For Registration of Subject for Dissertation To

Synopsis

For Registration of subject for dissertation to

Rajiv Gandhi University of Health Sciences

Karnataka, Bangalore

In Partial Fulfilment of Regulations

In Regard for the award of

Masters Degree in medicine

In respect of

SQN LDR M M PASHA

Department of medicine

Command Hospital Air Force Bangalore-560007

Rajiv Gandhi University of Health Science

Karnataka, Bangalore

Annexure – II

Proforma for registration of subject for dissertation

1. / Name of the candidate and address / SQN LDR M M PASHA
Department of medicine
command hospital( air force)
Bangalore-07
2. / Name of the institution / command hospital (air force) Bangalore
3. / Course of study and subject / MD medicine
4. / Date of admission to the course / 1st May 2008
5. / Title of the topic / BONE HEALTH IN INDIAN MALES IN ANKYLOSING SPONDYLITIS
6. / Brief resume of intended work / 6.1 Need for study : As per Appendix – I
6.2 Review of literature : As per Appendix – II
6.3 Objectives of study : As per Appendix – III
7. / Material and methods / 7.1 Source of data : As per Appendix – IV
7.2 Method of collection of data : As per Appendix – IV
7.3 Does the study require any
investigation to be conducted
on patients if so, describe briefly : As per Appendix – IV
7.3 Has ethicalclearance been
obtained from your institution
in case of 7.3 : Yes (copy enclosed)
8. / List of references / As per Appendix – V
9. / Signature of the candidate
10. / Remarks of the guide / .
11. / 11.1 Name and designation of the guide
11.2 Signature
11.3 Co-guide (1)
11.4 Signature
11.5 Co-guide (2)
11.6 Head of the department
Signature / col r muralidhar md
Professor & HOD
Department of
medicine
Chaf, Bangalore
wg cdr AJAY HANDA md dm
PULMONOLOGIST
associate PROFessor
department of medicine
chaf, bangalore
col r muralidhar md
Professor & HOD
Department of
medicine
Chaf, Bangalore
12. / 12.1 Remarks of the Principal
12. Signature

Appendix – I

NEED FOR STUDY

Ankylosing spondylitis (AS) is an inflammatory rheumatic disease characterized by spine and sacroiliac joint involvement that

mainly affects young male subjects. Its clinical spectrum varies from a simple

pelvic involvement (sacroiliitis) to a severe multisystemic and progressive disease (1). Syndesmophytes, which are due to new bone formation, are considered to be a hallmark of the disease. In parallel with this process, a reduction in bone formation also occurs. The presence of osteoporosis (OP) in AS patients has been confirmed by numerous researchers For several years it has been established that bone mineral density (BMD) loss occurs early in the AS disease course. However, the pathogenesis of OP remains controversial. (2). The clinical significance in OP lies in development of fractures. Osteoporotic vertebral fractures are relatively common, but frequently unrecognized complications of AS, that can contributes to spinal pain and deformity of AS patients. Fractures frequently occurred as a result of minimal trauma and were associated with severe neurological deficits in a high proportion of patients .

Although the main anatomic and radiological osteoarticular features of ankylosing spondylitis have been extensively investigated and described in the past, the same has not occurred for bone mineral density(BMD) changes related to clinical disease activity and chronicity.

These changes in BMD have previously been described by performing radiographic evaluation of spine in AS patients. However these radiographic changes related to bone loss were only described qualitatively and not evaluated in the early stages, being detected only when 30-50% of bone loss had already occurred. With the advent of bone densitometry techniques it is possible to make quantitative assessment of bone loss even in early stages of the disease.

The aims of this study are to determine bone mineral density (BMD) and the frequency of osteoporosis and osteopenia in AS.

This study proposes to assess the BMD in patients with AS and compare it with healthy controls.

Appendix – II

Review of Literature

Ankylosing spondylitis is a chronic inflammatory joint disease in which inflammation of the entheses gradually causes local ossification and ankylosis. Osteoporosis is a known complication of Ankylosing spondylitis (AS).1 Diffuse osteoporosis responsible for bone fragility has been established by recent data. The bone loss predominates at the spine and can cause vertebral fractures that are sources of mortality and morbidity late in the course of the disease.2 Vertebral fractures due to osteoporosis are a common but frequently unrecognized complication in established ankylosing spondylitis. It is known that inflammatory activity in rheumatic diseases (i.e., proinflammatory cytokines) itself plays a possible role in the pathophysiology of bone loss. Osteoporosis is frequent in AS and high disease activity is associated with an alteration in vitamin D metabolites and increased levels of bone resorption in active AS. There is a close association of bone mineral density (BMD), bone metabolism and inflammatory activity, possibly related to interactions between vitamin D and inflammation.

Criteria to diagnose spondyloarthropathy

ESSG criteria inflammatory spinal pain or synovitis and one of the following alternating buttock pain, enthesitis, sacroilitis, inflmatory bowel disease, positive family history.

New York criteria (1968): Definite ankylosing spondylitis is present if grade 3-4 bilateral sacroiliitis is associated with at least one clinical criterion or if grade 3-4 unilateral or grade 2 bilateral sacroiliitis is associated with clinical criterion 1 or with both clinical criteria 2 and 3. Probable ankylosing spondylitis is present if grade 3-4 bilateral sacroiliitis is associated with none of the criteria.

1. Limitation of motion of the lumbar spine in anterior flexion, lateral flexion, and extension
2. History of pain or the presence of pain at the thoracolumbar junction or in the lumbar spine
3. Limitation of chest expansion to 1 inch or less

Appendix - III

Objective of Study

To assess the Bone Mineral Density (BMD) in Indian Male Indian patients with Ankylosing spondylitis and to study the factors influencing BMD.

Appendix – IV

Materials and Methods

a)Inclusion criteria-

• Male
• Patients of Ankylosing spondylitis satisfying modified New York criteria
• > 5 years of disease duration.

b)Exclusion criteria-

• Female
• Overlap syndromes
• Age < 21 (i.e onset < 16 years, juvenile AS)
• > 60 years (age related loss of BMD very significant)

c)Sample size calculation-

• Normal BMD in lumbar spine = 0.965 g/cm2
• To detect a difference of 5% in BMD in both groups
• Alpha value= 0.05
• Power=80%
• Standard deviation (homodiastetic) Of patients=controls= 0.10 (estimated)
• Sample size required = 38 in each group

d)Sample size chosen

• Patient numbers- 40 patients
• Controls- 40 healthy male age-matched controls.

e)Assessment-

• Detailed clinical assessment.
• Assessment of various disease activity and functional indices (like BASDAI, BASFI and BASMI)
• Details of activity, exercise, dietary intake, drug therapy, and other potential contributing factors to osteoporosis will be collected from all the individuals in both groups
• Dual Energy X-ray Absorptiometry (DEXA) scan of two areas, Lumbar spine and femoral neck, for assessment of BMD and to quantitate the presence of osteopenia and/ or osteoporosis will be done for both patients and controls.
• Serum 25-hydroxyvitamin D3 levels levels will be done in all the study individuals to study the relation between vitamin D metabolism and osteoporosis in AS.

f)Statistical analysis-

• Comparison of BMD means of 2 groups - Student’s T test.
• Factors influencing BMD in patients with AS- Regression analysis.

proforma

NAME: CLINIC/OPD NO:

AGE/SEX: DATE:

ADDRESS:

TELEPHONE NO:

CARDIAC RISK FACTORS:

SMOKING: YES/NO

HYPERTENSION: YES/NO

DIABETES MELLITUS: YES/NO

DYSLIPIDEMIA: YES/NO

FAMILY H/O CAD: YES/NO

OBESITY: YES/NO

PHYSICAL INACTIVITY: YES/NO

BRIEF HISTORY:

PAST HISTORY:

ON EXAMINATION:

HEIGHT: WEIGHT:

BMI:

PR: (BIL SYMM – YES/NO)

BP:

TYPE OF OBESITYAPPLE \PEAR\OVOID

EAR LOBE CREASEACANTHOSIS NIGRICANS

SYSTEMIC EXAMINATION

INVESTIGATIONS:

HB:

TLC:

DLC:

PLATELETS:

FBS:

PPBS:

BUN:

S.CREATININE:

S.CHOLESTEROL:

LDL:

TG:

HDL:

VLDL:

S.BILIRUBIN:

SGOT:

SGPT:

SAP:

URINE RE:

CXR PA VIEW:

ECG:

AMIAWMIIWMILWMIPWMI

CORONARY ANATOMY:

NORMALSVDDVDTVD

PVD

CVAMCAACAPCA

PLATELET RESPONSE

RESPONDER SEMI RESPONDER NONRESPONDER

APPENDIX - V

APPENDIX - V

references

1. Aydin T, Karacan I et al.Bone loss in males with ankylosing spondylitis: its relation to sex hormone levels. Clin Endocrinol (Oxf). 2005 Oct;63(4):467-9.

2. El Maghraoui A. Osteoporosis and ankylosing spondylitis. Joint Bone Spine. 2004 Jul;71(4):291-5.

3. Lange U, Teichmann J et al. Association of 1.25 vitamin D3 deficiency, disease activity and low bone mass in ankylosing spondylitis. Osteoporos Int. 2005 Dec;16(12):1999-2004.

4. Lange U, Jung O, Teichmann J et al. Relationship between disease activity and serum levels of vitamin D metabolites and parathyroid hormone in ankylosing spondylitis. Osteoporos Int. 2001 Dec;12(12):1031-5.

5. Delmas PD, Esatell R, Garnero P et al. The use of biochemical markers of bone turnover in osteoporosis. Osteoporosis Int 2000; 11(Suppl 6): S2-S17

INFORMED CONSENT

I,______Age____yrs Relation ______No______Rank______Name______Unit______request Dr. ______

and His/her associates to perform upon me DEXA Scan alone.

Diagnosis and procedure: The following has been explained to me in general terms and I understand that:

My condition has been diagnosed as: ______

The nature of the procedure is to undergo a radiological investigation in the form of DEXA scan( dual energy x-ray absorbtiometry)..

The purpose of the procedure is to enhance the efficacy of detection of the bone mineral density in the involved joints in ankylosing spondylitis and thereby determine the extent of disease progression.

General Risks of procedure: As a result of the performance of this procedure there may be general risks involved such as : Radition risks as in normal screening. . In addition to these general risks there may be other possible risks involved in this procedure.

Likelihood of Success: The likelihood of success of the above procedure has been proved to be beneficial in enhancing the chances of detection of bone mineral density as indicated through osteopenic changes in the bone .

I understand and accept that during the procedure unexpected or unforeseen circumstances may make it necessary to abandon the procedure.

BY SIGNING THIS FORM, I ACKNOWLEDGE THAT I HAVE READ OR HAD THIS FORM READ AND EXPLAINED TO ME AND THAT I FULLY UNDERSTAND ITS CONTENTS.

I HAVE BEEN GIVEN AMPLE OPPORTUNITY TO ASK QUESTIONS AND ANY QUESTIONS I HAVE ASKED HAVE BEEN ANSWERED OR EXPLAINED IN A SATISFACTORY MANNER. ALL BLANKS OR STATAMENTS REQUIRING COMPLETION WERE FILLED IN AND ALL STATEMENTS WITH WHICH I DISAGREE WERE MARKED OUT BEFORE I SIGNED THIS FORM.

I accept that medicine is not an exact science and understand that no guarantees can be given as to the results. Understanding these limitations, I request Dr ______and his /her associates to proceed with the procedure.

______

Witness Person giving consent

Relationship to patient if not the

Patient______

Date:______

Additional materials used, if any during the informed consent process for this procedure include:

Date: ______Witness: ______

CERTIFICATE FROM THE HEAD OF THE INSTITUTION

Permission is hereby accorded to the student SQN LDR M M Pasha, to undergo MD MEDICINE course being conducted at Command Hospital (Air Force) Bangalore affiliated to Rajiv Gandhi University of Health Sciences Karnataka, Bangalore commencing from May 2008 under the guidance of COL R MURALIDHAR MD, PROFESSOR & HOD,DEPARTMENT OF MEDICINE, Command Hospital (Air Force) Bangalore- 560007

COMMANDANT AND PRINCIPAL

COMMAND HOSPITAL (AIR FORCE)

BANGALORE- 560007

CERTIFICATE FROM ETHICAL COMMITTEE

1.The committee has examined the scope including the aim, need, objectives, and method of data collection and human/animal intervention of the following study to be carried out by Sqn Ldr MM Pasha under the guidance of Col R Muralidhar,, Professor and HOD, Department of Medicine, the title of which is “BONE MINERAL DENSITY IN ANKYLOSING SPONDYLITIS IN INDIAN MALE”.

2.The committee has no objection for undertaking this study at Command Hospital (Air Force), Bangalore.

ARJUNLAL DAS SK AWASTHI RC PANDA AFTAB ALAM

COL GP CAPT GP CAPT GP CAPT

Prof & HOD Prof Prof ASSO. PROF

(DERMATOLOGY) (ENT) (GEN MEDICINE) (RADIOLOGY)

CHAIRMAN ETHICAL COMMITTEE

COMMAND HODPITAL (AIR FORCE)

BANGALORE – 560007

CERTIFICATE OF ACCEPTANCE BY THE GUIDE

I) COL R MURALIDHAR MD, PROFESSOR & HOD,DEPARTMENT OF MEDICINE, Command Hospital (Air Force) Bangalore, hereby certify that I accept Sqn Ldr M M Pasha as a candidate for MD (MED) course. The title of the dissertation is as follows:-

“BONE MINERAL DENSITY IN ANKYLOSING SPONDYLITIS IN INDIAN MALE”.

He will be under my guidance during the entire period of his study and thesis work.

DATE R Muralidhar

PLACE: Col

PROF& HOD

GENERAL MEDICINE

1