.59–3.36)

45–59 ml/min Trochanteric

HR 3.69

(1.21–11.24)

<45 ml/min HR 5.04

18

Study Definition of kidney

function

Fracture

site

Fracture risk (95%

CI)

(1.38–18.45)

Jamal et

al. (2007) <45 ml/min Any fracture

OR 1.3

(1.0–1.6)

Vertebral

OR 2.5

(1.6–3.9)

Fried et


HR 1.38

(0.99–1.94)

Per s.d. increase in

cystatin C Hip

HR 1.16

(1.01–1.33)

CI, confidence interval; CKD, chronic kidney disease; HR, hazard ratio; OR,

odds ratio.

20

RENAL OSTEODYSTROPHY

In 2004, the National Kidney Foundation defined renal osteodystrophy

(ROD) as a constellation of bone disorders, present or exacerbated by CKD, that

lead to bone fragility and fractures, abnormal mineral metabolism, and

extraskeletal manifestations. However, this definition did not gain international

acceptance, in part, because of its lack of bone specificity. The Kidney Disease:

Improving Global Outcomes (KDIGO) committee refined the definition of

ROD, specifically limiting the term to the various types of bone pathology

found in patients with CKD. Another term, CKD-mineral and bone disorders

(CKD-MBD), was chosen to refer more broadly to the clinical, biochemical,

and imaging abnormalities that are associated with ROD. CKD-MBD is defined

as a systemic disorder of mineral and bone metabolism due to CKD and

manifested by either one or a combination of

(1) abnormalities of calcium, phosphorous, PTH, or vitamin D metabolism;

(2) abnormalities of bone turnover, mineralization, volume, linear growth, or

strength; (3) vascular or other soft tissue calcification.

KDIGO recommends that the initial evaluation of CKD-MBD proceed

with biochemical testing (PTH, calcium, phosphorous, alkaline phosphatase,

bicarbonate, and imaging for soft tissue calcification). Bone biopsy is

recommended in cases where there are inconsistencies in biochemical

parameters, unexplained bone pain, or unexplained bone fracture.

21

PATHOGENESIS OF RENAL OSTEODYSTROPHY

22

RENAL OSTEODYSTROPHY - SPINE

23

OSTEOPOROSIS: DEFINITION, PATHOGENESIS AND DIAGNOSIS

Osteoporosis is generally considered to account for the majority of

fragility fractures. Osteoporosis is defined as a skeletal disorder characterized

by compromised bone strength that leads to an increased risk of fracture. The

amount of bone mineral present or the BMD is the major determinant of the

strength of bone in the general population. Although BMD can be measured by

a number of different radiographic and ultrasonographic techniques, the most

widespread imaging modality in clinical use for measurement of BMD is DXA

of the spine and proximal femur. However, the strength of bone is also

influenced by the quality of the bone that is present. Bone quality is, in turn,

determined by a number of material and structural characteristics of bone,

including architecture and microarchitecture, bone remodeling activity or

turnover, mineralization, collagen properties, and accumulation of

microdamage.

Histologically, osteoporosis is characterized by a reduced quantity of

normally mineralized bone. In addition, the osteoporotic bone is structurally

abnormal. Microstructural studies reveal thinning and increased porosity of the

cortices and fewer, disconnected, widely spaced bony trabeculae. The

microarchitectural changes usually result from an increase in the rate of bone

remodeling and/or an imbalance between the bone resorbing activity of

osteoclasts and the bone forming activity of osteoblasts.

24

The most common scenario leading to osteoporosis is one in which bone

resorption is increased and bone formation is also increased, but insufficiently

to compensate. However, the histological changes of osteoporosis can also

develop as a result of a decrease in bone formation whereas resorption proceeds

at a normal pace. Measurement of biochemical markers that reflect osteoclast

and osteoblast activities can be used to assess the rate of bone remodeling

activity.

In patients without kidney disease, the independent contribution of bone

microarchitecture to skeletal strength is becoming increasingly recognized.

Using a peripheral quantitative computed tomography (QCT) machine with a

resolution (∼80 μm) capable of imaging trabecular microstructure, Boutroy et

al. investigated a group of postmenopausal women with osteopenia, and

reported that those with a history of fracture had lower density of trabecular

bone and more heterogeneous trabecular distribution at the radius than those

without fracture, despite comparable BMD measurements.

26

DISORDERS OF CALCIUM AND PHOSPHATE METABOLISM:-

The principal complications of abnormalities of calcium and phosphate

metabolism in CKD occur in the skeleton and the vascular bed, with occasional

severe involvement of extraosseous soft tissues. It is likely that disorders of

bone turnover and disorders of vascular and soft tissue calcification are related

to each other .The major disorders of bone disease can be classified into those

associated with high bone turnover with increased PTH levels (including osteitis

fibrosa cystica, the classic lesion of secondary hyperparathyroidism) and low

bone turnover with low or normal PTH levels (adynamic bone disease and

osteomalacia).

1. The pathophysiology of secondary hyperparathyroidism and the

consequent high-turnover bone disease is related to abnormal mineral

metabolism through the following events:

2. declining GFR leads to reduced excretion of phosphate and, thus,

phosphate retention;

3. (the retained phosphate stimulates increased synthesis of both FGF-23 by

4. osteocytes and PTH and stimulates growth of parathyroid gland mass;

decreased levels of ionized calcium, resulting from suppression of calcitriol

production by FGF-23 and by the failing kidney, as well as phosphate retention,

also stimulate PTH production.

27

Low calcitriol levels contribute to hyperparathyroidism, both by leading

to hypocalcemia and also by a direct effect on PTH gene transcription. These

changes start to occur when the GFR falls below 60 mL/min. FGF-23 is part of

a family of phosphatonins that promotes renal phosphate excretion. Recent

studies have shown that levels of this hormone, secreted by osteocytes, increase

early in the course of CKD, even before phosphate retention and

hyperphosphatemia.

FGF-23 may defend normal serum phosphorus in at least three ways:

(1) increased renal phosphate excretion;

(2) stimulation of PTH, which also increases renal phosphate excretion; and

(3) suppression of the formation of 1,25(OH)2D3, leading to diminished

phosphorus absorption from the GI tract.

Interestingly, high levels of FGF-23 are also an independent risk factor

for left ventricular hypertrophy and mortality in CKD, dialysis, and renal

transplant patients. Moreover, elevated levels of FGF-23 may indicate the need

for therapeutic intervention (e.g., phosphate restriction), even when serum

phosphate levels are within the normal range.

Hyperparathyroidism stimulates bone turnover and leads to osteitis

fibrosa cystica. Bone histology shows abnormal osteoid, bone and bone marrow

fibrosis, and in advanced stages, the formation of bone cysts, sometimes with

28

hemorrhagic elements so that they appear brown in color, hence the term brown

tumor. Clinical manifestations of severe hyperparathyroidism include bone pain

and fragility, brown tumors, compression syndromes, and erythropoietin

resistance in part related to the bone marrow fibrosis. Furthermore, PTH itself is

considered a uremic toxin, and high levels are associated with muscle weakness,

fibrosis of cardiac muscle, and nonspecific constitutional symptoms. Low-

turnover bone disease can be grouped into two categories—adynamic bone

disease and osteomalacia.

Adynamic bone disease is increasing in prevalence, especially among

diabetics and the elderly. It is characterized by reduced bone volume and

mineralization and may result from excessive suppression of PTH production,

chronic inflammation, or both. Suppression of PTH can result from the use of

vitamin D preparations or from excessive calcium exposure in the form of

calcium-containing phosphate binders or high-calcium dialysis solutions.

Complications of adynamic bone disease include an increased incidence of

fracture and bone pain and an association with increased vascular and cardiac

calcification. Occasionally the calcium will precipitate in the soft tissues into

large concretions termed “tumoral calcinosis” .

Calcium, Phosphorus, and the Cardiovascular System Recent

epidemiologic evidence has shown a strong association between

hyperphosphatemia and increased cardiovascular mortality rate in patients with

29

stage 5 CKD and even in patients with earlier stages of CKD.

Hyperphosphatemia and hypercalcemia are associated with increased vascular

calcification, but it is unclear whether the excessive mortality rate is mediated

by this mechanism. Studies using computed tomography (CT) and electron-

beam CT scanning show that CKD patients have calcification of the media in

coronary arteries and even heart valves that appear to be orders of magnitude

greater than that in patients without renal disease.

The magnitude of the calcification is proportional to age and

hyperphosphatemia and is also associated with low PTH levels and low bone

turnover. It is possible that in patients with advanced kidney disease, ingested

calcium cannot be deposited in bones with low turnover and, therefore, is

deposited at extraosseous sites, such as the vascular bed and soft tissues. It is

interesting in this regard that there is also an association between osteoporosis

and vascular calcification in the general population. Finally, hyperphosphatemia

can induce a change in gene expression in vascular cells to an osteoblast-like

profile, leading to vascular calcification and even ossification. Other

complications of calcium and phosphorus metabolism:-

Calciphylaxis (calcific uremic arteriolopathy) is a devastating condition

seen almost exclusively in patients with advanced CKD. It is heralded by livedo

reticularis and advances to patches of ischemic necrosis, especially on the legs,

thighs, abdomen, and breasts . Pathologically, there is evidence of vascular

30

occlusion in association with extensive vascular and soft tissue calcification. It

appears that this condition is increasing in incidence. Originally it was ascribed

to severe abnormalities in calcium and phosphorus control in dialysis patients,

usually associated with advanced hyperparathyroidism. However, more

recently, calciphylaxis has been seen with increasing frequency in the absence

of severe hyperparathyroidism. Other etiologies have been suggested, including

the increased use of oral calcium as a phosphate binder. Warfarin is commonly

used in hemodialysis patients, and one of the effects of warfarin therapy is to

decrease the vitamin K– dependent regeneration of matrix GLA protein. This

latter protein is important in preventing vascular calcification. Thus, warfarin

treatment is considered a risk factor for calciphylaxis, and if a patient develops

this syndrome, this medication should be discontinued and replaced with

alternative forms of anticoagulation.

CALCIUM BALANCE IN CKD:-

Calcium-phosphate crystal lattice that makes up the majority of bone

mineral content and contributes to bone strength. Thus, calcium balance is often

used as a proxy of bone balance, and appropriate calcium balance values must

be viewed in context of what is expected to be happening at the level of the

skeleton. For example, in healthy adults, calcium balance and bone balance are

generally assumed to be neutral. On the other hand, growing children are

appropriately in high positive calcium balance (the positive calcium influx

31

being incorporated into newly formed bone), corresponding to their rapid rate of

skeletal accretion . Older adults and particularly post-menopausal women might

be expected to be in negative calcium balance, reflecting negative bone balance

and bone loss , as post-menopausal osteoporosis is foremost a disease of loss of

bone mass rather than net negative calcium balance from low calcium intake.

Simply from a bone perspective, one could conclude that negative

calcium balance = bad (i.e., bone loss) and positive calcium balance = good

(i.e., bone gain). However, for people who are not in skeletal anabolism,

positive calcium balance may instead be indicating soft tissue deposition. For

patients with CKD, both negative and positive calcium balance carry concerns.

Negative calcium balance favors loss of bone mineral, the risk for a specific

mineralization defect, increased risk for bone fragility fractures, and consequent

morbidity and mortality, whereas positive calcium balance favors soft tissue

calcification, consequent cardiovascular events, and related morbidity and

mortality. Thus, in the adult CKD patient, neutral calcium balance appears to be

the most desirable status to minimize risk of either adverse bone or vascular

consequences.

32

RENAL MAGNESIUM WASTING DISEASE-

• High excretion of magnesium causes low magnesium level in blood,

which results in high parathyroid hormone secretion.

• High parathyroid hormone causes hypocalcaemia, which follows

demineralization of calcium from bones.

33

SIGN AND SYMPTOMS:-

Renal osteodystrophy may exhibit no symptoms; if it does show symptoms,

they include:

• Bone pain

• Joint pain

• Bone deformation

• Bone fracture

• Short stature

• Growth retardation

• The broader concept of chronic kidney disease-mineral and bone disorder

(CKD-MBD) is not only associated with fractures but also with

cardiovascular calcification, poor quality of life and increased morbidity

and mortality in CKD patients (the so-called bone-vascular axis).

RENAL RICKETS:-

• Children-

o Renal Osteodystrophy tends to be more serious in children as

the bones in their body are still in the growth phase.

o Symptoms of Renal Osteodystrophy can be observed in children

with kidney diseases even before beginning dialysis.

34

• Renal Rickets-Renal Osteodystrophy slows down growth of bone and

may also lead to other deformities of the bone. An example of such

deformity is bowed leg where the legs are bent inwards or outwards.

o The skeletal abnormalities are known as Renal Rickets.

o Renal rickets prevents normal development of skeletal system and

patient remains of short stature.

o Patient suffering with renal rickets caused by renal osteodystrophy

often end up with frequent bone fracture.

36

ALUMINIUM – RENAL OSTEODYSTROPHY:-

Bone disease is recognized as a major problem in dialysis patients.

initially, hyperparathyroidism was thought to be the major cause of bone disease

in these patients. However, an aluminum-related bone disease has been

identified in dialysis patients receiving exogenous aluminum. Patients with

hyperparathyroidism and aluminum toxicity present with similar clinical and

laboratory features; therefore, diagnosis of these two bone abnormalities is often

difficult. Understanding normal bone development helps to elucidate the

distinctions between aluminum and renal osteodystrophy.

Patients with either bone syndrome may present with hypercalcemia,

elevations in parathyroid hormone levels, bone pain, fractures, and radiographic

evidence of subperiosteal resorption. The subtleties of these syndromes must be

understood to avoid misdiagnosis. A diagnosis of hyperparathyroidism may lead

to a parathyroidectomy, exacerbating the development of aluminum toxicity.

Hyperparathyroidism is associated with increased surface osteoid, a high

bone formation rate, increased numbers of bone cells, abnormal "woven"

osteoid, and low serum aluminum levels. Aluminum toxicity is associated with

a low rate of bone turnover, paucity of bone cells, maintenance of a "laminar"

osteoid, and significant aluminum bone deposition. Serum aluminum level

measurements are key to the diagnosis of aluminum toxicity. For patients

displaying intermediate aluminum values, the deferoxamine (DFO) challenge

37

test is necessary for diagnosis. If non-invasive methods fail to determine a

definitive diagnosis, a bone biopsy is required.

OTHER MUSCULO SKELETAL ABNORMALITIES IN CKD:-

• Amyloid deposition

• Destructive spondyloarthropathy

• tendon rupture

• Crystal deposition,

• Infection

• Avascular necrosis.

CORTICAL BONE RESORPTION:-

Periosteal (subperiosteal) resorption is a nearly pathognomonic sign of

hyperparathyroidism . Increased intracortical resorption is indicative of high

bone turnover in general, occurring in hyperparathyroidism, hyperthyroidism,

acromegaly, etc. Endosteal resorption is the least specific type of bone

resorption; it may occur in conditions of high bone turnover together with

intracortical and periosteal resorptive changes or be limited solely to the

endosteal envelope in conditions of low bone turnover, e.g., involutional

osteoporosis.

38

DIAGNOSIS OF RENAL OSTEODYSTROPHY:-

Renal osteodystrophy is usually diagnosed after treatment for end-stage

kidney disease begins; however the CKD-MBD starts early in the course of

CKD. In advanced stages, blood tests will indicate decreased calcium and

calcitriol (vitamin D) and increased phosphate, and parathyroid hormone levels.

In earlier stages, serum calcium, phosphate levels are normal at the expense of

high parathyroid hormone and fibroblast growth factor-23 levels.

X-rays will also show bone features of renal osteodystrophy (subperiostic

bone resorption, chondrocalcinosis at the knees and pubic symphysis,

osteopenia and bone fractures) but may be difficult to differentiate from other

conditions. Since the diagnosis of these bone abnormalities cannot be obtained

correctly by current clinical, biochemical, and imaging methods (including

measurement of bone-mineral density), bone biopsy has been, and still remains,

the gold standard analysis for assessing the exact type of renal osteodystrophy.

NON INVASIVE BONE IMAGING TECHNOLOGIES IN CKD:-

• DXA

• Conventional and peripheral QCT

• Micro-magnetic resonance imaging

• Ultra-high-resolution peripheral QCT

39

Metacarpal measurements X-rays were obtained with commercial film

with a tube to film distance of 1 m. Changes in metacarpal cortical

measurements were used as one index of bone loss (Horsman & Simpson,

1975). The measurement of metacarpal cortical thickness (MCM) as described

by Horsman & Simpson (1975) proved to be very reproducible so that the loss

of bone which was significant was detectable in 61% of the present population

studied over a 1-6 years period. The MCM has advantages over photon

densitometry and the measurement of total body calcium by neutron activation,

the other principal techniques used to assess bone mass, in that the technique is

simple and requires the minimum of equipment yet has a reproducibility which

is equal to, if not greater than, that of the other methods (Fremlin, 1972; Nordin,

Horsman & Gallagher, 1974).

However, it must be remembered that MCM can only detect changes in

cortical bone volume, and not in bone composition or changes in cortical

porosity. With regard to the other technique used here, the precise errors of the

biopsy measurements in this study are unknown. Although there was a change

in biopsy technique during the study it is unlikely that this influenced the results

since a study by Visser, Niermans, Roelofs, Raymakers & Duursma (1977)

failed to show any difference in volumetric density obtained by transverse or

perpendicular biopsy of the iliac crest. In general, both metacarpal cortical

thickness and trabecular bone area measured in iliac biopsies tended to decrease

40

with time. However, there was no correlation between the absolute values for

these measurements or in the way in which they changed in individual patients.

Although lack of precision in the measurements used, particularly of bone area,

may explain the lack of correlation, the results may indicate that different parts

of the skeleton behave in different ways. Ritz, Krempien, Mehls & Bommer

(1973) found that, in 282 patients on dialysis, whereas cortical bone

progressively diminished the amount of cancellous bone either remained the

same or increased. Similarly Horsman, Bulusu, Bentley & Nordin (1970) found

that whereas there was good correlation between the density of the femur,

metacarpal, radius and ulna there was no correlation between these bones and

the density of the vertebrae.

42

METACARPOCORTICAL INDEX:-

Renal osteodystophy in CRF patients can be measured by simple reliable

and accessiblemethod of calculating metacarpocortical index.

Metacarpocortical index by measuring medial plus lateral cortical

thickness in the mid shaft of the second metacarpal bone divided by the total

thickness of the mid shaft of second metacarpal bone.

Calculation of MCI

X-ray of AP view of right hand is taken

MCI = Medial + lateral cortical thickness of second metacarpal

bone at midpoint / Total thickness of second metacarpal bone at mid point

43

It helps in predicting renal osteodystrophy early in asymptomatic stage

and helps in preventing grave complications of renal osteodystrophy by

earlyintervention and treatment.

The diagnosis of metabolic bone disease in patients with chronic renal

failure is largely based on indirect evaluation by radiologic and biochemical

values. Radiologic evaluation of changes in trabecular bone structure is often

difficult. The cortical bone, on the other hand, permits qualitative radiologic

assessment of bone resorption. Endosteal bone resorption increases the width of

the marrow cavity and measurements of the width of the cavity may indicate the

degree of the resorption. Periosteal (subperiosteal) resorption results in a

decrease of the cortical thickness. By determining the ratio cortical area/total

area of the second metacarpal bone at the midshaft, a calculation of total and

medullary cross sectional areas is possible . The changes in bone mass in

chronic renal failure with endosteal or subperiosteal resorption may be assessed

by measurement of the cortical bone mass.

Radiologic measurement of metacarpal bone mass is a simple procedure,

with a high reproducibility, quantitating the amount of cortical bone. The

method appears to be valuable in recording changes in bone mass during

chronic hemodialysis and following renal transplantation.

44

TREATMENT OF RENAL OSTEODYSTROPHY:-

The optimal management of secondary hyperparathyroidism and osteitis

fibrosa is prevention. Once the parathyroid gland mass is very large, it is

difficult to control the disease. Careful attention should be paid to the plasma

phosphate concentration in CKD patients, who should be counseled on a low-

phosphate diet as well as the appropriate use of phosphate-binding agents.

These are agents that are taken with meals and complex the dietary

phosphate to limit its GI absorption. Examples of phosphate binders are calcium

acetate and calcium carbonate. A major side effect of calcium- based phosphate

binders is calcium accumulation and hypercalcemia, especially in patients with

low-turnover bone disease. Sevelamer and lanthanum are non-calcium-

containing polymers that also function as phosphate binders; they do not

predispose CKD patients to hypercalcemia and may attenuate calcium

deposition in the vascular bed. Calcitriol exerts a direct suppressive effect on

PTH secretion and also indirectly suppresses PTH secretion by raising the

concentration of ionized calcium. However, calcitriol therapy may result in

hypercalcemia and/or hyperphosphatemia through increased GI absorption of

these minerals. Certain analogues of calcitriol are available (e.g., paricalcitol)

that suppress PTH secretion with less attendant hypercalcemia.

45

Recognition of the role of the extracellular calcium-sensing receptor has

led to the development of calcimimetic agents that enhance the sensitivity of the

parathyroid cell to the suppressive effect of calcium. This class of drug, which

includes cinacalcet, produces a dose-dependent reduction in PTH and plasma

calcium concentration in some patients. Current National Kidney Foundation

Kidney Disease Outcomes Quality Initiative guidelines recommend a target

PTH level between 150 and 300 pg/mL, recognizing that very low PTH levels

are associated with adynamic bone disease and possible consequences of

fracture and ectopic calcification. My study is intended to analyse the cost

effective methodology to assess renal osteodystrophy so that optimisation of

calcium and vitamin d3 therapy can be instituted at appropriate time period. The

findings of this study can be substituted in hospitals where only x ray facilities

are available and paratharmone and vitamin d 3 levels could not be assessed.

46

MATERIALS AND METHODS

STUDY POPULATION :

This study was conducted on 30 patients of chronic renal failure admitted

in Government Rajaji Hospital, Madurai in the department of General medicine

and Nephrology. A control group of 30 persons were studied.

INCLUSION CRITERIA :

STUDY GROUP:

• CRF of any cause

• Both male and female

• Age between 18 to 50 yrs in male

• Age between 18 to 45 yrs in female

CONTROL GROUP:

• No evidence of CRF

• Apparently healthy

• Age between 18 to 50 yrs in male

• Age between 18 to 45 yrs in female

47

EXCLUSION CRITERIA :

a) Acute renal failure

b) Bones changes other than CRF

c) Rickets

d) Drug intake (steroids)

ANTICIPATED OUTCOME :

X-ray of right hand for calculating MCI from second metacarpal bone can

predict quantitative bone changes which is useful in preventing complications of

osteodystrophy (ex : fractures).

DATA COLLECTION :

A detailed medical history, clinical examination and relevant laboratory

investigations was done as indicated in each patient.

LABORATARY INVESTIGATIONS:

• Serum urea,

• serum creatinine

• serum calcium,

• serum phosphorus,

48

• serum uric acid,

• serum alkaline phosphatase

• serum vitamin D3

• x ray right hand AP

• axial skeletal survey

DESIGN OF STUDY:

Hospital based cross sectional observational study

PERIOD OF STUDY: February 2017 to August 2017

COLLABORATING DEPARTMENTS:

Department of Radiology

Department of Biochemistry

Department of Nephrology

ETHICAL CLEARANCE:

Obtained (certificate enclosed)

CONSENT: Individual written and informed consent.

ANALYSIS: STATISTICAL ANALYSIS

CONFLICT OF INTEREST: NIL

FINANCIAL SUPPORT: NIL

49

RESULTS OF STUDY

A cross sectional observational study was carried out in government

Rajaji hospital from February 2017 to August 2017. 60 patients were included

in the study after an informed consent was obtained. Patients included in study

were divided into two groups. Study group were people with chronic renal

failure age between 18 to 50 years male and 18 to 45 years female . Control

group were people were apparently healthy individuals without chronic renal

failure age between 18 to 50 years male and 18 to 45 years female. History and

clinical examination was taken for each patients. Then X ray right hand AP

view taken and axial skeletal survey done . Relevant laboratory investigations

were done. Metacarpocortical index was calculated from X ray right hand and it

was statistically analysed with other laboratory parameters and results were

obtained. The statistical results of the study of the 60 patients were summarised

as follows :

AGE DISTRIBUTION:-

38% of patients were more than 40 years, 28% were between 30- 40

years, 27% were between 21 – 30 years and 7% were less than 20 years.

50

Age (in yrs)

N 60

Mean 36.2

SD 10.1

Minimum 18

Maximum 50

51

Age group (in yrs) No. (%)

≤20 4 (6.7)

21 – 30 16 (26.7)

31 – 40 17 (28.3)

>40 23 (38.3)

Total 60 (100.0)

Majority of the population for study were contributed by people of age

more than 40 years and least by people of 18 to 20 years.

52

SEX DISTRIBUTION:-

Among the 100 people studied 75 % were male and 25% were female.

Gender No. (%)

Male 45 (75.0)

Female 15 (25.0)

Total 60 (100.0)

Males formed the major population for study.

53

AVERAGE MCI BETWEEN CASE GROUP AND CONTROL

GROUP

Metacarpocortical index in study group is 0.42

Metacarpocortical index in control group is 0.69

54

Group

Metacarpocortical Index (MCI)

N Mean ± SD Minimum,

Maximum

Case 30 0.42 ± 0.10 0.22, 0.66

Control 30 0.69 ± 0.11 0.47, 0.88

Total 60 0.56 ± 0.17 0.22, 0.88

p-value <0.001 (Significant)

This study compares MCI between case and control group it was less in

case group indicating bone loss in chronic renal failure. Results were

statistically significant.

55

VARIOUS SERUM UREA LEVELS AND METACARPOCORTICAL

INDEX OF BOTH CASES AND CONTROLS:-

This graph shows that with increase in serum urea ,there is decrease in

Metacarpocortical index.

56

Serum Urea

(mg/dl)



Maximum

<40 29 0.69 ± 0.10 0.47, 0.87

40 – 99 10 0.54 ± 0.12 0.47, 0.88

100 – 199 17 0.42 ± 0.08 0.31, 0.66

≥200 4 0.26 ± 0.03 0.22, 0.31

Total 60 0.56 ± 0.17 0.22, 0.88


Above table shows that with increase in serum urea there is decline in

metacarpocortical index and it is statistically significant.

57

VARIOUS SERUM CREATININE LEVELS AND THE

CORRESPONDING METACARPOCORTICAL INDEX

This graph shows with increase in serum creatinine there is fall in

metacarpocortical index.

58

Serum Creatinine

(mg/dl)



Maximum

<1.4 30 0.69 ± 0.11 0.47, 0.88

1.4 – 5 12 0.52 ± 0.06 0.44, 0.66

6 – 10 9 0.41 ± 0.02 0.40, 0.45

11 – 15 3 0.37 ± 0.06 0.31, 0.44

>15 6 0.28 ± 0.03 0.22, 0.33

Total 60 0.56 ± 0.17 0.22, 0.88


This table shows with increase in srum creatinine there is fall in

metacarpocortical index and it is statistically significant.

59

VARIOUS SERUM CALCIUM LEVELS AND CORRESPONDING


This graph shows analysis between serum calcium and metacarpocortical

index It shows that with increase in serum calcium there is increase in


60

Serum Calcium

(mg/dl)



Maximum

7 – 8.9 22 0.39 ± 0.10 0.22, 0.72

9 – 10.4 29 0.64 ± 0.13 0.47, 0.88

≥10.5 9 0.71 ± 0.06 0.60, 0.80

Total 60 0.56 ± 0.17 0.22, 0.88


This table shows the statistical analysis between serum calcium and


It shows that with decrease in metacarpocortical index there is decrease in

serum calcium.

It is statistically significant.

61

VARIOUS SERUM PHOSPHORUS LEVELS AND CORESPONDING


This graph shows that with deccrease in metacarpocortical index there is

increase in serum phosphorus.

62

Serum

Phosphorus

(mg/dl)



Maximum

<4.5 39 0.64 ± 0.12 0.43, 0.88

4.5 – 9.0 21 0.40 ± 0.12 0.22, 0.76

Total 60 0.56 ± 0.17 0.22, 0.88


This table shows that with decrease in metacarpocortical index there is

increase in serum phosphorus and it is statistically significant.

63

VARIOUS SERUM ALKALINE PHOSPHATASE LEVELS AND

CORRESPONDING METACARPOCORTICAL INDEX :-

This graph shows that serum alkaline phosphatase increases with

decrease in metacarpocortical index.

64

Serum Alkaline

Phosphatase

(IU/L)



Maximum

60 - 100 31 0.67 ± 0.11 0.47, 0.88

101 – 150 16 0.52 ± 0.12 0.40, 0.77

>150 13 0.34 ± 0.07 0.22, 0.45

Total 60 0.56 ± 0.17 0.22, 0.88


This table shows there is decrease in metacarpocortical index with

increase in serum alkaline phosphatase and it is statistically significant.

65

VARIOUS SERUM URIC ACID LEVELS AND CORRESPONDING


This graph shows with decrease in metacarpocortical index there is

increase in serum uric acid.

66

Serum Uric Acid

(mg/dl)



Maximum

4 – 7 45 0.63 ± 0.13 0.41, 0.88

>7 15 0.35 ± 0.06 0.22, 0.44

Total 60 0.56 ± 0.17 0.22, 0.88


This table shows that metacarpocortical index decreases with increase in

serum uric acid.


67

VARIOUS SERUM VITAMIN D3 LEVELS AND CORRESPONDING


This graph shows as the metacarpocortical index decreases , there is

decrease in vitamin D3

68

Serum Vitamin

D3 (ng/ml)



Maximum

10 – 25 29 0.42 ± 0.11 0.22, 0.68

26 – 40 31 0.68 ± 0.11 0.47, 0.88

Total 60 0.56 ± 0.17 0.22, 0.88


This table shows that metacarpocortical index decreases with decrease in

vitamin D 3 level and it is statistically significant.

69

ANALYSIS BETWEEN METACARPOCORTICAL INDEX AND AXIAL

SKELETAL SURVEY:-

This graph shows with decrease in metacarpocortical index, there is

increase in osteoporosis.

70

Axial Skeletal Survey

–

X Ray DL Spine AP

View



Maximum

Normal 58 0.57 ± 0.16 0.22, 0.88

Osteoporosis 2 0.32 ± 0.07 0.27, 0.37

Total 60 0.56 ± 0.17 0.22, 0.88

p-value 0.041 (Significant)

This table shows with decrease in metacarpocortical index there is

increase in osteoporosis


71

DISCUSSION

This study mainly comprises of younger population 18- 50 years in

comparison of previous study done by R. G. Henderson et al which had elder

age group more than 55 years.

This study was conducted in patients with chronic renal failure to

document the renal osteodystrophy by measuring metacarpocortical index

(MCI) of second metacarpal bone of right hand and to correlate the MCI index

with serum levels of creatinine, urea, calcium, phosphorus, alkaline

phosphatase, uric acid, vitamin D 3 and axial skeletal survey. MCI was

calculated from 30 persons (control group) both male and female and this mean

MCI index was taken as reference and compared with MCI calculated in study

group (CRF). The results showing the MCI value in the study group (CRF)

(0.42) is declined in comparison with control group (0.69), indicating bone

changes . It was 0.38 in case group and was 0.57 in previous study conducted by

Dr D. Anil Kumar et al.

The results showed that as the serum creatinine values increases a decline

in the MCI was observed in the study group. In patients with serum creatinine

more than 15, MCI was 0.28. Whereas MCI was 0.34 in study conducted by Dr

D. Anil Kumar et al.

72

This study compared MCI in CRF patients with blood urea levels and

found the MCI was decreased in proportional raise in the levels of blood urea.

Patient with urea more than 200mg% had MCI of 0.26. It was 0.37 in Dr D.

Anil Kumar et al.

This study compared MCI in CRF patients with serum calcium levels and

found the MCI was increased in proportional elevated levels of serum calcium.

Patients with calcium less than 9 had MCI of 0.39. It was 0.38 in study

conducted by Dr D. Anil Kumar et al.

This study compared MCI in CRF patients with serum phosphorus levels

and found the MCI was decreased with elevated levels of serum phosphorus.

Patients with phosphorus more than 4.5 mg/dl had MCI of 0.40. It was 0.39 in

study conducted by Dr D. Anil Kumar et al.

This study compared MCI in CRF patients with serum alkaline

phosphatase levels and found the MCI was decline with elevated levels of

serum alkaline phosphatase. Patients with alkaline phosphatase level more than

150IU/L was 0.34. It was 0.35 in study conducted by Dr D. Anil Kumar et al.

This study compared MCI in CRF patients with serum uric acid levels

and found that as the uric acid levels elevated there is decline in the MCI is

observed. Patients with uric acid level more than 7 had MCI of 0.35. It was

0.40 in study conducted by Dr D. Anil Kumar et al.

73

This study compared MCI in CRF patients with serum Vitamin D 3

levels and found the MCI was decreased with decreased levels of serum

vitamin D 3 this was not done in previous study conducted by Dr D. Anil

Kumar et al. This study found that it was statistically significant.

74

CONCLUSION

This study concludes that

1) Quantitative bone changes in chronic renal failure patients can be measured

by calculating metacarpocortical index from second metacarpal bone of right

hand by the X-ray technique which is a simple and cost effective method.

2) Comparison between MCI in CRF patients with biochemical parameters like

serum creatinine, urea, calcium, phosphorus, alkaline phosphatase, uric acid,

vitamin D3 and axial skeletal survey concluded that MCI has been found to be

decline with elevated levels of serum creatinine, urea, phosphorus, alkaline

phosphatase and uric acid levels and MCI has been in found to be increased

with elevated serum calcium levels.

3) X-ray of right hand for calculating MCI from second metacarpal bone can

predict quantitative bone changes which is useful in preventing complications of

osteodystrophy (ex : fractures).

4) Quantitative bone changes occurring in CRF patients by measuring MCI can

be useful in the management and treatment in CRF. Thus MCI is a simple,

reliable, non-invasive and accessible method in predicting renal osteodystrophy

early in asymptomatic stage and helps in preventing grave complications of

renal osteodystrophy by early intervention and treatment.

75

LIMITATIONS OF STUDY:-

1) This study was done with less number of patients.

2) In this study serum paratharmone was not assessed.

3) This is single centre study.

4) There may be inter observer variation in X ray reporting.

i

ANNEXURES

PROFORMA

PARTICULARS OF THE PATIENT :

Name: Case

no :

Age/ Sex:

I.P. no:

Address:

Date of admission:

Date of discharge:

Final diagnosis:

COMPLAINTS WITH DURATION:

Past history: DM Y/N

HTN Y/N

CAD Y/N

CVA Y/N

CKD Y/N

ii

MALIGNANCY Y/N

TB Y/N

Personal history:

SMOKING Y/N

ALCOHOL Y/N

Family history:

On Examination:-

Vital signs:

Pulse:

B.P. :

R.R. :

SpO2 :

Temperature :

CVS :

RS :

ABDOMEN:

CNS:

iii

INVESTIGATION:

Hb:

RBS

UREA

CREATININE

SERUM CALCIUM

SERUM PHOSPHORUS

SERUM ALKALINE PHOSPHATASE pp

SERUM VITAMIN D3

X RAY HAND INCLUDING WRIST JOINT- AP VIEW

METACORPOCORTICAL INDEX:

AXIAL SKELETAL SURVEY

iv

MASTER CHART

S.NO NAME AGE SEX METACARPOCORTICAL INDEXSERUM UREA

(mg/dl)

SERUM CREATININE

(mg/dl)

SERUM CALCIUM (mg/dl)

SERUM PHOSPHORUS(mg/dl)

SERUM ALKALINE PHOSPHATASE(U/L)

SERUM URIC ACID (mg/dl)

SERUM VITAMIN D3(ng/ml)

AXIAL SKELETAL SURVEY - X RAY DL SPINE AP VIEW

1 ) MURUGAN 32 M 0.4 151 9.6 8 5 154 8 20 NORMAL STUDY2) RENGUSAMY 47 M 0.4 108 7.6 8 5.5 148 7.5 22 NORMAL STUDY3) MALAI RAJA 43 M 0.57 100.6 2.6 10 4 111 4 25 NORMAL STUDY4) GURUSAMY 50 M 0.5 60 2.7 9.5 4 114 5 26 NORMAL STUDY5) SUNDARAM 44 M 0.66 100 1.9 10.5 3.5 95 4.5 30 NORMAL STUDY6) RAJA 29 M 0.45 109 8.9 8.5 6 149 6.5 15 NORMAL STUDY7) PERUMAL 50 M 0.41 180 9.4 8.5 6.5 156 7 17 NORMAL STUDY8) SRINIVASAN 50 M 0.5 85 4.8 9 3.5 121 5 24 NORMAL STUDY9) KOOLU 50 M 0.37 142 12.9 7.5 6 164 8 15 OSTEOPOROSIS NOTED10) MAHESWARI 36 F 0.5 81 2.5 8 4.5 108 6 21 NORMAL STUDY11) THANDAPANI 50 M 0.43 169 6.5 8 4 142 7.5 23 NORMAL STUDY12) SURESH 45 M 0.6 51 1.9 10 3.5 90 4 26 NORMAL STUDY13) SELVI 38 F 0.44 116 5.4 8 4.5 138 8 21 NORMAL STUDY14) KARMEGAM 42 M 0.54 49 1.5 9 3.5 95 6 22 NORMAL STUDY15) ABITHA BANU 36 F 0.5 59 2.2 9.5 4 106 6.5 24 NORMAL STUDY16) UMA BARATHI 18 F 0.5 69 1.8 10 4 92 7 23 NORMAL STUDY17) KUMAR 38 M 0.4 131 10.4 7.5 6 160 7.5 20 NORMAL STUDY18) MUTHUMARI 18 F 0.22 211 19.5 7 8 177 8 15 NORMAL STUDY19) SONATCHI 45 F 0.4 195 6.5 8 5 149 7.5 22 NORMAL STUDY20) BOOMA 32 F 0.31 174 14.3 7.5 6 153 8 21 NORMAL STUDY21) RAJAVEL 22 M 0.47 87 5.1 8.5 4 101 6 23 NORMAL STUDY22) CHELLASAMY 50 M 0.27 223 21 7 8.5 173 8 14 OSTEOPOROSIS NOTED23) KADIRVEL 30 M 0.27 261 24 6.5 8 180 8.5 12 NORMAL STUDY24) ANDICHI 40 F 0.31 175 15.3 7.5 7 166 7.5 16 NORMAL STUDY25) SATHYAN 18 M 0.31 235 17.6 7 7.5 170 8 14 NORMAL STUDY26) PONNAR 34 M 0.45 146 9 8.5 6 158 6.5 22.5 NORMAL STUDY27) KARTHICK 35 M 0.41 171 7 8 5.5 143 7.5 21 NORMAL STUDY28) BALAMURUGAN 24 M 0.44 154 12.5 7.5 6.5 162 7 16 NORMAL STUDY29) ALAGAR 47 M 0.5 63 2.8 9 3.5 119 6 23.5 NORMAL STUDY30) MURUGESAN 43 M 0.33 172 16.4 7 8.5 169 8 19.5 NORMAL STUDY31) SELVAM 40 M 0.7 32 1 9 3.5 70 5 26 NORMAL STUDY32) PRIYANKA 38 F 0.68 20 0.8 10.5 3 86 6 25 NORMAL STUDY33) RAMESH 28 M 0.56 16 0.8 10 3.5 79 4.5 31 NORMAL STUDY34) RAMAN 32 M 0.6 18 0.9 11 3 90 5 33 NORMAL STUDY35) MAHESWARI 45 F 0.72 19 1 9.5 2.5 100 4 27 NORMAL STUDY36) IYYAPPAN 22 M 0.68 20 0.6 10 4 98 5.5 26 NORMAL STUDY37) PADMA 25 F 0.77 30 1.2 9 3 105 6 36 NORMAL STUDY38) MANIMARAN 42 M 0.87 38 1.2 10 3.5 84 7 38 NORMAL STUDY39) AATHIMOOLAM 46 M 0.66 21 0.8 10.5 2.5 77 6.5 28 NORMAL STUDY40) KAALEESWARI 32 F 0.68 26 1 9 3 70 5 24 NORMAL STUDY41) KRISTI 30 F 0.76 22 1 11 4 88 4.5 31 NORMAL STUDY42) SUBRAMANI 50 M 0.88 40 1.3 9.5 3.5 85 6 29 NORMAL STUDY43) SATHYA 35 F 0.5 21 0.6 10 3 97 6.5 29 NORMAL STUDY44) KAPILAN 27 M 0.7 24 1.1 9 4.5 68 5 26 NORMAL STUDY45) RAJA 30 M 0.75 22 1.2 11 4 101 7 30 NORMAL STUDY46) LAKSHMANAN 21 M 0.72 30 0.9 10.5 3 87 6.5 26 NORMAL STUDY47) MUTHUKRISHNAN 31 M 0.76 32 0.8 9 2.5 80 5 34 NORMAL STUDY48) KARTHICK RAJA 46 M 0.5 16 0.6 10 3.5 90 6 32 NORMAL STUDY49) JOHNY 32 M 0.57 20 0.9 9 3 79 5.5 31 NORMAL STUDY50) ILANGO 50 M 0.75 39 1.2 10 4 67 5 29 NORMAL STUDY51) PONNUSAMY 42 M 0.8 28 1.1 11 3.5 91 7 33 NORMAL STUDY52) PERIYAKARUPPAN 40 M 0.75 34 1.2 9.5 3 75 4.5 31 NORMAL STUDY53) PANDI 50 M 0.76 26 1 9 4.5 109 6 30 NORMAL STUDY54) PARTHIBAN 24 M 0.84 20 0.56 10 4 90 5 28 NORMAL STUDY55) PARKAVI 22 F 0.77 18 0.9 11 4 86 6.5 26 NORMAL STUDY56) SILAMBARASAN 29 M 0.85 24 1 9 3.5 83 5 36 NORMAL STUDY57) SEVAGAMOORTHY 29 M 0.57 30 1.1 9.5 4 80 4 32 NORMAL STUDY58) OYYAN 50 M 0.55 39 1.2 10 3 76 6 29 NORMAL STUDY59) VELANKANI 30 M 0.72 21 0.7 8.5 4 68 6 27 NORMAL STUDY60) MARIMUTHU 19 M 0.47 38 1 9 2.5 69 5 30 NORMAL STUDY

v

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viii

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